Abstract
BackgroundThe risk of sudden cardiac death (SCD) is known to be dynamic. However, the accuracy of a dynamic SCD prediction is unknown. We aimed to measure the dynamic predictive accuracy of ECG biomarkers of SCD and competing non-sudden cardiac death (non-SCD).MethodsAtherosclerosis Risk In Community study participants with analyzable ECGs in sinus rhythm were included (n = 15,716; 55% female, 73% white, age 54.2 ± 5.8 y). ECGs of 5 follow-up visits were analyzed. Global electrical heterogeneity and traditional ECG metrics (heart rate, QRS, QTc) were measured. Adjudicated SCD was the primary outcome; non-SCD was the competing outcome. Time-dependent area under the receiver operating characteristic curve (ROC(t) AUC) analysis was performed to assess the prediction accuracy of a continuous biomarker in a period of 3,6,9 months, and 1,2,3,5,10, and 15 years using a survival analysis framework. Reclassification improvement as compared to clinical risk factors (age, sex, race, diabetes, hypertension, coronary heart disease, stroke) was measured.ResultsOver a median 24.4 y follow-up, there were 577 SCDs (incidence 1.76 (95%CI 1.63–1.91)/1000 person-years), and 829 non-SCDs [2.55 (95%CI 2.37–2.71)]. No ECG biomarkers predicted SCD within 3 months after ECG recording. Within 6 months, spatial ventricular gradient (SVG) elevation predicted SCD (AUC 0.706; 95%CI 0.526–0.886), but not a non-SCD (AUC 0.527; 95%CI 0.303–0.75). SVG elevation more accurately predicted SCD if the ECG was recorded 6 months before SCD (AUC 0.706; 95%CI 0.526–0.886) than 2 years before SCD (AUC 0.608; 95%CI 0.515–0.701). Within the first 3 months after ECG recording, only SVG azimuth improved reclassification of the risk beyond clinical risk factors: 18% of SCD events were reclassified from low or intermediate risk to a high-risk category. QRS-T angle was the strongest long-term predictor of SCD (AUC 0.710; 95%CI 0.668–0.753 for ECG recorded within 10 years before SCD).ConclusionShort-term and long-term predictive accuracy of ECG biomarkers of SCD differed, reflecting differences in transient vs. persistent SCD substrates. The dynamic predictive accuracy of ECG biomarkers should be considered for competing SCD risk scores. The distinction between markers predicting short-term and long-term events may represent the difference between markers heralding SCD (triggers or transient substrates) versus markers identifying persistent substrate.
Highlights
The risk of sudden cardiac death (SCD) is known to be dynamic
Long-term, QRS-T angle was the strongest predictor of SCD (AUC 0.710; 95%CI 0.668-0.753 for ECG recorded within 10 years before SCD)
The distinction between markers predicting short-term and long-term events may represent the difference between markers heralding SCD versus markers identifying persistent substrate
Summary
The risk of sudden cardiac death (SCD) is known to be dynamic. the accuracy of a dynamic SCD prediction is unknown. We aimed to measure the dynamic predictive accuracy of ECG biomarkers of SCD and competing nonsudden cardiac death (non-SCD). Our group recently showed that global electrical heterogeneity (GEH), as measured by five metrics [spatial QRS-T angle, spatial ventricular gradient (SVG) azimuth, elevation, and magnitude, and sum absolute QRST integral (SAI QRST)] is independently (after comprehensive adjustment for time-updated CVD events and their risk factors) associated with SCD, representing an underlying substrate of SCD.[4] The subsequent discovery of 10 genetic loci, associated with GEH at a genome-wide significance level, confirmed the presence of several underlying mechanisms behind the GEH ECG phenotype.[5] We developed a competing risk score of SCD and showed that the addition of GEH measures to clinical risk factors significantly improves the reclassification of SCD risk.[4]
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