Arrhythmogenic RV Cardiomyopathy/Dysplasia Recent Advances

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Arrhythmogenic RV Cardiomyopathy/Dysplasia

Recent Advances

FRANKI. MARKUS

A^NDREAN^AVA GAETANOTHIENE

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F^RANK I. MÂRCUS • A^NDREA NÂVA • GÂETANO T^HIENE (Eds)

Arrhythmogenic RV Cardiomyopathy/

Dysplasia

Recent Advances

Indice III

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FRANKI. MARCUS

Section of Cardiology Department of Medicine Sarver Heart Center University of Arizona Tucson (AZ), USA ANDREANAVA

Department of Cardiological, Thoracic and Vascular Sciences

University of Padua, Italy GAETANOTHIENE

Department of Medical Diagnostic Sciences University of Padua, Italy

Library of Congress Control Number: 2007922495

ISBN 978-88-470-0489-4 Springer Milan Berlin Heidelberg New York

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IV Indice

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PREFACE

This book covers all the recent research highlights of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D), a recently discovered heart muscle disease which is a major threat to the life of affected young people. It summarizes near- ly 25 years of investigation on the etiology, genetics, pathology, clinical features, diagnosis, and treatment of ARVC/D. In particular, a 5-year research program supported by grants from both the European Community and the National Heart, Lung and Blood Institutes has contributed to the discovery of seven disease-causing genes, thus opening new avenues for the early identification of affected patients and prevention of sudden death.

A Workshop was held in Venice, Italy, October 3, 2005, as part of the Venice Ar- rhythmia Meeting, where the European and American investigators presented and discussed several major achievements which are now reported in this book. As a re- sult of these coordinated efforts, great advances have been made in the recognition and understanding of the disease, which are summarized in this book.

Molecular genetics has established this cardiomyopathy as a familial disorder caused by mutation of the genes that encode cell junction proteins, resulting in defective cellular adhesion with specific immunohistochemical and ultrastructural al- terations. Remodelling at the intercalated disk may trigger a cascade of events in- cluding apoptotic cell death, fibrofatty replacement, and electrical instability. The left ventricle may be involved early in the course of some genetic types of this disease. This finding alters the traditional concept of a disease confined to the right ventricle.

Genetic screening can detect symptomatic carriers in the early stage of the disease. Magnetic resonance imaging with gadolinium permits in vivo identification of fibrous tissue. Electroanatomic mapping can reveal areas of fibrofatty replacement of the right ventricular myocardium. The implantable cardioverter defibrillator has been shown to prevent sudden cardiac death. Whether it should be implanted for secondary as well as for primary prevention is still controversial.

Screening prior to participation in competitive sports has been found to be effec- tive for the identification of subjects at risk and is life-saving by disqualifying affected individuals and avoiding competitive type effort. Sudden death of young athletes declined fivefold after implementation of preparticipation screening, mainly due to identification of ARVC/D.

A panel of experts have contributed to writing this monograph, which will be an essential reference for clinicians and scholars in human genetics, pathology, cardiology, and radiology as well as in forensic and sports medicine.

We would like to express our gratitude to the European Commission, Brussels, CARIPARO Foundation, Padua, and Veneto Region, Venice, for their financial sup- port, which made this publication possible. A special thanks is given to Chiara Car- turan and Kathy Gear for their continuous, outstanding collaboration over the years of these investigations.

The Editors

Indice V

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LIST OF CONTRIBUTORS

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FRANÇOISEHIDDEN-LUCET, MD Department of Cardiac Arrhythmias Institute of Cardiology

B^ARBARAI^GNATIUK, MD, PhD

University of Padua, Italy JULIAINDIK, MD

Department of Cardiology Sarver Heart Center

University of Arizona College of Medicine Tucson (AZ), USA

MAREKKONKA, MD, PhD

Department of Congenital Heart Disease Institute of Cardiology

Warsaw, Poland JÉRÔMELACOTTE, MD

MARKS. LINK, MD

Tufts-New England Medical Center Cardiac Arrhythmia Service Boston (MA), USA

F^RANKI. MÂRCUS, MD Section of Cardiology Department of Medicine Sarver Heart Center University of Arizona Tucson (AZ), USA BÂRRYJ. MÂRON, MD

Hypertrophic Cardiomyopathy Center Minneapolis Heart Institute Foundation Minneapolis (MN), USA

