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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.

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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