Carotid Artery Stenting: Experience of a Single Institute in China

Summary

Concern regarding the safety of Carotid angioplasty and stenting (CAS) exists because of the risk of cerebral embolization during the procedure. The purpose of this article is to discuss that technology modification may improve the outcomes of this procedure.

Between October 1997 and October 2004, 439 consecutive patients with 478 stenotic carotid arteries were treated. 284 vessels were stented without the use of embolic protection devices and 194 vessels with protection. Among cases not using protection device, 201 arteries were stented with predilation alone, 63 with postdilation alone, six with both preand post-dilation, two with neither and twelve were stented with balloon expandable stents.

The technical success of 100%.The combined stroke and death rate during the procedure and the 30-day follow-up at 30 days was 1.67% overall. Three (0.63%) deaths occurred; one was due to a major infarction secondary to stent breakage, and two died of massive reperfusion intracerebral haemorrhage. There were total six ischemic stroke, of the five ischemic strokes wich developed in nonprotection group, two were among 201 cases with predilation alone (0.99%), which developed after stent deployment and postprocedure, and three among 63 cases with postdilation alone (4.76%), which developed immediately after postdilation.

The incidence of ischemic stroke was lower among those who were stented with predilation alone than among those who were stented with postdilation alone. This likely results from reduced intimal injury and decreased risk of embolic complications

Introduction

Cerebrovascular disease is the leading cause of death and disability both in the world and in China. Carotid occlusive disease is responsible for 25% of these strokes¹. Carotid angioplasty and stenting (CAS) is being increasingly used as an alternative of endarterectomy for the treatment of carotid stenosis. The goal of both therapies is to prevent stroke. The efficacy of CAS in preventing stroke depends on the ability to achieve complication-free results and good risk-benefit ratio. The purpose of this article is to discuss some factors related to endovascular technology and patient selection that might allow us to improve the outcomes of this procedure.

Methods

From October 1997 to October 2004, 439 consecutive patients (478 carotid arteries) underwent CAS in our hospital. Patients were included if they had symptomatic or asymptomatic stenosis of a extracranial carotid artery of more than 60% or 80% respectively, measured by North American Symptomatic Carotid Endarterectomy Trial (NASCET) method². Exclusion criteria were a previous cerebral infarction within six weeks, the presence of angiographically visible intraluminal thrombus and a stenosis that cannot be safely reached or crossed. Patient evaluation, intervention and follow-up were carried out by a team of neurologists, neurosurgeons and radiologists in accordance with a standardized protocol. Written informed consent for procedure was obtained from all patients.

Patient Evaluation

Before treatment, all patients received a thorough neurological examination by a neurologist. All patients underwent carotid Doppler, transcranial Doppler and cerebral CT scan or MRI. SPECT was carried out in 164 (37.4%) patients and Perfusion-weighted MRI in 151 (34.4%) patients to reveal cerebral hypoperfusion or metabolic abnormity ipsilateral of the stenotic artery. In all cases the diagnostic cervicocerebral angiography included visalization of brachiocephalic arteries from aortic arch, bilateral carotid arteries, bilateral vertebral arteries, and intracranial study of both carotid and the dominant vertebral artery. Status of intracranial collateral circulation and cerebral perfusion was noted, as well as any other extracranial and intracranial stenosis besides the target lesion. In some cases, 3D rotational angiography was performed to gain optimal demonstration of the lesion, in order to safely cross the stenosis under optimal projection during the CAS procedure. Patient and lesion characteristics are shown in table 1.

Table 1.

Characteristics of patients and carotid lesions.

