Diagnosis of myocarditis: death of Dallas criteria.

Determining the etiology of cardiac dysfunction in patients with heart failure influences management and prognosis.1 Myocarditis, diagnosed by the current histopathological Dallas criteria, accounts for 10% of patients with new-onset cardiac dysfunction submitted to endomyocardial biopsy.1,2 Despite complete evaluation including history, physical examination, blood work, echocardiography, coronary angiography, and endomyocardial biopsy, 50% of patients with dilated cardiomyopathy have no etiology identified.1 Recent data suggest that patients in the “idiopathic” category may be suffering from myocardial inflammation due to persistent viral replication or autoimmune activation after a viral infection. These studies raise the question of whether the current histopathological criteria for myocardial inflammation (the Dallas criteria) are sensitive enough to identify the population with viral or autoimmune-related heart compromise. The Dallas criteria were proposed in 1986 and provided a histopathological categorization by which the diagnosis of myocarditis could be established. Dallas criteria myocarditis requires an inflammatory infiltrate and associated myocyte necrosis or damage not characteristic of an ischemic event. Borderline myocarditis requires a less intense inflammatory infiltrate and no light microscopic evidence of myocyte destruction.3 These criteria have been used exclusively by American investigators over the last 2 decades. Sampling error, variation in expert interpretation, variance with other markers of viral infection and immune activation in the heart, and variance with treatment outcomes all suggest that the Dallas criteria are no longer adequate. Chow et al and Hauck et al4,5 demonstrated by biopsying postmortem hearts of patients who had died with myocarditis that, from a single endomyocardial biopsy, histological myocarditis could be demonstrated in only 25% of samples. With 5 biopsies, Dallas criteria myocarditis could be diagnosed in approximately two thirds of subjects. A recent MRI study used focal imaging abnormalities to guide heart biopsy investigation of possible myocarditis. The authors showed that the earliest myocardial inflammatory abnormalities were evident in the lateral wall of the left ventricle, and only these sites revealed myocarditis by histological examination.6 Therefore, there is considerable sampling error associated with establishing the diagnosis of myocarditis. In addition, there are variations in the interpretation of histological samples. Of the 111 patients included in the Myocarditis Treatment Trial diagnosed with myocarditis by heart biopsy,7 only 64% had that diagnosis confirmed by the expert pathology panel who reviewed the histopathological material. In a separate analysis, 7 expert pathologists’ interpretations of histopathological findings from endomyocardial biopsies of 16 patients with dilated cardiomyopathy varied remarkably in the assessment of significant fibrosis (25% to 69%), hypertrophy (19% to 88%), nuclear changes (31% to 94%), lymphocyte count per high-power field (0% to 38%), and the diagnosis of myocarditis. Definite or probable myocarditis was diagnosed in 11 of 16 patients by at least 1 pathologist. However, of the 11 patients, 3 of 7 pathologists agreed on the diagnosis of myocarditis in 3 patients, and 2 of 7 pathologists agreed on the diagnosis of myocarditis in 5 patients.8 Therefore, even expert observers do not agree on the interpretation of histopathological material that has undergone routine staining. Myocarditis may be associated with a number of conditions including HIV/AIDS, ischemia, and inflammatory states such as sarcoidosis and immune disease such as lupus erythematosus. Excluding causes of myocardial inflammation of known etiology allows investigators to address the larger and more important category of patients with “primary” (or postviral) myocarditis. Primary viral myocarditis includes several forms of myocarditis that are defined by their clinical pathological manifestations. These include fulminant, chronic active, eosinophilic, and giant cell myocarditis. Fulminant myocarditis has a distinct onset usually within 2 weeks of presentation. Patients present with profound left ventricular dysfunction but usually not left ventricular dilatation. The endomyocardial biopsy shows multiple foci of active inflammation and necrosis. Patients recover or die within 2 weeks with complete histological and functional recovery of the myocardium in survivors.9 Chronic active myocarditis has an indistinct onset with moderate ventricular dysfunction on presentation and active or borderline myocarditis by biopsy. These patients display ongoing inflammation and fibrosis resulting in the development of a restrictive cardiomyopathy usually 2 to 4 years after presentation.10 Eosinophilic myocarditis may be attributed to eosinophilic syndromes or allergic reactions resulting in left ventricular compromise,