The association of left ventricular ejection fraction, mortality, and cause of death in stable outpatients with heart failure

The aim of this study was to assess the prognostic importance of left ventricular ejection fraction (LVEF) in stable outpatients with heart failure (HF). Although LVEF is an accepted prognostic indicator of prognosis in HF patients, the relationship of LVEF and mortality across the full spectrum of LVEF is incompletely understood. We examined the association of LVEF and outcomes among 7,788 stable HF patients enrolled in the Digitalis Investigation Group trial. During mean follow-up of 37 months, mortality was substantial in all LVEF groups (range, LVEF ≤ 15%, 51.7%, LVEF > 55%, 23.5%). Among patients with LVEF ≤ 45%, mortality decreased in a near linear fashion across successively higher LVEF groups (LVEF < 15%, 51.7%; LVEF 36% to 45%, 25.6%; p < 0.0001). This association was present after multivariable adjustment, although the magnitude of this associated risk was reduced (LVEF ≤ 15%: hazard ratio [HR] 1.77, 95% confidence interval [CI] 1.48 to 2.11; LVEF 16% to 25%: HR 1.44, 95% CI 1.28 to 1.61; LVEF 26% to 35%: HR 1.10, 95% CI 0.98 to 1.28; LVEF 36% to 45%: referent). In contrast, mortality rates were comparable among patients with LVEF > 45% both before (LVEF 46% to 55%: 23.3%; LVEF > 55%: 23.5%; p = 0.25), and after multivariable adjustment (LVEF 46% to 55%: HR 0.92, 95% CI 0.77 to 1.10; LVEF > 55%: HR 0.88, 95% CI 0.71 to 1.09; LVEF 36% to 45%: referent). Patients with lower LVEF were at increased absolute risk of death due to arrhythmia and worsening HF, but these were leading causes of death in all LVEF groups. Among HF patients in sinus rhythm, higher LVEFs were associated with a linear decrease in mortality up to an LVEF of 45%. However, increases above 45% were not associated with further reductions in mortality.