Ventricular Fibrillation and Acute Coronary Syndrome [1 ed.] 9781617611674, 9781617289699

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Copyright © 2010. Nova Science Publishers, Incorporated. All rights reserved. Ventricular Fibrillation and Acute Coronary Syndrome, Nova Science Publishers, Incorporated, 2010. ProQuest Ebook Central,

Copyright © 2010. Nova Science Publishers, Incorporated. All rights reserved. Ventricular Fibrillation and Acute Coronary Syndrome, Nova Science Publishers, Incorporated, 2010. ProQuest Ebook Central,

CARDIOLOGY RESEARCH AND CLINICAL DEVELOPMENTS

Copyright © 2010. Nova Science Publishers, Incorporated. All rights reserved.

VENTRICULAR FIBRILLATION AND ACUTE CORONARY SYNDROME

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Ventricular Fibrillation and Acute Coronary Syndrome, Nova Science Publishers, Incorporated, 2010. ProQuest Ebook Central,

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Ventricular Fibrillation and Acute Coronary Syndrome, Nova Science Publishers, Incorporated, 2010. ProQuest Ebook Central,

CARDIOLOGY RESEARCH AND CLINICAL DEVELOPMENTS

VENTRICULAR FIBRILLATION AND ACUTE CORONARY SYNDROME

JOYCE E. MANDELL Copyright © 2010. Nova Science Publishers, Incorporated. All rights reserved.

EDITOR

Nova Science Publishers, Inc. New York

Ventricular Fibrillation and Acute Coronary Syndrome, Nova Science Publishers, Incorporated, 2010. ProQuest Ebook Central,

Copyright © 2011 by Nova Science Publishers, Inc. All rights reserved. No part of this book may be reproduced, stored in a retrieval system or transmitted in any form or by any means: electronic, electrostatic, magnetic, tape, mechanical photocopying, recording or otherwise without the written permission of the Publisher. For permission to use material from this book please contact us: Telephone 631-231-7269; Fax 631-231-8175 Web Site: http://www.novapublishers.com NOTICE TO THE READER The Publisher has taken reasonable care in the preparation of this book, but makes no expressed or implied warranty of any kind and assumes no responsibility for any errors or omissions. No liability is assumed for incidental or consequential damages in connection with or arising out of information contained in this book. The Publisher shall not be liable for any special, consequential, or exemplary damages resulting, in whole or in part, from the readers’ use of, or reliance upon, this material. Any parts of this book based on government reports are so indicated and copyright is claimed for those parts to the extent applicable to compilations of such works.

Copyright © 2010. Nova Science Publishers, Incorporated. All rights reserved.

Independent verification should be sought for any data, advice or recommendations contained in this book. In addition, no responsibility is assumed by the publisher for any injury and/or damage to persons or property arising from any methods, products, instructions, ideas or otherwise contained in this publication. This publication is designed to provide accurate and authoritative information with regard to the subject matter covered herein. It is sold with the clear understanding that the Publisher is not engaged in rendering legal or any other professional services. If legal or any other expert assistance is required, the services of a competent person should be sought. FROM A DECLARATION OF PARTICIPANTS JOINTLY ADOPTED BY A COMMITTEE OF THE AMERICAN BAR ASSOCIATION AND A COMMITTEE OF PUBLISHERS. Additional color graphics may be available in the e-book version of this book. LIBRARY OF CONGRESS CATALOGING-IN-PUBLICATION DATA Ventricular fibrillation and acute coronary syndrome / editor, Joyce E. Mandell. p. ; cm. Includes bibliographical references and index. ISBN:  (eBook) 1. Coronary heart disease. 2. Ventricular fibrillation. I. Mandell, Joyce E. [DNLM: 1. Acute Coronary Syndrome. 2. Ventricular Fibrillation. WG 300] RC685.C6V46 2010 616.1'23--dc22 2010027149

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Ventricular Fibrillation and Acute Coronary Syndrome, Nova Science Publishers, Incorporated, 2010. ProQuest Ebook Central,

CONTENTS vii 

Preface

Copyright © 2010. Nova Science Publishers, Incorporated. All rights reserved.

