title: Diuretic response in acute heart failure: clinical characteristics and prognostic significance.
abstract: OBJECTIVE
  Diminished diuretic response is common in patients with acute heart failure, although a clinically useful definition is lacking. Our aim was to investigate a practical, workable metric for diuretic response, examine associated patient characteristics and relationships with outcome.
  
  
  RESULTS
  We examined diuretic response (defined as Δ weight kg/40 mg furosemide) in 1745 hospitalized acute heart failure patients from the PROTECT trial. Day 4 response was used to allow maximum differentiation in responsiveness and tailoring of diuretic doses to clinical response, following sensitivity analyses. We investigated predictors of diuretic response and relationships with outcome. The median diuretic response was -0.38 (-0.80 to -0.13) kg/40 mg furosemide. Poor diuretic response was independently associated with low systolic blood pressure, high blood urea nitrogen, diabetes, and atherosclerotic disease (all P < 0.05). Worse diuretic response independently predicted 180-day mortality (HR: 1.42; 95% CI: 1.11-1.81, P = 0.005), 60-day death or renal or cardiovascular rehospitalization (HR: 1.34; 95% CI: 1.14-1.59, P < 0.001) and 60-day HF rehospitalization (HR: 1.57; 95% CI: 1.24-2.01, P < 0.001) in multivariable models. The proposed metric-weight loss indexed to diuretic dose-better captures a dose-response relationship. Model diagnostics showed diuretic response provided essentially the same or slightly better prognostic information compared with its individual components (weight loss and diuretic dose) in this population, while providing a less biased, more easily interpreted signal.
  
  
  CONCLUSIONS
  Worse diuretic response was associated with more advanced heart failure, renal impairment, diabetes, atherosclerotic disease and in-hospital worsening heart failure, and predicts mortality and heart failure rehospitalization in this post hoc, hypothesis-generating study.
authors.affiliation: Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Mattia A E
authors.initials: MA
authors.lastname: Valente
authors.affiliation: Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands a.a.voors@umcg.nl.
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Voors
authors.affiliation: Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Kevin
authors.initials: K
authors.lastname: Damman
authors.affiliation: Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Van Veldhuisen
authors.affiliation: University of California at San Francisco and San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA.
authors.forename: Barrie M
authors.initials: BM
authors.lastname: Massie
authors.affiliation: Duke University Medical Center, Durham, NC, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: O'Connor
authors.affiliation: University of Brescia, Brescia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Metra
authors.affiliation: Medical University, Clinical Military Hospital, Wroclaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Ponikowski
authors.affiliation: University of California at San Francisco and San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Teerlink
authors.affiliation: Momentum Research, Durham, NC, USA.
authors.forename: Gad
authors.initials: G
authors.lastname: Cotter
authors.affiliation: Momentum Research, Durham, NC, USA.
authors.forename: Beth
authors.initials: B
authors.lastname: Davison
authors.affiliation: University of Hull, Kingston upon Hull, UK.
authors.forename: John G F
authors.initials: JG
authors.lastname: Cleland
authors.affiliation: Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Givertz
authors.affiliation: Merck Research Laboratories, Rahway, NJ, USA.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Bloomfield
authors.affiliation: Duke University Medical Center, Durham, NC, USA.
authors.forename: Mona
authors.initials: M
authors.lastname: Fiuzat
authors.affiliation: Cardiovascular Research Center, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
authors.forename: Howard C
authors.initials: HC
authors.lastname: Dittrich
authors.affiliation: Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands Department of Epidemiology, University Medical Center Groningen, Groningen, Hanzeplein 1, 9713 GZ, The Netherlands.
authors.forename: Hans L
authors.initials: HL
authors.lastname: Hillege
mesh_terms: D000208:Acute Disease; D000368:Aged; D000704:Analysis of Variance; D050197:Atherosclerosis / Q000150:complications; D002034:Bumetanide / Q000008:administration & dosage; D048909:Diabetes Complications / Q000150:complications; D004232:Diuretics / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004417:Dyspnea / Q000517:prevention & control; D005260:Female; D005665:Furosemide / Q000008:administration & dosage; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007022:Hypotension / Q000150:complications; D008297:Male; D010359:Patient Readmission; D051437:Renal Insufficiency / Q000150:complications; D013449:Sulfonamides / Q000008:administration & dosage; D000077786:Torsemide; D016896:Treatment Outcome; D015431:Weight Loss / Q000187:drug effects; D014970:Xanthines / Q000008:administration & dosage
chemical_list: D004232:Diuretics; D013449:Sulfonamides; D014970:Xanthines; D002034:Bumetanide; C073525:rolofylline; D005665:Furosemide; D000077786:Torsemide
keywords: Cardiorenal syndrome; Diuretic resistance; Diuretics; Heart failure; Mortality; Prognosis; Rehospitalization; Renal dysfunction; Worsening renal function