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J Am Coll Cardiol, 2003; 42:736-742, doi:10.1016/S0735-1097(03)00789-7
© 2003 by the American College of Cardiology Foundation
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CLINICAL RESEARCH: HEART FAILURE

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

Jeptha P. Curtis, MD*, Seth I. Sokol, MD*, Yongfei Wang, MS*, Saif S. Rathore, MPH*, Dennis T. Ko, MD*, Farid Jadbabaie, MD*, Edward L. Portnay, MD*, Stephen J. Marshalko, MD, PhD*, Martha J. Radford, MD, FACC*§ and Harlan M. Krumholz, MD, SM, FACC*{dagger}{ddagger},*

* Section of Cardiovascular Medicine, Department of Internal Medicine and Section of Health Policy and Administration, Yale University School of Medicine, New Haven, Connecticut, USA
{dagger} Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut, USA
{ddagger} Yale-New Haven Hospital Center for Outcomes Research and Evaluation, New Haven, Connecticut, USA
§ Yale-New Haven Health Center for Outcomes Research and Evaluation, New Haven, Connecticut, USA

Manuscript received February 24, 2003; revised manuscript received March 28, 2003, accepted April 8, 2003.

* Reprint requests and correspondence: Dr. Harlan M. Krumholz, Yale University School of Medicine, 333 Cedar Street, PO Box 208025, New Haven, Connecticut 06520-8025, USA.
harlan.krumholz{at}yale.edu

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 ≤ 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.

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.

Abbreviations and Acronyms
  BMI = body mass index
  DIG = Digitalis Investigation Group
  ERNA = equilibrium radionuclide angiography
  HF = heart failure
  LVEF = left ventricular ejection fraction
  MI = myocardial infarction




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