{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T01:47:53Z","timestamp":1790732873606,"version":"4.1.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T00:00:00Z","timestamp":1675987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,4,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Elevated BNP and the N-terminal fragment of the proBNP (NT-proBNP) are hallmarks of heart failure (HF). Generally, both biomarkers parallel each other. In patients receiving sacubitril\/valsartan, BNP remained stable while NT-proBNP decreased. As BNP and NT-proBNP assays have limited specificity due to cross-reactivity, we quantified by mass spectrometry (MS) the contributing molecular species.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We included 356 healthy volunteers, 100 patients with acute dyspnoea (49 acute decompensated HF; 51 dyspnoea of non-cardiac origin), and 73 patients with chronic HF and reduced ejection fraction treated with sacubitril\/valsartan. BNP and NT-proBNP immunoreactivities (BNPir and NT-proBNPir) were measured by immunoassays (Abbott ARCHITECT and Roche Diagnostics proBNPII) and proBNP-derived peptides and glycosylation at serine 44 by MS on plasma samples.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>BNPir corresponded to the sum of proBNP1\u2013108, BNP1\u201332, BNP3\u201332, and BNP5\u201332 (R2 = 0.9995), while NT-proBNPir corresponded to proBNP1\u2013108 and NT-proBNP1\u201376 not glycosylated at serine 44 (R2 = 0.992). NT-proBNPir was better correlated (R2 = 0.9597) than BNPir (R2 = 0.7643) with proBNP signal peptide (a surrogate of proBNP production). In patients receiving sacubitril\/valsartan, non-glycosylated NT-proBNP1\u201376 remained constant (P = 0.84) despite an increase in NT-proBNP1\u201376 and its glycosylation (P &amp;lt; 0.0001). ProBNP1\u2013108 remained constant (P = 0.12) while its glycosylation increased (P &amp;lt; 0.0001), resulting in a decrease in non-glycosylated proBNP1\u2013108 (P &amp;lt; 0.0001), and in NT-proBNPir.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Glycosylation interfered with NT-proBNPir measurement, explaining the discrepant evolution of these 2 biomarkers in patients receiving sacubitril\/valsartan. Both BNPir and NT-proBNPir are surrogates of proBNP1\u2013108 production, NT-proBNPir being more robust in the clinical contexts studied.<\/jats:p><\/jats:sec>","DOI":"10.1093\/clinchem\/hvac225","type":"journal-article","created":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T08:16:49Z","timestamp":1676017009000},"page":"350-362","source":"Crossref","is-referenced-by-count":7,"title":["Deconvolution of BNP and NT-proBNP Immunoreactivities by Mass Spectrometry in Heart Failure and Sacubitril\/Valsartan Treatment"],"prefix":"10.1093","volume":"69","author":[{"given":"H\u00e9l\u00e8ne","family":"Nougu\u00e9","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9 and Inserm UMR-S 942 , Paris , France"},{"name":"Department of Anesthesiology and Intensive Care, Saint-Louis and Lariboisi\u00e8re Hospital , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thibault","family":"Michel","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9 and Inserm UMR-S 942 , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Picard","sequence":"additional","affiliation":[{"name":"Heart Failure Unit, Haut-L\u00e9v\u00eaque Hospital , Pessac , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Lassus","sequence":"additional","affiliation":[{"name":"Heart and Lung Center, Helsinki University and Helsinki University Hospital , Helsinki , Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malha","family":"Sadoune","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9 and Inserm UMR-S 942 , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Said","family":"Laribi","sequence":"additional","affiliation":[{"name":"Emergency Medicine Department, Tours University Hospital , Tours , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1055-2231","authenticated-orcid":false,"given":"Alain","family":"Cohen-Solal","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9 and Inserm UMR-S 942 , Paris , France"},{"name":"Department of Cardiology, Lariboisi\u00e8re Hospital , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damien","family":"Logeart","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9 and Inserm UMR-S 942 , Paris , France"},{"name":"Department of Cardiology, Lariboisi\u00e8re Hospital , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Marie","family":"Launay","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9 and Inserm UMR-S 942 , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8087-387X","authenticated-orcid":false,"given":"Nicolas","family":"Vodovar","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9 and Inserm UMR-S 942 , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,2,10]]},"reference":[{"key":"2023040316225778000_","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1002\/ejhf.592","article-title":"2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC","volume":"18","author":"Ponikowski","year":"2016","journal-title":"Eur J Heart Fail"},{"key":"2023040316225778000_","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1016\/j.jacc.2017.04.025","article-title":"2017 ACC\/AHA\/HFSA focused update of the 2013 ACCF\/AHA guideline for the management of heart failure: a report of the American College of Cardiology\/American Heart Association task force on clinical practice guidelines and the Heart Failure Society of America","volume":"70","author":"Yancy","year":"2017","journal-title":"J Am Coll