starting a carotid artery stenting program is safe

PERIPHERAL VASCULAR DISEASE

Original Studies

Starting a Carotid Artery Stenting Program is Safe

Marco Roffi,1* MD, Matthias Greutmann,1 MD, Franz R. Eberli,1 MD,Lisa Rainoni,2 RN, Thomas F. Luscher,1 MD, Beatrice Amann-Vesti,2 MD,

and Urs Schwarz,3 MD

Background: Little is known on the performance of newly initiated carotid artery stent-ing (CAS) programs. The safety of the procedure is being questioned following thepublication of the EVA-3S trial, a study criticized for the limited interventional experi-ence required to enroll patients. Methods: Within a newly started academic CAS pro-gram, patient data and outcomes were collected prospectively. The outcomes of thefirst 100 consecutive patients treated are reported. A CAS-fellowship-trained interven-tionalist was involved in all procedures. All patients underwent clinical assessment bya neurologist before and after the procedure, and serial ECG and cardiac enzymeswere routinely obtained. Primary outcome measures included 30-day major adverseevents (MAE), defined as death, stroke, or myocardial infarction, while on follow-updeaths and ipsilateral strokes were added. Results: Between July 2003 and November2006, 92 patients had a single internal carotid artery treated, while 7 underwent stagedbilateral CAS. In one patient, the procedure was aborted prior to lesion treatment. The30-day MAE rate per procedure was 1.9% (one major and one minor stroke). By amean follow-up of 16 months (range 2–42 months), one patient had died of refractoryheart failure, while one patient had a minor ipsilateral stroke and three had minor con-tralateral strokes, corresponding to total MAE per patient of 4%. The rate of any strokeor death was 7%. The rate of restenosis ≥50% per lesion by ultrasound was 3.8%.Conclusion: This single center experience suggests that it is safe to start a CAS pro-gram following dedicated fellowship. ' 2008 Wiley-Liss, Inc.

Key words: carotid artery stenting; learning curve; training

INTRODUCTION

Stroke is the second leading cause of death in West-ern countries following ischemic heart disease and isthe number one condition of permanent disability [1].It has been estimated that significant stenosis of theinternal carotid artery may be the predisposing condi-tion in 5–12% of all strokes [2]. Large-scale random-ized clinical trials have established the superiority ofcarotid endarterectomy (CEA) over medical treatmentin patients with high-grade stenosis of the internal ca-rotid artery, particularly in the presence of related is-chemic events. In recent years, carotid artery stenting(CAS) has emerged as an alternative treatment to sur-gery [3]. However, the premature termination of theEVA-3S (endarterectomy versus angioplasty in patientswith severe symptomatic stenosis) trial because ofincreased adverse event rates in the endovascular armraised safety concerns [4]. While the trial has beencriticized for the limited interventional experience

requested for participation in the study, consensus onminimal training requirements and performance data ofnewly initiated CAS programs are lacking.

1Department of Cardiology, University Hospital, Zurich, Swit-zerland2Department of Angiology, University Hospital, Zurich, Switzer-land3Department of Neurology, University Hospital, Zurich, Switzer-land

*Correspondence to: Marco Roffi, MD, FESC, FACC, Andreas

Gruntzig Cardiovascular Catheterization Laboratories, Department of

Cardiology, University Hospital, Raemistrasse 100, CH-8091 Zurich,

Switzerland. E-mail: [email protected]

Received 3 September 2007; Revision accepted 9 October 2007

DOI 10.1002/ccd.21434

Published online 25 February 2008 in Wiley InterScience (www.

interscience.wiley.com).

' 2008 Wiley-Liss, Inc.

