title: Panel of emerging cardiac biomarkers contributes for prognosis rather than diagnosis in chronic heart failure.
abstract: BACKGROUND
  As complex disease, heart failure is associated with various pathophysiological and biochemical disorders. No single biomarker is able to display all these characteristics. Therefore, we evaluated a multimarker panel together with the biochemical gold-standard NT-proBNP. Part of the panel are markers for angiogenesis (Endostatin, IBP-4, IBP-7, sFlt-1 as antiangiogenetic factors and PLGF as angiogenectic factor), myocyte stress (GDF-15), extracellular matrix remodelling (galectin-3, mimecan and TIMP-1), inflammation (galectin-3) and myocyte injury (hs-TnT).
  
  
  METHODS
  All markers (Roche Diagnostics, Penzberg, Germany) were assessed in a cohort of 149 patients with chronic heart failure and 84 healthy controls.
  
  
  RESULTS
  All markers were positively correlated with ln NT-proBNP (each p < 0.05). Furthermore, they were significantly elevated in patients with chronic heart failure (each p < 0.05). All markers increased significantly with severity of LV dysfunction and severity of New York Heart Association class (each p < 0.05), except for PLGF and Mimecan (each p = NS). With the exception of endostatin, mimecan and PLGF, all other markers were further significant predictors for all-cause mortality in a 3-year follow-up. In a multimarker approach of the five biomarkers with the best performance (NT-proBNP, hs-TnT, TIMP-1, GDF-15 and IBP-4), the event rate was superior to NT-proBNP alone and increased significantly and progressively with the number of elevated biomarkers.
  
  
  CONCLUSIONS
  All emerging markers increased stepwise with the severity of symptoms and LV dysfunction and offer important prognostic information in chronic heart failure, except for PLGF and mimecan. Five biomarkers with different pathophysiological background incorporated additive prognostic value in heart failure. Prognostication in heart failure may be further improved through a multimarker approach.
authors.affiliation: Department of Cardiology, Klinik & Poliklinik fuer Innere Medizin II, Universitätsklinikum Regensburg, Regensburg, Germany.
authors.forename: Carsten G
authors.initials: CG
authors.lastname: Jungbauer
authors.forename: Julia
authors.initials: J
authors.lastname: Riedlinger
authors.forename: Dirk
authors.initials: D
authors.lastname: Block
authors.forename: Stefan
authors.initials: S
authors.lastname: Stadler
authors.forename: Christoph
authors.initials: C
authors.lastname: Birner
authors.forename: Monika
authors.initials: M
authors.lastname: Buesing
authors.forename: Wolfgang
authors.initials: W
authors.lastname: König
authors.forename: Günter
authors.initials: G
authors.lastname: Riegger
authors.forename: Lars
authors.initials: L
authors.lastname: Maier
authors.forename: Andreas
authors.initials: A
authors.lastname: Luchner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins; D002908:Chronic Disease; D043169:Endostatins / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D037502:Galectin 3 / Q000097:blood; D037161:Galectins; D055436:Growth Differentiation Factor 15 / Q000097:blood; D006333:Heart Failure / Q000097:blood* / Q000175:diagnosis* / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000097:blood; D011379:Prognosis; D015996:Survival Rate; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D020107:Troponin T / Q000097:blood; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D043169:Endostatins; C526140:GDF15 protein, human; D037502:Galectin 3; D037161:Galectins; D055436:Growth Differentiation Factor 15; D036341:Intercellular Signaling Peptides and Proteins; C428445:LGALS3 protein, human; C063488:OGN protein, human; C000608036:PGF protein, human; D010446:Peptide Fragments; D011257:Pregnancy Proteins; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D020107:Troponin T; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D000072483:Placenta Growth Factor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: GDF-15; chronic heart failure; emerging biomarkers; highly sensitive troponin; natriuretic peptides