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.