Catheterization and Cardiovascular Interventions 71:469–473 (2008)

METHODS

Patient Selection

Within a newly initiated academic CAS program,baseline patient characteristics, procedural data, and out-comes were prospectively entered in a database. Theoutcomes of the first 100 consecutive patients, treatedbetween July 2003 and November 2006, are reported. ACAS-fellowship-trained interventionalist was involved inall cases. In addition to full training in coronary and pe-ripheral interventions, his prior experience included over100 diagnostic cerebral angiographies and 40 CAS pro-cedures performed as first or second operator duringdedicated fellowship training at a major US CAS center.Patients were considered for revascularization in thepresence of a �70% asymptomatic or a �50% sympto-matic stenosis of the internal carotid artery. A stenosiswas considered symptomatic in the presence of transientischemic attack or stroke affecting the corresponding ter-ritory in the preceding 6 months. Stenosis severity wasassessed by Duplex ultrasound and if necessary con-firmed by CT or MR angiography. The indication for re-vascularization was approved case by case by a neurolo-gist. All patients had a baseline imaging of the brainwith CT or MR. A neurologist examined all patientsbefore and after the procedure. ECG as well as and crea-tine kinase (CK), CK-MB, and troponin were obtainedsystematically on admission and the day after CAS.In seven patients undergoing diagnostic angiography

with the intent to proceed to CAS, the revascularizationprocedure was not attempted and were thereforeexcluded from the analysis. Reasons for not performingthe procedure were the absence of a severe stenosis onangiography (N 5 3), angiographic filling defects sug-gestive of intraluminal thrombus (N 5 2), or recanal-ized carotid occlusion (N 5 2). In these patients, thediagnostic angiography resulted in no neurologic or car-diovascular complications.

Technique

Four-vessel angiography, consisting of at least aselective angiography of both common carotid arteriesand a nonselective angiography of one vertebral artery,was performed using 5F diagnostic catheters unlesscontraindicated (e.g., in the presence of renal insuffi-ciency, severe calcification or tortuousity of the aorticarch or the supraaortic vessels). Digital subtractionangiography of each vessel was obtained at the cervi-cal and intracranial level. The stenting procedure wasperformed with either a 8F guiding catheter advancedover a 125 cm-long 5F diagnostic catheter with tele-scoping technique or a 6F 90 cm-long sheath. To pre-vent bradycardia and hypotension, 0.5–1.0 mg of atro-pine were routinely administered intravenously prior to

balloon inflation or stenting if no predilatation wasperformed. The patients were pretreated with aspirinand clopidogrel and during the procedure unfractio-nated heparin was administered to achieve an acti-vated clotting time of 250–300 sec. Following stent-ing, aspirin was continued indefinitely and clopidogrelfor at least 1 month. Antihypertensive medicationswere usually continued the day of the interventionand reinstalled stepwise thereafter. Follow-up con-sisted of Duplex ultrasound and clinical examinationat 1 month, 6 months, 12 months, and yearly there-after. Medical records were requested if an adverseevent was suspected.

Outcome Measures

The primary outcome measures were in accordanceto the Stenting and Angioplasty with Protection inPatients at HIgh Risk for Endarterectomy (SAPPHIRE)trial [5]. At 30 days, major adverse events (MAE) con-sisted of the composite occurrence of death, stroke, ormyocardial infarction (MI), while on follow-up deathand ipsilateral strokes were added. In addition, the rateof death or any stroke at follow-up was tracked. Minorstroke was defined as focal neurological deficit lastingmore than 24 hr with a Rankin score �2 and NIHstroke score �4, while major stroke was diagnosed inthe presence of a Rankin score >3 or NIH score �15.Any rise in CK-MB or troponin or new pathologicalQ-waves on ECG defined MI. Restenosis was diag-nosed in the presence of a �50% luminal narrowing asassessed by flow velocities using Duplex ultrasound.Technical success was defined by the coverage of thecarotid lesion with a stent in the presence of a residualstenosis <50% and normal flow.

Statistics

Continuous variables were expressed as the mean 61 standard deviation, and differences among the groupsof patients were tested with Student’s t-test. Categori-cal data were presented as actual numbers and percen-tages, and comparisons among the groups were per-formed with Chi-squared test. A value of P < 0.05was considered statistically significant.

