Clinical presentation and diagnosis of myocarditis

Myocarditis represents a challenging diagnosis, mainly because there is no pathognomonic clinical presentation, and the disease may masquerade as a variety of non-inflammatory myocardial diseases. Thus, in the 1996 WHO/International Society and Federation of Cardiology (WHO/ISFC)(1) and in the 2007 European Society of Cardiology (ESC) classifications of cardiomyopathies,(2) as well as in the 2013 ESC myocarditis Task Force report,(3) the disease is defined histologically as an inflammatory disease of the myocardium diagnosed on endomyocardial biopsy (EMB), based upon histological, immunological, immunohistochemical and molecular findings to detect possible infectious causes.(1-6) The term inflammatory cardiomyopathy may be used for histologically confirmed myocarditis in association with cardiac dysfunction (box 1).(1) Although EMB remains the diagnostic gold standard for myocarditis and it is the only tool that, at present, provides distinction of its aetiological forms,(1-6) it is not widely used. This results in lack of certainty in the epidemiological impact and the natural history of the disease. Myocarditis may resolve spontaneously, recur or become chronic, leading about 1/3 of biopsy-proven cases to dilated cardiomyopathy (DCM), death or heart transplantation.(7) Traditionally, when the diagnosis was only based upon the histological Dallas diagnostic criteria, myocarditis was considered to be a relatively rare cause of heart failure and/or of sudden cardiac death.(8 9) Nowadays, the use of highly sensitive immunohistochemical and molecular tools applied to EMB10-18 and of cardiovascular MR (CMR) for non-invasive imaging(19-21) suggests that we may be indeed facing the tip of an iceberg, with a substantial underestimation of myocarditis frequency and of its causative role in DCM.