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


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.
Dib
Nabil
N
Arizona Heart Institute, Phoenix, AZ 85006, USA. Ndib@azheart.com
Michler
Robert E
RE
Pagani
Francis D
FD
Wright
Susan
S
Kereiakes
Dean J
DJ
Lengerich
Rose
R
Binkley
Philip
P
Buchele
Diane
D
Anand
Inder
I
Swingen
Cory
C
Di Carli
Marcelo F
MF
Thomas
James D
JD
Jaber
Wael A
WA
Opie
Shaun R
SR
Campbell
Ann
A
McCarthy
Patrick
P
Yeager
Michael
M
Dilsizian
Vasken
V
Griffith
Bartley P
BP
Korn
Ronald
R
Kreuger
Steven K
SK
Ghazoul
Marwan
M
MacLellan
W Robb
WR
Fonarow
Gregg
G
Eisen
Howard J
HJ
Dinsmore
Jonathan
J
Diethrich
Edward
E
D000328:Adult; D000368:Aged; D002125:Calcium Gluconate; D009202:Cardiomyopathies / Q000401:mortality / Q000601:surgery*; D004452:Echocardiography; D019560:Echocardiography, Three-Dimensional; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D032446:Myoblasts / Q000637:transplantation*; D017202:Myocardial Ischemia / Q000628:therapy; D012449:Safety; D016019:Survival Analysis; D014182:Transplantation, Autologous / Q000009:adverse effects / Q000401:mortality; D016277:Ventricular Function, Left
D002125:Calcium Gluconate