RESULTS

Single carotid intervention was performed in 92patients, while 7 patients underwent bilateral stagedCAS. In one patient, intubation of the common carotidartery was attempted but rapidly aborted because ofmajor tortuousity of the supraaortic vessels in the ab-sence of neurologic or cardiovascular complications.The patient was subsequently treated conservatively.The mean age of the patients was 68 6 9.5 years and

470 Roffi et al.

Catheterization and Cardiovascular Interventions DOI 10.1002/ccd.Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).

18% of them were females (Table I). The carotidlesions were symptomatic in 25% of patients. Fre-quently associated conditions were previous coronaryrevascularization (51%), previous MI (28%), upcomingopen heart surgery (17%), and contralateral internal ca-rotid artery occlusion (11%). One or more high-riskfeatures for surgery according to the SAPPHIRE trialwere identified in 50 patients and two or more werepresent in 13 patients [5].Diagnostic four-vessel angiography was performed

in 90 patients in the absence of neurologic complica-tions. Balloon-predilatation and stent-postdilatationwere performed in 78 and 100% of cases, respectively(Table II). In two patients, two stents were required tocover the carotid lesion. Filter emboli protection devi-ces were used in 95% of the procedures in the absenceof related complications. Spasm of the internal carotidartery at the site of the emboli protection device wasobserved in 15% of cases (Table III) but in all casesspasm resolved in the absence of neurologic symptomseither spontaneously of following the administration ofintraarterial nitroglycerine. No case of distal emboliza-tion requiring mechanical or pharmacologic neurologi-cal rescue was observed. One patient suffered a seizurebecause of prolonged hypotension for few hours fol-lowing the procedure that spontaneously resolved, andfour patients received blood transfusions because ofhemoglobin drop in the absence of an identifiable

source of blood loss. The anemia was likely the resultof the administration of large volumes of intravenousfluid in addition to blood loss though the catheters atthe time of the procedure. Other than two groin hema-tomas treated conservatively, no access site complica-tions were discovered.Thirty-day MAE included one major (case number

12) and one minor stroke (case number 64) for a total

TABLE I. Baseline Characteristics

N 5 100

Age, gender

Mean age 6 SD (years) 68 6 9.5

Range age (years) 38–87

Age � 80 years 9

Male gender 82

Cardiovascular risk factors

Diabetes mellitus 24

History of dyslipidemia 86

History of hypertension 88

Current smoking 29

History of cardiovascular disease

Previous PCI or CABG 51

Previous myocardial infarction 28

Planned open heart surgery 17

Congestive heart failure 9

Previous cerebrovascular accident or TIA 46

SAPPHIRE high risk characteristics

�1 high-risk features 50

�2 high-risk features 13

Carotid lesion characteristics N 5 107

Symptomatic stenosis (%) 25

Contralateral occlusion (%) 11

Recurrent stenosis after endarterectomy (%) 8

PCI, percutaneous coronary intervention; CABG, coronary artery bypass

grafting; TIA, transient ischemic attack; SAPPHIRE, Stenting and Angio-

plasty with Protection in Patients at HIgh Risk for Endarterectomy trial [5].

