{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T05:28:59Z","timestamp":1784179739772,"version":"3.55.0"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,1,20]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Atrial fibrillation is associated with heart failure (HF) through a complex cause\u2010and\u2010effect relationship. We performed multiplex screening of plasma proteins in patients with atrial fibrillation to identify biomarkers and pathways associated with hospitalization for HF. Additionally, we aimed to identify potential pathophysiological differences between HF with reduced ejection fraction and HF with preserved ejection fraction at baseline in patients with atrial fibrillation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">Using a case\u2013cohort design of patients with atrial fibrillation from the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial, 596 cases with HF hospitalizations during follow\u2010up and 4029 randomly selected controls without HF hospitalization. Plasma obtained at randomization was analyzed with conventional immunoassays and proximity extension assay panels. Biomarker associations with HF hospitalization were evaluated using random survival forest, Boruta, and Cox\u2010regression analyses. Associations between biomarkers and HF subtype were evaluated with Wilcoxon\u2212Mann\u2013Whitney test with Bonferroni\u2013Holm adjustment for multiplicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      The biomarkers most strongly and significantly associated with increased risk of HF hospitalization after adjustment for clinical characteristics, renal function, and cardiac biomarkers, and after correction for multiplicity (\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      \u22640.00027), were NT\u2010proBNP (N\u2010terminal pro\u2010B\u2010type natriuretic peptide), BNP (B\u2010type natriuretic peptide), hs\u2010cTnT (high\u2010sensitivity cardiac troponin T), fibroblast growth factor 23, spondin 1, insulin\u2010like growth factor binding protein 7, urokinase\u2010type plasminogen activator receptor, osteopontin, pentraxin\u2010related protein 3, and transferrin receptor protein 1R. Among patients with prevalent HF, 9 biomarkers remained significant after adjustment for multiplicity; NT\u2010proBNP, BNP, hs\u2010cTnT, renin, angiotensin\u2010converting enzyme 2, growth differentiation factor 15, and interleukin\u20106 levels were higher in HF with reduced ejection fraction, whereas levels of stem cell factor and leptin were higher in HF with preserved ejection fraction (all\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      &lt;0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Of 268 evaluated biomarkers, this study identified biomarkers representing mechanisms strongly associated with subsequent HF hospitalization. HF with reduced ejection fraction was more strongly associated with cardiorenal dysfunction and inflammation markers, while HF with preserved ejection fraction was associated with adipose metabolism and tissue repair proteins.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.045970","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T11:45:26Z","timestamp":1768391126000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Plasma Biomarkers Associated With Heart Failure Hospitalization Among Patients With Atrial Fibrillation and Subtypes of Heart Failure"],"prefix":"10.1161","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6239-199X","authenticated-orcid":false,"given":"Tymon","family":"Pol","sequence":"first","affiliation":[{"name":"Uppsala University","place":["Uppsala, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6473-8798","authenticated-orcid":false,"given":"Johan","family":"Lindb\u00e4ck","sequence":"additional","affiliation":[{"name":"Uppsala Clinical Research Center","place":["Uppsala, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9969-3921","authenticated-orcid":false,"given":"Jonas","family":"Oldgren","sequence":"additional","affiliation":[{"name":"Uppsala University","place":["Uppsala, Sweden"]},{"name":"Uppsala Clinical Research Center","place":["Uppsala, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1444-2462","authenticated-orcid":false,"given":"John H.","family":"Alexander","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute","place":["Durham"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3955-5671","authenticated-orcid":false,"given":"Agneta","family":"Siegbahn","sequence":"additional","affiliation":[{"name":"Uppsala Clinical Research Center","place":["Uppsala, Sweden"]},{"name":"Uppsala University","place":["Uppsala, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0378-6531","authenticated-orcid":false,"given":"Lars","family":"Wallentin","sequence":"additional","affiliation":[{"name":"Uppsala University","place":["Uppsala, Sweden"]},{"name":"Uppsala Clinical Research Center","place":["Uppsala, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7420-743X","authenticated-orcid":false,"given":"Ziad","family":"Hijazi","sequence":"additional","affiliation":[{"name":"Uppsala