Birgit Assmus1, Samer Alakmeh2, Salvatore De Rosa2, Halvard Bönig3, Eva Hermann4, Wayne C Levy5, Stefanie Dimmeler6, Andreas M Zeiher7. 1. 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. 2. Division of Cardiology, Department of Medicine III, Goethe University Frankfurt, Theodor-Stern-Kai 7, Frankfurt 60590, Germany. 3. German Red Cross Blood Service Baden-Wuerttemberg-Hessen and Institute for Transfusion Medicine and Immunohematology Goethe University, Frankfurt, Germany. 4. German Center for Cardiovascular Research DZHK, Partner Site Frankfurt Rhine-Main, Berlin, Germany Institute of Biostatistics and Mathematical Modeling, Goethe University Frankfurt, Frankfurt, Germany. 5. Division of Cardiology, University of Washington, Seattle, WA 98195, USA. 6. German Center for Cardiovascular Research DZHK, Partner Site Frankfurt Rhine-Main, Berlin, Germany Institute for Cardiovascular Regeneration, Molecular Medicine, Goethe University Frankfurt, Frankfurt, Germany. 7. 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.
Abstract
AIMS: 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. METHODS AND RESULTS: 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). CONCLUSION: 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. Published on behalf of the European Society of Cardiology. All rights reserved.
RCT Entities:
AIMS: 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. METHODS AND RESULTS: The results of an ongoing single-centre registry including 297 post-infarction heart failurepatients 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). CONCLUSION: 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. Published on behalf of the European Society of Cardiology. All rights reserved.
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