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

While many studies evaluate predictors for 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 for ventricular arrhythmias (sustained ventricular tachycardia/fibrillation (VT/VF), appropriate implantable cardioverter-defibrillator therapy, or sudden cardiac death) in definite ARVC patients, borderline ARVC patients, and ARVC-associated mutation carriers. In 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 (IQR 60) patients and 5.0 (IQR 3.5) years follow-up. The arrhythmic outcome was observed in 10.6%/year in definite ARVC patients, 10.0%/year in borderline ARVC patients, and 3.7%/year in mutation carriers. Predictors for ventricular arrhythmias were population-dependent: consistently predictive risk factors in definite ARVC patients were male sex, syncope, T-wave inversion >V3, right ventricular (RV) dysfunction, and prior (non)sustained VT/VF; in borderline ARVC patients, two additional predictors (inducibility at 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/pre-syncope 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%/year depending on the ARVC population. Male sex, syncope, T-wave inversion >V3, RV dysfunction, and prior (non)sustained VT/VF consistently predict ventricular arrhythmias in all ARVC population