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

OBJECTIVES: The aim of this study was to assess the prognostic importance of left ventricular ejection fraction (LVEF) in stable outpatients with heart failure (HF). BACKGROUND: 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. METHODS: We examined the association of LVEF and outcomes among 7,788 stable HF patients enrolled in the Digitalis Investigation Group trial. RESULTS: During mean follow-up of 37 months, mortality was substantial in all LVEF groups (range, LVEF <or= 15%, 51.7%, LVEF > 55%, 23.5%). Among patients with LVEF <or= 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 <or= 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. CONCLUSIONS: 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.