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, β-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.
Evaluation by MRI of left ventricular remodeling and global functional recovery in patients treated with granulocyte-colony stimulating factor (G-CSF) after acute myocardial infarction (AMI)
