Myocarditis and heart failure: need for better diagnostic, predictive, and therapeutic tools.

Viral infection of the heart is increasingly recognized as an important cause of both acute and chronic heart failure. Enteroviruses and adenoviruses have been considered the most common pathogens of viral cardiomyopathy (CMP), but parvovirus B19 (PVB19) is increasingly found in endomyocardial biopsies of patients with acute myocarditis or idiopathic dilated cardiomyopathy (ICM). In addition to direct cytopathic effects of these cardiotropic viruses, there is convincing evidence that autoimmune responses induced by viruses contribute to the heart disease in a significant subset of patients with myocarditis. Caforio et al. present a prospective study in 174 consecutive patients with myocarditis included between 1992 and 2005. They identify biventricular dysfunction as the main predictor of death or transplantation. A myocardial biopsy and serum anti-heart autoantibodies (AHA)-driven diagnosis and classification of myocarditis patients are used. As such, viral genome present in biopsies is further identified as a univariate predictor of adverse prognosis. Importance of a thoughtful and generally accepted classification of patients with myocarditis to allow further studies on pathogenesis, prognosis, and treatment of myocarditis is underlined by this study. Clinically, patients with acute viral myocarditis will spontaneously recover in about three-fourth of cases, whereas the remaining one-fourth will develop progressive heart failure. Cardiac biopsies and autoimmune serology are therefore essential in the diagnostic process of myocarditis evolving to ICM. Recent biopsy series in patients with ICM have revealed that long-term persistence of cardiotrophic viruses triggers heart failure at long term: .70% of patients with ICM carry a cardiotrophic virus in the heart. Elimination of the virus after acute myocarditis, either spontaneously or after treatment, results in improvement of cardiac function, supporting a causal role of viral infection in ICM. Understanding the pathogenesis of heart failure induced by viral myocarditis is essential to better focus diagnostic tools. Direct cytopathic effects and immune dysregulation induced by the viral myocarditis trigger cardiac dysfunction. Cardiotrophic viruses are able to degrade cell–cell, cell–matrix, and intracellular elements. These proteases aim to facilitate the entry of the virus into cells, but result in myocyte slippage, injury, and cardiac dilatation. Cardiotrophic viruses also trigger adverse inflammation, further increasing degradation of the extracellular matrix and myocyte skeleton by increased production of proteases including matrix metalloproteinases, evolving in dilated CMP. Thus, future diagnosis and treatment should concentrate on targeting inflammation, proteases, and immune modulation. As viruses, inadequate inflammation, and autoimmune processes all facilitate cardiac dysfunction during myocarditis, the lonesome use of Dallas criteria in myocarditis is therefore inadequate. Dallas criteria do not classify patients with myocarditis in the perspective of the viral cause, autoimmunity, or inflammation. Dallas criteria myocarditis at biopsy, proposed in 1986, only requires an inflammatory infiltrate with or without associated myocyte necrosis or damage and is analysed by a simple haematoxylin–eosin staining. Sampling error of inflammation, variation in expert reading, in addition to variance with other markers of viral infection, and immune activation in the heart are other arguments against the use of Dallas criteria. Also, the present study confirms a lack of sensitivity for myocarditis when using the Dallas criteria, as more than half of their patients would not have been unmistakably diagnosed in the absence of immunohistochemistry for leucocytes. Beside histopathology for leucocytes and viral PCR in cardiac biopsies, detection of autoantibodies (AHA) in blood or HLA staining in cardiac biopsies adds to the diagnostic work-up in myocarditis. In the study of Caforio et al., AHA were present in 56% of patients with myocarditis, which is high compared with other studies, but probably mirrors a group of patients included in the acute phase of inflammation where AHA are more often detected than in the more chronic stage of myocarditis. AHA induce inadequate inflammation in the heart and directly injure The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology.