Clinical Approach to Sudden Cardiac Death Syndromes (eBook)

Preface 5
Acknowledgments 7
Contents 8
Contributors 11
Part I Sudden Unexplained Death 15
Sudden Unexplained Death in the Community 16
1.1 Magnitude of the Problem 16
1.2 Relationship with Gender 17
1.3 Diagnostic Considerations and Role of the Molecular Autopsy 17
1.4 Conclusions 18
References 18
Sudden Infant Death Syndrome: Gene– Environment Interactions 20
2.1 Introduction 20
2.2 Genetic Risk Factors 21
2.3 Environmental Risk Factors 24
2.4 Phenotypes Associated with Increased Risk for SIDS 28
2.5 Gene–Environment Interactions 29
2.6 Summary 30
References 30
Part II Arrhythmias and sudden cardiac death. The initial investigation 35
Unexplained Syncope 36
3.1 Unexplained Syncope 36
3.2 Definition and Pathophysiology of Syncope 36
3.3 Etiology of Syncope 36
3.4 Risk Stratification 39
3.5 Initial Evaluation 39
3.6 Noninvasive Tests 40
3.7 Invasive Testing 41
3.8 Diagnostic Approach of Unexplained Syncope 42
References 44
Arrhythmias and Sudden Cardiac Death in Adult Congenital Heart Disease 47
4.1 Atrial Septal Defect 48
4.2 Ventricular Septal Defect 51
4.3 Atrioventricular Canal Defect 51
4.4 Left Ventricular Outflow Tract Obstruction 52
4.5 L-Transposition of the Great Arteries (L-TGA) 52
4.6 Ebstein’s Anomaly 53
4.7 Heterotaxy Syndromes 53
4.8 Single Ventricle Physiology 54
4.9 Fontan Palliation 56
4.10 Tetralogy of Fallot 57
4.11 D-Transposition of the Great Arteries ( D- TGA) 59
4.12 Summary 61
References 61
Endurance Sport Practice and Arrhythmias 67
5.1 Athlete’s Heart: Anatomical and Electrical Considerations 67
5.2 EKG of the Athlete: From Physiological Adaptation to Pathological Condition 69
5.3 Sudden Death and Ventricular Arrhythmias 70
5.4 Hypertrophic Myocardiopathy 71
5.5 Right Ventricular Arrhythmias: Arrhythmogenic Right Ventricle Dysplasia 72
5.6 Ventricular Premature Beats and Ventricular Complex Arrhythmias 73
5.7 Commotio Cordis 73
5.8 Supraventricular Arrhythmias 73
5.9 Screening Athletes 75
5.10 Sport Eligibility 77
5.11 Automated External Defibrillators 78
5.12 Differences in Race 78
5.13 Syncope in Athletes 79
References 79
Electrocardiograms Not to Miss 83
6.1 Brugada Syndrome 83
6.2 Ventricular Repolarization Components 85
6.3 Long QT Syndrome 87
6.4 Electrocardiographic and Electrophysiological Characteristic of Torsade De Pointes 89
6.5 Electrophysiological Mechanism 89
6.6 Cardinal Sign 91
6.7 Most Common Causes 91
6.8 Arrhythmogenic Right Ventricular Dysplasia 91
6.9 Short QT Syndrome 93
6.10 Catecholaminergic Polymorphic Ventricular Tachycardia 96
6.11 Clue for Electrocardiographic Diagnosis of CPVT 99
References 99
Sudden Cardiac Death in Forensic Pathology 101
7.1 Introduction 101
7.2 Circumstances of Death and Clinical Informations Relevant to the Autopsy 104
7.3 The Autopsy Procedure 104
7.4 Laboratory Tests 107
7.5 Formulation of a Diagnosis: Main Findings at Postmortem Investigation 108
7.6 Forensic Report and Clinico- Pathological Summary 116
7.7 Conclusions 117
References 118
Part III Cardiac genetic syndromes 121
Genetic Studies 122
8.1 Introduction 122
8.2 Genetic Determinants of Disease 123
8.3 Mendelian Traits 123
8.4 Genetic Linkage Studies 124
8.5 Genetic Association Studies for Complex Traits 125
8.6 Challenges of Genetic Association Studies 127
8.7 In Conclusion 128
References 128
The Long QT Syndrome 130
9.1 Introduction 130
9.2 Clinical Manifestations 130
9.3 Diagnostic Tools 130
