Clinical Approach to Sudden Cardiac Death Syndromes978-1-84882-927-5/1.pdf · [email protected] Francis Collins National Human Genome Research Institute, National Institutes of

Clinical Approach to Sudden Cardiac Death Syndromes

Ramon Brugada (Ed.)

Clinical Approach to Sudden Cardiac Death Syndromes

ISBN: 978-1-84882-926-8 e-ISBN: 978-1-84882-927-5

DOI: 10.1007/978-1-84882-927-5

Springer London Dordrecht Heidelberg New York

Library of Congress Control Number: 2009938027

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Ramon BrugadaDean, School of MedicineDirector, Cardiovascular Genetics Center UdG-IDIBGiUniversitat de GironaPic de Peguera 1117003 Girona, Catalonia, Spain

Josep BrugadaMedical Director Hospital ClínicUniversitat de BarcelonaVillarroel 17008036 Barcelona, Catalonia, Spain

Pedro BrugadaScientific Director, Cardiovascular DivisionHead, Heart Rhythm Management Centre Free University of Brussels (UZ Brussel) VUBLaarbeeklaan 1011090 Brussels. Belgium

v

Preface

Much has changed in the field of arrhythmias and sudden cardiac death in these last decades. Successful innovative catheter therapies and protective devices have been determinant in enhancing treatment and prevention strategies of individuals at risk. However, despite the advances, sudden cardiac death still remains a major contributor to mortality in our society. While most deaths occur in adult cases and are associated with ischemic heart disease, occasionally the youngest and the fittest, even those who have become our role models for their athletic abilities, may also die suddenly, usu-ally from noncoronary cardiac causes. It has not been until the advent of molecular biology and genetics in cardiology when we have been able to further deepen in our knowledge of these dreadful events in the young.

In the last 20 years, genetic research in subjects and families with sudden cardiac death syndromes has brought a vast amount of information on genetic defects respon-sible for arrhythmogenesis, improving our understanding on how the abnormally codified proteins are involved in the pathogenesis of a disease and how this protein disrupts the myocyte electrical activity, generates a chaotic rhythm, and predisposes to ventricular fibrillation.

Inherited sudden cardiac death syndromes are indeed rare diseases, much rarer than hypertension or coronary artery disease. However, it is highly likely that as phy-sicians we will at some point encounter a patient with one of these genetic diseases, and we have to be aware of at least two clinical implications.

First, the field of cardiac genetics has brought a new tool, genetic screening, which is presently standing out as a key diagnostic test, complementing the highly sophisti-cated, but often inaccurate, clinical instruments. With the use of genetic information in our practice, we have moved the information from the bench to the bedside, from research to clinical care, translational medicine at its best.

Second, cardiac genetics is also bringing a fundamental change for our clinical practice, which is not to be taken lightly. With the care for patients with inherited arrhythmias, we have gone from facing the single patient to facing the family, from one individual with signs and symptoms of a disease to several family members with a genetic defect. Familial global care is a tremendous and complex new task that includes genetic screening, treatment decisions especially difficult in children, child-bearing choices, disease expression, and genetic penetrance. The family, with all its complexity, cannot be assumed by the lone physician but only by a multidisciplinary team of geneticists, cardiologists, psychologists, and genetic counselors.

Most cardiologists already appreciate that there is more to the sudden death of a young individual than just “natural” causes. Genetic information is changing the way we approach medical care in this genomic era. With this book, our goal is to provide

vi Preface

the latest information on sudden cardiac death and genetic syndromes, with the aim to guide the physician in this complex field.

