Despite the US Food and Drug Administration approval of a variety of carotid artery stent (CAS) systems, the initial projections on the proportion of patients receiving percutaneous interventions have fallen short (Figure 1). This may be for a variety of reasons, including the limited reimbursement dictated by CMS, which in turn is related to the high death/stroke rate in nontrial hospitals. The higher death/stroke rate in nontrial hospitals may be related to inexperience, learning curve, improper patient selection, and incomplete protection provided by the distal filters.

DISADVANTAGES OF DISTAL FILTERS
Currently in the United States, seven different CAS systems are approved for use. They all use the same principle of a distal basket that traps debris released during the stent deployment and angioplasty. The pores in the filter allow antegrade blood flow, which provides uninterrupted antegrade cerebral perfusion and the ability to visualize the target lesion at all points. The majority of the filters have 100-μm pores that allow small embolic particles to reach the brain. Additionally, the filter basket has to cross the lesion in an unprotected fashion before distal deployment. Additional disadvantages include the need for a distal landing zone (Figure 2), filter-related internal carotid artery damage, and others that are given in Table 1.

CONCEPT OF FLOW REVERSAL
Carotid endarterectomy (CEA) remains the gold standard and has been extensively evaluated in a variety of prospective randomized studies and other single- center reviews. Any percutaneous treatment option must meet the safety standards set by CEA. The most important concept of CEA involves achieving distal protection before the lesion is manipulated. The goal of distal control before lesion manipulation cannot be achieved by the use of distal filters. Flow reversal uses the concept of CEA (Figure 3) by avoiding guidewire manipulation of the target lesion before protection has been established. This technique involves balloon occlusion of the common and external carotid artery and siphoning the blood from the ipsilateral internal carotid artery via the femoral sheath. Lesion crossing is never attempted without establishing flow reversal in the internal carotid artery, thereby providing protection at all points. This provides a variety of advantages shown in Table 2. Disadvantages of the GORE Flow Reversal System (W. L. Gore & Associates, Flagstaff, AZ) include the need for a 9-F sheath and the learning curve associated with the concept of flow reversal. However, in the EMPiRE study evaluating the GORE Flow Reversal System, the complication rates did not change based on operator experience (Table 3). This suggests that this technique can be readily adapted with few complications, even among infrequent users.

EMORY EXPERIENCE WITH THE FORE FLOW REVERSAL SYSTEM
From March 30, 2007 to February 20, 2009, a total of 53 patients were treated with the GORE Flow Reversal System at Emory. Patient demographics are provided in Table 4. Overall, 20 out of 53 patients (38%) enrolled were symptomatic. Thirteen (24.5%) had a history of previous CEA. Indications for stenting are given in Table 5. All patients had a pre- and post-National Institutes of Health Stroke Scale evaluation by an uninvolved medical provider. Mean procedure time was 66 ± 28 minutes, mean flow reversal time was 11 ± 10 minutes, and mean fluoroscopy time was 14.1 ± 5.3 minutes. Intolerance to flow reversal was noted in four (7.6%) patients; however, the procedure was completed in all four subjects without any adverse clinical sequela. Flow intolerance manifested in the form of loss of consciousness in two patients and confusion in the other two patients.

The procedure was completed in two patients without the need for further manipulation or discontinuation of flow reversal. In the other two patients, the common carotid balloon was deflated, and systemic blood pressure was increased before reinstituting the flow reversal. This maneuver was successful in preventing the symptomatic cerebral steal. Six of the 53 patients enrolled had contralateral occlusion. Interestingly, none of the six patients had any flow intolerance, demonstrating that cerebral steal is a rare event and cannot be predicted based on the status of the contralateral internal carotid artery. Flow intolerance may be more closely related to the adequacy of collaterals in the Circle of Willis. Given the low incidence of flow intolerance and the lack of adverse events related to this, the authors do not believe that additional imaging of the intracranial circulation is warranted in an effort to predict flow intolerance. In our experience with 53 patients, our death/stroke/myocardial infarction rate was 0%. The mean length of stay was 2 ± 1.9 days.

LEARNING CURVE WITH FLOW REVERSAL
In the authors' experience with 53 procedures, an improvement was noted in the total procedure time (P = .003) and the flow reversal duration (P = .107). Total fluoroscopy time and contrast volume had no statistical difference (Table 6). No difference was noted in the death, stroke, transient ischemic attack, or myocardial infarction rates (all remained at 0 for the 53 patients). The improvements in the time for the procedure may have been primarily related to device preparation and having ancillary equipment ready and prepared. The significant drop in the flow reversal time may be related to the practice of loading the 0.014-inch crossing wire and stent in the sheath before inflation of the external and common carotid balloon. Additional steps, such as the use of a 9-F, 45-cm sheath in the femoral artery at the start of the procedure, minimized the need for additional manipulations in the iliac artery to overcome tortuosity, iliac calcification, etc. The low complication rate in the early part of the study indicates that this may be a safe technology, even for the infrequent user.

MICROEMBOLIZATION DURING CAROTID ANGIOPLASTY AND STENTING
Experience with transcranial Doppler monitoring during filter-protected carotid artery angioplasty and CAS demonstrates hundreds of microembolic signals to the brain. This has not resulted in a higher incidence of clinically evident strokes in the various carotid stent trials (Figure 4). Therefore, the clinical implication of microemboli to the brain has often been disregarded and is considered by most physicians as being unimportant. This is further complicated by the finding of new microinfarcts seen on diffusion-weighted magnetic resonance imaging (DW-MRI) after carotid angioplasty and stenting. These microinfarcts are also clinically asymptomatic in the perioperative period, resulting in the term silent infarcts. However, recent clinical data appear to contradict earlier findings.

