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

JOURNAL OF CARDIAC FAILURE

卷:27

Article

Dillon, Erica M.^1,2  Wei, Shouzuo D.¹  Gupta, Deepak K.^3,4  Nian, Hui⁵  Rodibaugh, Brooks S.¹  Bachmann, Katherine N.^3,6,7  Naftilan, Allen J.⁴  Stevenson, Lynne W.⁴  Brown, Nancy J.^1,2,8 

[1] Vanderbilt Univ, Div Clin Pharmacol, Med Ctr, Nashville, TN USA

[2] Vanderbilt Univ, Dept Internal Med, Med Ctr, Nashville, TN USA

[3] Vanderbilt Univ, Vanderbilt Translat & Clin Cardiovasc Res Ctr, Sch Med, Nashville, TN USA

[4] Vanderbilt Univ, Div Cardiovasc Med, Med Ctr, Nashville, TN USA

[5] Vanderbilt Univ, Div Biostat, Med Ctr, Nashville, TN USA

[6] Vet Adm Tennessee Valley Hlthcare Syst, Nashville, TN USA

[7] Vanderbilt Univ, Med Ctr, Div Diabet Endocrinol & Metab, Nashville, TN USA

[8] Yale Sch Med, Dept Internal Med, New Haven, CT USA

关键词: B-type natriuretic peptide (BNP);    BNP1-32;    NT-proBNP;    natriuretic peptides;    sacubitril/valsartan;    neprilysin;    mass spectrometry;    heart failure;   

DOI  :  10.1016/j.cardfail.2021.05.026

来源: Elsevier

【 摘 要 】

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 IIF, 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, BNP ms correlated with BNPia (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 BNPMS 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 BNPia (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 sacubdril/valsartan treatment.

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