{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T07:58:16Z","timestamp":1785225496593,"version":"3.55.0"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T00:00:00Z","timestamp":1631750400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> The feasibility of spironolactone withdrawal in dilated cardiomyopathy patients with improved ejection fraction remains unknown. This study sought to determine whether spironolactone can be withdrawn safely in this circumstance.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Consecutive patients with idiopathic dilated cardiomyopathy and prescribed spironolactone at discharge were included in this prospective, observational cohort using the Risk Evaluation and Management in Heart Failure Trial (NCT02998788) database. Those patients who experienced an absolute left ventricular ejection fraction (LVEF) improvement \u226510% and a second measurement of LVEF &amp;gt;40% would choose whether to continue spironolactone therapy and be included in final analysis. The primary endpoint was dilated cardiomyopathy relapse within 12 months, defined as a more than 10% reduction in LVEF, a 15% or greater increase in LVESVi, a 2-fold rise in NT-proBNP, or clinical signs of heart failure.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Seventy patients achieved an ejection fraction improvement and were included in the final analysis, of whom 30 chose to continue spironolactone and 40 decided to withdraw. In primary endpoint analysis, 23 (58%) patients from the withdrawal group and 4 (13%) patients from the continuation group relapsed (relative risk for relapse: 4.31; 95% CI: 1.67\u201311.11; <jats:italic>p<\/jats:italic> &amp;lt; 0.001). Patients from the withdrawal group experienced more symptom aggravation than the continuation group. No secondary safety endpoint was recorded. Improvements in cardiac structure parameters were no longer observed after spironolactone withdrawal, while improvements persisted in continuation group.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> Most dilated cardiomyopathy patients with improved ejection fraction will relapse after spironolactone withdrawal. These results should be weighed before spironolactone withdrawal was attempted.<\/jats:p>","DOI":"10.3389\/fcvm.2021.725399","type":"journal-article","created":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T04:35:55Z","timestamp":1631766955000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Outcomes of Spironolactone Withdrawal in Dilated Cardiomyopathy With Improved Ejection Fraction"],"prefix":"10.3389","volume":"8","author":[{"given":"Yanjia","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeping","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuxiu","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanyi","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1056\/NEJM199909023411001","article-title":"The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized aldactone evaluation study investigators","volume":"341","author":"Pitt","year":"1999","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2388","DOI":"10.1093\/eurheartj\/ehn309","article-title":"ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM)","volume":"29","author":"Dickstein","year":"2008","journal-title":"Eur J Heart Failure"},{"key":"B3","doi-asserted-by":"publisher","first-page":"2129","DOI":"10.1093\/eurheartj\/ehw128","article-title":"2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC","volume":"37","author":"Ponikowski","year":"2016","journal-title":"Eur Heart J"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1787","DOI":"10.1093\/eurheartj\/ehs104","article-title":"ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the task force for the diagnosis and treatment of acute and chronic heart failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC","volume":"33","author":"McMurray","year":"2012","journal-title":"Eur Heart J"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1810","DOI":"10.1161\/CIR.0b013e31829e8807","article-title":"2013 ACCF\/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation\/American Heart Association Task Force on practice guidelines","volume":"128","author":"Yancy","year":"2013","journal-title":"Circulation"},{"key":"B6","doi-asserted-by":"publisher","first-page":"2264","DOI":"10.1016\/j.jacc.2017.08.063","article-title":"Phenotype and clinical outcomes of titin cardiomyopathy","volume":"70","author":"Tayal","year":"2017","journal-title":"J Am Coll Cardiol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1468","DOI":"10.1016\/j.jacc.2010.11.030","article-title":"Prevalence and prognostic significance of left ventricular reverse remodeling in dilated cardiomyopathy receiving tailored medical treatment","volume":"57","author":"Merlo","year":"2011","journal-title":"J Am Coll Cardiol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"2380","DOI":"10.1161\/CIRCULATIONAHA.113.006855","article-title":"Heart failure with recovered ejection fraction: clinical description, biomarkers, and outcomes","volume":"129","author":"Basuray","year":"2014","journal-title":"Circulation"},{"key":"B9","doi-asserted-by":"publisher","first-page":"e001504","DOI":"10.1161\/JAHA.114.001504","article-title":"Persistent recovery of normal left ventricular function and dimension in idiopathic dilated cardiomyopathy during long-term follow-up: does real healing exist?","volume":"4","author":"Merlo","year":"2015","journal-title":"J Am Heart Assoc"},{"key":"B10","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1002\/ejhf.2115","article-title":"Universal definition and classification of heart failure: a report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure","volume":"23","author":"Bozkurt","year":"2021","journal-title":"Eur J Heart