Methods

A single-operator, prospective, elective, carotid artery stent registry (n = 296) was reviewed for patients who underwent retreatment for early (within 6 months) ISR after CAS. Patients with ISR were identified with ultrasound performed as part of a routine CAS follow-up protocol at 1, 6, and 12 months and then annually in some cases. The ultrasound exams were performed at one facility (Maplewood Vascular Clinic), which was an American College of Radiology-accredited facility from 2002 to 2006 and the Intersocietal Commission for Accreditation of Vascular Laboratories accredited from 2007 to 2009. Moderate restenosis (50–69%) was defined as a peak systolic velocity (PSV) >200 seconds. Severe restenosis (70–99%) was defined as a PSV >200 and end diastolic velocity (EDV) >135 or internal carotid artery/common carotid artery (ICA/CCA) ratio >4. These criteria, utilized empirically since 2002, are very similar to those reported by Levy et al³ and those recently reported by Setacci et al in Stroke based on a prospective study of 814 carotid stents.⁶ (Setacci suggested a PSV >175 for >50% stenosis, and an EDV >140 or ICA/CCA ratio >3.8 for >70% stenosis.)

Patients who developed severe ISR by ultrasound, and whose general health was good enough that treatment of an asymptomatic restenosis was thought beneficial, were advised to undergo angiography. Retreatment with cutting balloon angioplasty (and possible restenting) was performed if the stenosis angiographically was 70% or greater. All eight patients who developed severe ISR by ultrasound underwent angiography. One patient was occluded at the time of angiography. In a second patient, the stenosis measured only 40%. A stenosis of >70% was confirmed in six patients, and all subsequently were treated with cutting balloon angioplasty (none required additional stent placement).

The cutting balloon (Boston Scientific, Natick, Massachussetts, USA) is a non-compliant balloon with three or four (depending on the size of the balloon) microsurgical blades mounted longitudinally on the outer surface. It is prepared and used similarly to other angioplasty balloons. The directions for use recommend sizing the balloon no more than 1.1:1 relative to the native artery for coronary angioplasty, in order to decrease the risk of perforation. The nominal inflation pressure is 6 atmospheres, and it should not be inflated beyond 10 atmospheres. The largest balloon in a rapid-exchange platform is 4 mm. An 8F guide catheter or larger is recommended.

All patients undergoing intervention for ISR were pre-treated with clopidogrel for at least 5 days and aspirin 325 mg for at least 2 days. The more recent patients were treated with clopidogrel for at least 7 days. Patients were maintained on aspirin and clopidogrel for at least 3 months post-procedure, and aspirin either 325 or 81 mg daily thereafter unless clopidogrel was continued for other reasons. Assays for platelet inhibition were not performed. After gaining femoral access, unfractionated heparin was administered for an activated clotting time >250 seconds. A 6 French Shuttle sheath (Cook) was used for access. After confirming adequate anticoagulation, the lesions were then crossed with a 0.014 wire in the initial case, or filter in five cases (Accunet (Abbott Vascular, Redwood City, California, USA) or Angioguard (Cordis Endovascular, New York, New York, USA)). In each case a 4 mm cutting balloon was used, followed by dilation with a 5 mm standard coronary balloon in two cases. The cutting balloon can be entirely within the stent (fig 1), or partially within the native artery in the case of a restenosis at the margin of the stent (fig 2), as long as the balloon is not oversized compared with the native artery. The filter was then retrieved. Patients were observed overnight.

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Figure 1

(A) In-stent restenosis. (B) Cutting balloon angioplasty. (C) Post-treatment angiogram.

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Figure 2

(A) Restenosis at the margin of the stent. (B) Cutting balloon angioplasty. (C) Post-treatment angiogram.

Ultrasound and clinical follow-up were then obtained at 1, 6, and 12 months, and then annually. Criteria for determining stenosis were identical as those used for the initial CAS follow-up protocol.

Results

There were no procedural complications and all patients were discharged home the following morning. An initial angiographic result of <20% stenosis was achieved in all patients. Follow-up and patient details are presented in Table 1. At 1 month after angioplasty, an 82-year-old female initially treated for a severe carotid stenosis with a left hemispheric stroke, had already recurred (PSV = 512, EDV = 182). As she was asymptomatic and frail at this point, further intervention was not attempted. At 20 months' follow-up she was still asymptomatic and the vessel still patent. There have been no ischemic events during the follow-up period in any of the six patients. The other five patients have not had recurrent stenosis, with 4/5 with at least 20 months' follow-up. Hence, the 1-month patency without restenosis after cutting balloon angioplasty is 5/6 (83%), and the patency without restenosis at 20 or more months is 4/5 (80%).

Discussion

Severe carotid artery in-stent restenosis is not a benign condition as it may progress to complete occlusion and may present with ischemic symptoms or stroke in as many as 10% of patients with severe ISR.^{4 5} There are several treatment options. CEA and bypass surgery have been reported,^{5 7 8} but are not commonly performed. There has been one case of successful treatment with brachytherapy reported, with 6 months' follow-up.⁹ Usage of drug-eluting stents has been reported.^{10 11} This strategy has the disadvantage of committing the patient to long-term dual anti-platelet therapy, which can be detrimental in the event bleeding or need for surgery develops. Kinking of balloon-expandable stents placed in the carotid artery is also a recognized complication.¹² Conventional balloon angioplasty has been utilized successfully to treat carotid in-stent restenosis.^{3 4 5} For treatment of coronary in-stent restenosis, cutting balloon angioplasty compared with conventional angioplasty has demonstrated some procedural advantages, such as fewer balloons and higher initial success rate, and a lower need for future revascularization, but has not demonstrated superiority in any clinical endpoint.^{13 14} There have been no direct comparisons of conventional angioplasty and cutting balloon angioplasty in the carotid arteries. Repeat carotid angioplasty and stent placement is an option with reports of long-term success,^{1 4 5} but placing a stent inside a stent obviously has limitations, and exposes the patient to another stent, which may have been a contributor to the aggressive intimal response in the first place. Using another option initially leaves the re-stenting option or open surgical techniques available for later if necessary.

Cutting balloon angioplasty for carotid artery in-stent restenosis was initially reported by Bendok et al in three cases with good initial results, but no long-term follow-up.¹⁵ One of the three required additional stent placement. Zhou et al reported four cases of cutting balloon angioplasty alone and one case combined with restenting.² Follow-up of the cutting balloon patients ranged from 3 to 14 months, with a mean follow-up of 8 months. One of the four recurred at 8 months and was retreated with cutting balloon angioplasty. Setacci reported four cases with a mean follow-up of 6 months (range 3.5–10 months), with no recurrences.¹ Others have reported isolated cases with short-term follow-up.^{3 16 17} There have been no reports of procedural complications. Combining the five cases with long-term follow-up reported here with the six cases with 6 months or more follow-up from Zhou and Setacci, cutting balloon angioplasty has been initially technically successful in all patients, and durable in 9/11 (82%) at least to 6 months, with more than 20 months' follow-up in four patients.

In conclusion, the limited data available indicate that cutting balloon angioplasty is a safe and effective procedure for the initial treatment of carotid artery in-stent restenosis, and durable in most cases. Cutting balloon angioplasty is our preferred option for the initial treatment for carotid in-stent restenosis. Repeat carotid stent placement should be reserved for patients with suboptimal initial results from cutting balloon angioplasty or second recurrences after the initial ISR intervention. More invasive surgical options should be reserved for patients with multiple recurrences.