title: G-CSF stimulation and coronary reinfusion of mobilized circulating mononuclear proangiogenic cells in patients with chronic ischemic heart disease:five-year results of the TOPCARE-G-CSF trial.
abstract: Prognosis of patients with heart failure remains poor despite improved conventional and interventional treatment regimens. The improvement of neovascularization and repair processes by administration of bone marrow-derived cells modestly improved the recovery after acute myocardial infarction. However, circulating patient-derived cells are reduced in number and function particularly in chronic heart failure. Therefore, we tested the hypothesis whether the mobilization of circulating mononuclear proangiogenic cells (CPCs) by G-CSF may overcome some of these limitations. In the present pilot study, 32 patients with at least 3-month-old myocardial infarction were randomized to G-CSF alone (G-CSF group) or intracoronary infusion of G-CSF-mobilized and cultured CPCs into the infarct-related artery (G-CSF/CPC group). Primary endpoint of the study was safety. Efficacy parameters included serial assessment of LV function, NT-proBNP levels, and cardiopulmonary exercise testing. G-CSF effectively mobilized circulating CD34(+)CD45(+) cells after 5 days in all patients (408 ± 64%) without serious adverse events. At 3 months, NYHA class and global LV function did not show significant improvements in both treatment groups (G-CSF: ΔLVEF 1.6 ± 2.4%; p = 0.10; G-CSF/CPC: ΔLVEF 1.4 ± 4.1%; p = 0.16). In contrast, target area contractility improved significantly in the G-CSF/CPC group. During 5-year follow-up, one patient died after rehospitalization for worsening heart failure. Eleven patients underwent further revascularization procedures. NT-proBNP levels, cardiopulmonary exercise capacity, and NYHA class remained stable in both treatment groups. The results from our pilot trial indicate that administration of G-CSF alone or G-CSF-mobilized and cultured CPCs can be performed safely in patients with chronic ischemic heart disease. However, only minor effects on LV function, NT-proBNP levels, and NYHA classification were observed during follow-up, suggesting that the enhancement of CPCs by G-CSF alone does not substantially improve intracoronary cell therapy effects in patients with chronic ischemic heart failure.
authors.affiliation: Division of Cardiology, Department of Medicine III, Goethe University Frankfurt, Frankfurt, Germany.
authors.forename: Joerg
authors.initials: J
authors.lastname: Honold
authors.forename: Ulrich
authors.initials: U
authors.lastname: Fischer-Rasokat
authors.forename: Ralf
authors.initials: R
authors.lastname: Lehmann
authors.forename: David M
authors.initials: DM
authors.lastname: Leistner
authors.forename: Florian H
authors.initials: FH
authors.lastname: Seeger
authors.forename: Volker
authors.initials: V
authors.lastname: Schachinger
authors.forename: Hans
authors.initials: H
authors.lastname: Martin
authors.forename: Stefanie
authors.initials: S
authors.lastname: Dimmeler
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Zeiher
authors.forename: Birgit
authors.initials: B
authors.lastname: Assmus
mesh_terms: D000368:Aged; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D005260:Female; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006333:Heart Failure / Q000628:therapy*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000628:therapy*
chemical_list: D016179:Granulocyte Colony-Stimulating Factor