{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T01:43:31Z","timestamp":1788227011404,"version":"build-2803163510"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2018,12,28]],"date-time":"2018-12-28T00:00:00Z","timestamp":1545955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"},{"start":{"date-parts":[[2018,12,28]],"date-time":"2018-12-28T00:00:00Z","timestamp":1545955200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100011125","name":"University of Rochester School of Medicine and Dentistry","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011125","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008497","name":"Boston Scientific, St. Paul, Minnesota","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008497","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011125","name":"School of Medicine and Dentistry, University of Rochester","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011125","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008497","name":"Boston Scientific Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008497","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Despite our prior report suggesting heart failure (HF) risk reduction from cardiac resynchronization therapy with defibrillator (CRT-D) in mild HF patients with higher left ventricular ejection fraction (LVEF &amp;gt;\u200930%), data on mortality benefit in this cohort are lacking. We aimed to assess long-term mortality benefit from CRT-D in mild HF patients by LVEF &amp;gt;\u200930%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Among 1274 patients with mild HF and left bundle branch block enrolled in MADIT-CRT, we analysed long-term effects of CRT-D vs. implantable cardioverter defibrillator (ICD) therapy only, and reverse remodelling to CRT-D (left ventricular end-systolic volume percent change\u2009\u2265\u2009median at 1\u2009year), on all-cause mortality and HF for the LVEF \u2264\u200930% and LVEF &amp;gt;\u200930 subgroups using Kaplan\u2013Meier and Cox analyses. During long-term follow-up, CRT-D vs. ICD was associated with reduction in all-cause mortality in both patients with LVEF &amp;gt;\u200930% and LVEF \u2264\u200930% [hazard ratio (HR) 0.47, 95% confidence interval (CI) 0.25\u20130.85, P\u2009=\u20090.036 vs. HR\u20090.69, 95% CI 0.49\u20130.98, P\u2009=\u20090.013, interaction P\u2009=\u20090.261]. The efficacy of CRT-D vs. ICD only to reduce HF was similar in those with LVEF above and below 30% (HR\u20090.36, 95% CI 0.35\u20130.61, P\u2009&amp;lt;\u20090.001 vs. HR\u20090.46, 95% CI 0.35\u20130.61, P\u2009&amp;lt;\u20090.001; interaction P\u2009=\u20090.342). Patients with CRT-D-induced reverse remodelling had significant mortality reduction when compared to ICD, with either LVEF &amp;gt;\u200930% or LVEF \u2264\u200930% (HR 0.17 and 0.39), but no mortality benefit was seen in patients with less reverse remodelling. HF events, however, were reduced in both CRT-D-induced high and low reverse remodelling vs. ICD only, in both LVEF subgroups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In MADIT-CRT, left bundle branch block patients with higher LVEF (&amp;gt;\u200930%) derive long-term mortality benefit from CRT-D when exhibiting significant reverse remodelling.<\/jats:p>\n                    <jats:p>Clinical Trial registration: ClinicalTrials.gov ID NCT00180271, NCT01294449, and NCT02060110<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.1357","type":"journal-article","created":{"date-parts":[[2018,12,28]],"date-time":"2018-12-28T05:13:33Z","timestamp":1545974013000},"page":"360-369","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Long-term Outcomes of Cardiac Resynchronization Therapy by Left Ventricular Ejection Fraction"],"prefix":"10.1093","volume":"21","author":[{"given":"Valentina","family":"Kutyifa","sequence":"first","affiliation":[{"name":"University of Rochester Medical Center , Rochester, NY ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Vermilye","sequence":"additional","affiliation":[{"name":"University of Rochester Medical Center , Rochester, NY ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott D.","family":"Solomon","sequence":"additional","affiliation":[{"name":"Brigham and Women's Hospital, Harvard Medical School , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"McNitt","sequence":"additional","affiliation":[{"name":"University of Rochester Medical Center , Rochester, NY ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur J.","family":"Moss","sequence":"additional","affiliation":[{"name":"University of Rochester Medical Center , Rochester, NY ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Usama A.","family":"Daimee","sequence":"additional","affiliation":[{"name":"University of Rochester Medical Center , Rochester, NY ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,12,28]]},"reference":[{"key":"2026011721294883900_ejhf1357-bib-0001","doi-asserted-by":"crossref","first-page":"2140","DOI":"10.1056\/NEJMoa032423","article-title":"Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure","volume":"350","author":"Bristow","year":"2004","journal-title":"N