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(Circulation. 2005;112:1748-1755.)
© 2005 American Heart Association, Inc.

Heart Failure

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

Four-Year Follow-Up

Nabil Dib, MD, MSc; Robert E. Michler, MD; Francis D. Pagani, MD, PhD; Susan Wright, BS, RN; Dean J. Kereiakes, MD; Rose Lengerich, RN; Philip Binkley, MD; Diane Buchele, BSN, CNOR; Inder Anand, MD, DPhil; Cory Swingen, MS; Marcelo F. Di Carli, MD; James D. Thomas, MD; Wael A. Jaber, MD; Shaun R. Opie, PhD; Ann Campbell, BSN, RN; Patrick McCarthy, MD; Michael Yeager, RN; Vasken Dilsizian, MD; Bartley P. Griffith, MD; Ronald Korn, MD, PhD; Steven K. Kreuger, MD; Marwan Ghazoul, MD; W. Robb MacLellan, MD; Gregg Fonarow, MD; Howard J. Eisen, MD; Jonathan Dinsmore, PhD; Edward Diethrich, MD

From the Arizona Heart Institute (N.D., S.R.O., A.C., M.G., E.D.), Phoenix; the Cleveland Clinic Foundation (M.Y.), Cleveland, Ohio; the University of Michigan (F.D.P., S.W.), Ann Arbor; the University of California at Los Angeles (W.R.M., G.F.); Temple University (H.J.E.), Philadelphia, Pa; Ohio State University (R.E.M., P.B., D.B.), Columbus; the Lindner Clinical Trial Center (D.K., R.L., R.K.), Cincinnati, Ohio; the University of Maryland Medical Center (V.D., B.P.G.), Baltimore; the University of Minnesota (I.A., C.S.), Minneapolis; Brigham and Women’s Hospital (M.F.D.C.), Division of Nuclear Medicine, Boston, Mass; Scottsdale Medical Imaging Ltd (R.K.), Scottsdale, Ariz; GenVec, Inc (J.D.), Charlestown, Mass; Northwestern University (P.M.), Chicago, Ill; the Cleveland Clinic Foundation (J.T., W.J.), Section of Cardiovascular Imaging, Cleveland, Ohio; and the Bryan LGH Heart Institute (S.K.K.), Lincoln, Neb.

Correspondence to Nabil Dib, MD, Arizona Heart Institute, 2632 N 20th St, Phoenix, AZ 85006. E-mail Ndib{at}azheart.com

Received March 7, 2005; revision received May 4, 2005; accepted May 31, 2005.

Background— 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.

Methods and Results— 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.

Conclusions— 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.

Key Words: myocardial infarction • cells • transplantation • trials • heart failure

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