Elective Stenting of the Extracranial Carotid Arteries
Background Surgical endarterectomy has been shown to be superior to medical management in the management of severe carotid stenosis in both symptomatic and asymptomatic patients. Endarterectomy, although effective, does have limitations, and percutaneous techniques may offer an alternative method of treatment.
Methods and Results The feasibility and safety of percutaneous carotid angioplasty and elective (primary) stenting was evaluated prospectively in a consecutive series of 107 patients. One hundred twenty-six carotid arteries with significant stenosis were treated. This series represented a high-risk subset that included patients with previous ipsilateral endarterectomy and severe medical comorbidity. Forty-five percent of the patients were referred by surgeons. Patients had independent neurological examinations before and after the procedure and follow-up cerebral angiography at 6 months. The mean (±SD) stenosis was reduced from 78±14% to 2±5%. There were 7 minor strokes, 2 major strokes, and 1 death during the initial hospitalization and first 30 days after the procedure. For the combined end point of all strokes and death, the incidence was 7.9%. For ipsilateral major stroke and death, the incidence was 1.6%. There were no strokes during the follow-up period. Mean angiographic stenosis at 6 months in 81 patients was 18±16% (range, −21% to 57%). Four (4.9%) of these 81 patients had asymptomatic restenosis. Five asymptomatic patients had repeat intervention: 2 had angioplasty for restenosis, 2 had angioplasty for stent deformation, and 1 had endarterectomy for restenosis.
Conclusions In a high-risk group of patients, percutaneous carotid angioplasty and stenting are feasible and can be performed with low restenosis and repeat intervention rates.
Atherosclerotic stenosis of the extracranial carotid artery causes a significant portion of the 500 000 strokes that occur each year in the United States. The North American Symptomatic Carotid Endarterectomy Trial (NASCET) demonstrated the superiority of endarterectomy over medical management for symptomatic carotid stenosis ≥70%.1 More recently, the Asymptomatic Carotid Atherosclerosis Study (ACAS) showed a statistically significant reduction in stroke incidence after carotid endarterectomy in asymptomatic carotid stenosis of ≥60%.2 These landmark studies provide convincing evidence of the benefit of relieving severe obstruction of the extracranial carotid artery.
Surgery, however, does have several limitations. In NASCET, the risk of stroke or death was 5.8%, but in high-risk patients with significant coronary artery disease, morbidity and mortality rates as high as 18% have been reported.1 3 4 Endarterectomy is generally confined to the cervical portion of the carotid artery. Cranial nerve palsies occur in 7.6% to 27% of patients.1 5 Restenosis (≥50% stenosis) after endarterectomy has been inadequately studied but appears to occur in 5% to 19% of patients.6 7
Percutaneous techniques have the potential for being safer, less traumatic, more cost-effective, and usable in patients at high surgical risk and are not limited to the cervical carotid artery. Percutaneous carotid balloon angioplasty was first performed in 1980, but several unresolved issues have prevented its development. These include embolization, acute vessel closure, maintenance of cerebral perfusion, preprocedural and postprocedural neurological assessment, and angiographic follow-up.8 9 10 11 12 13 14 15
The present study was undertaken to evaluate the outcome of elective stenting of the extracranial carotid arteries in a consecutive series of patients.
Between March 1994 and November 1995, 112 patients underwent carotid angioplasty at the University of Alabama at Birmingham Hospital. The initial 5 patients were treated with a variety of angioplasty techniques, including cerebral protection and perfusion balloons, but were not stented. We standardized our protocol with patient No. 6, and the last 107 consecutive patients (126 vessels) had angioplasty with elective stenting and form the basis for the study population. Initially, only patients with symptomatic stenosis of ≥70% of the carotid arteries were eligible. After the results of ACAS were released, the institutional review board granted permission to expand the protocol to symptomatic and asymptomatic patients with ≥60% stenosis. For patient screening and enrollment purposes, stenoses were measured by hand with calipers. These measurements were made on radiographic films recorded during previous four-vessel angiography. During the procedures, on-line quantitative angiography was performed and used for subsequent data analysis.
