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

Int J Cardiol. 2010 Mar 18;139(3):269-75. doi: 10.1016/j.ijcard.2008.10.029. Epub 2008 Dec 3.

Abstract

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.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angioplasty, Balloon, Coronary* / adverse effects
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Granulocyte Colony-Stimulating Factor / adverse effects
  • Granulocyte Colony-Stimulating Factor / therapeutic use*
  • Hematopoietic Stem Cell Mobilization / adverse effects
  • Hematopoietic Stem Cell Mobilization / methods*
  • Humans
  • Hyperplasia / diagnostic imaging
  • Hyperplasia / pathology
  • Hyperplasia / prevention & control
  • Male
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / pathology*
  • Middle Aged
  • Myocardial Infarction / diagnostic imaging
  • Myocardial Infarction / pathology*
  • Myocardial Infarction / therapy*
  • Neointima / diagnostic imaging
  • Neointima / pathology*
  • Prospective Studies
  • Recombinant Proteins
  • Stents* / adverse effects
  • Treatment Outcome
  • Ultrasonography

Substances

  • Recombinant Proteins
  • Granulocyte Colony-Stimulating Factor