{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:25:22Z","timestamp":1792797922249,"version":"4.5.0"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Soluble ST2 (sST2) is associated with cardiac remodeling and fibrosis. In chronic heart failure, the predictive value of sST2 has not been evaluated in a model that includes both NT-proBNP (N-terminal pro-B-type natriuretic peptide) and hs-TnT (high-sensitivity cardiac troponin T), in a trial in which treatment had a major impact. Therefore, the effects of treatment on sST2 levels in PARADIGM-HF trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure), the relationships between sST2 and outcomes, and the prognostic utility of various sST2 partition values were examined.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results:<\/jats:title>\n            <jats:p>\n              Baseline (n=2002), 1-month (n=1936), and 8-month postrandomization (n=1758) sST2 levels were compared between treatment groups (sacubitril\/valsartan versus enalapril). Relationships between baseline sST2 and (1) heart failure hospitalization, (2) cardiovascular death, and (3) combined heart failure hospitalization and cardiovascular death were assessed using restricted cubic spline models. Adjusted Cox proportional hazards models were used to examine the impact of sST2 change from baseline to 1 month on the hazard of experiencing each outcome. Sacubitril\/valsartan led to more reductions and fewer increases in sST2 levels versus enalapril. After adjusting for other predictors, including NT-proBNP and hs-TnT, baseline sST2 remained an independent predictor of outcomes. Associations between baseline sST2 and outcomes were linear. sST2 increases at 1 month were associated with worse subsequent outcomes and decreased with better outcomes (\n              <jats:italic>P<\/jats:italic>\n              =0.001, 0.012, and 0.009 for the 3 outcomes, respectively).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Sacubitril\/valsartan resulted in greater reductions and less increases in sST2 levels than enalapril. No specific threshold was associated with risk, as linear relationships between baseline sST2 and outcomes were observed. Changes in sST2 from baseline to 1 month were independently associated with the risk of outcomes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Clinical Trial 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: NCT01035255.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circheartfailure.117.004446","type":"journal-article","created":{"date-parts":[[2018,5,10]],"date-time":"2018-05-10T09:15:26Z","timestamp":1525943726000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":68,"title":["Independent Prognostic Value of Serum Soluble ST2 Measurements in Patients With Heart Failure and a Reduced Ejection Fraction in the PARADIGM-HF Trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure)"],"prefix":"10.1161","volume":"11","author":[{"given":"Eileen","family":"O\u2019Meara","sequence":"first","affiliation":[{"name":"Montreal Heart Institute Department of Medicine (Cardiology) and Research Centre, and Universit\u00e9 de Montr\u00e9al, QC, Canada (E.O., J.L.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret F.","family":"Prescott","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation, East Hanover, NJ (M.F.P., L.-M.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Claggett","sequence":"additional","affiliation":[{"name":"Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Boston, MA (B.C., S.D.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean L.","family":"Rouleau","sequence":"additional","affiliation":[{"name":"Montreal Heart Institute Department of Medicine (Cardiology) and Research Centre, and Universit\u00e9 de Montr\u00e9al, QC, Canada (E.O., J.L.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu-May","family":"Chiang","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation, East Hanover, NJ (M.F.P., L.-M.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott D.","family":"Solomon","sequence":"additional","affiliation":[{"name":"Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Boston, MA (B.C., S.D.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milton","family":"Packer","sequence":"additional","affiliation":[{"name":"Baylor Heart and Vascular Hospital, Baylor University Medical Center, Dallas, TX (M.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.V.","family":"McMurray","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Centre, University of Glasgow, United Kingdom (J.J.V.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Zile","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina and Ralph H. Johnson Veterans Administration Medical Center, Charleston (M.R.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000038705.69871.d9"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000047274.66749.fe"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.2217\/bmm.09.56"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2005.09.015"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2660"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI30634"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.114.001785"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.08.047"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2015.01.034"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.728022"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000127958.21003.5A"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0706824"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2009.08.010"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.07.041"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.108.833707"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2008.07.042"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2007.096560"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2007.05.014"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.273"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2016.09.010"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.113.001036"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1409077"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1177\/0091270009343932"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.114.013748"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.09.931"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hft052"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2010.07.014"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-130-6-199903160-00002"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.113.000207"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.110.958223"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2013.10.005"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfr156"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0085466"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfs006"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12265-016-9713-1"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.543"}],"container-title":["Circulation: Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCHEARTFAILURE.117.004446","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T01:38:21Z","timestamp":1715564301000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCHEARTFAILURE.117.004446"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5]]},"references-count":36,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2018,5]]}},"alternative-id":["10.1161\/CIRCHEARTFAILURE.117.004446"],"URL":"https:\/\/doi.org\/10.1161\/circheartfailure.117.004446","relation":{},"ISSN":["1941-3289","1941-3297"],"issn-type":[{"value":"1941-3289","type":"print"},{"value":"1941-3297","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,5]]},"assertion":[{"value":"2017-07-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-06-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e004446"}}