Ramon, Josep and Pedro Brugada

vii

Acknowledgments

A la nostra germana

A la nostra família

A totes les famílies

To our sister,

to our family,

to all families.

ix

Contents

Part I Sudden Unexplained Death. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

1 Sudden Unexplained Death in the Community. . . . . . . . . . . . . . . . . . . 3Sumeet S. Chugh, Carmen Teodorescu, Audrey Evanado, and Kyndaron Reinier

2 Sudden Infant Death Syndrome: Gene–Environment Interactions. . . . 7Carl E. Hunt, and Fern R. Hauck

Part II Arrhythmias and sudden cardiac death. The initial investigation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23

3 Unexplained Syncope. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25Carlos A. Morillo and Víctor Expósito-García

4 Arrhythmias and Sudden Cardiac Death in Adult Congenital Heart Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37Paul Khairy

5 Endurance Sport Practice and Arrhythmias . . . . . . . . . . . . . . . . . . . . 57Eduard Guasch and Lluís Mont

6 Electrocardiograms Not to Miss . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73Andres Perez-Riera

7 Sudden Cardiac Death in Forensic Pathology. . . . . . . . . . . . . . . . . . . . 91Antonio Oliva and Vincenzo L. Pascali

Part III Cardiac genetic syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111

8 Genetic Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113Marie-Pierre Dubé and John Rioux

9 The Long QT Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121Ramon Brugada and Oscar Campuzano

10 Brugada Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131Begoña Benito, Ramon Brugada, Josep Brugada, and Pedro Brugada

x Contents

11 Short QT Syndrome. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149Christian Wolpert, Christian Veltmann, Rainer Schimpf, and Martin Borggrefe

12 Catecholaminergic Polymorphic Ventricular Tachycardia . . . . . . . . . 157M. Juhani Junttila, Olli Anttonen, and Heikki V. Huikuri

13 Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia . . . . 163Michela Bevilacqua, Federico Migliore, Cristina Basso, Gaetano Thiene, and Domenico Corrado,

14 Atrial Fibrillation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173Oscar Campuzano and Ramon Brugada

15 Dilated Cardiomyopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179Michelle S. C. Khoo, Luisa Mestroni, and Matthew R. G. Taylor

16 Hypertrophic Cardiomyopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191A. J. Marian

17 Genetic Lipoprotein Disorders and Cardiovascular Disease . . . . . . . . 203Khalid Alwaili, Khalid Alrasadi, Zari Dastani, Iulia Iatan, Zuhier Awan, and Jacques Genest

18 A Systematic Approach to Marfan Syndrome and Hereditary Forms of Aortic Dilatation and Dissection . . . . . . . . . . . . . . . . . . . . . . 223Peter N. Robinson and Yskert von Kodolitsch

19 Inherited Metabolic Diseases: Emphasis on Myocardial Disease and Arrhythmogenesis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233Eduardo Back Sternick

20 Clinical Genetics in Congenital Heart Disease . . . . . . . . . . . . . . . . . . . 259Georgia Sarquella Brugada and Gregor Andelfinger

Part IV Polygenic cardiovascular genetics . . . . . . . . . . . . . . . . . . . . . . . . . 271

21 Pharmacogenomics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 273Simon de Denus, Michael Phillips, and Jean-Claude Tardif

22 Polygenic Studies in the Risk of Arrhythmias. . . . . . . . . . . . . . . . . . . . 289Moritz F. Sinner and Stefan Kääb

23 The Genetic Challenge of Coronary Artery Disease. . . . . . . . . . . . . . . 297Robert Roberts, George Wells, and Li Chen

Contents xi

Part V Ethical, legal and Social implications . . . . . . . . . . . . . . . . . . . . . . . 309

24 Psychological Implications of Genetic Investigations . . . . . . . . . . . . . . 311April Manuel, Fern Brunger, and Kathy Hodgkinson

25 Participation in Recreational Sports for Young Patients with Genetic Cardiovascular Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . 317Barry J. Maron

26 Genetic Counseling in Cardiovascular Conditions . . . . . . . . . . . . . . . . 327Laura Robb

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 337

xiii

Contributors

Khalid Alrasadi Medical Biochemistry, McGill University, Royal Victoria Hospital, Montreal, QC, Canada H3A 1A1

Khalid Alwaili Medical Biochemistry, McGill University, Royal Victoria Hospital, Montreal, QC, Canada H3A 1A1

G. Andelfinger Department of Pediatrics, CHU Sainte Justine, University of Montreal, Montreal, QC, Canada H3A 1A1

Olli Anttonen Department of Cardiology, Päijät Häme Central Hospital, Lahli, Finland