Engl J Med"},{"key":"2026011721294883900_ejhf1357-bib-0002","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1056\/NEJMoa050496","article-title":"The effect of cardiac resynchronization on morbidity and mortality in heart failure","volume":"352","author":"Cleland","year":"2005","journal-title":"N Engl J Med"},{"key":"2026011721294883900_ejhf1357-bib-0003","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1111\/j.1542-474X.2005.00073.x","article-title":"Multicenter automatic defibrillator implantation trial-cardiac resynchronization therapy (MADIT-CRT): design and clinical protocol","volume":"10","author":"Moss","year":"2005","journal-title":"Ann Noninvasive Electrocardiol"},{"key":"2026011721294883900_ejhf1357-bib-0004","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1056\/NEJMoa0906431","article-title":"Cardiac-resynchronization therapy for the prevention of heart-failure events","volume":"361","author":"Moss","year":"2009","journal-title":"N Engl J Med"},{"key":"2026011721294883900_ejhf1357-bib-0005","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1056\/NEJMoa1401426","article-title":"Survival with cardiac-resynchronization therapy in mild heart failure","volume":"370","author":"Goldenberg","year":"2014","journal-title":"N Engl J Med"},{"key":"2026011721294883900_ejhf1357-bib-0006","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1016\/j.jacc.2012.11.051","article-title":"The influence of left ventricular ejection fraction on the effectiveness of cardiac resynchronization therapy: MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy)","volume":"61","author":"Kutyifa","year":"2013","journal-title":"J Am Coll Cardiol"},{"key":"2026011721294883900_ejhf1357-bib-0007","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.jacc.2008.02.032","article-title":"ACC\/AHA\/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology\/American Heart Association Task Force on Practice Guidelines (writing committee to revise the ACC\/AHA\/NASPE 2002 guideline update for implantation of cardiac pacemakers and antiarrhythmia devices) developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons","volume":"51","author":"Epstein","year":"2008","journal-title":"J Am Coll Cardiol"},{"key":"2026011721294883900_ejhf1357-bib-0008","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1016\/j.echo.2005.10.005","article-title":"Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology","volume":"18","author":"Lang","year":"2005","journal-title":"J Am Soc Echocardiogr"},{"key":"2026011721294883900_ejhf1357-bib-0009","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1161\/CIRCULATIONAHA.110.955039","article-title":"Effect of cardiac resynchronization therapy on reverse remodeling and relation to outcome: multicenter automatic defibrillator implantation trial: cardiac resynchronization therapy","volume":"122","author":"Solomon","year":"2010","journal-title":"Circulation"},{"key":"2026011721294883900_ejhf1357-bib-0010","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1093\/eurheartj\/ehr185","article-title":"Relationship between improvement in left ventricular dyssynchrony and contractile function and clinical outcome with cardiac resynchronization therapy: the MADIT-CRT trial","volume":"32","author":"Pouleur","year":"2011","journal-title":"Eur Heart J"},{"key":"2026011721294883900_ejhf1357-bib-0011","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1161\/01.CIR.101.14.1638","article-title":"Implantable cardioverter defibrillator therapy: the sickest patients benefit the most","volume":"101","author":"Moss","year":"2000","journal-title":"Circulation"},{"key":"2026011721294883900_ejhf1357-bib-0012","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1111\/j.1540-8167.2006.00612.x","article-title":"Effect of cardiac resynchronization therapy in patients with moderate left ventricular systolic dysfunction and wide QRS complex: a prospective study","volume":"17","author":"Fung","year":"2006","journal-title":"J Cardiovasc Electrophysiol"},{"key":"2026011721294883900_ejhf1357-bib-0013","doi-asserted-by":"crossref","first-page":"S186","DOI":"10.1111\/j.1540-8159.2008.02280.x","article-title":"Cardiac resynchronization therapy in patients with mildly impaired left ventricular function","volume":"32","author":"Foley","year":"2009","journal-title":"Pacing Clin Electrophysiol"},{"key":"2026011721294883900_ejhf1357-bib-0014","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1093\/eurjhf\/hfq009","article-title":"Cardiac resynchronization therapy may benefit patients with left ventricular ejection fraction &gt;35%: a PROSPECT trial substudy","volume":"12","author":"Chung","year":"2010","journal-title":"Eur J Heart Fail"},{"key":"2026011721294883900_ejhf1357-bib-0015","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1016\/j.jacc.2008.08.027","article-title":"Randomized trial