Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia

Abstract

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an inherited heart muscle disease that predominantly affects the right ventricle (RV). It is characterized pathologically by RV myocardial atrophy with fibrofatty replacement and clinically by ventricular electric instability with ventricular tachycardia or ventricular fibrillation that may lead to sudden death, primarily in young people and athletes.1 Later in the disease evolution, progression of RV muscle disease and left ventricular involvement may result in heart failure.2 The condition was initially believed to be a developmental defect of the RV myocardium, leading to the original designation of “dysplasia.” This concept has evolved over the last 25 years into the current perspective of a genetically determined “cardiomyopathy.”3 Clinical diagnosis of ARVC/D is often difficult because of the nonspecific nature of disease features and the broad spectrum of phenotypic manifestations. The advent of the molecular genetic era has provided new insights in understanding the pathophysiology of ARVC/D, showing that it is a desmosomal disease resulting from defective cell adhesion proteins such as plakoglobin, desmoplakin, plakophilin-2, and desmoglein-2.4–7 The availability of molecular testing for mutation screening of disease genes offers the possibility to identify genetically affected individuals. Potential clinical impact of genotype determination includes diagnosis (family screening and preclinical diagnosis); prediction of clinical phenotype (penetrance, gene-specific clinical manifestations); risk stratification (assessment of malignant versus benign mutations); clinical and genetic counseling (restriction of physical activity, family planning); and therapy (prevention of sudden death by implantable cardioverter/defibrillator [ICD]). Articles p 1641 and p 1650 In this issue of Circulation , studies by Dalal et al8 in the United States and van Tintelen et al9 in the Netherlands address the prevalence and clinical expression of mutations in the plakophilin-2 gene ( PKP2 ) in ARVC/D patient populations of comparable size and fulfilling the task force diagnostic criteria. …