Journal Article

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

Povsic, Thomas J., Losordo, Douglas W., Henry, Timothy D., Story, Kenneth, Harrington, Robert A., Junge, Candice E., Schatz, Richard A.

2012

Overview

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. 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 × 105/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. 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. 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.

• Publisher: Elsevier Inc,Mosby,Elsevier Limited
• Subject: Acute coronary syndromes / Adult / Aged / Aged, 80 and over / Angina Pectoris - blood / Angina Pectoris - therapy / Antigens, CD34 / Biological and medical sciences / Biomarkers / Biomarkers - blood / Blood Component Removal / Cardiology / Cardiology. Vascular system / Cardiovascular / Catheters / Coronary Disease - epidemiology / Coronary Disease - etiology / Creatinine - blood / Female / Follow-Up Studies / Granulocyte Colony-Stimulating Factor - therapeutic use / Heart attacks / Heart failure / Hospitalization / Humans / Incidence / Logistic Models / Male / Medical sciences / Middle Aged / Myocardium / Randomized Controlled Trials as Topic / Stem Cell Transplantation - adverse effects / T-Lymphocytes / Transplantation, Autologous / Troponin I - blood