{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:40:15Z","timestamp":1786977615171,"version":"build-2736575974"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":188,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T00:00:00Z","timestamp":1755129600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Dutch Network for Cardiovascular Research"},{"DOI":"10.13039\/501100014470","name":"Netherlands Heart Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014470","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Dutch Cardiac Society"},{"name":"National Heart Failure Working Group as partners of Dutch Cardiovascular Alliance"},{"name":"Netherlands Heart Registration"},{"DOI":"10.13039\/501100014470","name":"Netherlands Heart Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014470","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018890","name":"Dutch Cardiovascular Alliance","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018890","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008084","name":"Neurof\u00f6rbundet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008084","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Guideline-recommended medical therapy (GRMT) improves outcomes in heart failure (HF) with reduced ejection fraction (HFrEF), yet implementation remains suboptimal. TITRATE-HF prospectively evaluated GRMT implementation across different HFrEF stages, and its effect on 1-year prognosis and left ventricular ejection fraction (LVEF).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>TITRATE-HF is an observational cohort study across 48 hospitals in the Netherlands (June 2022\u2013February 2024). A total of 4288 patients were enrolled. This primary analysis includes 12-month follow-up data of all HFrEF patients (n\u2009=\u20093367), stratified into de novo, chronic, and worsening HF. Longitudinal trends in GRMT prescription rates and dosages were analysed. Serial echocardiographic data assessed changes in LVEF between baseline and 12\u2009months. Kaplan\u2013Meier analysis assessed the composite endpoint of all-cause death or HF hospitalization. Median age was 71\u2009years (interquartile range [IQR] 63\u201378), 29% were female, and 56% had non-ischaemic cardiomyopathy. In de novo HFrEF (n\u2009=\u20091353), quadruple therapy was 47.2% at 6\u2009weeks, 64.7% at 3\u2009months, 69.5% at 6\u2009months, and 64.4% at 12\u2009months. In chronic\/worsening HFrEF (n\u2009=\u20091625), quadruple therapy increased from 44.6% at baseline to 54.6% at 12\u2009months, primarily driven by greater sodium\u2013glucose co-transporter 2 inhibitor uptake (66.0% to 78.5%). Among de novo HFrEF patients with serial echocardiograms (n\u2009=\u2009752), median LVEF improved by 10% (IQR 3\u201317%) in ischaemic versus 15% (IQR 9\u201324%) in non-ischaemic cardiomyopathy (p\u2009&amp;lt;\u20090.001). Early quadruple GRMT initiation (within 6\u2009weeks) and higher 6-month doses were associated with greater LVEF improvement. At 12\u2009months, the composite endpoint occurred in 13.3%, 13.3%, and 43.8% of de novo, chronic, and worsening HFrEF patients, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings highlight the importance of early and intensive GRMT implementation, and emphasize the need for continuous dose titration beyond the initial phase to improve LVEF and clinical outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.70006","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T07:45:38Z","timestamp":1755157538000},"page":"2735-2746","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Real-Life Implementation of Guideline-Recommended Medical Therapy in Heart Failure with Reduced Ejection Fraction: Effects on Prognosis and Left Ventricular Ejection Fraction. Primary results of TITRATE-HF"],"prefix":"10.1093","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-1561-3542","authenticated-orcid":false,"given":"Jishnu","family":"Malgie","sequence":"first","affiliation":[{"name":"Cardiovascular Institute, Erasmus MC, Department of Cardiology, Thorax Center , Rotterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari\u00eblle I.","family":"Wilde","sequence":"additional","affiliation":[{"name":"Cardiovascular Institute, Erasmus MC, Department of Cardiology, Thorax Center , Rotterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Koudstaal","sequence":"additional","affiliation":[{"name":"Cardiovascular Institute, Erasmus MC, Department of Cardiology, Thorax Center , Rotterdam ,","place":["The Netherlands"]},{"name":"Department of Cardiology, Groene Hart Ziekenhuis , Gouda ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Denham","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Admiraal de Ruyter Ziekenhuis , Goes ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos A.","family":"da Fonseca","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Frisius MC , Leeuwarden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henk P.","family":"Swart","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Antonius Ziekenhuis , Sneek ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara E.E.","family":"van Ofwegen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Diakonessenhuis , Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayten","family":"Yilmaz","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Bernhoven , Uden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron","family":"Pisters","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Rijnstate , Arnhem ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard C.M.","family":"Linssen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hospital Group Twente , Almelo Hengelo ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikola","family":"Faber","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Bravis Ziekenhuis , Bergen op Zoom Roosendaal ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loek","family":"van Heerebeek","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Onze Lieve Vrouwe Gasthuis , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio E.C.","family":"van de Swaluw","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Beatrixziekenhuis , Gorinchem ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf A.","family":"de Boer","sequence":"additional","affiliation":[{"name":"Cardiovascular Institute, Erasmus MC, Department of Cardiology, Thorax Center , Rotterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Peter","family":"Brunner-La Rocca","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Maastricht University Medical Centre , Maastricht ,","place":["The Netherlands"]},{"name":"School for Cardiovascular Diseases (CARIM), University of Maastricht , Maastricht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasper J.","family":"Brugts","sequence":"additional","affiliation":[{"name":"Cardiovascular Institute, Erasmus MC, Department of Cardiology, Thorax Center , Rotterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,8,14]]},"reference":[{"key":"2026021721522784900_ejhf70006-bib-0001","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1002\/ejhf.2333","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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