PT  - JOURNAL ARTICLE
AU  - Sharon Chih
AU  - Peter S Macdonald
AU  - Jane A McCrohon
AU  - David Ma
AU  - John Moore
AU  - Michael P Feneley
AU  - Matthew Law
AU  - Jason C Kovacic
AU  - Robert M Graham
TI  - Granulocyte colony stimulating factor in chronic angina to stimulate neovascularisation: a placebo controlled crossover trial
AID  - 10.1136/heartjnl-2011-300751
DP  - 2012 Feb 15
TA  - Heart
PG  - 282--290
VI  - 98
IP  - 4
4099  - http://heart.bmj.com/content/98/4/282.short
4100  - http://heart.bmj.com/content/98/4/282.full
SO  - Heart2012 Feb 15; 98
AB  - Background Experimental studies demonstrate that granulocyte colony stimulating factor (G-CSF) promotes neovascularisation and confers cardioprotection.Objective To assess the efficacy of repeated low dose G-CSF plus exercise on myocardial ischaemia in patients with severe chronic ischaemic heart disease.Methods 18 patients with Canadian Cardiovascular Society class III–IV angina completed a randomised, double blind, crossover study of dose adjusted G-CSF versus placebo. Exercise was commenced 6 weeks prior and continued for the duration of the study. G-CSF or placebo was administered daily for 5 consecutive days at fortnightly intervals for three cycles, followed by crossover after 6 weeks. Primary outcome was myocardial perfusion by cardiac magnetic resonance imaging (MRI). Secondary outcomes were: Seattle Angina and Utility Based Quality of Life Heart Questionnaire (SAQ/UBQ-H), Exercise Stress Test (EST) and quantification of endothelial progenitor cells (EPC) by flow cytometry and angiogenic cytokines by immunoassay.Results Compared with placebo, G-CSF had no effect on myocardial ischaemia by cardiac MRI, EST or SAQ/UBQ-H, despite effective EPC mobilisation (peak fold increase: CD34+=19, CD34+CD133+=37, CD34+ vascular endothelial growth factor receptor 2 (VEGFR-2)+=5, CD34+CD133+VEGFR-2+=3; all p<0.05 vs placebo). Plasma levels of stromal cell derived factor 1, angiopoietin 1, interleukin 8 and tumour necrosis factor α decreased after a symptom limited EST while vascular endothelial growth factor and platelet derived growth factor remained unchanged. All cytokines were unchanged following G-CSF. Seven troponin I positive events occurred with G-CSF compared with three with placebo (p=0.289). High sensitivity C reactive protein and N terminal prohormone brain natriuretic peptide increased with G-CSF (both p<0.01 vs placebo).Conclusion In patients with chronic ischaemic heart disease, G-CSF mobilises EPCs but does not improve myocardial perfusion or angina. G-CSF increases plasma levels of adverse prognostic cardiac biomarkers.Clinical trial registration information Australian New Zealand Clinical Trials Registry: http://www.anzctr.org.au. Unique identifier: ACTRN012607000354482.