Active B-Type Natriuretic Peptide Measured by Mass Spectrometry and Response to Sacubitril/Valsartan

Background: B-type natriuretic peptide (BNP) immunoassays (BNP_ia) do not differentiate active and inactive forms. Inactive NT-proBNP is used to track heart failure (HF) during treatment with sacubitril/valsartan, which inhibits BNP degradation. Mass spectrometry (MS) may better assess effects of HF treatment on biologically active BNP1-32.

Methods and results: We developed a MS assay with immediate protease inhibition to quantify BNP1-32 over a linear range, using labeled recombinant BNP standard. In 4 healthy volunteers, BNP1-32 by MS (BNP_MS) increased from below the 5 pg/mL detection limit to 228 pg/mL after nesiritide. In patients with HF, BNP_MS was measured in parallel with BNP and NT-proBNP immunoassays before and during sacubitril/valsartan treatment. BNP_MS was 4.4-fold lower than BNP_ia in patients with HF. Among patients not taking sacubitril/valsartan and without end-stage renal disease, BNP_MS correlated with BNP_ia (r_s = 0.77, P < .001) and NT-proBNP (r_s = 0.74, P < .001). After a median of 8 weeks on sacubitril/valsartan, active BNP_MS levels decreased by 50% (interquartile range -98.3% to 41.7%, n = 22, P = .048) and correlated with NT-proBNP (r_s = 0.64, P < .001), but not with BNP_ia (r_s = 0.46, P = .057).

Conclusions: Active BNP measured by MS accounts for only a small amount of BNP measured by immunoassays. Although decreased BNP production was anticipated to be masked by inhibition of degradation, levels of active BNP decreased during chronic sacubitril/valsartan treatment.