NT-proBNP testing for heart failure diagnosis in people with atrial fibrillation: A diagnostic accuracy study

N-terminal pro-B-type natriuretic peptides (NT-proBNP) are important in the assessment of suspected heart failure (HF). However, NT-proBNP concentrations are elevated in atrial fibrillation (AF), creating diagnostic uncertainty. The aim of this study was to assess the diagnostic accuracy of NT-proBNP for HF in people with AF, overall and by age, sex and BMI.

Retrospective study of all patients with a NT-proBNP test in their primary care electronic health record among English GP practices provided through the Clinical Practice Research Datalink (2004-2018) and linked to secondary care data. The accuracy of NT-proBNP for diagnosing HF within six months was assessed for people with and without AF at thresholds of 125, 400, 660 and 2,000 pg/mL, including by age, sex and BMI. Among 155,347 people who had an NT-proBNP test organized in primary care (median age 61 years), 17,403 (11.2%) had pre-existing AF. Of the 155,347 people included, 14,585 (9.4%) were subsequently diagnosed with HF, including 4,168/17,403 (23.9%) people with AF (median NT-proBNP = 1,852 pg/mL, interquartile range (IQR) [974, 3,459] pg/mL) and 10,417/137,944 (7.6%) without AF (1,110 pg/mL, IQR [434, 3,108] pg/mL). NT-proBNP discriminated better overall among people without AF (AUC = 0.877 (95% confidence interval (CI) [0.873, 0.881]) than with AF (AUC = 0.743 (95% CI [0.735, 0.751]). Among people with AF, NT-proBNP sensitivity and specificity at a 125 pg/mL threshold was 98.8% (95% CI [98.5%, 99.1]) and 13.2% (95% CI [12.6%, 13.7]) and at 400 pg/mL 93.2% (95% CI [92.4, 93.9]) and 35.5% (95% CI [34.7, 36.3]). Among people without AF the corresponding results were 92.9% (95% CI [92.4, 93.4]) and 53.8% (95% CI [53.6, 54.1]) at 125 pg/mL and 77.1% (95% CI [76.3, 77.9]) and 84.9% (95% CI [84.7, 85.1]) at 400 pg/mL. NT-proBNP discriminated less well among people with AF aged ≥65 years compared to <65years (e.g., AUC in people aged 65-75 years was 0.725, 95% CI [0.712, 0.739]). Increasing the threshold for a positive test among people with AF from 125 pg/mL to 660 pg/mL would reduce the number of false positive results by 26.0%, whilst retaining a negative predictive value of 91.5 (95% CI [90.8, 92.1]), albeit with a 10.6% increase in the proportion of those tested with AF having a missed or delayed HF diagnosis. The main limitation of the study is that it relies on routinely collected primary care data and people with an NT-proBNP result <400 pg/mL may not have been referred for further assessment, impacting upon the diagnostic accuracy below this threshold.

NT-proBNP discriminates more accurately for HF among people without AF than with AF. A higher referral threshold could be considered in AF to account for higher median NT-proBNP levels but this would also increase missed HF diagnoses.