Cardiac Repolarization: Basic Science and Clinical Management

352 Pages·2020·14.467 MB·English

by  Nabil El-Sherif

Cardiac
Repolarization
Basic Science and Clinical
Management
Nabil El-Sherif
Editor
123
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
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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 electrophysiolo-
gists 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 potas-
sium 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, begin-
ning 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
vi Foreword
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 dis-
cussed 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 clini-
cal 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 identi-
fied 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 (<340 ms) as well as too long and pro-
voke ventricular arrhythmias, as discussed in Chap. 18, “The Short QT
Syndrome.”
A relatively newly described entity, the J-wave syndromes, appears to be a
constellation of several clinical entities characterized by J-wave abnormali-
ties, such as the early repolarization syndrome associated with variants in
seven different genes, discussed in Chap. 14, “Genetics, Molecular Biology
and Emerging Concepts of Early Repolarization Syndrome.” Chapter 15,
“Electrocardiographic J-wave and Cardiovascular Risk in the General
Population,” presents the prevalence and significance of the ECG pattern of
early repolarization in the general population, while Chap. 16, “Benign
Versus Malignant Early Repolarization Patterns,” differentiates benign from
arrhythmogenic J waves, emphasizing the J-wave proper, the ST-segment,
and the ensuing T-waves.
Brugada syndrome appears to be part of the J-wave group and is discussed
in Chap. 17, “Genetic Architecture, Pathophysiology, and Clinical
Management of Brugada Syndrome,” in which the authors stress the under-
standing of the pathophysiological mechanism(s), the ongoing efforts to
reappraise the genetic architecture, and the advances in risk stratification and
therapeutic approaches.
Foreword vii
Chapter 20, the final chapter, “Action Potential Dynamics in Human Atrial
Fibrillation,” explores the action potential variability in the most common
sustained arrhythmia that affects more than 30 million people worldwide,
atrial fibrillation.
This textbook, ably edited by Nabil El-Sherif and written by him along
with a multitude of electrophysiology experts, is a must for basic and clinical
electrophysiologists interested in cardiac repolarization.
Douglas P. Zipes, MD
Distinguished Professor
Indiana University School of Medicine
Krannert Institute of Cardiology
Indianapolis, IN, USA
Preface
Cardiac repolarization is a vital aspect for understanding normal cardiac
rhythm, and its abnormal modulation is the basis of many potentially lethal
cardiac arrhythmias. The last book that dealt exclusively with cardiac repolar-
ization was published in 2003. It is overdue to readdress the many significant
changes in the field.
This book was designed to provide a comprehensive up-to-date coverage
of clinical and research aspects of cardiac repolarization, with several sec-
tions that are the domain of practicing physicians. The 20 chapters are sub-
grouped into 4 parts. Part I deals with the basic, molecular biology and
clinical aspects of cardiac repolarization at large, including the influence of
the autonomic system, remodeling in organic heart disease, racial and gender
difference in cardiac repolarization and arrhythmic risk, ECG-derived evalu-
ation of cardiac repolarization, and future role of stem cells studies of cardiac
repolarization.
Part II provides a comprehensive coverage of pathophysiology, molecular
biology, and clinical aspects of long QT syndromes. While basic and clinical
aspects of congenital long QT syndrome and torsade de pointes are usually
the domain of academic cardiologists and cardiac electrophysiologists,
acquired and drug-induced long QT syndrome should be of interest to a
majority of medical professionals who prescribe drugs and take care of
patients.
Part III provides updated basic and clinical coverage of the subject of early
repolarization (ER), also called J-wave syndromes, and expound currently
controversial aspects such as benign versus malignant ER in the 12-lead ECG
