Abstract
Background
B-type natriuretic peptide (BNP) immunoassays (BNPia) 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 (BNPMS) increased from below the 5 pg/mL detection limit to 228 pg/mL after nesiritide.
In patients with HF, BNPMS was measured in parallel with BNP and NT-proBNP immunoassays before and during sacubitril/valsartan
treatment. BNPMS was 4.4-fold lower than BNPia in patients with HF. Among patients not taking sacubitril/valsartan and without end-stage
renal disease, BNPMS correlated with BNPia (rs = 0.77, P < .001) and NT-proBNP (rs = 0.74, P < .001). After a median of 8 weeks on sacubitril/valsartan, active BNPMS levels decreased by 50% (interquartile range –98.3% to 41.7%, n = 22, P = .048) and correlated with NT-proBNP (rs = 0.64, P < .001), but not with BNPia (rs = 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.
Key Words
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Article info
Publication history
Published online: June 13, 2021
Accepted:
May 21,
2021
Received in revised form:
May 14,
2021
Received:
February 1,
2021
Footnotes
Supported by HL143619, HL145293, HL128928, HL133860, HL148661, TR002243 and T32GM007569 from the National Institutes of Health (NIH) and 1IK2CX001678 from the U.S. Department of Veterans Affairs Clinical Sciences Research and Development (CSR&D) Program.
Identification
Copyright
© 2021 Elsevier Inc. All rights reserved.
