{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T19:34:13Z","timestamp":1789587253849,"version":"build-2803163510"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2015,7,27]],"date-time":"2015-07-27T00:00:00Z","timestamp":1437955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title\/>\n                  <jats:p>Cell therapy is an evolving option for patients with end-stage heart failure and ongoing symptoms despite optimal medical therapy. Our goal was to evaluate retrograde bone marrow cell delivery in patients with either ischemic heart failure (IHF) or nonischemic heart failure (NIHF). This was a prospective randomized, multicenter, open-label study of the safety and feasibility of bone marrow aspirate concentrate (BMAC) infused retrograde into the coronary sinus. Sixty patients were stratified by IHF and NIHF and randomized to receive either BMAC infusion or control (standard heart failure care) in a 4:1 ratio. Accordingly, 24 subjects were randomized to the ischemic BMAC group and 6 to the ischemic control group. Similarly, 24 subjects were randomized to the nonischemic BMAC group and 6 to the nonischemic control group. All 60 patients were successfully enrolled in the study. The treatment groups received BMAC infusion without complications. The left ventricular ejection fraction in the patients receiving BMAC demonstrated significant improvement compared with baseline, from 25.1% at screening to 31.1% at 12 months (p = .007) in the NIHF group and from 26.3% to 31.1% in the IHF group (p = .035). The end-systolic diameter decreased significantly in the nonischemic BMAC group from 55.6 to 50.9 mm (p = .020). Retrograde BMAC delivery is safe. All patients receiving BMAC experienced improvements in left ventricular ejection fraction, but only those with NIHF showed improvements in left ventricular end-systolic diameter and B-type natriuretic peptide. These results provide the basis for a larger clinical trial in HF patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Significance<\/jats:title>\n                  <jats:p>This work is the first prospective randomized clinical trial using high-dose cell therapy delivered via a retrograde coronary sinus infusion in patients with heart failure. This was a multinational, multicenter study, and it is novel, translatable, and scalable. On the basis of this trial and the safety of retrograde coronary sinus infusion, there are three other trials under way using this route of delivery.<\/jats:p>\n               <\/jats:sec>","DOI":"10.5966\/sctm.2015-0070","type":"journal-article","created":{"date-parts":[[2015,7,28]],"date-time":"2015-07-28T00:39:56Z","timestamp":1438043996000},"page":"1021-1027","source":"Crossref","is-referenced-by-count":42,"title":["REVIVE Trial: Retrograde Delivery of Autologous Bone Marrow in Patients With Heart Failure"],"prefix":"10.1093","volume":"4","author":[{"given":"Amit N.","family":"Patel","sequence":"first","affiliation":[{"name":"University of Utah, Salt Lake City, Utah, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Mittal","sequence":"additional","affiliation":[{"name":"Heart Institute, Medanta MediCity, Gurgoan, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goekmen","family":"Turan","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Rostock University Hospital, Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amalia A.","family":"Winters","sequence":"additional","affiliation":[{"name":"University of Utah, Salt Lake City, Utah, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy D.","family":"Henry","sequence":"additional","affiliation":[{"name":"Cedars-Sinai Heart Institute, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hueseyin","family":"Ince","sequence":"additional","affiliation":[{"name":"Vivantes Klinikum, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naresh","family":"Trehan","sequence":"additional","affiliation":[{"name":"Heart Institute, Medanta MediCity, Gurgoan, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,7,27]]},"reference":[{"key":"2021122704330821000_R1"},{"key":"2021122704330821000_R2","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1161\/CIR.0b013e318282ab8f","article-title":"Executive summary: Heart disease and stroke statistics\u20142013 Update: A report from the American Heart Association","volume":"127","author":"Go","year":"2013","journal-title":"Circulation"},{"key":"2021122704330821000_R3","doi-asserted-by":"crossref","first-page":"2388","DOI":"10.1056\/NEJMsa053935","article-title":"Explaining the decrease in U.S. deaths from coronary disease, 1980-2000","volume":"356","author":"Ford","year":"2007","journal-title":"N Engl J Med"},{"key":"2021122704330821000_R4"},{"key":"2021122704330821000_R5"},{"key":"2021122704330821000_R6","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1016\/j.jacc.2012.08.1029","article-title":"Patient selection for ventricular assist devices: A moving target","volume":"61","author":"Miller","year":"2013","journal-title":"J Am Coll Cardiol"},{"key":"2021122704330821000_R7","doi-asserted-by":"crossref","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":"2021122704330821000_R8","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1161\/CIRCRESAHA.113.300219","article-title":"Cell therapy for heart failure: A comprehensive overview of experimental and clinical studies, current challenges, and future directions","volume":"113","author":"Sanganalmath","year":"2013","journal-title":"Circ Res"},{"key":"2021122704330821000_R9","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1161\/CIRCRESAHA.113.302895","article-title":"Cardiac stem cell biology: Glimpse of the past, present, and future","volume":"114","author":"Matsa","year":"2014","journal-title":"Circ Res"},{"key":"2021122704330821000_R10","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1172\/JCI62837","article-title":"Potential of gene therapy as a treatment for heart failure","volume":"123","author":"Hajjar","year":"2013","journal-title":"J Clin Invest"},{"key":"2021122704330821000_R11","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1161\/CIRCULATIONAHA.111.086074","article-title":"Adult bone marrow cell therapy improves survival and induces long-term improvement in cardiac parameters: A systematic review and meta-analysis","volume":"126","author":"Jeevanantham","year":"2012","journal-title":"Circulation"},{"key":"2021122704330821000_R12","doi-asserted-by":"crossref","first-page":"963","DOI":"10.3727\/096368907783338190","article-title":"Adipose-derived