TABLE II. Procedural Data

N 5 107

Angiographic and Doppler parameters

Angiographic degree of stenosis (%)a 83

Doppler flow velocitiesb

Vmax ICA systolic/diastolic (cm/s) 342/122

Vmax ICA/Vmax CCA 5.9

Drug regimen

Pretreatment with aspirin and clopidogrel (%) 99

Atropine administration (%) 98

Any periprocedural norepinephrine (%) 42

Norepinephrine boluses (%) 41

Norepinephrine drip at end of procedure (%) 9

Unfractionated heparin (%) 100

Aspirin and clopidogrel at discharge (%)c 99

Technical characteristics

Procedural success (%) 99

Emboli protection device use (%) 95

Angioguard (%) 60

Spider (%) 13

Filterwire (%) 22

Lesion predilatation (%) 78

Stents (%) 99

More than 1 stent (%) 2

Type of Stent

Precise (%) 81

Acculink (%) 1

Vivexx (%) 13

Nexstent (%) 4

Postdilatation (%) 100

The Angioguard Capture Guidewire is a product of Cordis Corporation,

Miami, FL; the Spider embolic protection device is a product of Ev3,

Plymouth, MN; the Filterwire is a product of Boston Scientific, Natick,

MA; The Precise stent is a product of Cordis; The Acculink stent is a

product of Abbott Vascular, Redwood City, CA; The Vivexx stent is a

product of Bard Medical, Covington, GA; the Nexstent is a product of

Boston Scientific.aVisual estimate.bDoppler velocities available for 83% of the lesions.cOne patient with aspirin allergy was treated periprocedurally with addi-

tional tirofiban and discharged on clopidogrel 150 mg/day for 1 month

and 75 mg/day indefinitely.

TABLE III. Periprocedural Findings and Complications

N 5 107

Internal carotid artery spasm (%) 15

Seizure (%) 1

Transfusion of packed red blood cells (%) 4

Femoral pseudoaneurysm, arteriovenous fistulas 0

Endovascular or surgical treatment of femoral access required 0

Starting Carotid Stenting 471


death, MI, or stroke rate of 1.9% (Table IV). Themajor stroke was due to intraprocedural air emboliza-tion caused by a balloon defect. The second patientsuffered a periprocedural minor stroke in the contralat-eral carotid territory, likely as a consequence of guid-ing catheter manipulation in the aortic arch. Postproce-dural cardiac enzymes measurements were availablefor 95% of the procedures and no MI was detected.All patients survived the initial 30-day period.Clinical follow-up was available for all patients. By a

mean of 15.6 months (range: 2–42 months), one patienthad died of refractory heart failure, four suffered aminor stroke, and two had MI—one at the time of aorto-coronary bypass surgery 6 weeks after CAS and one 20months after the procedure in the presence of end-stageof coronary artery disease (Table IV). With respect tothe minor strokes, one was due to a stent occlusionoccurring 17 months post CAS in a patient who hadfour prior episodes of restenosis following endarterec-tomy. The lesion was successfully treated surgically.While second event occurred at the time of cardiac sur-gery in the contralateral carotid territory 2 months postCAS, the third was a contralateral recurrence of retinalartery embolism 9 months following the procedure inthe presence of an internal carotid artery occlusion. Thefourth minor stroke occurred 30 months after CAS inthe contralateral internal carotid territory in a patientwith newly detected atrial fibrillation. The overall MAEaccording to the SAPPHIRE trial at follow up was 4%and the overall death or any stroke rate was 7%. ADuplex ultrasound imaging at 6 months or later (mean

13 6 8 months), was available for 100/106 lesionstreated (94%). A restenosis �50% was observed, inaddition to the patient with late total occlusion of thestent previously mentioned, in three patients whoremained asymptomatic and required no treatment (totalrestenosis rate per lesion 3.8%).

DISCUSSION

Currently, there is no consensus on the minimalrequirements in terms of experience prior to independ-ently perform CAS. Concerns about the safety of theprocedure were raised following the recent publicationof the randomized EVA-3S trial, a study prematurelyterminated because of increased event rates in the CASgroup compared with endarterectomy [4]. The studywas heavily criticized because of the limited interven-tional experience required to participate in the trial.Our analysis of the first 100 consecutive patientstreated with CAS within a newly initiated program inan academic setting suggests that dedicated fellowshiptraining enables the attainment of favorable proceduraland long-term patient outcomes in a moderate-to-high-risk patient population.In all but one case, the carotid artery lesion was