Patients were excluded if any of the following was applicable: an intracranial tumor or arteriovenous malformation was present; they were severely disabled as a result of stroke or dementia; they had intracranial stenosis that exceeded the severity of the extracranial stenosis; they had severe renal insufficiency and were not yet on dialysis; they had peripheral vascular disease of sufficient severity to prevent vascular access; or they were unable to give informed consent. During the period of this study, 107 of the 109 patients referred for this treatment were accepted. Of the 2 patients refused, 1 had severe renal insufficiency and 1 had severe aortic disease precluding percutaneous access. The study protocol was approved by the institutional review board of the University of Alabama at Birmingham Hospital.
Clinical and Imaging Protocol
A complete neurological history was taken and an examination was performed on all patients by an experienced neurologist. The study protocol required that an independent neurologist not involved in the interventional procedure evaluate patients using the NIH Stroke Scale before the procedure and at 24 hours, 6 weeks, and 6 months after the procedure.16 17 Furthermore, all hospital records were critically reviewed by the surgical members of the study team.
MRI or computed tomography of the head and complete diagnostic cerebral angiography, including intracranial views and assessment of the collateral circulation, were performed on all patients. If a patient had neurological deterioration after angioplasty and stenting, MRI or computed tomography of the head was repeated. Follow-up angiography was planned for all patients at 6 months.
Balloon Angioplasty and Stenting Protocol
Patients received aspirin 325 mg/d for at least 2 days before the procedure as well as on the morning of the procedure. Ticlopidine 250 mg PO BID was started the day of the procedure. Heparin 5000 U was given by intra-arterial boluses to maintain the activated clotting time during the procedure at 200 to 250 seconds. The activated clotting time was kept in a lower range than during coronary angioplasty because of concern about intracranial bleeding in elderly patients with cerebrovascular disease. Frequent neurological checks were performed by a neurologist during the procedure. Femoral venous access was gained in all patients, and a transvenous pacemaker was immediately available. Atropine 1 mg was given as required during balloon inflation. Blood pressure was carefully monitored and modulated with boluses of metaraminol or intravenous nitroglycerin as required.
Carotid stenting was performed by use of coaxial catheterization techniques adopted from coronary interventions. Percutaneous access was gained from the femoral artery. Appropriately sized guiding catheters were positioned in the carotid artery just proximal to the segment to be treated. Angular angiographic views were recorded to fully display the stenosis and the tip of the guiding catheter. Quantitative carotid angiography (QCA) was then undertaken to measure the diameter of the vessel and facilitate sizing of the balloons and stents to be deployed.
Stenoses were crossed with flexible coronary guidewires that were exchanged for extra-support coronary wires before balloon and stent placement. Lesions were dilated before stent placement. High-pressure (10 to 16 atm) balloon inflations were routinely performed within the stent after placement. In these 107 patients, 189 stents were used. Of the 189 stents, 130 (69%) were Palmaz medium biliary stents (Johnson & Johnson Interventional Systems Co), 38 (20%) were Flex-Stents (Cook Inc), and 21 (11%) were Wallstents (Schneider). Contrast injections through the guiding catheter aided in precise stent positioning. On completion of the procedure, ipsilateral intracranial angiography was performed to exclude major branch vessel embolic occlusions.
The vascular sheaths were removed later on the same day as the procedure, and poststent anticoagulation was not used. Patients were discharged on either the first or second day after the procedure and given aspirin 325 mg BID permanently and ticlopidine 250 mg BID for 3 weeks.
Data Collection and End Points
All clinical, angiographic, and stenting data were prospectively recorded on standard forms by a physician. QCA was performed on all vessels before stenting, after stenting, and at 6-month follow-up by use of an on-line system (Integris-Phillips Medical Systems). Diameter stenosis was determined with the use of the NASCET criteria, with the distal nontapering portions of the internal carotid artery serving as the reference segment.1 Minimum lumen diameter was measured after calibration of the system with use of the known diameter of the guiding catheter. Clinical and laboratory details were recorded continuously during the hospitalization. The primary clinical end points were: (1) any minor or major stroke, myocardial infarction, or death within the first 30 days; (2) ipsilateral minor or major stroke within the first 30 days; and (3) repeat intervention by angioplasty or endarterectomy at 6 months. The clinical end points were critically reviewed by surgical members of the study group. Angiographic end points were: (1) minimum lumen diameter and percent stenosis after stenting; (2) angiographic success rate, defined as achieving a <50% residual stenosis; and (3) minimum lumen diameter and percent stenosis on the follow-up angiogram at 6 months. Restenosis was defined as a stenosis ≥50%.
