title: Implications of Using Different Definitions on Outcomes in Worsening Heart Failure.
abstract: In-hospital worsening heart failure (WHF) is an important event that has inconsistent definitions used across trials. We used data from 2 acute heart failure (HF) trials from the National Institutes of Health HF Network, DOSE (Diuretic Optimization Strategies Evaluation) and ROSE (Renal Optimization Strategies), to understand event rates associated with different WHF definitions.
  
  
  
  We pooled data from 668 patients in DOSE and ROSE and assessed the relationship between WHF and the composite end point of rehospitalization, emergency room visits for HF, and mortality through 60 days. We also assessed for a differential relationship between the timing of WHF development and outcomes. The overall incidence of WHF was 14.6% (24.1% in DOSE, 6.3% in ROSE, and 5.0% in DOSE using the ROSE definition). WHF was associated with an increase in the composite end point (hazard ratio [HR], 1.64; 95% confidence interval [CI], 1.11-2.42; P=0.01). However, the association between WHF and outcomes was significantly stronger in ROSE than in DOSE (HR, 2.67; 95% CI, 1.45-4.91; P<0.01 and HR, 1.28; 95% CI, 0.79-2.08; P=0.31, respectively). Development of WHF between baseline to 24 hours compared with 24 to 48 hours or 48 to 72 hours demonstrated a trend toward improved outcomes (HR, 0.49; 95% CI, 0.21-1.17; P=0.11 and HR, 0.45; 95% CI, 0.20-1.04; P=0.06, respectively).
  
  
  
  A WHF definition that excluded the intensification of diuretics resulted in a lower event rate but a stronger association with outcomes. These data support the need for continued efforts to standardize WHF definitions in clinical trials.
  
  
  
  URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00577135 (DOSE) and NCT01132846 (ROSE).
authors: From the Duke Clinical Research Institute, Duke Medicine, Durham, NC (J.P.K., L.B.C., D.G., K.J.A.,C.M.O'C., R.J.M., A.F.H., M.F.); Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC (J.P.K., L.B.C., C.M.O'C., R.J.M., A.F.H., M.F.); Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (H.H.C., M.M.R.); and Inova Heart and Vascular Institute, Falls Church, VA (C.M.O'C.). Jacob.kelly@duke.edu.
authors: Jacob P
authors: JP
authors: Kelly
authors: From the Duke Clinical Research Institute, Duke Medicine, Durham, NC (J.P.K., L.B.C., D.G., K.J.A.,C.M.O'C., R.J.M., A.F.H., M.F.); Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC (J.P.K., L.B.C., C.M.O'C., R.J.M., A.F.H., M.F.); Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (H.H.C., M.M.R.); and Inova Heart and Vascular Institute, Falls Church, VA (C.M.O'C.).
authors: Lauren B
authors: LB
authors: Cooper
authors: From the Duke Clinical Research Institute, Duke Medicine, Durham, NC (J.P.K., L.B.C., D.G., K.J.A.,C.M.O'C., R.J.M., A.F.H., M.F.); Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC (J.P.K., L.B.C., C.M.O'C., R.J.M., A.F.H., M.F.); Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (H.H.C., M.M.R.); and Inova Heart and Vascular Institute, Falls Church, VA (C.M.O'C.).
authors: Dianne
authors: D
authors: Gallup
authors: From the Duke Clinical Research Institute, Duke Medicine, Durham, NC (J.P.K., L.B.C., D.G., K.J.A.,C.M.O'C., R.J.M., A.F.H., M.F.); Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC (J.P.K., L.B.C., C.M.O'C., R.J.M., A.F.H., M.F.); Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (H.H.C., M.M.R.); and Inova Heart and Vascular Institute, Falls Church, VA (C.M.O'C.).
authors: Kevin J
authors: KJ
authors: Anstrom
authors: From the Duke Clinical Research Institute, Duke Medicine, Durham, NC (J.P.K., L.B.C., D.G., K.J.A.,C.M.O'C., R.J.M., A.F.H., M.F.); Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC (J.P.K., L.B.C., C.M.O'C., R.J.M., A.F.H., M.F.); Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (H.H.C., M.M.R.); and Inova Heart and Vascular Institute, Falls Church, VA (C.M.O'C.).
authors: Horng H
authors: HH
authors: Chen
authors: From the Duke Clinical Research Institute, Duke Medicine, Durham, NC (J.P.K., L.B.C., D.G., K.J.A.,C.M.O'C., R.J.M., A.F.H., M.F.); Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC (J.P.K., L.B.C., C.M.O'C., R.J.M., A.F.H., M.F.); Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (H.H.C., M.M.R.); and Inova Heart and Vascular Institute, Falls Church, VA (C.M.O'C.).
authors: Margaret M
authors: MM
authors: Redfield
authors: From the Duke Clinical Research Institute, Duke Medicine, Durham, NC (J.P.K., L.B.C., D.G., K.J.A.,C.M.O'C., R.J.M., A.F.H., M.F.); Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC (J.P.K., L.B.C., C.M.O'C., R.J.M., A.F.H., M.F.); Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (H.H.C., M.M.R.); and Inova Heart and Vascular Institute, Falls Church, VA (C.M.O'C.).
authors: Christopher M
authors: CM
authors: O'Connor
authors: From the Duke Clinical Research Institute, Duke Medicine, Durham, NC (J.P.K., L.B.C., D.G., K.J.A.,C.M.O'C., R.J.M., A.F.H., M.F.); Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC (J.P.K., L.B.C., C.M.O'C., R.J.M., A.F.H., M.F.); Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (H.H.C., M.M.R.); and Inova Heart and Vascular Institute, Falls Church, VA (C.M.O'C.).
authors: Robert J
authors: RJ
authors: Mentz
authors: From the Duke Clinical Research Institute, Duke Medicine, Durham, NC (J.P.K., L.B.C., D.G., K.J.A.,C.M.O'C., R.J.M., A.F.H., M.F.); Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC (J.P.K., L.B.C., C.M.O'C., R.J.M., A.F.H., M.F.); Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (H.H.C., M.M.R.); and Inova Heart and Vascular Institute, Falls Church, VA (C.M.O'C.).
authors: Adrian F
authors: AF
authors: Hernanadez
authors: From the Duke Clinical Research Institute, Duke Medicine, Durham, NC (J.P.K., L.B.C., D.G., K.J.A.,C.M.O'C., R.J.M., A.F.H., M.F.); Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC (J.P.K., L.B.C., C.M.O'C., R.J.M., A.F.H., M.F.); Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (H.H.C., M.M.R.); and Inova Heart and Vascular Institute, Falls Church, VA (C.M.O'C.).
authors: G Michael
authors: GM
authors: Felker
mesh_terms: D000208:Acute Disease; D000368:Aged; D002317:Cardiovascular Agents / Q000627:therapeutic use; D018450:Disease Progression; D004232:Diuretics / Q000627:therapeutic use; D004636:Emergency Service, Hospital; D005260:Female; D006333:Heart Failure / Q000145:classification* / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality; D006760:Hospitalization; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010359:Patient Readmission; D011237:Predictive Value of Tests; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D012307:Risk Factors; D009626:Terminology as Topic; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D002317:Cardiovascular Agents; D004232:Diuretics
keywords: diuretics; heart failure; hospitalization; outcome assessment (health care)