Document Type
Article
Publication Date
4-12-2025
Abstract
AIMS: B-type natriuretic peptide (BNP) and mid-regional pro-atrial natriuretic peptide (MR-proANP) testing are guideline-recommended to aid in the diagnosis of acute heart failure. Nevertheless, the diagnostic performance of these biomarkers is uncertain.
METHODS AND RESULTS: We performed a systematic review and individual patient-level data meta-analysis to evaluate the diagnostic performance of BNP and MR-proANP. We subsequently developed and externally validated a decision-support tool called CoDE-HF that combines natriuretic peptide concentrations with clinical variables using machine learning to report the probability of acute heart failure. Fourteen studies from 12 countries provided individual patient-level data in 8493 patients for BNP and 3899 patients for MR-proANP, in whom, 48.3% (4105/8493) and 41.3% (1611/3899) had an adjudicated diagnosis of acute heart failure, respectively. The negative predictive value (NPV) of guideline-recommended thresholds for BNP (100 pg/mL) and MR-proANP (120 pmol/L) was 93.6% (95% confidence interval 88.4-96.6%) and 95.6% (92.2-97.6%), respectively, whilst the positive predictive value (PPV) was 68.8% (62.9-74.2%) and 64.8% (56.3-72.5%). Significant heterogeneity in the performance of these thresholds was observed across important subgroups. CoDE-HF was well calibrated with excellent discrimination in those without prior acute heart failure for both BNP and MR-proANP [area under the curve of 0.914 (0.906-0.921) and 0.929 (0.919-0.939), and Brier scores of 0.110 and 0.094, respectively]. CoDE-HF with BNP and MR-proANP identified 30% and 48% as low-probability [NPV of 98.5% (97.1-99.3%) and 98.5% (97.7-99.0%)], and 30% and 28% as high-probability [PPV of 78.6% (70.4-85.0%) and 75.1% (70.9-78.9%)], respectively, and performed consistently across subgroups.
CONCLUSION: The diagnostic performance of guideline-recommended BNP and MR-proANP thresholds for acute heart failure varied significantly across patient subgroups. A decision-support tool that combines natriuretic peptides and clinical variables was more accurate and supports more individualized diagnosis.
STUDY REGISTRATION: PROSPERO number, CRD42019159407.
Recommended Citation
Doudesis, Dimitrios; Lee, Kuan Ken; Anwar, Mohamed; Singer, Adam J.; Hollander, Judd E.; Chenevier-Gobeaux, Camille; Claessens, Yann-Erick; Wussler, Desiree; Weil, Dominic; Kozhuharov, Nikola; Strebel, Ivo; Sabti, Zaid; deFilippi, Christopher; Seliger, Stephen; Mesquita, Evandro Tinoco; Wiemer, Jan C.; Möckel, Martin; Coste, Joel; Jourdain, Patrick; Kimiaki, Komukai; Yoshimura, Michihiro; Ibrahim, Irwani; Ooi, Shirley Beng Suat; Kuan, Win Sen; Gegenhuber, Alfons; Mueller, Thomas; Hanon, Olivier; Vidal, Jean-Sébastien; Cameron, Peter; Lam, Louisa; Freedman, Ben; Chung, Tommy; Collins, Sean P.; Lindsell, Christopher J.; Newby, David E.; Japp, Alan G.; Shah, Anoop S. V.; Villacorta, Humberto; Richards, A. Mark; McMurray, John J V; Mueller, Christian; Januzzi, James L.; Mills, Nicholas L.; Moe, Gordon; Fernando, Carlos; Gaggin, Hanna K.; Bayes-Genis, Antoni; Van Kimmenade, Roland RJ; Pinto, Yigal; Rutten, Joost H. W.; Van Den Meiracker, Anton H.; Gargani, Luna; Pugliese, Nicola R.; Christopher, Pemberton; Neumaier, Michael; Behnes, Michael; Akin, Ibrahim; Bombelli, Michele; Grassi, Guido; Nazerian, Peiman; Albano, Giovanni; and Bahrmann, Philipp, "Machine Learning to Optimize Use of Natriuretic Peptides in the Diagnosis of Acute Heart Failure" (2025). Department of Emergency Medicine Faculty Papers. Paper 270.
https://jdc.jefferson.edu/emfp/270
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Supplementary Data
PubMed ID
40219913
Language
English
Comments
This article is the author's final published version in European Heart Journal: Acute Cardiovascular Care, Volume 14, Issue 8, August 2025, Pages 474–488.
The published version is available at https://doi.org/10.1093/ehjacc/zuaf051. Copyright © The Author(s) 2025.