Temporal Changes in Periprocedural Events in the Carotid Revascularization Endarterectomy Versus Stenting Trial.

BACKGROUND AND PURPOSE: Post-hoc, we hypothesized that over the recruitment period of the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST), increasing experience and improved patient selection with carotid stenting, and to a lesser extent, carotid endarterectomy would contribute to lower periprocedural event rates. METHODS: Three study periods with approximately the same number of patients were defined to span recruitment. Composite and individual rates of periprocedural stroke, myocardial infarction, and death rate were calculated separately by treatment assignment (carotid stenting/carotid endarterectomy). Temporal changes in unadjusted event rates, and rates after adjustment for temporal changes in patient characteristics, were assessed. RESULTS: For patients randomized to carotid stenting, there was no significant temporal change in the unadjusted composite rates that declined from 6.2% in the first period, to 4.9% in the second, and 4.6% in the third (P=0.28). Adjustment for patient characteristics attenuated the rates to 6.0%, 5.9%, and 5.6% (P=0.85). For carotid endarterectomy-randomized patients, both the composite and the combined stroke and death outcome decreased between periods 1 and 2 and then increased in period 3. CONCLUSIONS: The hypothesized temporal reduction of stroke+death events for carotid stenting-treated patients was not observed. Further adjustment for changes in patient characteristics between periods, including the addition of asymptomatic patients and a >50% decrease in proportion of octogenarians enrolled, resulted in practically identical rates. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00004732.

The Carotid Revascularization Endarterectomy versus Stenting Trial: credentialing of interventionalists and final results of lead-in phase.

The success of carotid artery stenting in preventing stroke requires a low risk of periprocedural stroke and death. A comprehensive training and credentialing process was prerequisite to the randomized Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) to assemble a competent team of interventionalists with low periprocedural event rates. Interventionalists submitted cases to a multidisciplinary Interventional Management Committee. This committee evaluated 427 applicants. Of these, 238 (56%) were selected to participate in the training program and the lead-in phase, 73 (17%) who had clinical registry experience and satisfactory results with the devices used in CREST were exempt from training and were approved for the randomized phase, and 116 (27%) did not qualify for training. At 30 days in the lead-in study, stroke, myocardial infarction, or death occurred in 6.1% of symptomatic subjects and 4.8% of asymptomatic subjects. Stroke or death occurred in 5.8% of symptomatic subjects and 3.8% of asymptomatic subjects. Outcomes were better for younger subjects and varied by operator training. Based on experience, training, and lead-in results, the Interventional Management Committee selected 224 interventionalists to participate in the randomized phase of CREST. We believe that the credentialing and training of interventionalists participating in CREST have been the most rigorous reported to date for any randomized trial evaluating endovascular treatments. The study identified competent operators, which ensured that the randomized trial results fairly contrasted outcomes between endarterectomy and stenting.

Outcome of carotid artery stenting for primary versus restenotic lesions.

