Optimizing clinical use of biomarkers in high-risk acute heart failure patients

Demissei, B. G. et al. (2016) Optimizing clinical use of biomarkers in high-risk acute heart failure patients. European Journal of Heart Failure, 18(3), pp. 269-280. (doi:10.1002/ejhf.443) (PMID:26634889)

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Abstract

Aim: The clinical value of single biomarkers at single time-points to predict outcomes in patients with acute heart failure (AHF) is limited. We performed a multimarker, multi-time-point analysis of biomarkers for the prediction of post-discharge clinical outcomes in high-risk AHF patients. Methods and results: A set of 48 circulating biomarkers were measured in the PROTECT trial which enrolled 2033 patients with AHF. Associations between baseline levels of biomarkers and outcomes (30-day all-cause mortality, 30-day death or rehospitalization for renal/cardiovascular causes and 180-day all-cause mortality) were evaluated. Prognostic accuracies of baseline, days 2 or 3, 7, and 14 biomarker measurements were estimated and compared utilizing a time-dependent area under the curve (AUC) analysis. Forty-four biomarkers were significantly associated with outcomes, but 42 had limited prognostic value (C-index < 0.70). However, multimarker models combining best-performing biomarkers from different clusters had a much stronger prognostic value. Combining blood urea nitrogen (BUN), chloride, interleukin (IL)-6, cTnI, sST-2 and VEGFR-1 into a clinical model yielded a 11% increase in C-index to 0.84 and 0.78 for 30-day and 180-day all-cause mortality, respectively, and cNRI of 0.86 95% CI [0.55–1.11] and 0.76 95% CI [0.57–0.87]. Prognostic gain was modest for the 30-day death/rehospitalization for cardiovascular or renal causes endpoint. Comparative time-dependent AUC analysis indicated that late measurements provided superior accuracy for the prediction of all-cause mortality over 180 days, with few exceptions including BUN and galectin-3. However, the predictive value of most biomarkers showed a diminishing pattern over time irrespective of moment of measurement. Conclusions: Multimarker models significantly improve risk prediction. Subsequent measurements, beyond admission, are needed for majority of biomarkers to maximize prognostic value over time, particularly in the long term.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Cleland, Professor John
Authors: Demissei, B. G., Valente, M. A.E., Cleland, J. G.F., O'Connor, C. M., Metra, M., Ponikowski, P., Teerlink, J. R., Cotter, G., Davison, B., Givertz, M. M., Bloomfield, D. M., Dittrich, H., van der Meer, P., van Veldhuisen, D. J., Hillege, H. L., and Voors, A. A.
Subjects:R Medicine > R Medicine (General)
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
Journal Name:European Journal of Heart Failure
Publisher:Wiley
ISSN:1388-9842
ISSN (Online):1879-0844
Published Online:03 December 2015

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