Inflammatory Cardiomyopathy (DCMi) - Pathogenesis and Therapy (eBook)

Cardiomyopathy is one of the most frequent causes of heart failure, and a leading entity of cardiac transplantation in the era of modern heart failure regimens. This volume focuses on major advances in inflammatory cardiomyopathy (DCMi) during the past 10 years. The book is divided up into the following sections: 1. Myocarditis and inflammatory cardiomyopathy – clinical management, epidemiology and prognosis; 2. Animal Models of myocarditis – autoimmunity and viral infection; therapeutic interventions; 3. Alterations of the immune system in human viral and inflammatory cardiomyopathy; 4. Diagnosis of inflammatory and viral cardiomyopathy; 5. Treatment strategies in inflammatory cardiomyopathy patients. An international group of authors discusses topics as the histological Dallas criteria for clinical diagnostics, emerging relevance of immunohistological detection of DCMi and detectability of viruses in EMBs, and epidemiology and standard clinical treatment of acute myocarditis and dilated cardiomyopathy patients. This volume serves as a valuable source for cardiologists and cardiovascular pathologists to update their knowledge on DCMi, a still enigmatic and fascinating cardiovascular disorder, which has made major steps from bench to bedside in the past decade.

Title Page 3
Copyright Page 4
Table of Contents 5
List of contributors 7
Preface 10
Myocarditis and inflammatory cardiomyopathy – clinical management, epidemiology and prognosis 12
Pathogenesis, diagnosis and treatment of pericarditis 13
Classification and etiology of pericardial disease 13
Pericardial syndromes 16
Acute pericarditis 16
Clinical presentation 16
Electrocardiogram 16
Laboratory results 16
Echocardiography 16
Chronic pericarditis 17
Recurrent (relapsing) pericarditis 19
Pericardial effusion 20
Cardiac tamponade 23
Constrictive pericarditis 25
Specific forms of pericarditis 26
Viral pericarditis 27
Bacterial (purulent) pericarditis 29
Tuberculous pericarditis 29
Pericarditis in renal failure 29
Autoreactive pericarditis 30
Post-cardiac injury syndrome 30
Post-pericardiotomy syndrome 30
Post-infarction pericarditis 30
Traumatic pericardial effusion 31
Neoplastic pericarditis 31
References 31
Epidemiology and prognosis of myocarditis and dilated cardiomyopathy: Predictive value of clinical parameters and biopsy findings 35
Pathological features 36
Clinical presentations 37
Natural history 38
Predictors of outcome 39
Indications for endomyocardial biopsy 41
Conclusions 42
References 43
Animal models of myocarditis – autoimmunity and viral infection therapeutic interventions45
Autoimmune murine myocarditis and immunomodulatory interventions 46
The murine autoimmune myocarditis models 46
Targeting the recruitment of inflammatory cells in murine autoimmune myocarditis 47
Targeting T cells in autoimmune murine myocarditis 48
Modulating different T helper cell subsets in murine autoimmune myocarditis 48
Pharmacological interventions in murine autoimmune myocarditis 49
Conclusions 50
References 53
Coxsackievirus-induced murine myocarditis and immunomodulatory interventions 59
Introduction 59
CVB-induced myocarditis in inbred murine strains – A clue to the genetics of disease susceptibility 60
Pathogenesis and distinct phases of CVB-induced myocarditis 61
Specific therapeutic strategies in CVB-induced murine myocarditis 63
Interference with viral entry mechanisms and antiviral immunomodulation 65
Immunosuppression 66
Immunomodulation of T cell response 66
Immunomodulation of humoral response 67
Immunomodulation with cytokines 67
Immunomodulation of the innate immune system 68
References 69
Myocardial proteases and matrix remodeling ina cute myocarditis and inflammatory cardiomyopathy 78
Introduction 78
Inflammation and cytokines in AMC and DCM 79
Myocardial ECM: Collagen network, regulation of MMPs and TIMPs, and effects of cytokines 80
Heart failure, cytokines and ECM remodeling 83
Remodeling of the ECM in AMC and DCMi 84
Conclusions 86
References 86
Alterations of the immune system in human viral and inflammatory cardiomyopathy 96
Molecular genetics of cardiomyopathies and myocarditis 97
Introduction 97
Normal cardiac structure 98
Dilated cardiomyopathy 101
Clinical genetics of DCM 102
Molecular genetics of DCM 103
X-linked cardiomyopathies 103
Autosomal dominant DCM 105
Lamin A/C 108
Muscle is muscle: Cardiomyopathy and skeletal myopathy genes overlap 108
Hypertrophic cardiomyopathy 109