Carotid artery stenting (CAS) for restenosis (RS) after carotid endarterectomy (CEA) is presumed to have fewer complications than CAS for primary atherosclerotic (PA) lesions. It has been proposed that interventionalists may limit themselves to CAS for RS initially, while they gain additional experience during their learning curve. However, there are few studies objectively comparing the outcomes of the two groups of patients to substantiate this assumption. We analyzed prospectively collected data on CAS performed at our institution from 1996 to April 2006. Complication rates were compared between CAS performed for RS versus PA lesions. Specific end points studied included in-hospital and 30-day stroke and death rates. The incidence of transient ischemic attack (TIA) was also recorded. Patient demographic features (gender, age, hypertension, diabetes mellitus, coronary artery disease, smoking, hypercholesterolemia, and presence of preoperative neurological symptoms) were recorded. A neurologist examined all patients before and after CAS. Patients with previous CAS with in-stent RS and tandem common carotid artery-internal carotid artery or arch ostial stenoses were excluded from this analysis. CAS procedures (n = 217) performed on 210 patients fulfilled inclusion criteria for this study. Indications for CAS included RS (n = 118, 54%) and PA (n = 99, 46%). The two groups were well matched for all demographic features except hypercholesterolemia, which was more common in the PA group. Thirty-day stroke and stroke + death rates for the entire series were 2.8% and 4.1%, respectively. Within this cohort, 30-day stroke and stroke + death rates were not significantly different between the RS (2.5% and 5.1%) and PA (3.0% and 3.0%) groups. Within the RS group, these outcomes were also similar when patients treated for late recurrence (>24 months after CEA, n = 49) were compared to those treated for early recurrence (< or = 24 months after CEA, n = 67). Only when stroke and TIA were combined was a difference observed between the late recurrence (10.0%) and the early recurrence (1.5%) groups (p = 0.049). Contrary to general opinion, 30-day stroke and stroke + mortality rates from CAS for RS versus PA were not significantly different. Lower neurological event rates were only seen in CAS for early RS compared with late RS after endarterectomy when TIAs were included as an end point in the analysis. CAS for RS must therefore not be considered a low-risk procedure. Technical proficiency for CAS must be equivalent regardless of the etiology of the stenosis. These observations also underscore the need for appropriate patient selection and close follow-up of all patients undergoing CAS.

"Buddy wire" technique to overcome proximal coronary tortuosity during rotational atherectomy.

We report a case in which rotational atherectomy was planned for the treatment of a severely calcified obstructive lesion in the middle right coronary artery. Severe proximal vessel tortuosity prevented the advancement of the Rotablator burr. We utilized the "buddy wire" technique, allowing facilitated advancement of the Rotablator and successful atherectomy and stenting. We propose this old technique as an alternative method to allow advancement of the Rotablator burr through tortuous and calcified vessels.

Management of mobile floating carotid plaque using carotid artery stenting.

PURPOSE: To present management techniques for dealing with mobile floating carotid plaque (MFCP), which represents an indeterminate risk of embolic cerebrovascular events. CASE REPORTS: Two high-risk patients with a history of carotid endarterectomy were diagnosed with MFCP by duplex ultrasound scanning. One patient had a left hemispheric transient ischemic attack while the other was asymptomatic with a moderate stenosis. Both were successfully treated with carotid artery stenting, achieving complete coverage of the MFCP. Their outcomes were uneventful, and sustained patency of the stented arteries has been observed during an event-free survival of 32 and 44 months, respectively. CONCLUSIONS: Based upon the unique nature of these lesions and our satisfactory clinical results, we believe that carotid stenting may be a viable option for the treatment of MFCP.

Carotid artery stenting: is there a need to revise ultrasound velocity criteria?

