Cardiac Repolarization: Basic Science and Clinical Management [1st ed. 2020] 978-3-030-22671-8, 978-3-030-22672-5

Table of contents :
Front Matter ....Pages i-xv
Front Matter ....Pages 1-1
Physiology and Molecular Biology of Ion Channels Underlying Ventricular Repolarization of the Mammalian Heart (Thomas W. Comollo, Chuangeng Zhang, Xinle Zou, Robert S. Kass)....Pages 3-47
Neuromodulation of Cardiac Repolarization and Arrhythmogenesis (Fabrice Extramiana, Pierre Maison-Blanche)....Pages 49-76
Repolarization Remodeling in Structural Heart Disease (Andreas S. Barth, Gordon F. Tomaselli)....Pages 77-85
Cardiac Repolarization and Stem Cells: An Emerging Path Toward Precision Medicine (Massimiliano Gnecchi, Luca Sala, Peter J. Schwartz)....Pages 87-107
Role of Late Sodium Current During Repolarization and Its Pathophysiology (Mohamed Chahine)....Pages 109-117
Age, Sex and Racial Differences in Cardiac Repolarization and Arrhythmogenesis (Arja Suzanne Vink, Sally-Ann B. Clur, Pieter G. Postema, Nico A. Blom, Arthur A. M. Wilde)....Pages 119-129
ECG-Derived Evaluation of Cardiac Repolarization (Gioia Turitto, Nabil El-Sherif)....Pages 131-138
Front Matter ....Pages 139-139
Genotype-Phenotype Correlation in Congenital LQTS: Implications for Diagnosis and Risk Stratification (Ilan Goldenberg)....Pages 141-164
Clinical Management of LQTS Patients (Wojciech Zareba)....Pages 165-184
Drug-Induced Long QT Syndrome and Torsades de Pointes (Raymond L. Woosley, Peter J. Schwartz)....Pages 185-200
Acquired Long QT Syndrome and Electrophysiology of Torsade de Pointes (Nabil El-Sherif, Gioia Turitto, Mohamed Boutjdir)....Pages 201-216
Pathogenesis of Autoimmune-Associated Long QT Syndrome (Mohamed Boutjdir, Pietro Enea Lazzerini, Pier Leopoldo Capecchi, Franco Laghi-Pasini, Nabil El-Sherif)....Pages 217-226
The Role of Inflammation and Autoimmunity in Long QT Syndrome (Pietro Enea Lazzerini, Franco Laghi-Pasini, Nabil El-Sherif, Mohamed Boutjdir, Pier Leopoldo Capecchi)....Pages 227-251
Front Matter ....Pages 253-253
Genetics, Molecular Biology, and Emerging Concepts of Early Repolarization Syndrome (Charles Antzelevitch, Gregory Dendramis)....Pages 255-268
Electrocardiographic J Wave and Cardiovascular Risk in the General Population (Heikki V. Huikuri)....Pages 269-276
Benign Versus Malignant Early Repolarization Patterns (Raphael Rosso, Sami Viskin)....Pages 277-283
Genetic Architecture, Pathophysiology, and Clinical Management of Brugada Syndrome (John R. Giudicessi, Michael J. Ackerman)....Pages 285-299
Front Matter ....Pages 301-301
The Short QT Syndrome (Chiara Scrocco, Fiorenzo Gaita, Carla Giustetto)....Pages 303-311
Microvolt T-Wave Alternans: Pathophysiology and Clinical Aspects (Richard L. Verrier)....Pages 313-331
Action Potential Dynamics in Human Atrial Fibrillation (Junaid Ahmed Bakhtiyar Zaman, Sanjiv M. Narayan, Michael R. Franz)....Pages 333-345
Back Matter ....Pages 347-354

Citation preview

Cardiac Repolarization Basic Science and Clinical Management Nabil El-Sherif  Editor

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Cardiac Repolarization

Nabil El-Sherif Editor

Cardiac Repolarization Basic Science and Clinical Management

Editor Nabil El-Sherif Department of Medicine and Physiology State University of New York Downstate Medical Center VA New York Harbor Healthcare Center Brooklyn, NY USA

ISBN 978-3-030-22671-8    ISBN 978-3-030-22672-5 (eBook) https://doi.org/10.1007/978-3-030-22672-5 © Springer Nature Switzerland AG 2020 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland

