Competing Risks for Monomorphic versus Non-Monomorphic Ventricular Arrhythmias in Primary Prevention Implantable Cardioverter Defibrillator Recipients: Global Electrical Heterogeneity and Clinical Outcomes (GEHCO) Study

Background and Aims Ablation of monomorphic ventricular tachycardia (MMVT) has been shown to reduce shock frequency and improve survival. We aimed to compare cause-specific risk factors of MMVT and polymorphic ventricular tachycardia (PVT)/ventricular fibrillation (VF) and to develop predictive models. Methods The multicenter retrospective cohort study included 2,668 patients (age 63.1±13.0 y; 23% female; 78% white; 43% nonischemic cardiomyopathy, left ventricular ejection fraction 28.2±11.1%). Cox models were adjusted for demographic characteristics, heart failure severity and treatment, device programming, and ECG metrics. Global electrical heterogeneity was measured by spatial QRS-T angle (QRSTa), spatial ventricular gradient elevation (SVGel), azimuth, magnitude (SVGmag), and sum absolute QRST integral (SAIQRST). We compared the out-of-sample performance of the lasso and elastic net for Cox proportional hazards and the Fine-Gray competing risk model. Results During a median follow-up of 4 years, 359 patients experienced their first sustained MMVT with appropriate ICD therapy, and 129 patients had their first PVT/VF with appropriate ICD shock. The risk of MMVT was associated with wider QRSTa (HR 1.16; 95%CI 1.01-1.34), larger SVGel (HR 1.17; 95%CI 1.05-1.30), and smaller SVGmag (HR 0.74; 95%CI 0.63-0.86) and SAIQRST (HR 0.84; 95%CI 0.71-0.99). The best-performing 3-year competing risk Fine-Gray model for MMVT (ROC(t)AUC 0.728; 95%CI 0.668-0.788) identified high-risk (> 50%) patients with 75% sensitivity, 65% specificity, and PVT/VF prediction model had ROC(t)AUC 0.915 (95%CI 0.868-0.962), both satisfactory calibration. Conclusion We developed and validated models to predict the competing risks of MMVT or PVT/VF that could inform procedural planning and future RCTs of prophylactic VT ablation.