Development and validation of a decision support tool for the diagnosis of acute heart failure: systematic review, meta-analysis, and modelling study

Lee, K. K. et al. (2022) Development and validation of a decision support tool for the diagnosis of acute heart failure: systematic review, meta-analysis, and modelling study. British Medical Journal, 377, e068424. (doi: 10.1136/bmj-2021-068424) (PMID:35697365) (PMCID:PMC9189738)

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Objectives: To evaluate the diagnostic performance of N-terminal pro-B-type natriuretic peptide (NT-proBNP) thresholds for acute heart failure and to develop and validate a decision support tool that combines NT-proBNP concentrations with clinical characteristics. Design: Individual patient level data meta-analysis and modelling study. Setting: Fourteen studies from 13 countries, including randomised controlled trials and prospective observational studies. Participants: Individual patient level data for 10 369 patients with suspected acute heart failure were pooled for the meta-analysis to evaluate NT-proBNP thresholds. A decision support tool (Collaboration for the Diagnosis and Evaluation of Heart Failure (CoDE-HF)) that combines NT-proBNP with clinical variables to report the probability of acute heart failure for an individual patient was developed and validated. Main outcome measure: Adjudicated diagnosis of acute heart failure. Results: Overall, 43.9% (4549/10 369) of patients had an adjudicated diagnosis of acute heart failure (73.3% (2286/3119) and 29.0% (1802/6208) in those with and without previous heart failure, respectively). The negative predictive value of the guideline recommended rule-out threshold of 300 pg/mL was 94.6% (95% confidence interval 91.9% to 96.4%); despite use of age specific rule-in thresholds, the positive predictive value varied at 61.0% (55.3% to 66.4%), 73.5% (62.3% to 82.3%), and 80.2% (70.9% to 87.1%), in patients aged <50 years, 50-75 years, and >75 years, respectively. Performance varied in most subgroups, particularly patients with obesity, renal impairment, or previous heart failure. CoDE-HF was well calibrated, with excellent discrimination in patients with and without previous heart failure (area under the receiver operator curve 0.846 (0.830 to 0.862) and 0.925 (0.919 to 0.932) and Brier scores of 0.130 and 0.099, respectively). In patients without previous heart failure, the diagnostic performance was consistent across all subgroups, with 40.3% (2502/6208) identified at low probability (negative predictive value of 98.6%, 97.8% to 99.1%) and 28.0% (1737/6208) at high probability (positive predictive value of 75.0%, 65.7% to 82.5%) of having acute heart failure. Conclusions: In an international, collaborative evaluation of the diagnostic performance of NT-proBNP, guideline recommended thresholds to diagnose acute heart failure varied substantially in important patient subgroups. The CoDE-HF decision support tool incorporating NT-proBNP as a continuous measure and other clinical variables provides a more consistent, accurate, and individualised approach.

Item Type:Articles
Additional Information:Funding: This study was supported by the British Heart Foundation through a clinical research training fellowship (FS/18/25/33454), intermediate clinical research fellowship (FS/19/17/34172), chair award (CH/F/21/90010), programme grant (RG/20/10/34966), and research excellence award (RE/18/5/34216) and by the Medical Research Council (MR/N013166/1), Chief Scientist Office (CGA/19/01), and a joint grant from the Medical Research Council Confidence in Concept Scheme and the Data Driven Innovation programme (MRC/CIC8/79).
Keywords:Diagnosis, Differential, Heart Failure - diagnosis, Predictive Value of Tests, Peptide Fragments, Prospective Studies, Natriuretic Peptide, Brain, Biomarkers, Observational Studies as Topic, Humans
Glasgow Author(s) Enlighten ID:McMurray, Professor John
Authors: Lee, K. K., Doudesis, D., Anwar, M., Astengo, F., Chenevier-Gobeaux, C., Claessens, Y.-E., Wussler, D., Kozhuharov, N., Strebel, I., Sabti, Z., deFilippi, C., Seliger, S., Moe, G., Fernando, C., Bayes-Genis, A., van Kimmenade, R. R. J., Pinto, Y., Gaggin, H. K., Wiemer, J. C., Möckel, M., Rutten, J. H. W., van den Meiracker, A. H., Gargani, L., Pugliese, N. R., Pemberton, C., Ibrahim, I., Gegenhuber, A., Mueller, T., Neumaier, M., Behnes, M., Akin, I., Bombelli, M., Grassi, G., Nazerian, P., Albano, G., Bahrmann, P., Newby, D. E., Japp, A. G., Tsanas, A., Shah, A. S. V., Richards, A. M., McMurray, J. J. V., Mueller, C., Januzzi, J. L., Mills, N. L., and on behalf of the CoDE-HF investigators,
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:British Medical Journal
Publisher:BMJ Publishing Group
ISSN (Online):0959-8138
Copyright Holders:Copyright © 2022 The Author(s)
First Published:First published in British Medical Journal 377: e068424
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
304005MRC Precision Medicine Training GrantMorven BarlassMedical Research Council (MRC)MR/N013166/1-LGH/MS/MED25CAMS - Cardiovascular Science