THURSDAY, Nov. 15, 2001 (HealthDayNews) -- A gene that promotes the growth of new blood vessels may reinvigorate diseased and damaged hearts.
New research shows that a gene from a naturally occurring hormone called vascular endothelial growth factor (VEGF), when injected directly into damaged heart muscle, improved the conditions of patients who were in the final stages of heart disease. At the end of two separate studies, a majority of the patients reported less angina or chest pain and increased physical function, the researchers say.Both reports, one that followed heart patients for one year and another that tracked them for two years, were presented recently at the American Heart Association's Scientific Sessions meeting in Anaheim, Calif.
Although the results are promising, cardiologists emphasize that a larger, randomized trial that includes a control group not receiving the growth factor needs to be the next step.
"It's more important for what didn't happen," says Dr. Richard Schatz, senior author of the one-year study and director of cardiovascular interventions at Scripps Clinic in San Diego. "In the long term, the patients took a fairly benign course. There was no cancer, and there were no side effects. That's the real thunder. At the end of the two-year follow-up, they're still alive."
That's no small feat, Schatz notes, when you consider what shape the patients were in when they enrolled in the studies.
"It's pretty amazing because we took the sickest patients of all," Schatz says. "I'm frankly flabbergasted."
Jacque Braswell, who received VEGF therapy in July 1999 when she was 69, is just grateful.
She had already had open heart surgery early in life and a major bypass operation when she was 60. When she had a major heart attack as she approached 70, doctors discovered there was nothing more they could do for her because her arteries were so damaged.
"I was kind of at the end of my road, but I didn't feel like I was ready to die," she says. In desperation, she went to Schatz for tests. Two weeks later, the only thing he could offer her was a spot in the VEGF clinical trial if she met the qualifications. She did, and two years later she says she lives an active life.
"I've had no angina since then at all," says the 72-year-old woman who lives in La Mirada, Calif. "I've been to Ireland. I have a great life. It's such a wonderful miracle. It's like God gave me a new life. I feel like 16; I really do."
The results of the two studies suggest that Braswell isn't alone.
In each study, a slightly different variation of the VEGF gene was injected straight into damaged heart muscle during open-heart surgery.
In the one-year study, 57 percent of the 30 patients had Class IV angina before therapy, and 43 percent had Class III. Class IV angina is the most severe angina. At the end of the follow-up period, none of the patients had Class IV angina, 17 percent had Class III angina, and 83 percent had Class I or II angina.
In the two-year study, conducted at St. Elizabeth's Hospital in Boston, 27 of 30 patients reported fewer angina episodes per week -- from 56 a week to about four a week. And they also reported taking fewer nitroglycerin tablets for the condition per week -- from 60 a week to about three a week.
The New York Heart Association defines the categories this way: Class I: angina after heavy exercise; Class II: angina after walking; Class III: angina while talking/breathing; Class IV: angina at rest or upon waking.
The thinking behind VEGF therapy is that the gene triggers the growth of new blood vessels to feed oxygen-starved heart muscle. In previous studies, the gene has been delivered to the heart via a deactivated virus, which sometimes caused an inflammatory response in the patient. But these two studies avoided that problem by injecting a single stand of DNA into the blood-starved part of the heart muscle, Schatz says.
Another concern with VEGF therapy has been that it may inadvertently spur the growth of cancerous tumors. But in both studies, each of which followed 30 patients, the only case of cancer that cropped up was unrelated to the therapy.
The next step, Schatz says, is a larger, randomized study that has a placebo control group. That's now possible because another researcher has developed a way to deliver the gene directly to the heart with the use of a catheter, so that either VEGF or a saline solution can be used without the patient's knowledge. The researchers are trying to set up a 10-center study of almost 200 heart patients across the country, Schatz says.
"Three-quarters of the people get a pretty impressive improvement in their conditions. The data looked too good, and it was not randomized. I understand that," Schatz says. "The big study should really follow suit, with short-term and long-term results."
One cardiologist doesn't put much stock in the early findings.
"I consider these results meaningless. It does not appear to do overwhelming harm. But until proven otherwise, it's a pure placebo effect," says Dr. Jonathan Marmur, an assistant professor of medicine in the cardiology division at Mount Sinai School of Medicine in New York City. "This should be seen strictly as preliminary data to serve as a basis to do a serious trial."
One curious thing about the results was that patients responded immediately or had no improvement whatsoever, Schatz notes.
"It's an almost all-or-nothing phenomenon. You can't prove new blood vessels are there, but there's increased blood flow [to the heart]," he says. "We don't know why some [patients] do good, and some don't."
And at this point, VEGF therapy only works in the area where it's injected, Schatz notes.
"It's not a cure for the entire heart yet. The area has to be damaged live tissue first," he says, adding that that fact doesn't dampen his enthusiasm for the therapy. "There's enough evidence in the preliminary phases that whatever it is, it's going to be pretty darn good. There's something there."
What To Do
Check out this primer on VEGF.
And here's more news on VEGF therapy.
The AHA has this article on a large study last year that looked at the safety and effectiveness of VEGF therapy.