Instent neointimal hyperplasia after percutaneous intervention for ST-elevation myocardial infarction and treatment with granulocyte-colony stimulating factor. Results from the stem cells in myocardial infarction (STEMMI) trial.
BACKGROUND
Recombinant granulocyte-colony stimulating factor (G-CSF) mobilized pluripotent cells from the bone marrow are proposed to have a regenerative potential. Though, a report of excessive instent restenosis, in patients treated with G-CSF before percutaneous coronary intervention (PCI) warrants caution.


METHODS
Patients (n=59) enrolled in the STEMMI trial, a randomized and double blind study, comparing G-CSF and placebo after large ST-elevation myocardial infarctions, had an intracoronary ultrasound imaging at 6 months follow-up with a quantitative analysis of instent neointimal hyperplasia.


RESULTS
During G-CSF treatment leukocyte counts, and CD34+ and CD45-/CD34- cell fractions in peripheral blood increased markedly (p<0.0001 vs. placebo). At follow-up, there were no differences in intracoronary late lumen loss, expressed as neointima volume per mm of stent (1.6 mm(3)± 1.2 [G-CSF group] vs. 1.9 mm(3)± 1.3 [placebo group]; p=0.38), and in minimal instent lumen area (5.4 mm(2)± 2.4 vs. 5.3 mm(2)± 2.6, p=0.90). In the placebo group, plasma concentration of stromal cell-derived factor-1 (SDF-1) increased significantly after STEMI. This SDF-1 response was completely suppressed during G-CSF treatment. A rebound increase of SDF-1 was observed after withdrawal of G-CSF (p=0.001). Plasma concentration of SDF-1 at the time of stent implantation correlated positively to neointimal hyperplasia (p=0.025).


CONCLUSIONS
G-CSF treatment, initiated after PCI, does not lead to excessive instent neointimal hyperplasia or restenosis in patients with STEMI. The timing of G-CSF, in relation to the PCI, might be important, as G-CSF influences SDF-1.
Jørgensen
Erik
E
Cardiac Catheterization Laboratory, Department of Cardiology, Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark. erik.joergensen@rh.regionh.dk
Baldazzi
Federica
F
Ripa
Rasmus S
RS
Friis
Tina
T
Wang
Yongzong
Y
Helqvist
Steffen
S
Kastrup
Jens
J
D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects / Q000627:therapeutic use*; D019650:Hematopoietic Stem Cell Mobilization / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D006965:Hyperplasia / Q000000981:diagnostic imaging / Q000473:pathology / Q000517:prevention & control; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000473:pathology*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000473:pathology* / Q000628:therapy*; D058426:Neointima / Q000000981:diagnostic imaging / Q000473:pathology*; D011446:Prospective Studies; D011994:Recombinant Proteins; D015607:Stents / Q000009:adverse effects; D016896:Treatment Outcome; D014463:Ultrasonography
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor