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

254 Citations (Scopus)

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

Fingerprint

Autologous Transplantation
Myoblasts
Cardiomyopathies
Safety
Skeletal Myoblasts
Coronary Artery Bypass
Heart-Assist Devices
Heart Transplantation
Myocardium
Stroke Volume
Transplantation
Survival
Graft Survival
Positron-Emission Tomography
Multicenter Studies
Cicatrix
Echocardiography
Heart Diseases
Animal Models
Myocardial Infarction

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Safety and feasibility of autologous myoblast transplantation in patients with ischemic cardiomyopathy : Four-year follow-up. / Dib, Nabil; Michler, Robert E.; Pagani, Francis D.; Wright, Susan; Kereiakes, Dean J.; Lengerich, Rose; Binkley, Philip; Buchele, Diane; Anand, Inder; Swingen, Cory; Di Carli, Marcelo F.; Thomas, James D.; Jaber, Wael A.; Opie, Shaun R.; Campbell, Ann; McCarthy, Patrick; Yeager, Michael; Dilsizian, Vasken; Griffith, Bartley P.; Korn, Ronald; Kreuger, Steven K.; Ghazoul, Marwan; MacLellan, W. Robb; Fonarow, Gregg; Eisen, Howard J.; Dinsmore, Jonathan; Diethrich, Edward.

In: Circulation, Vol. 112, No. 12, 20.09.2005, p. 1748-1755.

Research output: Contribution to journalArticle

Dib, N, Michler, RE, Pagani, FD, Wright, S, Kereiakes, DJ, Lengerich, R, Binkley, P, Buchele, D, Anand, I, Swingen, C, Di Carli, MF, Thomas, JD, Jaber, WA, Opie, SR, Campbell, A, McCarthy, P, Yeager, M, Dilsizian, V, Griffith, BP, Korn, R, Kreuger, SK, Ghazoul, M, MacLellan, WR, Fonarow, G, Eisen, HJ, Dinsmore, J & Diethrich, E 2005, 'Safety and feasibility of autologous myoblast transplantation in patients with ischemic cardiomyopathy: Four-year follow-up', Circulation, vol. 112, no. 12, pp. 1748-1755. https://doi.org/10.1161/CIRCULATIONAHA.105.547810
Dib, Nabil ; Michler, Robert E. ; Pagani, Francis D. ; Wright, Susan ; Kereiakes, Dean J. ; Lengerich, Rose ; Binkley, Philip ; Buchele, Diane ; Anand, Inder ; Swingen, Cory ; Di Carli, Marcelo F. ; Thomas, James D. ; Jaber, Wael A. ; Opie, Shaun R. ; Campbell, Ann ; McCarthy, Patrick ; Yeager, Michael ; Dilsizian, Vasken ; Griffith, Bartley P. ; Korn, Ronald ; Kreuger, Steven K. ; Ghazoul, Marwan ; MacLellan, W. Robb ; Fonarow, Gregg ; Eisen, Howard J. ; Dinsmore, Jonathan ; Diethrich, Edward. / Safety and feasibility of autologous myoblast transplantation in patients with ischemic cardiomyopathy : Four-year follow-up. In: Circulation. 2005 ; Vol. 112, No. 12. pp. 1748-1755.
@article{8cd8e4ef3ace46b0a04f07dd7845bd8a,
title = "Safety and feasibility of autologous myoblast transplantation in patients with ischemic cardiomyopathy: Four-year follow-up",
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.",
keywords = "Cells, Heart failure, Myocardial infarction, Transplantation, Trials",
author = "Nabil Dib and Michler, {Robert E.} and Pagani, {Francis D.} and Susan Wright and Kereiakes, {Dean J.} and Rose Lengerich and Philip Binkley and Diane Buchele and Inder Anand and Cory Swingen and {Di Carli}, {Marcelo F.} and Thomas, {James D.} and Jaber, {Wael A.} and Opie, {Shaun R.} and Ann Campbell and Patrick McCarthy and Michael Yeager and Vasken Dilsizian and Griffith, {Bartley P.} and Ronald Korn and Kreuger, {Steven K.} and Marwan Ghazoul and MacLellan, {W. Robb} and Gregg Fonarow and Eisen, {Howard J.} and Jonathan Dinsmore and Edward Diethrich",
year = "2005",
month = "9",
day = "20",
doi = "10.1161/CIRCULATIONAHA.105.547810",
language = "English (US)",
volume = "112",
pages = "1748--1755",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins",
number = "12",

}

TY - JOUR

T1 - Safety and feasibility of autologous myoblast transplantation in patients with ischemic cardiomyopathy

T2 - Four-year follow-up

AU - Dib, Nabil

AU - Michler, Robert E.

AU - Pagani, Francis D.

AU - Wright, Susan

AU - Kereiakes, Dean J.

AU - Lengerich, Rose

AU - Binkley, Philip

AU - Buchele, Diane

AU - Anand, Inder

AU - Swingen, Cory

AU - Di Carli, Marcelo F.

AU - Thomas, James D.

AU - Jaber, Wael A.

AU - Opie, Shaun R.

AU - Campbell, Ann

AU - McCarthy, Patrick

AU - Yeager, Michael

AU - Dilsizian, Vasken

AU - Griffith, Bartley P.

AU - Korn, Ronald

AU - Kreuger, Steven K.

AU - Ghazoul, Marwan

AU - MacLellan, W. Robb

AU - Fonarow, Gregg

AU - Eisen, Howard J.

AU - Dinsmore, Jonathan

AU - Diethrich, Edward

PY - 2005/9/20

Y1 - 2005/9/20

N2 - 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.

AB - 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.

KW - Cells

KW - Heart failure

KW - Myocardial infarction

KW - Transplantation

KW - Trials

UR - http://www.scopus.com/inward/record.url?scp=25444462742&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=25444462742&partnerID=8YFLogxK

U2 - 10.1161/CIRCULATIONAHA.105.547810

DO - 10.1161/CIRCULATIONAHA.105.547810

M3 - Article

C2 - 16172284

AN - SCOPUS:25444462742

VL - 112

SP - 1748

EP - 1755

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 12

ER -