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(Circulation. 2005;112:I-73 – I-80.)
© 2005 American Heart Association, Inc.

Cell Transplantation and Tissue Engineering

Prevention of Left Ventricular Remodeling With Granulocyte Colony-Stimulating Factor After Acute Myocardial Infarction

Final 1-year Results of the Front-Integrated Revascularization and Stem Cell Liberation in Evolving Acute Myocardial Infarction by Granulocyte Colony-Stimulating Factor (FIRSTLINE-AMI) Trial

Hüseyin Ince, MD; Michael Petzsch, MD; Hans Dieter Kleine, MD; Heike Eckard, MD; Tim Rehders, MD; Detlev Burska, MD; Stephan Kische, MD; Mathias Freund, MD; Christoph A. Nienaber, MD

From the Department of Medicine, Divisions of Cardiology (H.I., M.P., H.E., T.R., D.B., S.K., C.A.N.) and Hematology (H.D.K., M.F.), the University Hospital Rostock, Rostock School of Medicine, Rostock, Germany.

Correspondence to Christoph A. Nienaber, MD, FACC, FESC, Division of Cardiology, University Hospital Rostock, Rostock School of Medicine, Ernst-Heydemann-Str. 6, 18057 Rostock, Germany. E-mail christoph.nienaber{at}med.uni-rostock.de

Background— Experimental and clinical evidence has recently shown that pluripotent stem cells can be mobilized by granulocyte colony-stimulating factor (G-CSF) and may enhance myocardial regeneration early after primary percutaneous coronary intervention (PCI) management of acute myocardial infarction. Sustained or long-term effects of mobilized CD34-positive mononuclear stem cells, however, are unknown.

Methods and Results— Thirty consecutive patients with ST-elevation myocardial infarction undergoing primary PCI with stenting and abciximab were selected for the study 85±30 minutes after PCI; 15 patients were randomly assigned to receive subcutaneous G-CSF at 10 µg/kg body weight for 6 days in addition to standard care including aspirin, clopidogrel, an angiotensin-converting enzyme inhibitor, ß-blocking agents, and statins. In patients with comparable demographics and clinical and infarct-related characteristics, G-CSF stimulation led to sustained mobilization of CD34 positive mononuclear cells (MNC^CD34+), with a 20-fold increase (from 3±2 at baseline to 66±54 MNC^CD34+/µL on day 6; P<0.001); there was no evidence of leukocytoclastic effects, accelerated restenosis rate, or any late adverse events. Within 4 months, G-CSF–induced MNC^CD34+ mobilization led to enhanced resting wall thickening in the infarct zone of 1.16±0.29 mm (P<0.05 versus control), which was sustained at 1.20±0.28 after 12 months (P<0.001 versus control). Similarly, left ventricular ejection fraction improved from 48±4% at baseline to 54±8% at 4 months (P<0.005 versus control) and 56±9% at 12 months (P<0.003 versus control and paralleled by sustained improvement of wall-motion score index from 1.70±0.22 to 1.42±0.26 and 1.33±0.21 at 4 and 12 months, respectively), after G-CSF (P<0.05 versus baseline and P<0.03 versus controls). Accordingly, left ventricular end-diastolic diameter showed no remodeling and stable left ventricular dimensions after G-CSF stimulation, whereas left ventricular end-diastolic diameter in controls revealed enlargement from 55±4 mm at baseline to 58±4 mm (P<0.05 versus baseline) at 12 months after infarction and no improvement in diastolic function.

Conclusion— Mobilization of MNC^CD34+ by G-CSF after primary PCI may offer a pragmatic strategy for improvement in ventricular function and prevention of left ventricular remodeling 1 year after acute myocardial infarction.

Key Words: myocardial infarction • remodeling • cells • stents