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European Journal of Radiology 75 (2010) 12–22

Contents lists available at ScienceDirect

European Journal of Radiology

journa l homepage: www.e lsev ier .com/ locate /e j rad

arotid artery stenting: Rationale, technique, and current concepts

asan Yilmaza,∗, Vitor Mendes Pereiraa, Ana-Paula Narataa, Roman Sztajzelb, Karl-Olof Lovblada

Department of Interventional and Diagnostic Neuroradiology, University Hospital of Geneva, SwitzerlandDepartment of Neurology, University Hospital of Geneva, Switzerland

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rticle history:eceived 25 March 2010ccepted 31 March 2010

eywords:arotid artery stentingVA-3SREST

CSSPACE

a b s t r a c t

Carotid stenosis is a major risk factor for stroke. With the aging of the general population and the avail-ability of non-invasive vascular imaging studies, the diagnosis of a carotid plaque is commonly madein medical practice. Asymptomatic and symptomatic carotid stenoses need to be considered separatelybecause their natural history is different. Two large randomized controlled trials (RCTs) showed theeffectiveness of carotid endarterectomy (CEA) in preventing ipsilateral ischemic events in patients withsymptomatic severe stenosis. The benefit of surgery is much less for moderate stenosis and harmful inpatients with stenosis less than 50%. Surgery has a marginal benefit in patients with asymptomatic steno-sis. Improvements in medical treatment must be taken into consideration when interpreting the resultsof these previous trials which compared surgery against medical treatment available at the time the trials

were conducted. Carotid artery stenting (CAS) might avoid the risks associated with surgery, includingcranial nerve palsy, myocardial infarction, or pulmonary embolism. Therefore and additionally to well-established indications of CAS, this endovascular approach might be a valid alternative particularly inpatients at high surgical risk. However, trials of endovascular treatment of carotid stenosis have failed toprovide enough evidence to justify routine CAS as an alternative to CEA in patients suitable for surgery.More data from ongoing randomized trials of CEA versus CAS will be soon available. These results willhelp determining the role of CAS in the management of patients with carotid artery stenosis.

. Introduction

Carotid artery stenosis is a major risk factor for stroke andransient ischemic attack (TIA). Approximately 20% of strokesan be attributed to carotid artery occlusive disease [1]. Histo-ogical studies, showed the difference between symptomatic andsymptomatic carotid plaques [2], making the clear separationetween symptomatic and asymptomatic patients with a carotidrtery stenosis critical and necessary when considering an inva-ive treatment such as carotid endarterectomy (CEA) or carotidrtery stenting (CAS). Therefore, when dealing with carotid arterycclusive disease, symptomatic and asymptomatic stenoses shoulde viewed as separate entities, because the risks and benefits ofreatment are very different. The publication of the North Ameri-an Symptomatic Carotid Endarterectomy Trial and the European

arotid Surgery Trial results established CEA as the treatmentf choice for moderate and severe symptomatic carotid arterytenosis [3,4]. The Asymptomatic Carotid Surgery Trial showed amall benefit of early CEA in asymptomatic patients with stenosis

∗ Corresponding author at: University Hospital of Geneva, Rue Gabrielle-Perret-entil 4, 1211 Geneve 14, Switzerland.

E-mail address: hasan.yilmaz@hcuge.ch (H. Yilmaz).

720-048X/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved.oi:10.1016/j.ejrad.2010.04.010

© 2010 Elsevier Ireland Ltd. All rights reserved.

greater than 60%, provided the periprocedural risk is lower than 3%[5].

However, these randomized controlled trials (RCTs), comparedCEA to best medical treatment available at the time the studieswere conducted. Since then, medical treatment has evolved, withnewer antiplatelet agents, and the use of lipid-lowering medica-tion, a more aggressive and effective management of risk factorsassociated with carotid artery stenosis is performed. Disadvan-tages of CEA include a neck incision with the risk of cranial nervepalsy and wound complications [6]. Medical risks associated withthe procedure include myocardial infarction (MI) [7], and not allpatients are suitable for surgery. During the past 2 decades, therapid evolution of endovascular techniques that began with carotidartery angioplasty have evolved to stent-supported angioplasty andcombined the use of different cerebral embolic protection devices.Carotid artery angioplasty and stenting have gained widespreadacceptance after the publication of the first large series. This mini-mally invasive approach seemed interesting particularly in patientsexcluded from large RCTs which demonstrated the benefit of CEA

over medical treatment in patients with carotid stenosis. Severalrandomized trials have then been undertaken to compare CASand CEA, but have failed to demonstrate equivalence of the treat-ment modalities [8–10]. This article summarizes recent data onthe management of carotid artery stenosis. Endovascular technique

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or carotid revascularization is described, indications, advantages,rocedure-related limitations and complications are discussed. Aeview of recent randomized trials comparing CAS and CEA is pre-ented.

. Carotid artery revascularization strategies

.1. Carotid endarterectomy

.1.1. Symptomatic patientsIn patients with symptomatic carotid artery disease, CEA is

ffective in preventing future ipsilateral ischemic events, providedhat the perioperative combined risk of stroke and death is notigher than 6% [11].

