Clinical/Translational Research Intramyocardial, Autologous CD34 Cell Therapy for Refractory Angina

Rationale: 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. Methods and Results: In this prospective, double-blind, randomized, phase II study (ClinicalTrials.gov identifier: NCT00300053), 167 patients with refractory angina received 1 of 2 doses (110 5 or 510 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 (6.81.1 versus 10.91.2, P0.020) and 12 months (6.31.2 versus 11.01.2, P0.035); 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: 139151 versus 69122 seconds, P0.014; 12 months: 140171 versus 58146 seconds, P0.017) 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 cellmobilization and -collection procedures were associated with cardiac enzyme elevations, which will be addressed in future studies. (Circ Res. 2011;109:428-436.)