title: Changes in natriuretic peptides after acute hospital presentation for heart failure with preserved ejection fraction: A feasible surrogate trial endpoint? A report from the prospective Karen study.
abstract: BACKGROUND
  In acute decompensated heart failure (ADHF) with preserved ejection fraction (HFpEF) there are no surrogate endpoints for early phase trials. The aim of the current study was to evaluate whether a reduction in natriuretic peptides (NP) between acute hospital presentation to stable follow-up is associated with improved mortality and morbidity.
  
  
  METHODS
  Patients presenting acutely to the hospital for ADHF with HFpEF enrolled in the Karolinska Rennes (KaRen) study and reporting N-terminal pro-B-type NP or B-type NP assessment at baseline hospital presentation and at 4-8weeks follow-up were prospectively studied. Logistic regression analyses were performed to detect the predictors of baseline and changes in NPs. Cox regression models were performed to assess the impact of NP reductions on mortality and the composite of mortality and HF hospitalization.
  
  
  RESULTS
  Of 361 patients (median follow-up 585days), 267 (74%) reported an improvement in NPs, while 94 (26%) reported worsening. At baseline, the independent predictors of lower NPs were higher glomerular filtration rate (Odds Ratio [OR] per unit: 1.013; 95% Confidence Interval [CI]: 1.005-1.021) and younger age (OR per year: 0.972; CI: 0.947-0.998). Improvement in NPs at follow-up was predicted by higher heart rate at baseline (OR per bpm: 1.014; CI: 1.003-1.025). After adjustments, the hazard ratio for all-cause death was 0.730 (CI: 0.456-1.169) and for the composite outcome 0.814 (CI: 0.582-1.139) for patients who improved vs. worsened in NP levels.
  
  
  CONCLUSIONS
  In patients presenting acutely to the hospital with HFPEF, an improvement in NP levels did not independently and significantly predict improved mortality and/or morbidity. NPs as surrogate endpoints in acute HFpEF require further study.
authors: Karolinska Institutet, Department of Medicine, Stockholm, Sweden. Electronic address: gianluigi.savarese@ki.se.
authors: Gianluigi
authors: G
authors: Savarese
authors: Département de Cardiologie & CIC-IT U 804, Centre, Hospitalier Universitaire de Rennes, France; LTSI, Université Rennes 1, INSERM 1099, Rennes, France.
authors: Erwan
authors: E
authors: Donal
authors: Karolinska Institutet, Department of Medicine, Stockholm, Sweden; Karolinska University Hospital, Department of Cardiology, Stockholm, Sweden.
authors: Camilla
authors: C
authors: Hage
authors: INSERM, Clinical Investigation Center CIC-1414, Rennes, France.
authors: Emmanuel
authors: E
authors: Oger
authors: Karolinska Institutet, Department of Clinical Sciences Danderyd, Stockholm, Sweden; Danderyd Hospital, Department of Cardiology, Stockholm, Sweden.
authors: Hans
authors: H
authors: Persson
authors: Département de Cardiologie & CIC-IT U 804, Centre, Hospitalier Universitaire de Rennes, France; LTSI, Université Rennes 1, INSERM 1099, Rennes, France.
authors: Jean-Claude
authors: JC
authors: Daubert
authors: Karolinska Institutet, Department of Medicine, Stockholm, Sweden; Karolinska University Hospital, Department of Cardiology, Stockholm, Sweden.
authors: Cecilia
authors: C
authors: Linde
authors: Karolinska Institutet, Department of Medicine, Stockholm, Sweden; Karolinska University Hospital, Department of Cardiology, Stockholm, Sweden.
authors: Lars H
authors: LH
authors: Lund
mesh_terms: D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood* / Q000175:diagnosis* / Q000628:therapy; D006760:Hospitalization / Q000639:trends*; D006801:Humans; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood; D045265:Natriuretic Peptides / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood; D011446:Prospective Studies; D058028:Research Report; D013318:Stroke Volume / Q000502:physiology*
chemical_list: D015415:Biomarkers; D045265:Natriuretic Peptides; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain
keywords: Acute decompensated heart failure with preserved ejection fraction; Acute heart failure, heart failure with preserved ejection fraction; Heart failure; Natriuretic peptides