Several randomized controlled trials demonstrated that carotidndarterectomy was more effective than medical therapy inatients with recently symptomatic carotid stenosis. The Euro-ean Carotid Surgery Trial (ECST) [12] randomized patients withny degree of stenosis and compared patients treated by CEA withatients managed by best medical treatment alone. The Northmerican Symptomatic Carotid Endarterectomy Trial (NASCET) [4]ad a similar design, but only recruited patients with more than 30%arotid stenosis. However, investigators have made different rec-mmendations about the degree of stenosis above which surgerys effective. Different methods used to measure the carotid arterytenosis can explain this variability. Analysis of pooled data [13]rom these two major randomized controlled trials including datarom the Veteran Affairs Trial [14], allowed to accurately assess theverall effect of surgery by reanalysis of carotid angiograms. Dataor 6092 patients, with 35,000 patient–years of follow-up, wereooled. The results showed that surgery was harmful in patientsith less than 30% stenosis, had no effect in patients with 30–49%

tenosis, was of marginal benefit in those with 50–69% steno-is. Surgery was highly beneficial in patients with 70% stenosisr greater, without near-occlusion (absolute risk reduction of 16%ver 5 years). In patients with near-occlusion of the carotid arterycollapse of the internal carotid artery beyond the stenosis), no sig-ificant difference between CEA and medical treatment was found.

Pooled analysis of the RCTs suggested that the benefit from CEAas greatest if patients had the surgery within 2 weeks after the

schemic event. The benefit of surgery is reduced if patients with arevious TIA or non-disabling stroke are treated after 2 weeks fromhe symptoms onset. The risk of recurrent stroke with time whileaiting for surgery is up to 40% when the treatment is delayed

s long as 90 days after a qualifying event [15]. Recent guidelinesor secondary stroke prevention recommend that CEA should beerformed within 2 weeks for patients presenting with a TIA orinor stroke [11].

.1.2. Asymptomatic patientsThere have been two large randomized trials examining the ben-

fits of CEA for asymptomatic stenosis [5,16]. These trials showedhat CEA was more effective than medical treatment in prevent-ng strokes in carefully selected patients who had severe carotidrtery stenosis but no recent symptoms considered related to thearotid disease. In the analysis of these 2 trials and their conclu-ions, it is important to consider that the patients constituted aighly selected group which is not representative of the patientseen in clinical practice. These patients had no severe cardiac dis-ase, or other serious comorbidities and were operated by selected

urgeons who had low complication rates.

In these 2 trials, surgery provided a modest benefit in strokerevention, reducing the risk of stroke from 2% per year to 1%er year. This benefit is only maintained when the perioperativeisks of stroke and death are less than 3% [11,16]. Patients with

f Radiology 75 (2010) 12–22 13

a life expectancy of less than 5 years are unlikely to benefit fromthe modest risk reduction obtained by surgery [5]. In the Asymp-tomatic Carotid Surgery Trial, surgery did not benefit patients aged75 years and above. A combined analysis of these 2 trials showed noapparent benefit during a mean follow-up of 2–3 years in women[17]. The results of these CEA trials need to be considered cau-tiously. In all the trials, surgery was compared with the medicaltreatment available at the time. The main difference today is theuse of lipid-lowering medication. In the NASCET trial, the propor-tion of patients under lipid-lowering treatment varied from 16%at the beginning of the study, to 40% at the time the trial wascompleted [4]. Several trials have since found statins to lowerthe risk of recurrent stroke [18,19]. Identification of asymptomaticpatients who are at increased risk of stroke would help cliniciansin selecting the patients in whom an invasive treatment is indi-cated. Predictors of increased risk of ipsilateral ischemic events inasymptomatic patients with carotid stenosis are the following: astenosis of increased severity, a progressive stenosis, a history ofcontralateral symptomatic carotid artery stenosis, and increasedserum creatinine concentrations. [20] The place of CAS has to bedetermined in asymptomatic patients with severe carotid arterystenosis, particularly in patients aged 75 years or older in whom theAsymptomatic Carotid Surgery Trial [5], CEA did not show a clearbenefit, but also in asymptomatic patients excluded from these tri-als because of severe comorbidities such as severe cardiac disease[3–5,12,16].

2.2. Carotid revascularization by angioplasty and stenting

2.2.1. Evolution and rationaleSince the 1980s, interventional neuroradiology techniques have

become an important therapeutic alternative for many cerebrovas-cular diseases. Kerber et al. [21] published the first report of carotidartery balloon angioplasty in 1980.

A second small series was reported in 1983 [22] and in 1987,Theron et al. [23] published a larger series including 48 patientsin whom technical success rate was 94% with a major stroke mor-bidity of 4.1%. By 1995, a review of worldwide experience among523 patients claimed favorable results with 96.2% technical suc-cess, 2.1% morbidity, 6.3% transient minor complications, and nodeaths [24]. Operator experience was important in determining thetechnical success and treatment outcomes: centers with limitedexperience (<50 cases) reported nearly twice the rate of com-plications (5.9% versus 2.6%) than those with more substantialexperience [25,26].

The CAS procedure does not remove the source of intra-arterialemboli and carries the risk of plaque debris dislodgement duringthe passage of the stenosis and particularly during the postdilationof the stent. Therefore, it seemed necessary to develop a cerebralprotection system during a CAS procedure. Theron was one of thepioneers who developed and used a temporary balloon occlusiondevice as a cerebral protection during angioplasty and stenting forcarotid stenosis [27,28]. Three types of cerebral protection devices(CPDs) are nowadays available: distal filters and distal or proxi-mal occlusion balloons, each has its advantages and disadvantages[29].

2.2.2. Patient selection and current indications of CAS2.2.2.1. Patient selection and defining a “high surgical risk”?. Eventhough CEA became the standard method of treating carotid arterystenosis when the large randomized trials were published [3,4,12],

these trials evaluating CEA have systematically excluded patientsconsidered to be at “high risk for surgery“(Table 1). These impor-tant limitations were behind the rationale for developing CAS as aless-invasive endovascular approach to carotid revascularization.Endovascular treatment of carotid stenosis has been proposed as

14 H. Yilmaz et al. / European Journal of Radiology 75 (2010) 12–22

Table 1Exclusion criteria for CEA trials.

