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A broken heart is hard to mend, or so the saying goes. That may be true for hearts "broken" by love -- but for hearts scarred by heart attacks, weakened by viruses or damaged by disease, healing is next to impossible.
With no chance to rest and mend as it constantly pumps blood throughout the body, a damaged heart can start to fail. Hundreds of thousands of Americans live with heart muscle damage -- also called heart failure -- that leaves them weak and gasping for breath. And nearly 4,000 are so sick they're on the waiting list for a heart transplant, a scarce and expensive "gift of life" they may not live long enough to receive.
But hope is on the horizon for these broken hearts. Doctors and researchers at the University of Michigan Cardiovascular Center and other institutions are working to find ways to help heal the damaged muscle, or to help it pump.
They're testing a promising technique that transplants cells from a patient's own leg muscles into the damaged part of the heart, in an effort to encourage the growth of healthy new tissue. And, they're helping severely ill patients live longer and better by implanting high-tech devices in their chests to help their hearts pump blood.
Last fall, the U-M team reported the first direct evidence that muscle cells transplanted from within a patient's body could help heal their damaged heart muscle. The results came from three patients who had cells removed from their thigh muscles, grown in a laboratory, and injected into their heart muscle while they awaited a heart transplant. After they received a new heart, the patients allowed their old, damaged hearts to be examined for signs of cell growth.
Since the transplanted cells were from a kind of muscle called skeletal muscle, and the heart is made of a different kind of muscle, called cardiac muscle, scientists didn't know for sure if the cell transplant would work. But with a shortage of available donor hearts for transplants, and thousands more patients suffering heart damage each day, they decided to try.
"Cell transplantation is really focused on healing the damaged areas of the heart, rather than replacing the entire heart," explains Francis Pagani, M.D., Ph.D., head of the Heart Transplant Program at the U-M Cardiovascular Center. "This research is in a very early stage, but what we have determined from this initial small study is that the method appears to be safe, with no serious side effects."
Even as Pagani and his team try the cell transplant technique, they're also relying on advanced technology to keep failing hearts going: implanted heart-assist devices.
The device they use, called a HeartMate, is one of a class of heart implants called left-ventricular assist devices, or LVADs. LVADs don't replace the heart, but rather help do the job of the heart's main pumping chamber.
HeartMate is available to patients awaiting a new heart, those who can't tolerate a heart transplant, and those who are too old, too ill, or have too many other health conditions to qualify for a new heart. It has helped keep many patients alive until transplant, which is crucial because of the shortage of hearts from human donors.
The U-M team has performed more HeartMate operations than all but two hospitals in the United States, and implanted 25 patients in 2002 alone. This vast experience in the selection, care and follow-up of those who receive the device improves the success rate for patients. Now, the U-M team is looking forward to participating in clinical trials for next-generation heart-assist devices now in development.
In the meantime, HeartMate continues to show its value in helping keep patients alive. The three patients who received the transplanted muscle cells in the recent study were also U-M HeartMate recipients, as is one other patient who also had the cell transplant, but is still waiting for a heart transplant.
"For our part of the study, we selected patients who were awaiting heart transplants, who were very ill and needed an LVAD," explains Pagani, who is an associate professor of surgery at the U-M Medical School. "At the time of the LVAD operation, we injected the muscle cells into their heart. Several months later, when we identified a potential heart donor, we removed the patient's old heart and replaced it with their new heart. So, we were able to examine the old heart for evidence of cell growth and differentiation of the skeletal muscle cells."
This differentiation, as it's called, is the key to the future of cell transplantation. In order to help heal the damaged muscle, the cells must grow and mature, and join with other nearby cells to form muscle fibers that can contract and expand to help the heart beat.
At the same time, other cells in the area need to recognize the presence of the new muscle cells, and grow tiny blood vessels to feed them. Early signs of such blood vessel formation were seen in the three U-M patients, and in one patient who took part in the study at Temple University in Philadelphia.
Other hospitals tried the procedure on patients having heart bypass surgery, although this meant that they couldn't remove the heart to look for cell growth. But that part of the study also showed that the procedure was safe and produced no major side effects.
Pagani stresses that these early results, while encouraging, are merely the first steps in testing skeletal muscle cell transplants. The initial results may help the researchers determine how to proceed toward evaluations of whether cell transplants can actually help heal patients' hearts.
He explains, "The next big questions that we have to answer are, 'Is this therapy effective? Does it have a benefit?' That's going to be accomplished with studies in a larger number of patients."
Pagani, who evaluates dozens of desperately ill heart patients each year for possible heart transplants and LVAD operations, knows that new options are sorely needed for the growing number of people who survive heart attacks, heart infections and other cardiovascular problems each year. Over time, the damage from those events will weaken and harden their hearts further -- until they eventually need help to stay alive.
"This therapy could be applicable to a large number of patients because the number of people in the United States who suffer from heart failure as a result of many heart attacks is large," Pagani notes. "So if this therapy does pan out and prove beneficial, then theoretically there will be a huge number of patients who could potentially benefit."
Until then, the broken hearts of the nation will continue to rely on an inadequate supply of donated hearts, and technology that can sustain damaged organs. It may not yet be possible to truly mend a broken heart, but someday it may not be impossible.
In addition to Pagani, the research team includes U-M cardiologist and transplant program medical director Keith Aaronson, M.D. and research coordinator Sue Wright, B.S., R.N., and several researchers from Massachusetts General Hospital. The study was sponsored by Diacrin, Inc.
Facts about heart damage, heart transplantation, and cell transplantation:
-According to the American Heart Association, 7.6 million Americans alive today have had a heart attack, and 4.9 million have congestive heart failure. -Within six years of a heart attack, 22 percent of men and 46 percent of women will be disabled with heart failure, which results from damage done during the heart attack. -The heart's muscle can be damaged by heart attack, infection, or other causes. Since the heart muscle is constantly moving, the damage does not heal on its own.-Animal studies have suggested that muscle cells from other parts of the body could be transplanted into the heart and grow new tissue to replace the damaged tissue. Recent small studies in humans suggest that transplanted cells may grow in people, too.-New studies are being proposed to test the therapy in larger groups of patients.-For patients who are awaiting a heart transplant, or are not eligible for a transplant because of age or illness, implanted devices can help their damaged heart pump blood.-One such device, the HeartMate left ventricular assist device, has been implanted in more than 100 U-M patients, including 25 in the year 2002 alone. The U-M has implanted more patients with HeartMates than all but two hospitals in the United States.
For more information, visit these Web sites:
U-M Health System study results: Muscle cell transplantationhttp://www.med.umich.edu/opm/newspage/2002/musclecell.htm
U-M Health Topics A to Z: Heart Transplanthttp://www.med.umich.edu/1libr/heart/surg02.htm
U-M Cardiovascular Centerhttp://www.med.umich.edu/cvc/
National Heart Lung and Blood Institute: Heart Failure http://www.nhlbi.nih.gov/health/public/heart/other/hrtfail.htm
American Heart Associationhttp://www.americanheart.org
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