EXPEDITED REVIEW
Autologous Bone Marrow Stem Cell Mobilization Induced by Granulocyte Colony-Stimulating Factor After Subacute ST-Segment Elevation Myocardial Infarction Undergoing Late Revascularization
Final Results From the G-CSF-STEMI (Granulocyte Colony-Stimulating Factor ST-Segment Elevation Myocardial Infarction) Trial
Markus G. Engelmann, MD*,
Hans D. Theiss, MD*,
Christine Hennig-Theiss*,
Armin Huber, MD ,
Bernd J. Wintersperger, MD,
Anja-Eva Werle-Ruedinger,
Stefan O. Schoenberg, MD,
Gerhard Steinbeck, MD* and
Wolfgang-M. Franz, MD*,*
* Medical Clinic I—Department of Cardiology, Ludwig Maximilians University, Klinikum Grosshadern, Munich, Germany
Department of Clinical Diagnostic Radiology, Ludwig Maximilians University, Klinikum Grosshadern, Munich, Germany
Manuscript received January 20, 2006;
revised manuscript received June 29, 2006,
accepted July 3, 2006.
* Reprint requests and correspondence: Prof. Dr. med. Wolfgang-M. Franz, Ludwig Maximilians University, Medical Clinic I—Department of Cardiology Klinikum Grosshadern, Marchioninistr. 15, D-81377 Munich, Germany. (Email: wolfgang.franz{at}med.uni-muenchen.de).
OBJECTIVES: The purpose of this investigator-driven, prospective, randomized, double-blinded, placebo-controlled phase II study was to compare the effects of granulocyte colony-stimulating factor (G-CSF) on the improvement of myocardial function in patients undergoing delayed percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI).
BACKGROUND: Experimental and early clinical studies suggest that transplantation of stem cells improves cardiac regeneration and neovascularization after acute myocardial infarction. Most investigators have utilized either a direct injection or intracoronary infusion of bone marrow–derived cells, but early cytokine-mediated mobilization of stem cells has been reported to show similar improvement in cardiac function.
METHODS: Forty-four patients with late revascularized subacute STEMI were treated either with G-CSF or placebo over 5 days after successful PCI. Primary end points were change of global and regional myocardial function from baseline (1 week after PCI) to 3 months after PCI assessed by magnetic resonance imaging (MRI). Secondary end points consisted of characterization of mobilized stem cell populations, assessment of safety parameters up to 12 months including 6-month angiography, as well as myocardial perfusion assessed by MRI.
RESULTS: Global myocardial function from baseline (1 week after PCI) to 3 months improved in both groups, but G-CSF was not superior to placebo ( ejection fraction 6.2 ± 9.0 vs. 5.3 ± 9.8%, p = 0.77). A slight but non-significant improvement of regional function occurred in both groups. Granulocyte colony-stimulating factor resulted in mobilization of endothelial progenitor cell populations and was well tolerated with a similar rate of target lesion revascularization from in-stent restenosis. In both groups major adverse cardiovascular events occurred in a comparable frequency. Granulocyte colony-stimulating factor resulted in significant improvement of myocardial perfusion 1 week and 1 month after PCI.
CONCLUSIONS: Granulocyte colony-stimulating factor treatment after PCI in subacute STEMI is feasible and relatively safe. However, patients do not benefit from G-CSF when PCI is performed late. Granulocyte colony-stimulating factor results in improved myocardial perfusion of the infarcted area, which may reflect enhanced neovascularization.
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Abbreviations and Acronyms
| | EF = ejection fraction | | FIRSTLINE-AMI = Front-Integrated Revascularization and Stem Cell Liberation in Evolving Acute Myocardial Infarction by Granulocyte Colony-Stimulating Factor Trial | | G-CSF = granulocyte colony-stimulating factor | | ISR = in-stent restenosis | | MACE = major adverse cardiovascular events | | MI = myocardial infarction | | MRI = magnetic resonance imaging | | PCI = percutaneous coronary intervention | | STEMI = ST-segment elevation myocardial infarction | | TLR = target lesion revascularization |
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