Chapter I

Clopidogrel Response in Acute Coronary Syndrome: Clinical Implications and Emerging Therapies Antonio De Miguel Castro, Alejandro Diego Nieto,   Juan Carlos Cuellas Ramón, Armando Pérez de Prado,   Javier Gualis Cardona and Felipe Férnandez-Vázquez 

Chapter II

Proteomics of Acute Coronary Syndrome Gloria Alvarez-Llamas, Fernando de la Cuesta,   Felix Gil-Dones, Irene Zubiri, Maria Posada,   Maria G. Barderas and Fernando Vivanco 

Chapter III

Major Bleeding in Acute Coronary Syndrome: Definitions, Magnitude of the Problem, Predictors, Outcomes, Management, and Prevention Douraid K. Shakir and Jassim Al Suwaidi 

Chapter IV

Novel Antiplatelets in Acute Coronary Syndromes Burak Pamukcu and Huseyin Oflaz 

Chapter V

Uncontrolled Immune Response in Acute Myocardial Infarction Vicente Bodí Peris and María José Forteza de los Reyes 

Chapter VI

Tissue Transglutaminase Enzyme and Anti-Tissue Transglutaminase Antibodies: Implication for Acute Coronary Syndrome Marco Di Tola and Antonio Picarelli 

Chapter VII

Electrocardiographic Predictors of Fibrillatory Events in Ventricular Early Repolarization Xingpeng Liu, Ashok J. Shah, Nicolas Derval, Frederic Sacher, Shinsuke Miyazaki, Amir S. Jadidi, Andrei Forclaz, Isabelle Nault, Lena Rivard, Nick Linton, Olivier Xhaet, Daniel Scherr,   Pierre Bordachar, Philippe Ritter, Meleze Hocini,   Pierre Jais and Michel Haissaguerre.  

Ventricular Fibrillation and Acute Coronary Syndrome, Nova Science Publishers, Incorporated, 2010. ProQuest Ebook Central,

1 

29 

61  89  115 

139 

159 

vi Chapter VIII

Contents Impact of Sodium Channel Dysfunction on Arrhythmogenesis in Brugada Syndrome Hiroshi Morita, Douglas P. Zipes,   Satoshi Nagase and Jiashin Wu 

171 

Chapter IX

Ventricular Fibrillation: Causes, Symptoms and Treatment Pasquale Notarstefano, Aureliano Fraticelli,   Raffaele Guida and Leonardo Bolognese 

185 

Chapter X

Primary Ventricular Fibrillation in “Tako-Tsubo” Syndrome J. Villegas del Ojo, E. Moreno Millán, A.M. García Fernandez, F. Bocanegra Martin, and P. Martinez Romero 

195 

Chapter XI

Ventricular Fibrillation in the Absence of Apparent Structural Heart Disease: Electrophysiological Mechanisms, Clinical Prognosis and Therapeutic Management. Osmar Antonio Centurión 

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Index

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203  223 

Copyright © 2010. Nova Science Publishers, Incorporated. All rights reserved.

