Competing risks of monomorphic vs. non-monomorphic ventricular arrhythmias in primary prevention implantable cardioverter-defibrillator recipients: Global Electrical Heterogeneity and Clinical Outcomes (GEHCO) study

Abstract

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 for MMVT and polymorphic ventricular tachycardia (PVT)/ventricular fibrillation (VF) and to develop predictive models.

Methods and results: The multicentre retrospective cohort study included 2668 patients (age 63.1 ± 13.0 years; 23% female; 78% white; 43% non-ischaemic cardiomyopathy; left ventricular ejection fraction 28.2 ± 11.1%). Cox models were adjusted for demographic characteristics, heart failure severity and treatment, device programming, and electrocardiogram 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. During a median follow-up of 4 years, 359 patients experienced their first sustained MMVT with appropriate implantable cardioverter-defibrillator (ICD) therapy, and 129 patients had their first PVT/VF with appropriate ICD shock. The risk of MMVT was associated with wider QRSTa [hazard ratio (HR) 1.16; 95% confidence interval (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 [time-dependent area under the receiver operating characteristic curve (ROC(t)AUC) 0.728; 95% CI 0.668-0.788] identified high-risk (> 50%) patients with 75% sensitivity and 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 randomized controlled trials of prophylactic ventricular tachycardia ablation.

Clinical trial registration: URL:www.clinicaltrials.gov Unique identifier:NCT03210883.

Keywords: HF; ICD; MMVT; PVT/VF; VCG.

Graphical abstract

Figure 1

Characteristics of the study population according to tertiles of GEH metrics. The darker shade orange color indicates a rising trend across the tertiles. The darker shade green color shows a falling trend across the tertiles. AADs, antiarrhythmic drug; BUN, blood urea nitrogen; CI, confidence interval; CRT-D, cardiac resynchronization therapy defibrillator; eGFR, estimated glomerular filtration rate; GEH, global electrical heterogeneity; ICD, implantable cardioverter–defibrillator; LVEF, left ventricular ejection fraction; NICM, non-ischaemic cardiomyopathy; SAIQRST, sum absolute QRST integral; SVG, spatial ventricular gradient.

Figure 2

The proportion of patients with (A) MMVT and (B) PVT/VF outcome according to tertiles of GEH variables. The mean proportion of patients with each outcome is shown according to tertile 1 (square), tertile 2 (circle), and tertile 3 (triangle). Whiskers indicate a 95% CI. CI, confidence interval; GEH, global electrical heterogeneity; MMVT, monomorphic ventricular tachycardia; PVT, polymorphic ventricular tachycardia; SAIQRST, sum absolute QRST integral; SVG, spatial ventricular gradient; VF, ventricular fibrillation.

Figure 3

Adjusted (model 4) cause-specific Cox HRs for sustained MMVT with appropriate ICD therapies (squares) and sustained PVT/VF with appropriate ICD shocks (circles) with 95% CIs (shown by whiskers). Red labels highlight statistically significant differences (P < 0.05) between HRs. AAD, antiarrhythmic drug; CI, confidence intervals; HRs, hazard ratios; ICD, implantable cardioverter–defibrillator; ICM, infarct-related cardiomyopathy; LVEF, left ventricular ejection fraction; MMVT, monomorphic ventricular tachycardia; NICM, non-ischaemic cardiomyopathy; PVT, polymorphic ventricular tachycardia; SAIQRST, sum absolute QRST integral; SD, standard deviation; SVG, spatial ventricular gradient; VF, ventricular fibrillation; VT, ventricular tachycardia.

Figure 4

Importance of predictors ranking for (A) MMVT and (B) PVT/VF based on the IPA for each predictor. ACEI, angiotensin-converting enzyme inhibitors; AAD, antiarrhythmic drug; AF, atrial fibrillation; ARB, angiotensin 2 receptor blockers; eGFR, estimated glomerular filtration rate; ICD, implantable cardioverter–defibrillator; IPA, index of predictive accuracy; LVEF, left ventricular ejection fraction; MI, myocardial infarction; MMVT, monomorphic ventricular tachycardia; PVT, polymorphic ventricular tachycardia; SAIQRST, sum absolute QRST integral; SVG, spatial ventricular gradient; VF, ventricular fibrillation; VP, ventricular pacing; VT, ventricular tachycardia.

Figure 5

Observed percent of patients with MMVT (blue), PVT/VF (red), undefined VT/VF (green), death without VT/VF (indigo) competing outcomes, and those who were censored (yellow) across deciles of predicted risk of MMVT (A) and PVT/VF (B). MMVT, monomorphic ventricular tachycardia; PVT, polymorphic ventricular tachycardia; VF, ventricular fibrillation; VT, ventricular tachycardia.

Figure 6

Predicted probabilities and observed cumulative incidence fraction of (A) MMVT and (B) PVT/VF presented as non-linear calibration curves. CIF, cumulative incidence fraction; MMVT, monomorphic ventricular tachycardia; PVT, polymorphic ventricular tachycardia; VF, ventricular fibrillation.