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(Circulation. 2005;111:2454-2460.)
© 2005 American Heart Association, Inc.

Heart Failure

Lower Serum Sodium Is Associated With Increased Short-Term Mortality in Hospitalized Patients With Worsening Heart Failure

Results From the Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF) Study

Liviu Klein, MD; Christopher M. O’Connor, MD; Jeffrey D. Leimberger, PhD; Wendy Gattis-Stough, PharmD; Ileana L. Piña, MD; G. Michael Felker, MD; Kirkwood F. Adams, Jr, MD; Robert M. Califf, MD; Mihai Gheorghiade, MD, for the OPTIME-CHF Investigators

From Northwestern University Feinberg School of Medicine (L.K., M.G.), Chicago, Ill; Duke Clinical Research Institute (C.M.O., J.D.L., W.G.-S., G.M.F., R.M.C.), Durham, NC; Case Western Reserve University (I.L.P.), Cleveland, Ohio; and University of North Carolina (K.F.A.), Chapel Hill, NC.

Correspondence to Mihai Gheorghiade, MD, Division of Cardiology, Northwestern University Feinberg School of Medicine, Galter 10-240, 201 E Huron St, Chicago, IL 60611. E-mail m-gheorghiade{at}northwestern.edu

Received June 8, 2004; revision received January 26, 2005; accepted February 3, 2005.

Background— The prognostic value of serum sodium in patients hospitalized for worsening heart failure has not been well defined.

Methods and Results— The Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF) study randomized 949 patients with systolic dysfunction hospitalized for worsening heart failure to receive 48 to 72 hours of intravenous milrinone or placebo in addition to standard therapy. In a retrospective analysis, we investigated the relationship between admission serum sodium and the primary end point of days hospitalized for cardiovascular causes within 60 days of randomization, as well as the secondary end points of in-hospital mortality, 60-day mortality, and 60-day mortality/rehospitalization. The number of days hospitalized for cardiovascular causes was higher in the lowest sodium quartile: 8.0 (4.5, 18.5) versus 6 (4, 13) versus 6 (4, 11.5) versus 6 (4, 12) days (P<0.015 for comparison with the lowest quartile). Lower serum sodium was associated with higher in-hospital and 60-day mortality: 5.9% versus 1% versus 2.3% versus 2.3% (P<0.015) and 15.9% versus 6.4% versus 7.8% versus 7% (P=0.002), respectively. There was a trend toward higher mortality/rehospitalization for patients who were in the lowest sodium quartile. Multivariable-adjusted Cox proportional hazards analysis showed that serum sodium on admission, when modeled linearly, predicted increased 60-day mortality: sodium (per 3-mEq/L decrease) had a hazard ratio of 1.18 with a 95% CI of 1.03 to 1.36 (P=0.018).

Conclusions— In patients hospitalized for worsening heart failure, admission serum sodium is an independent predictor of increased number of days hospitalized for cardiovascular causes and increased mortality within 60 days of discharge.

Key Words: heart failure • prognosis • sodium • risk factors

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