title: Serum Osmolality and Postdischarge Outcomes After Hospitalization for Heart Failure.
abstract: Serum osmolality may fluctuate with neurohormonal activation and in response to certain therapeutics in patients with heart failure (HF). The clinical relevance of osmolality in patients with HF has not been defined. In this post hoc analysis of the Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan trial, we analyzed serum osmolality measured at discharge in 3,744 patients hospitalized for HF and reduced ejection fraction (EF ≤40%). Median follow-up was 9.9 months. The association between discharge osmolality and all-cause mortality (ACM) and composite cardiovascular mortality or HF hospitalization was nonlinear; and thus, patients were divided into low (≤284), normal (285 to 300), and high (≥300 mOsm/kg) osmolality. Median serum osmolality at discharge was 297 (290 to 304) mOsm/kg. Patients in the low osmolality group (n = 454,12.1%) were more likely to be younger, men, have lower rates of hypertension, coronary artery disease, chronic kidney disease, diabetes, and have lower serum sodium, creatinine, systolic blood pressure, and EF (all p <0.001). Low discharge osmolality was associated with higher ACM (low 29.3%; normal 23.6%; high 25.2%; p = 0.04) and the composite endpoint (low 45.6%; normal 39.3%; high 41.8%; p = 0.04). After risk adjustment, a 15 mOsm/kg decrease in osmolality was predictive of higher ACM (hazard ratio 1.61, 95% CI 1.19 to 2.17) and the composite endpoint (hazard ratio 1.37, 95% CI 1.06 to 1.75) in the low osmolality group. These associations were not seen in patients with normal or high osmolality. Interaction analyses for tolvaptan treatment were nonsignificant (p >0.4). In conclusion, low discharge serum osmolality was independently predictive of worse postdischarge mortality and readmission. Further study is required to clarify the clinical utility of serum osmolality in hospitalized patients with HF.
authors: Brigham and Women's Hospital Heart and Vascular Center, Harvard Medical School, Boston, Massachusetts.
authors: Muthiah
authors: M
authors: Vaduganathan
authors: Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia.
authors: Catherine N
authors: CN
authors: Marti
authors: Duke University Medical Center, Durham, North Carolina.
authors: Robert J
authors: RJ
authors: Mentz
authors: Duke University Medical Center, Durham, North Carolina.
authors: Stephen J
authors: SJ
authors: Greene
authors: Duke University Medical Center, Durham, North Carolina.
authors: Andrew P
authors: AP
authors: Ambrosy
authors: Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors: Haris P
authors: HP
authors: Subacius
authors: Ahmanson-University of California Los Angeles Cardiomyopathy Center, Ronald Reagan-University of California Los Angeles Medical Center, Los Angeles, California.
authors: Gregg C
authors: GC
authors: Fonarow
authors: Institute of Cardiovascular Diseases "Prof. C. Iliescu", Cardiology, Bucuresti, Romania.
authors: Ovidiu
authors: O
authors: Chioncel
authors: Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors: Hasan
authors: H
authors: Bazari
authors: Italian Association of Hospital Cardiologists Research Center, Florence, Italy.
authors: Aldo P
authors: AP
authors: Maggioni
authors: Department of Cardiology, Nancy University, Nancy, France.
authors: Faiez
authors: F
authors: Zannad
authors: Tufts Medical Center, Boston, Massachusetts.
authors: Marvin A
authors: MA
authors: Konstam
authors: Nippon Medical School Musashi-Kosugi Hospital, Tokyo, Japan.
authors: Naoki
authors: N
authors: Sato
authors: Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors: Mihai
authors: M
authors: Gheorghiade
authors: Division of Cardiology, Stony Brook University, Stony Brook, New York. Electronic address: javed.butler@stonybrookmedicine.edu.
authors: Javed
authors: J
authors: Butler
mesh_terms: D000368:Aged; D065092:Antidiuretic Hormone Receptor Antagonists / Q000627:therapeutic use*; D001552:Benzazepines / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood* / Q000188:drug therapy* / Q000401:mortality; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D011237:Predictive Value of Tests; D013318:Stroke Volume; D000077602:Tolvaptan; D016896:Treatment Outcome
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D000077602:Tolvaptan