Simple electrocardiographic measures improve sudden arrhythmic death prediction in coronary disease.

AIMS: To determine whether the combination of standard electrocardiographic (ECG) markers reflecting domains of arrhythmic risk improves sudden and/or arrhythmic death (SAD) risk stratification in patients with coronary heart disease (CHD). METHODS AND RESULTS: The association between ECG markers and SAD was examined in a derivation cohort (PREDETERMINE; N = 5462) with adjustment for clinical risk factors, left ventricular ejection fraction (LVEF), and competing risk. Competing outcome models assessed the differential association of ECG markers with SAD and competing mortality. The predictive value of a derived ECG score was then validated (ARTEMIS; N = 1900). In the derivation cohort, the 5-year cumulative incidence of SAD was 1.5% [95% confidence interval (CI) 1.1-1.9] and 6.2% (95% CI 4.5-8.3) in those with a low- and high-risk ECG score, respectively (P for Δ < 0.001). A high-risk ECG score was more strongly associated with SAD than non-SAD mortality (adjusted hazard ratios = 2.87 vs. 1.38 respectively; P for Δ = 0.003) and the proportion of deaths due to SAD was greater in the high vs. low risk groups (24.9% vs. 16.5%, P for Δ = 0.03). Similar findings were observed in the validation cohort. The addition of ECG markers to a clinical risk factor model inclusive of LVEF improved indices of discrimination and reclassification in both derivation and validation cohorts, including correct reclassification of 28% of patients in the validation cohort [net reclassification improvement 28 (7-49%), P = 0.009]. CONCLUSION: For patients with CHD, an externally validated ECG score enriched for both absolute and proportional SAD risk and significantly improved risk stratification compared to standard clinical risk factors including LVEF. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT01114269. ClinicalTrials.gov ID NCT01114269.

Sudden Death in Patients With Coronary Heart Disease Without Severe Systolic Dysfunction.

Importance: The majority of sudden and/or arrhythmic deaths (SAD) in patients with coronary heart disease occur in those without severe systolic dysfunction, for whom strategies for sudden death prevention are lacking. Objective: To provide contemporary estimates of SAD vs other competing causes of death in patients with coronary heart disease without severe systolic dysfunction to search for high-risk subgroups that might be targeted in future trials of SAD prevention. Design, Setting, and Participants: This prospective observational cohort study included 135 clinical sites in the United States and Canada. A total of 5761 participants with coronary heart disease who did not qualify for primary prevention implantable cardioverter defibrillator therapy based on left ventricular ejection fraction (LVEF) of more than 35% or New York Heart Association (NYHA) heart failure class (LVEF >30%, NYHA I). Exposures: Clinical risk factors measured at baseline including age, LVEF, and NYHA heart failure class. Main Outcomes and Measures: Primary outcome of SAD, which is a composite of SAD and resuscitated ventricular fibrillation arrest. Results: The mean (SD) age of the cohort was 64 (11) years. During a median of 3.9 years, the cumulative incidence of SAD and non-SAD was 2.1% and 7.7%, respectively. Sudden and/or arrhythmic death was the most common mode of cardiovascular death accounting for 114 of 202 cardiac deaths (56%), although noncardiac death was the primary mode of death in this population. The 4-year cumulative incidence of SAD was lowest in those with an LVEF of more than 60% (1.0%) and highest among those with LVEF of 30% to 40% (4.9%) and class III/IV heart failure (5.1%); however, the cumulative incidence of non-SAD was similarly elevated in these latter high-risk subgroups. Patients with a moderately reduced LVEF (40%-49%) were more likely to die of SAD, whereas those with class II heart failure and advancing age were more likely to die of non-SAD. The proportion of deaths due to SAD varied widely, from 14% (18 of 131 deaths) in patients with NYHA II to 49% (37 of 76 deaths) in those younger than 60 years. Conclusions and Relevance: In a contemporary population of patients with coronary heart disease without severe systolic dysfunction, SAD accounts for a significant proportion of overall mortality. Moderately reduced LVEF, age, and NYHA class distinguished SAD and non-SAD, whereas other markers were equally associated with both modes of death. Absolute and proportional risk of SAD varied significantly across clinical subgroups, and both will need to be maximized in future risk stratification efforts.