Abstract 13695: Global Electrical Heterogeneity Risk Score Predicts Sudden Cardiac Death in the General Population

Abstract

Background: The majority of sudden cardiac deaths (SCDs) in the general population occur in asymptomatic individuals. Our goal was to develop and validate a SCD risk score for use in the general population. Methods: The prospective Atherosclerosis Risk in Communities (ARIC) study [n=15,366; age 45-64 yr; 45% male; 73% white; 5% prevalent coronary heart disease (CHD), median 14 yrs of follow-up] was used for risk score development. ECG markers of global electrical heterogeneity (GEH) [sum absolute QRST integral (SAI QRST), spatial ventricular gradient (SVG), and spatial QRS-T angle] were measured on standard 12-lead ECGs and abnormal values were derived using the Youden index. Competing risk models were evaluated using C-statistics, integrated discrimination improvement, net reclassification improvement (NRI), and Akaike Information Criterion. Internal cross-validation was performed in 5 partitions. Adjudicated SCD was the primary outcome. Results: Overall SCD incidence was 1.51 (95% CI 1.35-1.69) per 1,000 person-yrs. The most accurate risk model included gender-, race-, and CHD-specific GEH ECG parameters [SAI QRST, spatial QRS-T angle, and SVG direction (azimuth and elevation)], demographics (sex, race, age≥55 y), clinical characteristics (CHD, diabetes, hypertension, stroke), QTc interval, and 1 interaction term (abnormal SVG azimuth in age≥55 yrs). C-statistic was 0.842 (95% CI 0.814-0.859) in the whole cohort and ranged 0.782-0.866 in 5 cross-validation partitions. The risk score classified 10-yr SCD risk as low (0 to <1%), intermediate (1-10%), and high (>10%) in 65.5%, 32.3%, and 2.2% of participants, respectively. With addition of GEH ECG markers to clinical/demographic factors C-statistic increased from 0.813 to 0.837 (p=0.004), 28/311 (9%) of participants were appropriately reclassified from intermediate to high risk, and only 4/311 (1.3%) were inappropriately reclassified from high to intermediate risk. NRI was 13.3% (P<0.001). The score was highly specific (98.2%) for SCD, and predicted SCD better than non-sudden cardiac death. Negative predictive value for SCD was up to 99.5%. Conclusion A risk score using basic clinical characteristics and novel GEH ECG parameters accurately predicted SCD in the general population.