{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T12:34:39Z","timestamp":1769085279232,"version":"3.49.0"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":1241,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T00:00:00Z","timestamp":1657670400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"1\u00b73\u00b75 Project for disciplines of excellence\u2013Clinical Research Incubation Project, West China Hospital, Sichuan University","award":["2020HXFH045"],"award-info":[{"award-number":["2020HXFH045"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81470508"],"award-info":[{"award-number":["81470508"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81470508"],"award-info":[{"award-number":["81470508"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Patients with persistent or de novo left ventricular (LV) dilation and\/or reduced ejection fraction (EF) after correction for primary aortic (AR) or mitral (MR) regurgitation (i.e. residual LV remodelling) have not been well studied with regard to guideline-directed medical therapy after successful aetiology-reversing surgery. We aim to (i) compare the effectiveness of sacubitril\/valsartan vs. valsartan in promoting LV reverse remodelling and (ii) explore the safety of medication withdrawal after LV recovery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>The ReReRe study is a multicentre, randomized, open-label, parallel trial that consists of two consecutive parts. A total of 371 patients with an LV end-diastolic diameter (LVEDD) &amp;gt; 60 mm or LVEF &amp;lt; 50%, assessed by transthoracic echocardiography (TTE) 7\u201314 days after valve surgery for significant AR or primary MR will be enrolled. The 1st randomization into the sacubitril\/valsartan or valsartan groups and structured follow-up (1, 3, 6, 9, and 12 months after randomization) will be conducted to observe the primary objective as the rate of complete recovery of LV remodelling (i.e. LVEDD &amp;lt; 55 mm and LVEF \u2265 60% by TTE at two consecutive visits). Those who have complete recovery of LV remodelling will be enrolled in Study Part 2; consequently, they will receive the 2nd randomization into the medication withdrawal or maintenance group and 6-monthly visits for the observation of the primary objective as the rate of LV remodelling relapse (LVEDD &amp;gt; 60 mm or LVEF &amp;lt; 50%). The secondary objectives include the rate of composite clinical outcomes and the degree of change in 6-min walk distance and Kansas City Cardiomyopathy Questionnaire scores.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The ReReRe study will provide new evidence for the treatment of patients with residual LV remodelling after curable unloaded surgery, as well as the duration of treatment. The study results will fill the gap in identifying an appropriate medical therapy regimen for this group of patients and perhaps for those with reversible aetiologies of heart failure.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.14058","type":"journal-article","created":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T06:18:45Z","timestamp":1657693125000},"page":"3585-3592","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["ARNI or ARB Treats\n                    <u>Re<\/u>\n                    Sidual Left Ventricular\n                    <u>Re<\/u>\n                    modelling After Surgery for Valvular\n                    <u>Re<\/u>\n                    gurgitation: ReReRe Study Protocol"],"prefix":"10.1093","volume":"9","author":[{"given":"Yu","family":"Kang","sequence":"first","affiliation":[{"name":"Department of Cardiology, West China Hospital, Sichuan University , Chengdu ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zi-xuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, West China Hospital, Sichuan University , Chengdu ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu-lu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, West China Hospital, Sichuan University , Chengdu ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Kong","sequence":"additional","affiliation":[{"name":"The Heart Failure Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China , Chengdu ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences , Beijing ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Chinese PLA General Hospital (301 Hospital) , Beijing ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Xinqiao Hospital, Third Military Medical University (Army Medical University) , Chongqing ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi-jun","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shengjing Hospital of China Medical University , Shenyang ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heart Center of Henan Provincial People's Hospital, Central China Fuwai Hospital of Zhengzhou University , Zhengzhou ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Evidence-Based Medicine and Clinical Epidemiology, West China Hospital, Sichuan University , Chengdu ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying-qiang","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, West China Hospital, Sichuan University , Chengdu ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, West