Abstract 3361: Randomized, Double Blind, Placebo Controlled Pilot Trial of Intramyocardial Autologous CD34 Cell Therapy for Intractable Angina
Background: Pre-clinical studies have indicated that human CD34+ cells induce neovascularization in ischemic myocardium, enhancing perfusion and function.
Methods: 24 pts(19M; 5F; age 48 – 84 ) with CCS class 3 or 4 angina on optimal medical Rx and who were not candidates for mechanical revasc were enrolled in a dose escalating double blind randomized controlled trial. Pts received GCSF(G) 5ug/kg/d for 5d with leukoapheresis on the 5th day. Selection of CD34+ cells was performed with Isolex 300i(Baxter). NOGA electromechanical LV mapping was performed to identify ischemic but viable regions of myocardium for injection of cells (vs. saline). The total dose of cells was distributed in 10 intramyocardial(IMyo) injections performed with the Myostar catheter. Pts were required to have an ICD or to wear a LifeVest wearable defibrillator.
Results: Mobilization of CD34+ cells with G resulted in a transient increase in angina frequency in 54.2% of patients. There was no incidence of MI induced by mobilization or intramyocardial injection. The intramyocardial injection of cells/saline did not result in perforation or pericardial effusion. ICD/LifeVest recordings revealed no incidence of VT/VF during the administration of G or IMyo injections. One patient with a hx of SCD/VT/VF had catheter induced VT during mapping requiring cardioversion. In blinded f/u the treated pts had greater reductions in angina frequency (3mo:-11.6 vs. +6.5; 6mo:-12.6 vs. -4.5; 12mo: -15.6 vs. -10.3) and CCS class(3mo:-1.1 vs. -0.5, 6mo:-1.4 vs. -0.8, 12mo:-1.7 vs. -1.0). Automated, blinded analysis of serial SPECT perfusion scans revealed a reduction in the SSS (3mo: -0.6 vs +1.3, 6mo: -0.4 vs. +0.5) and SDS (3mo:-2.4 vs. -1.5, 6mo:-2.3 vs -0.7) in treated vs controls.
Conclusion: A double-blind placebo controlled trial of IMyo injection of autologous CD34+ cells in pts with intractable angina resulted in no safety events referable to treatment and trends in clinical and objective parameters favoring the active treatment group. These data will be extended in an ongoing phase 2 study planned for enrollment of 150 pts.