{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T13:29:22Z","timestamp":1787146162872,"version":"build-2736575974"},"reference-count":12,"publisher":"Walter de Gruyter GmbH","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Heart failure with improved ejection fraction (HFimpEF) is characterized by recovery of left ventricular systolic function after treatment for heart failure with reduced ejection fraction. The safety of withdrawing guideline-directed medical therapy (GDMT) after recovery remains uncertain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate the effects of GDMT withdrawal versus continuation in patients with recovered or improved left ventricular systolic function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A systematic review was conducted according to PRISMA 2020 guidelines. MEDLINE, Embase, LILACS, and the Cochrane Central Register of Controlled Trials were searched through March 2025. Comparative studies evaluating GDMT withdrawal versus continuation in HFimpEF were included. The primary outcome was relapse of left ventricular systolic dysfunction. Secondary outcomes were heart failure hospitalization, mortality, and quality of life.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Eight studies were included. Relapse of left ventricular dysfunction occurred in up to 58% of patients after therapy withdrawal in recovered dilated cardiomyopathy, whereas most patients with atrial fibrillation\u2013mediated cardiomyopathy maintained preserved ventricular function during short-term follow-up. In a meta-analysis of three prospective studies (n = 133), GDMT withdrawal was associated with a significantly increased risk of relapse compared with continued therapy (OR 15.37, 95% CI 2.75\u201385.82; I\n                      <jats:sup>2<\/jats:sup>\n                      = 0%). Observational studies consistently reported higher rates of heart failure hospitalization and adverse cardiovascular outcomes after treatment withdrawal.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>GDMT withdrawal may increase the risk of recurrent ventricular dysfunction and adverse cardiovascular outcomes in HFimpEF. The available evidence supports continuation of therapy in most patients, although further randomized studies are needed to identify patients who may safely discontinue treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2478\/rjim-2026-0015","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T04:56:37Z","timestamp":1784782597000},"source":"Crossref","is-referenced-by-count":0,"title":["Withdrawal versus continuation of guideline-directed medical therapy in heart failure with improved ejection fraction: a systematic review and meta-analysis"],"prefix":"10.2478","author":[{"given":"Juan Camilo Hern\u00e1ndez","family":"Jaramillo","sequence":"first","affiliation":[{"name":"Corporaci\u00f3n Universitaria Remington , Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Esteban Su\u00e1rez","family":"Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n Universitaria Aut\u00f3noma de las Am\u00e9ricas , Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Cristina Oviedo","family":"Arroyo","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n Universitaria San Mart\u00edn , Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Jos\u00e9 D\u00edaz","family":"Guti\u00e9rrez","sequence":"additional","affiliation":[{"name":"Universidad Metropolitana de Barranquilla , Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3759-5448","authenticated-orcid":false,"given":"Gloria Ibis Tirado","family":"Romero","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n Universitaria de Ciencias de la Salud , Bogot\u00e1 , Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"2026081913080299000_j_rjim-2026-0015_ref_001","unstructured":"HEIDENREICH PA, BOZKURT B, AGUILAR D, ALLEN LA, BYUN JJ, COLVIN MM, et al. AHA\/ACC\/HFSA guideline for the management of heart failure: a report of the American College of Cardiology\/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022;79(17)."