Assessment of the diagnostic value of NT-proBNP in heart failure with preserved ejection fraction

Heart failure with preserved ejection fraction (HFpEF) is a common concern in the medical field due to its prevalence in an ageing western population. HFpEF is associated with significant morbidity and mortality not dissimilar to heart failure (HF) with reduced ejection fraction. N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and echocardiography are the guideline diagnostic indicators of HF and their use is being examined in this study, with the aim to consider NT-proBNP thresholds performance as a rule-out test. The current National Institute for Health and Care Excellence (NICE) and European guidelines recommend a single NT-proBNP threshold of >400 ng/L and >125 ng/L, respectively, to trigger echocardiographic assessment of HF in the outpatient setting. NT-proBNP levels are known to increase with age and worsening renal function. Unsurprisingly, a single threshold significantly increases demand for echocardiography. NT-proBNP measurements and echocardiograms performed within six months of each other were included for 469 patients with suspected HF. A significant relationship between NT-proBNP levels and diastolic dysfunction was established. NT-proBNP levels and age are significant predictors of diastolic dysfunction in uni-variant (odds ratio 1.251, 95% confidence interval [CI], p<0.001) and multi-variant analysis (odds ratio 1.174, 95%CI, p=0.002). High negative-predictive values (NPVs) were obtained in severe diastolic impairment with the NPV being 95% at the European NT-proBNP cut-off of 125 ng/L, 95% at the NICE cut-off of 400 ng/L, 93% at 1,000 ng/L and 92% at 2,000 ng/L. There is a significant association between NT-proBNP and diastolic dysfunction. NT-proBNP and age can predict diastolic dysfunction, and age can predict NT-proBNP levels, thus, these variables should be considered when considering referral for an echocardiogram. Most importantly, at higher NT-proBNP cut-offs the NPVs remain above 90% suggesting that different thresholds for subpopulations could yield a more effective strategy and mitigate the increased demand for echocardiography.