Patients	n
Population	439 (100%)
Age
Mean±SD, in years	68 ±5
Range	36~85
Male	269 (61.3%)
Symptomatic
TIA	336 (76.5%)
Stroke	74 (16.9%)
Asymptomatic	29 (6.6%)
Lesion
Vessel	478 (100%)
Pathomechanism of lesion
Primary atherosclerosis	476 (99.2%)
Cervical radiotherapy	4 (0.8%)
Angiographic evaluation
Degree of stenosis (mean ±SD), %	85.6±7.4
Stenosis ≥90%	167 (34.9%)
Ulcerated plaque	176 (37.2%)
Bilateral carotid disease	132 (30.1%)
Bilateral stenosis >80%	71 (16.2%)
Contralateral carotid occlusion	38 (8.7%)
Hypoperfusion by SPECT	96 (58.5%)

Treatment Description

Treatment with aspirin 300 mg/d plus clopidogrel 75 mg/d or ticlopidine 250mg/d was started 3-5 days before the procedure and continued for at least eight weeks postprocedure. Most procedures were performed under local anesthesia along with neuroleptic analgesia, if the patient had contralateral carotid occlusion, general anesthesia was given in case that these patients may not tolerate internal carotid occlusion during balloon dilation. Haparin was administered intravenously with a bolus of 85 U/kg, further boluses were given as needed to maintain the activated clotting time between 200-250 seconds.

The procedure was started with a selective angiography of the target carotid, finally determining the extent of the stenosis according to NASCET method. Then through the 5F diagnostic catheter already in the CCA, a 0.035inch 260 cm exchange wire was placed into the external carotid artery. After withdrawing the 5F catheter, a 90 cm guiding catheter was advanced into the CCA proximally to the lesion.

284 vessels were stented without the use of embolic protection devices in the early years of our experience, whereas 194 vessels with protection. The protection devices used were: Johnson & Johnson-Cordis Angioguard Filter (47%), Boston Scientific FilterWire EX (42%), EV3 Microvena Trap Filter (11%).

In the cases without protection, a steerable exchange-length 0.018-inch guidewire was passed across the lesion; if a protection device used, the stenosis was crossed with the filter device which was positioned 5 cm distally to the lesion. Then, the stent was implanted either directly or after predilation. We used balloon-expandable stents (Johnson & Johnson-Cordis Palmaz) in the early years (12,2.5%), afterwards we used only self-expandable stents, consisting of Boston Scientific Wallstent (268,56.1%), Cordis Smart (76,15.9%), Johnson & JohnsonCordis Precise (72,15.1%) and EV3 Protégé GPS (50,10.5%).

Predilation was performed with a 4-, 5-, or 6mm low profile balloon, depending on the distal nondiseased vessel diameter. Postdilation was performed only if the residual stenosis after stent deployment was >30%, mostly in cases without predilation, using a appropriate balloon on the basis of vessel size. Atropine of 0.5 to 1 mg was given to conteract bradycardia associated with balloon dilation. After stenting angiography was repeated to evaluate recanalization and exclude embolization into intracranial circulation.

The neurologic examination of the patient was obtained after each step of the procedure, and continuous physiological monitoring including heart rhythm, blood pressure and pulse oximetry was performed throughout the procedure.

Follow-up and Definitions

After the procedure, patients were closely observed for neurological status and vital signs in ICU for 24 hours. If a patient exhibited a neurological deterioration, brain CT and carotid Doppler or angiography were conducted immediately. A neurologic examination was performed routinely 24 hours and 30 days after stenting. Carotid Doppler was repeated one and twelve months postprocedure and annually thereafter.

Technical success was defined as the ability to access the carotid artery and successfully stent the lesion with residual stenosis of no more than 30%. Stroke was defined as an ischemic neurologic deficit that persisted for more than 24 hours. Since we did not use the National Institutes of Health Stroke Scale for neurologic assessment, stroke was not classified as minor or major, but described as reversible (having a duration of >24 hours and <= 30 days) or permanent (having a duration of >30 days).

Statistical Analysis

Proportions were compared by using x 2 tests. Two-sided p values are reported. P < 0.05 was considered significant.

Results

A total of 478 carotid arteries in 438 patients were treated with a technical success of 100%. Among the 284 vessels treated not using protection device, 201 (70.8%) arteries were stented with predilation alone, 63 (22.2%) with postdilation alone, six (2.1%) with both pre and post-dilation, two without any dilation and 12 were stented with balloon expandable stents. In cases with protection, most patients were stented with predilation alone.