PREFACE Ventricular fibrillation is a cause of cardiac arrest and sudden cardiac death. The ventricular muscle twitches randomly, rather than contracting in a coordinated fashion (from the apex of the heart to the outflow of the ventricles), and so the ventricles fail to pump blood into the arteries and into systemic circulation. Ventricular fibrillation is a sudden lethal arrhythmia responsible for many deaths mostly brought on by ischaemic heart disease. Acute coronary syndrome (ACS) is a set of signs and symptoms related to the heart. ACS is compatible with a diagnosis of acute myocardial ischemia. This book presents current research from across the globe in the study of ventricular fibrillation and acute coronary syndrome, including clopidogrel response in acute coronary syndrome; primary ventricular fibrillation in "tako-tsubo" syndrome; and ECG predictors of fibrillatory events. Chapter I - The benefits of clopidogrel on the treatment of acute coronary syndromes are well established. However, not all patients respond in the same way to clopidogrel therapy, and there are patients who suffer major adverse cardiovascular events despite being on treatment, emerging the concept of clopidogrel resistance. This chapter is focused on this topic, mainly in the definition, response assessment, clinical implications, patients’ management and emerging therapies (prasugrel, cangrelor and ticagrelor). There is an interindividual variability in response to clopidogrel therapy, and lower response has been correlated with recurrent adverse cardiovascular events, including late stent thrombosis. Nevertheless, there is not clear and consensual definition of clopidogrel resistance. Clopidogrel response follows a normal distribution, so it would be more appropriate to refer to as variable response to clopidogrel rather than clopidogrel resistance, with its clinical implications: the lower response, the higher probability of suffering thrombotic events. Due to the misleading definition of “resistance” and non-standardized method to assess platelet inhibition, current guidelines do not routinely recommend the use of platelet function assays to monitor the inhibitory effect of antiplatelet drugs and guide therapies. Clopidogrel loading doses higher than 300 mg and daily maintenance doses higher than 75 mg are not routinely recommended by current guidelines, although 600 mg clopidogrel loading dose seems to be safe and effective, and could be used when a faster onset of action is required. Unfortunately, the management of patients with low response to clopidogrel remains uncertain. Strict control of risk factors may improve clopidogrel response. Recently, emerging therapies such as prasugrel and ticagrelor have shown better results than clopidogrel in the prevention of death from cardiovascular cause, nonfatal myocardial infarction, or stroke, but at expenses of a higher rate of bleeding events. It remains

Ventricular Fibrillation and Acute Coronary Syndrome, Nova Science Publishers, Incorporated, 2010. ProQuest Ebook Central,

Copyright © 2010. Nova Science Publishers, Incorporated. All rights reserved.

viii

Joyce E. Mandell

uncertain whether patients who suffer a thrombotic event being on clopidogrel treatment would benefit from switching to prasugrel or ticagrelor therapy. Chapter II - Atherosclerosis is a chronic inflammatory disease of the vascular system. It is a complex multifactorial disease characterized by the accumulation of inflammatory cells (macrophages, lymphocytes), lipoproteins and fibrous tissue in the wall of large arteries. This results in the development of necrotic/lipidic cores within the intima of arteries at particular site in the circulation. These lesions form in the settings of a pre-existing intimal hyperplasia characterized by the proliferation of VSMC within the intima. In advanced lesions, necrosis of macrophages and VSMC results in a lipid-rich core covered by a fibrous cap, which protects the lesions from rupture and consists mainly of collagen and extracellular matrix (ECM) proteins, synthesized by vascular cells. Plaque rupture, resulting from inflammatory activation and MMPs secretion, and the ensuing thrombosis commonly causes the most acute complications of atherosclerosis such as unstable angina or myocardial infarction (acute coronary syndrome) or stroke. Chapter III - Acute coronary syndrome forms the vast majority of cases seen in daily cardiology clinical practice. It is usually managed using antiplatelet, antithrombotic, and anticoagulation agents, all of which are double-edged swords that also increase the risk of bleeding with an associated increase in morbidity and mortality. Predicting the occurrence of major bleeding and preventing it may help save lives, improve outcomes, and reduce costs. The definition of major bleeding in acute coronary syndrome poses a great challenge when using data from studies and registries around the world to explore the magnitude, predictors, and management of this problem. Different definitions have resulted in inconsistent prevalence and outcomes data. In this chapter, the author explore these issues based on data extracted from a large number of clinical trials and registries, and suggest strategies to address this serious complication of acute coronary syndrome management. Chapter IV - Atherosclerotic coronary artery disease and acute coronary syndromes are the major cause of death in developed countries and their prevalance are increasing in the developing world. Damaged endothelium, impaired coronary flow and finally almost always rupture in a vulnerable atherosclerotic plaque results with thrombus formation and total luminal occlusion at the atherosclerotic lesion site. Atherothrombosis, the latest phase of the atherosclerotic process, is one of the most studied stages that recent studies provided important evidence for its prevention. In 1980s, aspirin became the first line antiaggregant agent in patients with acute coronary syndromes. However, researchers aimed to discover optimal antiplatelet agents with improved efficacy and reasonable safety profile. Developments in the percutaneous coronary interventions (PCI) and especially the stent technology established requirement for newer antiplatelet agents, which was the beginning of ‘age of thienopyridines’. Ticlopidine was the first line thienopyridine, however, serious side effects (neutropenia and severe allergic reactions) limited its clinical use. Then, the ADP P2Y12 receptor antagonist ‘clopidogrel’ became the most commonly used antiplatelet agent after PCI. Subsequently, new generation and more potent ADP receptor antagonists, prasugrel and ticagrelor were developed. The spectrum of antithrombotics is enlarging by the development of vonWillebrand (eg, ARC1779), thrombin (PAR-1 antagonists, eg, SCH530348) and thromboxane receptor antagonists (eg, terutroban). Novel antiplatelet agents aim to reduce atherothrombosis more efficiently than recent ones but without increasing major or life threathenning bleeding. In this chapter the author aim to focus on recent