Cardiol"},{"key":"2023040316225778000_","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1373\/clinchem.2010.143883","article-title":"Processing of pro-b-type natriuretic peptide: furin and corin as candidate convertases","volume":"56","author":"Semenov","year":"2010","journal-title":"Clin Chem"},{"key":"2023040316225778000_","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.abb.2006.03.028","article-title":"The precursor to b-type natriuretic peptide is an o-linked glycoprotein","volume":"451","author":"Schellenberger","year":"2006","journal-title":"Arch Biochem Biophys"},{"key":"2023040316225778000_","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1373\/clinchem.2008.113373","article-title":"Processing of pro-brain natriuretic peptide is suppressed by O-glycosylation in the region close to the cleavage site","volume":"55","author":"Semenov","year":"2009","journal-title":"Clin Chem"},{"key":"2023040316225778000_","doi-asserted-by":"crossref","first-page":"3434","DOI":"10.1093\/eurheartj\/ehu314","article-title":"Post-translational modifications enhance NT-proBNP and BNP production in acute decompensated heart failure","volume":"35","author":"Vodovar","year":"2014","journal-title":"Eur Heart J"},{"key":"2023040316225778000_","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1373\/clinchem.2010.157438","article-title":"Secretion of glycosylated pro-B-type natriuretic peptide from normal cardiomyocytes","volume":"57","author":"Tonne","year":"2011","journal-title":"Clin Chem"},{"key":"2023040316225778000_","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1373\/clinchem.2005.057638","article-title":"Dipeptidyl-peptidase IV converts intact B-type natriuretic peptide into its des-SerPro form","volume":"52","author":"Brandt","year":"2006","journal-title":"Clin Chem"},{"key":"2023040316225778000_","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/S0006-291X(05)81194-5","article-title":"Degradation of brain natriuretic peptide by neutral endopeptidase: species specific sites of proteolysis determined by mass spectrometry","volume":"175","author":"Norman","year":"1991","journal-title":"Biochem Biophys Res Commun"},{"key":"2023040316225778000_","doi-asserted-by":"crossref","DOI":"10.1056\/NEJMoa1409077","article-title":"Angiotensin-neprilysin inhibition versus enalapril in heart failure","author":"McMurray","year":"2014","journal-title":"N Engl J Med"},{"key":"2023040316225778000_","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1002\/ejhf.1342","article-title":"Effects of sacubitril\/valsartan on neprilysin targets and the metabolism of natriuretic peptides in chronic heart failure: a mechanistic clinical study","volume":"21","author":"Nougue","year":"2019","journal-title":"Eur J Heart Fail"},{"key":"2023040316225778000_","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1161\/CIRCULATIONAHA.114.013748","article-title":"Angiotensin receptor neprilysin inhibition compared with enalapril on the risk of clinical progression in surviving patients with heart failure","volume":"131","author":"Packer","year":"2015","journal-title":"Circulation"},{"key":"2023040316225778000_","doi-asserted-by":"crossref","first-page":"2425","DOI":"10.1016\/j.jacc.2016.09.931","article-title":"Prognostic implications of changes in n-terminal pro-B-type natriuretic peptide in patients with heart failure","volume":"68","author":"Zile","year":"2016","journal-title":"J Am Coll Cardiol"},{"key":"2023040316225778000_","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1016\/j.jacc.2019.01.018","article-title":"B-type natriuretic peptide during treatment with sacubitril\/valsartan: the PARADIGM-HF trial","volume":"73","author":"Myhre","year":"2019","journal-title":"J Am Coll Cardiol"},{"key":"2023040316225778000_","doi-asserted-by":"crossref","first-page":"17442","DOI":"10.1073\/pnas.0508782102","article-title":"Quantitative mass spectral evidence for the absence of circulating brain natriuretic peptide (BNP-32) in severe human heart failure","volume":"102","author":"Hawkridge","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2023040316225778000_","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1373\/clinchem.2007.097998","article-title":"Cross-reactivity of BNP, NT-proBNP, and proBNP in commercial BNP and NT-proBNP assays: preliminary observations from the IFCC Committee for standardization of markers of cardiac damage","volume":"54","author":"Luckenbill","year":"2008","journal-title":"Clin Chem"},{"key":"2023040316225778000_","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1161\/CIRCHEARTFAILURE.110.960260","article-title":"Comparison of mass spectrometry and clinical assay measurements of circulating fragments of B-type natriuretic peptide in patients with chronic heart failure","volume":"4","author":"Miller","year":"2011","journal-title":"Circ Heart Fail"},{"key":"2023040316225778000_","doi-asserted-by":"crossref","first-page":"e75174","DOI":"10.1371\/journal.pone.0075174","article-title":"Depletion of proBNP1-108 in patients with heart failure prevents cross-reactivity with natriuretic peptides","volume":"8","author":"Roubille","year":"2013","journal-title":"PLoS One"},{"key":"2023040316225778000_","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1373\/clinchem.2006.076141","article-title":"The brain natriuretic peptide (BNP) precursor is the major immunoreactive form of BNP in patients with heart failure","volume":"53","author":"Seferian","year":"2007","journal-title":"Clin Chem"},{"key":"2023040316225778000_","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1016\/j.cardfail.2021.05.026","article-title":"Active