531 IMPACT-CABG trial: Implantation of CD133+ stem cells in patients undergoing coronary bypass surgery, analysis of security, feasibility and efficacy for the first five open-labeled patients

Abstract

Cellular transplantation is a novel strategy to improve ischemic myocardium healing. Bone marrow CD133+ cells are distinct early progenitor group of hematopoietic stem cells that possess high engraftment, pluripotent and angiogenic capacity and appear valuable for cardiac repair by promoting neovascularization, cardiomyogenesis and inhibition of apoptosis. The aim is to report the feasibility, security and beneficial effects of intramyocardial injection of CD133+ stem cells. We report herein the 6 month follow-up on the first 5 patients treated in an open labeled fashion in the IMPACT-CABG study. This is a randomized-controlled phase II clinical trial aiming to assess the safety and effects of intramyocardial injections of autologous CD 133+ selected stem cells in coronary artery bypass grafting (CABG) patients with chronic ischemic cardiomyopathy (left ventricular ejection fraction (LVEF) below 45%). Cardiac function and myocardial viability was assessed by stress echocardiography and magnetic resonance imaging (MRI) before and 6 months after surgery. Bone marrow aspiration and cell selection, using the CliniMACS system, are performed the morning of the surgical procedure and cells are injected intramyocardially after completion of the distal anastomosis before weaning from cardiopulmonary bypass. Five males, mean age 65 ± 10 years, underwent CABG for 3 ± 1 bypasses. A total of 10 millions CD133+ cells were injected in 15 sites (total cell suspension volume 2.0 ml). Post-operative course was uneventful for each patient. There was no peri-operative complication related to this protocol, and no Major Adverse Cardiac Event (MACE) defined as cardiac death, myocardial infarction, repeated coronary revascularization or sustained ventricular arrhythmias. Pre- and 6 months post-operative LVEF were 34.0 ± 2.2 and 39.0 ± 11.9 respectively (P = ns). Moreover, MRI studies suggested that LV end-diastolic and end-systolic volumes decreased after cell implantation compared to baseline. Echocardiographic regional wall motion index for all patients in the ischemic stem cell-injected territories improve at 6 months of follow-up in all patients compared to baseline. The NYHA functional class improved for every patient from class III to class I. This work represents the first Canadian experience with CD133+ stem cells for the treatment of chronic ischemic cardiomyopathy and relies on state-of-the-art methods for assessing myocardial functional recovery and viability. These encouraging results support the safety and feasibility of intramyocardial injections of CD 133+ cells in addition to CABG. IMPACT-CABG trial with further double-blind randomization between CD 133+ cells vs. placebo will test the beneficial impact of this approach.