Influence of demographic and behavioral risk factors on cardiovascular mortality in arrhythmogenic cardiomyopathy.

Importance: Arrhythmogenic cardiomyopathy is a leading cause of sudden cardiac death, but its clinical course and the prediction of arrhythmic risk are poorly defined. Objective: To describe the natural history of 301 patients affected by arrhythmogenic cardiomyopathy, exploring the influence of demographic, behavioral and genetic risk factors on disease progression and survival. Design: Retrospective cohort study on consecutive arrhythmogenic cardiomyopathy patients referred to our center between 1999 and 2014. Setting: The study was performed at a tertiary referral center for inherited arrhythmias and cardiomyopathies. Patients were followed with ambulatory care in institutional practice. Participants: The diagnosis of arrhythmogenic cardiomyopathy was confirmed on 163/273 suspected cases referred to our center. Additional 138 patients were identified through familial cascade screening, totaling 301 patients under study. Main Outcome and measures: The primary endpoints of the study were: 1) occurrence of the first life-threatening arrhythmic event (sudden cardiac death, aborted cardiac arrest, appropriate implantable defibrillator shock ); 2) cardiovascular mortality (i.e. death due to sudden death, heart failure or stroke). Results: Over 44±19 years, 73/301 (24%) patients experienced one or more life-threatening arrhythmic events (54 males, 74%) 31/301 (10%) patients died for cardiovascular causes, with a steady increase of risk throughout adult life. Besides a history of arrhythmic syncope or sustained ventricular arrhythmias, participation in strenuous sport (HR 2.10; 95% CI:1.22-3.64; p=0.008) and male gender (HR 2.03; 95% CI:1.16-3.56; p=0.001) were independent predictors of life-threatening arrhythmias. Fifty-three percent of life-threatening arrhythmic events and 71% of cardiovascular deaths occurred in asymptomatic patients: in this subset, participation in strenuous sport remained an independent risk factor for experiencing life-threatening arrhythmic events (HR 6.36; 95% CI:2.06-19.61; p=0.001) and cardiovascular mortality (HR 3.86; 95% CI:1.49-9.99; p=0.005). Conclusions and Relevance: Syncope and ventricular tachycardia increase by three-fold the occurrence of severe arrhythmias indicating the need of a defibrillator in patients with these symptoms. However most life-threatening arrhythmias occur in asymptomatic patients and are associated with male gender and high intensity strenuous exercise. Accordingly, prevention of death among asymptomatic patients requires early detection of affected individuals that should be achieved through screening programs in the population.