title: Intramyocardial, autologous CD34+ cell therapy for refractory angina.
abstract: BACKGROUND
  A growing number of patients with coronary disease have refractory angina. Preclinical and early-phase clinical data suggest that intramyocardial injection of autologous CD34+ cells can improve myocardial perfusion and function.
  
  
  OBJECTIVE
  Evaluate the safety and bioactivity of intramyocardial injections of autologous CD34+ cells in patients with refractory angina who have exhausted all other treatment options.
  
  
  RESULTS
  In this prospective, double-blind, randomized, phase II study (ClinicalTrials.gov identifier: NCT00300053), 167 patients with refractory angina received 1 of 2 doses (1×10(5) or 5×10(5) cells/kg) of mobilized autologous CD34+ cells or an equal volume of diluent (placebo). Treatment was distributed into 10 sites of ischemic, viable myocardium with a NOGA mapping injection catheter. The primary outcome measure was weekly angina frequency 6 months after treatment. Weekly angina frequency was significantly lower in the low-dose group than in placebo-treated patients at both 6 months (6.8±1.1 versus 10.9±1.2, P=0.020) and 12 months (6.3±1.2 versus 11.0±1.2, P=0.035); measurements in the high-dose group were also lower, but not significantly. Similarly, improvement in exercise tolerance was significantly greater in low-dose patients than in placebo-treated patients (6 months: 139±151 versus 69±122 seconds, P=0.014; 12 months: 140±171 versus 58±146 seconds, P=0.017) and greater, but not significantly, in the high-dose group. During cell mobilization and collection, 4.6% of patients had cardiac enzyme elevations consistent with non-ST segment elevation myocardial infarction. Mortality at 12 months was 5.4% in the placebo-treatment group with no deaths among cell-treated patients.
  
  
  CONCLUSIONS
  Patients with refractory angina who received intramyocardial injections of autologous CD34+ cells (10(5) cells/kg) experienced significant improvements in angina frequency and exercise tolerance. The cell-mobilization and -collection procedures were associated with cardiac enzyme elevations, which will be addressed in future studies.
authors: Division of Cardiology, Northwestern Memorial Hospital, Northwestern University, Chicago, IL 60611, USA. d-losordo@northwestern.edu
authors: Douglas W
authors: DW
authors: Losordo
authors: Timothy D
authors: TD
authors: Henry
authors: Charles
authors: C
authors: Davidson
authors: Joon
authors: J
authors: Sup Lee
authors: Marco A
authors: MA
authors: Costa
authors: Theodore
authors: T
authors: Bass
authors: Farrell
authors: F
authors: Mendelsohn
authors: F David
authors: FD
authors: Fortuin
authors: Carl J
authors: CJ
authors: Pepine
authors: Jay H
authors: JH
authors: Traverse
authors: David
authors: D
authors: Amrani
authors: Bruce M
authors: BM
authors: Ewenstein
authors: Norbert
authors: N
authors: Riedel
authors: Kenneth
authors: K
authors: Story
authors: Kerry
authors: K
authors: Barker
authors: Thomas J
authors: TJ
authors: Povsic
authors: Robert A
authors: RA
authors: Harrington
authors: Richard A
authors: RA
authors: Schatz
mesh_terms: D000368:Aged; D000787:Angina Pectoris / Q000209:etiology / Q000401:mortality / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D018952:Antigens, CD34 / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D001781:Blood Component Removal; D002317:Cardiovascular Agents / Q000627:therapeutic use; D003326:Coronary Circulation; D004311:Double-Blind Method; D042783:Endothelial Cells / Q000276:immunology / Q000637:transplantation*; D005080:Exercise Test; D017079:Exercise Tolerance; D005260:Female; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000150:complications / Q000401:mortality / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D009206:Myocardium / Q000473:pathology*; D018919:Neovascularization, Physiologic; D011446:Prospective Studies; D012038:Regeneration; D012044:Regression Analysis; D018570:Risk Assessment; D012307:Risk Factors; D011795:Surveys and Questionnaires; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014481:United States
chemical_list: D018952:Antigens, CD34; D015415:Biomarkers; D002317:Cardiovascular Agents