The complications observed during the procedure and the 30-day follow-up were detailed in tables 2 and 3. The combined stroke and death rate at 30 days was 1.67% overall, 2.1% in nonprotction group and 1.0% in protection group. Three (0.63%) deaths occurred; one was due to a major infarction secondary to stent breakage, and two died of a massive reperfusion intracerebral haemorrhage arising 3-5 hours after intervention. There were six ischemic strokes, all ipsilateral to the treated artery, and neurologic deficits occurred during the procedure or within one hour after completion of the endovascular procedure. Timing of any appearance of neurologic symptoms was documented (table 3). Five ischemic strokes developed in nonprotection group in procedures carried out with either predilation or postdilation alone, two among 201 cases with predilation (0.99%), which developed after stent deployment and postprocedure; while three among 63 cases with postdilation (4.76%), which developed immediately after postdilation (p = 0.166) (figure 1).

Table 2.

Complications within 30 days.

	N	%
Death	3	0.63
Stroke	6	1.26
Intracranial haemorrhage	2	0.42
Stent breakage	1	0.21
Stent thrombolysis	1	0.21
Bradycardia	110	25.1

Table 3.

Ischemic stroke within 30 days.

	Protection device	Pre dilation	Post dilation	Timing	Category
1	-	+	-	After stent deployment	Reversible
2	-	+	-	Postprocedure	Permanent
3	-	-	+	After postdilation	Reversible
4	-	-	+	After postdilation	Permanent
5	-	-	+	After postdilation	Fatal
6	+	+	+	Postprocedure	Permanent

Figure 1.

A patient with ischemic stroke after stenting. A) Left internal carotid artery with 95% stenosis. B) A Wallstent was placed directly in the left internal carotid artery. C) An arteriogram after postdilation of the stent. D) MRI showed cerebral infarctions in the left hemisphere.

The case of stent breakage happened in a patient with preocclusive carotid stenosis who was stented without predilation, subsequent postdilation broke the stent with visible fracture (figure 2), and stent occlusion was observed in the following arteriography. Local intraarterial thrombolysis with Urokinase of 500,000IU reopened the carotid artery, and we implanted an additional stent to cover the first one. However, the patient suffered a major stroke and died one week later.

Figure 2.

A patient complicated by stent breakage. A) Right internal carotid artery with 85% eccentric stenosis. B) The stent broke (arrows) after postdilation of the stent placed directly without predilation. C) Right carotid injection shows stent occlusion. D) Intraarterial thrombolysis reopened the carotid artery and an additional stent was implanted.

There was one asymptomatic acute stent thrombosis which was dissolved by immediate thrombolysis without clinical sequelae.

Bradycardia (heart rate below 50/min) was noted in 25.2% patients. Most of them recovered sevral minutes after Atropin injection. Three patients had prolonged bradycardia for more than 24 hours, one of them lasting for threedays. But they all resolved finally by pharmalogical correction.

341 patients (78%) were followed up for three months to five years. The mean follow up period was 18 months. We use carotid Doppler to evaluate the patients. Restenosis >50% was observed in eight of the 341 patients (2.3%).

Discussion

In recent years, CAS has been shown to be an effective and relatively safe means of treating carotid occlusive disease. But the risk of periprocedure ischemic stroke remains the main concern regarding the safety of CAS. There has been controversy about whether predilation should be performed. Some operaters practice routine predilation, other authors think that the risk of embolism is high during this stage and avoid predilation whenever possible ³. Until present, it cannot be determined which approach is associated with auperior outcome. From our data, the incidence of ischemic stroke was lower among those who was stented with predilation alone than among those who was stented with postdilation alone (0.99% vs. 4.7%, p = 0.166), though there was not significant difference because of small number of clinical events.

The predilation may tear or crush the plaque during balloon expansion, causing plaque debris dislogement. But if a protection device is used, emboli can be captured. Immediate stent placement may cover the lesion and prolapsing tissue, thus decrease the risk of further plaque dislocation.