9.4 Differential Diagnosis 132
9.5 Molecular Genetics 132
9.6 Autosomal Dominant Long QT Syndrome ( Romano- Ward Syndrome) 132
9.7 Autosomal Recessive Long QT Syndrome ( Jervell and Lange- Nielsen Syndrome) 134
9.8 Genotype–Phenotype Correlation in LQT Syndrome 134
9.9 Risk Stratification 134
9.10 Management Strategies 135
9.11 Prevention 136
References 136
Brugada Syndrome 139
10.1 Introduction 139
10.2 Diagnostic Criteria and General Characteristics 139
10.3 Genetics of the Brugada Syndrome 141
10.4 Clinical Manifestations of the Brugada Syndrome 142
10.5 ECG and Modulating Factors 145
10.6 Diagnostic Tools: Drug Challenge 147
10.7 Prognosis and Risk Stratification 148
10.8 Treatment 151
References 153
Short QT Syndrome 157
11.1 Clinical Manifestations 157
11.2 Clinical Diagnosis 157
11.3 Differential Diagnosis 160
11.4 Risk Stratification Parameters 160
11.5 Therapeutic Approach to the Disease 161
11.6 Genetic Basis 161
11.7 Role of Genetics in Diagnosis, Risk Stratification and Therapy 162
11.8 Prevention Strategies 163
References 163
Catecholaminergic Polymorphic Ventricular Tachycardia 165
12.1 Clinical Manifestations 165
12.2 Clinical Diagnosis 165
12.3 Differential Diagnosis 166
12.4 Risk Stratification 167
12.5 Therapeutic Approach to the Disease 167
12.6 Role of Genetics in Diagnosis, Risk Stratification, and Therapy 168
12.7 Prevention Strategies 168
12.8 Controversial Issues in Clinical Diagnosis and Management 168
References 169
Arrhythmogenic Right Ventricular Cardiomyopathy/ Dysplasia 171
13.1 Introduction 171
13.2 Clinical Presentation 171
13.3 Clinical Diagnosis 172
13.4 Management Strategies 176
References 178
Atrial Fibrillation 180
14.1 Introduction 180
14.2 Genetic Disease 181
14.3 Genetic Predisposition to Nonfamilial AF 182
14.4 Future 183
14.5 Clinical Implications in Familial Atrial Fibrillation 184
References 184
Dilated Cardiomyopathy 186
15.1 Introduction 186
15.2 Epidemiology and Genetic Basis 186
15.3 Clinical Diagnosis 188
15.4 Clinical Diagnosis 188
15.5 Differential Diagnosis 189
15.6 Diagnosis 190
15.7 Genetic Basis 192
15.8 Management and Treatment Strategies 193
15.9 General Measures 193
15.10 Asymptomatic Left Ventricular Dysfunction 194
15.11 Genetic Counseling 195
15.12 Unresolved Questions 196
References 196
Hypertrophic Cardiomyopathy 198
Abbreviations 198
16.1 Introduction 198
16.2 Clinical Manifestations 198
16.3 Clinical Diagnosis 199
16.4 Molecular Genetics 200
16.5 Risk Factors for SCD in HCM 201
16.6 Genetic Testing and SCD in HCM 203
16.7 Evaluation and Management of Risk of SCD 204
16.8 Concluding Remarks 205
References 205
Genetic Lipoprotein Disorders and Cardiovascular Disease 209
Abbreviations 209
17.1 Introduction 209
17.2 Lipoprotein Transport System 210
17.3 Lipoprotein Disorders 216
17.4 Practical Approach 224
References 226
A Systematic Approach to Marfan Syndrome and Hereditary Forms of Aortic Dilatation and Dissection 228
18.1 Introduction 228
18.2 The Causes of Aortic Aneurysm and Dissection 228
18.3 Marfan Syndrome 228
18.4 The Fibrillin-1 Gene and Type-1 Fibrillinopathies 229
18.5 Loeys Dietz Syndrome 231
18.6 Other Hereditary Forms of Thoracic Aortic Aneurysm and Dissection 232
18.7 Bicuspid Aortic Valve 233
18.8 Clinical Management 234
References 235
Inherited Metabolic Diseases: Emphasis on Myocardial Disease and Arrhythmogenesis 238
19.1 Introduction 238
19.2 Limitations to Classification of Secondary Cardiomyopathies 238