There is a cumulative burden of data that appear to suggest that the microemboli (resulting in the silent infarcts) may lead to long-term cognitive dysfunction termed as vascular dementia. In a Japanese study of patients with Alzheimer's disease, one-third of the patients had silent brain infarcts revealed by MRI. This finding is similar to autopsy findings in clinicopathological studies among patients with dementia. This is in stark contrast to population-based studies with a reported low incidence (2%–3%) of silent infarcts seen in MRI imaging among patients with no dementia. Furthermore, the results of the Rotterdam Scan Study showed that the presence of silent brain infarcts more than doubles the risk of dementia, including Alzheimer's disease. The Cardiovascular Health Study also confirmed that silent brain infarcts were a risk factor for mild cognitive impairment.

Based on current data, we can assume that microembolic signals during CAS result in silent infarcts, as seen in DW-MRI images, and this in turn may result in long-term cognitive dysfunction. Based on this hypothesis, we evaluated the incidence of microembolic signals to the brain during filter-protected CAS and compared this to flow-reversal-protected CAS. There was a significantly lower incidence of embolic debris reaching the brain using the GORE Flow Reversal System (Table 7). The major decrease in microembolic signals to the brain happened during the protection phase.

The authors believe that cerebral infarcts, silent or not, cannot be disregarded. It would be safe to assume that most patients would prefer not to have any infarcts seen in their cerebral hemispheres. If in fact these silent infarcts are proven to result in longterm cognitive dysfunction after carotid angioplasty and stenting, the current distal filter technology may become unacceptable and unethical. This urgently calls for prospective studies evaluating cerebral microemboli and their long-term implications, as well as studies comparing the different techniques of percutaneous carotid revascularization to open surgery and best medical therapy.

Karthikeshwar Kasirajan, MD, is Assistant Professor of Surgery, Department of Surgery, Emory University School of Medicine in Atlanta, Georgia. He has disclosed that he receives research funding from W. L. Gore & Associates and Medtronic, Inc. Dr. Kasirajan may be reached at (404) 727-8407; kkasira@emory.edu.
Luke Brewster, MD, is with Emory University School of Medicine in Atlanta, Georgia. He has disclosed that he holds no financial interest in any product or manufacturer mentioned herein. Dr. Brewster may be reached at (404) 727-8407; luke.brewster@emoryhealthcare.org.

SUGGESTED READING:
Maleux G, Demaerel P, Verbeken E, et al. Cerebral ischemia after filter-protected carotid artery stenting is common and cannot be predicted by the presence of substantial amount of debris captured by the filter device. Am J Neuroradiol. 2006;27:1830-1833.
Faraglia V, Palombo G, Stella N, et al. Cerebral embolization during transcervical carotid stenting with flow reversal: a diffusion-weighted magnetic resonance study. Ann Vasc Surg. 2009;23:429-435.
Russell D. Cerebral microemboli and cognitive impairment. J Neurol Sci. 2002;203:211-214.
Bendszus M, Stoll G. Silent cerebral ischemia: hidden fingerprints of invasive medical procedures. Lancet Neurol. 2006;5:364-372.
Lacroix V, Hammer F, Astarci P, et al. Ischemic cerebral lesions after carotid surgery and carotid stenting. Eur J Vasc Endovasc Surg. 2007;33:430-435.
Rapp JH, Wakil L, Sawhney R, et al. Subclinical embolization after carotid artery stenting: new lesions on diffusion-weighted magnetic resonance imaging occur postprocedure. J Vasc Surg. 2007;45:867-872.
van Heesewijk HP, Vos JA, Louwerse ES, et al. New brain lesions at MR imaging after carotid angioplasty and stent placement. Radiology. 2002;224:361-365.
Gonzalez A, Pinero P, Martinez E, et al. Silent cerebral ischemic lesions after carotid artery stenting with distal cerebral protection. Neurol Res. 2005;27(suppl 1):S79-S83.
Lal BK. Cognitive function after carotid artery revascularization. Vasc Endovasc Surg. 2007;41:5-13.
Vermeer SE, Prins ND, den Heijer T, et al. Silent brain infarcts and the risk of dementia and cognitive decline: the Rotterdam Scan study. N Engl J Med 2003;348:1215-1222.
Lopez OL, Jagust WJ, Becker JT, et al. Risk factors for mild cognitive impairment in the Cardiovascular Health Study Cognition Study, part 2. Arch Neurol. 2003;60:1394-1399.
Snowdon DA, Greiner LH, Mortimer JA, et al. Brain infarction and the clinical expression of Alzheimer disease: the Nun study. JAMA. 1997;277:813-817.
Matsui T, Nemoto M, Maruyama M, et al. Plasma homocysteine and risk of coexisting silent brain infarction in Alzheimer's disease. Neurodegenerative Dis. 2005;2:299-304.
Bennett DA, Schneider JA, Bienias JL, et al. Mild cognitive impairment is related to Alzheimer's disease pathology and cerebral infarctions. Neurology. 2005;64:834-841.