Arrhythmogenic Cardiomyopathy

Abstract

Arrhythmogenic right ventricular cardiomyopathy (ARVC) (Online Mendelian Inheritance in Man 107970) is a clinically and genetically heterogeneous heart muscle disorder associated with an increased risk of sudden cardiac death, particularly in young persons and athletes.1–3 The pathological hallmark of ARVC consists of progressive (either diffuse or segmental) loss of cardiac myocytes that are replaced by fibrofatty tissue, leading to electric instability with or without impaired mechanical function.4–6 Right ventricular (RV) aneurysms in the so-called “triangle of dysplasia” are considered a pathognomic feature of the disease. With an estimated prevalence of the disease of ≈1:2500 to 1:5000, ARVC can be listed among the rare cardiovascular disorders.6 The first comprehensive clinical description of ARVC was reported in 1982 by Marcus et al7 in adults with ventricular tachyarrhythmias of left bundle branch block (LBBB) morphology. In 1994, an international task force provided standardized criteria to establish the diagnosis of ARVC,8 and these diagnostic criteria have been updated recently to increase sensitivity but with the important requisite of maintaining specificity.9 Onset of clinical symptoms and signs usually occurs in adolescence or young adulthood10 and often is triggered by effort.11 Main clinical features of the disease comprise arrhythmias of RV origin that are commonly associated with syncope or sudden cardiac death, thus underscoring the crucial role of risk stratification to identify patients who require an implantable cardioverter-defibrillator.12 In 1988, a familial background consistent with an autosomal-dominant trait was described in ≈50% of patients with ARVC.13 To date, human genetics studies have identified 12 independent loci and 8 disease genes for this disorder inherited mostly as autosomal-dominant traits with incomplete penetrance and variable expressivity.2,3 Five of the 8 causative genes encode major components of the cardiac desmosomes, namely plakoglobin …