Incidence and clinical significance of cardiac biomarker elevation during stem cell mobilization, apheresis, and intramyocardial delivery: an analysis from ACT34-CMI

Am Heart J. 2012 Nov;164(5):689-697.e3. doi: 10.1016/j.ahj.2012.06.022.


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.

Trial registration: NCT00300053.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angina Pectoris / blood
  • Angina Pectoris / therapy*
  • Antigens, CD34*
  • Biomarkers / blood
  • Blood Component Removal*
  • Coronary Disease / epidemiology
  • Coronary Disease / etiology
  • Creatinine / blood*
  • Female
  • Follow-Up Studies
  • Granulocyte Colony-Stimulating Factor / therapeutic use
  • Humans
  • Incidence
  • Logistic Models
  • Male
  • Middle Aged
  • Myocardium
  • Randomized Controlled Trials as Topic
  • Stem Cell Transplantation / adverse effects*
  • T-Lymphocytes*
  • Transplantation, Autologous
  • Troponin I / blood*


  • Antigens, CD34
  • Biomarkers
  • Troponin I
  • Granulocyte Colony-Stimulating Factor
  • Creatinine

Associated data