Older than 79 years of ageHeart, kidney, liver or lung failureCancer likely to cause death within 5 yearsCardiac valvular lesion or rhythm disorder likely to be associated with

cardioembolic strokePrevious ipsilateral CEAContralateral CEA within 4 monthsAngina or Myocardial Infarction within the previous 6 monthsProgressive neurological signsMajor surgical procedure within 30 daysSevere comorbidity due to other surgical illnessCerebrovascular events in the distribution of the study

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Table 3Criteria for high risk (at least one factor required) in the SAPPHIRE study.

Clinically significant cardiac disease (congestive heart failure, abnormal stress,or need for open-heart surgery)

Severe pulmonary diseaseContralateral carotid occlusionContralateral laryngeal-nerve palsy

CA with ongoing disabling symptomsSymptoms referable to the contralateral side within the previous 45 daysMore severe stenosis of an intracranial lesion than of the treated lesion

valid alternative to CEA after the publication of first reports andase series.

At our institution, each patient with a carotid artery stenosiss discussed in a weekly multidisciplinary team meeting includingpecialists from vascular surgery, neurology, cardiology, internaledicine, angiology, and interventional neuroradiology. A clear

eparation between symptomatic and asymptomatic carotid arterytenosis is critical, because we know from histological studies,hat the asymptomatic carotid plaque looks very different fromymptomatic carotid plaques [2]. Advantages and disadvantages ofurgery and endovascular treatment are assessed for each patient.f a high surgical risk or any contraindication for CEA is suspected,he patient is referred to CAS. The wide definition of a “high surgicalisk” is based on previous reports analyzing patients’ risks factorsor CEA [30,31], and on the exclusion criteria for CEA trials for aubgroup of patients.

A retrospective analysis by Sundt et al. [31], of 3111 consecu-ive patients who underwent CEA stratified patients into six risklasses according to neurologic status, coexisting morbid condi-ions, and angiographic variables: this study revealed a very low

ajor complication rate (permanent stroke, myocardial infarction,r death) for patients with class I or II disease, whereas patientsith class IV disease had an 8.1% risk (with a 2.9% mortality rate).

actors correlating with increased surgical morbidity and mortalityates included unstable neurologic status; the presence of coexis-ent morbid conditions; age greater than 70 years; and contralateralnternal carotid artery occlusion. Tables 2 and 3 summarize “Theundt definition” of a high-risk patient for surgery and criteria for

igh-risk patients included in the SAPPHIRE study [32].

.2.2.2. Current indications of CAS. The well-established indicationsf CAS as a first therapeutic option for a carotid revascularization

able 2Sundt” definition of medical, neurologic, and angiographic risk for carotid arteryurgery.

Risk Definition

Medical Coronary artery disease (angina, myocardial infarction <6months, congestive heart failure),hypertension(>180/110 mm Hg), severe peripheralvascular disease, chronic obstructive pulmonary disease,age >70 years, severely obese

Neurologic Neurologic deficit within 24 h, general cerebral ischemia,recent cerebrovascular accident (<7 days), frequenttransient ischemic attacks

Vascularanatomy

Contralateral internal carotid artery stenosis or occlusion,Intracranial stenosis or occlusion, plaque >3 cm distally ininternal carotid artery >5 cm proximal in common carotidartery, bifurcation at C2 vertebra, short thick neck, and softthrombus extending from an ulcerative lesion

Previous radical neck surgery or radiation therapy to the neckRecurrent stenosis after endarterectomyAge >80 years

are the following: recurrent stenosis after CEA, radiation-inducedcarotid stenosis, anatomical features (high carotid bifurcation nearthe skull base), tandem lesions (proximal common carotid arterystenosis or distal stenosis in the carotid siphon associated with thecarotid bifurcation stenosis).

Compared with CEA, CAS has the advantage that it can be donewith the patient under mild sedation, requires no incision and thusavoids the risk of cranial nerve palsy, and has fewer cardiovascularcomplications. For its acceptance as a valid alternative to CEA, CASmust fulfill the same criteria of safety, effectiveness and durability.

2.2.2.3. CAS in acute stroke treatment?. With the evolution anddevelopment of endovascular therapy of stroke, including intra-arterial thrombolysis [33,34], and mechanical revascularizationdevices [35], interventional neuroradiologists are facing more andmore clinical situations where they have to treat both in anemergency setting the cervical carotid occlusion or near-occlusionresponsible for the stroke, and the intracranial occluded vessels.The feasibility of combined intracranial thrombolysis and CAS inacute ischemic stroke has been reported previously [36–39]. In astudy of 25 patients with acute stroke who underwent a cervi-cal carotid artery stent implantation in the acute phase [40], ICArecanalization was successful in 21 patients, with 2 patients expe-riencing symptomatic hemorrhage. This management seemed toimprove the outcome of patients treated by endovascular approachcompared to a group of patient who received medical treatmentonly. These reports require further studies to define the role of suchan approach in the management of acute stroke.

2.2.3. Carotid artery stenting technique2.2.3.1. Procedural overview. Variations in protocol and techniquehave been described by many experienced operators, producinggood results. The following descriptions represent a guide to tech-nique while recognizing that substantial diversity currently existsand that both endovascular devices and procedure protocol areevolving.

Baseline imaging of the brain and vessels is required, includingmagnetic resonance angiography (MRA) or, CT scan angiography(CTA). Both CTA and MRA will be done with contrast agents. Patientswith preexistent renal disease will benefit from intravenous hydra-tion 1 day prior to the procedure. In some cases MR techniques suchas diffusion and perfusion imaging can help assess both the lesionand obtain an approximative visualization of hemodynamics.