A minor stroke was defined as a new neurological deficit that either resolved completely within 7 days or increased the NIH Stroke Scale score by ≤3. A major stroke was defined as a new neurological deficit that persisted after 7 days and increased the NIH Stroke Scale score by ≥4. Myocardial infarction was defined as the development of new pathological Q waves or elevation of creatine kinase to more than twice normal with an elevated MB fraction.
All values are expressed as mean±SD. Cumulative frequency distributions were constructed for minimum lumen diameter and percent stenosis. The χ2 test was used for comparison of discrete variables, and a value of P≤.05 was considered statistically significant.
The demographic and clinical characteristics of the 107 treated patients are shown in Table 1⇓. Sixty-four percent of the patients were symptomatic, and 58% of the arteries were associated with symptoms; 9% of the patients had contralateral carotid occlusions, and 11% had a previous ipsilateral endarterectomy. Sixty-eight percent of the patients had significant coronary artery disease, and 45% (48 patients) were referred to us by vascular surgeons or neurosurgeons.
Our patients were predominantly grade 3 or 4 on the Mayo Clinic carotid endarterectomy risk-classification scheme (Table 2⇓).3 Combined revascularization procedures involving either both carotid arteries (n=8), carotid and coronary arteries (n=7), or the carotid and another artery (n=4) were performed in a total of 19 patients. The mean length of hospitalization after the procedure was 1.9±1.4 days (range, 1 to 10 days).
The 107 patients required 122 procedures for treatment of the 126 separate vessels. Balloon dilation and stent placement were ultimately successful in all patients and in all arteries, although 1 patient required two procedures; this patient had extremely tortuous arteries, and guide catheter placement was not successful in the initial procedure.
One hundred eighty-nine stents were implanted in the 126 vessels. There was one case of stent/vessel thrombosis (0.8%). The mean stenosis before the procedure was 78±14% (range, 53% to 100%), and it was 2±5% after stenting (range, −10% to 25%). The preprocedural minimum lumen diameter was 1.3 ±.8 mm. After stenting, it was 5.0±1.0 mm, for an acute gain of 3.7 mm. Sixteen arteries that had been referred for treatment on the basis of significant lesions documented on four-vessel angiography had slightly <60% stenoses when on-line QCA was performed during the procedure. Because all of these arteries had caused symptoms, these patients were treated and included in the study. The mean stenosis in this group was 54%. The mean poststent balloon inflation pressure was 12±3 atm. Figs 1⇓ and 2⇓ show the cumulative frequency distribution of the minimum lumen diameter and percentage of stenosis. Typical angiographic results are shown in Figs 3⇓ and 4.⇓
Procedural Results and Complications
The clinical events are shown in Table 3⇓. There was one in-hospital death. This patient had ostial left common carotid and internal carotid lesions. The origin of the left common carotid artery had a severe stenosis and was at a very acute angle with respect to the aortic arch and could not be entered, and direct retrograde puncture of the common carotid artery was performed under general anesthesia. The internal and common carotid arteries were successfully stented. This patient also had sheaths placed in the right and left femoral arteries and died of a right retroperitoneal hematoma.
There were six minor and one major procedural strokes and one minor postprocedural stroke. Clinical details of the patients suffering minor strokes are presented in Table 4⇓. The single major procedural stroke occurred in the patient who suffered the stent thrombosis. This patient, who had suffered a previous stroke and had undergone two failed carotid endarterectomies, had extremely tortuous vessels, and access to the common carotid artery was obtained with great difficulty. The internal carotid artery was 4 mm in diameter. The patient was noted to have a major neurological deficit within 2 hours after the procedure, and repeat angiography revealed stent thrombosis. Despite immediate reopening, a significant neurological deficit remained.
There was one major nonprocedural, nonipsilateral, in-hospital stroke in a patient with a prosthetic mitral valve and chronic atrial fibrillation, which had previously caused him to suffer a right hemispheric stroke. On day 2 after successful stenting of a symptomatic left internal carotid stenosis, he had an embolism to the right middle cerebral artery documented by immediate cerebral angiography. The embolism was presumed to be cardiogenic.
In the 74 symptomatic carotid artery procedures, there were 1 death, 2 major strokes, and 5 minor strokes, for a total of 8 complications (10.8%). In the 52 asymptomatic carotid artery procedures, there were 2 minor strokes (4%). The difference in the complication rates between the symptomatic and asymptomatic arteries was not statistically significant (P=.17).
