Autoimmunological features in inflammatory cardiomyopathy.

During recent years, increasing evidence has been obtained that cellular as well as humoral autoimmunity is involved in the pathogenesis of dilated cardiomyopathy (DCM). The immune system is generally activated by viral infections with the objective of virus elimination from the myocardium. However, a relevant number of patients demonstrate viral persistence and/or chronic inflammation in the myocardium. This chronic myocardial inflammation, defined by chronic inflammation, is termed "inflammatory cardiomyopathy" according to the WHO classification of cardiomyopathies. Chronic inflammation is frequently followed by the development of autoimmunity. A breakdown in the control mechanisms protecting against autoimmune reactions by both presentation of normally not accessible self-antigens and bystander- activation, induced by the pathogen, leads to the formation of autoreactive antibodies and T cells. The auto-reactive antibodies interact directly with heart tissue resulting in altered signal transduction or complement activation, whereas the T cell-mediated mechanisms include direct attack by cytotoxic T cells or indirect effects of cytotoxic cytokines released by stimulated T cells or macrophages.

Immunomodulatory treatment strategies in inflammatory cardiomyopathy: current status and future perspectives.

Chronic autoimmunity and viral persistence constitute prognostic factors for adverse outcome in dilated cardiomyopathy patients. Inflammatory cardiomyopathy is a specific cardiomyopathy entity diagnosed in approximately 50% of dilated cardiopmyopathy patients by immunohistological quantification of immunocompetent infiltrates and cell adhesion molecule abundance. Patients with autoimmune inflammatory cardiomyopathy benefit from immunosuppressive treatment and immunoadsorption by improvement of left ventricular ejection fraction and heart failure symptoms, paralleled by a significant suppression of intramyocardial inflammation. However, dilated cardiomyopathy patients with viral persistence do not respond favorably to immunosuppression.

Current insights into the pathogenesis, diagnosis and therapy of inflammatory cardiomyopathy.

Persistence of cardiotropic viruses (enterovirus, adenovirus) and anticardiac autoimmunity constitute the predominant etiopathogenic pathways of dilated cardiomyopathy (DCM). The diagnosis of inflammatory cardiomyopathy (InfCM) imposes sensitivity and specificity requirements, which are not fulfilled by the histological Dallas Criteria. The immunohistological quantification and characterization of immunocompetent infiltrates and cell adhesion molecule (CAM) expression has endorsed a new entity of secondary cardiomyopathies acknowledged by the World Health Organization (WHO), InfCM, in approximately 50% of DCM patients. In the absence of viral persistence, InfCM patients benefit from immunosuppressive treatment. Enteroviral and adenoviral genomes have been detected in a significant proportion of DCM patients. Enteroviral persistence is associated with an adverse prognosis. The induction of the coxsackie-adenovirus receptor (CAR) exclusively in 63% of DCM patients, but not in other cardiomyopathies, might constitute a key molecular determinant for cardiotropic viral infections in DCM. In InfCM patients with enterovirus or adenoviral persistence, interferon-beta administration leads to viral elimination and cessation of the intramyocardial inflammation, paralleled by a significant improvement of left ventricular systolic function and heart failure symptoms. The biopsy-guided etiopathogenic differentiation of DCM has endorsed specific treatment strategies: immunosuppressive regimens are favorable in autoimmune InfCM, whereas patients with viral persistence benefit from antiviral immunomodulation.