{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T10:27:37Z","timestamp":1775816857389,"version":"3.50.1"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:00:00Z","timestamp":1760486400000},"content-version":"vor","delay-in-days":719,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T00:00:00Z","timestamp":1698364800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007225","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["MOST 107-2314-B-650-010"],"award-info":[{"award-number":["MOST 107-2314-B-650-010"]}],"id":[{"id":"10.13039\/100007225","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007225","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["MOST 107\u20102314\u2010B\u2010650\u2010010"],"award-info":[{"award-number":["MOST 107\u20102314\u2010B\u2010650\u2010010"]}],"id":[{"id":"10.13039\/100007225","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Patients with heart failure (HF) and reduced left ventricular ejection fraction (LVEF) accompanied by significant mitral regurgitation (MR) had poor outcome. Several vasodilator trials showed neutral results. We aimed to investigate the effect of early up-titration of hydralazine combined with conventional treatment in acute HF with severe systolic dysfunction and significant MR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>The study was open-labelled, one-to-one ratio randomized designed. Consecutively hospitalized patients with decompensated HF symptoms, LVEF &amp;lt; 35%, and MR more than moderate severity were enrolled after exclusion. All participants with inadequate preload should have intake promotion with\/without fluid supply. Patients receiving evidence-based medications (EBMs) as conventional treatment served as the control. Hydralazine + conventional treatment group received up-titration of hydralazine at Days 1\u20135 of the index admission combined with EBMs and throughout the course of follow-up. The endpoints included cardiovascular (CV) death and HF rehospitalization. Totally, 408 patients were enrolled (203 in conventional treatment and 205 in hydralazine + conventional treatment). The mean follow-up period was 3.5 years. The mean dose of hydralazine was 191 mg at index admission and 264 mg at study end in hydralazine + conventional treatment group. Both groups did not significantly differ in prescription rates and dosages of EBMs (all P &amp;gt; 0.05) at study end. Side effects did not differ between the two groups. Finally, 51% (104 out of 203 cases) reached endpoints in conventional group and 34.6% (71 out of 205 cases) in hydralazine + conventional treatment group, which had a significant reduction in CV events (hazard ratio 0.613, 95% confidence interval 0.427\u20130.877, P &amp;lt; 0.001). In-hospital death during the index admission was significantly higher in conventional group (5.4% vs. 0.5%, respectively; P = 0.001).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>When administered without inadequate preload, combining early up-titration of hydralazine with EBMs improves outcome in patients with severe systolic dysfunction and significant MR, and it is safe and well tolerated.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.14564","type":"journal-article","created":{"date-parts":[[2023,10,28]],"date-time":"2023-10-28T02:11:54Z","timestamp":1698459114000},"page":"198-208","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Hydralazine Combined with Conventional Therapy Improved Outcomes in Severe Systolic Dysfunction and Mitral Regurgitation"],"prefix":"10.1093","volume":"11","author":[{"given":"Shih-Hung","family":"Hsiao","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, E-Da Hospital, I-Shou University , Kaohsiung ,","place":["Taiwan"]},{"name":"School of Medicine, National Yang-Ming University , Taipei ,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao-Sheng","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, E-Da Hospital, I-Shou University , Kaohsiung ,","place":["Taiwan"]},{"name":"Department of Internal Medicine, College of Medicine, Fu Jen Catholic University , New Taipei City ,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jau-Wen","family":"Shiau","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering, National Chung Hsing University , Taichung ,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kuan-Rau","family":"Chiou","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital , New Taipei City ,","place":["Taiwan"]},{"name":"School of Medicine, Taipei Medical University , Taipei ,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,10,27]]},"reference":[{"key":"2026012113072145100_ehf214564-bib-0001","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1093\/eurheartj\/ehab368","article-title":"2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure of the European Society of Cardiology (ESC). 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