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Peter Magnusson From Division of Cardiology, Department of Medicine, Solna Karolinska Institutet, Stockholm, Sweden IMPLANTABLE CARDIOVERTER DEFIBRILLATOR TREATMENT IN PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY Peter Magnusson Stockholm 2020 Cover illustration by Todd Cooper. All previously published papers were reproduced with permission from the publisher. All illustrations produced with permission. Published by Karolinska Institutet. Printed by E-print AB 2020. © Peter Magnusson, 2020 ISBN 978-91-7831-873-5 IMPLANTABLE CARDIOVERTER DEFIBRILLATOR TREATMENT IN PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY THESIS FOR DOCTORAL DEGREE (Ph.D.) Public defense at Karolinska Universitetssjukhuset Solna, J3:04 Torsten N Wiesel, entrance Eugeniavägen 3. Friday, November 6th, 2020 at 09:00 am. By Peter Magnusson Principal Supervisor: Opponent: Associate professor Stellan Mörner Professor Perry Elliott Umeå University University College London Department of Public Health and Clinical Medicine Centre for Heart Muscle Disease Section of Medicine Institute of Cardiological Sciences Co-supervisor: Examination Board: Associate professor Fredrik Gadler Associate professor Kristjan Karason Karolinska Institutet University of Gothenburg Department of Medicine, Solna Sahlgrenska Academy Division of Cardiology Institute of Medicine Department of Clinical and Molecular Medicine Professor Ella Danielson University of Gothenburg Sahlgrenska Academy Institute of Health and Care Sciences Associate professor Anders Englund Karolinska Institutet Department of Clinical Sciences and Education, Södersjukhuset Chairperson: Professor Karin Schenck-Gustafsson Karolinska Institutet Department of Medicine, Solna Division of Cardiology To my wife Marita and our children Lukas, Melvin, David, and future generations CONTENTS 1 PROLOGUE .................................................................................................................... 1 2 ABSTRACT .................................................................................................................... 2 2.1 Key words .............................................................................................................. 3 3 LIST OF SCIENTIFIC PAPERS ................................................................................... 4 4 ABBREVIATIONS ........................................................................................................ 5 5 INTRODUCTION .......................................................................................................... 6 5.1 History of hypertrophic cardiomyopathy and sudden death ................................ 6 5.2 Definition and diagnostic principles ..................................................................... 8 5.3 Epidemiology ........................................................................................................ 9 5.4 Nomenclature ...................................................................................................... 10 5.5 Clinical evaluation ............................................................................................... 10 5.5.1 Diagnostic work-up ................................................................................. 10 5.5.2 Symptoms ................................................................................................ 10 5.5.3 Physical examination .............................................................................. 11 5.5.4 Laboratory testing ................................................................................... 12 5.5.5 The electrocardiogram ............................................................................ 12 5.5.6 Exercise test ............................................................................................. 13 5.5.7 Misclassification ..................................................................................... 14 5.6 Cardiac imaging................................................................................................... 14 5.6.1 Echocardiography ................................................................................... 14 5.6.2 Cardiac magnetic resonance ................................................................... 15 5.6.3 Computerized tomography and scintigraphy ......................................... 16 5.6.4 Positron emission tomography ............................................................... 17 5.7 Atrial fibrillation and heart failure ...................................................................... 17 5.7.1 Atrial fibrillation ..................................................................................... 17 5.7.2 Heart failure ............................................................................................. 18 5.8 Genetic testing ..................................................................................................... 18 5.9 Sudden cardiac death ........................................................................................... 19 5.10 Risk stratification in hypertrophic cardiomyopathy ........................................... 21 5.11 ICD treatment ...................................................................................................... 23 5.11.1 ICD complications .................................................................................. 24 5.11.2 The subcutaneous ICD ............................................................................ 25 5.12 Pacemaker treatment ........................................................................................... 26 5.13 Cardiac resynchronization therapy ..................................................................... 27 5.14 Pharmacological treatment .................................................................................. 27 5.15 Septum reductive treatment................................................................................. 28 5.16 Lifestyle modification ......................................................................................... 29 5.17 Prognosis and sex differences ............................................................................. 29 6 RATIONALE OF THE THESIS .................................................................................. 31 7 AIMS ............................................................................................................................. 32 7.1 General aim .......................................................................................................... 32 7.2 Specific aims ........................................................................................................ 32 8 MATERIALS AND METHODS ................................................................................. 33 8.1 Study design ........................................................................................................ 33 8.2 Setting .................................................................................................................. 33 8.3 Participants .......................................................................................................... 33 8.3.1 Paper Ⅰ, Ⅱ, and Ⅲ: recruitment and data collection ............................... 33 8.3.2 Paper Ⅳ: recruitment and data collection .............................................. 35 8.3.3 Paper Ⅴ: recruitment and data collection ............................................... 35 8.4 Variables .............................................................................................................. 35 8.4.1 Primary and secondary prevention ......................................................... 35 8.4.2 Risk factors .............................................................................................. 36 8.5 Data sources ......................................................................................................... 38 8.5.1 Swedish Pacemaker and ICD Registry ................................................... 38 8.5.2 SF-36 ....................................................................................................... 38 8.5.3 PET technology ....................................................................................... 39 8.5.4 Echocardiography ................................................................................... 43 8.6 Study size ............................................................................................................. 43 8.7 Statistical methods ............................................................................................... 44 8.7.1 Descriptive data ....................................................................................... 44 8.7.2 Statistical models ..................................................................................... 44 8.7.3 Significance level .................................................................................... 46 8.7.4 Effect size ................................................................................................ 46 8.7.5 Computer software .................................................................................. 46 8.8 Qualitative methods ............................................................................................. 47 8.8.1 Practical approach to the interviews ....................................................... 47 8.8.2 Hermeneutics and content analysis ......................................................... 49 8.8.3 Analysis and interpretation of text .........................................................
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