Arrhythmogenic Right Ventricular Cardiomyopathy: Clinical Course and Predictors of Arrhythmic Risk

J Am Coll Cardiol. 2016 Dec 13;68(23):2540-2550. doi: 10.1016/j.jacc.2016.09.951.


Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a leading cause of sudden cardiac death, but its progression over time and predictors of arrhythmias are still being defined.

Objectives: This study sought to describe the clinical course of ARVC and occurrence of life-threatening arrhythmic events (LAE) and cardiovascular mortality; identify risk factors associated with increased LAE risk; and define the response to therapy.

Methods: We determined the clinical course of 301 consecutive patients with ARVC using the Kaplan-Meier method adjusted to avoid the bias of delayed entry. Predictors of LAE over 5.8 years of follow-up were determined with Cox multivariable analysis. Treatment efficacy was assessed comparing LAE rates during matched time intervals.

Results: A first LAE occurred in 1.5 per 100 person-years between birth and age 20 years, in 4.0 per 100 person-years between ages 21 and 40 years, and in 2.4 per 100 person-years between ages 41 and 60 years. Cumulative probability of a first LAE at follow-up was 14% at 5 years, 23% at 10 years, and 30% at 15 years. Higher risk of LAE was predicted by atrial fibrillation (hazard ratio [HR]: 4.38; p = 0.002), syncope (HR: 3.36; p < 0.001), participation in strenuous exercise after the diagnosis (HR: 2.98; p = 0.028), hemodynamically tolerated sustained monomorphic ventricular tachycardia (HR: 2.19; p = 0.023), and male sex (HR: 2.49; p = 0.012). No difference was observed in the occurrence of LAE before and after treatment with amiodarone, beta-blockers, sotalol, or ablation. A total of 81 patients received an implantable cardioverter-defibrillator, 34 were successfully defibrillated.

Conclusions: The high risk of life-threatening arrhythmias in patients with ARVC spans from adolescence to advanced age, reaching its peak between ages 21 and 40 years. Atrial fibrillation, syncope, participation in strenuous exercise after the diagnosis of ARVC, hemodynamically tolerated sustained monomorphic ventricular tachycardia, and male sex predicted lethal arrhythmias at follow-up. The lack of efficacy of antiarrhythmic therapy and the life-saving role of the implantable cardioverter-defibrillator highlight the importance of risk stratification for patient management.

Keywords: athletes; genetics; implantable cardioverter-defibrillator; sudden cardiac death; ventricular tachycardia.

MeSH terms

  • Adolescent
  • Adult
  • Arrhythmogenic Right Ventricular Dysplasia / complications
  • Arrhythmogenic Right Ventricular Dysplasia / diagnosis*
  • Arrhythmogenic Right Ventricular Dysplasia / epidemiology
  • Child
  • Child, Preschool
  • Death, Sudden, Cardiac / epidemiology
  • Death, Sudden, Cardiac / etiology*
  • Death, Sudden, Cardiac / prevention & control
  • Defibrillators, Implantable
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Infant
  • Infant, Newborn
  • Italy / epidemiology
  • Male
  • Middle Aged
  • Retrospective Studies
  • Risk Assessment / methods*
  • Risk Factors
  • Survival Rate / trends
  • Time Factors
  • Young Adult