Published online before print November 7, 2005, doi: 10.1161/CIRCULATIONAHA.105.541433
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(Circulation. 2005;112:3097-3106.)
© 2005 American Heart Association, Inc.
Heart Failure |
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)
From the Department of Internal Medicine, Divisions of Cardiology and Hematology (H.D.K., M.F.), and the Department of Nuclear Medicine (C.S.) at 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-Straße 6, 18057 Rostock, Germany. E-mail christoph.nienaber{at}med.uni-rostock.de
Received February 7, 2005; revision received July 22, 2005; accepted July 25, 2005.
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 (MNCCD34+), 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, ß-blocking agents, and statins. By use of CellQuest software on peripheral blood samples incubated with CD45 and CD34, mobilized MNCCD34+ were quantified on a daily basis. With homogeneous demographics and clinical and infarct-related characteristics, G-CSF stimulation led to mobilization of MNCCD34+ to between 3.17±2.93 MNCCD34+/µL at baseline and 64.55±37.11 MNCCD34+/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 MNCCD34+ 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 18F-deoxyglucose uptake in the infarct zone (P<0.001 versus control).
Conclusions— G-CSF and mobilization of MNCCD34+ after reperfusion of infarcted myocardium may offer a pragmatic strategy for preservation of myocardium and prevention of remodeling without evidence of aggravated restenosis.
Key Words: myocardial infarction • remodeling • cells • angioplasty • glucose
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