November 17, 2002
IL (AHA) – Researchers safely
transplanted 16 patients' skeletal muscle cells into their own
severely damaged hearts in the first human testing in the United
States, according to a study reported at the American Heart
Association’s Scientific Sessions 2002.
"We have been
able to regenerate dead heart muscle, or scar tissue, in the
area of heart attack without increasing risk of death," says
lead author Nabil Dib, M.D., director of cardiovascular research
at the Arizona Heart Institute in Phoenix. "Our findings will
allow us to move forward with testing if the procedure can
improve the contractility of the heart."
results indicate the procedure is safe and feasible, he says.
suffer a heart attack, scar tissue develops, resulting in a
decrease in heart contractility – its ability to compress and
force blood through its chambers. Since heart cells can’t repair
themselves, this damage is irreversible and eventually results
in heart failure.
conducted the multi-center trial, overseen by the U.S. Food and
Drug Administration, in patients who had suffered heart attacks
or heart failure and whose hearts had reduced pumping ability
evidenced by left-ventricular ejection fraction (EF) less than
30 percent. EF measures the quantity of blood pumped from the
heart with each beat. A healthy heart pumps out a little more
than half the heart’s volume of blood with each beat for an EF
of 55 percent or higher.
were undergoing coronary artery bypass surgery (CABG) and five
were having a left ventricular assist device (LVAD) implanted.
An LVAD helps a failing heart until a donor heart becomes
available for transplant.
myoblasts cells (immature cells that become muscle cells) were
extracted from thigh muscle. Large quantities of the cells were
grown in the laboratory for three to four weeks using a
controlled cell expansion manufacturing process. During the
surgery, one to 30 direct injections – containing 10 million
cells each – were made into the damaged area of the hearts. The
dosages ranged from 10 million to 300 million cells.
"We found that
the transplanted myoblasts survived and thrived in patients.
Areas damaged by heart attack and cardiovascular disease showed
evidence of repair and viability," Dib says.
adverse reactions were found related to the cell transplant
procedure in either group of patients in follow-up testing nine
There was one
death due to infection of the device in the LVAD group three
months after cell transplantation, and one patient in the CABG
group had non-sustained ventricular tachycardia – a fast heart
rate that starts in the lower chambers (ventricles).
While the trial
was not designed to evaluate the effect of cell transplant on
cardiac function, Dib calls the results extremely encouraging.
Examining the heart by echocardiogram, magnetic resonance
imaging (MRI), and positron emission tomography (PET scan)
showed evidence of scar tissue regeneration in the area of the
graft, which indicates repair.
improved, on average, from 22.7 percent to 35.8 percent – a 58
percent increase – after 12 weeks.
finding in the LVAD clinical study, is that we were able to
directly examine and observe histological changes in the heart
muscle of patients after they received a new heart and their old
one was removed," Dib says.
The results were
also compared against a group of historical controls from a Yale
University study, published in the Journal of the American
College of Cardiology (93:22:1411-7) of 83 patients with EF less
than 30 percent before bypass surgery. In the Yale group, there
was a 13 percent overall death rate and an 11 percent heart
death rate at one year.
After bypass, the
Yale group’s EF improved from 24.6 percent to 33.2 percent – a
36 percent increase.
Sessions 2000, French researchers described the first human
experience with autologous skeletal myoblast transplantation.
The transplant improved EF in a 72-year-old man undergoing a
bypass procedure. Subsequent procedures in other patients have
been reported at other meetings. Those studies showed similar
improvement in viability of dead or damaged heart tissue, but
several adverse reactions, such as life-threatening arrhythmias
also were reported.
complications were found in this study, Dib notes.
cellular and molecular procedures are being explored as ways to
repair and strengthen the damaged heart by replacing
dysfunctional or dead heart cells with cells from other sites
and those grown in laboratories, Dib says. These include
embryonic and adult cardiomyocytes, embryonic stem cells,
genetically altered fibroblasts, smooth muscle cells, bone
marrow-derived cells, and adult skeletal myoblasts.
Patrick McCarthy, M.D.; Ann Campbell, R.N.; Johnathan Dinsmore,
Ph.D.; Michael Yeager, R.N.; Francis D. Pagani, M.D.; Susan
Wright, R.N.; W. Robb MacLellan, M.D.; Gregg Fonarow, M.D.;
Howard J. Eisen, M.D.; Satoshi Furukawa, M.D.; Robert E. Michler,
M.D.; Diane Buchele, R.N.; Marwan Ghazoul, M.D.; and Edward B.
Diethrich, M.D. The study was funded by Diacrin, Inc.