Margriet Fokkema

Stenting Versus Surgery in Patients With Carotid Stenosis After Previous Cervical Radiation Therapy Systematic Review and Meta-Analysis

Background and Purpose— Patients with both carotid stenosis and previously cervical radiation therapy are considered “high risk” for carotid endarterectomy (CEA). Carotid angioplasty and stenting (CAS) seems a reasonable alternative, but neither the operative risk for CEA nor the effectiveness of CAS has been proven. The purpose of this study was to evaluate perioperative and long-term outcome of both procedures in patients with radiation therapy. Methods— A systematic search strategy with the synonyms “carotid artery stenosis” and “cervical irradiation” was conducted in MEDLINE and EMBASE databases. To provide and compare estimates of outcomes, pooled and metaregression analyses were performed. Results— Twenty-seven articles comprising 533 patients undergoing radiation therapy (361 CAS and 172 CEA) fulfilled our inclusion criteria. Pooled analysis showed perioperative risk for “any cerebrovascular adverse event” (CVE) of 3.9% (95% CI, 2.3%–6.7%) in CAS studies against 3.5% (95% CI, 1.5%–8.0%) in CEA studies (P=0.77). Risk for cranial nerve injury (CNI) after CEA was 9.2% (95% CI, 3.7%–21.1%) versus none after CAS. Late outcome showed rates of CVE favoring CEA (P=0.014). The rate of restenosis >50% was significantly higher in patients treated with CAS compared with CEA (P<0.003). Conclusions— Both CAS and CEA proved to be feasible revascularization techniques with low risk for CVE. Although patients undergoing CEA had more temporary CNI, higher rates of late CVE and restenosis were identified after CAS.

Relative importance of aneurysm diameter and body size for predicting abdominal aortic aneurysm rupture in men and women

OBJECTIVE Women have been shown to have up to a fourfold higher risk of abdominal aortic aneurysm (AAA) rupture at any given aneurysm diameter compared with men, leading to recommendations to offer repair to women at lower diameter thresholds. Although this higher risk of rupture may simply reflect greater relative aortic dilatation in women who have smaller aortas to begin with, this has never been quantified. Our objective was therefore to quantify the relationship between rupture and aneurysm diameter relative to body size and determine whether a differential association between aneurysm diameter, body size, and rupture risk exists for men and women. METHODS We performed a retrospective review of all patients in the Vascular Study Group of New England (VSGNE) database who underwent endovascular or open AAA repair. Height and weight were used to calculate each patients body mass index and body surface area (BSA). Next, indices of each measure of body size (height, weight, body mass index, BSA) relative to aneurysm diameter were calculated for each patient. To generate these indices, we divided aneurysm diameter (in cm) by the measure of body size; for example, aortic size index (ASI) = aneurysm diameter (cm)/BSA (m(2)). Along with other relevant clinical variables, we used these indices to construct different age-adjusted and multivariable-adjusted logistic regression models to determine predictors of ruptured repair vs elective repair. Models for men and women were developed separately, and different models were compared using the area under the curve. RESULTS We identified 4045 patients (78% male) who underwent AAA repair (53% endovascular aortic aneurysm repairs). Women had significantly smaller diameter aneurysms, lower BSA, and higher BSA indices than men. For men, the variable that increased the odds of rupture the most was aneurysm diameter (area under the curve = 0.82). Men exhibited an increased rupture risk with increasing aneurysm diameter (<5.5 cm: odds ratio [OR], 1.0; 5.5-6.4 cm: OR, 0.9; 95% confidence interval [CI], 0.5-1.7; P = .771; 6.5-7.4 cm: OR, 3.9; 95% CI, 1.9-1.0; P < .001; ≥ 7.5 cm: OR, 11.3; 95% CI, 4.9-25.8; P < .001). In contrast, the variable most predictive of rupture in women was ASI (area under the curve = 0.81), with higher odds of rupture at a higher ASI (ASI >3.5-3.9: OR, 6.4; 95% CI, 1.7-24.1; P = .006; ASI ≥ 4.0: OR, 9.5; 95% CI, 2.3-39.4; P = .002). For women, aneurysm diameter was not a significant predictor of rupture after adjusting for ASI. CONCLUSIONS Aneurysm diameter indexed to body size is the most important determinant of rupture for women, whereas aneurysm diameter alone is most predictive of rupture for men. Women with the largest diameter aneurysms and the smallest body sizes are at the greatest risk of rupture.