University","place":["Uppsala, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.i4482"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab368"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.02.092"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.312706"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.15420\/cfr.2021.37"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.112.129437"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.49"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2012.03.015"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2010.03.011"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2016.09.010"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.980"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.117.008108"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000097109.90783.FC"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.122.009694"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","unstructured":"Granger CB Alexander JH McMurray JJ Lopes RD Hylek EM Hanna M Al\u2010Khalidi HR Ansell J Atar D Avezum A et\u00a0al. Apixaban versus warfarin in patients with atrial fibrillation. 2011;365:981\u2013992. doi: 10.1056\/NEJMoa1107039","DOI":"10.1056\/NEJMoa1107039"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0095192"},{"key":"e_1_3_1_18_2","first-page":"22","article-title":"A comparison of the proximity extension assay with established immunoassays","author":"Siegbahn A","year":"2017","unstructured":"Siegbahn A, Eriksson S, Lindb\u00e4ck J, Wallentin L. A comparison of the proximity extension assay with established immunoassays. Science. 2017;22\u201325. sponsored supplement.","journal-title":"Science"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.07.093"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2012.11.082"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.114.011204"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2015.09.018"},{"key":"e_1_3_1_23_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2016.1170"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1214\/08-AOAS169"},{"key":"e_1_3_1_25_2","first-page":"1","article-title":"Feature selection with the Boruta package","volume":"36","author":"Witold RRM","year":"2010","unstructured":"Witold RRM. Feature selection with the Boruta package. J Stat Softw. 2010;36:1\u201313.","journal-title":"J Stat Softw"},{"key":"e_1_3_1_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.120.018984"},{"key":"e_1_3_1_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvab262"},{"key":"e_1_3_1_28_2","doi-asserted-by":"publisher","unstructured":"Siegbahn A Lindback J Hijazi Z Aberg M Alexander JH Eikelboom JW Lopes RD Pol T Oldgren J Granger CB et\u00a0al. Multiplex protein screening of biomarkers associated with major bleeding in patients with atrial fibrillation treated with oral anticoagulation. 2021;19:2726\u20132737. doi: 10.1111\/jth.15498","DOI":"10.1111\/jth.15498"},{"key":"e_1_3_1_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2022.03.009"},{"key":"e_1_3_1_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.121.056663"},{"key":"e_1_3_1_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-44680-3"},{"key":"e_1_3_1_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2018.01.119"},{"key":"e_1_3_1_33_2","doi-asserted-by":"publisher","DOI":"10.1159\/000450573"},{"key":"e_1_3_1_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.414"},{"key":"e_1_3_1_35_2","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2016.255174"},{"key":"e_1_3_1_36_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00392-019-01513-y"},{"key":"e_1_3_1_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.431"},{"key":"e_1_3_1_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.1482"},{"key":"e_1_3_1_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2023.06.031"},{"key":"e_1_3_1_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature00786"},{"key":"e_1_3_1_41_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.303587"},{"key":"e_1_3_1_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)31964-4"},{"key":"e_1_3_1_43_2","doi-asserted-by":"publisher","DOI":"10.1177\/1470320316668435"},{"key":"e_1_3_1_44_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00046.2011"},{"key":"e_1_3_1_45_2","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12675"},{"key":"e_1_3_1_46_2","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/534320"},{"key":"e_1_3_1_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2016.11.194"},{"key":"e_1_3_1_48_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000083716.82622.FD"},{"key":"e_1_3_1_49_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvac120"},{"key":"e_1_3_1_50_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.123.010618"},{"key":"e_1_3_1_51_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehac632"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.125.045970","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T11:11:53Z","timestamp":1782990713000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.125.045970"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,20]]},"references-count":50,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,1,20]]}},"alternative-id":["10.1161\/JAHA.125.045970"],"URL":"https:\/\/doi.org\/10.1161\/jaha.125.045970","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,20]]},"assertion":[{"value":"2025-09-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e045970"}}