Patient preparation with adequate antiplatelet and anticoagu-lation therapy is essential. Experimental data suggest aspirin andclopidogrel have a synergistic effect on platelet anti-aggregation, onanti-thrombotic activity, and in preventing myointimal prolifera-tion [41,42]. Therefore, patients receive a dual antiplatelet regimenconsisting of aspirin (100 mg daily) and clopidogrel (75 mg daily).This treatment is started at least 3 days before the stenting. A load-

ing dose of clopidogrel (300–600 mg) administered early on the dayof the procedure is an alternative for patients who are already tak-ing aspirin. This dual anti-aggregation is maintained for 1 monthafter the stenting, and one antiplatelet agent (aspirin) is continuedwithout interruption.

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Patients receiving long-term anticoagulation should discon-inue warfarin 3 days prior to the procedure and are admitted theay before to switch for heparin administration.

The procedure is performed under local anesthesia in an angiog-aphy suite with biplane digital subtraction and road-mappingapabilities. The patient is under conscious sedation. Blood pres-ure, oxygen saturation, and cardiac rhythm are monitored. Thearotid artery is generally approached percutaneously after punc-uring the femoral artery. The interventional neuroradiologisthould also be familiar with radial and brachial approaches in caseemoral artery access is not possible. Direct carotid artery punctureas also been described in difficult accesses [43].

An aortic angiogram and catheterization of both carotid and ver-ebral arteries is not always indicated as the pre-operative imagings including MR or CT angiography studies. Avoiding unneces-ary vessel catheterization will decrease the thrombo-embolicomplications of the procedure especially in these patients withtherosclerotic arteries. Performing a brain parenchymography asescribed by Theron et al. [44] allows the assessment of collateralirculation thus avoiding selective vessels catheterization.

A sheath is inserted into the common femoral artery, and aaseline activated clotting time is obtained. The patient receivesn intravenous loading dose of heparin (50–70 U/kg). An activatedlotting time of 250–300 s is maintained throughout the procedure.he heparin infusion is usually discontinued at the end of the pro-edure. The sheath size vary from 6-to-10-French (Fr), dependentn the protection device and stent that will be used, but in most ofhe cases, the procedure is successfully performed through a 6-to-Fr sheath. The target carotid artery is catheterized with a 5-Friagnostic catheter (H1 Beacon Tip Torcon NB, JB2 Slip-Cath Bea-on Tip, or Simmon 2; Cook Inc., Bloomington, USA) in combinationith a 0.035-in. guide wire (Terumo Medical Corporation Elkton,D, USA). Standard angiographic projections for demonstrating the

arotid bifurcation are anteroposterior, lateral and ipsilateral ante-ior oblique (30–45◦) projection. Standard intracranial views arelso obtained prior to the treatment to assess the collateral cir-ulation and to document any intracranial stenotic lesions. Afterompletion of the diagnostic angiography step and positioningf the catheter in the CCA, an exchange-length 0.035-in. wire isnserted under road mapping into the external CA. The diagnosticatheter is exchanged over the wire for a 90-cm, 6-to 8-Fr guid-ng catheter (Vista Brite Tip, Cordis, Miami, FL, USA) or long 90 cmheath (Destination Guiding Carotid Sheath, Terumo, Medical Cor-oration Elkton, MD, USA) that is then advanced into the commonarotid artery (CCA) below the bifurcation.

A double coaxial catheterization technique is useful in diffi-ult and tortuous anatomy. This system consists of two catheters:Vista Brite Tip guiding catheter of 80 cm (Cordis, Miami, FL,

SA), specially designed for neurovascular procedures, a diagnos-ic catheter of 100 cm inside the guiding catheter (H1 Beacon Tiporcon NB, JB2 Slip-Cath Beacon Tip, or Simmon 2; Cook Inc.,loomington, USA), and the 0.035-in. wire. We use two differentized systems: an 8-Fr Vista Brite Tip with a 6-Fr catheter, or a-Fr Vista Brite Tip with a 5-Fr diagnostic catheter. The 2-Fr differ-nce between the two catheters is required to allow the continuousaline flushing.

The target artery is first accessed with the tip of the 6-Fr or 5-Fratheter over the wire, then the 7-Fr or 8-Fr guiding catheter is gen-ly and progressively advanced over the inner catheter. Togetherhe inner catheter and the wire can be placed distally into thexternal carotid artery, offering enough stability to allow the guid-

ng catheter to advance into the CCA below the stenosis. Thesewo catheters should always be continuously flushed during thispproach. Once the guiding catheter is in place, an optimal work-ng projection of the stenosis is obtained. Depending on the severityf the stenosis, the lesion can be firstly crossed by the protection

f Radiology 75 (2010) 12–22 15

device in case of a filter protection is used. A predilation with a2–3 mm diameter and 20 mm length balloon is performed (Ultra-soft SV monorail, Boston Scientific Corporation, Natick, MA, USA)if the stenosis is very severe. A single, brief (<30 s) balloon infla-tion is performed. Bradycardia or asystole usually do not occurin the predilation step. In very difficult cases when crossing thelesion with the filter protection device alone is not possible, amicrocatheter with a microguide wire (Excel 14 microcatheterwith 0.014-in. Transend wire, Boston Scientific Corporation,) isnecessary. Once the lesion in crossed, the tip of microcatheter ispositioned into the cavernous portion of the ICA, and a 300 cmexchange microguide wire (Transend 300 Floppy 0.014 in., BostonScientific Corporation; or Wizdom 0.014 in., 300 cm, Cordis) is usedto remove the microcatheter. Alternatively, the lesion can be ini-tially crossed using the 0.014-in. exchange guide wire within themicrocatheter. The whole procedure is usually performed withrapid-exchange monorail devices. Some authors advocate the usefor cerebral protection during CAS, a temporary balloon occlusiondevice, because the risk to dislodge plaque debris is less whencrossing or dilating the lesion with the carotid flow under control.The TwinOne (Minvasys; Gennevilliers, France) cerebral protectiondevice recently described by Theron et al. [45] is a very interestingand promising tool allowing the positioning in one step of a distalballoon occlusion system with the post-angioplasty balloon afterthe deployment of the stent. The temporary occlusion protectiondevice is useful in dangerous lesions such as ulcerated plaques orwhen a floating clot is suspected inside the carotid artery.

