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 × 105/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.
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Conflicts of Interest: Timothy D. Henry and Richard A. Schatz were members of the Scientific Advisory Board for the ACT34-CMI study. Drs Harrington and Povsic are employees of the Duke Clinical Research Institute which has received research funding from Baxter. They have received modest funding for consulting to Baxter. Douglas W. Losordo, Candice E. Junge, and Kenneth Story are employed by Baxter Healthcare.