{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:12:27Z","timestamp":1790759547093,"version":"4.1.0"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Sacubitril\/valsartan (S\/V) treatment is associated with reverse cardiac remodeling and reductions in biomarkers reflecting ventricular wall stress and myocardial injury, such as NT-proBNP (N-terminal pro-B-type natriuretic peptide), hs-cTnT (high-sensitivity cardiac troponin T), and soluble suppressor of tumorigenicity 2 (sST2). How longitudinal changes in these biomarkers analyzed collectively are associated with cardiac remodeling in patients with heart failure with reduced ejection fraction treated with S\/V is uncertain.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>In a prospective study of S\/V in patients with heart failure with reduced ejection fraction, this prespecified exploratory analysis included patients with serially collected biomarkers and echocardiographic measures of cardiac remodeling through 12 months of treatment. A multivariate latent growth curve model assessed associations between simultaneous changes in biomarkers and left ventricular ejection fraction and left atrial volume index.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              Seven hundred fifteen out of 794 total study participants were included (mean age 65 years, 73% male). Mean baseline left ventricular ejection fraction and left atrial volume index were 29% and 40 mL\/m\n              <jats:sup>2<\/jats:sup>\n              , respectively. Adjusted geometric mean baseline concentrations for biomarkers included NT-proBNP of 649 pg\/mL, hs-cTnT of 15.9 ng\/L, and sST2 of 24.7 ng\/mL. Following initiation of S\/V, circulating concentrations of NT-proBNP, hs-cTnT, and sST2 significantly decreased within 30 days and remained significantly different than baseline at all subsequent timepoints. From baseline to month 12, decreases in adjusted biomarker concentrations averaged \u221227.9% (95% CI, \u221235.1% to \u221220.7%;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001) for NT-proBNP; \u22126.7% (95% CI, \u22128.8% to \u22124.7%;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001) for hs-cTnT; and \u22121.6% (95% CI, \u22122.9% to \u22120.4%;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001) for sST2. NT-proBNP concentrations were predictive of later changes in hs-cTnT. The magnitude of reductions in NT-proBNP and hs-cTnT concentrations associated with improvements in left ventricular ejection fraction and left atrial volume index. There was no association between changes in sST2 and changes in other measures.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Following initiation of S\/V, NT-proBNP, hs-cTnT, and sST2 concentrations decreased significantly. Longitudinal changes in NT-proBNP and hs-cTnT together associated with left atrial and left ventricular reverse remodeling.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Registration:<\/jats:title>\n            <jats:p>\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              ; Unique identifier: NCT02887183.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circheartfailure.120.008410","type":"journal-article","created":{"date-parts":[[2021,5,15]],"date-time":"2021-05-15T13:30:19Z","timestamp":1621085419000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":40,"title":["Association Between Angiotensin Receptor\u2013Neprilysin Inhibition, Cardiovascular Biomarkers, and Cardiac Remodeling in Heart Failure With Reduced Ejection Fraction"],"prefix":"10.1161","volume":"14","clinical-trial-number":[{"clinical-trial-number":"nct02887183","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5928-5974","authenticated-orcid":true,"given":"Sean P.","family":"Murphy","sequence":"first","affiliation":[{"name":"Massachusetts General Hospital, Boston (S.P.M., A.C., R.R.K., J.L.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret F.","family":"Prescott","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals, East Hanover, NJ (M.F.P., J.H.W., K.M.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan S.","family":"Maisel","sequence":"additional","affiliation":[{"name":"University of California, San Diego School of Medicine (A.S.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javed","family":"Butler","sequence":"additional","affiliation":[{"name":"University of Mississippi Medical Center, Jackson (J.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4986-7129","authenticated-orcid":true,"given":"Ileana L.","family":"Pi\u00f1a","sequence":"additional","affiliation":[{"name":"Detroit Medical Center, Detroit, MI (I.L.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5931-1239","authenticated-orcid":true,"given":"G. 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