WILLIAMJ. MCKENNA, MD, DSc, FRCP Department of Medicine

University College London and

University College London Hospitals Trust London, UK

ANDREANAVA, MD

University of Padua, Italy M^ATTHIASP^AUL, MD

Department of Cardiology and Angiology University Hospital of Münster

Münster, Germany

MICHAELH. PICARD, MD Cardiac Ultrasound Laboratory Massachusetts General Hospital Boston (MA), USA

K^ATARZYNAP^IOTROWICZ, MD Heart Research Follow-up Program Division of Cardiology

University of Rochester Medical Center Rochester (NY), USA

N^IKOSPROTONOTARIOS, MD

Yannis Protonotarios Medical Centre Hora Naxos, Naxos, Greece

ALESSANDRARAMPAZZO, BSc, PhD Department of Biology

University of Padua, Italy J^EFFREYS^AFFITZ, MD, PhD Harvard Medical School and Department of Pathology Beth Israel Deaconess Medical Center Boston (MA), USA

S^RIJITAS^EN-C^HOWDHRY, MA, MBBS, MRCP Department of Medicine

University College London and

D^UANES^HERRILL, PhD

Mel and Enid Zuckerman College of Public Health

University of Arizona Tucson (AZ), USA P^ETROSS^YRRIS, PhD Department of Medicine University College London and

H^ARIKRISHNAT^ANDRI, MD Division of Cardiology

Johns Hopkins Medical Institutions Baltimore (MD), USA

GAETANOTHIENE, MD

JEFFREYA.TOWBIN, MD Pediatric Cardiology Texas Children’s Hospital Baylor College of Medicine Houston (TX), USA

ADALENATSATSOPOULOU, MD

Yannis Protonotarios Medical Centre Hora Naxos, Naxos, Greece

X List of Contributors

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List of Contributors XI PIETROTURRINI, MD, PhD

Department of Cardiology Civil Hospital of Camposampiero Camposampiero (PD), Italy MARIALUISAVALENTE, MD

M^ATTEOV^ATTA, PhD Pediatric Cardiology Texas Children’s Hospital Baylor College of Medicine Houston (TX), USA DEIRDREWARD, MRCPI Department of Medicine University College London and

THOMASWICHTER, MD, FESC

Department of Cardiology and Angiology University Hospital of Münster

Münster, Germany

ELZBIETAKATARZYNAWLODARSKA, MD, PhD Department of Congenital Heart Disease Institute of Cardiology

Warsaw, Poland ZHAOYANG, MD Pediatric Cardiology Texas Children’s Hospital Baylor College of Medicine Houston (TX), USA

DANITAYOERGER-SANBORN, MD, MMSc Cardiac Ultrasound Laboratory Cardiology Division

Massachusetts General Hospital Harvard Medical School Boston (MA), USA

WOJCIECHZAREBA, MD, PhD Heart Research Follow-up Program and Clinical Cardiology Research Division of Cardiology

University of Rochester Medical Center Rochester (NY), USA

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Elenco degli autori XIII

FRANKI. MARCUS, MD

Frank Marcus is Professor of Medicine at the Sarver Heart Center, University of Arizona, Tucson, USA. He reported the first clinical series of ARVC/D patients and continues to contribute to the understanding of the diagnosis and treatment of this disease. He is the principal investigator of the North American Multidiscipli- nary study of ARVC/D supported by the NHLBI, that consists of a registry, a data coordination center, a genetic laboratory and several international core laboratories.

ANDREANAVA, MD

Andrea Nava is Professor of Cardiology at the University of Pad- ua, Italy. He first recognized the familial occurrence of ARVC/D in the Veneto Region and has made major contributions to the early identification, discovery of defective genes and phenotypic expression of the disease. He is in charge of the family screening program that consists of clinical and genetic investigations.

GAETANOTHIENE, MD

Gaetano Thiene is Professor of Cardiovascular Pathology and Di- rector of the Institute of Pathological Anatomy at the University of Padua, Italy. He was trained both in Cardiology and Pathology.

He first reported ARVC/D as a major cause of sudden, unexpect- ed death in the young and in athletes and established diagnostic criteria for endomyocardial biopsy. He coordinates the European study and has implemented the European Registry of ARVC/D supported by the European Commission.