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Preface

ix

developments and future therapeutic antithrombotic perspectives in patients with acute coronary syndromes. Chapter V - Recently, the theory that hyperinflammation is the body's primary response to potent stimulus has been challenged. Indeed, a deregulation of the immune system could be the cause of multiple organ failure. So far, clinicians have focused on the last steps of the inflammatory cascade. However, little attention has been paid to lymphocytes, which play an important role as strategists of the inflammatory response. Experimental evidence suggests a crucial role of T lymphocytes in the pathophysiology of atherosclerosis and acute myocardial infarction (AMI). In summary, from the bottom of an imaginary inverted pyramid, a few regulatory T-cells control the upper parts represented by the wide spectrum of the inflammatory cascade. In AMI, a loss of regulation of the inflammatory system occurs in patients with a decreased activity of regulatory T-cells. As a consequence, aggressive T-cells boost and anti-inflammatory T-cells drop. A pleiotropic proinflammatory imbalance with damaging effects in terms of left ventricular performance and patient outcome is the result of this uncontrolled immune response. Nowadays, in order to reduce infarct size and microvascular obstruction, a broad range of innovative therapeutic approaches have been proposed, i.e.: cell therapy with regulatory Tcells, inhibition of pro-inflammatory cytokines (TNF-α antagonists), anti-inflammatory cytokines (IL-10 therapy), vaccination with antigens responsables of the immune response in atherosclerosis (vaccination with LDLox or vaccination with Heat Shock Protein 60 HSP60), or the use of gene therapy. The aim of this review is to get an insight into the pathophysiology of the role of the immune system in AMI as well as to describe new therapeutic options on the basis of the regulation of the immune system. Chapter VI - The type II or tissue transglutaminase (TG2) is an ubiquitous enzyme involved in angiogenesis, fibrogenesis, wound healing, cell adhesion/migration, intracellular signaling pathways, respiratory chain assembly, cell proliferation/differentiation, neurite formation, apoptosis, and inflammation. Some years ago, an increased extracellular localization of TG2 has been demonstrated in damaged or inflamed portions of the small intestine from patients with celiac disease (CD). This antigenic overexpression is able to explain, at least in part, the anti-TG2 antibody induction observable in CD patients. On the other hand, anti-TG2 antibodies have been recently described in patients affected from disorders in which the target organ is located at a distance from the intestine, such as acute coronary syndrome (ACS), dilated cardiomyopathy (DCM), valvular heart disease and other causes of end-stage heart failure. In this regard, a cardiac TG2 overexpression has been described in some experimental models of heart failure and in occurrence of myocardial ischemia/reperfusion injury. In the arteries with or without minimal atherosclerosis, TG2 is detectable only in the medium and along the luminal endothelial border while in the atherosclerotic arteries, especially coronaries and carotid vessels, this enzyme is also evident in the fibrous cup and in shoulder regions of the plaque. Consequently, an anti-TG2 antibodyinducing mechanism similar to those taking part in the intestine of CD patients may also occur in the cardiovascular tissues affected from an acute or chronic disorder. Consistent with this hypothesis, anti-TG2 antibodies seem to be related to severity of the acute coronary event, as well as to extent of the myocardial tissue lesion occurring in ACS patients. Furthermore, since TG2 enzymatic activity may result in myocardial wound healing and stabilization of atherosclerotic plaque, anti-TG2 antibodies could have biological effects able to define a prognostic significance. In this light, vulnerable or ruptured atherosclerotic plaque,

