By RONDA WENDLER
Texas Medical Center News
Houston [April 2004]
A procedure that for more than a year has been bringing South American heart failure patients back from near-death has been approved for testing in the Texas Medical Center.
The "green light," issued March 16 by the Food and Drug Administration, makes physicians at the Texas Heart Institute and St. Luke's Episcopal Hospital among the first in the nation to conduct a clinical trial of stem cell therapy for advanced heart-failure patients.
Since December 2001, the Texas Medical Center doctors have been making frequent trips to Brazil, where they have collaborated with physicians at Pro-Cardiaco Hospital to treat damaged human hearts with stem cells taken from the patients' own bone marrow. The doctors wanted to know whether these bone marrow stem cells, when implanted in the heart, could help strengthen damaged heart muscle.
A year later, they had their answer. Patients not only improved – but they wildly improved – surpassing all expectations. Results documenting the Brazilian trial's success were enough to convince FDA officials to allow a similar trial here in the United States.
"These people in Brazil were reborn. The stem cell injections 'woke up' their hearts," says Emerson Perin, M.D., Ph.D., director of New Interventional Cardiovascular Technology at the Texas Heart Institute. Perin, a native Brazilian who maintains close clinical and research ties with Pro-Cardiaco Hospital in Rio de Janeiro, performed the stem cell implantations in Brazil.
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| It may look like a fishing rod, but the device held by Emerson Perin, MD, PhD, is actually a catheter that delivers bone marrow stem cells straight to the heart. |
Bouncing Back in Brazil
A classic success story is Nelson Aguia, 70, a native of Rio de Janeiro. Two years ago, Aguia lay in bed, waiting to die. Brought down by the effects of end-stage heart failure, he was too weak to walk from one room to the next or to finish a sentence without excruciating chest pain and shortness of breath.
Doctors had tried all the conventional therapies – bypass surgery, angioplasty, medication, but nothing worked. "I was told to prepare for one final, fatal heart attack," says Aguia. "There was nothing left to do but wait for the inevitable. I started planning my funeral to spare my wife the burden."
Then, Aguia's daughter who is a pediatrician in Brazil, read a newspaper article about an experimental trial that she believed could provide her father with one last chance for recovery. "I never accepted the fact that my father would die ... I always held out hope," says Terezinha Aguia, who is labeled a "guardian angel" by her father.
At his daughter's urging, doctors at Pro-Cardiaco Hospital offered a fast-failing Aguia an opportunity to become the first of 21 patients enrolled in the Houston/ Brazilian study, believed to be the largest cardiovascular stem cell study in the world.
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| Success story—After doctors from Texas Heart Institute implanted stem cells into his heart, Nelson Aguia, right, has bounced back from end-stage heart failure. Aguia, a native of Brazil, is shown here with his Brazilian cardiologist, Hans Fernando Dohmann, MD. |
Six months after receiving the stem cell therapy and continuing today, Aguia is walking three miles around Brazil's largest soccer stadium twice a week, swimming three times a week, and working eight hours a day as a pharmaceutical sales representative – a job he gave up years ago. During Brazil's annual Carnival celebration each February, he dances in the streets.
"I'm ready for anything. This treatment has restored my life," said a grateful Aguia. Other participants agree. Only two months after being implanted with stem cells, the hearts of the Brazilian patients were pumping much more efficiently. Patients did well on treadmill tests and their angina, or chest pain, decreased. Subsequent months showed steady improvement.
Now, selected Houston-area patients have the opportunity to reap the same benefits. "This is encouraging news for cardiac patients who have exhausted all treatment options and reached the end of the road," Perin said. "Now we have hope on the horizon."
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| | Before and after—The image on the left shows heart damage, which appears as blue and purple in this 3-D image of a heart's left ventricle. The image on the right shows the same ventricle after stem cell therapy. The red area and surrounding bright colors depict improvement. | |
The Houston Study
In the Houston trial, 30 patients with end-stage heart failure are participating. Twenty will receive stem cell injections, and 10 will not. Because the trial is randomized, patients won't know whether they received the treatment or not.