and in the general population at large. Finally, Part IV covers the pathophysi-
ology and clinical aspects of special cardiac repolarization syndromes that
include short repolarization syndrome, repolarization alternans, the impor-
tant role of microvolt T-wave alternans in arrhythmia risk stratification, and
the recently recognized role of atrial repolarization and arrhythmogenesis.
The wide-ranging features of the book should be of interest not only to
academic and clinical cardiologists and cardiac electrophysiologists but also
to a much larger group of practicing internists and other medical profession-
als who would like to keep abreast of the important developments in this field.
Brooklyn, NY, USA Nabil El-Sherif
ix
Contents
Part I P athophysiology, Molecular Biology, and Clinical Aspects
of Cardiac Repolarization
1 Physiology and Molecular Biology of Ion Channels
Underlying Ventricular Repolarization of the Mammalian
Heart . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Thomas W. Comollo, Chuangeng Zhang, Xinle Zou,
and Robert S. Kass
2 Neuromodulation of Cardiac Repolarization and
Arrhythmogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
Fabrice Extramiana and Pierre Maison-Blanche
3 Repolarization Remodeling in Structural Heart Disease . . . . . . 77
Andreas S. Barth and Gordon F. Tomaselli
4 Cardiac Repolarization and Stem Cells: An Emerging
Path Toward Precision Medicine . . . . . . . . . . . . . . . . . . . . . . . . . . 87
Massimiliano Gnecchi, Luca Sala, and Peter J. Schwartz
5 Role of Late Sodium Current During Repolarization
and Its Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109
Mohamed Chahine
6 Age, Sex and Racial Differences in Cardiac
Repolarization and Arrhythmogenesis . . . . . . . . . . . . . . . . . . . . . 119
Arja Suzanne Vink, Sally-Ann B. Clur, Pieter G. Postema,
Nico A. Blom, and Arthur A. M. Wilde
7 ECG-Derived Evaluation of Cardiac Repolarization . . . . . . . . . 131
Gioia Turitto and Nabil El-Sherif
Part II P athophysiology, Molecular Biology, and Clinical
Aspects of Long QT Syndromes
8 Genotype-Phenotype Correlation in Congenital LQTS:
Implications for Diagnosis and Risk Stratification . . . . . . . . . . . 141
Ilan Goldenberg
9 Clinical Management of LQTS Patients . . . . . . . . . . . . . . . . . . . . 165
Wojciech Zareba
xi
xii Contents
10 Drug-Induced Long QT Syndrome and Torsades
de Pointes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 185
Raymond L. Woosley and Peter J. Schwartz
11 Acquired Long QT Syndrome and Electrophysiology
of Torsade de Pointes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201
Nabil El-Sherif, Gioia Turitto, and Mohamed Boutjdir
12 Pathogenesis of Autoimmune- Associated Long
QT Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 217
Mohamed Boutjdir, Pietro Enea Lazzerini,
Pier Leopoldo Capecchi, Franco Laghi-Pasini,
and Nabil El-Sherif
13 The Role of Inflammation and Autoimmunity
in Long QT Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 227
Pietro Enea Lazzerini, Franco Laghi-Pasini, Nabil El-Sherif,
Mohamed Boutjdir, and Pier Leopoldo Capecchi
Part III Pathophysiology, Molecular Biology, and Clinical
Aspects of Early Repolarization Syndromes
14 Genetics, Molecular Biology, and Emerging Concepts
of Early Repolarization Syndrome . . . . . . . . . . . . . . . . . . . . . . . . 255
Charles Antzelevitch and Gregory Dendramis
15 Electrocardiographic J Wave and Cardiovascular Risk
in the General Population. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 269
Heikki V. Huikuri
16 Benign Versus Malignant Early Repolarization Patterns . . . . . . 277
Raphael Rosso and Sami Viskin
17 Genetic Architecture, Pathophysiology, and Clinical
Management of Brugada Syndrome . . . . . . . . . . . . . . . . . . . . . . . 285
John R. Giudicessi and Michael J. Ackerman
Part IV P athophysiology and Clinical Aspects of Special
Cardiac Repolarization Syndromes
18 The Short QT Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 303
Chiara Scrocco, Fiorenzo Gaita, and Carla Giustetto
19 Microvolt T-Wave Alternans: Pathophysiology
and Clinical Aspects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 313
Richard L. Verrier
20 Action Potential Dynamics in Human Atrial Fibrillation . . . . . . 333
Junaid Ahmed Bakhtiyar Zaman, Sanjiv M. Narayan,
and Michael R. Franz
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 347