Preservation From Left Ventricular Remodeling by Front-Integrated Revascularization and Stem Cell Liberation in Evolving Acute Myocardial Infarction by Use of Granulocyte-Colony–Stimulating Factor (FIRSTLINE-AMI)

Abstract

Background— Considering experimental evidence that stem cells enhance myocardial regeneration and granulocyte colony–stimulating factor (G-CSF) mediates mobilization of CD34+ mononuclear blood stem cells (MNC CD34+ ), we tested the impact of G-CSF integrated into primary percutaneous coronary intervention (PCI) management of acute myocardial infarction in man. Methods and Results— Fifty consecutive patients with ST-segment elevation myocardial infarction were subjected to primary PCI stenting with abciximab and followed up for 6 months; 89±35 minutes after successful PCI, 25 patients were randomly assigned in this pilot study (PROBE design) to receive subcutaneous G-CSF at 10 μg/kg body weight for 6 days in addition to standard care, including aspirin, clopidogrel, an ACE inhibitor, β-blocking agents, and statins. By use of CellQuest software on peripheral blood samples incubated with CD45 and CD34, mobilized MNC CD34+ were quantified on a daily basis. With homogeneous demographics and clinical and infarct-related characteristics, G-CSF stimulation led to mobilization of MNC CD34+ to between 3.17±2.93 MNC CD34+ /μL at baseline and 64.55±37.11 MNC CD34+ /μL on day 6 ( P <0.001 versus control); there was no indication of leukocytoclastic effects, significant pain, impaired rheology, inflammatory reactions, or accelerated restenosis at 6 months. Within 35 days, G-CSF and MNC CD34+ liberation led to enhanced resting wall thickening in the infarct zone of between 0.29±0.22 and 0.99±0.32 mm versus 0.49±0.29 mm in control subjects ( P <0.001); under inotropic challenge with dobutamine (10 μg · kg −1 · min −1 ), wall motion score index showed improvement from 1.66±0.23 to 1.41±0.21 ( P <0.004 versus control) and to 1.35±0.24 after 4 months ( P <0.001 versus control), respectively, coupled with sustained recovery of wall thickening to 1.24±0.31 mm ( P <0.001 versus control) at 4 months. Accordingly, resting wall motion score index improved with G-CSF to 1.41±0.25 ( P <0.001 versus control), left ventricular end-diastolic diameter to 55±5 mm ( P <0.002 versus control), and ejection fraction to 54±8% ( P <0.001 versus control) after 4 months. Morphological and functional improvement with G-CSF was corroborated by enhanced metabolic activity and 18 F-deoxyglucose uptake in the infarct zone ( P <0.001 versus control). Conclusions— G-CSF and mobilization of MNC CD34+ after reperfusion of infarcted myocardium may offer a pragmatic strategy for preservation of myocardium and prevention of remodeling without evidence of aggravated restenosis.