OBJECTIVES: Ultrasound (US) velocity criteria have not been well-established for patients undergoing carotid artery stenting (CAS). A potential source of error in using US after CAS is that reduced compliance in the stented artery may result in elevated velocity relative to the native artery. We measured arterial compliance in the stented artery, and developed customized velocity criteria for use early after CAS. METHODS: US was performed before and within 3 days after CAS, and after 1 month in a subset of 26 patients. Post-procedural peak systolic velocity (PSV) and end-diastolic velocity (EDV) of the internal carotid artery (ICA), PSV/EDV ratio, and internal carotid artery to common carotid artery ratio (ICA/CCA) were recorded. These were compared with degree of in-stent residual stenosis determined at carotid angiography performed at the completion of CAS. Peterson's elastic modulus (Ep) and compliance (Cp) of the ICA were determined in a subgroup of 20 patients at the distal end of the stent and in the same region in the native ICA before stenting. RESULTS: Ninety CAS procedures were analyzed. Mean (+/-SD) angiographic residual stenosis after CAS was 5.4 +/- 9.1%, whereas corresponding PSV by US was 120.4 +/- 32.4 cm/s; EDV, 41.4 +/- 18.6 cm/s; PSV/EDV ratio, 3.3 +/- 1.2; and ICA/CCA ratio, 1.6 +/- 0.5. PSV was unchanged at 1 month. Post-CAS PSV and ICA/CCA ratio correlated most with degree of stenosis (P <.0001 for both). Only six patients demonstrated in-stent residual stenosis 20% or greater, but the standard US threshold of PSV 130 cm/s or greater (validated for >20% ICA stenosis in our laboratory) categorized 38 of 90 patients as having stenosis 20% or greater. Receiver operator curve analysis demonstrated that a combined threshold of PSV 150 cm/s or greater and ICA/CCA ratio 2.16 or greater were optimal for detecting residual stenosis of 20% or greater, with sensitivity 100%, specificity 98%, positive predictive value 75%, and negative predictive value 100%. After placement of a stent, the ICA demonstrated significantly increased Ep (1.2 vs 4.4 x 10(3) mm Hg; P =.004) and decreased Cp (9.8 vs 3.2 %mm Hg x 10(-2); P =.0004). CONCLUSIONS: Currently accepted US velocity criteria validated in our laboratory for nonstented ICAs falsely classified several stented ICAs with normal diameter on carotid angiograms as having residual in-stent stenosis 20% or greater. We propose a new criterion that defines PSV less than 150 cm/s, with ICA/CCA ratio less than 2.16, as the best correlate to a normal lumen (0%-19% stenosis) in the recently stented ICA. This was associated with increased stiffness of the stented ICA (increased Ep, decreased Cp). These preliminary results suggest that placement of a stent in the carotid artery alters its biomechanical properties, which may cause an increase in US velocity measurements in the absence of a technical error or residual stenotic disease.

Technical challenges in a program of carotid artery stenting.

OBJECTIVES: Successful carotid artery stenting (CAS) involves gaining access to the common carotid artery, characterizing and crossing the lesion, deploying an anti-embolic device and stent, and retrieving the anti-embolic device. These steps are critical determinants of the complexity of the procedure. The frequency with which technical challenges are encountered during CAS is ill-defined. The purpose of this investigation was to review the incidence and types of technical challenges encountered during CAS and determine their effect on outcome. METHODS: Data were prospectively collected for 194 consecutive CAS procedures (177 patients) and separated into group 1, standard CAS technique, and group 2, procedures with technical challenges requiring modifications to the technique. Technical challenges were defined as difficult femoral arterial access (aortoiliac occlusive disease), complex aortic arch anatomy (elongated or bovine arch, deep takeoff of the innominate artery, tandem stenoses (CCA, innominate artery), difficult internal carotid artery anatomy (tortuosity, high-grade stenosis), and circumferential internal carotid artery calcification. The incidence of technical challenges, types of technical modifications required, and effect on outcomes were determined. RESULTS: Fifty technically challenging situations (26%) were encountered in 194 CAS procedures (group 2), which required advanced technical skills. Standard methods were used in the other 144 procedures (group 1, 74%). No significant differences in 30-day stroke and death rates were noted between the groups (group 1, 3.1%; group 2, 2.0%; P = .564). CONCLUSIONS: Twenty-six percent of the procedures required a modification in the standard technique for successful CAS. Circumferential calcification and severe tortuosity continue to be relative contraindications to CAS. Recognition of these technical challenges and increasing facility with the methods to manage them will enable expanded use of CAS without increased morbidity and mortality.

Carotid artery closure for endarterectomy does not influence results of angioplasty-stenting for restenosis.

