Kai C Wollert1, Gerd P Meyer1, Jochen Müller-Ehmsen2, Carsten Tschöpe3, Vernon Bonarjee4, Alf Inge Larsen4, Andreas E May5, Klaus Empen6, Emmanuel Chorianopoulos7, Ulrich Tebbe8, Johannes Waltenberger9, Heiko Mahrholdt10, Benedikta Ritter1, Jens Pirr1, Dieter Fischer1, Mortimer Korf-Klingebiel1, Lubomir Arseniev11, Hans-Gert Heuft12, Jan E Brinchmann13, Diethelm Messinger14, Bernd Hertenstein15, Arnold Ganser15, Hugo A Katus7, Stephan B Felix6, Meinrad P Gawaz5, Kenneth Dickstein4, Heinz-Peter Schultheiss3, Dennis Ladage2, Simon Greulich10, Johann Bauersachs1. 1. Department of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany. 2. Department of Cardiology, University Heart Centre Cologne, Kerpener Straße 62, 50937 Cologne, Germany. 3. Department of Cardiology, Charité University Hospital, Charitéplatz 1, 10117 Berlin, Germany. 4. University of Bergen, Stavanger University Hospital, Gerd-Ragna Bloch Thorsens Gate 8, 4011 Stavanger, Norway. 5. Department of Cardiology, University of Tübingen, Otfried-Müller-Straße 10, 72076 Tübingen, Germany. 6. Department of Cardiology, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475 Greifswald, Germany. 7. Department of Cardiology, Angiology, and Pneumology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. 8. Department of Cardiology, Angiology, and Intensive Care Medicine, District Hospital Lippe-Detmold, Röntgenstraße 18, 32756 Detmold, Germany. 9. Department of Cardiovascular Medicine, University of Münster, Albert-Schweitzer-Campus 1, 48149 Münster, Germany. 10. Department of Cardiology, Robert-Bosch-Hospital, Auerbachstraße 110, 70376 Stuttgart, Germany. 11. Cellular Therapy Centre, Hannover Medical School, Feodor-Lynen-Straße 21, 30625 Hannover, Germany. 12. Institute for Transfusion Medicine, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany. 13. Institute of Immunology, Oslo University Hospital, Sognsvannsveien 20, 0372 Oslo, Norway. 14. Professional Medical Trials and Information System (Prometris), Soldnerstraße 1, 68219 Mannheim, Germany. 15. Department of Haematology, Haemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany.
Abstract
AIMS: Intracoronary infusion of autologous nucleated bone marrow cells (BMCs) enhanced the recovery of left ventricular ejection fraction (LVEF) after ST-segment elevation myocardial infarction (STEMI) in the randomised-controlled, open-label BOOST trial. We reassessed the therapeutic potential of nucleated BMCs in the randomised placebo-controlled, double-blind BOOST-2 trial conducted in 10 centres in Germany and Norway. METHODS AND RESULTS: Using a multiple arm design, we investigated the dose-response relationship and explored whether γ-irradiation which eliminates the clonogenic potential of stem and progenitor cells has an impact on BMC efficacy. Between 9 March 2006 and 16 July 2013, 153 patients with large STEMI were randomly assigned to receive a single intracoronary infusion of placebo (control group), high-dose (hi)BMCs, low-dose (lo)BMCs, irradiated hiBMCs, or irradiated loBMCs 8.1 ± 2.6 days after percutaneous coronary intervention (PCI) in addition to guideline-recommended medical treatment. Change in LVEF from baseline (before cell infusion) to 6 months as determined by MRI was the primary endpoint. The trial is registered at Current Controlled Trials (ISRCTN17457407). Baseline LVEF was 45.0 ± 8.5% in the overall population. At 6 months, LVEF had increased by 3.3 percentage points in the control group and 4.3 percentage points in the hiBMC group. The estimated treatment effect was 1.0 percentage points (95% confidence interval, -2.6 to 4.7; P = 0.57). The treatment effect of loBMCs was 0.5 percentage points (-3.0 to 4.1; P = 0.76). Likewise, irradiated BMCs did not have significant treatment effects. BMC transfer was safe and not associated with adverse clinical events. CONCLUSION: The BOOST-2 trial does not support the use of nucleated BMCs in patients with STEMI and moderately reduced LVEF treated according to current standards of early PCI and drug therapy. Published on behalf of the European Society of Cardiology. All rights reserved.
AIMS: Intracoronary infusion of autologous nucleated bone marrow cells (BMCs) enhanced the recovery of left ventricular ejection fraction (LVEF) after ST-segment elevation myocardial infarction (STEMI) in the randomised-controlled, open-label BOOST trial. We reassessed the therapeutic potential of nucleated BMCs in the randomised placebo-controlled, double-blind BOOST-2 trial conducted in 10 centres in Germany and Norway. METHODS AND RESULTS: Using a multiple arm design, we investigated the dose-response relationship and explored whether γ-irradiation which eliminates the clonogenic potential of stem and progenitor cells has an impact on BMC efficacy. Between 9 March 2006 and 16 July 2013, 153 patients with large STEMI were randomly assigned to receive a single intracoronary infusion of placebo (control group), high-dose (hi)BMCs, low-dose (lo)BMCs, irradiated hiBMCs, or irradiated loBMCs 8.1 ± 2.6 days after percutaneous coronary intervention (PCI) in addition to guideline-recommended medical treatment. Change in LVEF from baseline (before cell infusion) to 6 months as determined by MRI was the primary endpoint. The trial is registered at Current Controlled Trials (ISRCTN17457407). Baseline LVEF was 45.0 ± 8.5% in the overall population. At 6 months, LVEF had increased by 3.3 percentage points in the control group and 4.3 percentage points in the hiBMC group. The estimated treatment effect was 1.0 percentage points (95% confidence interval, -2.6 to 4.7; P = 0.57). The treatment effect of loBMCs was 0.5 percentage points (-3.0 to 4.1; P = 0.76). Likewise, irradiated BMCs did not have significant treatment effects. BMC transfer was safe and not associated with adverse clinical events. CONCLUSION: The BOOST-2 trial does not support the use of nucleated BMCs in patients with STEMI and moderately reduced LVEF treated according to current standards of early PCI and drug therapy. Published on behalf of the European Society of Cardiology. All rights reserved.
Authors: Andreas Seitz; Kai C Wollert; Gerd P Meyer; Jochen Müller-Ehmsen; Carsten Tschöpe; Andreas E May; Klaus Empen; Emmanuel Chorianopoulos; Benedikta Ritter; Jens Pirr; Lubomir Arseniev; Hans-Gert Heuft; Arnold Ganser; Eed Abu-Zaid; Hugo A Katus; Stephan B Felix; Meinrad P Gawaz; Heinz-Peter Schultheiss; Dennis Ladage; Johann Bauersachs; Heiko Mahrholdt; Simon Greulich Journal: Clin Res Cardiol Date: 2019-08-10 Impact factor: 5.460
Authors: Mohammad R Ostovaneh; Raj R Makkar; Bharath Ambale-Venkatesh; Deborah Ascheim; Tarun Chakravarty; Timothy D Henry; Glen Kowalchuk; Frank V Aguirre; Dean J Kereiakes; Thomas J Povsic; Richard Schatz; Jay H Traverse; Janice Pogoda; Rachel D Smith; Linda Marbán; Eduardo Marbán; Joao A C Lima Journal: Open Heart Date: 2021-07