title: 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.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Cardiology, Deptartment of Medicine III, Goethe University Frankfurt, Theodor-Stern-Kai 7, Frankfurt 60590, Germany birgit_assmus@web.de.
authors.forename: Birgit
authors.initials: B
authors.lastname: Assmus
authors.affiliation: Cardiology, Deptartment of Medicine III, Goethe University Frankfurt, Theodor-Stern-Kai 7, Frankfurt 60590, Germany.
authors.forename: David M
authors.initials: DM
authors.lastname: Leistner
authors.affiliation: Cardiology, Deptartment of Medicine III, Goethe University Frankfurt, Theodor-Stern-Kai 7, Frankfurt 60590, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Schächinger
authors.affiliation: Cardiology, Deptartment of Medicine III, Goethe University Frankfurt, Theodor-Stern-Kai 7, Frankfurt 60590, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Erbs
authors.affiliation: Cardiology, Deptartment of Medicine III, Goethe University Frankfurt, Theodor-Stern-Kai 7, Frankfurt 60590, Germany.
authors.forename: Albrecht
authors.initials: A
authors.lastname: Elsässer
authors.affiliation: Cardiology, Deptartment of Medicine III, Goethe University Frankfurt, Theodor-Stern-Kai 7, Frankfurt 60590, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Haberbosch
authors.affiliation: Cardiology, Deptartment of Medicine III, Goethe University Frankfurt, Theodor-Stern-Kai 7, Frankfurt 60590, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Hambrecht
authors.affiliation: Cardiology, Deptartment of Medicine III, Goethe University Frankfurt, Theodor-Stern-Kai 7, Frankfurt 60590, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sedding
authors.affiliation: Cardiology, Deptartment of Medicine III, Goethe University Frankfurt, Theodor-Stern-Kai 7, Frankfurt 60590, Germany.
authors.forename: Jiangtao
authors.initials: J
authors.lastname: Yu
authors.affiliation: Cardiology, Deptartment of Medicine III, Goethe University Frankfurt, Theodor-Stern-Kai 7, Frankfurt 60590, Germany.
authors.forename: Roberto
authors.initials: R
authors.lastname: Corti
authors.affiliation: Cardiology, Deptartment of Medicine III, Goethe University Frankfurt, Theodor-Stern-Kai 7, Frankfurt 60590, Germany.
authors.forename: Detlef G
authors.initials: DG
authors.lastname: Mathey
authors.affiliation: Cardiology, Deptartment of Medicine III, Goethe University Frankfurt, Theodor-Stern-Kai 7, Frankfurt 60590, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Barth
authors.affiliation: Cardiology, Deptartment of Medicine III, Goethe University Frankfurt, Theodor-Stern-Kai 7, Frankfurt 60590, Germany.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Mayer-Wehrstein
authors.affiliation: Cardiology, Deptartment of Medicine III, Goethe University Frankfurt, Theodor-Stern-Kai 7, Frankfurt 60590, Germany.
authors.forename: Iris
authors.initials: I
authors.lastname: Burck
authors.affiliation: Cardiology, Deptartment of Medicine III, Goethe University Frankfurt, Theodor-Stern-Kai 7, Frankfurt 60590, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Sueselbeck
authors.affiliation: Cardiology, Deptartment of Medicine III, Goethe University Frankfurt, Theodor-Stern-Kai 7, Frankfurt 60590, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Dill
authors.affiliation: Cardiology, Deptartment of Medicine III, Goethe University Frankfurt, Theodor-Stern-Kai 7, Frankfurt 60590, Germany.
authors.forename: Christian W
authors.initials: CW
authors.lastname: Hamm
authors.affiliation: Cardiology, Deptartment of Medicine III, Goethe University Frankfurt, Theodor-Stern-Kai 7, Frankfurt 60590, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Tonn
authors.affiliation: Cardiology, Deptartment of Medicine III, Goethe University Frankfurt, Theodor-Stern-Kai 7, Frankfurt 60590, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Dimmeler
authors.affiliation: Cardiology, Deptartment of Medicine III, Goethe University Frankfurt, Theodor-Stern-Kai 7, Frankfurt 60590, Germany.
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Zeiher
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016026:Bone Marrow Transplantation / Q000379:methods* / Q000401:mortality; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D036502:Infusions, Intralesional; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000637:transplantation*; D009203:Myocardial Infarction / Q000401:mortality / Q000628:therapy*; D010359:Patient Readmission / Q000706:statistics & numerical data; D062645:Percutaneous Coronary Intervention / Q000379:methods / Q000401:mortality; D012008:Recurrence; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000401:mortality / Q000628:therapy; D055815:Young Adult
keywords: Acute myocardial infarction; Bone marrow-derived cells; Cell therapy; Clinical outcome