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

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 mu g/kg body weight for 6 days in addition to standard care including aspirin, clopidogrel, an angiotensin-converting enzyme inhibitor, P-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 (MNCCD34+), with a 20-fold increase (from 3 +/- 2 at baseline to 66 +/- 54 MNCCD34+/mu L 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 MNCD34+ 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 MNCD34+ by G-CSF after primary PCI may offer a pragmatic strategy for improvement in ventricular function and prevention of left ventricular remodeling I year after acute myocardial infarction.