The diameter of the stent should be sized to the caliber of thelargest segment of the carotid artery to be covered (usually 1–2 mmmore than the normal caliber of the CCA). Oversizing of the stentin the ICA does not usually result in adverse events. The use of atapered stent can better conform to the vessel anatomy. The proxi-mal part (into the CCA) and the distal end of the stent (into the ICA)should be placed in normal segments of the carotid artery. There-fore, selection of a stent that is long enough to cover the entire lesionis important. The stents used are self-expanding, with a closed-cell or open-cell design. The mostly used sizes range from 8 to9 mm diameter and 30–40 mm length (Carotid Wallstent Monorail;Boston Scientific is a closed-cell; Precise stent, Cordis and ProtégéRx tapered stent, EV3 Inc., Plymouth, MN, USA are open-cell). Theuse of a closed-cell or open-cell design stent is based on vascularanatomy. The open-cell stent will better conform to a very tortu-ous anatomy [46]. After the deployment of the stent, a postdilationis performed using a 5–6 mm diameter and 20 mm length balloon(Ultra-soft SV monorail, Boston Scientific Corporation). The balloonshould be inflated for no longer than 30 s at 8–10 atm. Prior to bal-loon inflation, 0.5 mg of atropine is administered intravenously toprevent bradycardia and asystole, which may occur in 5–10% ofpatients. The embolic protection device is then removed, using itsretrieval catheter. When a balloon occlusion is used for cerebralprotection, an aspiration is performed before deflation and retrievalof the balloon in order to eliminate potential embolic debris. Themost common settings for difficulty in capturing deployed filterprotection devices are with an open-celled stent on a significantvessel curve (in which a stent strut may impinge on the vesselintima) and when the device is parked in a tortuous distal vessel.Advancing the guide catheter into the stent will bias the wire awayfrom the stent wall, allowing the recapture sheath to pass.

Anteroposterior and lateral cerebral angiograms should beobtained after stent placement in all cases to exclude any embolicbranch occlusion and to document new patterns of flow.

A vascular closure device can be used at the femoral access site.Different devices are available on the market. The choice is basedon the operator’s experience, patient’s anatomy, and the size of thepuncture (Perclose and Starclose closure device, Abbott Vasc Inc.,Redwood, CA, USA; or Angioseal, St Jude Medical).

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.2.3.2. Postintervention follow-up. The patient is usually mon-tored in the intensive care unit for 12–24 h after treatment,

ith a careful control of the arterial pressure. Hypotensionnd hypertension should be avoided. The patient is carefullyxamined neurologically. Neurologic deficits may be due tontracranial embolism, hemorrhage, or reperfusion injury [47].he phenomenon of reperfusion hemorrhage following surgi-al endarterectomy is well described. Ouriel et al. [48], in aeview of 1471 patients undergoing surgical endartererectomy,eported 0.75% incidence of intracerebral hemorrhage. Hemor-hage occurred at a median of 3 days post-operatively andccounted for 35% of the total perioperative neurologic events.eath of massive hemorrhage occurred in 36% of cases. Factorsorrelating with an increased hemorrhage risk were hypertension,igh-grade ipsilateral stenosis or occlusion, and younger age. Post-rocedural prolonged bradycardia and/or hypotension may occurs a result of carotid sinus dysfunction, necessitating appropriatereatment.

The patient is discharged after 2 or 3 days. A duplex sonographys performed the day after the stenting, with a control at 6 months,

year, and then annually thereafter. Magnetic resonance studyith diffusion-weighted imaging has also been used to the moni-

oring of neuroendovascular procedures [49]. The dual antiplateletegimen of aspirin and clopidogrel is maintained for 4–6 weeksost-treatment. Administration of aspirin is continued indefinitely.

.2.4. Durability of CASResults of mid-term and long-term follow-up of RCTs comparing

EA and CAS showed that the incidence of restenosis was higher inhe endovascular group compared to surgical group. The estimated-year incidence of restenosis was about three times more commonfter endovascular treatment than endarterectomy, but patientsreated with a stent in the endovascular arm, had a significantlyower risk of developing restenosis of 70% or greater compared withhose treated with balloon angioplasty alone [50].

The reported results up to 4 years in EVA-3S study [51], showedhat after the periprocedural period, the risk of ipsilateral strokeas low and similar in both treatment groups, and suggested

hat carotid stenting is as effective as carotid endarterectomy foriddle-term prevention of ipsilateral stroke. The 2 years follow-

p results of SPACE study demonstrated that even if the recurrenttenosis of 70% or more was significantly higher in the stentingroup compared with the endarterectomy group (10.7% versus 4.6%espectively) the rate of recurrent ipsilateral ischemic stroke wasimilar for both treatment groups [52].

The low rate of long-term stroke after endovascular treatmentupports the use of CAS to prevent long-term stroke in patients inhom carotid endarterectomy is contraindicated.