Foreword

Normal cardiac repolarization is vital to maintain optimal mechanical and electrical cardiac function. Repolarization that is too long or too short, or otherwise abnormal, puts the patient at risk for developing life-threatening cardiac arrhythmias. It is essential that scientists and clinical electrophysiologists understand cardiac repolarization. The textbook Cardiac Repolarization: Basic Science and Clinical Management, edited by Nabil El-Sherif, provides information critical to that understanding. Chapter 1, “Physiology and Molecular Biology of Ion Channels Underlying Ventricular Repolarization of the Mammalian Heart,” reviews the key ion channels that underlie cardiac repolarization and focuses on critical potassium ion channels, while the Chap. 2, “Neuromodulation of Cardiac Repolarization and Arrhythmogenesis,” explores autonomic modulation of this activity at the cardiac channel, cellular, and organ levels. Heart failure can predispose to the development of potentially fatal arrhythmias via multiple mechanisms including altered calcium handling, stretch, and changes in myocyte electrical and metabolic properties, as explored in Chap. 3, “Repolarization Remodeling in Structural Heart Disease.” A major advance in studying mechanisms impacting repolarization has been the use of pluripotent stem cell-derived cardiomyocytes to model cardiac disease states, a major advance presented in Chap. 4, “Cardiac Repolarization and Stem Cells: An Emerging Path Toward Precision Medicine.” Voltage-gated sodium channels, responsible for the rapid upstroke of the action potential, are vital to maintain electrical excitability and coordinate excitation-contraction coupling, as explored in Chap. 5, “Role of Late Sodium Current during Repolarization and Its Pathophysiology.” How age, sex, and race impact cardiac repolarization and arrhythmogenesis is presented in Chap. 6, “Age, Sex, and Racial Differences in Cardiac Repolarization and Arrhythmogenesis,” emphasizing that testosterone appears to shorten the QTc interval in males, while in females, there is a more complex interaction between progesterone and estrogen. With the initial chapters serving as a scientific foundation for clinical events involving repolarization, the text now turns to the clinical arena, beginning with a consideration of the standard electrocardiogram (ECG), still one of the most useful methods for risk stratification for sudden cardiac death, and an analysis of the QT interval, as explained in Chap. 7, “ECG-derived Evaluation of Cardiac Repolarization.” Microvolt T-wave analysis represents v

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another approach for investigating the QT interval to track T-wave alternans, a beat-to-beat fluctuation in ST-segment or T-wave morphology, and is discussed in Chap. 19, “Microvolt T-Wave Alternans: Pathophysiology and Clinical Aspects.” The next several chapters feature clinical manifestations of the long QT interval. Chapter 8 delves into the phenotype-genotype relationship of clinical presentations, ECG patterns, risk stratification for cardiac events, and therapy in “Genotype-Phenotype Correlation in Congenital LQTS: Implications for Diagnosis and Risk Stratification,” concentrating on the three genes KCNQ1, KCNH2, and SCN5A underlying LQT1, LQT2, and LQT3, respectively, which account for about 95% of patients with an identified genetic cause. Chapter 9 discusses the clinical management of patients with the inherited long QT syndrome, “Clinical Management of LQTS Patients,” focusing on minimizing the adrenergic response, shortening the QTc, decreasing the dispersion of refractoriness, and improving the function of dysfunctional ion channel. Chapter 10, “Drug-Induced Long QT Syndrome and Torsades de Pointes,” emphasizes drug-induced LQTS and its ventricular arrhythmia, noting that QT prolongation is a useful but imperfect predictor of patients at high risk of developing the serious and life-threatening arrhythmia, torsades de pointes. Chapter 11, “Acquired Long QT Syndrome and Electrophysiology of Torsade de Pointes,” stresses the electrophysiological mechanisms of acquired LQTS, its electrocardiographic (ECG) characteristics, clinical presentation, and management of the acquired long QT interval. New mechanisms of QT prolongation are explored in Chap. 12, “Pathogenesis of Autoimmune-Associated Long QT Syndrome,” and Chap. 13, “The Role of Inflammation and Autoimmunity in Long-QT Syndrome.” The QTc interval can be too short (960 ms, QT intervals are significantly longer in the VT group. However, at RR intervals