Prevention of sudden cardiac deaths in arrhythmogenic right ventricular cardiomyopathy: how to evaluate risk and when to implant a cardioverter-defibrillator?

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically determined myocardial disease resulting in fibrofatty degeneration of myocardium. Most known mutations associated with the development of this disease affect genes responsible for coding information on desmosomal proteins. The primary function of these proteins is to form intercellular junctions. Disruption of desmosomes invariably leads to cell death, and resulting tissue remodeling impairs electrical conduction creating conditions for re-entry. The natural history of ARVC involves three clinical stages [1, 2]: — initial asymptomatic phase; — focal structural changes with electrical instability; — global impairment of contractility with symptomatic heart failure. The incidence of ARVC is estimated at 1:5,000 to 1:10,000. The disease usually manifests at young age, mostly in the second or third decade of life. Patients present with ventricular arrhythmia followed later by symptoms of heart failure. Cardiac arrest may also be an initial presentation. Studies show that ARVC is one of the most common causes of sudden cardiac death in young, apparently healthy people, accounting for 5–11% of sudden deaths in subjects below 35 years of age [3]. The disease is more common among men, although gender seems not to affect the risk of sudden cardiac death. Most fatal cases occur in the fourth decade of life (mean age 35.5 ± 12.0 years), and yearly mortality rate is about 2.8%, with 1/3 of deaths occuring suddenly and the remaining 2/3 due to advanced heart failure [4]. ARVC is also one of the most common causes of sudden deaths during sport participation. According to some authors, up to 22% of sudden deaths among athletes may be related to this form of cardiomyopathy. Studies performed in the 1980s in a large population of competitive athletes in Italy showed that intensive physicial training is associated with a 5-fold increase in risk of a sudden cardiac death. Sudden deaths in ARVC usually occur during daily life activities (76% of cases), stressful situations (10%) or in the perioperative period (10%). Only 3.5% of deaths occur during intensive physical activity, which is likely related to a limited number of subjects participating in competitive sports [3].