.2.5. Complications of CAS

.2.5.1. Access site complications. The most common access prob-ems include retrograde dissection, pseudoaneurysm, arteriove-ous fistula, extravasation of blood around the sheath, and the

nability to gain access. Femoral artery occlusion or bleeding canlso occur in an acute or delayed fashion.

The external carotid artery and its branches are used to sup-ort a guidewire during the exchange of a diagnostic catheter to a

arger guiding catheter or sheath prior to the stent delivery. Ves-el perforation [53] in this setting has been reported. Vessel spasmr embolic complication in the external carotid artery could be oflinical importance in case of anatomical variation and dangerous

nastomosis with intracranial circulation.

Spasm can occur in tortuous internal carotid arteries particu-arly when a filter cerebral protection is used and straightens or

oves a kink in the vessel. Once the filter protection device iseployed in the distal ICA, avoidance of unnecessary movement of

f Radiology 75 (2010) 12–22

the filter will decrease the incidence of spasm. This spasm resolveswhen the filter is removed. Therefore, it is important to rapidlyperform the stenting and angioplasty after the deployment of thefilter, and to remove all intravascular devices to avoid any emboliccomplication.

2.2.5.2. Neurological and systemic complications. Stroke can occurduring the diagnostic angiography of supra-aortic vessels or duringthe revascularization of the target artery. During the procedure, themostly encountered stroke is ischemic due to embolism. Therefore,to avoid such a complication, it is important to limit as far as pos-sible the catheterization maneuvers to the target vessel. In most ofcases, pre-operative diagnostic imaging modalities with MRA andCTA are enough to accurately assess the vascular anatomy and cere-bral circulation. Ischemic complication can be due to large vesselocclusion or shower or emboli. If a clear large vessel cutoff can beseen, an immediate attempt should be undertaken to recanalize theoccluded vessel. This recanalization can be today achieved withmechanical thrombectomy devices (thromboaspiration catheter,clot retriever devices), thus avoiding the use of intra-arterial lysis.If the angiogram documents slow flow or distal embolism, IIb/IIIaantiplatelet agents can be administered.

Hemorrhagic complications can occur and are mostly reportedin the postprocedural phase [54]. If a hemorrhage is identified andoccurred during the early phase, heparin anticoagulation given dur-ing the procedure is reversed with protamine, the blood pressure istightly controlled, and a repeat CT scan is obtained within 6–12 h.Life-threatening hematomas in neurologically salvageable patientscan be evacuated.

Systemic complications may occur with CAS, including seizures[55], myocardial infarction, contrast material nephropathy andcontrast material allergy.

2.2.6. Trials comparing CEA and CAS in stroke prevention2.2.6.1. CAVATAS. The Carotid and Vertebral Artery TransluminalAngioplasty Study (CAVATAS) [56], was the first large randomizedtrial to systematically compare balloon angioplasty with or with-out stenting to CEA for carotid artery revascularization, with 90% ofpatients having symptomatic stenosis. Among the 504 patients ran-domized during 5 years, (253 to CEA and 251 to CAS), no significantdifference in the risk of stroke or death related to either procedurewas found. The rate of any stroke lasting more than 7 days or deathwithin 30 days of treatment even unacceptably high (around 10%)were similar in both the surgical and angioplasty groups. Prelim-inary analysis of long-term survival showed no difference in therate of ipsilateral stroke or any disabling stroke in patients up to 3years after randomization.

The rate of severe (70–99%) restenosis 1 year after treatmentwas 14% in the endovascular group and 4% in the surgical group. Itis important to remind that only 26% of patients in the endovascu-lar group received a stent, and might explain the high incidenceof restenosis in this arm. No embolic protection devices wereused in this study. The estimated 5-year incidence of restenosiswas about three times more common after endovascular treat-ment than endarterectomy, but patients treated with a stent inthe endovascular arm, had a significantly lower risk of devel-oping restenosis of 70% or greater compared with those treatedwith balloon angioplasty alone [50]. The reported long-term rateof ipsilateral stroke in the CAVATAS study [57] was similar tothat recorded in the endarterectomy arms of previous trials: theECST [58] reported a 10-year risk of ipsilateral stroke after CEA

(excluding perioperative events) of 9.7%, which is similar to the8-year risk of 8.6% after surgery and 11.3% after endovascular treat-ment reported in the long-term follow-up of CAVATAS. There wasno statistical difference in the stroke outcome measure in bothendovascular and endarterectomy group in the long-term follow-

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p of the CAVATAS study [50]. The low rate of long-term strokefter endovascular treatment supports the use of CAS to preventong-term stroke in patients in whom CEA is contraindicated. How-ver, the study was underpowered with wide confidence intervals50].

.2.6.2. The stenting and angioplasty with protection in patientst high risk for endarterectomy (SAPPHIRE). This study comparedarotid stenting using an embolic protection device to endarterec-omy in surgically “high-risk” patients with specific comorbidities32]. A total of 334 patients with more than 50% symptomatictenosis, or with more than 80% asymptomatic stenosis were ran-omized. The majority of patients (approximately 70%) included inhe SAPPHIRE study had asymptomatic carotid stenosis. The cumu-ative incidence of a major cardiovascular event at 1 year was lowern the endovascular group (12.2% versus 20.1%). The authors con-luded that stenting with distal embolic protection was not inferioro endarterectomy. Limits to the SAPPHIRE study included the facthat 22% of patients in each group had recurrent stenosis follow-ng a prior endarterectomy, a condition that potentially favors CAS.dditionally, inclusion of myocardial infarction in the compositendpoint obscures the effects of stroke and death which were pri-ary endpoints in the large endarterectomy trials. The trial was

erminated early, because the recruitment of patients slowed afteronrandomized stent registries were established. Subsequently,

t appeared that the Principle Investigator received undeclaredoyalties from sales of the embolic protection device used in theAPPHIRE trial.

