Advances in Imaging Renew Interest in Carotid Bypass Surgery


Long abandoned as ineffective at secondary stroke prevention, carotid artery bypass surgery for complete atherosclerotic occlusion is getting a second look.

Known as extracranial/intracranial (EC/IC) bypass, the procedure involves surgical anastomosis of the superficial temporal artery to the middle cerebral artery (STA-MCA). It is getting its second chance to prove its effectiveness in selected patients for complete carotid occlusion because technologic advances, such as refinement of PET, have made it possible to identify which patients are the best candidates for the procedure.

EC/IC bypass surgery has been shown in a series of small studies to normalize the oxygen extraction fraction (OEF), a marker of impaired cerebral blood flow in patients with carotid occlusion.

Whether that translates into a decreased stroke risk is the subject of the Carotid Occlusion Surgery Study (COSS), a $21-million, 7-year trial funded by the National Institutes of Health that is now underway in 28 U.S. centers.

Candidates for the trial must be patients with symptomatic carotid occlusion and increased OEF on PET. To date, 169 patients have enrolled, and 38 patients have been randomized to treatment.

Enrollment in the nonblinded, controlled clinical trial has been slow, in part because few neurologists knew the option of bypass surgery existed, said Colin Derdeyn, M.D., principal investigator for the Washington University site in St. Louis.

The First EC/IC Bypass Study

STA-MCA surgical anastomosis was developed in 1967 and routinely performed on patients with carotid occlusion throughout the 1970s and mid-1980s.

However, data from the EC/IC Bypass Study showed no benefit for the prevention of subsequent stroke among 808 patients with symptomatic carotid occlusion, despite restoring blood flow to the carotid artery in 96% of cases (N. Engl. J Med. 1985;313:1191-200).

The researchers were unable to assess whether the procedure was more appropriate for one or another group of patients based on their cerebral hemodynamics because at the time the technology necessary to understand and measure cerebral blood flow had not been developed, according to M. Gazi Yasargil, M.D., professor of neurosurgery at the University of Arkansas, Little Rock, the Swiss neurosurgeon who pioneered the surgical procedure. “The time is ripe to work out a perfect indication for bypass surgery,” he said.

Identifying Hemodynamics

PET has made it possible to measure OEF, a proven predictor of which patients have significantly decreased cerebral blood flow and are at increased stroke risk.

When there is unrestricted cerebral blood flow, the brain extracts about 40% of the oxygen delivered to it in the blood. Blood vessels dilate and constrict to maintain an equal OEF across the brain. When cerebral blood flow falls because of reduced perfusion pressure, the brain increases the fraction of oxygen extracted from the blood to 70% or 80% to support normal oxygen metabolism. This elevated OEF allows the brain to maintain normal function, but it puts patients at increased risk for stroke in the future.

Two prospective natural history studies, one conducted in the United States (JAMA 1998;280:1055-69) and the other in Japan (J. Nucl. Med. 1999;40:1992-8), have shown that having an increased OEF as measured by PET is an independent predictor of future stroke in medically treated patients with symptomatic carotid artery occlusion.

Depending on the precise clinical and PET criteria used, the 2-year ipsilateral stroke rates ranged from 26% to 57% in patients with an elevated OEF, compared with stroke rates of 5%-15% in patients with normal OEF, according to Dr. Derdeyn, coauthor of the U.S. study.

“The best information we have right now, as far as connecting an abnormality by physiologic imaging with a risk factor, is for increased oxygen extraction,” Dr. Derdeyn told INTERNAL MEDICINE NEWS. OEF is a powerful and independent predictor of stroke. “It identifies a high-risk subgroup, without question,” he said.

William J. Powers, M.D., principal investigator of COSS, agreed on the importance of identifying subsets of patients most likely to benefit from EC/IC. “It's absolutely clear that if [EC/IC bypass] is ever going to work, there has to be some more refined selection criteria to pick out the people, number one, who would be at particularly high risk if treated with medical therapy, and number two, in whom the subsequent risk of stroke seems to be related to a problem that the bypass would fix,” he told this newspaper.

COSS is based on the hypothesis that surgical anastomosis of the superficial temporal artery to the middle cerebral artery, when added to the best medical therapy, can reduce subsequent ipsilateral ischemic stroke by 40% at 2 years' follow-up in this highly select patient population, despite perioperative stroke and death.