Essential Cardiac Electrophysiology With Self Assessment Zainul Abedin, MD, FRCP(C ) Associate Professor of Clinical Medicine Texas Tech University Health Sciences Center El Paso, TX Adjunct Associate Professor of Electrical Engineering and Computer Science University of Texas at El Paso Robert Conner, RN Essential Cardiac Electrophysiology With Self Assessment In loving memory of my brother Husainali and To my wife Karuna whose patience and understanding made this project possible and To my children Moeen, Sakena and Zameer Zainul Abedin To all the students of cardiac electrophysiology Robert Conner Essential Cardiac Electrophysiology With Self Assessment Zainul Abedin, MD, FRCP(C ) Associate Professor of Clinical Medicine Texas Tech University Health Sciences Center El Paso, TX Adjunct Associate Professor of Electrical Engineering and Computer Science University of Texas at El Paso Robert Conner, RN © 2007 Zainul Abedin & Robert Conner Published by Blackwell Publishing Blackwell Futura is an imprint of Blackwell Publishing Blackwell Publishing, Inc., 350 Main Street, Malden, Massachusetts 02148-5020, USA Blackwell Publishing Ltd, 9600 Garsington Road, Oxford OX4 2DQ, UK Blackwell Publishing Asia Pty Ltd, 550 Swanston Street, Carlton, Victoria 3053, Australia All rights reserved. No part of this publication may be reproduced in any form or by any form or by any electronic or mechanical means, including information storage and retrieval systems, without permission in writing from the publisher, except by a reviewer who may quote brief passages in a review. First published 2007 1 2007 Library of Congress Cataloging-in-Publication Data Abedin, Zainul, MD. Essential cardiac electrophysiology : self assessment/by Zainul Abedin and Robert Conner. p. ; cm. Includes bibliographical references and index. ISBN-13: 978-1-4051-5108-5 (pbk. : alk. paper) ISBN-10: 1-4051-5108-0 (pbk. : alk. paper) 1. Heart–Electric properties–Handbooks, manuals, etc. 2. Arrhythmia–Pathophysiology–Handbooks, manuals, etc. 3. Electrophysiology–Handbooks, manuals, etc. 4. Heart conduction system–Handbooks, manuals, etc. I. Conner, Robert P. II. Title. [DNLM: 1. Arrhythmia–physiopathology–Handbooks. 2. Arrhythmia–therapy–Handbooks. 3. Electrophysiologic Techniques, Cardiac–Handbooks. WG 39 A138e 2007] QP112.5.E46A24 2007 612.1’71–dc22 2006015740 ISBN-13: 978-1-4051-51085 ISBN-10: 1-4051-51080 A catalogue record for this title is available from the British Library Acquisitions Editor: Gina Almond Development Editor: Lauren Brindley Editorial Assistant: Victoria Pittman Production Controller: Debbie Wyer Set in 9/12pt Meridien by Newgen Imaging Systems (P) Ltd., Chennai, India Printed and bound by Replika Press Pvt Ltd, Haryana, India For further information on Blackwell Publishing, visit our website: www.blackwellfutura.com Address comments to essentialep@gmail.com The publisher’s policy is to use permanent paper from mills that operate a sustainable forestry policy, and which has been manufactured from pulp processed using acid-free and elementary chlorine-free practices. Furthermore, the publisher ensures that the text paper and cover board used have met acceptable environmental accreditation standards. Blackwell Publishing makes no representation, express or implied, that the drug dosages in this book are correct. Readers must therefore always check that any product mentioned in this publication is used in accordance with the prescribing information prepared by the manufacturers. The author and the publishers do not accept responsibility or legal liability for any errors in the text or for the misuse or misapplication of material in this book. Contents Foreword, vii Preface, ix Acknowledgements, xi List of Abbreviations, xiii 1 Ions, channels, and currents, 1 1.1 Potassium channels and currents, 6 1.2 Sodium channels and currents, 12 1.3 Calcium channels and currents, 16 2 Electrophysiologic effects of cardiac autonomic activity, 21 2.1 Adrenergic receptors, 23 2.2 Cholinergic receptors, 25 2.3 Purinergic receptors, 26 3 Mechanisms of arrhythmias, 30 4 Sinus node dysfunction and AV blocks, 43 5 Supraventricular tachycardia, 57 5.1 Atrial flutter , 72 5.2 Atrial tachycardias, 77 5.3 Atrial fibrillation, 83 5.4 Automatic junctional tachycardia, 93 5.5 AV node reentry tachycardias, 94 5.6 AV reentrant tachycardia, 103 6 Differential diagnosis of wide complex tachycardia, 127 v vi Contents 7 Ventricular tachycardia and ventricular fibrillation, 132 7.1 Ventricular tachycardia in the presence of coronary artery disease, 145 7.2 Arrhythmogenic right ventricular dysplasia/cardiomyopathy ARVD/C, 153 7.3 Ventricular arrhythmias in hypertrophic and dilated ardiomyopathy, 159 7.4 Long QT syndrome and Torsade de Pointes, 167 7.5 Brugada syndrome, 177 7.6 Ventricular tachycardia in structurally normal heart, 183 7.7 Bundle branch reentry ventricular tachycardia, 190 7.8 Catecholaminergic polymorphic ventricular tachycardia, 194 7.9 Miscellaneous forms of ventricular arrhythmias, 197 8 Sudden cardiac death and risk stratification, 202 9 Cardiac arrhythmias in patients with neuro-muscular disorders, 214 10 Syncope, 218 11 Pharmacologic therapy of arrhythmias, 229 11.1 Pharmacologic principles as applied to antiarrhythmic drugs, 230 11.2 Antiarrhythmic drugs, 234 11.3 Beta blockers, 239 11.4 Class III antiarrhythmic drugs, 240 11.5 Calcium channel blockers, 246 11.6 Adenosine, 247 11.7 Digoxin, 249 12 Electrical therapy for cardiac arrhythmias, 254 12.1 Cardioversion defibrillation, 256 12.2 Pacemakers, 258 12.3 Implantable defibrillators, 266 Self-assessment answers, 275 Index, 279 [...]