19.3 The Elusive Concept of Hypertrophy 239
19.4 Hypertrophy in Children 240
19.5 Pathophysiology of Myocardial Abnormalities 241
19.6 Clinical Course and Management of the Inherited Metabolic Disorders Associated with Cardiomyopathy and Arrhythmogenesis ( Diagram 19.1) 245
19.7 Approaching the Child with Suspicion of Having an Inborn Error of the Metabolism (IEM) 259
References 261
Clinical Genetics in Congenital Heart Disease 264
20.1 Genetic Basis in CHD: Clinical Implications 265
20.2 Decision Trees for Cardiac Defects 266
20.3 Conclusion 272
References 274
Part IV Polygenic cardiovascular genetics 276
Pharmacogenomics 277
21.1 Introduction 277
21.2 The Complexity of Drug Effects 278
21.3 Cytochromes P450 279
21.4 Drug Transporters 281
21.5 Pharmacodynamics 282
21.6 Impact of Nongenetic Factors on Associations Between Genotypes and Phenotypes 285
21.7 Pharmacogenomics: Hope or Hype? 286
References 286
Polygenic Studies in the Risk of Arrhythmias 292
22.1 Polygenic Studies in the Risk of Arrhythmias 292
22.2 Common Genetic Variants as Modifiers of Arrhythmia Risk in the Context of Monogenic Diseases 292
22.3 Common Genetic Variants in Candidate Genes Modify the Risk for Supraventricular Arrhythmias 293
22.4 Common Genetic Variants in Candidate Genes Modify the Risk for Ventricular Arrhythmias 293
22.5 Searching for the Genetic Susceptibility to Common Cardiac Arrhythmias 293
References 297
The Genetic Challenge of Coronary Artery Disease 300
23.1 The Genetic Challenge of Coronary Artery Disease 300
23.2 A Significant Porportionof Susceptibility for CAD Is Genetic 300
23.3 Single Gene vs. Polygenic Disorders 301
23.4 Genetic Basis for Predisposition to Disease 302
23.5 Case Control Association Studies 303
23.6 Direct Association Studies Using the Candidate Gene Approach Have Been Relatively Unsuccessful 303
23.7 Genome-Wide Case Control Association Studies: A New Era for Common Polygenic Disorders 303
23.8 Overview of Statistical Interpretation of GWAS 305
23.9 Results of Recent GWAS for Noncardiac Causes 305
23.10 The First Common Genetic Variant for CAD: 9p21 May Unravel a Novel Pathway 305
23.11 The Importance of Phenotyping and Selecting Controls 306
23.12 Gene To Gene Combinations and Their Interaction with the Environment 307
23.13 Personalized Medicine: The Beginning of a Reality 307
23.14 Functional Analysis of Genetic Variant: A Challenge for the Future 308
References 308
Part V Ethical, legal and Social implications 311
Psychological Implications of Genetic Investigations 312
24.1 Psycho-Social Effects of Genetic Testing 312
24.2 Living with Hereditary SCD Syndrome 313
24.3 The Firing of the ICD as Symptom 314
24.4 Variations on the Illness Experience 315
24.5 Children as the “ Presymptomatic Ill” 315
24.6 Future Directions 315
24.7 Conclusion 316
References 316
Participation in Recreational Sports for Young Patients with Genetic Cardiovascular Diseases 318
25.1 Introduction 318
25.2 Definitions 319
25.3 Scope of the Problem 319
25.4 Premises 320
25.5 Other Specific Considerations and Potential Limitations 321
25.6 Recommendations 321
25.7 Implantable Cardioverter- Defibrillators 325
References 325
Genetic Counseling in Cardiovascular Conditions 328
26.1 Introduction 328
26.2 Sudden Cardiac Death and Genetics 328
26.3 Genetic Counseling in Sudden Cardiac Death 329
26.4 Implications for the Immediate Family with a Known Mutation 332
26.5 Conclusion 334
References 335
Index 337