Electrocardiographic Markers and Left Ventricular Ejection Fraction Have Cumulative Effects on Risk of Sudden Cardiac Death

Abstract

ObjectivesThis study assessed potential improvement in predicting risk of sudden cardiac death (SCD) by adding selected risk markers from the 12-lead electrocardiogram (ECG) to the measurement of left ventricular ejection fraction (LVEF). BackgroundNovel strategies to improve risk stratification for SCD are needed. Given the modest odds associated with most individual risk markers, combining multiple markers may be a useful approach. MethodsFrom the ongoing Oregon Sudden Unexpected Death Study, SCD cases with pre-event LVEF data available were compared with those of matched control subjects with coronary artery disease. Resting heart rate, QRS duration (QRSD), and JTc intervals were measured from archived ECGs prior to and unrelated to the SCD event. Independent odds of SCD for individual and combined ECG markers were calculated. ResultsSCD cases (n = 317; 67.9 ± 12.9 years of age) were more likely than controls (n = 317; 67.9 ± 12.8 years of age) to have LVEF ≤35% (26% vs. 11%, respectively). Mean heart rate, QRSD, and JTc were significantly higher in cases (all p < 0.0001). In adjusted analyses, higher heart rate (odds ratio [OR]: 2.6 [95% confidence interval [CI]: 1.8 to 3.7]), QRSD (OR: 1.5 [95% CI: 1.0 to 2.5]), and JTc (OR: 2.3 [95% CI: 1.6 to 3.4]) were independently associated with SCD. When ECG markers were combined, SCD odds progressively increased with 1 (OR: 3.4 [95% CI: 2.1 to 5.4]) and ≥2 elevated markers (OR: 6.3 [95% CI: 3.3 to 12.1]). Addition of ECG markers to an adjusted model with LVEF improved discrimination (C statistic improved from 0.642 to 0.724) and net reclassification (by 22.7%; p < 0.0001). ConclusionsCombining selected 12-lead ECG markers with LVEF improves SCD risk prediction and warrants further investigation in prospective studies.