of cardiac resynchronization in mildly symptomatic heart failure patients and in asymptomatic patients with left ventricular dysfunction and previous heart failure symptoms","volume":"52","author":"Linde","year":"2008","journal-title":"J Am Coll Cardiol"},{"key":"2026011721294883900_ejhf1357-bib-0016","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.tcm.2015.05.011","article-title":"MADIT-CRT and his many sons","volume":"26","author":"Rogers","year":"2016","journal-title":"Trends Cardiovasc Med"},{"key":"2026011721294883900_ejhf1357-bib-0017","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.ijcard.2005.07.007","article-title":"Acute and chronic haemodynamic effects of biventricular pacing and of switching to different pacing modalities in heart failure patients","volume":"110","author":"Boriani","year":"2006","journal-title":"Int J Cardiol"},{"key":"2026011721294883900_ejhf1357-bib-0018","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1067\/mhj.2002.119616","article-title":"Acute effects of cardiac resynchronization therapy on left ventricular Doppler indices in patients with congestive heart failure","volume":"143","author":"Breithardt","year":"2002","journal-title":"Am Heart J"},{"key":"2026011721294883900_ejhf1357-bib-0019","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/S0735-1097(02)02937-6","article-title":"Acute effects of cardiac resynchronization therapy on functional mitral regurgitation in advanced systolic heart failure","volume":"41","author":"Breithardt","year":"2003","journal-title":"J Am Coll Cardiol"},{"key":"2026011721294883900_ejhf1357-bib-0020","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1111\/jce.13171","article-title":"Effect of cardiac resynchronization therapy on myocardial fibrosis and relevant cytokines in a canine model with experimental heart failure","volume":"28","author":"Wang","year":"2017","journal-title":"J Cardiovasc Electrophysiol"},{"key":"2026011721294883900_ejhf1357-bib-0021","doi-asserted-by":"crossref","first-page":"3738","DOI":"10.1161\/CIRCULATIONAHA.105.561423","article-title":"Influence of ejection fraction on cardiovascular outcomes in a broad spectrum of heart failure patients","volume":"112","author":"Solomon","year":"2005","journal-title":"Circulation"},{"key":"2026011721294883900_ejhf1357-bib-0022","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1161\/CIRCULATIONAHA.110.960898","article-title":"Effectiveness of cardiac resynchronization therapy by QRS morphology in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT)","volume":"123","author":"Zareba","year":"2011","journal-title":"Circulation"},{"key":"2026011721294883900_ejhf1357-bib-0023","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.hrthm.2014.11.014","article-title":"The effect of reverse remodeling on long-term survival in mildly symptomatic patients with heart failure receiving cardiac resynchronization therapy: results of the REVERSE study","volume":"12","author":"Gold","year":"2015","journal-title":"Heart Rhythm"},{"key":"2026011721294883900_ejhf1357-bib-0024","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.ahj.2005.12.002","article-title":"Socioeconomic status, treatment, and outcomes among elderly patients hospitalized with heart failure: findings from the National Heart Failure Project","volume":"152","author":"Rathore","year":"2006","journal-title":"Am Heart J"},{"key":"2026011721294883900_ejhf1357-bib-0025","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.ijcard.2015.09.023","article-title":"Cardiac resynchronization therapy in chronic heart failure with moderately reduced left ventricular ejection fraction: lessons from the Multicenter InSync Randomized Clinical Evaluation MIRACLE EF study","volume":"202","author":"Linde","year":"2016","journal-title":"Int J Cardiol"}],"container-title":["European Journal of Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fejhf.1357","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ejhf.1357","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ejhf.1357","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/21\/3\/360\/66195388\/eurjhf_21_3_360.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/21\/3\/360\/66195388\/eurjhf_21_3_360.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T02:29:58Z","timestamp":1768703398000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eurjhf\/article\/21\/3\/360\/8408157"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,28]]},"references-count":25,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2018,12,28]]},"published-print":{"date-parts":[[2019,3,1]]}},"URL":"https:\/\/doi.org\/10.1002\/ejhf.1357","relation":{},"ISSN":["1388-9842","1879-0844"],"issn-type":[{"value":"1388-9842","type":"print"},{"value":"1879-0844","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,3]]},"published":{"date-parts":[[2018,12,28]]},"assertion":[{"value":"2018-07-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-12-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}