Progress in Cardiac Arrythmia Research

269 Pages·2009·12.19 MB·English

by  Ira R. Tarkowicz

P C
ROGRESS IN ARDIAC
ARRHYTHMIA RESEARCH

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P C
ROGRESS IN ARDIAC
ARRHYTHMIA RESEARCH

IRA R. TARKOWICZ
EDITOR

Nova Biomedical Books
New York
Copyright © 2008 by Nova Science Publishers, Inc.

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Library of Congress Cataloging-in-Publication Data
Progress in cardiac arrythmia research / Ira R. Tarkowicz (editor).
p. ; cm.
Includes bibliographical references and index.
ISBN: 978-1-61668-973-5 (E-Book)
1. Arrhythmia. I. Tarkowicz, Ira R.
[DNLM: 1. Arrhythmia. WG 330 P9632 2007]
RC685.A65P77 2007
616.1'28--dc22 2007021895

Published by Nova Science Publishers, Inc. (cid:30) New York
Contents

Preface vii

Expert Commentaries 1

Population-Based Developments in Genetic 3
Screening for long QT Syndrome
Stephen M. Modell

Thrombolytic Therapy in Patients with Ventricular Fibrillation 11
W. Lederer and A. Amann

Research and Review Studies 17

Chapter 1 Drug-Induced Torsadogenesis: Evolving 19
Trends and New Technologies
Peter Hoffmann, Berengere Dumotier, Robert Pearlstein
and Barbara Warner

Chapter 2 The Role of Antagonists of the Renin-Angiotensin System 67
in the Prevention of Atrial Fibrillation
Maryse Palardy, Peter G. Guerra and Anique Ducharme

Chapter 3 Arrhythmogenicity of Anti-Ro/SSA-Antibodies: 81
From the Newborn to the Adult?
Pietro Enea Lazzerini, Pier Leopoldo Capecchi
and Franco Laghi Pasini

Chapter 4 Development and Evaluation of a High-Fidelity Simulator 109
Prototype for Electrophysiology
Roberto De Ponti, Raffaella Marazzi, Fabrizio Caravati
and Jorge A. Salerno-Uriarte

Chapter 5 NIP-141/NIP-142: A Novel Mixed Channel Blocker for 125
Treatment of Atrial Fibrillation
Norio Hashimoto and Hikaru Tanaka
vi Contents
Chapter 6 A Combination Algorithm for Automatic 141
QRS Complex Detection in ECG Signals
Carsten Meyer, José Fernández Gavela and Matthew Harris

Chapter 7 Differential Effect of I and I Block on Action 169
Kr Ks
Potential in Isolated Rabbit Heart
Samar Al Makdessi, Hicham Sweidan and Ralph F. Bosch

Chapter 8 Cardiac Arrhythmias in the Intensive Care Patient – A Review 183
Elisabeth Paramythiotou, Dimitrios Karakitsos,
Evangelos Matsakas and Andreas Karabinis

Chapter 9 Sudden Cardiac Death Syndrome- Arrhythmogenic Right 207
Ventricular Dysplasia/Cardiomyopathy as most Frequent
Cause of Fatal Arrhythmias
Ivana I. Vranic and Tijana Simic