Fig. 1. Case 1: radiation-ind

f Radiology 75 (2010) 12–22 17

2.2.6.3. Endarterectomy versus angioplasty in patients with severecarotid stenosis study (EVA-3S). This multicenter randomizedFrench study [9] included only patients with symptomatic carotidstenosis greater than 60%. A total of 527 patients were randomized.The rates of stroke and death were higher in the stent group thanthe surgical group. The frequency of stroke or death at 30 days was3.9% in the endarterectomy group and 9.6% in the stented group.The study was stopped early because of safety concerns. Resultsof this study must be judged with caution. At the beginning of thetrial, the use of a cerebral protection device was not performed inall patients allocated to endovascular therapy. The study was puton hold 3 years after the start of randomization for a short period oftime, and the use of cerebral protection devices was then manda-tory. Patients treated without embolic protection device had a 25%30-day stroke or death rate versus 7.9% in those treated with acerebral protection. Surgeons were fully trained and completed 25endarterectomies in the year before enrollment. However, inter-ventionists were certified after performing as few as five carotidstent procedures (5 carotid stents among at least 35 stent proce-dures of supra-aortic vessels or 12 carotid stents) or were allowed toenroll patients in the trial while they were receiving their trainingin carotid stenting.

2.2.6.4. SPACE. The multicenter Stent-Protected Angioplasty ver-sus Carotid Endarterectomy in symptomatic patients (SPACE) trial[10] enrolled only patients with symptomatic carotid stenosisgreater than 70%. A total of 1183 patients were randomized. Therate of death or ipsilateral ischemic stroke 30 days after endovas-

uced carotid stenosis.

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ular treatment or surgery was similar (6.84% versus 6.34%). SPACEailed to prove non-inferiority of CAS compared with CEA for theeriprocedural complication rate.

.2.6.5. International carotid stenting study (ICSS). The finding ofigher rates of stenosis in the endovascular group of the CAVATAStudy resulted in the initiation of a second prospective, randomizedrial: the International Carotid Stenting Study (ICSS), also known asAVATAS-2 [59]. The ICSS trial is a randomized double-blind study

Fig. 2. Case 2: transradial approach using a

f Radiology 75 (2010) 12–22

comparing stenting with endarterectomy in patients with symp-tomatic carotid stenosis of greater than 50% within 6 months priorto randomization. According to the study protocol, use of a cerebralprotection device is recommended whenever the operator thinks

that the device can be safely deployed. A total of 1710 patientswere included in the intention-to-treat analysis, 853 randomizedto stenting and 857 to surgery. The early results presented at thelast European stroke conference (Brown MM, Ederle J, Bonati LH, etal. Safety results of the International Carotid Stenting Study: Early

TwinOne balloon protection device.

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utcome of patients randomized between carotid stenting andndarterectomy for symptomatic carotid stenosis. European Strokeonference 2009; May 27, 2009: Stockholm, Sweden), showed thatatients randomized to CEA had a significantly lower proceduralisk than patients randomized to CAS (5.1% versus 8.5% respec-ively). In addition, a subgroup of ICSS patients who underwenterial MR imaging had significantly more early and ultimately per-isting new ischemic brain lesions following CAS (despite cerebralrotection) than after CEA. In the ICSS trial, approximately 80% ofatients allocated to stenting had distal-protection devices usedut the analysis of outcomes with and without protection was notet completed at the time the initial results were presented. Morenteresting is that in this MRI substudy, patients treated with stent-ng without protection had a significantly lower incidence of silentschemic lesions on imaging than those treated using protection.he final results of the ICSS study should be published soon.

.2.6.6. CREST. The Carotid Revascularization Endarterectomy ver-us Stenting Trial [60] is a randomized study that compares thefficacy of CEA with that of CAS using cerebral protection device in

he prevention of stroke, MI, and death in symptomatic patientsTIA or ipsilateral non-disabling stroke within the previous 180ays) with more than 50% stenosis and asymptomatic patients withore an 70% stenosis. The primary endpoints are death, stroke, orI at 30 days or ipsilateral stroke within 60 days of the proce-

Fig. 3. Case 3: tand

f Radiology 75 (2010) 12–22 19

dure. The trial started in 2000, with a planned sample size of 2500patients. A credentialing phase for interventionists was includedthat required previous carotid stenting experience and monitoringof the performance of up to 20 procedures using the Acculink Stentand Acculink embolic protection system [61].

During the lead-in phase [61,62], major adverse event rates were5.7% for symptomatic patients and 3.5% for asymptomatic patients.The 30-day composite rate of stroke and death for symptomaticpatients was slightly lower than the rates reported in NASCET andECST. For asymptomatic patients, 30-day stroke and death rateshave been slightly higher than those reported in ACAS [63,64],but slightly lower than those reported in the ACST [5]. Similarperiprocedural morbidity was observed in women and men [65]and for those treated with or without an embolic protection device.For octogenarians, the 30-day stroke and death rate was 11.9%,which was significantly higher than for patients aged 79 years andyounger [62].

The publication of CREST in 2010 will provide important infor-mation concerning the role of CAS and its use in the clinical practice.

2.2.7. Illustrative cases2.2.7.1. Case 1: radiation-induced carotid stenosis. A 60-year oldman with a history of previous neck surgery and radiation fora tumor of the mandible presented two episodes of amaurosisfugax on the right side. He had already been treated for a right

em lesions.