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as well as injured myocardium (following an infarction, myocarditis, etc.) may be sources of TG2 antigen resulting in formation of anti-TG2 antibodies that in turn, by neutralizing TG2 enzymatic activity, could promote destabilization of the plaque or impaired myocardial wound healing, thereby contributing to a chronic disorder such as DCM. The finding that anti-TG2 antibodies are able to induce proliferation and inhibit differentiation of intestinal epithelial cell, increase epithelial permeability, activate monocytes, and disturb angiogenesis in CD patients suggests that they may have a functional role also in cardiovascular disorders. In the near future, these observations and related hypothesis could to become the subject of interesting researches. Chapter VII - Early repolarization (ER) pattern is a common electrocardiographic (ECG) variant, characterized by J point elevation manifested either as QRS slurring (at the transition from the QRS segment to the ST segment) or notching (a positive deflection inscribed on terminal S wave), ST-segment elevation with upper concavity and prominent T waves in at least two contiguous leads. The prevalence of ER pattern in normal population varies from 1% to 13%, depending on the age (predominant in young adults), the race (highest amongst black population), and the criterion for J point elevation (0.05 mV vs. 0.1 mV). Since first described by Tomashewski in 1938, ER pattern has been largely considered as an innocent ECG phenomenon for decades. However, this long-held concept has been getting some new momentum by recently published reports. ER pattern has been associated with ventricular fibrillation (VF) in patients with aborted sudden cardiac arrest. It has also emerged as a marker of increased long-term cardiovascular mortality in the general population. Thus, ER pattern is probably not so benign as traditionally believed. Under such a situation, now, the critical clinical question is how to identify the ER subjects who are potentially at risk of arrhythmia. In this chapter, the author review the currently available knowledge on this issue. Chapter VIII - (Background) Patients with Brugada syndrome (BS) have sodium channel (Na-Ch) SCN5A mutations (20%) as well as calcium channel (Ca-Ch) mutations (8%) that reduce the inward current and affect the action potential (AP). The author investigated the affects of Na-Ch dysfunction on arrhythmogenesis in patients with BS and in experimental models of BS to understand the mechanisms of arrhythmogenesis and the origins of the ECG characteristics of BS. (Methods) Clinical study: the author evaluated 80 BS patients [22 with prior ventricular fibrillation (VF) and implantation of a cardioverter defibrillator], and compared ECG parameters and recurrent VF episodes between the patients with and without SCN5A mutation. Experimental study: The author created 2 experimental models of BS in 18 canine right ventricular preparations: 1) Na-Ch dysfunction model (Na-model) by using pilsicainide and pinacidil (n=11); and 2) Ca-Ch dysfunction model (Ca-model) by using verapamil (n=7). The author then optically mapped multisite APs on the transmural surface of these tissue models, and analyzed the mechanisms of arrhythmogenesis and origins of characteristic BS ECGs. (Results) Clinical Study: Patients with the SCN5A mutation had longer PQ interval (202 ± 31 ms) than patients without the mutation (182 ± 31 ms, p