**7. Conclusions and therapeutic perspectives**

To improve histological diagnosis of viral myocarditis, additional virological evaluation of cardiac tissues is required with immunohistochemical and polymerase chain reaction (PCR) techniques allowing identification and quantification of viral infection markers. The diagnostic gold standard is endomyocardial biopsy (EMB) with the histological Dallas criteria, in association with new immunohistochemical and PCR analyses of cardiac tissues. These new viral diagnostic approaches can lead to better identification of the aetiology of myocarditis and can improve the clinical or therapeutic monitoring of viral causes of human myocarditis. Therapeutic strategies adapted specifically to the phase of the disease are currently under evaluation and may improve prognosis and clinical outcomes significantly. It might be more efficient to use positive immunomodulators (interleukins, interferon alpha, interferon gamma) alone or in combination with specific antiviral components such as ribavirin in the initial phase of the disease when viral replication activity can be detected in the cardiomyocytes (Külh et al., 2003). By contrast, immunosuppressive drugs would be more appropriate in the chronic phase of myocarditis, when no or low viral replication activities are detectable in cardiac tissues by immunohistochemistry assays.

Further specific strategies could consist to specifically block the entry of the virus in target cardiac cells, by preventing interaction of viruses with their cellular receptor and their

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consequent signalling amplification systems, such as the tyrosine kinase p56lck, phosphatase CD45 and downstream ERK1/2 (Dennert et al., 2008). Preventing direct viral damage using antiviral therapy is another possible approach by use of specific viral drugs (anti-protease or inhibitors of RNA/DNA polymerases) or by use of general antiviral strategies (interfering RNA). Future randomized placebo-controlled trials should be based upon aetiological diagnosis (viral vs. other causes) and may provide novel treatment options and possibly a better prognosis for these selected patients.
