ESC Heart Failure Association age-adjusted natriuretic peptide thresholds for a new diagnosis of heart failure: diagnostic accuracy study
Authors: Taylor C J , Taylor K S , Ordonez-Mena J M , Jones N R , Bayes-Genis A , Hobbs F D R 
Published: October 2024

Abstract

Background
Natriuretic peptide (NP) testing is an important part of the heart failure (HF) diagnostic pathway. The European Society of Cardiology (ESC) HF guidelines currently recommend a NT-proBNP cut-off &lt;125pg/mL to rule out HF in the community.1 However, NP level increases with age and an NT-proBNP above 125pg/mL is common in older people in the general population. The ESC Heart Failure Association (HFA) recently published a practical algorithm for early diagnosis of HF recommending age-specific rule-in NT-proBNP thresholds: ≥125pg/ml for patients aged under 50 years, ≥250pg/ml for patients aged 50-75 years, and ≥500pg/ml for patients over 75 years (Figure 1).2

Purpose
Our aim was to assess NT-proBNP test performance for HF diagnosis at the ESC HFA age-specific thresholds.

Method
We analysed our existing diagnostic accuracy study dataset containing primary care data from the Clinical Practice Research Datalink (CPRD) linked to inpatient Hospital Episode Statistics (HES) inpatient data between 2004 and 2018. NT-proBNP results were taken from the GP record (index test) and the primary outcome (reference standard) was a HF diagnostic code entered in CPRD or HES within six months of the test. NT-proBNP accuracy for HF was assessed by calculating sensitivity, specificity, positive predictive values (PPV), and negative predictive value (NPV). Receiver operating characteristic (ROC) curves were plotted to assess overall test performance.

Results
In total, 229,580 patients had an NP test and 21,102 (9.2%) were diagnosed with HF. The current ESC NT-proBNP threshold ≥125pg/mL had sensitivity 94.6% (95% confidence intervals [CI] 94.2 to 95.0), specificity 50.0% (95%CI 49.7 to 50.3), PPV 16.4% (16.1 to 16.6), NPV 98.9% (98.8 to 99.0)). Area under the ROC curve was 0.874 (0.871 to 0.877).
Age-specific NT-proBNP thresholds performance:
Below 50 years (≥125pg/mL): 32,882 people tested, HF prevalence 3.8%. Sensitivity 83.5 % (81.3 to 85.5), specificity 77.6% (77.2 to 78.1), PPV 13.0% (12.2 to 13.7), NPV 99.2% (99.0 to 99.3).
50 to 75 years ≥250pg/mL: 105,771 people tested, HF prevalence 9.8%. Sensitivity 88.5% (87.9 to 89.1), specificity 67.8% (67.5 to 68.0), PPV 23.1% (22.6 to 23.5), NPV 98.2% (98.1 to 98.3).
Above 75 years ≥500pg/mL: 16,694 people tested, HF prevalence 17.5%. Sensitivity 84.4% (83.0 to 85.7), specificity 63.5% (62.7 to 64.3), PPV 32.8% (31.7 to 33.9), NPV 95.0% (94.6 to 95.5).

Conclusion
The age-specific NT-proBNP thresholds in the HFA practical algorithm had higher specificity so fewer people without HF would be referred, reducing demand for echocardiography and cardiology assessment overall meaning people with HF could be seen earlier. However, lower sensitivity means some cases of HF would initially be missed. NT-proBNP was a reliable ‘rule-out’ test at population level. The optimal NT-proBNP threshold will depend on the priorities and capacity of the national healthcare system.