Jefferson Scientists Studying Radiation
as an Alternative to Angioplasty and Surgery

One of the most frustrating aspects of caring for the heart patient is the tendency of coronary arteries to reclose afterballoon angioplasty has opened them. This process, known as restenosis, usually occurs within three to six months, when the artery walls again begin to narrow, filling with scar tissue in the original treatment area. Of the more than 500,000 heart patients who undergo angioplasty in the United States each year, more than a quarter of those patients require another angioplasty procedure or bypass surgery within the first year. Stents, which prop open coronary arteries, help, but they aren't a complete cure.

Now, researchers at Jefferson Medical College think they may have a new weapon to keep arteries clean: radiation. The method involves the temporary placement of tiny radioactive "seeds" inside the coronary artery, providing low-dose radiation therapy, termed brachytherapy, in conjunction with balloon angioplasty. Brachytherapy is already being used to treat other conditions such as prostate cancer. The low-dose radiation is delivered through the Beta-CathTM System, a device developed by Novoste Corporation (Norcross, Ga.).

Two factors drive restenosis. Treated arteries tend to shrink or collapse over time. In addition, balloons injure the artery as they stretch it, triggering a healing response that causes scar tissue to build up and obstruct blood flow.

Jefferson researchers have begun a large, multicenter trial to assess the effectiveness of radiation in reducing restenosis in coronary arteries. Patients with new blockages as well as patients with recurrent blockages after angioplasty are candidates for this trial. The trial is a randomized, double-blind study, comparing angioplasty with radiation to angioplasty alone. In patients with unsatisfactory results from balloon angioplasty, stents will also be used to optimize the acute result of the procedure. Thomas Jefferson University Hospital is the Core Angiography Laboratory, angiograms of all 1,100 patients enrolled in the trial. Some other institutions participating in the trial include Emory University, Atlanta, Massachusetts General Hospital, Boston, and Scripps Clinic, La Jolla. The study is expected to run until the end of 1998.

Low Doses Are Key

According to Michael Savage, MD, associate professor of medicine and principal investigator of the study, the angioplasty balloon that opens the clogged vessel also injures the vessel wall. In time, scar tissue proliferates inside the vessel, reforming a blockage. "The radiation delivered at the site destroys the proliferation of [scar tissue] cells at the treated site," says Dr. Savage. Radiation is minimal, he notes, and is based on short-range beta radiation that penetrates only a few millimeters from original blockage with much less whole-body radiation than one would receive from a chest X-ray."

"The doses are based on artery size," he explains, adding that the procedure is performed during angioplasty. "Because of the size of the catheters delivering radiation, the arteries must be fairly large." Placing the Beta-Cath System Catheters is simple, adding only five minutes to the procedure.  The Beta-Cath System Catheters are snaked through the femoral artery in the thigh and into the heart to balloon the blockage. Radioactive seeds are stored within a hand-held device, which is used to deliver the radiation through the catheter to the coronary artery.

"[Radiation] treatments may be more concentrated than normal, and less normal tissue is irradiated, which theoretically carries a smaller chance of toxic side effects," notes Richard Valicenti, MD, assistant professor of radiation oncology, and a co-investigator on the trial. "While there's the potential that it could cause the arteries to close off, over time, because of accumulating scar tissue," the radiation for any single treatment is negligible. "The idea is to have one procedure that permanently keeps arteries clear," he says.

The procedure requires close cooperation between the interventional cardiologist, radiation oncologist, and physicist, among others, explains David Fischman, MD, associate professor of medicine, and director of Jefferson's Core Angiography Laboratory responsible for analyzing the catheterization films for this national study.

Watching For Signs

To date, restenosis has been uncommon and there have been no long-term negative effects, according to preliminary studies at other institutions.

The researchers will watch for certain signs to indicate the effectiveness of the procedure. These trial "endpoints" include restenosis (the artery is more than 50 percent re- narrowed), or other complications, such as angina or failing a stress test, and the need for additional procedures, such as angioplasty or bypass. All patients will have an angiogram at eight months to measure the effectiveness of this new therapy.

In September 1997, Drs. Savage, Fischman and colleagues at Jefferson reported in The New England Journal of Medicine that treating vein grafts in post-bypass patients with stents instead of angioplasty lowers the risk of complications and improves the long-term outcomes.

"Our stent studies were a grand slam for patients with heart disease; this [project] is trying to get another one," says Dr. Savage. "It's too soon to say how successful we'll be. It's exciting, and certainly very promising in attempting to combat restenosis."

Dr. Savage suggests that brachytherapy could someday become standard treatment to prevent restenosis in angioplasty patients. "It's hard to predict," he comments. "There are a lot of unknowns, and potential obstacles. It's also expensive and we need to monitor for potential side effects. Still, if the radiation procedure is proven cost-effective, he believes it will eventually be available at community hospitals.

Novoste Corporation, a leader in developing this technology, sponsors the work.

Originally printed in Jefferson Cardiology, 3/98
A publication of Thomas Jefferson University Hospital