Zuhier Awan Medical Biochemistry, McGill University, Royal Victoria Hospital, Montreal, QC, Canada H3A 1A1

Eduardo Back Sternick Arrhythmia and Electrophysiology Unit, Biocor Instituto, Nova Lima, Minas Gerais, Brazil [email protected]

Cristina Basso Department of Cardiac, Division of Cardiology, Thoracic and Vascular Sciences and Cardiovascular Pathology, University of Padua, Padova, Italy

Begoña Benito Research Center, Montreal Heart Institute, 5000 Rue Belanger Montreal, H1T 1C8 Canada

Michela Bevilacqua Department of Cardiac, Division of Cardiology, Thoracic and Vascular Sciences and Cardiovascular Pathology, University of Padua, Padova, Italy

Martin Borggrefe Department of Medicine – Cardiology, University Hospital Mannheim, Mannheim 68167, Germany

Josep Brugada Department of Cardiology, The Thorax Institute, Hospital Clinic of Barcelona, Barcelona, Spain

Pedro Brugada Heart Rhythm Management Centre, Cardiovascular Institute, UZ Brussel, VUB Brussels, Belgium

Ramon Brugada Cardiovascular Genetics Center UdG-IDIBGi, School of Medicine, University of Girona, Girona, Spain [email protected]

Fern Brunger Memorial University of Newfoundland, St. John’s, Newfoundland, Canada A1B 3V6

xiv Contributors

Oscar Campuzano Cardiovascular Genetics Center, UdG-IDIBGI, Girona, Spain [email protected]

Li Chen Cardiovascular Research Methods Centre, University of Ottawa Heart Institute, Ottawa, ON, Canada K1Y 4W7

Sumeet S. Chugh Associate Director, the Heart Institute, Cedars-Sinai Medical Center, Los Angeles CA, USA 90048. [email protected]

Francis Collins National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20894, USA

Domenico Corrado Professor of Cardiovascular Medicine, Department of Cardiac, Thoracic and Vascular Sciences, University of Padua Medical School, Via Giustiniani, 2 35121Padua, Italy [email protected]

Zari Dastani Human Genetics, McGill University, Montreal, QC, Canada H3A 1A1

Simon de Denus Université de Montréal, Montreal Heart Institute, Montreal, QC, Canada H3A 1A1 [email protected]

Marie-Pierre Dubé Department of medicine, Montreal Heart Institute Research Center, and Université de Montréal, 5000, Bélanger, Montreal, QC, Canada H1T1C8 [email protected]

Víctor Expósito-García Universitary Hospital “Marqués de Valdecilla,” Santander – Cantabria, Spain

Audrey Evanado Cardiac Arrhythmia Center, Division of Cardiovascular Medicine, Oregon Health Sciences University, Portland, OR 97239, USA

Jacques Genest Division of Cardiology, McGill University, Royal Victoria Hospital, 687 Pine Avenue West, Montreal, QC, Canada H3A 1A1 [email protected]

Eduard Guasch Department of Cardiology, Thorax Institute, Hospital Clinic, University of Barcelona, Barcelona, Spain

Fern R. Hauck University of Virginia, Charlottesville, VA 22903, USA

Kathy Hodgkinson Clinical Epidemiology Unit, Memorial University, St. John’s, Newfoundland, Canada A1B 3V6

Heikki V. Huikuri Department of Medicine, Institute of Clinical Medicine, University of Oulu, Oulu, Finland [email protected]

Carl E. Hunt Uniformed University of the Health Sciences, 4550 North Park Avenue, Suite 405, Chevy Chase, MD 20815, USA [email protected] [email protected]

Lulia Latan Biochemistry, McGill University, Montreal, QC, Canada H3A 1A1

Contributors xv

Juhani M. Junttila Department of Medicine, Institute of Clinical Medicine, University of Oulu, PO Box 5000, Oulu 90014, Finland [email protected]

Stefan Kääb Ludwig-Maximilians University Klinikum Grosshadern, Medizinische Klinik und Poliklinik I, Marchioninistrasse 15, Munich 81377, Germany [email protected]