Accuracy of administrative data versus clinical data to evaluate carotid endarterectomy and carotid stenting.

OBJECTIVE Administrative data have been used to compare carotid endarterectomy (CEA) and carotid artery stenting (CAS). However, there are limitations in defining symptom status, Centers for Medicare and Medicaid Services high-risk status, as well as complications. Therefore, we did a direct comparison between administrative data and physician chart review as well as between data collected for the National Surgical Quality Improvement Program (NSQIP) and physician chart review for CEA and CAS. METHODS We performed an outcomes analysis on all CEA and CAS procedures from 2005 to 2011. We obtained International Classification of Diseases, Ninth Revision diagnosis codes from hospital discharge records regarding symptom status, high-risk status, and perioperative stroke. We also obtained data on all CEA patients submitted to NSQIP over the same time period. One of the study authors (R.B.) then performed a chart review of the same patients to determine symptom status, high-risk status, and perioperative strokes and the results were compared. RESULTS We identified 1342 patients who underwent CEA or CAS between 2005 and 2011 and 392 patients who underwent CEA that were submitted to NSQIP. Administrative data identified fewer symptomatic patients (17.0% vs 34.0%), physiologic high-risk patients (9.3% vs 23.0%), and anatomic high-risk patients (0% vs 15.2%). Although administrative data identified a similar proportion of perioperative strokes (1.9% vs 2.0%), this was due to the fact that these data identified eight false positive and nine false negative perioperative strokes. NSQIP data identified more symptomatic patients compared with chart review (44.1% vs 30.3%), fewer physiologic high-risk patients (13.0% vs 18.6%), fewer anatomic high-risk patients (0% vs 6.6%), and a similar proportion of perioperative strokes (1.5% vs 1.8%, only one false negative stroke and no false positives). CONCLUSIONS Administrative data are unreliable for determining symptom status, high-risk status, and perioperative stroke and should not be used to analyze CEA and CAS. NSQIP data do not adequately identify high-risk patients, but do accurately identify perioperative strokes and to a lesser degree, symptom status.

Clinical Relevance of Cranial Nerve Injury following Carotid Endarterectomy

OBJECTIVES The benefit of carotid endarterectomy (CEA) may be diminished by cranial nerve injury (CNI). Using a quality improvement registry, we aimed to identify the nerves affected, duration of symptoms (transient vs. persistent), and clinical predictors of CNI. METHODS We identified all patients undergoing CEA in the Vascular Study Group of New England (VSGNE) between 2003 and 2011. Surgeon-observed CNI rate was determined at discharge (postoperative CNI) and at follow-up to determine persistent CNI (CNIs that persisted at routine follow-up visit). Hierarchical multivariable model controlling for surgeon and hospital was used to assess independent predictors for postoperative CNI. RESULTS A total of 6,878 patients (33.8% symptomatic) were included for analyses. CNI rate at discharge was 5.6% (n = 382). Sixty patients (0.7%) had more than one nerve affected. The hypoglossal nerve was most frequently involved (n = 185, 2.7%), followed by the facial (n = 128, 1.9%), the vagus (n = 49, 0.7%), and the glossopharyngeal (n = 33, 0.5%) nerve. The vast majority of these CNIs were transient; only 47 patients (0.7%) had a persistent CNI at their follow-up visit (median 10.0 months, range 0.3-15.6 months). Patients with perioperative stroke (0.9%, n = 64) had significantly higher risk of CNI (n = 15, CNI risk 23.4%, p < .01). Predictors for CNI were urgent procedures (OR 1.6, 95% CI 1.2-2.1, p < .01), immediate re-exploration after closure under the same anesthetic (OR 2.0, 95% CI 1.3-3.0, p < .01), and return to the operating room for a neurologic event or bleeding (OR 2.3, 95% CI 1.4-3.8, p < .01), but not redo CEA (OR 1.0, 95% CI 0.5-1.9, p = .90) or prior cervical radiation (OR 0.9, 95% CI 0.3-2.5, p = .80). CONCLUSIONS As patients are currently selected in the VSGNE, persistent CNI after CEA is rare. While conditions of urgency and (sub)acute reintervention carried increased risk for postoperative CNI, a history of prior ipsilateral CEA or cervical radiation was not associated with increased CNI rate.

