Implantable Cardioverter-Defibrillator Therapy in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy: Predictors of Appropriate Therapy, Outcomes, and Complications

Abstract

Background: Arrhythmogenic right ventricular dysplasia/cardiomyopathy is characterized by ventricular arrhythmias and sudden cardiac death. Once the diagnosis is established, risk stratification to determine whether implantable cardioverter-defibrillator (ICD) placement is warranted is critical.

Methods and results: The cohort included 312 patients (163 men, age at presentation 33.6±13.9 years) with definite arrhythmogenic right ventricular dysplasia/cardiomyopathy who received an ICD. Over 8.8±7.33 years, 186 participants (60%) had appropriate ICD therapy and 58 (19%) had an intervention for ventricular fibrillation/flutter. Ventricular tachycardia at presentation (hazard ratio [HR]: 1.86; 95% confidence interval [CI], 1.38-2.49; P<0.001), inducibility on electrophysiology study (HR: 3.14; 95% CI, 1.95-5.05; P<0.001), male sex (HR: 1.62; 95% CI, 1.20-2.19; P=0.001), inverted T waves in ≥3 precordial leads (HR: 1.66; 95% CI, 1.09-2.52; P=0.018), and premature ventricular contraction count ≥1000/24 hours (HR: 2.30; 95% CI, 1.32-4.00; P=0.003) were predictors of any appropriate ICD therapy. Inducibility at electrophysiology study (HR: 2.28; 95% CI, 1.10-4.70; P=0.025) remained as the only predictor after multivariable analysis. The predictors for ventricular fibrillation/flutter were premature ventricular contraction ≥1000/24 hours (HR: 4.39; 95% CI, 1.32-14.61; P=0.016), syncope (HR: 1.85; 95% CI, 1.10-3.11; P=0.021), aged ≤30 years at presentation (HR: 1.76; 95% CI, 1.04-3.00; P<0.036), and male sex (HR: 1.73; 95% CI, 1.01-2.97; P=0.046). Younger age at presentation (HR: 3.14; 95% CI, 1.32-7.48; P=0.010) and high premature ventricular contraction burden (HR: 4.43; 95% CI, 1.35-14.57; P<0.014) remained as independent predictors of ventricular fibrillation/flutter. Complications occurred in 66 participants (21%), and 64 (21%) had inappropriate ICD interventions. Overall mortality was low at 2%, and 4% underwent heart transplantation.

Conclusion: These findings represent an important step in identifying predictors of ICD therapy for potentially fatal ventricular fibrillation/flutter and should be considered when developing a risk stratification model for arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Keywords: arrhythmogenic right ventricular cardiomyopathy/dysplasia; implantable cardioverter defibrillator; sudden cardiac death; tachyarrhythmias; ventricular fibrillation.

Figure 1

Appropriate ICD therapy in arrhythmogenic right ventricular dysplasia/cardiomyopathy patients. Kaplan–Meier analysis of cumulative survival free from any appropriate ICD interventions (A) and from ICD intervention for VF/VFL (B). ICD indicates implantable cardioverter‐defibrillator; VF/VFL, ventricular fibrillation/flutter.

Figure 2

Cumulative survival from first appropriate ICD intervention (VT/VF) stratified by inducibility on EPS (A), sex (B), number of TWIs (C), PVCs on Holter monitor (D), history of VT at presentation (E), and primary vs secondary prevention (VT/VF) (F). EPS indicates electrophysiology study; ICD, implantable cardioverter‐defibrillator; PVC, premature ventricular contraction; TWI, T‐wave inversion; VT/VF, ventricular tachycardia/ventricular fibrillation.

Figure 3

Cumulative survival from ICD intervention for VF/VFL (cycle length ≤240 ms) stratified by sex (A), PVCs on Holter monitor (B), syncope (C), age at presentation (D), history of VT at presentation (E), and primary vs secondary prevention (VT/VF) (F). ICD indicates implantable cardioverter defibrillator; PVC, premature ventricular contraction; VF/VFL, ventricular fibrillation/flutter; VT/VF, ventricular tachycardia/ventricular fibrillation.