Index 235
Preface

Cardiac arrhythmia is a term that denotes a disturbance of the heart rhythm. Cardiac
arrhythmias can range in severity from entirely benign to immediately life-threatening. A
cardiac arrhythmia, also called cardiac dysrhythmia, is a disturbance in the regular rhythm of
the heartbeat. Several forms of cardiac arrhythmia are life-threatening and a medical
emergency.Cardiac arrhythmias sometimes are classified according to their origin as either
ventricular arrhythmias (originating in the ventricles) or supraventricular arrhythmias
(originating in heart areas above the ventricles, typically the atria). They also can be classified
according to their effect on the heart rate, with bradycardia indicating a heart rate of less than
60 beats per minute and tachycardia indicating a heart rate of more than 100 beats per minute.
This new book presents important research in the field from around the globe.
The chances for successful restoration of spontaneous circulation (ROSC) in cardiac
arrest follwing ventricular fibrillation (VF) deteriorate rapidly with time. Improved
myocardial reperfusion, e.g. by way of cardiopulmonary resuscitation (CPR), may improve
the prospect for successful defibrillation. In addition, electrocardiographic (ECG) waveform
analysis can help determine the optimal timing for defibrillation and thus prevent unnecessary
damage caused to the myocardium by unsuccessful electric shocks. Computer-assisted ECG
analysis with removal of CPR-associated noise and artifacts allows the outcome of
defibrillation to be predicted without causing potentially detrimental interruptions in CPR.
The likelihood that defibrillation in patients with sustained VF will be successful can be
further improved by administering thrombolytics during CPR. While dissolution of coronary
artery thrombosis resolves the underlying cause of myocardial infarction in the majority of
patients, improved microcirculatory reperfusion and alteration of the electrical activity of the
fibrillation process may increase the likelihood of restoring spontaneous circulation during
resuscitation. An increase in fibrillation frequency, fibrillation amplitude or in amplitude
spectrum area (AMSA) as calculated from electrocardiography (ECG) signals indicates that
thrombolytic therapy is improving ventricular fibrillation status, thus improving the chances
for successful defibrillation.
As presented in Chapter 1, contemporary preclinical in vitro and in vivo methods have
been imperfect in predicting drug-induced Torsades de Pointes (TdP) arrhythmia in humans.
A better understanding of additional relevant factors in the genesis of drug-induced TdP
besides the relationships between hERG inhibition, action potential duration, and QT interval
is necessary and supports the evolution of new methods to assess the cardiovascular safety of
new drug candidates in the future.
viii Ira R. Tarkowicz
New, sophisticated in vitro techniques, such as arterially perfused ventricular wedge
preparations or isolated perfused hearts, potentially offer a better understanding of
torsadogenic mechanisms and a refinement of drug testing. Of particular interest are the
dispersion of repolarization and the refractoriness of different cell types across the ventricular
wall, triangulation of the action potential, reverse use dependence and instability of the action
potential duration. In vivo models in conscious and anesthetized non-rodents are currently
refined by establishing the relevance of parameters such as beat-to-beat-variability and T-
wave morphology as derived from the in vitro proarrhythmia indices. Animal models of
proarrhythmia are to date not recommended for routine evaluation, since the models are
insufficiently established to provide any certainty of detecting relevant effects. This holds true
for in vitro and in vivo techniques.
Pharmacodynamic interactions with combinations of torsadogenic compounds at the level
of the hERG channel on the plasma membrane and interactions with other channel proteins is
another area to be considered. Little is known about channel/receptor cross talk, although
considerable evidence exists that cardiac G protein-coupled receptors can modulate hERG
channel function. More investigations are necessary to further evaluate the role of altered
gene expression, mutations and polymorphisms in drug-induced TdP. Down-regulation of
hERG channels under pathophysiological conditions contributes significantly to the enhanced
liability of the repolarization process. A recently discovered mechanism of drug-induced
torsadogenesis is the reduced expression of hERG channel protein on the plasma membrane
due to a trafficking defect.
Pharmacokinetic and metabolism data of NCE are crucial for calculating the risk of a
torsadogenic potential in man. Consideration of intracardiac accumulation via effects on
active transport mechanisms that facilitate access of the drug to the "active site" may help in
delineating any pharmacokinetic-pharmacodyamic relationships and potential
pharmacokinetic drug-drug interactions that may occur beyond the hepatic cytochrome P450
level.
In silico methods possess the potential to improve the prediction of torsadogenic risk. For
early risk assessment of new drug candidates, virtual screening procedures to predict hERG
block would become a promising tool. The role of in silico modeling of TdP arrhythmia is
likely to become increasingly important, however, the pathogenesis of arrhythmias is
complex and vast amounts of data need to be considered. At present in silico methods cannot
replace existing preclinical models.
Chapter 2 discusses the role of antagonists of the renin-angiotensin system in the
prevention of atrial fibrillation.
Background: Atrial fibrillation (AF) is the most frequently encountered arrhythmia in
clinical practice and is associated with increased mortality and morbidity. Its incidence has
grown due to the increasing prevalence of risk factors for AF development, which include
age, diabetes, hypertension, heart failure (HF), valvular and ischemic heart diseases.
Retrospective studies and small prospective trials have suggested a preventive effect of
antagonists of the renin-angiotensin system (RAS), including angiotensin-converting enzyme
(ACE) inhibitors and angiotensin-II receptor blockers (ARB), on AF occurence.
Method and Results: The authors performed a systematic literature search on the role of
RAS antagonists in the prevention of AF. They looked in particular at the pathophysiology of
AF, including the concepts of atrial ionic and anatomical changes induced by AF, called
electrical and structural remodelling. The authors reviewed the published data on the potential