title: Worsening Heart Failure Following Admission for Acute Heart Failure: A Pooled Analysis of the PROTECT and RELAX-AHF Studies.
abstract: OBJECTIVE
  These studies conducted analyses to examine patient characteristics and outcomes associated with worsening heart failure (WHF).
  
  
  BACKGROUND
  WHF during an admission for acute heart failure (AHF) represents treatment failure and is a potential therapeutic target for clinical trials of AHF.
  
  
  METHODS
  Individual patient data from the PROTECT (Placebo-Controlled Randomized Study of the Selective A1 Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized with Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function) and RELAX-AHF (Relaxin in Acute Heart Failure) phase II and III studies were pooled for analysis.
  
  
  RESULTS
  Of 3,691 patients, death or WHF through day 5 occurred in 12.4%, ranging from 9.5% to 14.5% among studies. A multivariable model provided modest discrimination between patients who did or did not develop WHF (C-index = 0.68). After multivariable adjustment, WHF was associated with a mean increase in length of stay of 5.2 days (95% confidence interval [CI]: 4.6 to 5.8 days) and increased risks of 60-day HF or renal failure readmission or cardiovascular death (hazard ratio [HR]: 1.64, 95% CI: 1.34 to 2.01) and 180-day mortality (HR: 1.93, 95% CI: 1.55 to 2.41) (all p < 0.001). The risk of mortality was higher in patients whose WHF required intravenous inotropes or mechanical therapy (HR: 3.03, 95% CI: 2.11 to 4.36) compared with patients whose WHF was treated with intravenous loop diuretic alone (HR: 1.80, 95% CI: 1.36 to 2.36) (both p < 0.001). WHF was associated with larger increases in markers of renal and hepatic dysfunction during the first days of admission, but remained significantly associated with adverse outcomes after adjustment for these changes.
  
  
  CONCLUSIONS
  WHF during the first 5 days of admission for AHF occurred in approximately 10% to 15% of patients and was associated with longer length of stay and higher risk for readmission and death.
authors.affiliation: Momentum Research Inc., Durham, North Carolina. Electronic address: bethdavison@momentum-research.com.
authors.forename: Beth A
authors.initials: BA
authors.lastname: Davison
authors.affiliation: Cardiology, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Metra
authors.affiliation: Momentum Research Inc., Durham, North Carolina.
authors.forename: Gad
authors.initials: G
authors.lastname: Cotter
authors.affiliation: Division of Cardiology, School of Medicine, University of California-San Francisco, San Francisco, California.
authors.forename: Barry M
authors.initials: BM
authors.lastname: Massie
authors.affiliation: Department of Cardiology, University of Hull, Kingston upon Hull, United Kingdom; National Heart and Lung Institute, Royal Brompton and Harefield Hospitals National Health Service Trust, Imperial College, London, United Kingdom.
authors.forename: John G F
authors.initials: JGF
authors.lastname: Cleland
authors.affiliation: NovaCardia, San Diego, California.
authors.forename: Howard C
authors.initials: HC
authors.lastname: Dittrich
authors.affiliation: Momentum Research Inc., Durham, North Carolina.
authors.forename: Christopher
authors.initials: C
authors.lastname: Edwards
authors.affiliation: Department of Cardiology, Athens University Hospital, Attikon, Athens, Greece.
authors.forename: Gerasimos
authors.initials: G
authors.lastname: Filippatos
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Givertz
authors.affiliation: Division of Cardiology, University of California at San Diego, San Diego, California.
authors.forename: Barry
authors.initials: B
authors.lastname: Greenberg
authors.affiliation: Department of Cardiology, Medical University, Clinical Military Hospital, Wroclaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Ponikowski
authors.affiliation: Department of Cardiology, University of Groningen, Groningen, the Netherlands.
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Voors
authors.affiliation: Division of Cardiology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: O'Connor
authors.affiliation: Division of Cardiology, School of Medicine, University of California-San Francisco, San Francisco, California; Section of Cardiology, San Francisco Veterans Affairs Medical Center, San Francisco, California.
authors.forename: John R
authors.initials: JR
authors.lastname: Teerlink
mesh_terms: D000208:Acute Disease; D018450:Disease Progression; D004232:Diuretics / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000175:diagnosis* / Q000503:physiopathology / Q000628:therapy; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D008297:Male; D011379:Prognosis; D012065:Relaxin / Q000627:therapeutic use*; D016896:Treatment Outcome; D014970:Xanthines / Q000627:therapeutic use*
chemical_list: D004232:Diuretics; D014970:Xanthines; C073525:rolofylline; D012065:Relaxin
keywords: acute heart failure; heart failure readmission; mortality; prognosis; renal function; worsening heart failure