Safety and feasibility of autologous myoblast transplantation in patients with ischemic cardiomyopathy: Four-year follow-up

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

Research output: Contribution to journalArticle

257 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1748-1755
Number of pages8
JournalCirculation
Volume112
Issue number12
DOIs
StatePublished - Sep 20 2005
Externally publishedYes

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Keywords

  • Cells
  • Heart failure
  • Myocardial infarction
  • Transplantation
  • Trials

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Dib, N., Michler, R. E., Pagani, F. D., Wright, S., Kereiakes, D. J., Lengerich, R., Binkley, P., Buchele, D., Anand, I., Swingen, C., Di Carli, M. F., Thomas, J. D., Jaber, W. A., Opie, S. R., Campbell, A., McCarthy, P., Yeager, M., Dilsizian, V., Griffith, B. P., ... Diethrich, E. (2005). Safety and feasibility of autologous myoblast transplantation in patients with ischemic cardiomyopathy: Four-year follow-up. Circulation, 112(12), 1748-1755. https://doi.org/10.1161/CIRCULATIONAHA.105.547810