cells","volume":"16","author":"Meliga","year":"2007","journal-title":"Cell Transplant"},{"key":"2021122704330821000_R13","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1056\/NEJMcibr1013069","article-title":"Reprogramming fibroblasts into cardiomyocytes","volume":"364","author":"Murry","year":"2011","journal-title":"N Engl J Med"},{"key":"2021122704330821000_R14","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/nature11139","article-title":"Heart repair by reprogramming non-myocytes with cardiac transcription factors","volume":"485","author":"Song","year":"2012","journal-title":"Nature"},{"key":"2021122704330821000_R15","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1161\/CIRCRESAHA.111.243154","article-title":"Role of cardiac stem cells in cardiac pathophysiology: A paradigm shift in human myocardial biology","volume":"109","author":"Leri","year":"2011","journal-title":"Circ Res"},{"key":"2021122704330821000_R16","doi-asserted-by":"crossref","first-page":"513","DOI":"10.3727\/096368912X655064","article-title":"Mesenchymal stem cell population isolated from the subepithelial layer of umbilical cord tissue","volume":"22","author":"Patel","year":"2013","journal-title":"Cell Transplant"},{"key":"2021122704330821000_R17","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/1479-5876-11-56","article-title":"Endometrial regenerative cells for treatment of heart failure: A new stem cell enters the clinic","volume":"11","author":"Bockeria","year":"2013","journal-title":"J Transl Med"},{"key":"2021122704330821000_R18","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/S0140-6736(00)03617-5","article-title":"Myoblast transplantation for heart failure","volume":"357","author":"Menasch\u00e9","year":"2001","journal-title":"Lancet"},{"key":"2021122704330821000_R19","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.jcin.2009.12.013","article-title":"Recommendations for successful training on methods of delivery of biologics for cardiac regeneration: A report of the International Society for Cardiovascular Translational Research","volume":"3","author":"Dib","year":"2010","journal-title":"JACC Cardiovasc Interv"},{"issue":"suppl H","key":"2021122704330821000_R20","doi-asserted-by":"crossref","first-page":"H46","DOI":"10.1093\/eurheartj\/sul066","article-title":"Stem cell therapy in end-stage ischaemic heart failure: A catheter-based therapeutic strategy targeting myocardial viability","volume":"8","author":"Perin","year":"2006","journal-title":"Eur Heart J Suppl"},{"key":"2021122704330821000_R21","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1378\/chest.115.1.135","article-title":"Can retrograde cardioplegia alone provide adequate protection for cardiac valve surgery?","volume":"115","author":"Talwalkar","year":"1999","journal-title":"Chest"},{"key":"2021122704330821000_R22","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1186\/1479-5876-9-183","article-title":"Safety and feasibility of percutaneous retrograde coronary sinus delivery of autologous bone marrow mononuclear cell transplantation in patients with chronic refractory angina","volume":"9","author":"Tuma","year":"2011","journal-title":"J Transl Med"},{"key":"2021122704330821000_R23","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/j.healun.2014.03.006","article-title":"Retrograde coronary vein infusion of cardiac explant-derived c-Kit+ cells improves function in ischemic heart failure","volume":"33","author":"Zakharova","year":"2014","journal-title":"J Heart Lung Transplant"},{"key":"2021122704330821000_R24","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.hfc.2014.12.006","article-title":"Stem cell therapy for heart failure","volume":"11","author":"Patel","year":"2015","journal-title":"Heart Fail Clin"},{"key":"2021122704330821000_R25","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/j.healun.2013.08.006","article-title":"The registry of the International Society for Heart and Lung Transplantation: Thirtieth official adult heart transplant report\u20142013; focus theme: Age","volume":"32","author":"Lund","year":"2013","journal-title":"J Heart Lung Transplan"},{"key":"2021122704330821000_R26","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.yjmcc.2010.08.005","article-title":"Paracrine mechanisms of stem cell reparative and regenerative actions in the heart","volume":"50","author":"Mirotsou","year":"2011","journal-title":"J Mol Cell Cardiol"},{"key":"2021122704330821000_R27","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1001\/jama.2013.282909","article-title":"Transendocardial mesenchymal stem cells and mononuclear bone marrow cells for ischemic cardiomyopathy: The TAC-HFT randomized trial","volume":"311","author":"Heldman","year":"2014","journal-title":"JAMA"},{"key":"2021122704330821000_R28","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1161\/CIRCRESAHA.115.304554","article-title":"Safety and efficacy of ixmyelocel-T: An expanded, autologous multi-cellular therapy, in dilated cardiomyopathy","volume":"115","author":"Henry","year":"2014","journal-title":"Circ Res"},{"issue":"suppl 1","key":"2021122704330821000_R29","first-page":"S42","article-title":"Comparison of transendocardial and intracoronary CD34+ cell transplantation in patients with nonischemic dilated cardiomyopathy","volume":"128","author":"Vrtovec","year":"2013","journal-title":"Circulation"}],"container-title":["Stem Cells Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.5966%2Fsctm.2015-0070","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.5966%2Fsctm.2015-0070","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/stcltm\/article-pdf\/4\/9\/1021\/41864192\/stcltm_4_9_1021.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/stcltm\/article-pdf\/4\/9\/1021\/41864192\/stcltm_4_9_1021.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T02:49:42Z","timestamp":1642560582000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/stcltm\/article\/4\/9\/1021-1027\/6397298"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,7,27]]},"references-count":29,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2015,7,27]]},"published-print":{"date-parts":[[2015,9,1]]}},"URL":"https:\/\/doi.org\/10.5966\/sctm.2015-0070","relation":{},"ISSN":["2157-6564","2157-6580"],"issn-type":[{"value":"2157-6564","type":"print"},{"value":"2157-6580","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2015,9,1]]},"published":{"date-parts":[[2015,7,27]]}}}