... and hypercalcemia 8 Essential Cardiac Electrophysiology Rapidly activating delayed rectifier IKr • It is blocked by methane sulfonamide, class III agents (D-Sotalol) • Inward rectification of IKr results in a small outward current • It plays an important role in atrial pacemaker cells It rapidly recovers from inactivation and it peaks at −40 mV • KCNH2 (HERG, Human Ether Related-a-go-go gene protein) encodes... It will be delayed if the K currents are blocked as in LQT1 and LQT2 or when inward depolarizing currents 14 Essential Cardiac Electrophysiology • • • • persist during repolarization as in LQT3 In LQT3 SCN5A, an Na channel remains open during repolarization resulting in continued inward current This causes prolongation of the QT interval Voltage-dependent opening of Na channel occurs as voltage decreases... induces IKs Expression of both these proteins is 1 necessary for normal function of IKs • MinK, a protein, acts as a function altering β subunit of KvLQT1 MinK modifies KvLQT1 gating and pharmacology • Mutation in MinK and KvLQT1 causes congenital long QT syndrome (LQTS) • MinK suppression leads to inner ear abnormalities and deafness, seen in the Jarvell Lange-Nielson syndrome • Reduced activity of IKs... Sotalol 6 Which of the following statements is incorrect? A ICaL participates in the occurrence of DAD B Phase-3 EAD shares the mechanisms of DAD C EAD is associated with bradycardia and prolongation of APD D DAD is associated with increased heart rate and Ca overload Ions, Channels, and Currents I to 7 I Ks I Kr I Kur I K1 IKatp/ach I Kp Fig 1. 1 Outward currents • K channels carry a positive charge, which... Permanent pacemaker C Mexiletine D Exercise-induced sinus tachycardia 1 3 CA L CIUM CH A N N E LS A N D C U R R E N T S 1 In which one of the following is there no contribution from Calcium current ICaL ? A EAD B Electrical remodeling of the atrium during AF C DAD D Depolarization of the SA and AV nodes 2 Which of the following statements is incorrect? A β-Adrenergic agonists increase ICaL channel... potassium ion leak during prolonged depolarization In addition to IK1 , IKatp and IKach are also inward rectifiers • Intracellular magnesium, calcium, and polyamines block IK1 Increase in intracellular pH inactivates IK1 Increase in extracellular potassium depolarizes the resting membrane • Inwardly rectifying potassium channels (K1) produce less outward currents than inward currents They stabilize... glycolytic pathway is preferentially sensed by the Katp channel • IKatp is a weak inward rectifier but produces a large outward current during depolarization and its activation decreases APD 10 Essential Cardiac Electrophysiology • It is responsible for ischemia preconditioning where brief episodes of ischemia protect the myocardium from prolonged episodes of ischemia • During ischemia, intracellular... channels are activated during upstroke of AP • Rapidly activating and inactivating voltage sensitive transient outward current produces phase 1 of repolarization Ions, Channels, and Currents 11 • Slowly activating delayed rectifier potassium current, and inward rectifier IK1 , which includes fast inactivating rapid component IKr and slow component IKs , contributes to plateau and phase 3 of AP • Potassium... Selective IKr blockers (D-Sotalol) lose efficiency at high rates and during sympathetic stimulation • IKr and IKs are present in the human atrium and ventricle Slowly activating delayed rectifier IKs • IKs is controlled by the gene KvLQT1 (voltage-dependent potassium controlling protein) and MinK (minimal potassium current controlling protein) MinK combined with protein of KvLQT1 induces IKs Expression... Lidocaine • Class 1B drugs have dissociation constant of less than one second These drugs have no effect on the conduction of normal tissue but decrease the conduction following closely coupled premature ventricular contractions (PVCs) and in diseased (ischemic) cells • Class 1C drugs have the slowest dissociation of 12 seconds This results in slowing of conduction and widening of QRS • Class 1A drugs have . 3. Electrophysiologic Techniques, Cardiac Handbooks. WG 39 A138e 2007] QP 112 .5.E46A24 2007 612 .1 71 dc22 2006 015 740 ISBN -1 3 : 97 8 -1 -4 05 1- 5 10 85 ISBN -1 0 : 1- 4 05 1- 5 10 80 A catalogue record for this. cm. Includes bibliographical references and index. ISBN -1 3 : 97 8 -1 -4 05 1- 5 10 8-5 (pbk. : alk. paper) ISBN -1 0 : 1- 4 05 1- 5 10 8-0 (pbk. : alk. paper) 1. Heart–Electric properties–Handbooks, manuals, etc. 2 drugs, 230 11 .2 Antiarrhythmic drugs, 234 11 .3 Beta blockers, 239 11 .4 Class III antiarrhythmic drugs, 240 11 .5 Calcium channel blockers, 246 11 .6 Adenosine, 247 11 .7 Digoxin, 249 12 Electrical