Division of Vascular Surgery

Clinical Research and Trials

Neurocognition After Carotid Revascularization Trial

Brajesh K. Lal, MD

Twenty to 30% of strokes occur due to atheroembolization from carotid plaque. Carotid endarterectomy (CEA) reduces the incidence of stroke in patients with high-grade carotid stenosis (CS). The role of carotid artery stenting (CAS) is currently the subject of a NIH-sponsored multicenter trial. Data on stroke, myocardial infarction and death from the NIH trial will influence future practice significantly. However, as advances in treatment reduce the incidence of these end points, it will become increasingly important to obtain information on residual cognitive morbidity. Neurocognitive morbidity has considerable impact on the well being of patients. This issue is overlooked in medical assessments aimed at identifying gross neurological deficits. None of the randomized trials comparing CAS with CEA include cognitive function as an endpoint. Moreover, existing information on cognitive function after CAS or CEA is limited and inconsistent. A decline in cognitive function could occur from microembolic ischemia during carotid clamping or intravascular instrumentation. Intra-plaque hemorrhage and lipid core disruption may predispose to atheroembolization and downstream ischemia. Pre-procedural identification of these features by non-invasive imaging may allow identification of patients at high risk for cognitive complications during carotid revascularization. To address this important medical problem we hypothesize that CAS is advantageous over CEA in terms of cognitive preservation and that post-procedural cognitive function relates to plaque composition. The primary aims of this proposal are to 1) establish the incidence of cognitive dysfunction after CEA and CAS each, with respect to controls and to 2) contrast the incidence of cognitive dysfunction after CEA vs. CAS. Secondary aims of the proposal are to 1) estimate the incidence of microembolization in the two procedures and correlate these with cognitive dysfunction, and 2) determine whether plaque composition is related to the incidence of microembolization and cognitive dysfunction.

Carotid Revascularization-Endarterectomy versus Stent Trial (CREST)

Robert W Hobson II MD

While rapidly expanding in its use, carotid artery stenting (CAS) remains a relatively new procedure. Its growth is due, at least in part, to the perceived advantages of a less invasive technique. However, the clinical effectiveness of CAS has not been established, and relatively little data has been reported on morbidity and mortality associated with specific devices and techniques. The aim of this NIH funded clinical trial, Carotid Revascularization Endarterectomy vs. Stent Trial (CREST), is to contrast the relative efficacy of CAS versus carotid endarterectomy (CEA) in preventing stroke, myocardial infarction or death during a 30-day peri-procedural period, or ipsilateral stroke over the follow-up period (extending up to 4 years) in patients with symptomatic extracranial carotid stenosis. Funding for this national multi-center trial will continue for 5 years.

Guidant Acculink ® stent and Accunet® anti-embolism device being used in the CREST trial.

Useful links:

• More information on carotid stenosis: http://www.vascularweb.org/VascularWeb_Contribution_Pages/Patient_Information/Carotid_Artery_Disease.html
• What does a vascular surgeon do for carotid stenosis?: http://www.vascularweb.org/VascularWeb_Contribution_Pages/Patient_Information/Carotid_Artery_Disease.html#q6
• CREST carotid stenting trial: http://www.umdnj.edu/crestweb/
• Stroke warning signs: http://www.americanheart.org/presenter.jhtml?identifier=4742
• Stroke: http://www.americanheart.org/presenter.jhtml?identifier=4755
• Society for Vascular Surgery: www.vascularweb.org
• American Stroke Association: www.strokeassociation.org
• National Stroke Association: www.stroke.org
• The Internet Stroke Center: http://www.strokecenter.org/

Endograft Repair of Aortic Aneurysms Open versus Endovascular Repair of Abdominal Aortic Aneurysm (OVER)

Frank Padberg Jr MD, Brajesh K Lal MD, Robert W Zickler, MD

Patients with AAA >5.0cm are eligible for randomization between these two management strategies. Open repair has a known durable outcome, but requires an abdominal incision with a longer hospital and ICU stay. Endovascular repair is a new therapy which offers reduced immediate post-op effects, but whose durability is, as yet, incompletely defined; since secondary rupture has been reported after endovascular repair, this is not an inconsequential issue. The study is funded by VA Cooperative Studies Program and will continue for 5-8 years from its inception in 2002.

Physical Therapy in Chronic Venous Insufficiency

Frank Padberg Jr MD, Mark V Johnston PhD, Sue Ann Sisto PhD

This project is designed to evaluate the efficacy of a structured program of physical therapy for ameliorating the adverse consequences of severe chronic venous insufficiency (CVI). The relationship between measures of CVI to measures of lower limb muscle strength and mobility will be investigated. It is hypothesized that physical conditioning structured to enhance calf muscle strength and ankle mobility should improve venous hemodynamics by improving calf muscle pump function. The design is prospective, with subjects randomized between therapy and a wait listed control group. Eligible patients must be able to complete the testing protocol and have confirmed evidence of venous insufficiency. Funded by VA Merit Review.

Ex-Vivo Treatment with an E2F decoy (CGT003) of Peripheral Vein Grafts in Patients Undergoing Peripheral Arterial Bypass Graft Procedures

Peter J Pappas MD, Brajesh K Lal MD

Cell-cycle blockade by ex-vivo gene therapy of experimental vein grafts inhibits the neointimal hyperplasia and subsequent accelerated atherosclerosis that lead to human bypass-graft failure. This prospective, randomised, multi-center, controlled trial is investigating the safety and biological efficacy of intraoperative gene therapy in patients receiving bypass vein grafts. Gene therapy involves the use of decoy oligodeoxynucleotide, which binds and inactivates the pivotal cell-cycle transcription factor E2F.