"I'm sensitive about the 10 who get left out," Perin says. "Six months into the study, they will be offered the stem cells as well. Most of the benefits resulting from the treatment occur within six weeks of implantation, so by six months, we've got solid data. It's not a problem to let the control group have the stem cells at that point."
Patients' progress will be evaluated at one, three, six and 12 months, using the most sophisticated imaging techniques available. As Perin says, "We're going to follow the hell out of these people."
To the Rescue
The procedure is minimally invasive, and uses a catheter to carry harvested bone marrow stem cells straight to the heart. Under the right conditions, stem cells will potentially give rise to, or differentiate into, the cell types that make up the organism into which they are injected – in this case, the heart muscle.
"The goal of this treatment is to replace damaged heart muscle cells and promote the growth of new blood vessels that will supply oxygen to the damaged heart muscle. The stem cells are going 'to the rescue' to accomplish this," explains Perin.
"One thing is very clear. The injected stem cells improve the blood flow to the heart," says James T. Willerson, director of Cardiology Research at the Texas Heart Institute and chief of Cardiology at St. Luke's.
Using a 3-D map of the heart shown on a video screen, doctors identify the areas of the heart that are suffering the most and target those specific areas for injection.
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To conduct the procedure, doctors harvest stem cells from a patient's bone marrow, select out those cells most likely to develop into the cell type needed in the heart, culture them for three hours, then inject the candidate cells into the heart. The cells are carried to the left ventricle – the main pumping chamber of the heart – through a small catheter that is inserted into a tiny incision in the patient's groin and threaded upward through the body, into the heart. A needle then is sent traveling through the catheter until it emerges into the left ventricle, where the catheter ends.
Using a 3-D map of the heart shown on a video screen, doctors identify the areas of the heart that are suffering the most and target those specific areas for injection. "We make sure the tip of the catheter is perfectly situated against the heart wall, then we inject the needle into the heart muscle, delivering millions of stem cells to that one little spot," says Perin.
Injections are placed into the areas of the heart that are in greatest need of repair. Physicians estimate each U.S. patient will receive 2 million stem cells at 15 injection sites along the heart's left ventricle – a total of 30 million cells per patient. To prevent infection, the entire procedure – from harvesting bone marrow to injecting stem cells – is done in one day. "Take the cells out of the marrow, get them into the heart quickly – that's the goal. The longer the cells are exposed, the greater the risk of infection," explains Perin.
Elegantly Simple
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| | Keeping the beat—Yong J. Geng, MD, PhD., displays a microscopic view of stem cells pulsating in a culture dish. These cells develop a synchronated pulse much like a heartbeat within two weeks of harvesting. | |
The therapy stems from Texas Heart Institute research conducted by Willerson and Yong J. Geng, M.D., Ph.D., director of the Texas Heart Institute Heart Failure Laboratory, in which stem cells from dog embryos were used to treat adult dogs with heart attacks. After two weeks of treatment, scar tissue which forms where heart muscle dies after a heart attack was reduced in the adult dogs by 30 percent.
Willerson and Perin praise the therapy because it is inexpensive, simple to perform, and poses no risk of rejection, since patients are donating their own cells. "Patients usually go home the next day ... it's elegant in its simplicity," Perin says.
The Houston study began the week of April 12, and like its Brazilian counterpart, will last one year. The study is funded by St. Luke's Episcopal Hospital. If the Houston trial goes well, the next step is to conduct additional trials at centers throughout the United States and the world. "Then we can talk treatment. If these studies produce spectacular results, and we have every reason to believe they will, it'll be a whole new ball game for patients with heart disease," Perin says.
See also on other sites:
The initial report published in Circulation, the Journal of the American Heart Association (2003;107:2294.).
The American Heart Association's summary of this research.
Return to Stories from the Heart main page.
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