{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T16:22:06Z","timestamp":1790180526696,"version":"4.1.0"},"reference-count":18,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T00:00:00Z","timestamp":1607904000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000833","name":"Rosetrees Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000833","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":[[2021,2]]},"abstract":"\n Aims<\/jats:title>\n To characterize adverse ventricular remodelling after withdrawing therapy in recovered dilated cardiomyopathy (DCM).<\/jats:p>\n <\/jats:sec>\n \n Methods and results<\/jats:title>\n \n TRED\u2010HF was a randomized controlled trial with a follow\u2010on single\u2010arm cross\u2010over phase that examined the safety and feasibility of therapy withdrawal in patients with recovered DCM over 6\u00a0months. The primary endpoint was relapse of heart failure defined by (i) a reduction in left ventricular (LV) ejection fraction >10% and to <50%, (ii) >10% increase in LV end\u2010diastolic volume and to above the normal range, (iii) a twofold rise in N\u2010terminal pro\u2010B\u2010type natriuretic peptide and to >400\u2009ng\/L, or (iv) evidence of heart failure. LV mass, LV and right ventricular (RV) global longitudinal strain (GLS) and extracellular volume were measured using cardiovascular magnetic resonance at baseline and follow\u2010up (6\u00a0months or relapse) for 48 patients. LV cell and extracellular matrix masses were derived. The effect of withdrawing therapy, stratified by relapse and genotype, was investigated in the randomized and follow\u2010on phases. In the randomized comparison, withdrawing therapy led to an increase in mean LV mass [5.4\u00a0g\/m\n 2<\/jats:sup>\n ; 95% confidence interval (CI) 1.3\u20139.5] and cell mass (4.2\u00a0g\/m\n 2<\/jats:sup>\n ; 95% CI 0.5\u20138.0) and a reduction in LV (3.5; 95% CI 1.6\u20135.5) and RV (2.4; 95% CI 0.1\u20134.7) GLS\n .<\/jats:italic>\n In a non\u2010randomized comparison of all patients (\n n<\/jats:italic>\n \u00a0=\u200947) who had therapy withdrawn in either phase\n ,<\/jats:italic>\n there was an increase in LV mass (6.2\u00a0g\/m\n 2<\/jats:sup>\n ; 95% CI 3.6\u20138.9;\n P<\/jats:italic>\n \u00a0=\u20090.0001), cell mass (4.0\u00a0g\/m\n 2<\/jats:sup>\n ; 95% CI 1.8\u20136.2;\n P<\/jats:italic>\n \u00a0=\u20090.0007) and matrix mass (1.7\u00a0g\/m\n 2<\/jats:sup>\n ; 95% CI 0.7\u20132.6;\n P<\/jats:italic>\n \u00a0=\u20090.001) and a reduction in LV GLS (2.7; 95% CI 1.5\u20134.0;\n P<\/jats:italic>\n \u00a0=\u20090.0001). Amongst those who had therapy withdrawn and did not relapse\n ,<\/jats:italic>\n similar changes were observed (\n n<\/jats:italic>\n \u00a0=\u200928; LV mass: 5.1\u2009g\/m\n 2<\/jats:sup>\n , 95% CI 1.5\u20138.8,\n P<\/jats:italic>\n \u00a0=\u20090.007; cell mass: 3.7\u00a0g\/m\n 2<\/jats:sup>\n , 95% CI 0.3\u20137.0,\n P<\/jats:italic>\n \u00a0=\u20090.03; matrix mass: 1.7\u00a0g\/m\n 2<\/jats:sup>\n , 95% CI 0.4\u20133.0,\n P<\/jats:italic>\n \u00a0=\u20090.02; LV GLS: 1.7, 95% CI 0.1\u20133.2,\n P<\/jats:italic>\n \u00a0=\u20090.04). Patients with\n TTN<\/jats:italic>\n variants (\n n<\/jats:italic>\n \u00a0=\u200910) who had therapy withdrawn had a greater increase in LV matrix mass (mean effect of\n TTN<\/jats:italic>\n : 2.6\u00a0g\/m\n 2<\/jats:sup>\n ; 95% CI 0.4\u20134.8;\n P<\/jats:italic>\n \u00a0=\u20090.02).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n In TRED\u2010HF, withdrawing therapy caused rapid remodelling, with early tissue and functional changes, even amongst patients who did not relapse.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/ejhf.2063","type":"journal-article","created":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T01:36:51Z","timestamp":1606095411000},"page":"293-301","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Myocardial remodelling after withdrawing therapy for heart failure in patients with recovered dilated cardiomyopathy: insights from\n TRED\u2010HF<\/scp>"],"prefix":"10.1093","volume":"23","author":[{"given":"Brian P.","family":"Halliday","sequence":"first","affiliation":[{"name":"Cardiovascular Research Centre Royal Brompton Hospital & National Heart Lung Institute, Imperial College London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Owen","sequence":"additional","affiliation":[{"name":"London School of Hygiene and Tropical Medicine London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Gregson","sequence":"additional","affiliation":[{"name":"London School of Hygiene and Tropical Medicine London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vassilios","family":"S. Vassiliou","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Sciences Norwich Medical School, University of East Anglia Norwich UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuyu","family":"Chen","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Centre Royal Brompton Hospital & National Heart Lung Institute, Imperial College London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Wage","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Centre Royal Brompton Hospital & National Heart Lung Institute, Imperial College London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amrit S.","family":"Lota","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Centre Royal Brompton Hospital & National Heart Lung Institute, Imperial College London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zohya","family":"Khalique","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Centre Royal Brompton Hospital & National Heart Lung Institute, Imperial College London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Upasana","family":"Tayal","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Centre Royal Brompton Hospital & National Heart Lung Institute, Imperial College London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Hammersley","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Centre Royal Brompton Hospital & National Heart Lung Institute, Imperial College London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard E.","family":"Jones","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Centre Royal Brompton Hospital & National Heart Lung Institute, Imperial College London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. John","family":"Baksi","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Centre Royal Brompton Hospital & National Heart Lung Institute, Imperial College London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin R.","family":"Cowie","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Centre Royal Brompton Hospital & National Heart Lung Institute, Imperial College London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G.F.","family":"Cleland","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Centre Royal Brompton Hospital & National Heart Lung Institute, Imperial College London UK"},{"name":"Robertson Centre for Biostatistics, University of Glasgow Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dudley J.","family":"Pennell","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Centre Royal Brompton Hospital & National Heart Lung Institute, Imperial College London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay K.","family":"Prasad","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Centre Royal Brompton Hospital & National Heart Lung Institute, Imperial College London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,12,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2828(08)80028-4"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmg.2019.05.033"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.1734"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2010.11.030"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32484-X"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.1216"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehx808"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmg.2019.10.002"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.930636"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/10976640600572889"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehl336"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.002518"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmg.2017.06.013"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2017.08.063"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2017.07.011"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1137325"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1002659"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2017.06.046"}],"container-title":["European Journal of Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ejhf.2063","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ejhf.2063","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ejhf.2063","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T12:15:17Z","timestamp":1767701717000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ejhf.2063"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,14]]},"references-count":18,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,2]]}},"alternative-id":["10.1002\/ejhf.2063"],"URL":"https:\/\/doi.org\/10.1002\/ejhf.2063","archive":["Portico"],"relation":{},"ISSN":["1388-9842","1879-0844"],"issn-type":[{"value":"1388-9842","type":"print"},{"value":"1879-0844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,14]]},"assertion":[{"value":"2020-10-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-11-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}