Individualised N-terminal Pro-B-type Natriuretic Peptide Thresholds for the Diagnosis of Heart Failure: A Proof-of-Concept Study

Background Heart failure (HF) is underdiagnosed in the community. N-terminal pro-B-type natriuretic peptide (NT-proBNP) has variable sensitivity for HF across different subgroups, particularly for HF with preserved ejection fraction (HFpEF). We calculated individualised NT-proBNP thresholds with 90% sensitivity for the detection of HF, adjusted for age and comorbidities. We investigated whether individualised thresholds had greater sensitivity for the detection of HF, and whether adverse event rates were similarly low in patients with NT-proBNP levels below individualised and fixed thresholds. Methods A total of 1320 patients were recruited from a prospective clinical cohort referred for cardiovascular magnetic resonance (CMR). The diagnostic performance of individualised and fixed NT-proBNP thresholds for detecting HF was compared. The associations between individualised thresholds and the primary composite outcome of first HF hospitalisation or cardiovascular death were investigated. Results Individualised NT-proBNP thresholds ranged from 31 to 2295 pg/ml. Individualised thresholds were more sensitive for the detection of all HF (0.90; 0.80 for 125 pg/ml; 0.55 for 400 pg/ml), HFpEF (0.87; 0.74 for 125 pg/ml; 0.43 for 400 pg/ml), and HF with reduced ejection fraction (0.98; 0.94 for 125 pg/ml; 0.83 for 400 pg/ml) and achieved a high sensitivity of ~0.90 in all patient subgroups. Individualised thresholds associated with adverse outcomes (hazard ratio and 95% confidence interval 6.88 (3.04-15.60)). Patients with NT-proBNP levels below individualised thresholds and a fixed threshold of 125 pg/ml had similarly low event rates. Conclusions Individualised NT-proBNP thresholds, optimised for increased sensitivity, may inform future investigation in community settings.