Ejection fraction and mortality: a nationwide register‐based cohort study of 499 153 women and men
Simon Stewart, David Playford, G. Scalia, Philip J. Currie, David S. Celermajer, David Prior, Jim Codde, Geoff Strange, on behalf of the NEDA Investigators
Abstract
AIMS: We investigated the sex-based risk of mortality across the spectrum of left ventricular ejection fraction (LVEF) in a large cohort of patients in Australia. METHODS AND RESULTS: Quantified levels of LVEF from 237 046 women (48.1%) and 256 109 men undergoing first-time, routine echocardiography (2000-2019) were linked to 119 232 deaths (median 5.6 years of follow-up). Overall, 17.6% of men vs. 8.3% of women had an LVEF <50%. An LVEF <40% was associated with the highest crude cardiovascular-related and all-cause mortality at 5 years (∼20-30% and ∼ 40-50%, respectively). Thereafter, actual cardiovascular-related and all-cause mortality at 5 years in both sexes steeply improved to a nadir LVEF of 65.0-69.9% (reference group). Below this LVEF level, the adjusted hazard ratio (HR) for cardiovascular-related mortality for a LVEF of 55.0-59.9% was 1.36 [95% confidence interval (CI) 1.16-1.59; P < 0.001] in women and 1.21 (95% CI 1.05-1.39; P = 0.008) in men. In women, an LVEF of 60.0-64.9% was also associated with a HR 1.33 (95% CI 1.16-1.52; P < 0.001) for cardiovascular-related mortality. These associations were most striking in women and men aged <65 years and were replicated in those with suspected heart failure (32 403 cases aged 65.2 ± 16.1 years, 57.0% women). For pre-existing heart failure (33 738 cases aged 67.6 ± 16.9 years, 46.5% women), the specific threshold of increased mortality was at and below 50.0-54.9%. CONCLUSIONS: Among patients investigated for suspected or established cardiovascular disease, we found clinically relevant sex-based differences in the distribution and mortality associated with an LVEF <65.0-69.9%. Specifically, they suggest a greater risk of mortality at higher LVEF levels among women.