20 H. Yilmaz et al. / European Journal of Radiology 75 (2010) 12–22

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arotid artery stenosis 2 years ago by endarterectomy. The newmaging studies demonstrated a recurrent right carotid stenosisecondary to radiation therapy. Angiography confirmed a severend long stenosis of the right internal carotid artery (ICA), (Fig. 1a).he carotid stenting is performed after predilation of this veryevere stenosis to allow the delivery of a Carotid Wallstent (9 mmiameter, 40 mm length, BSC). Several maneuvers of post-stentingngioplasties are necessary to fully open the stent in this situa-ion because of a very long and severe stenosis. Angioplasty iserformed from proximal segment to distal segment of the ICAFig. 1b–d). A filter protection device has been used during the pro-edure (Emboshield, Abbott Vasc Inc., Redwood, CA, USA), and cane seen in the superior cervical ICA segment. Post-operative controlhows a satisfactory result (Fig. 1e).

.2.7.2. Case 2: transradial approach using a TwinOne balloon protec-ion device (case performed with Theron). A 76-year old woman withsevere symptomatic left ICA stenosis was referred to endovascular

reatment after our multidisciplinary discussion. After the failure of

he first attempt to access the lesion by a femoral approach (Fig. 2a),right transradial access was successful (Fig. 2b). An exchange pro-edure over the wire allowed to catheterize the carotid artery with7-Fr guiding catheter (Lumax Flex Neuroradiology Angled Coaxialuiding catheter, Cook Inc., Bloomington, USA). A Carotid Wallstent

ysis with acute carotid stenting.

(7 mm diameter and 50 mm length) was deployed and then a tem-porary balloon occlusion cerebral protection (Twin One) was used(Fig. 2c). The system is made of a distal small occlusion balloon forthe protection and a proximal post-angioplasty balloon. The occlu-sive balloon is dilated inside the stent in its distal end to avoidvasospasm of the ICA. A hand injection is performed to check theefficient occlusion (Fig. 2d) of the vessel. Angioplasty of the stentis then performed under distal occlusion of the ICA (Fig. 2e). Afterdeflation of the angioplasty balloon, aspiration of blood inside thestent to remove any plaque debris is performed while the distal bal-loon is still inflated (Fig. 2f). The control angiograms demonstratesatisfactory results with normal brain circulation (Fig. 2g). Thereis a small kinking of the ICA at the distal end of the stent withouthemodynamic effect (Fig. 2h).

2.2.7.3. Case 3: tandem lesions. A 71-year old man with ahistory of coronary artery by-pass surgery and recurrent post-endarterectomy left carotid stenosis presented with transientischemic attack (TIA) in the ipsilateral carotid territory. Diagnos-

tic imaging studies demonstrated a proximal stenosis at the originof left common carotid artery (CCA) (Fig. 3a), and associated steno-sis in the left ICA (Fig. 3.b). The proximal stenosis is treated witha balloon-expandable stent (Fig. 3c). Secondary, the distal stenosisis treated with a self-expanding Carotid Wallstent. The procedure

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s performed under filter protection device with monitoring of theiddle cerebral artery flow by transcranial Doppler (Fig. 3d). Anal-

sis of the cerebral protection device at the end of the procedureemonstrates plaque debris trapped inside the filter (Fig. 3e).

.2.7.4. Case 4: intra-arterial thrombolysis and acute carotid arterytenting. A 79-year old man was admitted to hospital 3 h afterymptoms onset of stroke. Initial CT angiography demonstrated ancclusion of the right middle cerebral artery (MCA) at M1–M2 junc-ion, with no contraindication for a thrombolysis, and the patientas referred to endovascular therapy. Angiography revealed a

evere stenosis of the right cervical ICA with a near-occlusion ofhe vessel (Fig. 4a). Intracerebral injection confirmed the occlu-ion site (Fig. 4b). The decision to perform a CAS in emergency wasade with the neurologist. The stenting immediately improved the

arotid circulation (Fig. 4c). Additional intra-arterial thrombolysis15 mg of rtPA) through a microcatheter allowed a full recanaliza-ion of the MCA (Fig. 4d). The neurological status of the patientmproved and control CT scan demonstrated a limited infarct in theight superficial sylvian territory without any sign of hemorrhageFig. 4e).

. Conclusion

Trials comparing CAS and CEA in the management of symp-omatic carotid artery stenosis have failed to demonstrate thequivalence of both treatment modalities. However, the publi-ation of long-term follow-up of three major trials [51,52,57]uggested that both methods of treatment had similar efficacyn preventing long-term ipsilateral stroke after the initial treat-

ent period. The low rate of long-term stroke longer than 30ays after endovascular treatment supports the use of endovas-ular treatment to prevent long-term stroke in patients in whomEA is contraindicated. The Cochrane systematic review of trialsomparing CEA and CAS, indicated that most trials compared expe-ienced carotid surgeons against less experienced interventionists66].

Stenting avoids some of the minor complications of CEA andherefore would be the treatment of choice in any subgroups inhich it could be shown to have equivalent safety and long-term

utcome. With the rapid evolution of technology in stenting anderebral protection devices, the safety and long-term effective-ess of endovascular treatment for carotid artery stenosis should

mprove.The Carotid Revascularization Endarterectomy versus Stenting

rial (CREST) and the International Carotid Stenting Study (ICSS)ave completed enrolment, and several new trials of stenting ver-us surgery for asymptomatic carotid stenosis are in the early stagesf recruiting patients. The Carotid Stenting Trialists Collaborationill analyze the pooled data from recent large trials, in order to

stablish more clearly in which subgroups CEA is the treatment ofhoice and in which subgroups endovascular treatment has equiva-ent risks. The results of these studies will improve the managementf patients with carotid artery stenosis defining more precisely theole of carotid artery stenting compared to surgery.

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