Development and validation of a decision support tool for the diagnosis of acute heart failure: systematic review, meta-analysis, and modelling study
Authors: Lee Kuan Ken , Doudesis Dimitrios , Anwar Mohamed , Astengo Federica , Chenevier-Gobeaux Camille , Claessens Yann-Erick , Wussler Desiree , Kozhuharov Nikola , Strebel Ivo , Sabti Zaid , deFilippi Christopher , Seliger Stephen , Moe Gordon , Fernando Carlos , Bayes-Genis Antoni , van Kimmenade Roland R J , Pinto Yigal , Gaggin Hanna K , Wiemer Jan C , Möckel Martin , Rutten Joost H W , van den Meiracker Anton H , Gargani Luna , Pugliese Nicola R , Pemberton Christopher , Ibrahim Irwani , Gegenhuber Alfons , Mueller Thomas , Neumaier Michael , Behnes Michael , Akin Ibrahim , Bombelli Michele , Grassi Guido , Nazerian Peiman , Albano Giovanni , Bahrmann Philipp , Newby David E , Japp Alan G , Tsanas Athanasios , Shah Anoop S V , Richards A Mark , McMurray John J V , Mueller Christian , Januzzi James L , Mills Nicholas L 
Published: June 2022

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.

Study registration

PROSPERO CRD42019159407.