title: Clinical course of patients with hyponatremia and decompensated systolic heart failure and the effect of vasopressin receptor antagonism with tolvaptan.
abstract: BACKGROUND
  Patients with decompensated heart failure, volume overload, and hyponatremia are challenging to manage. Relatively little has been documented regarding the clinical course of these patients during standard in-hospital management or with vasopressin antagonism.
  
  
  RESULTS
  The Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan database was examined to assess the short-term clinical course of patients hospitalized with heart failure and hyponatremia and the effect of tolvaptan on outcomes. In the placebo group, patients with hyponatremia (serum Na(+) <135mEq/L; n = 232), compared with those with normonatremia at baseline (n = 1785), had less relief of dyspnea despite receiving higher doses of diuretics (59.2% vs 69.2% improved; P < .01) and worse long-term outcomes. In the hyponatremia subgroup from the entire trial cohort (n = 475), tolvaptan was associated with greater likelihood of normalization of serum sodium than placebo (58% vs 20% and 64% vs 29% for day 1 and discharge, respectively; P < .001 for both comparisons), greater weight reduction at day 1 and discharge (0.7 kg and 0.8 kg differences, respectively; P < .001 and P = .008), and greater relief of dyspnea (P = .03). Among all hyponatremic patients, there was no effect of tolvaptan on long-term outcomes compared with placebo. In patients with pronounced hyponatremia (<130 mEq/L; n = 92), tolvaptan was associated with reduced cardiovascular morbidity and mortality after discharge (P = .04).
  
  
  CONCLUSIONS
  In patients with decompensated heart failure and hyponatremia, standard therapy is associated with less weight loss and dyspnea relief, and unfavorable longer-term outcomes compared to those with normonatremia. Tolvaptan is associated with more favorable in-hospital effects and, possibly, long-term outcomes in patients with severe hyponatremia.
authors.affiliation: Division of Cardiology, Department of Medicine, Saint Louis University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Hauptman
authors.forename: John
authors.initials: J
authors.lastname: Burnett
authors.forename: Mihai
authors.initials: M
authors.lastname: Gheorghiade
authors.forename: Liliana
authors.initials: L
authors.lastname: Grinfeld
authors.forename: Marvin A
authors.initials: MA
authors.lastname: Konstam
authors.forename: Dusan
authors.initials: D
authors.lastname: Kostic
authors.forename: Holly B
authors.initials: HB
authors.lastname: Krasa
authors.forename: Aldo
authors.initials: A
authors.lastname: Maggioni
authors.forename: John
authors.initials: J
authors.lastname: Ouyang
authors.forename: Karl
authors.initials: K
authors.lastname: Swedberg
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
authors.forename: Chris
authors.initials: C
authors.lastname: Zimmer
authors.forename: James E
authors.initials: JE
authors.lastname: Udelson
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000097:blood; D001552:Benzazepines / Q000627:therapeutic use*; D004232:Diuretics / Q000627:therapeutic use; D004417:Dyspnea / Q000188:drug therapy / Q000209:etiology; D005260:Female; D005665:Furosemide / Q000627:therapeutic use; D054143:Heart Failure, Systolic / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D007010:Hyponatremia / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D000077602:Tolvaptan; D015431:Weight Loss / Q000187:drug effects
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D004232:Diuretics; D001127:Arginine Vasopressin; D000077602:Tolvaptan; D005665:Furosemide