Predicting Arrhythmic Risk in Arrhythmogenic Right Ventricular Cardiomyopathy: A Systematic Review and Meta-Analysis

Laurens P. Bosman, Arjan Sammani, Cynthia A. James, Julia Cadrin-Tourigny, Hugh Calkins, J. Peter van Tintelen, Richard N.W. Hauer, Folkert W. Asselbergs, Anneline S.J.M. te Riele

Heart Rhythm 18. (29 October 2017): S1547-5271.

While many studies evaluate predictors of ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy (ARVC), a systematic review consolidating this evidence is currently lacking. Therefore, we searched MEDLINE and Embase for studies analyzing predictors of ventricular arrhythmias (sustained ventricular tachycardia/fibrillation (VT/VF), appropriate implantable cardioverter-defibrillator therapy, or sudden cardiac death) in patients with definite ARVC, patients with borderline ARVC, and ARVC-associated mutation carriers. In the case of multiple publications on the same cohort, the study with the largest population was included. This yielded 45 studies with a median cohort size of 70 patients (interquartile range 60 patients) and a median follow-up of 5.0 years (interquartile range 3.5 years). The arrhythmic outcome was observed in 10.6%/y in patients with definite ARVC, 10.0%/y in patients with borderline ARVC, and 3.7%/y in mutation carriers. Predictors of ventricular arrhythmias were population dependent: consistently predictive risk factors in patients with definite ARVC were male sex, syncope, T-wave inversion in lead >V3, right ventricular dysfunction, and prior (non)sustained VT/VF; in patients with borderline ARVC, 2 additional predictors-inducibility during electrophysiology study and strenuous exercise-were identified; and in mutation carriers, all aforementioned predictors as well as ventricular ectopy, multiple ARVC-related pathogenic mutations, left ventricular dysfunction, and palpitations/presyncope determined arrhythmic risk. Most evidence originated from small observational cohort studies, with a moderate quality of evidence. In conclusion, the average risk of ventricular arrhythmia ranged from 3.7 to 10.6%/y depending on the population with ARVC. Male sex, syncope, T-wave inversion in lead >V3, right ventricular dysfunction, and prior (non)sustained VT/VF consistently predict ventricular arrhythmias in all populations with ARVC.