Arrhythmogenic right ventricular cardiomyopathy/dysplasia: a review and update

Abstract

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a predominantly genetically determined and heritable form of cardiomyopathy that is characterized pathologically by the replacement of myocytes by adipose and fibrous tissue and leads to right ventricular failure, arrhythmias, and sudden cardiac death. The estimated prevalence of ARVC/D in the general population ranges from 1 in 2,000 to 1 in 5,000, men are more frequently affected than women, with an approximate ratio of 3:1. ARVC/D can be inherited as an autosomal dominant disease with reduced penetrance and variable expression, autosomal recessive inheritance is also described. There have been 12 genes identified which are linked to ARVC/D, encoding several components of the cardiac desmosome. Dysfunctional desmosomes resulting in defective cell adhesion proteins, such as plakoglobin (JUP), desmoplakin (DSP), plakophilin-2 (PKP-2), and desmoglein-2 (DSG-2) consequently cause loss of electrical coupling between cardiac myocytes, leading to myocyte cell death, fibrofatty replacement and arrhythmias. Diagnosis is based on the finding a combination of characteristic abnormalities in family history, electrocardiography, cardiac imaging as well as endomyocardial biopsy (original task force criteria). Therapeutic options remain limited because of the progressive nature of ARVC/D. Competitive athletics should be avoided. Patients with ARVC/D with a history of having been resuscitated from sudden cardiac death, patients with syncope, very young patients, and those who have marked right ventricular involvement are at the highest risk for arrhythmic death and also, the presence of left ventricular involvement is a risk factor. Several authors concluded that patients who meet the Task Force criteria for ARVC/D are at high risk for sudden cardiac death and should undergo ICD placement for primary and secondary prevention, regardless of electrophysiologic testing results. The role of electrophysiologic study and VT catheter ablation in ARVC/D remains poorly defined, and is frequently used as a palliative measure for patients with refractory VT. The progressive nature of ARVC/D suggests that catheter ablation would not be a long-term curative procedure. Sotalol proved to be highly effective in patients with ARVC/D and inducible as well as non-inducible ventricular tachycardia; if it is ineffective in inducible ventricular tachycardia response to other antiarrhythmic drugs is unlikely and therefore non-pharmacological therapy without further drug testing should be considered. Orthotopic heart transplantation is considered in patients with progressive heart failure and intractable recurrent ventricular arrhythmias.