Fail"},{"key":"B11","doi-asserted-by":"publisher","first-page":"2837","DOI":"10.1161\/CIRCULATIONAHA.104.500546","article-title":"Mechanisms and models in heart failure: the biomechanical model and beyond","volume":"111","author":"Mann","year":"2005","journal-title":"Circulation"},{"key":"B12","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/j.jacc.2018.04.070","article-title":"Medical therapy for heart failure with reduced ejection fraction: the CHAMP-HF registry","volume":"72","author":"Greene","year":"2018","journal-title":"J Am Coll Cardiol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1284","DOI":"10.1002\/ejhf.900","article-title":"Mineralocorticoid receptor antagonist pattern of use in heart failure with reduced ejection fraction: findings from BIOSTAT-CHF","volume":"19","author":"Ferreira","year":"2017","journal-title":"Eur J Heart Fail"},{"key":"B14","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1016\/j.ijcard.2016.11.006","article-title":"Lack of evidence of lower 30-day all-cause readmission in Medicare beneficiaries with heart failure and reduced ejection fraction discharged on spironolactone","volume":"227","author":"Lam","year":"2017","journal-title":"Int J Cardiol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1002\/ehf2.12635","article-title":"Mineralocorticoid receptor antagonist use following heart failure hospitalization","volume":"7","author":"Duran","year":"2020","journal-title":"ESC Heart Fail"},{"key":"B16","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1161\/CIRCHEARTFAILURE.109.906909","article-title":"Randomized, double-blind, multicenter, placebo-controlled study evaluating the effect of aldosterone antagonism with eplerenone on ventricular remodeling in patients with mild-to-moderate heart failure and left ventricular systolic dysfunction","volume":"3","author":"Udelson","year":"2010","journal-title":"Circ Heart Fail"},{"key":"B17","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1093\/eurjhf\/hfn015","article-title":"Anti-remodelling effect of canrenone in patients with mild chronic heart failure (AREA IN-CHF study): final results","volume":"11","author":"Boccanelli","year":"2009","journal-title":"Eur J Heart Fail"},{"key":"B18","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1093\/eurheartj\/ehaa758","article-title":"The effect of spironolactone on cardiovascular function and markers of fibrosis in people at increased risk of developing heart failure: the heart 'OMics' in AGEing (HOMAGE) randomized clinical trial","volume":"42","author":"Cleland","year":"2021","journal-title":"Eur Heart J"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1326","DOI":"10.1002\/ejhf.1182","article-title":"Factors associated with underuse of mineralocorticoid receptor antagonists in heart failure with reduced ejection fraction: an analysis of 11 215 patients from the Swedish Heart Failure Registry","volume":"20","author":"Savarese","year":"2018","journal-title":"Eur J Heart Fail"},{"key":"B20","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1038\/nrcardio.2017.139","article-title":"Reverse remodelling and myocardial recovery in heart failure","volume":"15","author":"Kim","year":"2018","journal-title":"Nat Rev Cardiol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1426","DOI":"10.1016\/j.jacc.2020.01.040","article-title":"Withdrawal of neurohumoral blockade after cardiac resynchronization therapy","volume":"75","author":"Nijst","year":"2020","journal-title":"J Am Coll Cardiol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e002054","DOI":"10.1161\/JAHA.115.002054","article-title":"Effects of cardiac resynchronization therapy on cardiac remodeling and contractile function: results from resynchronization reverses remodeling in systolic left ventricular dysfunction (REVERSE)","volume":"4","author":"St John Sutton","year":"2015","journal-title":"J Am Heart Assoc"},{"key":"B23","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1016\/j.jacc.2020.05.075","article-title":"Heart failure with recovered left ventricular ejection fraction: JACC scientific expert panel","volume":"76","author":"Wilcox","year":"2020","journal-title":"J Am Coll Cardiol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1557","DOI":"10.1016\/j.jacc.2018.06.070","article-title":"Heart failure with recovered ejection fraction","volume":"72","author":"Merken","year":"2018","journal-title":"J Am Coll Cardiol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1001\/jamacardio.2016.0208","article-title":"Recovery of cardiac function in cardiomyopathy caused by titin truncation","volume":"1","author":"Felkin","year":"2016","journal-title":"JAMA Cardiol"},{"key":"B26","doi-asserted-by":"publisher","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":"B27","doi-asserted-by":"publisher","first-page":"2601","DOI":"10.1056\/NEJMc1602671","article-title":"Shared genetic predisposition in peripartum and dilated cardiomyopathies","volume":"374","author":"Biteker","year":"2016","journal-title":"N Engl J Med"},{"key":"B28","doi-asserted-by":"publisher","first-page":"2293","DOI":"10.1016\/j.jacc.2018.03.462","article-title":"Genetic etiology for alcohol-induced cardiac toxicity","volume":"71","author":"Ware","year":"2018","journal-title":"J Am Coll Cardiol"},{"key":"B29","doi-asserted-by":"publisher","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":"Lancet"}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2021.725399\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T04:35:59Z","timestamp":1631766959000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2021.725399\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,16]]},"references-count":29,"alternative-id":["10.3389\/fcvm.2021.725399"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2021.725399","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,16]]},"article-number":"725399"}}