title: Triple head-to-head comparison of fibrotic biomarkers galectin-3, osteopontin and gremlin-1 for long-term prognosis in suspected and proven acute heart failure patients.
abstract: BACKGROUND
  To comparatively evaluate long-term prognostic values of fibrotic biomarkers galectin-3, gremlin-1 and osteopontin in patients presenting to the emergency department (ED) suspected of acute heart failure (AHF).
  
  
  METHODS
  Patients with acute dyspnea or peripheral edema were enrolled in the ED. Biomarkers were measured and added to prognostic models including 11 conventional risk factors plus NT-proBNP assessing state-of-the-art statistics of discrimination, calibration, reclassification and Cox regression analyses. Prognostic outcomes were long-term all-cause mortality (ACM) and AHF-related rehospitalization (AHF-RH) at 1 and 5 years.
  
  
  RESULTS
  401 patients including 122 AHF patients were enrolled (mean age 67 years, males 51%). During 5 years follow-up 129 patients (30%) died and 73 (18%) were re-hospitalized because of AHF. In multivariate analysis, galectin-3 (hazard ratios (HR) range 1.4–1.9; p = 0.03) and osteopontin (HR range 1.2–1.4; p = 0.001) remained associated with ACM overall and in the AHF population at 5 years, whereas gremlin-1 remained associated with AHF-RH at 1 year in AHF patients (HR 1.3; p = 0.002). ACM in whole cohort was best discriminated (AUC = 0.85, p = 0.0001), calibrated and re-classified (NRI + 0.50 to + 0.56, p = 0.0001) by galectin-3, whereas in AHF patients ACM was best discriminated by osteopontin (AUC range: 0.82–0.84, p = 0.0001; NRI + 0.34 to + 0.38, p < 0.1) and AHF-RH at 1 year by gremlin-1 (AUC range: 0.82–0.92, p = 0.0001; NRI + 0.59 to + 0.60, p = 0.006).
  
  
  CONCLUSIONS
  A panel of fibrotic biomarkers, including osteopontin, galectin-3 and gremlin-1, might be useful for long term risk-stratification of symptomatic ED patients being suspected of AHF.
authors.affiliation: First Department of Medicine, University Medical Centre Mannheim (UMM), Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany. Electronic address: michael.behnes@umm.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Behnes
authors.affiliation: Institute of Clinical Chemistry, Laboratory Medicine and Transfusion Medicine, General Hospital Nuremberg, Paracelsus Medical University, Nuremberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bertsch
authors.affiliation: Department for Statistical Analysis, University Medical Centre Mannheim (UMM), Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Christel
authors.initials: C
authors.lastname: Weiss
authors.affiliation: Institute for Microbiology and Laboratory Medicine, HELIOS Klinikum Wuppertal, University of Witten/Herdecke, Wuppertal, Germany.
authors.forename: Parviz
authors.initials: P
authors.lastname: Ahmad-Nejad
authors.affiliation: First Department of Medicine, University Medical Centre Mannheim (UMM), Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Akin
authors.affiliation: First Department of Medicine, University Medical Centre Mannheim (UMM), Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Fastner
authors.affiliation: First Department of Medicine, University Medical Centre Mannheim (UMM), Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: El-Battrawy
authors.affiliation: First Department of Medicine, University Medical Centre Mannheim (UMM), Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Lang
authors.affiliation: Institute for Clinical Chemistry, University Medical Centre Mannheim (UMM), Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Neumaier
authors.affiliation: First Department of Medicine, University Medical Centre Mannheim (UMM), Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Borggrefe
authors.affiliation: First Department of Medicine, University Medical Centre Mannheim (UMM), Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Hoffmann
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D018618:Echocardiography, Doppler, Color; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D037502:Galectin 3 / Q000097:blood*; D005858:Germany / Q000453:epidemiology; D006333:Heart Failure / Q000097:blood* / Q000175:diagnosis / Q000401:mortality; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D053495:Osteopontin / Q000097:blood*; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate / Q000639:trends; D013997:Time Factors; D055815:Young Adult
chemical_list: D015415:Biomarkers; C486399:GREM1 protein, human; D037502:Galectin 3; D036341:Intercellular Signaling Peptides and Proteins; D053495:Osteopontin
keywords: Acute heart failure; Galectin-3; Gremlin-1; Mortality; Osteopontin; Prognosis; Rehospitalization