The NIH Stroke Scale score can range from 0 to 42. An increase in the Stroke Scale score represents worsening of the neurological status. The mean preprocedural NIH Stroke Scale score in the present study was 1.0±2.8; at 24 hours after the procedure, it was 1.1±2.7; at 6 weeks after the procedure, it was 1.0±2.2; and at 6 months after the procedure, it was 0.8±1.2. Six patients had an increase in their NIH Stroke Scale score at 24 hours after the procedure compared with baseline. Two patients with minor strokes did not have a change in their NIH Stroke Scale score at 24 hours. Four patients with fixed, stable neurological deficits had a decrease in their deficits and Stroke Scale scores at 24 hours after the procedure compared with baseline.
Cranial nerve palsies did not occur. Most patients (71%) experienced significant bradycardia with balloon inflation in the carotid sinus. Such bradycardia may persist for a few minutes after balloon deflation. There were no cases of prolonged or permanent second- or third-degree AV block. Four patients, all with contralateral carotid occlusions, had transient loss of consciousness with balloon inflation.
Six-month clinical follow-up was available on all patients. Eighty-one patients (76%) had either follow-up angiography (71 patients) or ultrasound (10 patients). The mean angiographic stenosis by QCA at 6 months was 18±16%, with a range of −21% to 57%. Late aneurysm formation did not occur; all patients with a negative stenosis at follow-up had a negative stenosis at the conclusion of the procedure. The minimum lumen diameter at 6 months was 4.1±1.3 mm, for a late loss of 25% (0.9 mm). Four (4.9%) of 81 patients had restenosis; all were asymptomatic.
Some degree of deformation was noted in eight Palmaz stents. This was considered significant in only two of these cases, and all of these patients have been asymptomatic. Four patients (4.9%) had repeat angioplasty at the time of their angiographic follow-up, two for restenosis and two for stent deformation. None of these patients were symptomatic. One of the three patients classified as having restenosis (48% stenosis by quantitative arteriography) had successful elective endarterectomy performed by the referring surgeon.
There have been no strokes after discharge from the hospital. One patient with dilated cardiomyopathy has had anterior and posterior circulation transient ischemic attacks during follow-up. Repeat angiography has been performed in this patient twice since discharge and has demonstrated a widely patent stent site. One patient required a permanent pacemaker 3 days after carotid stenting. Two patients (3.2%) died at 5 months after the procedure of pneumonia and aortic stenosis.
In this study, we have shown that it is possible to treat extracranial carotid atherosclerotic disease with percutaneous balloon angioplasty and stenting. With elective carotid stenting, the incidence of major stroke or death by 30 days was 3 (2.4%) of 126 carotid revascularizations. This was a high-risk group of patients, of whom 77% would have been excluded from the NASCET or ACAS studies. Of the 10 patients having complications, all would have been excluded from NASCET or ACAS. We deliberately minimized our exclusion criteria so as to have a series that was a realistic representation of the general patient population with cerebrovascular disease. In NASCET, the incidence of major stroke, myocardial infarction, or death in the surgical group was 3.1%. The inclusion of minor strokes increased the complication rate to 6.7% in the NASCET study. In NASCET, a minor stroke was defined as a stroke with functional recovery within 90 days, whereas we required functional recovery within 7 days to qualify as a minor stroke. Additionally, there was a 7.6% incidence of cranial nerve palsies in NASCET. In ACAS, there was a 2.3% incidence of perioperative stroke or death. The exclusion criteria for ACAS were also designed to minimize comorbid conditions.2 18
Many of our patients were thought to be very poor surgical candidates because of secondary conditions such as severe coronary artery disease, pulmonary disease, advanced age, severe cerebrovascular disease, or other factors that elevated the risk of surgery. Forty-five percent of the patients were referred by surgeons. Our patients had an average score of 3.5 on the Mayo Clinic Carotid Endarterectomy Risk Scale. In the Mayo Clinic series, the incidence of major complications (permanent stroke, myocardial infarction, or death) was 3.1% for grade 3 patients and 8.1% for grade 4 patients.3
In addition, 16% of our patients had combined revascularization procedures involving the other carotid artery or the coronaries. Because bilateral carotid endarterectomy is not usually performed, no data are available for comparison. Data are available on combined coronary artery bypass grafting and carotid endarterectomy. Stroke rates of 4.5% to 7.1% and mortality rates of 5.4% to 5.7% have been reported.19 The procedural minor stroke rate per artery in the present study was 4.7%. These events were nondisabling, and the majority occurred in patients having complex combined procedures (Table 4⇑).
