title: A multimarker approach to diagnose and stratify heart failure.
abstract: BACKGROUND
  We have previously demonstrated that circulating NT-proBNP is truncated at the N and C termini. Aims of this study are three-fold: firstly to determine whether the NT-proBNP levels correlate with NYHA functional classes when measuring with different antibody pairs; secondly to evaluate the diagnostic potential of ProBNP and; thirdly to investigate whether combining NT-proBNP assays with or without ProBNP would lead to better diagnostic accuracies.
  
  
  METHODS
  Plasma samples were collected from healthy controls (n=52) and HF patients (n=46). Customized AlphaLISA® immunoassays were developed and validated to measure the concentrations of proBNP and NT-proBNP (with antibodies targeting 13-45, 13-76, 28-76). The diagnostic performance and predictive value of proBNP and NT-proBNP assays and their combinations were evaluated.
  
  
  RESULTS
  Plasma proBNP assay showed acceptable diagnostic performance. NT-proBNP13-76 assay is useful in diagnosing and stratifying HF patients. The diagnostic performance of NT-proBNP13-76 demonstrated improvement over commercial NT-proBNP tests. The combination of NT-proBNP13-76 with NT-proBNP28-76 assays gave the best diagnostic assay performance.
  
  
  CONCLUSIONS
  Our results demonstrate that while there is major heterogeneity in circulating NT-proBNP, specific epitopes of the peptides are extraordinarily stable, providing ideal targets for clinically useful diagnostic assays. Future new clinical diagnostic clinical trials should include a multimarker approach rather than using a single marker to diagnose HF.
authors.affiliation: The University of Queensland Diamantina Institute, The University of Queensland, The Translational Research Institute, Woolloongabba, Australia.
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Wan
authors.affiliation: The University of Queensland Diamantina Institute, The University of Queensland, The Translational Research Institute, Woolloongabba, Australia.
authors.forename: Xi
authors.initials: X
authors.lastname: Xhang
authors.affiliation: Department of Cardiology, Royal Brisbane and Women's Hospital, Australia; School of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: John J
authors.initials: JJ
authors.lastname: Atherton
authors.affiliation: Department of Cardiology, Mater Adult Hospital, Brisbane, Queensland, Australia.
authors.forename: Karam
authors.initials: K
authors.lastname: Kostner
authors.affiliation: School of Medicine, The University of Queensland, Brisbane, Queensland, Australia; Chemical Pathology Princess Alexandra Hospital, Brisbane, Queensland, Australia.
authors.forename: Goce
authors.initials: G
authors.lastname: Dimeski
authors.affiliation: The University of Queensland Diamantina Institute, The University of Queensland, The Translational Research Institute, Woolloongabba, Australia. Electronic address: chamindie.punyadeera@qut.edu.au.
authors.forename: Chamindie
authors.initials: C
authors.lastname: Punyadeera
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000175:diagnosis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain
keywords: Classify heart failure; NT-proBNP; proBNP