A U-shaped relationship between left ventricular ejection fraction and risk of worsening heart failure.

AIMS Left ventricular ejection fraction (LVEF) is a key measure of cardiac function. While prior studies showed a U-shaped relationship between LVEF and mortality, its association with worsening heart failure (HF) remains unclear. We aimed to evaluate the association between the full spectrum of LVEF and the risk of worsening HF. METHODS AND RESULTS We analysed data from 93 694 consecutive participants (median age 62 years [interquartile range: 50-76 years], 51.4% men) undergoing echocardiography at a tertiary medical centre. LVEF, measured by biplane Simpson's method, was categorized into 5% intervals from <20% to ≥70%. The primary outcome was a composite of all-cause mortality or worsening HF, while the secondary outcomes included all-cause mortality, cardiovascular death, and worsening HF. The primary outcome occurred in 32 398 (34.6%) participants over a median follow-up of 8.3 years. A U-shaped relationship between LVEF and the primary outcome was observed, with a nadir at 60-70% and an increased risk when LVEF was ≥70% [adjusted hazard ratio (aHR) 1.12; 95% confidence interval (CI) 1.06-1.18]. Similar patterns were observed for the secondary outcomes. Participants with LVEF ≥70% also had a higher risk of worsening HF (aHR 1.13, 95% CI 1.03-1.23). This U-shaped association was consistent across subgroups stratified by age, sex, hypertension, and diabetes, and was observed for both incident and recurrent HF events. CONCLUSIONS Left ventricular ejection fraction demonstrated a U-shaped association with worsening HF, with the lowest risk at 60-70%. Supranormal LVEF (≥70%) identified a high-risk phenotype, underscoring the need for tailored management strategies for this subgroup.