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Cardiovascular Report - How to fight bypass failure

Cardiovascular Report Winter 2011

How to fight bypass failure

Date: February 28, 2011

Matt Gordon
Physician assistant Matt Gordon inspects a saphenous vein for use in CABG.
photo by Keith Weller

Pity the poor venous graft. Though they may provide the most plentiful source of replacement vessels for surgeons facing an extensively diseased heart, veins harvested from a patient’s legs are never a surgeon’s first choice.

But after a lengthy four-center study into vein graft failures, Johns Hopkins scientists are preparing to wage a better argument with veins’ intelligent designer. “God did not make veins to be turned into arteries,” says cardiologist Jeffrey Rade. “When you try to do that, they can act in unpredictable ways.”

The trick now, says Rade, is to devise new methods to reduce the unpredictabilities of venous grafts. But first, scientists had to untangle the mysteries behind why they clot off too easily.

The background is that cardiac surgeons have been forced to make peace with vein grafts. According to study co-investigator John Conte, surgeons usually count on one or two single available arteries—the left and right internal mammary arteries—conveniently located within every rib cage right next to the heart. But for additional bypass, surgeons typically resort to the leg veins.

The trouble with veins, as surgeons know, stems from venous tissues’ native purpose of moving the body’s low-pressure blood flow back to the heart. When asked to do the job of an artery, veins can suffer from the unaccustomed stress on their vessel walls, prompting lesions around which sticky blood platelets might gather and bloom.

In response, cardiologists have learned to equip post-bypass patients with agents aimed at reducing the likelihood of venous graft clotting, typically using low-cost anticoagulants such as aspirin or Coumadin, or more specialized medicines like clopidogrel.

Yet the advances too often come up short. It’s well known in cardiac circles, says Rade, that more than half of venous grafts will be completely blocked off within 10 years after the surgery. It also turns out, according to the new Hopkins-led study results, that one in five vein grafts blocks off within six months of surgery, usually because of blood clots.

To find out why, Rade and his research colleagues first drilled down into the world of platelets, hoping to learn which of the many anticoagulation agents did the best job. Their chief suspect was aspirin, which many physicians have come to believe meets with resistance in an unknown number of patients.

Each of the 297 study patients was equipped with a daily aspirin. In the course of what Rade calls “a broad array of assays” to assess relationships between anticoagulation therapies and graft patency, Rade’s group found that a teensy 1 percent of patients showed evidence of so-called aspirin resistance.

But what did show up in a surprising number of patients with occluded vein grafts was an unusually high level of the metabolite thromboxane, a clotting-related factor. “So aspirin is doing what aspirin should do in over 99 percent of people,” says Rade, but the thromboxane rise posed a new mystery. “Our conclusion is that thromboxane may not be coming from platelets,” says Rade, “but somehow thromboxane is predicting risk.”

When combined with some of the study’s other assays—most prominently one that could gauge the physiological effects of “shear stress” on platelet activation—Rade says anticoagulation regimens could be much more refined for future bypass patients.

“This is a very impressive but subtle finding,” he says. “It’s more complicated than we first thought. This is the first study to say that there are specific coagulation-related factors that impact graft failure. The practical application is this: Is there a way we can measure people preoperatively and stratify them into high- and low-risk groups?”

If yes, then high-risk patients can be recommended for less-invasive solutions like angioplasty and/or medicine. If bypass is still deemed necessary, surgeons can remain more conservative with grafting in favor of arteries only. 

And then, what Rade calls the “opening of a whole new field of study” can spur the search for identifying other platelet inhibitors that can do what aspirin cannot. “There’s been a problem here,” says Rade, “and now we’re figuring out what that problem is.

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