cardiovascular disorders
Arrhythmogenic Right Ventricular Cardiomyopathy
Introduction
Arrhythmogenic right ventricular cardiomyopathy (ARVC), also called arrhythmogenic right ventricular dysplasia (ARVD), is a genetic cardiac disorder affecting mainly the right ventricle and causing ventricular tachyarrhythmias and increased risk of sudden death. Symptoms include palpitations, syncope, and cardiac arrest, and with worsening disease, manifestations of right ventricular failure. Diagnosis includes ECG, cardiac imaging, and consensus criteria. Treatment requires limitation of physical exertion, and usually a beta-blocker and an implantable cardioverter-defibrillator (ICD). (See also Overview of Arrhythmogenic Cardiomyopathies and A number of genetic mutations adversely affect the structure and function of the intercalated disk, the structure that connects cardiac myocytes. Most commonly, the mutations affect the component of the disk known as the desmosome (the adhesive intercellular junction that tethers intermediate filaments to cell membranes). Desmosomes help connect cells in tissues that undergo mechanical stress, such as cardiac myocytes. The desmosomal proteins that may be affected include plakophilin, desmoplakin, and desmoglein. When abnormal, these proteins are prone to damage by mechanical stress (eg, from increased cardiac workload as from prolonged exertion). Healing of the damage leads to replacement of myocytes by fibrofatty tissue, predominantly in the triangle between the right ventricular outflow tract, the right ventricular inflow tract, and the right ventricular apex, but sometimes also involving the posterolateral left ventricle. Disease manifestations are the result of both electrophysiologic and structural changes, initially manifesting as ventricular premature beats and ventricular tachyarrhythmias but eventually causing right ventricular structural abnormalities (eg, dilation and thinning), resulting in congestive right ventricular cardiomyopathy. Most commonly, the mutations are inherited with an autosomal dominant pattern with variable penetrance; however, autosomal recessive mutations are known. The incidence of ARVC has regional variation from 1 in 2000 to 1 in 5000. It is thought that sustained, heavy exertion (eg, from endurance athletics) hastens onset and progression of disease. Patients may be asymptomatic, but those who are symptomatic usually present first with ventricular tachycardia (VT), ventricular fibrillation (VF), or sudden death. ARVC is responsible for approximately 10% of sudden deaths in young adults. Ventricular tachyarrhythmias are particularly likely to occur during emotional or physical stress. Atrial Fibrillation and signs of right ventricular systolic failure (eg, dependent edema, ascites) are usually manifestations of advanced disease. 