OBJECTIVE: Carotid angioplasty and stenting (CAS) has been recommended by some authors for the management of postendarterectomy restenosis. However, some authors have expressed concern about the influence of primary closure and patch angioplasty performed during carotid endarterectomy (CEA) on the incidence rate of complications after CAS. METHODS: We analyzed our consecutive series of 54 CAS procedures performed for restenosis after prior CEA. These procedures accounted for 75% of the 72 CAS procedures performed at our institution for all indications during the last 4 years. Of these 54 patients, 28 (52%) were men and 26 (48%) were women, with a mean age of 69 years. The mean clinical follow-up period was 18 months (range, 1 to 48 months). The mean interval between prior CEA and CAS was 16 months (range, 6 to 62 months). Nineteen patients were symptomatic (35%), and 35 were asymptomatic (65%). The mean severity of restenosis was 84% +/- 7% (standard deviation). The mean residual stenosis after CAS was 8% +/- 3% (standard deviation). RESULTS: Among the 54 prior CEAs, eight cases were performed with primary closure (15%), five procedures used patch closure with autologous vein (9%), and 41 operations used Dacron patch closures (76%). All patients were managed successfully with CAS with predeployment angioplasty with low profile balloons, self-expanding stents, and poststent angioplasty to approximate the transverse diameter of the carotid artery. No instances of contrast extravasation, arterial disruption, or subintimal dissection were observed. One stroke (1.8%), a retinal infarction with partial field of vision loss, occurred in a patient with prior CEA and Dacron patch closure, and no deaths were observed in the series. CONCLUSION: Performance of CAS for restenosis after CEA with autologous or synthetic patch angioplasty was technically successful in all 54 procedures. The method of closure of the arteriotomy during CEA, primary closure or patch angioplasty, did not influence the incidence of complications.

Carotid artery stenting: analysis of data for 105 patients at high risk.

OBJECTIVES: Carotid artery stenting (CAS) has been recommended as an alternative to carotid endarterectomy (CEA) by some clinicians. However, recently published clinical trials have reported 30-day stroke and death rates of 10% to 12%. This prompted review of our experience with CAS in patients at high risk, to document our results and guide further use of CAS. METHODS: From September 1996 to the present, we performed 114 consecutive CAS procedures in 105 patients. Sixty-three patients were men (60%) and 42 patients were women (40%), with mean age of 70 years (range, 45-93 years). Indications for CAS included recurrent stenosis after previous CEA in 74 patients (65%), primary lesions in 32 patients at high risk (28%), and carotid stenosis with previous ipsilateral radiation therapy in 8 patients (7%). Asymptomatic stenosis (>80%) was managed in 70 patients (61%), and symptomatic lesions (>50%) were treated in 44 patients (39%). RESULTS: CAS was technically successful in all patients. Mean severity of stenosis before CAS was 87% +/- 6%, compared with 9% +/- 4% after CAS. Two patients (1.9%) died, 1 of reperfusion-intracerebral hemorrhage and 1 of myocardial infarction 10 days after discharge; and 1 patient (0.95%) had a stroke (retinal infarction), for a 30-day stroke and death rate of 2.85%. Two patients (1.9%) had transient neurologic events. No cranial nerve deficits were noted. No neurologic complications have been noted in the last 27 patients (26%). CONCLUSIONS: A 30-day stroke and death rate of 2.85% in our experience demonstrates acceptability of CAS as an alternative to repeat operation or primary CEA in patients at high risk or in patients with radiation-induced stenosis. We recommend further clinical investigation of CAS and participation in clinical trials by vascular surgeons.

In-stent recurrent stenosis after carotid artery stenting: life table analysis and clinical relevance.

