Proband status (HR 7.7; 95% CI 2.8-22.5), ≥3 T-wave inversions (HR 4.2), and male sex (HR 1.8) independently predicted first arrhythmic events in ARVD/C mutation carriers.
Cohort (n=215)
Pedigree evaluation, ECG, and Holter examination provide comprehensive arrhythmic risk stratification in patients with ARVD/C-associated mutations, with proband status, ≥3 T-wave inversions, and male sex as independent predictors.
Hazard Ratio: 7.7 (95% CI 2.8–22.5)
p-value: p=<0.001
BACKGROUND: We investigated the role of phenotypic characteristics in stratifying the risk of sustained ventricular arrhythmias in patients harboring arrhythmogenic right ventricular dysplasia/cardiomyopathy-associated mutations. METHODS AND RESULTS: Clinical, electrocardiographic, and arrhythmic outcome (composite measure of first occurrence of sustained ventricular tachycardia/resuscitated sudden cardiac death/sudden cardiac death/appropriate implantable cardioverter-defibrillator therapy) data were obtained for 215 patients (104 families; 85% PKP-2). During a mean follow-up of 7 years, 86 (40%) patients experienced the arrhythmic outcome. Event-free survival was significantly lower among probands (P<0.001) and symptomatic (P<0.001) patients. Integration of ECG repolarization and depolarization abnormalities allowed for differential risk categorization. Event-free survival at 5 years for the low-risk ECG group (0-1 T inversions or minor depolarization changes) was 97% versus 81% for the intermediate-risk ECG group (2 T inversions+minor depolarization changes) versus 33% for the high-risk ECG group (≥3 T inversions±major or minor depolarization changes; P<0.001). Incremental arrhythmic risk was seen in patients with increasing premature ventricular complex count on a Holter (P<0.001). Proband status (hazard ratio, 7.7; 95% confidence interval, 2.8-22.5; P<0.001), ≥3 T-wave inversions (hazard ratio, 4.2; 95% confidence interval, 1.2-14.5; P=0.035), and male sex (hazard ratio, 1.8; 95% confidence interval, 1.2-2.8; P=0.004) were independent predictors of the first arrhythmic event on multivariable analysis. CONCLUSIONS: Pedigree evaluation, an ECG, and a Holter examination provide for comprehensive arrhythmic risk stratification in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy-associated mutations. We propose an approach to risk stratification based on these variables.
Bhonsale et al. (2013) conducted a cohort in Arrhythmogenic right ventricular dysplasia/cardiomyopathy-associated desmosomal mutation carriers (n=215). Proband status vs. Non-proband status was evaluated on Composite of first occurrence of sustained ventricular tachycardia, resuscitated sudden cardiac death, sudden cardiac death, or appropriate implantable cardioverter-defibrillator therapy (HR 7.7, 95% CI 2.8-22.5, p=<0.001). Proband status (HR 7.7; 95% CI 2.8-22.5), ≥3 T-wave inversions (HR 4.2), and male sex (HR 1.8) independently predicted first arrhythmic events in ARVD/C mutation carriers.