China Hospital, Sichuan University , Chengdu ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,7,13]]},"reference":[{"key":"2026012114160099600_ehf214058-bib-0001","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1136\/hrt.2004.042614","article-title":"Aortic regurgitation","volume":"92","author":"Maurer","year":"2006","journal-title":"Heart"},{"key":"2026012114160099600_ehf214058-bib-0002","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1016\/S0140-6736(16)00586-9","article-title":"Management strategies and future challenges for aortic valve disease","volume":"387","author":"Bonow","year":"2016","journal-title":"The Lancet"},{"key":"2026012114160099600_ehf214058-bib-0003","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1016\/S0140-6736(16)00558-4","article-title":"Mitral valve disease\u2014Current management and future challenges","volume":"387","author":"Nishimura","year":"2016","journal-title":"The Lancet"},{"key":"2026012114160099600_ehf214058-bib-0004","first-page":"e183","article-title":"2020 ACC\/AHA guideline for the management of patients with valvular heart disease: A Report of the American College of Cardiology\/American Heart Association Joint Committee on Clinical Practice Guidelines","volume":"162","author":"Writing Committee","year":"2021","journal-title":"J Am Coll Cardiol"},{"key":"2026012114160099600_ehf214058-bib-0005","doi-asserted-by":"crossref","first-page":"2752","DOI":"10.1016\/j.jtcvs.2014.07.029","article-title":"Left ventricular dysfunction after mitral valve repair--The fallacy of \u201cnormal\u201d preoperative myocardial function","volume":"148","author":"Quintana","year":"2014","journal-title":"J Thorac Cardiovasc Surg"},{"key":"2026012114160099600_ehf214058-bib-0006","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1093\/ejechocard\/jer128","article-title":"Predicting left ventricular dysfunction after valve repair for mitral regurgitation due to leaflet prolapse: Additive value of left ventricular end-systolic dimension to ejection fraction","volume":"12","author":"Tribouilloy","year":"2011","journal-title":"Eur J Echocardiogr"},{"key":"2026012114160099600_ehf214058-bib-0007","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.amjcard.2019.04.010","article-title":"Effect of left ventricular reverse remodeling on long-term outcomes after aortic valve replacement","volume":"124","author":"Izumi","year":"2019","journal-title":"Am J Cardiol"},{"key":"2026012114160099600_ehf214058-bib-0008","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1002\/clc.23268","article-title":"GDMT for heart failure and the clinician's conundrum","volume":"42","author":"Samarendra","year":"2019","journal-title":"Clin Cardiol"},{"key":"2026012114160099600_ehf214058-bib-0009","doi-asserted-by":"crossref","first-page":"2739","DOI":"10.1093\/eurheartj\/ehx391","article-title":"ESC\/EACTS guidelines for the management of valvular heart disease","volume":"2017","author":"Baumgartner","year":"2017","journal-title":"Eur Heart J"},{"key":"2026012114160099600_ehf214058-bib-0010","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1056\/NEJMoa1409077","article-title":"Angiotensin-neprilysin inhibition versus enalapril in heart failure","volume":"371","author":"McMurray","year":"2014","journal-title":"N Engl J Med"},{"key":"2026012114160099600_ehf214058-bib-0011","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.119.012272","article-title":"Effects of the angiotensin-receptor neprilysin inhibitor on cardiac reverse remodeling: Meta-analysis","volume":"8","author":"Wang","year":"2019","journal-title":"J Am Heart Assoc"},{"key":"2026012114160099600_ehf214058-bib-0012","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.echo.2018.06.004","article-title":"Guidelines for performing a comprehensive transthoracic echocardiographic examination in adults: recommendations from the American Society of Echocardiography","volume":"32","author":"Mitchell","year":"2019","journal-title":"J Am Soc Echocardiogr"},{"key":"2026012114160099600_ehf214058-bib-0013","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s12968-020-00610-6","article-title":"Standardized image interpretation and post-processing in cardiovascular magnetic resonance - 2020 update: Society for Cardiovascular Magnetic Resonance (SCMR): Board of Trustees Task Force on Standardized Post-Processing","volume":"22","author":"Schulz-Menger","year":"2020","journal-title":"J Cardiovasc Magn Reson"},{"key":"2026012114160099600_ehf214058-bib-0014","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.jjcc.2016.11.011","article-title":"Efficacy and safety of sacubitril\/valsartan (LCZ696) in Japanese patients with chronic heart failure and reduced ejection fraction: Rationale for and design of the randomized, double-blind PARALLEL-HF study","volume":"70","author":"Tsutsui","year":"2017","journal-title":"J Cardiol"},{"key":"2026012114160099600_ehf214058-bib-0015","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/S0735-1097(03)00649-1","article-title":"Echocardiographic prediction ofleft ventricular dysfunction aftermitral valve repair for mitral regurgitation as anindicator to decide the optimal timing of