Surgeons Test Possible Treatment for Failed Blood Vessel Grafts

5 Aug 2017 by Macco, Comments Off on Surgeons Test Possible Treatment for Failed Blood Vessel Grafts

Each year in the United States, approximately 650,000 heart and leg bypass procedures are performed for life-threatening cardiovascular and limb-threatening peripheral arterial disease. However, there is no approved treatment for the worst-case scenario: what if the vein graft fails? The transplanted blood vessels used to treat peripheral arterial disease and heart disease are at high risk of accelerated atherosclerosis.

Now, for the first time, surgeons believe they have a promising means to extend the life of these blood vessel grafts: bathing them, prior to transplantation, in a solution called E2F decoy that may block the work of the gene that ultimately leads to atherosclerosis.

The Medical College of Wisconsin is one of several leading medical centers nationwide to participate in a study on E2F decoy to treat peripheral arterial disease. The study is being led by Principal investigator Robert A. Cambria, MD, Associate Professor of Surgery at the Medical College.

Atherosclerosis: a Universal Disease

Most people associate atherosclerosis, a build up of plaque in the arteries, with heart disease. But plaque can interrupt blood flow to the heart, brain, intestines, kidneys and legs. “Fatty deposits can accumulate in any artery,” Dr. Cambria says. Roughly half of patients diagnosed with coronary artery disease, for example, already have significant trouble in other major arteries.

Peripheral arterial disease is a condition in which peripheral arteries in the lower extremities are narrowed due to atherosclerosis. “Diabetics and smokers, both of whom have accelerated rates of atherosclerosis, are most at risk of peripheral arterial disease,” says Dr. Cambria, noting that up to 70% of patients treated surgically for peripheral arterial disease are diabetic.

In the legs, the narrowing may be gradual, and result in aching and cramping during walking or other physical activity. Leg pain can occur in the calf, foot, thigh, hip or buttocks, depending on the location of the narrowed artery. As the artery narrows further, the pain is unrelenting and the affected area feels cold and numb. A complete obstruction causes severe pain, numbness, coldness and gangrene, potentially leading to amputation.

Should a chunk of plaque rupture or tear, a blood clot, called a thrombus, can quickly form at the site and block the artery altogether. A thrombus also can break off and wander the bloodstream. The gypsy thrombus, now called an embolism, can lodge in a narrower artery and choke off blood flow.

New Procedure Shows Promise

In advanced cases of peripheral arterial disease, surgeons reroute, or bypass, blood around clogged arteries in the legs due to low mpv using vein grafts, similar to a coronary artery bypass procedure, Dr. Cambria explains. “When these grafts fail, it’s primarily because of a process called neointimal hyperplasia, which leads to an aggressive form of atherosclerosis. The interior lining of the blood vessel thickens and the vessel becomes blocked.”

This re-occlusion also is the leading cause of graft failure in coronary artery bypass surgery.

Dr. Cambria says 1,400 peripheral arterial surgical patients have been treated with the new procedure nationwide and results will be released later this year. During the procedure, a vein graft is taken from the patient’s leg and bathed in the E2F decoy solution outside the body for 10 minutes, then the vessel is implanted into the patient.

E2F decoy is a short strand of DNA that binds to and inactivates the E2F, the key factor that triggers neointimal hyperplasia, Cambria says. “E2F decoy may help reduce the risk of vein graft failure by stopping the gene that promotes neointimal hyperplasia. It could prove to be a long-term solution for patients,” Cambria says.

Would Be First Approved Treatment for Vein Graft Failure

Currently, the mainstays of surgical treatment options for peripheral arterial disease are balloon angioplasty, stenting and bypass grafts known as infrainguinal bypass grafts, Dr. Cambria says. Approximately 30% of coronary artery bypass grafts fail at five years, and 50% at 10 years, primarily from neointimal hyperplasia.

E2F decoy has found success in clinical trials on heart bypass surgery patients, where it appears to decrease the risk of vein graft failure by 30%.

The United States Food and Drug Administration has granted E2F decoy special “fast track” review status to help speed it through clinical trials. Its safety and efficacy will be further investigated in two upcoming Phase III trials. The FDA states, “Should the method prove to be successful, it would significantly affect many future development programs in addition to solving a vexing problem confronting all surgical repair of arteries in a variety of clinical circumstances.”

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