},{"key":"2026081913080299000_j_rjim-2026-0015_ref_002","doi-asserted-by":"crossref","unstructured":"BOZKURT B, COATS AJS, TSUTSUI H, ABDELHAMID CM, ADAMOPOULOS S, ALBERT N, et al. Universal definition and classification of heart failure. Eur J Heart Fail. 2021;23(3):352\u201380","DOI":"10.1002\/ejhf.2115"},{"key":"2026081913080299000_j_rjim-2026-0015_ref_003","doi-asserted-by":"crossref","unstructured":"BASURAY A, FRENCH B, KY B, VOROVICH E, OLT C, SWEITZER NK, et al. Heart failure with recovered ejection fraction: clinical description, biomarkers, and outcomes. Circulation. 2014;129(23):2380\u20132387.","DOI":"10.1161\/CIRCULATIONAHA.113.006855"},{"key":"2026081913080299000_j_rjim-2026-0015_ref_004","doi-asserted-by":"crossref","unstructured":"MANN DL, BARGER PM, BURKHOFF D. Myocardial recovery and the failing heart: myth, magic, or molecular target? J Am Coll Cardiol. 2012;60(24):2465\u20132472.","DOI":"10.1016\/j.jacc.2012.06.062"},{"key":"2026081913080299000_j_rjim-2026-0015_ref_005","doi-asserted-by":"crossref","unstructured":"HALLIDAY BP, WASSALL R, LOTA AS, KHALIQUE Z, GREGSON J, NEWSOME S, et al. Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy (TRED-HF): an open-label, pilot, randomised trial. Lancet. 2019;393(10166):61\u201373.","DOI":"10.1016\/S0140-6736(18)32484-X"},{"key":"2026081913080299000_j_rjim-2026-0015_ref_006","doi-asserted-by":"crossref","unstructured":"BAKHSH A, THANASSOULIS G, ENGERT JC, ELSTEIN E, HUYNH T, GIANNETTI N. Withdrawal of beta-blockers and ACE inhibitors after left ventricular systolic function recovery in dilated cardiomyopathy. Eur Heart J. 2020;41(Suppl 2):ehaa946.081.","DOI":"10.1093\/ehjci\/ehz872.081"},{"key":"2026081913080299000_j_rjim-2026-0015_ref_007","doi-asserted-by":"crossref","unstructured":"SEGAN L, KISTLER PM, NANAYAKKARA S, TAYLOR A, HARE J, COSTELLO B, et al. Withdrawal of heart failure therapy after atrial fibrillation rhythm control with ejection fraction normalization: the WITHDRAW-AF trial. Eur Heart J. 2026;47(2):250\u2013262.","DOI":"10.1093\/eurheartj\/ehaf563"},{"key":"2026081913080299000_j_rjim-2026-0015_ref_008","doi-asserted-by":"crossref","unstructured":"CHEN QF, LU Y, KATSOURAS CS, PENG Y, SUN J, LI M, et al. Characteristics, outcomes, and the necessity of continued guideline-directed medical therapy in patients with heart failure with improved ejection fraction. Ann Med. 2025;57(1):2442535.","DOI":"10.1080\/07853890.2024.2442535"},{"key":"2026081913080299000_j_rjim-2026-0015_ref_009","unstructured":"VADUGANATHAN M, CLAGGETT BL, JHUND PS, CUNNINGHAM JW, FERREIRA JP, ZANNAD F, et al. Continuation versus withdrawal of guideline-directed medical therapy in heart failure with improved ejection fraction. Circulation. 2024."},{"key":"2026081913080299000_j_rjim-2026-0015_ref_010","doi-asserted-by":"crossref","unstructured":"CHEN Y, QIU Z, JIANG J, SU X, HUANG F, TANG J, et al. Outcomes of spironolactone withdrawal in dilated cardiomyopathy with improved ejection fraction. Front Cardiovasc Med. 2021;8:725399.","DOI":"10.3389\/fcvm.2021.725399"},{"key":"2026081913080299000_j_rjim-2026-0015_ref_011","doi-asserted-by":"crossref","unstructured":"LEE SH, RHEE TM, SHIN D, HONG D, CHOI KH, KIM HK, et al. Prognosis after discontinuing the renin-angiotensin-aldosterone system inhibitor for heart failure with restored ejection fraction after acute myocardial infarction. Sci Rep. 2023;13:3539.","DOI":"10.1038\/s41598-023-30700-1"},{"key":"2026081913080299000_j_rjim-2026-0015_ref_012","doi-asserted-by":"crossref","unstructured":"BASILE C, LINDBERG F, BENSON L, GUIDETTI F, DAHLSTR\u00d6M U, PIEPOLI MF, et al. Withdrawal of guideline-directed medical therapy in patients with heart failure and improved ejection fraction. Circulation. 2025;151(13):931\u2013945.","DOI":"10.1161\/CIRCULATIONAHA.124.072855"}],"container-title":["Romanian Journal of Internal Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/reference-global.com\/pdf\/10.2478\/rjim-2026-0015","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T13:09:45Z","timestamp":1787144985000},"score":1,"resource":{"primary":{"URL":"https:\/\/reference-global.com\/article\/10.2478\/rjim-2026-0015"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,22]]},"references-count":12,"alternative-id":["10.2478\/rjim-2026-0015"],"URL":"https:\/\/doi.org\/10.2478\/rjim-2026-0015","relation":{},"ISSN":["2501-062X"],"issn-type":[{"value":"2501-062X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,22]]}}}