Myocarditis is defined as an inflammatory condition of the heart muscle and is caused by multiple organisms and conditions. The diagnosis of myocarditis remains a challenge, with conflicting views among clinicians and investigators as to whether clinical or histologic diagnostic criteria should predominate.1-4 When the clinical suspicion of myocarditis (sudden onset of heart failure or ventricular arrhythmias in association with or soon after a febrile illness) accords with the histologic diagnosis, there is little diagnostic problem. However, when the clinical presentation of myocarditis is not associated with biopsy evidence of myocyte damage and T-lymphocyte infiltration, this is a dilemma.
In the Myocarditis Treatment Trial,5 most patients with clinically suspected myocarditis did not have biopsy evidence of myocarditis. In this trial, all patients underwent biopsy who had suspected myocarditis based on the new onset of unexplained heart failure during the 2 years preceding enrollment. The endomyocardial biopsy samples were reviewed according to the Dallas criteria by a panel of 7 pathologists and a consensus diagnosis was reached. The pathologists found histopathologic evidence of myocarditis on endomyocardial biopsy in just 214 of 2,233 patients (less than 10%). Other smaller series also reported a poor concordance between the clinical and histologic diagnoses of myocarditis, "possibly because the clinical diagnosis is wrong or the histologic criteria used by pathologists are inappropriate."6
The ongoing European Study of Epidemiology and Treatment of Cardiac Inflammatory Diseases (ESETCID) has expanded the light microscopic Dallas criteria for myocarditis by including immunohistochemical variables of myocardial inflammation.7 Endomyocardial biopsy specimens are screened not only for infiltrating cells but also for the presence of persisting viral genome (enterovirus, cytomegalovirus, and adenovirus). This method shows inflammatory processes in the heart in 17.2% of the 3,055 patients screened. Only 182 of these patients showed a reduced ejection fraction below 45%, fulfilling the entrance criteria for the ESETCID trial. These data indicate that, in symptomatic patients, myocarditis should always be considered and relatively well-preserved left ventricular function does not exclude the diagnosis. In the ESETCID trial, viral genome was detected in 11.8% of patients (enterovirus 2.2%, cytomegalovirus 5.4%, adenovirus 4.2%).
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