Paul Khairy Montreal Heart Institute, University of Montreal, Montreal, QC, Canada H3A 1A1 [email protected]

Michelle S. C. Khoo University of Colorado Denver, 12401 East 17th. Avenue, Leprino Building, Room 559, Aurora, CO 80045, USA [email protected]

Yskert von Kodolitsch Abteilung Kardiologie, Universitaires Herzzentrum, UKE, Martinistrasse 52, 20246 Hamburg, Germany

April Manuel Memorail University of Newfoundland and Labrador, St. John’s, Newfoundland, Canada A1B 3V6 [email protected]

A. J. Marian Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center, 6770 Bertner Street, Texas Heart Institute at St. Luke’s Episcopal Hospital, DAC 900A, Houston, TX 77030, USA [email protected]

Barry J. Maron The Hypertrophic Cardiomyopathy Center, Minneapolis Heart Institute Foundation, 920 E. 28th Street, Suite 620, Minneapolis, MN 55407, USA [email protected]

Luisa Mestroni Electrophysiology Division, Medicine/Cardiology, University of Colorado Denver, Aurora, CO 80909, USA

Federico Migliore Department of Cardiac, Division of Cardiology, Thoracic and Vascular Sciences and Cardiovascular Pathology, University of Padua, Padova, Italy

Lluís Mont Thorax Institute, Department of Cardiology, Hospital Clinic, University of Barcelona, Villarroel 170, Barcelona 08036, Spain [email protected]

Carlos A. Morillo Department of Internal Medicine, Cardiology Division, McMaster University, Hamilton Health Sciences, HGH-McMaster Clinic 5th Floor, 237 Barton Street East, Hamilton, ON, Canada L8L2X2 [email protected]

Antonio Oliva Institute of Forensic Medicine, Catholic University, School of Medicine, Rome, Italy [email protected]

Vincenzo L. Pascali Institute of Forensic Medicine, Catholic University, School of Medicine, Rome, Italy

xvi Contributors

Andres Perez Riera Electro-Vectocardiography, ABC Foundation, São Paulo, [email protected]

Michael Phillips The Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA

Kyndaron Reinier Cardiac Arrhythmia Center, Division of Cardiovascular Medicine, Oregon Health Sciences University, Portland, OR 97239, USA

John Rioux Department of medicine, University of Montreal, Montreal Heart Institute, 5000 Bélanger, Montreal, QC, Canada H1T1C8

Laura Robb Cardiovascular Genetic Centre, Montreal Heart Institute, Montreal, QC, Canada H3A 1A1 [email protected]

Robert Roberts Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON, Canada K1Y 4W7 [email protected]

Peter N. Robinson Institut für Medizinische Genetik, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany [email protected]

Georgia Sarquella-Brugada Department of Pediatrics, CHU Sainte Justine, University of Montreal, Montreal, QC, Canada H3A 1A1

Rainer Schimpf Department of Medicine – Cardiology, University Hospital Mannheim, Mannheim 68167, Germany

Moritz F. Sinner Ludwig-Maximilians University Klinikum Grosshadern, Medizinische Klinik und Poliklinik I, Marchioninistrasse 15, Munich 81377, Germany [email protected]

Jean-Claude Tardif University of Montreal/Montreal Heart Institute, Montreal, QC, Canada H3A 1A1

Matthew R.G. Taylor Electrophysiology Division, Medicine/Cardiology, University of Colorado Denver, Aurora, CO 80909, USA

Carmen Teodorescu Cardiac Arrhythmia Center, Division of Cardiovascular Medicine, Oregon Health Sciences University, Portland, OR 97239, USA

Gaetano Thiene Division of Cardiology, Department of Cardiac, Thoracic and Vascular Sciences and Cardiovascular Pathology, University of Padua, Padova, Italy

Christian Veltmann Department of Medicine – Cardiology, University Hospital Mannheim, Mannheim 68167, Germany

George Wells Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, ON, Canada K1Y 4W7

Christian Wolpert Department of Medicine-Cardiology, Klinikum Ludwigsburg, Ludwigsburg, Germany [email protected]