A multimarker approach to diagnose and stratify heart failure

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 (R) 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-proBNP(13-76) assay is useful in diagnosing and stratifying HF patients. The diagnostic performance of NT-proBNP(13-76) demonstrated improvement over commercial NT-proBNP tests. The combination of NT-proBNP(13-76) with NT-proBNP(28-76) assays gave the best diagnostic assay performance. Conclusion: 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. (C) 2014 Elsevier Ireland Ltd. All rights reserved.