Using stenting, we were able to reduce balloon inflation times and minimize interruptions of cerebral blood flow to 15 to 30 seconds. This was well tolerated by patients, even those with contralateral carotid occlusions. In our early experience with balloon angioplasty alone, we had a patient who developed severe dissection and acute closure leading to stroke and death. Therefore, we believe that the major threat to the patient from carotid angioplasty is severe dissection and acute closure of the artery with resultant severe cerebral ischemia. Even if the artery is reopened expeditiously, significant damage may occur. In the present series, elective stenting limited the possibility of acute closure and was associated with only a single thrombotic event. Stenting also leads to excellent angiographic results with essentially zero or negative residual stenosis. Because of their size, the extracranial vessels are well suited to stenting and, with good deployment and use of high-pressure inflations, anticoagulation may not be necessary.
Of particular interest are the four patients whose neurological deficits and Stroke Scale scores were lower 24 hours after the procedure than at baseline. Reversal of long-standing neurological deficits with revascularization suggests that the brain may also be capable of entering a “hibernating” state, as has been demonstrated in the heart.20 Further studies are planned using magnetic resonance spectroscopy for metabolic information along with the perfusion information obtained from single photon emission computed tomography.
We carefully quantified neurological status using the NIH Stroke Scale before and after the procedure and did not find an increase in the mean or median scores. Indeed, the mean and median scores decreased from baseline; this trend most likely represents the usual recovery in patients with recent strokes. There were no late strokes after the patients had been discharged from the hospital.
Of the 61 patients reaching the 6-month angiographic follow-up, 3 have had asymptomatic restenosis, with 1 of these patients being treated with repeat balloon dilation. One patient who had endarterectomy and stent removal after the procedure could have been treated with repeat dilation. The low incidence of restenosis is probably due to the large size of the vessels and the optimal initial result from stenting.
Carotid stenting is very well tolerated by patients. Minimal sedation is required. Communication with the patient and neurological assessment during the procedure are thus facilitated. Because postprocedural anticoagulation is not used, the poststenting hospital course tends to be brief and uneventful, with discharge at 24 to 48 hours after the procedure.
All of these procedures were performed by a team consisting of interventional cardiologists, neurologists, and interventional neuroradiologists. A vascular surgeon and neurosurgeon were readily available if needed. We believe that the satisfactory clinical and angiographic outcomes in this series are due in large part to our multidisciplinary approach, which brought a vast amount of experience to bear on this clinical problem. It also emphasizes the benefits of cooperation between different medical specialties in advancing patient care.
It is important to note that this series of patients represents the earliest clinical experience with this technique for extracranial carotid revascularization. The catheter, balloon, and stent technologies used in this study were all adapted from either coronary, neurovascular, or peripheral vascular applications, and none were developed specifically for carotid applications. Accordingly, the devices and techniques used have the potential for significant improvement. Increasing experience with the technique and development of better devices will likely further improve the results. This study also provides a foundation for research into using angioplasty for revascularization in acute stroke.
This carefully conducted, prospective study has demonstrated that an experienced multidisciplinary group of operators can safely treat high-risk patients with extracranial carotid disease with percutaneous techniques. This is a small, single-center series and requires confirmation in a larger, multicenter study. Ultimately, a randomized trial comparing percutaneous stenting with carotid endarterectomy may be indicated.
The authors wish to acknowledge the valuable contributions of Camilo Gomez, MD, Department of Neurology; Van Wadlington, MD, Division of Neuroradiology; Dennis Doblar, MD, PhD, and Natalia Plyushcheva, MD, PhD, Department of Anesthesia; James Mountz, MD, PhD, Division of Nuclear Medicine; and Ronald Levine, MD, and Christopher Goods, MD, Division of Cardiovascular Disease, University of Alabama at Birmingham.
Reprint requests to Gary S. Roubin, MD, PhD, Interventional Cardiovascular Section, Boshell Diabetes Bldg, Seventh Ave S, University of Alabama at Birmingham, Birmingham, AL 35294-0012.
Dr Yadav is now with the Atlanta Cardiology Group, St Joseph's Stroke Institute, Atlanta, Ga.
- Received April 18, 1996.
- Revision received July 8, 1996.
- Accepted August 8, 1996.
- Copyright © 1997 by American Heart Association
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