Fig. 7. Gaps in evidence for endomyocardial biopsy-guided therapy in myocarditis and inflammatory cardiomyopathy.

Patients with myocarditis or inflammatory cardiomyopathy can be classified into four groups on the basis of endomyocardial biopsy (EMB) results: inflammation-negative, virus-negative; inflammation-positive, virus-negative; inflammation-negative, virus-positive; and inflammation-positive, virus-positive. In patients with virus-positive inflammatory cardiomyopathy, a clear distinction between virus-active and virus-associated inflammatory cardiomyopathy is required. Given the different aetiologies and clinical presentations of the four groups, specific therapy regimens are suggested for each group (blue boxes), in addition to approved optimal medical therapy for heart failure and risk-adjusted therapy. Immunosuppressive therapy is mandatory for specific forms of virus-negative autoimmune myocarditis, such as eosinophilic myocarditis, giant-cell myocarditis and cardiac sarcoidosis. Immunosuppressive therapy is also safe and effective in clinically unstable or non-resolving lymphocytic virus-negative myocarditis and in lymphocytic virus-negative myocarditis refractory to standard heart failure therapy. Autoantibody targeting can be achieved with immunoadsorption or with newly developed small molecules (aptamers) that neutralize specific autoantibodies. Autoantibody targeting is also under investigation for the treatment of non-primary inflammatory heart diseases, in which autoimmunity could have a role in disease progression. However, knowledge gaps remain about the type and length of immunosuppression and on novel biological agents to target specific immune pathways or autoantibodies. Data from registries and large randomized clinical trials are needed to evaluate the efficacy of the different proposed regimens, which will contribute to improving the clinical value of EMB-guided diagnosis. The role of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in myocarditis and corresponding treatment options are still unclear; therefore, SARS-CoV-2 is not included in the figure. (?) denotes unclear, needs further investigation; B19V, parvovirus B19; HCV, hepatitis C virus; IVIG, intravenous immunoglobulins.