Arrhythmogenic right ventricular cardiomyopathy - Dysplasia, 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. EGG, 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 ultra-structural 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.