repair","volume":"42","author":"Matsumura","year":"2003","journal-title":"J Am Coll Cardiol"},{"key":"2026012114160099600_ehf214058-bib-0016","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1161\/CIRCULATIONAHA.115.015371","article-title":"Clinical impact of changes in left ventricular function after aortic valve replacement: Analysis from 3112 patients","volume":"132","author":"Une","year":"2015","journal-title":"Circulation"},{"key":"2026012114160099600_ehf214058-bib-0017","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1055\/s-0039-1692664","article-title":"Persistence of reduced left ventricular function after aortic valve surgery for aortic valve regurgitation: Bicuspid versus tricuspid","volume":"69","author":"Petersen","year":"2021","journal-title":"Thorac Cardiovasc Surg"},{"key":"2026012114160099600_ehf214058-bib-0018","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1536\/ihj.20-671","article-title":"The use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers is associated with the recovered ejection fraction in patients with dilated cardiomyopathy","volume":"62","author":"Enzan","year":"2021","journal-title":"Int Heart J"},{"key":"2026012114160099600_ehf214058-bib-0019","doi-asserted-by":"crossref","first-page":"2058","DOI":"10.1002\/ehf2.13285","article-title":"Reverse remodelling by sacubitril\/valsartan predicts the prognosis in heart failure with reduced ejection fraction","volume":"8","author":"Moon","year":"2021","journal-title":"ESC Heart Fail"},{"key":"2026012114160099600_ehf214058-bib-0020","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/S0140-6736(18)32484-X","article-title":"Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy (TRED-HF): An open-label, pilot, randomised trial","volume":"393","author":"Halliday","year":"2019","journal-title":"The Lancet"},{"key":"2026012114160099600_ehf214058-bib-0021","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.jcmg.2010.10.008","article-title":"Left ventricular remodeling in heart failure: Current concepts in clinical significance and assessment","volume":"4","author":"Konstam","year":"2011","journal-title":"JACC Cardiovasc Imaging"},{"key":"2026012114160099600_ehf214058-bib-0022","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.jchf.2019.02.015","article-title":"Outcomes and effect of treatment according to etiology in HFrEF: An analysis of PARADIGM-HF","volume":"7","author":"Balmforth","year":"2019","journal-title":"JACC Heart Fail"},{"key":"2026012114160099600_ehf214058-bib-0023","doi-asserted-by":"crossref","first-page":"505","DOI":"10.2217\/fca-2019-0089","article-title":"ARNI in cardiovascular disease: Current evidence and future perspectives","volume":"16","author":"Kuchulakanti","year":"2020","journal-title":"Future Cardiol"},{"key":"2026012114160099600_ehf214058-bib-0024","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.jacc.2019.11.014","article-title":"Peripartum cardiomyopathy: JACC state-of-the-art review","volume":"75","author":"Davis","year":"2020","journal-title":"J Am Coll Cardiol"},{"key":"2026012114160099600_ehf214058-bib-0025","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejim.2017.06.014","article-title":"Alcoholic cardiomyopathy: What is known and what is not known","volume":"43","author":"Mirijello","year":"2017","journal-title":"Eur J Intern Med"},{"key":"2026012114160099600_ehf214058-bib-0026","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.ahj.2006.02.008","article-title":"Improved outcomes in peripartum cardiomyopathy with contemporary","volume":"152","author":"Amos","year":"2006","journal-title":"Am Heart J"},{"key":"2026012114160099600_ehf214058-bib-0027","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1080\/14779072.2016.1199273","article-title":"Peripartum cardiomyopathy: Challenges in diagnosis and management","volume":"14","author":"Fett","year":"2016","journal-title":"Expert Rev Cardiovasc Ther"},{"key":"2026012114160099600_ehf214058-bib-0028","doi-asserted-by":"crossref","first-page":"c214","DOI":"10.1159\/000235241","article-title":"Cohort studies: Prospective versus retrospective","volume":"113","author":"Euser","year":"2009","journal-title":"Nephron Clin Pract"}],"container-title":["ESC Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ehf2.14058","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ehf2.14058","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/eschf\/article-pdf\/9\/5\/3585\/65352150\/eschf_9_5_3585.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eschf\/article-pdf\/9\/5\/3585\/65352150\/eschf_9_5_3585.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T19:19:09Z","timestamp":1769023149000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eschf\/article\/9\/5\/3585\/8323054"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,13]]},"references-count":28,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,7,13]]},"published-print":{"date-parts":[[2022,10,1]]}},"URL":"https:\/\/doi.org\/10.1002\/ehf2.14058","relation":{},"ISSN":["2055-5822"],"issn-type":[{"value":"2055-5822","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,10]]},"published":{"date-parts":[[2022,7,13]]},"assertion":[{"value":"2021-08-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}