successfully treated and with few exceptions emboliprotection devices could be used in the absence ofrelated complications. The 30-day death, stroke, or MIrate of 1.9% lied well within the limits set by theAmerican Heart Association for CEA, namely a peri-procedural death or stroke rate of 6% for symptomaticpatients and of 3% for asymptomatic patients [6]. Inaddition, the outcomes observed compared favorablywith those of large CAS registries showing a 30-dayadverse event rate ranging from 2.1 to 8.5% [2]. Thelow incidence of ipsilateral stroke (1.9%) and of reste-nosis (3.8%) at follow-up parallels results of random-ized trials and large series documenting the excellentlong-term durability of the procedure [7,8].Notable was the lack of periprocedural MI observed

despite routine postprocedural cardiac enzyme andECG assessment. This finding may be particularly rele-vant since patients with carotid artery stenosis areknown to have a high prevalence of coronary arterydisease even in the absence of cardiac symptoms [9].In addition, even asymptomatic troponin release fol-lowing vascular surgery has been found to be predic-tive of mortality at follow-up [10]. The advantage ofCAS over CEA in terms of lower periprocedural ische-mic cardiac events was for the first time unequivocallydemonstrated in the SAPPHIRE trial [5]. In the study,the statistical significant reduction in periproceduralMI was the main factor driving the favorable resultsobserved in the endovascular arm.

TABLE IV. Major Adverse Events

Within 30 days 107 Procedures

Death 0

Stroke (%) 2 (1.9)

Major ipsilateral 1 (0.9)

Major nonipsilateral 0

Minor ipsilateral 0

Minor nonipsilateral 1 (0.9)

Myocardial infarction 0

Death, stroke or myocardial

infarction (%)

2 (1.9)

After 30 days 100 Patients

Death 1

Stroke (%) 4

Major ipsilateral 0

Major nonipsilateral 0

Minor ipsilateral 1

Minor nonipsilateral 4

Myocardial infarction (%) 2

Overall 100 Patients

Death, stroke, or myocardial

infarction at 30 days plus

death or ipsilateral stroke

within 31 days of follow-up

4

Death or any stroke 7

472 Roffi et al.


The periprocedural adverse events we observed werespread within the series, suggesting a lack of learningcurve following dedicated fellowship. Several single-cen-ter studies have demonstrated the impact of a learningcurve for CAS on clinical events [11,12] and on markersof embolization such as the appearance of new cerebrallesions on MRI [13]. At times, it may be difficult toseparate the impact on outcomes of the learning curvefrom equipment improvements occurring over time, asfor example the use of emboli protection devices. In thisrespect however, a reduction of complications withincreasing operators experience has been observed bothin the absence and in the presence of emboli protectiondevices [11,14]. In addition, simulator-based data supportthe notion that the learning curve matters in the perform-ance of carotid angiography [15]. Opposing this concepthowever, a recent large-scale registry has failed to detecta learning curve in the performance of CAS [16].The present report suggests that an experience of

40 CAS obtained within a dedicated fellowship allowsfor favorable patient outcomes. A clinical competencestatement of the US Societies of Vascular Medicine,Cardiology, and Vascular Surgery defined the minimalrequirements as 30 supervised diagnostic cervicocere-bral angiographies and 25 supervised CAS procedures[17]. Diagnostic and interventional procedures wereweighted differently in the document edited by the USSocieties of Neuroradiology and Interventional Neuro-logy, mandating the performance of �200 superviseddiagnostic cervicocerebral angiography and �4 super-vised CAS cases [18]. Higher standards were recentlyoutlined in the Italian Consensus on Carotid Stenting,a document endorsed by the National Societies of Car-diology, Neuroradiology, Vascular Surgery, Neurology,and Radiology [19]. For the first time, a dedicated fel-lowship was recommended. The requirements to achievecompetence included �150 procedures of supra-aorticvessel engagement (during diagnostic as well as inter-ventional procedures) and �75 CAS procedures perfor-med within a 2-year fellowship.In conclusion, our single center experience suggests

that following dedicated fellowship a CAS programcan be started with favorable patient outcomes.

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Starting Carotid Stenting 473


starting a carotid artery stenting program is safe

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