title: Incidence and clinical significance of cardiac biomarker elevation during stem cell mobilization, apheresis, and intramyocardial delivery: an analysis from ACT34-CMI.
abstract: BACKGROUND
  Cell therapy is a promising therapeutic for a variety of cardiovascular conditions including refractory angina. Elevation of cardiac biomarkers during cell delivery has been frequently described, but the clinical implications have never been studied.
  
  
  METHODS
  ACT34-CMI was a randomized double-blind study assessing the use of intramyocardial delivery of autologous CD34(+) cells for the treatment of refractory angina. Patients (n = 167) underwent G-CSF-mediated (5 μg/[kg day] × 5 days) stem cell mobilization, apheresis, and intramyocardial injection of 1 × 10(5)/kg or 5 × 10(5)/kg CD34(+) cells or placebo. Troponin and creatinine kinase MB were assessed at baseline (n = 161), after cell mobilization and apheresis (n = 153 and 143, respectively), and post-intramyocardial injection (n = 155 and 141, respectively). Major adverse cardiac events (MACE) included death, myocardial infarction, acute congestive heart failure, urgent revascularization, or sustained ventricular arrhythmia.
  
  
  RESULTS
  Seven (4.3%) subjects had troponin above the upper limits of normal (ULN) at baseline. Thirty-four (22.2%) and 11 (7.2%) subjects had troponin levels > ULN or >3× ULN after cell mobilization and apheresis, whereas 72 (46.1%) and 39 (25.2%) subjects had troponin elevations > ULN or >3× ULN, respectively, after intramyocardial injections. Age, but no other preprocedural factors, was predictive of troponin elevation. Periprocedural troponin elevation was not associated with an increased risk of MACE during 1 year, especially in cell therapy-treated patients.
  
  
  CONCLUSIONS
  Troponin elevation is common during stem cell harvesting and intramyocardial administration, is usually asymptomatic, and does not appear to be associated with long-term MACE in subjects undergoing stem cell mobilization and intramyocardial injection.
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27705, USA. Elthomas.povsic@duke.edu
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Povsic
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Losordo
authors.forename: Kenneth
authors.initials: K
authors.lastname: Story
authors.forename: Candice E
authors.initials: CE
authors.lastname: Junge
authors.forename: Richard A
authors.initials: RA
authors.lastname: Schatz
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Henry
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000787:Angina Pectoris / Q000097:blood / Q000628:therapy*; D018952:Antigens, CD34; D015415:Biomarkers / Q000097:blood; D001781:Blood Component Removal; D003327:Coronary Disease / Q000453:epidemiology / Q000209:etiology; D003404:Creatinine / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009206:Myocardium; D016032:Randomized Controlled Trials as Topic; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D013601:T-Lymphocytes; D014182:Transplantation, Autologous; D019210:Troponin I / Q000097:blood*
chemical_list: D018952:Antigens, CD34; D015415:Biomarkers; D019210:Troponin I; D016179:Granulocyte Colony-Stimulating Factor; D003404:Creatinine