{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T02:35:43Z","timestamp":1787884543296,"version":"build-2784847793"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2022,8,22]],"date-time":"2022-08-22T00:00:00Z","timestamp":1661126400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["CORE grant RE\/18\/6\/34217"],"award-info":[{"award-number":["CORE grant RE\/18\/6\/34217"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Heart Fail"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Reflecting both increased venous pressure and reduced cardiac output, abnormal liver tests are common in patients with severe heart failure and are associated with adverse clinical outcomes. We aimed to investigate the prognostic significance of abnormal liver tests in ambulatory patients with heart failure with reduced ejection fraction (HFrEF), explore any treatment interaction between bilirubin and sodium\u2013glucose cotransporter 2 (SGLT2) inhibitors and examine change in liver tests with SGLT2 inhibitor treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      We explored these objectives in the Dapagliflozin And Prevention of Adverse outcomes in Heart Failure (DAPA\u2010HF) trial, with focus on bilirubin. We calculated the incidence of cardiovascular death or worsening heart failure by bilirubin tertile. Secondary cardiovascular outcomes were examined, along with the change in liver tests at the end\u2010of\u2010study visit. Baseline bilirubin was available in 4720 patients (99.5%). Participants in the highest bilirubin tertile (T3) have more severe HFrEF (lower left ventricular ejection fraction, higher N\u2010terminal pro\u2010B\u2010type natriuretic peptide [NT\u2010proBNP] and worse New York Heart Association class), had a greater burden of atrial fibrillation but less diabetes. Higher bilirubin (T3 vs. T1) was associated with worse outcomes even after adjustment for other predictive variables, including NT\u2010proBNP and troponin T (adjusted hazard ratio for the primary outcome 1.73 [95% confidence interval 1.37\u20132.17],\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001; and 1.52 [1.12\u20132.07],\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.01 for cardiovascular death). Baseline bilirubin did not modify the benefits of dapagliflozin. During follow\u2010up, dapagliflozin had no effect on liver tests.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Bilirubin concentration was an independent predictor of worse outcomes but did not modify the benefits of dapagliflozin in HFrEF. Dapagliflozin was not associated with change in liver tests.<\/jats:p>\n                    <jats:p>Clinical Trial Registration: ClinicalTrials.gov NCT03036124.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.2649","type":"journal-article","created":{"date-parts":[[2022,8,6]],"date-time":"2022-08-06T07:59:26Z","timestamp":1659772766000},"page":"1856-1868","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Liver tests and outcomes in heart failure with reduced ejection fraction: findings from\n                    <scp>DAPA\u2010HF<\/scp>"],"prefix":"10.1093","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7019-7329","authenticated-orcid":false,"given":"Carly","family":"Adamson","sequence":"first","affiliation":[{"name":"BHF Cardiovascular Research Centre University of Glasgow  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorna M.","family":"Cowan","sequence":"additional","affiliation":[{"name":"BHF Cardiovascular Research Centre University of Glasgow  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf A.","family":"de Boer","sequence":"additional","affiliation":[{"name":"Department of Cardiology University Medical Center and University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirta","family":"Diez","sequence":"additional","affiliation":[{"name":"Division of Cardiology Institute Cardiovascular de Buenos Aires  Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaros\u0142aw","family":"Dro\u017cd\u017c","sequence":"additional","affiliation":[{"name":"Department Cardiology Medical University of Lodz  Lodz Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"Duk\u00e1t","sequence":"additional","affiliation":[{"name":"Fifth Department of Internal Medicine Comenius University in Bratislava  Bratislava Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvio E.","family":"Inzucchi","sequence":"additional","affiliation":[{"name":"Section of Endocrinology Yale School of Medicine  New Haven CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"K\u00f8ber","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Rigshospitalet Copenhagen University Hospital  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail N.","family":"Kosiborod","sequence":"additional","affiliation":[{"name":"Saint Luke's Mid America Heart Institute University of Missouri  Kansas City MO USA"},{"name":"The George Institute for Global Health University of New South Wales  Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotta E.A.","family":"Ljungman","sequence":"additional","affiliation":[{"name":"Institute of Medicine, Department of Molecular and Clinical Medicine\/Cardiology, Sahlgrenska Academy University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe A.","family":"Martinez","sequence":"additional","affiliation":[{"name":"Universidad Nacional de C\u00f3rdoba  C\u00f3rdoba Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Ponikowski","sequence":"additional","affiliation":[{"name":"Center for Heart Diseases, University Hospital Wroclaw Medical University  Wroclaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc S.","family":"Sabatine","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Division of Cardiovascular Medicine Brigham and Women's Hospital  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Lindholm","sequence":"additional","affiliation":[{"name":"Late Stage Development, Cardiovascular, Renal 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