title: Improved outcome with repeated intracoronary injection of bone marrow-derived cells within a registry: rationale for the randomized outcome trial REPEAT.
abstract: Regenerative therapies have evolved as a promising new option in the treatment of post-infarction heart failure. A major limitation of intracoronary application of autologous bone marrow-derived mononuclear cells (BM-MNCs) is that homing of the applied cells is profoundly reduced in patients with post-infarction heart failure compared with patients with acute myocardial infarction. However, early pilot and also randomized controlled trials have demonstrated significant improvements in overall cardiac function. The aim of the present analysis was to quantify a potential mortality risk reduction and reduced hospitalization in order to provide data for a prospective outcome trial.
  
  
  
  The results of an ongoing single-centre registry including 297 post-infarction heart failure patients suggest that repeated intracoronary application of autologous bone marrow-derived cells is associated with a significant better 2-year survival compared with a single BM-MNC application (2-year survival 93.6 vs. 84.0%, P = 0.03). Likewise, mortality is significantly lower at 2-year follow-up compared with the mortality estimated by the use of the Seattle Heart Failure Model (SHFM) in patients receiving repeated BM-MNC application (observed mortality 6.4%, predicted mortality 16.2%, P = 0.02). Although the trend persisted at 3-year follow-up, the mortality reduction was no longer statistically significant between single and repeated treatment (mortality 21.9 vs. 13.7%, P = 0.06).
  
  
  
  Repeated intracoronary administration of BM-MNC appears to be associated with improved clinical outcome compared with single treatment at 2 years. This registry provides the rationale for the design of the multicentre randomized, controlled, open-label REPEAT trial, which prospectively compares the effects of single vs. repeated intracoronary application of autologous BM-MNC on total and SHFM-predicted mortality in patients with chronic post-infarction heart failure.
authors.affiliation: Division of Cardiology, Department of Medicine III, Goethe University Frankfurt, Theodor-Stern-Kai 7, Frankfurt 60590, Germany German Center for Cardiovascular Research DZHK, Partner Site Frankfurt Rhine-Main, Berlin, Germany b.assmus@em.uni-frankfurt.de.
authors.forename: Birgit
authors.initials: B
authors.lastname: Assmus
authors.affiliation: Division of Cardiology, Department of Medicine III, Goethe University Frankfurt, Theodor-Stern-Kai 7, Frankfurt 60590, Germany.
authors.forename: Samer
authors.initials: S
authors.lastname: Alakmeh
authors.affiliation: Division of Cardiology, Department of Medicine III, Goethe University Frankfurt, Theodor-Stern-Kai 7, Frankfurt 60590, Germany.
authors.forename: Salvatore
authors.initials: S
authors.lastname: De Rosa
authors.affiliation: German Red Cross Blood Service Baden-Wuerttemberg-Hessen and Institute for Transfusion Medicine and Immunohematology Goethe University, Frankfurt, Germany.
authors.forename: Halvard
authors.initials: H
authors.lastname: Bönig
authors.affiliation: German Center for Cardiovascular Research DZHK, Partner Site Frankfurt Rhine-Main, Berlin, Germany Institute of Biostatistics and Mathematical Modeling, Goethe University Frankfurt, Frankfurt, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Hermann
authors.affiliation: Division of Cardiology, University of Washington, Seattle, WA 98195, USA.
authors.forename: Wayne C
authors.initials: WC
authors.lastname: Levy
authors.affiliation: German Center for Cardiovascular Research DZHK, Partner Site Frankfurt Rhine-Main, Berlin, Germany Institute for Cardiovascular Regeneration, Molecular Medicine, Goethe University Frankfurt, Frankfurt, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Dimmeler
authors.affiliation: Division of Cardiology, Department of Medicine III, Goethe University Frankfurt, Theodor-Stern-Kai 7, Frankfurt 60590, Germany German Center for Cardiovascular Research DZHK, Partner Site Frankfurt Rhine-Main, Berlin, Germany.
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Zeiher
mesh_terms: D000368:Aged; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation / Q000379:methods* / Q000401:mortality; D005260:Female; D006333:Heart Failure / Q000209:etiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000401:mortality / Q000628:therapy*; D011446:Prospective Studies; D012042:Registries; D012307:Risk Factors; D016896:Treatment Outcome
keywords: Cell therapy; Chronic heart failure; Ischaemic cardiomyopathy; Outcome trial