If the stent was placed directly, postdilation of the constricted stenotic segment would cut the plaque radically and longitudinally by the mesh wires, and result in more smaller fragments, which may increase the risk of particulate embolization. Even a protection device is used, there still be the possibility of delayed dislogement of small plaque fragments postprocedure. Cremonesi A ⁴ reported five intraprocedure embolic events and four postprocedure ones in a series of 442 protected carotid stenting in which all patients except one were postdilated, and concluded that protection devices allowed operators to protect the procedure but did not affect late embolic events.

Furthermore, postdilation cause more severe intimal injury because of the doubled trauma effect of both plaque tearing and cutting, which would lead to a higher rate of late restenosis.

In case of high grade stenosis, and predilation not performed, if a stent of laser-cut construction is employed, due to its good apposition to the vessel wall, postdilation may crumple the stent at the acutely narrowing segment, or even broke it (one occurence in our data), associated by severe vessel wall damage and clinical complication. If a woven construction stent (like the mostly used Wallstent) is employed, as the narrowest part expand outword, the adjacently proximal and distal mesh wires, which have already fully expanded and fixed against or into the vessel wall, must also move simutaneously, scraping intima, and emboli may be released. Broadbent LP et Al⁵ reported a vessel rupture within the stent and contrast material extravasation caused by postdilation after direct stenting of carotid artery, though the patient remained haemodynamically stable. Cremonesi A ⁴ et Al reported one case of carotid artery fissuration with a periarterial extravasation immediately after stent postdilation.

In author's opinion, for those with high grade stenosis which necessitate balloon angiography, it might be advantageous to employ predilation other than direct stenting with routine postdilation, since this would decrease the risk of vessel injury and embolic complications.

Concerning patient selection of asymptomatic carotid stenosis, although we use >80% stenosis as inclusion criteria, not all such patients were refered to CAS. We performed detailed evaluation before making treatment option, including detection of silent infarction by CT or MRI, certain plaque morphology (ulceration, potential emboli as high-intensity transient signals) associated with increased risk of cerebral embolization event by Doppler, inadequate collateral circulation by angiography, decreased cerebral perfusion and vascular reserves by SPECT.

We use one positive finding of these tests as indication to CAS. The stroke risk is shown to be low for patients with asymptomatic carotid stenosis ^6-8, and no trial has compared CAS with best contemporary medical therapy for reducing stroke risk in asymptomatic patients. Carotid revascularization by endarterectomy (CE) also has not sufficiently demonstrated its benefit versus medicine.

Two randomized trials did not find benefit for CE^9,10, only one trial (ACAS)⁶ has shown surgery to be beneficial versus aspirin alone only for minor stroke, not major stroke. But a second analysis of the CT scans of ACAS patients found that cea did not reduce the frequency of CT-identifiable ipsilateral infarction in patients with high-grade asymptomatic carotid stenosis ¹¹. Nearly half of the ischemic strokes in asymptomatic patients will not respond to carotid revascularization because these strokes are caused from heart or intracranial arteries resource rather than the stenosis itself¹². Furthermore, in the recent SAPPHIRE trial¹³, the stroke and death rate was 5.4% for the asymptomatic protected-stenting group, which was worse than medical therapy in ACAS (annual event rate of 2.2%), and exceed the recommended rate of <3% from AHA guidelines for treatment benefit¹⁴, though in different population. In view of these findings, further studies for application of CAS for asymptomatic patients are required.

Conclusions

Our data suggest that the incidence of ischemic stroke was lower among those who were stented with predilation alone than among those who was stented with postdilation alone. This likely results from reduced intimal injury and decreased risk of embolic complications. Besides, it ha not been clearly determined whether asymptomatic patients will benefit from CAS, further studies are needed to evaluated the safety and efficacy of balloon-predilation stenting compared with direct stenting during CAS pplication of CAS for asymptomatic patients are required.