IN-VIVO EVIDENCE OF APOPTOSIS IN ARRHYTHMOGENIC RIGHT-VENTRICULAR CARDIOMYOPATHY

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a primary he art muscle disease characterized by progressive atrophy of the right v entricular myocardium with fibro-fatty replacement and the risk of ele ctrical instability and sudden death, The disease is often familial an d the aetiopathogenesis is still unknown, Recently apoptosis (genetica lly determined cell death) was postulated to account for progressive l oss of myocardium, To establish whether apoptosis is present in ARVC, right ventricular endomyocardial biopsies from 20 patients with clinic al and histological diagnosis of ARVC were examined by electron micros copy and terminal deoxynucleotidyl transferase-mediated dUTP-biotin ni ck end-labeling method (TUNEL). Apoptotic index was calculated as the percentage of positive nuclei in sections stained by TUNEL, Cell proli feration activity was also assessed by argyrophilic staining of the nu cleolar organizer region (AgNOR) and MIB-1 antibody analysis. Twenty b iopsies taken from patients during monitoring of cardiac transplantati on (grade 0 rejection) served as control. Occurrence of apoptosis was correlated with clinical history duration and the presence of acute sy mptoms and signs like angina, pyrexia, erythrocyte sedimentation rate and creatine phosphokinase elevation, as well as ST segment elevation on basal electrocardiogram. Electron microscopy and TUNEL revealed pre sence of apoptotic myocytes in seven cases (35%) with a mean apoptotic index of 24.4 +/- 9.8, The remaining 13 patients and all of the 20 co ntrols were negative both at the electron microscopy and TUNEL. Presen ce of apoptosis appeared to be significantly related to clinical histo ry duration of less than 6 months (P < 0.001) and presence of acute sy mptoms and signs (P = 0.007), AgNOR staining and MIB-1 antibody analys is ruled out cell proliferation activity. In conclusion, apoptosis is present in endomyocardial biopsies of patients with ARVC, especially i n the early symptomatic phase of disease. Myocardial destruction with replacement by fat may be episodic rather than gradual and continuous.