Stenting versus endarterectomy for restenosis following prior ipsilateral carotid endarterectomy : An individual patient data meta-analysis

OBJECTIVE To study perioperative results and restenosis during follow-up of carotid artery stenting (CAS) versus carotid endarterectomy (CEA) for restenosis after prior ipsilateral CEA in an individual patient data (IPD) meta-analysis. BACKGROUND The optimal treatment strategy for patients with restenosis after CEA remains unknown. METHODS A comprehensive search of electronic databases (Medline, Embase) until July 1, 2013, was performed, supplemented by a review of references. Studies were considered for inclusion if they reported procedural outcome of CAS or CEA after prior ipsilateral CEA of a minimum of 5 patients. IPD were combined into 1 data set and an IPD meta-analysis was performed. The primary endpoint was perioperative stroke or death and the secondary endpoint was restenosis greater than 50% during follow-up, comparing CAS and CEA. RESULTS In total, 13 studies were included, contributing to 1132 unique patients treated by CAS (10 studies, n = 653) or CEA (7 studies; n = 479). Among CAS and CEA patients, 30% versus 40% were symptomatic, respectively (P < 0.01). After adjusting for potential confounders, the primary endpoint did not differ between CAS and CEA groups (2.3% vs 2.7%, adjusted odds ratio 0.8, 95% confidence interval (CI): 0.4-1.8). Also, the risk of restenosis during a median follow-up of 13 months was similar for both groups (hazard ratio 1.4, 95% (CI): 0.9-2.2). Cranial nerve injury (CNI) was 5.5% in the CEA group, while CAS was in 5% associated with other procedural related complications. CONCLUSIONS In patients with restenosis after CEA, CAS and CEA showed similar low rates of stroke, death, and restenosis at short-term follow-up. Still, the risk of CNI and other procedure-related complications should be taken into account.

The impact of Centers for Medicare and Medicaid Services high-risk criteria on outcome after carotid endarterectomy and carotid artery stenting in the SVS Vascular Registry

OBJECTIVE The Centers for Medicare and Medicaid Services (CMS) require high-risk (HR) criteria for carotid artery stenting (CAS) reimbursement. The impact of these criteria on outcomes after carotid endarterectomy (CEA) and CAS remains uncertain. Additionally, if these HR criteria are associated with more adverse events after CAS, then existing comparative effectiveness analysis of CEA vs CAS may be biased. We sought to elucidate this using data from the SVS Vascular Registry. METHODS We analyzed 10,107 patients undergoing CEA (6370) and CAS (3737), stratified by CMS HR criteria. The primary endpoint was composite death, stroke, and myocardial infarction (MI) (major adverse cardiovascular event [MACE]) at 30 days. We compared baseline characteristics and outcomes using univariate and multivariable analyses. RESULTS CAS patients were more likely to have preoperative stroke (26% vs 21%) or transient ischemic attack (23% vs 19%) than CEA. Although age ≥ 80 years was similar, CAS patients were more likely to have all other HR criteria. For CEA, HR patients had higher MACEs than normal risk in both symptomatic (7.3% vs 4.6%; P < .01) and asymptomatic patients (5% vs 2.2%; P < .0001). For CAS, HR status was not associated with a significant increase in MACE for symptomatic (9.1% vs 6.2%; P = .24) or asymptomatic patients (5.4% vs 4.2%; P = .61). All CAS patients had MACE rates similar to HR CEA. After multivariable risk adjustment, CAS had higher rates than CEA for MACE (odds ratio [OR], 1.2; 95% confidence interval [CI], 1.0-1.5), death (OR, 1.5; 95% CI, 1.0-2.2), and stroke (OR, 1.3; 95% CI,1.0-1.7), whereas there was no difference in MI (OR, 0.8; 95% CI, 0.6-1.3). Among CEA patients, age ≥ 80 (OR, 1.4; 95% CI, 1.02-1.8), congestive heart failure (OR, 1.7; 95% CI, 1.03-2.8), EF <30% (OR, 3.5; 95% CI, 1.6-7.7), angina (OR, 3.9; 95% CI, 1.6-9.9), contralateral occlusion (OR, 3.2; 95% CI, 2.1-4.7), and high anatomic lesion (OR, 2.7; 95% CI, 1.33-5.6) predicted MACE. Among CAS patients, recent MI (OR, 3.2; 95% CI, 1.5-7.0) was predictive, and radiation (OR, 0.6; 95% CI, 0.4-0.8) and restenosis (OR, 0.5; 95% CI, 0.3-0.96) were protective for MACE. CONCLUSIONS Although CMS HR criteria can successfully discriminate a group of patients at HR for adverse events after CEA, certain CMS HR criteria are more important than others. However, CEA appears safer for the majority of patients with carotid disease. Among patients undergoing CAS, non-HR status may be limited to restenosis and radiation.

