Arrhythmogenic right ventricular cardiomyopathy. Displasia, dystrophy or myocarditis?

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a frequent cause of sudden death in young individuals and athletes. Although familial occurrence has been documented and a gene defect was recently localized on chromosome 14q23-q24 the etiopathogenesis of the disease is still obscure. METHODS AND RESULTS: A pathological study was conducted in 30 hearts with ARVC (age range, 15 to 65 years; mean, 28 years). In the 27 autopsy cases, the mode of death was sudden in 24 and congestive heart failure in 3. ECG, available in 19 cases, showed inverted T waves in the right precordial leads in 15 cases (79%) and ventricular arrhythmias in 15 (79%). Right ventricular aneurysms were present in 15 hearts (50%) and located in the inferior wall in 12. Left ventricle and ventricular septum were involved in 14 (47%) and 6 (20%) cases, respectively. Scattered foci of lymphocytes with myocardial death were observed in 20 cases (67%). Electron microscopy studies, although confirming the myocardial death and lymphocyte infiltrates, did not show any specific ultrastructural substrate. Two pathological patterns, fatty (40%) and fibrofatty (60%), were identified. The fibrofatty pattern was associated with a thinner right ventricular wall (P < .0001) and a higher occurrence of focal myocarditis (P < .001). In sections of right ventricular free wall with maximal fatty infiltration, the mean percentage area of fatty tissue was 35.9 +/- 11.1% in control versus 80.4 +/- 9.6% in the ARVC, fatty variety (P < .00001). Involvement of the left ventricle and/or ventricular septum, right ventricular aneurysms, and inflammation were found almost exclusively in the fibrofatty variety. CONCLUSIONS: In the fibrofatty variety of ARVC, the myocardial atrophy appears to be the consequence of acquired injury (myocyte death) and repair (fibrofatty replacement), mediated by patchy myocarditis. Whether the inflammation is a primary event or a reaction to spontaneous cell death remains unclear.