BNP and NT-proBNP Interpretation in the Neprilysin Inhibitor Era

Purpose of Review Describe the mechanisms that may influence change in measured natriuretic peptide levels when using the neprilysin inhibitor sacubitril to treat a patient with heart failure. Recent Findings Prior to the introduction of the neprilysin inhibitor sacubitril as part of a chemical combination with the angiotensin receptor blocker valsartan shown to reduce mortality and heart failure hospitalizations in patients with heart failure with reduced ejection fraction, the natriuretic peptide assays for B-type natriuretic peptide (BNP) and the amino-terminal proBNP (NT-proBNP) assays were shown to have similar diagnostic accuracy to differentiate heart failure from other etiologies of shortness of breath. Sacubitril/valsartan use has been shown to result in a modest and chronic elevation of BNP while reducing levels of NT-prBNP. This review explores the potential impact of these findings on interpreting natriuretic peptide results for diagnosis and prognosis, as well as explore the challenges associated with the heterogeneity of this finding, highlighting the impact of inhibiting neprilysin, a non-specific endopeptidase with multiple target sites within BNP and other proteins. With increased uptake of sacubitril/valsartan expected in patients with heart failure, interpretation of natriuretic peptide assays becomes somewhat more complex, particularly for BNP. However, knowing a baseline steady-state concentration and using the same assay can assist with BNP interpretation for diagnosis and prognosis.