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Long-term clinical outcome after intracoronary application of bone marrow-derived mononuclear cells for acute myocardial infarction: migratory capacity of administered cells determines event-free survival.
MedLine Citation:
PMID:  24569031     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: In the REPAIR-AMI trial, intracoronary infusion of bone marrow-derived cells (BMCs) was associated with a significantly greater recovery of contractile function in patients with acute myocardial infarction (AMI) at 4-month follow-up than placebo infusion. The current analysis investigates clinical outcome and predictors of event-free survival at 5 years.
METHODS AND RESULTS: In the multicentre, placebo-controlled, double-blind REPAIR-AMI trial, 204 patients received intracoronary infusion of BMCs (n = 101) or placebo (n = 103) into the infarct vessel 3-7 days following successful percutaneous coronary intervention. Fifteen patients died in the placebo group compared with seven patients in the BMC group (P = 0.08). Nine placebo-treated patients and five BMC-treated patients required rehospitalization for chronic heart failure (P = 0.23). The combined endpoint cardiac/cardiovascular/unknown death or rehospitalisation for heart failure was more frequent in the placebo compared with the BMC group (18 vs. 10 events; P = 0.10). Univariate predictors of adverse outcomes were age, the CADILLAC risk score, aldosterone antagonist and diuretic treatment, changes in left ventricular ejection fraction, left ventricular end-systolic volume, and N-terminal pro-Brain Natriuretic Peptide (all P < 0.01) at 4 months in the entire cohort and in the placebo group. In contrast, in the BMC group, only the basal (P = 0.02) and the stromal cell-derived factor-1-induced (P = 0.05) migratory capacity of the administered BMC were associated with improved clinical outcome.
CONCLUSION: In patients of the REPAIR-AMI trial, established clinical parameters are associated with adverse outcome at 5 years exclusively in the placebo group, whereas the migratory capacity of the administered BMC determines event-free survival in the BMC-treated patients. These data disclose a potency-effect relationship between cell therapy and long-term outcome in patients with AMI.
Authors:
Birgit Assmus; David M Leistner; Volker Schächinger; Sandra Erbs; Albrecht Elsässer; Werner Haberbosch; Rainer Hambrecht; Daniel Sedding; Jiangtao Yu; Roberto Corti; Detlef G Mathey; Christine Barth; Charlotte Mayer-Wehrstein; Iris Burck; Tim Sueselbeck; Thorsten Dill; Christian W Hamm; Torsten Tonn; Stefanie Dimmeler; Andreas M Zeiher;
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-2-25
Journal Detail:
Title:  European heart journal     Volume:  -     ISSN:  1522-9645     ISO Abbreviation:  Eur. Heart J.     Publication Date:  2014 Feb 
Date Detail:
Created Date:  2014-2-26     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8006263     Medline TA:  Eur Heart J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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