Clinical aspects of HCM 110
Genetics of familial HCM 111
Gene identification in FHC 112
Thick filament proteins 113
Myosin subunits 113
Myosin-binding protein C 114
Thin filament proteins 114
Z-disc and other proteins 115
Genotype-phenotype relations in FHC 115
Therapy in HCM 116
Infiltrative forms of HCM 117
AMP-activated protein kinase 119
Energy-dependent forms of HCM 120
Overlap disorders 121
Left ventricular noncompaction 121
Myocarditis 124
Etiology 124
Epidemiology 125
Clinical manifestations 126
Newborns and infants 126
Children, adolescents, and adults 126
Diagnostic tests 126
Pathophysiology 134
Pathology 135
Long-term sequelae 136
Support for viral cause-and-effect relationship with myocarditis 136
Treatment 137
Vaccination 139
Conclusions 140
References 141
Pathogenic relevance of autoantibodies in dilated cardiomyopathy 163
Introduction 163
Formation of cardiac autoantibodies 164
Pathogenic relevance of cardiac autoantibodies in DCM 165
Heat-shock proteins 166
Mitochondrial proteins 166
Myocyte structural proteins 167
Membrane receptor proteins 168
Clinical relevance of cardiac B1-AR antibodies and future perspectives 170
Acknowledgements 171
References 171
The role of cytokines in inflammation-induced cardiomyopathy: Pathogenesis and therapeutic implications 177
Introduction 177
Adaptive and maladaptive effects of pro-inflammatory cytokine signaling in the heart 178
Adaptive effects 178
Maladaptive effects 179
Adaptive and maladaptive effects of inflammatory mediators in viral myocarditis 181
Maladaptive effects of pro-inflammatory cytokines in viral myocarditis 181
Adaptive effects of pro-inflammatory cytokines in viral myocarditis 181
Therapeutic implications 183
Conclusion 183
References 184
Diagnosis of inflammatory and viral cardiomyopathy 188
Histology and immunohistology of myocarditis 189
Introduction 189
Classifications 190
The Dallas classification: Pros and cons 191
Quantification of inflammation and the issue of “normal myocardium” 192
Immunohistochemistry: A technical implementation 193
“Borderline myocarditis” 196
Diagnosis of viral myocarditis 198
Conclusions 198
Acknowledgements 199
References 199
Immunohistological diagnosis of inflammatory cardiomyopathy and diagnosis of cardiotropic viral infections 204
Definition of inflammatory cardiomyopathy 204
Epidemiology and clinical prognostic parameters of AMC and DCM 205
Pathogenic mechanisms of AMC and DCMi 206
Non-invasive diagnostic tools for DCMi 209
Diagnostic EMB procedures 209
Histological assessment of myocarditis 209
Immunohistological diagnosis of DCMi 210
Molecular biological detection of viral genomes in EMBs 216
References 220
Cardiac magnetic resonance imaging: A non-invasive approach for the detection of myocardial inflammation – Potentials and limitations 229
Cardiac magnetic resonance in myocarditis 229
CMR findings in myocarditis 230
Functional assessment 230
Pericardial effusion 230
Tissue characterization 230
Limitations of the current studies 235
References 235
Treatment strategies in inflammatory cardiomyopathy patients 238
Clinical management of acute myocarditis and cardiomyopathy 239
Introduction 239
Fulminant myocarditis 242
Giant cell myocarditis 244
Chronic active myocarditis 244
Eosinophilic myocarditis 246
Peripartum cardiomyopathy with myocarditis 246
Lyme myocarditis 247
Acute myocardial infarction with normal coronaries 247
Small pox vaccine-related myocarditis 248
HIV-related myocarditis 248
Treatment 248
Immunosuppressive therapy 248
Intravenous immunoglobulin 249
Immunoadsorption therapy 250
Summary 250
References 251
Immunosuppressive treatment of inflammatory cardiomyopathy patients 256
General view 256
Immunosuppressive treatment in inflammatory cardiomyopathy 257
Conclusions 260
References 260
Antiviral interferon-B treatment in patients with chronic viral cardiomyopathy 264
Introduction 264
Course of viral infection in human AMC and DCM 265
Antiviral immunomodulation with IFNs 266
Anti-viral IFN treatment in human chronic viral cardiomyopathy 267
The BICC Trial 272
References 272
Immunoadsorption in dilated cardiomyopathy patients 278
Abnormalities of the cellular and humoral immune system in dilated cardiomyopathy 278
Immunoadsorption as a new therapeutic principle for treatment of DCM 280
The beneficial effects of IA are related to removal of cardiac antibodies 282
Role of IgG subclass 3 antibodies 283
Fc y receptors IIa on cardiomyocytes and their potential functional relevance in DCM 284
References 285
Index 289