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

CoDE-HF investigators, Kuan Ken Lee, Dimitrios Doudesis, Mohamed Anwar, Federica Astengo, Camille Chenevier-Gobeaux, Yann-Erick Claessens, Desiree Wussler, Nikola Kozhuharov, Ivo Strebel, Zaid Sabti, Christopher deFilippi, Stephen Seliger, Gordon Moe, Carlos Fernando, Antoni Bayes-Genis, Roland RJ van Kimmenade, Yigal M Pinto, Hanna K Gaggin, Jan C WiemerMartin Möckel, Joost HW Rutten, Anton H van den Meiracker, Luna Gargani, Nicola R Pugliese, Christopher Pemberton, Irwani Ibrahim, Alfons Gegenhuber, Thomas Mueller, Michael Neumaier, Michael Behnes, Ibrahim Akin, Michele Bombelli, Guido Grassi, Peiman Nazerian, Giovanni Albano, Philipp Bahrmann, David E Newby, Alan Japp, Thanasis Tsanas, Anoop Sv Shah, A Mark Richards, John J. V. McMurray, Christian Mueller, James L Januzzi, Nicholas L Mills

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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: Researchers collaborated to pool individual patient-level data in 10,369 patients with suspected acute heart failure 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% (4,549/10,369) of patients had an adjudicated diagnosis of acute heart failure (73.3% and 29.0% in those with and without prior 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%), and despite using 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 those less than 50 years, 50-75 years and more than 75 years old, respectively. Performance varied in most subgroups, particularly those with obesity, renal impairment or prior heart failure. CoDE-HF was well calibrated with excellent discrimination in those with and without prior heart failure (area under the receiver operator curve [AUC] 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 those without prior heart failure, the diagnostic performance was consistent across all subgroups, and identified 40.3% (2,502/6,208) at low-probability (negative predictive value of 98.6% [97.8 to 99.1%]) and 28.0% (1,737/6,208) 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, we observed that 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.
Original languageEnglish
JournalBritish Medical Journal (BMJ)
Publication statusPublished - 13 Jun 2022


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