OBJECTIVES: Carotid artery stenting has been proposed as an alternative to carotid endarterectomy in cerebral revascularization. Although early results from several centers have been encouraging, concerns remain regarding long-term durability of carotid artery stenting. We report the incidence, characteristics, and management of in-stent recurrent stenosis after long-term follow-up of carotid artery stenting. METHODS: Carotid artery stenting (n = 122) was performed in 118 patients between September 1996 and March 2003. Indications included recurrent stenosis after previous carotid endarterectomy (66%), primary lesions in patients at high-risk (29%), and previous ipsilateral cervical radiation therapy (5%). Fifty-five percent of patients had asymptomatic stenosis; 45% had symptomatic lesions. Each patient was followed up with serial duplex ultrasound scanning. Selective angiography and repeat intervention were performed when duplex ultrasound scans demonstrated 80% or greater in-stent recurrent stenosis. Data were prospectively recorded, and were statistically analyzed with the Kaplan-Meier method and log-rank test. RESULTS: Carotid artery stenting was performed successfully in all cases, with the WallStent or Acculink carotid stent. Thirty-day stroke and death rate was 3.3%, attributable to retinal infarction (n = 1), hemispheric stroke (n = 1), and death (n = 2). Over follow-up of 1 to 74 months (mean, 18.8 months), 22 patients had in-stent recurrent stenosis (40%-59%, n = 11; 60%-79%, n = 6; > or =80%, n = 5), which occurred within 18 months of carotid artery stenting in 13 patients (60%). None of the patients with in-stent recurrent stenosis exhibited neurologic symptoms. Life table analysis and Kaplan-Meier curves predicted cumulative in-stent recurrent stenosis 80% or greater in 6.4% of patients at 60 months. Three of five in-stent recurrent stenoses occurred within 15 months of carotid artery stenting, and one each occurred at 20 and 47 months, respectively. Repeat angioplasty was performed once in 3 patients and three times in 1 patient, and repeat stenting in 1 patient, without complications. One of these patients demonstrated asymptomatic internal carotid artery occlusion 1 year after repeat intervention. CONCLUSIONS: Carotid artery stenting can be performed with a low incidence of periprocedural complications. The cumulative incidence of clinically significant in-stent recurrent stenosis (> or =80%) over 5 years is low (6.4%). In-stent restenosis was not associated with neurologic symptoms in the 5 patients noted in this cohort. Most instances of in-stent recurrent stenosis occur early after carotid artery stenting, and can be managed successfully with endovascular techniques.

Pixel distribution analysis of B-mode ultrasound scan images predicts histologic features of atherosclerotic carotid plaques.

BACKGROUND: The correlation of B-mode ultrasonographic morphology with histologic characteristics of atherosclerotic carotid plaques remains ill-defined. The classification of plaques with recently reported measures of plaque echogenicity and heterogeneity has been unsatisfactory. We used computer-assisted duplex ultrasound (DU) scan image analysis to determine echogenicity of specific tissues in control subjects. This information was used to quantify each tissue in imaged carotid plaques with pixel distribution analysis (PDA). These objective observations then were quantitatively compared with plaque histology in symptomatic and asymptomatic patients. METHODS: We performed standardized DU scanning of healthy tissues in 10 volunteer subjects and of 20 carotid artery plaques (7 symptomatic and 13 asymptomatic) in 19 patients with carotid stenosis. The plaques underwent histologic analysis after carotid endarterectomy. The grayscale intensity ranges of blood, lipid, fibromuscular tissue, and calcium were calculated in the control subjects. With computer-assisted image analysis, B-mode images of plaques were linearly scaled to normalize data. Pixel distribution within the images then was analyzed. The grayscale ranges of known tissues obtained from control subjects helped define the amount of intraplaque hemorrhage, lipid, fibromuscular tissue, and calcium within carotid plaque images. This analysis was correlated with tissue composition measurements on histologic sections of excised plaques. RESULTS: The median grayscale intensity (range) in control subjects was 2 (0 to 4) for blood, 12 (8 to 26) for lipid, 53 (41 to 76) for muscle, 172 (112 to 196) for fibrous tissue, and 221 (211 to 255) for calcium. PDA-derived predictions for blood, lipid, fibromuscular tissue, and calcium within carotid plaques correlated significantly with the histologic estimates of each tissue respectively (blood: P =.012; lipid: P =.0006; fibromuscular: P =.035; and calcium: P =.0001). A significantly higher amount of blood and lipid was seen within symptomatic plaques compared with asymptomatic ones (P =.0048 and P =.026, respectively). Conversely, a larger amount of calcification was noted within asymptomatic plaques (P =.0002). CONCLUSION: Computer-assisted PDA of DU scan images accurately quantified intraplaque hemorrhage, fibromuscular tissue, calcium, and lipid. Symptomatic plaques had lower calcium content but larger amounts of intraplaque hemorrhage and lipid. Quantitative PDA may be used to determine carotid plaque tissue composition to assist in the identification of symptomatic and potentially unstable asymptomatic plaques.