Inflammatory Dilated Cardiomyopathy (DCMI)

Abstract

Cardiomyopathies are heart muscle diseases, which have been defined by their central hemodynamics and macropathology and divided in five major forms: dilated (DCM), hypertrophic (HCM), restrictive (RCM), right ventricular (RVCM), and nonclassifiable cardiomyopathies (NCCM). Furthermore, the most recent WHO/WHF definition also comprises, among the specific cardiomyopathies, inflammatory cardiomyopathy as a distinct entity, defined as myocarditis in association with cardiac dysfunction. Idiopathic, autoimmune, and infectious forms of inflammatory cardiomyopathy were recognized. Viral cardiomyopathy has been defined as viral persistence in a dilated heart. It may be accompanied by myocardial inflammation and then termed inflammatory viral cardiomyopathy (or viral myocarditis with cardiomegaly). If no inflammation is observed in the biopsy of a dilated heart (< 14 lymphocytes and macrophages/mm(2)), the term viral cardiomyopathy or viral persistence in DCM should be applied according to the WHF Task Force recommendations. Within the German heart failure net it is the authors' working hypothesis, that DCM shares genetic risk factors with other diseases of presumed autoimmune etiology and, therefore, the same multiple genes in combination with environmental factors lead to numerous different autoimmune diseases including DCM. Therefore, the authors' primary goal is to acquire epidemiologic data of patients with DCM regarding an infectious and inflammatory etiology of the disease. Circumstantial evidence points to a major role of viral myocarditis in the etiology of DCM. The common presence of viral genetic material in the myocardium of patients with DCM provides the most compelling evidence, but proof of causality is still lacking. In addition, autoimmune reactions have been described in many studies, indicating them as an important etiologic factor. Nevertheless, data on the proportion of patients, in whom both mechanisms play a role are still missing.A pivotal role for autoimmunity in a substantial proportion of patients with DCM is supported by the presence of organ-specific autoantibodies, inflammatory infiltrates and pro-inflammatory cytotoxic cytokines. Furthermore, familial occurrence of DCM has been described in about 20-30% of cases, with the presence of autoantibodies and abnormal cytokine profiles in first-degree relatives with asymptomatic left ventricular enlargement. This suggests the involvement of a disrupted humoral and cellular immunity early in the development of the disease. A similar pattern of humoral and cellular immune dysregulation has been described in other autoimmune diseases. There is considerable evidence that genetic factors play an important role in the pathogenesis of DCM, either as contributors to the susceptibility to environmental factors or as determinants of functional and structural changes that characterize the phenotypic expression of the disease.Yet, it is not known whether the susceptibility to immunologically mediated myocardial damage reflects the presence of genetic risk fa...

Complex genetic control of host susceptibility to coxsackievirus B3-induced myocarditis

“…6 The observation of familial clustering, and the reported linkage to human lymphocyte antigen (HLA) class II suggest that the host genotype influences severity of disease. 7,8 Enteroviral infection, particularly by coxsackievirus B3 (CVB3), might explain 20-30% of all cases of myocarditis in human patients. 9 Unequivocal evidence that CVB3 can cause cardiac disease has been provided by experimental infection in mice.…”

TLR3 deficiency induces chronic inflammatory cardiomyopathy in resistant mice following coxsackievirus B3 infection: role for IL-4

“…The life expectancy after diagnosis of DCM is only 50% at 4 yr. Chronic myocardial inflammation, particularly following viral myocarditis, has been termed inflammatory DCM (iDCM) by the World Health Organization's classification of cardiomyopathies (35,44). Coxsackievirus B3 (CVB3), a common enterovirus, is a major cause of myocarditis leading to iDCM in Western populations (9,10,20).…”

HBEGF, SRA1, and IK: Three cosegregating genes as determinants of cardiomyopathy

“…For example, organ-specific auto-antibodies, inflammatory infiltrates, and proinflammatory cytokines have been observed in DCM patients (Maisch et al 2005). In addition, increased levels of cytokines such as tumor necrosis factor have been shown to impair myocardial contractility (Matsumori 1996).…”