[Familial predisposition and microbial etiology in dilated cardiomyopathy].

Cardiomyopathies are an important and diverse group of heart muscle diseases in which the heart muscle itself is structurally or functionally abnormal and in which coronary artery disease, hypertension, valvular and congenital heart disease are absent or do not sufficiently explain the observed myocardial abnormality. This often results in severe heart failure accompanied by arrhythmias and/or sudden death. Clinical and morphological diversity of cardiomyopathies can reflect the broad spectrum of distinct underlying molecular causes or genetic heterogeneity. In many cases the disease is inherited and is termed familial dilated cardiomyopathy (FDC), which may account for up to 30% of dilated cardiomyopathies (DCM). FDC is principally caused by genetic mutations in FDC genes that encode for cytoskeletal, nuclear and sarcomeric proteins in the cardiac myocyte. In addition, modifying genes, lifestyle and additional factors were reported to influence onset of disease, disease progression, and prognosis. The individual patient's phenotype may reflect a summation and/or interaction of the underlying mutation(s) with other genetic or environmental factors. During the last years major advances have been made in the understanding of the molecular and genetic basis of this type of disease. Nevertheless, much more progress in the identification of underlying mutations, susceptibility genes and modifier genes is important and indispensable for the development of new etiology-orientated forms of therapy. 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 goes ahead with the presence of autoantibodies and abnormal cytokine profiles in first-degree relatives with asymptomatic left ventricular enlargement. These relatives suffer from a higher risk for the development of DCM after years. This suggests the involvement of a disrupted humoral and cellular immunity early in the development of the disease. There is reasonable clinical and experimental evidence, that DCM in addition may occur as late stage of cardiac infection and inflammation. The large spectrum of clinical forms depends on several factors such as genetic determinants of the infective agent, the genetics, age and gender of the host, and the host immunocompetence. In general, infectious agents, including viruses such as entero-, cytomegalo-, and adenoviruses, bacteria such as Borrelia burgdorferi or Chlamydia pneumoniae, protozoa and even fungi can cause inflammatory heart disease leading to DCM. The infectious agents most often identified in DCM nowadays are parvovirus B19, human herpesvirus 3, and Epstein-Barr virus. Persistence of these viruses within the myocardium is associated with reduction of ejection fraction after 6 months. For patients with suspected inflammatory heart disease the immunohistochemical detection of inflammatory infiltrates is related to poor outcome. Many faces of inflammatory heart disease coexist where different phases of the disease progress simultaneously: phase 1 is dominated by viral infection itself, phase 2 by the onset of (probably) multiple autoimmune reactions, and phase 3 by the progression to cardiac dilatation. Further investigations with regard to the etiology of structural heart diseases should include an intensive clinical investigation of the given patient. A possible family history including a pedigree should be ascertained and with regard to a possible inflammatory or viral heart disease, endomyocardial biopsies should be investigated by polymerase chain reaction and immunohistochemistry.