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Mihai Gheorghiade, MD; Joseph S. Rossi, MD; William Cotts, MD; David D. Shin, MD; Anne S. Hellkamp, MS; Ileana L. Piña, MD; Gregg C. Fonarow, MD; Teresa DeMarco, MD; Daniel F. Pauly, MD, PhD; Joseph Rogers, MD; Thomas G. DiSalvo, MD, MPH; Javed Butler, MD; Joshua M. Hare, MD; Gary S. Francis, MD; Wendy Gattis Stough, PharmD; Christopher M. O’Connor, MD

Arch Intern Med. 2007;167(18):1998-2005.

Background  Mild hyponatremia is relatively common in patients hospitalized with heart failure (HF). To our knowledge, the association of hyponatremia with outcomes has not been evaluated in the context of in-hospital clinical course including central hemodynamics and changes in serum sodium level.

Methods  The ESCAPE trial (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) was a randomized, controlled study designed to evaluate the utility of a pulmonary artery catheter plus clinical assessment vs clinical assessment alone in guiding therapy in patients hospitalized with New York Heart Association class IV HF due to systolic dysfunction (left ventricular ejection fraction <30%). A Cox proportional hazards model with baseline serum sodium level as a continuous variable was used to examine the association of serum sodium level with 6-month postdischarge mortality, HF rehospitalization, and death or rehospitalization. A categorical analysis was also performed comparing persistent and corrected hyponatremia.

Results  A total of 433 hospitalized patients with HF were enrolled in ESCAPE. Hyponatremia (serum sodium level  134 mEq/L) was present in 103 patients (23.8%). (To convert serum sodium to millimoles per liter, multiply by 1.0.) Of these, 71 had persistent hyponatremia (68.9%). Hyponatremia was associated with higher 6-month mortality after covariate adjustment (hazard ratio [HR] for each 3-mEq/L decrease in sodium level, 1.23; 95% confidence interval [CI], 1.05-1.43) (P = .01). After controlling for baseline variables and clinical response, we found that patients with persistent hyponatremia had an increased risk of all-cause mortality (31% vs 16%; HR, 1.82) (P = .04), HF rehospitalization (62% vs 43%; HR, 1.52) (P = .03), and death or rehospitalization (73% vs 50%; HR, 1.54) (P = .01) compared with normonatremic patients.

Conclusion  Persistent hyponatremia was an independent predictor of mortality, HF hospitalization, and death or rehospitalization despite clinical and hemodynamic improvements that were similar to those in patients without hyponatremia.

Author Affiliations: Northwestern University Feinberg School of Medicine, Chicago, Illinois (Drs Gheorghiade, Rossi, Cotts, and Shin); Duke University Medical Center, Durham (Ms Hellkamp and Drs Rogers and O’Connor) and Department of Clinical Research, Campbell University School of Pharmacy, Research Triangle Park (Dr Stough), North Carolina; University Hospitals of Cleveland, Cleveland, Ohio (Dr Piña); University of California at Los Angeles (Dr Fonarow); University of California at San Francisco (Dr DeMarco); Shands Hospital, University of Florida, Gainesville (Dr Pauly); Massachusetts General Hospital, Boston (Dr DiSalvo); Vanderbilt University Medical Center, Nashville, Tennessee (Dr Butler); Johns Hopkins University, Baltimore, Maryland (Dr Hare); and Cleveland Clinic, Cleveland (Dr Francis).

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