Safety and Feasibility of Autologous Myoblast Transplantation in Patients With Ischemic Cardiomyopathy

TLDR

Autologous skeletal myoblast transplantation into infarcted myocardium has improved cardiac function in multiple animal models. The study aimed to assess the safety and feasibility of autologous myoblast transplantation during CABG or LVAD implantation and to obtain preliminary data on graft survival and cardiac function changes. In a phase I, nonrandomized, multicenter pilot, 30 patients with ischemic cardiomyopathy undergoing CABG (n = 24) or LVAD (n = 6) received concurrent autologous myoblast transplants, with follow‑up PET, echocardiography, and histological analysis of explanted hearts. All 30 patients tolerated the procedure without acute or long‑term adverse events, and imaging and histology revealed graft survival, new metabolic activity in infarcted myocardium, and modest improvements in left ventricular ejection fraction (28% to 35% at 1 year, 36% at 2 years).

Abstract

Successful autologous skeletal myoblast transplantation into infarcted myocardium in a variety of animal models has demonstrated improvement in cardiac function. We evaluated the safety and feasibility of transplanting autologous myoblasts into infarcted myocardium of patients undergoing concurrent coronary artery bypass grafting (CABG) or left ventricular assist device (LVAD) implantation. In addition, we sought to gain preliminary information on graft survival and any associated changes in cardiac function.Thirty patients with a history of ischemic cardiomyopathy participated in a phase I, nonrandomized, multicenter pilot study of autologous skeletal myoblast transplantation concurrent with CABG or LVAD implantation. Twenty-four patients with a history of previous myocardial infarction and a left ventricular ejection fraction <40% were enrolled in the CABG arm. In a second arm, 6 patients underwent LVAD implantation as a bridge to heart transplantation, and patients donated their explanted native hearts for testing at the time of heart transplantation. Myoblasts were successfully transplanted in all patients without any acute injection-related complications or significant long-term, unexpected adverse events. Follow-up positron emission tomography scans showed new areas of glucose uptake within the infarct scar in CABG patients. Echocardiography measured an average change in left ventricular ejection fraction from 28% to 35% at 1 year and of 36% at 2 years. Histological evaluation in 4 of 6 patients who underwent heart transplantation documented survival and engraftment of the skeletal myoblasts within the infarcted myocardium.These results demonstrate the survival, feasibility, and safety of autologous myoblast transplantation and suggest that this modality offers a potential therapeutic treatment for end-stage heart disease.