Diagnostic properties of natriuretic peptides and opportunities for personalized thresholds for detecting heart failure in primary care

Objectives: Heart failure (HF) is a prevalent syndrome with considerable disease burden, healthcare utilization and costs. Timely diagnosis is essential to improve outcomes. This study aimed to compare the diagnostic performance of B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) in detecting HF in primary care. Our second aim was to explore if personalized thresholds (using age, sex, or other readily available parameters) would further improve diagnostic accuracy over universal thresholds. Methods: A retrospective study was performed among patients without prior HF who underwent natriuretic peptide (NP) testing in the Amsterdam General Practice Network between January 2011 and December 2021. HF incidence was based on registration out to 90 days after NP testing. Diagnostic accuracy was evaluated with AUROC, sensitivity and specificity based on guideline-recommended thresholds (125ng/L for NT-proBNP and 35ng/L for BNP). We used inverse probability of treatment weighting to adjust for confounding. Results: A total of 15,234 patients underwent NP testing, 6,870 with BNP (4.5% had HF), and 8,364 with NT-proBNP (5.7% had HF). NT-proBNP was more accurate than BNP, with an AUROC of 89.9% (95% CI: 88.4-91.2) vs. 85.9% (95% CI 83.5-88.2), with higher sensitivity (95.3 vs. 89.7%) and specificity (59.1 vs. 58.0%). Differentiating NP cut-off by clinical variables modestly improved diagnostic accuracy for BNP and NT-proBNP compared with a universal threshold. Conclusions: NT-proBNP outperforms BNP for detecting HF in primary care. Personalized instead of universal diagnostic thresholds led to modest improvement.