A-023 NT-proBNP for Diagnosis of Acute Heart Failure: A Multicenter Prospective Observational Investigation of 1101 Patients in the Chinese Population

Abstract Background N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a standard biomarker for heart failure. Its age-independent rule-out cut-off of 300 ng/L and age-stratified rule-in cut-off of 450, 900 and 1800 ng/L for diagnosis in acute heart failure (AHF) were established in the ICON study. To date, most studies on NT-proBNP testing for AHF diagnosis were generated from Caucasian populations. Our study aims to evaluate the performance of a locally developed NT-proBNP assay using ICON cut-off values for AHF diagnosis in a Chinese population. Methods The study was designed to enroll patients admitted in emergency departments (ED) with suspicious AHF at three clinical sites in China. Dyspneic symptom as the primary compliant triggering presentation to ED was the major inclusion criteria. Age under 18 years and chronic kidney disease with eGFR < 30 ML/min/1.73 m² were key exclusion criteria. Blood specimens were collected and tested at baseline using the Beckman Coulter (Suzhou, China) Access NT-proBNP assay on DxI 800 Immunoassay Analyzer. The NT-proBNP results were compared to an adjudicated clinical diagnosis performed by an independent physician. Performance metrics included sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV) and Area Under Curve (AUC) for both rule-out cut-off (300 ng/L), and age-stratified rule-in cut-off of 450, 900, and 1800 ng/L for age <50, 50-75, and >75 years, respectively. Results A total of 1101 subjects were consecutively enrolled from August 2022 to October 2024. Of all subjects, 378 (34.33%) were adjudicated with AHF with a median age of 71 years, and distribution of 38.96% female. As shown in Table 1, the rule-out cut-off of 300 ng/L demonstrated 99.70% (95% confidence interval [CI]: 98.52% to 99.95) sensitivity and 99.75% (95% CI: 98.58 to 99.96) NPV. The age-stratified rule-in cut-offs had specificities of 85.93% (95% CI: 80.42 to 90.08), 82.83% (95% CI: 77.47 to 87.13) and 76.63% (95% CI: 71.44 to 81.13), and PPV of 67.82% (95% CI: 57.43 to 76.70), 79.59% (95% CI: 73.41 to 84.64), and 68.2% (95% CI: 61.71 to 74.09) for age <50, 50-75, and >75 years, respectively, consistent with ESC guidelines recommendation on NT-proBNP with high NPV (0.94 to 0.98) and lower PPV (0.66-0.67) for AHF. The AUC was 0.965 (95% CI: 0.955 to 0.974) for the age-independent group and 0.984 (95% CI: 0.967 to 1.000), 0.976 (95% CI: 0.965 to 0.988), and 0.950 (95% CI: 0.933to 0.968), for age <50, 50-75, and >75 years, respectively. Conclusion The diagnostic performance of AHF in a Chinese population is comparable to that in Caucasian populations. The study robustly validated the comparable performance of a new NT-proBNP assay using the ICON cut-off values in the diagnosis of AHF in Chinese population. The high PPVs of age-stratified rule-in cut-offs aligns with IFCC recommendations. And the AUC demonstrates excellent discriminative performance in diagnosing AHF. To conclude, the validated Access NT-proBNP assay would accurately allocate patients to AHF versus non-AHF in Chinese clinical settings.