Dynamic Predictive Accuracy of Electrocardiographic Biomarkers of Sudden Cardiac Death within a Survival Framework: The Atherosclerosis Risk in Communities (ARIC) study

Background The risk of sudden cardiac death (SCD) is known to be dynamic. However, an accuracy of a dynamic SCD prediction, and “expiration date” of ECG biomarkers is unknown. Our goal was to measure dynamic predictive accuracy of ECG biomarkers of SCD and competing outcomes. Methods Atherosclerosis Risk In Community study participants with analyzable digital ECGs were included (n=15,768; 55% female, 73% white, age 54.2±5.8 y). ECGs of 5 follow-up visits were analyzed. Global electrical heterogeneity (GEH) and traditional ECG metrics were measured. Adjudicated SCD served as the primary outcome; non-sudden cardiac death served as competing outcome. Time-dependent area under the (receiver operating characteristic) curve (AUC) analysis was performed to assess prediction accuracy of a continuous biomarker in a period of 3,6,9 months, and 1,2,3,5,10, and 15 years, using survival analysis framework. Results Over a median 24.4 y follow-up, there were 581 SCDs (incidence 1.77 (95%CI 1.63-1.92)/1,000 person-years), and 838 nonSCDs [2.55 (95%CI 2.39-2.73)]. Resting heart rate was the strongest (AUC 0.930) short-term (3-month) non-specific SCD predictor, whereas spatial peak QRS-T angle predicted specifically SCD 15 years after ECG recording (AUC 0.719). QRS duration (AUC 0.885) and QTc (AUC 0.711) short-term predicted advanced structural heart disease better than SCD. “Expiration date” for most ECG biomarkers was two years after ECG recording. GEH significantly improved reclassification of SCD risk beyond age, sex, race, diabetes, hypertension, coronary heart disease and stroke. Conclusion Short-term predictors of SCD, nonSCD, and biomarkers of long-term SCD risk differed, reflecting differences in transient vs. persistent SCD substrates.