Competing risks in patients with primary prevention implantable cardioverter-defibrillators: Global Electrical Heterogeneity and Clinical Outcomes study

Abstract

Background: Global electrical heterogeneity (GEH) is associated with sudden cardiac death in the general population. Its utility in patients with systolic heart failure who are candidates for primary prevention (PP) implantable cardioverter-defibrillators (ICDs) is unclear.

Objective: The purpose of this study was to investigate whether GEH is associated with sustained ventricular tachycardia/ventricular fibrillation leading to appropriate ICD therapies in patients with heart failure and PP ICDs.

Methods: We conducted a multicenter retrospective cohort study. GEH was measured by spatial ventricular gradient (SVG) direction (azimuth and elevation) and magnitude, QRS-T angle, and sum absolute QRST integral on preimplant 12-lead electrocardiograms. Survival analysis using cause-specific hazard functions compared the strength of associations with 2 competing outcomes: sustained ventricular tachycardia/ventricular fibrillation leading to appropriate ICD therapies and all-cause death without appropriate ICD therapies.

Results: We analyzed 2668 patients (mean age 63 ± 12 years; 624 (23%) female; 78% white; 43% nonischemic cardiomyopathy; left ventricular ejection fraction 28% ± 11% from 6 academic medical centers). After adjustment for demographic, clinical, device, and traditional electrocardiographic characteristics, SVG elevation (hazard ratio [HR] per 1SD 1.14; 95% confidence interval [CI] 1.04-1.25; P = .004), SVG azimuth (HR per 1SD 1.12; 95% CI 1.01-1.24; P = .039), SVG magnitude (HR per 1SD 0.75; 95% CI 0.66-0.85; P < .0001), and QRS-T angle (HR per 1SD 1.21; 95% CI 1.08-1.36; P = .001) were associated with appropriate ICD therapies. Sum absolute QRST integral had different associations in infarct-related cardiomyopathy (HR 1.29; 95% CI 1.04-1.60) and nonischemic cardiomyopathy (HR 0.78; 95% CI 0.62-0.96) (P_interaction = .022).

Conclusion: In patients with PP ICDs, GEH is independently associated with appropriate ICD therapies. The SVG vector points in distinctly different directions in patients with 2 competing outcomes.

Keywords: Competing risk; Global electrical heterogeneity; Heart failure; Implantable cardioverter-defibrillators; Ventricular tachycardia/Ventricular fibrillation.

Figure 1.

GEH measurements.

Figure 2.

Study flowchart.

Figure 3.

Statistically significantly different (P<0.05) or similar (P≥0.05) adjusted (model 3) cause-specific Cox HR(95% CI) of two competing outcomes: sustained VT/VF with appropriate ICD therapies (red ovals) and all-cause death without appropriate ICD therapies (blue rectangles).

Figure 4.

Adjusted (model 1) risk of (A) sustained VT/VF with appropriate ICD therapy and (B) competing death without appropriate ICD therapy associated with peak SVG azimuth. Restricted cubic spline with 95% CI shows a change in cause-specific Cox HR (Y-axis) in response to peak SVG azimuth change (X-axis). The 50^th percentile of the SVG azimuth is a reference. Knots of the peak SVG azimuth are at (-21)-42-75-137 degrees.

Figure 5.

Adjusted (model 1) risk of sustained VT/VF with appropriate ICD therapy associated with SAIQRST in ICM (A) and NICM (B). Restricted cubic spline with 95% CI shows a change in cause-specific Cox HR (Y-axis) in response to SAIQRST change (X-axis). The 50^th percentile of the SAIQRST is a reference. Knots of the SAIQRST in ICM are at 74-127-186-372 mVms, and in NICM are at 80-146-242-462 mVms.