N-terminal pro-B-type natriuretic peptide in the diagnosis of acute heart failure

Abstract

Abstract Background N-terminal pro-B-type natriuretic peptide (NT-proBNP) testing can aid in the evaluation of patients with suspected acute heart failure. Current approaches are based on thresholds selected to give good negative and positive predictive value, however the optimal means to utilise NT-proBNP is uncertain. Methods Embase, Medline and Cochrane central register of controlled trials were searched for studies evaluating NT-proBNP in patients with suspected acute heart failure. Individual patient-level data was requested and diagnostic performance for the guideline-recommended rule-out (300 pg/mL) and age-specific rule-in (450, 900 and 1,800 pg/mL) thresholds were evaluated with random-effects meta-analysis. A generalised linear mixed model was developed and validated as a decision-support tool that combines NT-proBNP with clinical characteristics to report the probability of acute heart failure (0–100) for an individual patient. Results Fourteen studies from 13 countries provided individual patient-level data in 10,365 patients, of which, 43.9% (4,549/10,365) had an adjudicated diagnosis of acute heart failure. At the rule-out threshold, the negative predictive value (NPV) was 94.6% (91.9%-96.4%), with significant heterogeneity across patient subgroups (see Figure). At the rule-in thresholds, the positive predictive values (PPV) for those <50 years, 50–75 years, and >75 years were 61.0% (55.3%-66.4%), 72.7% (62.1%-81.3%) and 80.5% (71.1%-87.4%), respectively. In patients without prior heart failure, our model had good discrimination and calibration (area under the curve of 0.931 [0.925–0.938], Brier score of 0.094). A score of <5.6 and ≥45.2 identified 42.3% of patients as low-probability of acute heart failure (NPV 98.5%, 97.6%-99.1%) and 30.5% as high-probability (PPV 75.1%, 67.7%-81.3%) with consistent performance across subgroups. Conclusions The diagnostic performance of NT-proBNP thresholds to rule-out and rule-in acute heart failure varies across patient subgroups. A model that uses NT-proBNP as a continuous measure provides a more consistent and individualised approach. NPV of NT-proBNP threshold of 300 pg/mL Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): British Heart Foundation