Operation Decoy
Heart bypass grafts are proven lifesavers, rerouting blood and restoring healthy flow after coronary arteries become blocked by plaque and inflammation. When successful, the operation prevents chest pain, heart attacks and deaths.
Yet almost half of these grafts fail within five years. “We’re seeing an epidemic of patients who have had surgeries two, three, even four times -- and each time the risks during surgery go up dramatically,” says Dr. P.K. Shah, director of cardiology at Cedars-Sinai Medical Center in Los Angeles.
He and other experts are hoping that an experimental drug called E2F Decoy will halt graft deterioration, reducing the need for repeated surgeries.
“This drug is an innovative approach to solving this problem,” Shah said, “and early tests have been promising.”
The principal reason the grafts fail is that they’re made of veins. Unlike the thicker, more muscular arteries, veins aren’t designed to be next to the pumping heart. The increased volume of blood moving through the veins as well as the heart’s contractions stress the veins. They react to this stress by forming lesions within their interior.
“The veins aren’t used to all this pressure,” says Dr. Victor J. Dzau, a cardiologist at Harvard Medical School in Boston who developed the drug. “They get this kind of pressure injury, which makes them prone to an accelerated form of arteriosclerosis.”
This thickening of the blood vessel wall, caused by a buildup of fatty plaque, is the reason bypasses are necessary in the first place. But the plaque buildup that takes years in a coronary artery can happen in months in a graft. Eventually, the grafts are so clogged that they close up.
The drug, being tested at medical centers across the country, seems to prevent certain cells in the grafted vein from replicating, which stops or slows arteriosclerosis.
The drug is composed of a synthesized snippet of DNA that fits neatly onto the surface of genes responsible for cell division. It works like a chemical monkey wrench, locking onto a key protein and preventing it from triggering the cell growth that causes the thickening of the vessel wall.
During the bypass graft, veins are harvested from the leg or arm and then are soaked in an E2F Decoy solution, which seems to seep into cells’ nuclei. The treated grafts are then inserted into the patient.
“When you block cell proliferation, the veins get more muscular -- what I call the Schwarzenegger effect -- and they behave more like arteries,” says Dzau.
Preliminary tests have been encouraging. In a 2000 study of 200 bypass patients, half were given normal grafts while the remaining patients received grafts treated with E2F Decoy. A year later, treated patients had 30% less graft blockage and a 31% reduction in graft wall thickness compared with the placebo group.
The drug is in the final phase of clinical trials and is being tested on 3,000 patients at 125 sites in the U.S. Results are expected at the end of 2004.
“We need an effective way to reduce risks of vein-graft closure because it is such a big problem,” says Shah, who will be testing the drug later this year on patients at Cedars-Sinai. “This looks like an exciting intervention -- but the trial will tell the tale.”
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Treating artery blockages
Patients can prevent plaque from building up on the arterial walls by eating a healthful diet, not smoking and taking cholesterol-lowering drugs. When the artery is dangerously narrowed, however, doctors may resort to surgery. Among their options:
Atherectomy: A laser catheter or rotating shaver is inserted into the body, usually threaded through a blood vessel in the groin, and moved to the area where the artery is blocked. The laser vaporizes the plaque; the blade shaves it off.
Angioplasty: A thin balloon is attached to a catheter and threaded through a blood vessel in the groin and into a coronary artery. The balloon is then inflated to squash the blockage and open up the artery.
A stent, which is a wire mesh tube, sometimes is used as an alternative to or in combination with angioplasty. The stent is collapsed, placed over an angioplasty balloon catheter and threaded through an artery to the area of blockage. When the balloon is inflated, the stent expands and locks into place, forming a rigid support to hold the artery open.
Bypass: Because it’s so invasive, this is considered a last resort. A vein is taken from the leg or sometimes the arm, and it is grafted over the diseased one.
