Arrhythmogenic right ventricular dysplasia/cardiomyopathy: clinical challenges in a changing disease spectrum

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited cardiomyopathy characterized by fibro-fatty replacement of predominantly the right ventricle (RV), which predisposes patients to life-threatening ventricular arrhythmias and usually slowly progressive ventricular dysfunction. The disease is inherited as an autosomal dominant trait with incomplete penetrance and variable expressivity. Increased appreciation of ARVD/C as a "disease of the desmosome" has fueled research into possible disease mechanisms, and insights into ARVD/C pathogenesis are rapidly advancing. Although ARVD/C is known to preferentially affect the RV, early and/or predominant left ventricular involvement is increasingly recognized. Diagnosis is made by combining multiple sources of diagnostic information as prescribed by the consensus-based Task Force criteria. Affected individuals typically present in the third to fifth decade of life with palpitations, lightheadedness, or syncope due to frequent ventricular ectopy or arrhythmias originating from the RV. However, disease expression is highly variable, even among subjects from the same family or those carrying the same mutation. Since sudden cardiac death can be the first manifestation of the disease, optimizing the approach to early detection and risk stratification of ARVD/C is of utmost importance. This review will discuss the changing spectrum of ARVD/C based on recent advances in diagnosis, genetics, and improved understanding of disease pathophysiology.