Morbid anatomy and pathobiology of arrhythmogenic right ventricular cardiomyopathy

Abstract

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a primary heart muscle disease characterized by progressive myocardial atrophy of the right ventricle, with massive fibro-fatty replacement accounting for ventricular electrical instability at risk of severe arrhythmias or even cardiac arrest. The disease was found to be the major cause of sudden death in the young and athlete in the Veneto region, Italy. A familial occurrence with autosomal dominant inheritance was then discovered and the prevalence estimated to be higher than 1 in 5000. Linkage analysis allowed to identify four loci, two mapping to chromosome 14, one to chromosome 1 and one to chromosome 2, suggesting genetic and clinical heterogeneity. The specific gene defects as well as the defective coded proteins have not yet been identified. ARVC was recently included among the cardiomyopathies in the revised WHO classification. Both the etiology and pathogenesis of the disease are still unknown. In particular, the mechanisms leading to progressive loss of myocardium and fibro-fatty replacement are speculative. According to the frequent finding of inflammatory infiltrates at histology, an inflammatory theory has been advanced and infective, toxic or immune mechanisms have been postulated. Recently, myocyte programmed cell death (apoptosis) has been demonstrated both in autoptic and bioptic material, suggesting that recurrent bouts of apoptosis may destroy the myocardium, which is then replaced by fibro-fatty tissue. This evidence may open new avenues not only to understand the disease but also to conceive new diagnostic and therapeutic strategies.