B-type natriuretic peptide measured by mass spectrometry and response to sacubitril\/valsartan","volume":"27","author":"Dillon","year":"2021","journal-title":"J Card Fail"},{"key":"2023040316225778000_","author":"IFCC"},{"key":"2023040316225778000_","doi-asserted-by":"crossref","DOI":"10.1373\/clinchem.2015.239673","article-title":"Influence of glycosylation on diagnostic and prognostic accuracy of N-terminal pro-B-type natriuretic peptide in acute dyspnea: data from the Akershus cardiac examination 2 study","author":"Rosjo","year":"2015","journal-title":"Clin Chem"},{"key":"2023040316225778000_","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1373\/clinchem.2016.263749","article-title":"Specificity of b-type natriuretic peptide assays: cross-reactivity with different BNP, NT-proBNP, and proBNP peptides","volume":"63","author":"Saenger","year":"2017","journal-title":"Clin Chem"},{"key":"2023040316225778000_","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1373\/clinchem.2007.100040","article-title":"Immunodetection of glycosylated NT-proBNP circulating in human blood","volume":"54","author":"Seferian","year":"2008","journal-title":"Clin Chem"},{"key":"2023040316225778000_","doi-asserted-by":"crossref","DOI":"10.1161\/CIRCRESAHA.122.320882","article-title":"ProANP metabolism provides new insights into sacubitril\/valsartan mode of action","author":"Michel","year":"2022;130:44\u201357","journal-title":"Circ Res"},{"key":"2023040316225778000_"},{"key":"2023040316225778000_","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1373\/clinchem.2019.302547","article-title":"ProBNP that is not glycosylated at threonine 71 is decreased with obesity in patients with heart failure","volume":"65","author":"Lewis","year":"2019","journal-title":"Clin Chem"},{"key":"2023040316225778000_","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.ijcard.2017.11.001","article-title":"Evolution of natriuretic peptide biomarkers in heart failure: implications for clinical care and clinical trials","volume":"254","author":"Vodovar","year":"2018","journal-title":"Int J Cardiol"},{"key":"2023040316225778000_","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1515\/cclm-2014-0592","article-title":"Head-to-head comparison of 10 natriuretic peptide assays","volume":"53","author":"Collin-Chavagnac","year":"2015","journal-title":"Clin Chem Lab Med"},{"key":"2023040316225778000_","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1373\/clinchem.2019.306621","article-title":"Educational recommendations on selected analytical and clinical aspects of natriuretic peptides with a focus on heart failure: a report from the IFCC Committee on clinical applications of cardiac bio-markers","volume":"65","author":"Kavsak","year":"2019","journal-title":"Clin Chem"},{"key":"2023040316225778000_","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1042\/bj2910083","article-title":"Hydrolysis of human and pig brain natriuretic peptides, urodilatin, C-type natriuretic peptide and some C-receptor ligands by endopeptidase-24.11","volume":"291","author":"Kenny","year":"1993","journal-title":"Biochem J"},{"key":"2023040316225778000_","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1373\/clinchem.2015.243626","article-title":"Unraveling N-terminal pro-B-type natriuretic peptide: another piece to a very complex puzzle in heart failure patients","volume":"61","author":"Jaffe","year":"2015","journal-title":"Clin Chem"},{"key":"2023040316225778000_","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.jchf.2020.09.013","article-title":"Atrial natriuretic peptide and treatment with sacubitril\/valsartan in heart failure with reduced ejection fraction","volume":"9","author":"Murphy","year":"2021","journal-title":"JACC Heart Fail"},{"key":"2023040316225778000_","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1056\/NEJMoa1812851","article-title":"Angiotensin-neprilysin inhibition in acute decompensated heart failure","volume":"380","author":"Velazquez","year":"2019","journal-title":"N Engl J Med"},{"key":"2023040316225778000_","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.jchf.2020.03.002","article-title":"Effects of sacubitril\/valsartan on N-terminal pro-B-type natriuretic peptide in heart failure with preserved ejection fraction","volume":"8","author":"Cunningham","year":"2020","journal-title":"JACC Heart Fail"},{"key":"2023040316225778000_","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1016\/j.jacc.2018.12.063","article-title":"Effect of neprilysin inhibition on various natriuretic peptide assays","volume":"73","author":"Ibrahim","year":"2019","journal-title":"J Am Coll Cardiol"}],"container-title":["Clinical Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/clinchem\/article-pdf\/69\/4\/350\/49733094\/hvac225.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/clinchem\/article-pdf\/69\/4\/350\/49733094\/hvac225.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,3]],"date-time":"2023-12-03T13:57:46Z","timestamp":1701611866000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/clinchem\/article\/69\/4\/350\/7033750"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,10]]},"references-count":36,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,2,10]]},"published-print":{"date-parts":[[2023,4,3]]}},"URL":"https:\/\/doi.org\/10.1093\/clinchem\/hvac225","relation":{},"ISSN":["0009-9147","1530-8561"],"issn-type":[{"value":"0009-9147","type":"print"},{"value":"1530-8561","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,4,3]]},"published":{"date-parts":[[2023,2,10]]}}}