Routine use of ultrasound-guided access reduces access site-related complications after lower extremity percutaneous revascularization

OBJECTIVE We sought to elucidate the risks for access site-related complications (ASCs) after percutaneous lower extremity revascularization and to evaluate the benefit of routine ultrasound-guided access (RUS) in decreasing ASCs. METHODS We reviewed all consecutive percutaneous revascularizations (percutaneous transluminal angioplasty or stent) performed for lower extremity atherosclerosis at our institution from 2002 to 2012. RUS began in September 2007. Primary outcome was any ASC (bleeding, groin or retroperitoneal hematoma, vessel rupture, or thrombosis). Multivariable logistic regression was used to determine predictors of ASC. RESULTS A total of 1371 punctures were performed on 877 patients (43% women; median age, 69 [interquartile range, 60-78] years) for claudication (29%), critical limb ischemia (59%), or bypass graft stenosis (12%) with 4F to 8F sheaths. There were 72 ASCs (5%): 52 instances of bleeding or groin hematoma, nine pseudoaneurysms, eight retroperitoneal hematomas, two artery lacerations, and one thrombosis. ASCs were less frequent when RUS was used (4% vs 7%; P = .02). Multivariable predictors of ASC were age >75 years (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.1-3.7; P = .03), congestive heart failure (OR, 1.9; 95% CI, 1.1-1.3; P = .02), preoperative warfarin use (OR, 2.0; 95% CI, 1.1-3.5; P = .02), and RUS (OR, 0.4; 95% CI, 0.2-0.7; P < .01). Vascular closure devices (VCDs) were not associated with lower rates of ASCs (OR, 1.1; 95% CI, 0.6-1.9; P = .79). RUS lowered ASCs in those >75 years (5% vs 12%; P < .01) but not in those taking warfarin preoperatively (10% vs 13%; P = .47). RUS did not decrease VCD failure (6% vs 4%; P = .79). CONCLUSIONS We were able to decrease the rate of ASCs during lower extremity revascularization with the implementation of RUS. VCDs did not affect ASCs. Particular care should be taken with patients >75 years old, those with congestive heart failure, and those taking warfarin.

Carotid stenting versus endarterectomy in patients undergoing reintervention after prior carotid endarterectomy

BACKGROUND Outcomes for patients undergoing intervention for restenosis after prior ipsilateral carotid endarterectomy (CEA) in the era of carotid angioplasty and stenting (CAS) are unclear. We compared perioperative results and durability of CAS vs CEA in patients with symptomatic or asymptomatic restenosis after prior CEA and investigated the risk of reintervention compared with primary procedures. METHODS Patients undergoing CAS and CEA for restenosis between January 2003 and March 2012 were identified within the Vascular Study Group of New England (VSGNE) database. End points included any stroke, death or myocardial infarction (MI) within 30 days, cranial nerve injury at discharge, and restenosis ≥ 70% at 1-year follow-up. Multivariable logistic regression was done to identify whether prior ipsilateral CEA was an independent predictor for adverse outcome. RESULTS Out of 9305 CEA procedures, 212 patients (2.3%) underwent redo CEA (36% symptomatic). Of 663 CAS procedures, 220 patients (33%) underwent CAS after prior ipsilateral CEA (31% symptomatic). Demographics of patients undergoing redo CEA were comparable to patients undergoing CAS after prior CEA. Stroke/death/MI rates were statistically similar between redo CEA vs CAS after prior CEA in both asymptomatic (4.4% vs 3.3%; P = .8) and symptomatic patients (6.6% vs 5.8%; P = 1.0). No significant difference in restenosis ≥ 70% was identified between redo CEA and CAS after prior CEA (5.2% vs 3.0%; P = .5). Redo CEA vs primary CEA had increased stroke/death/MI rate in both symptomatic (6.6% vs 2.3%; P = .05) and asymptomatic patients 4.4% vs 1.7%; P = .03). Prior ipsilateral CEA was an independent predictor for stroke/death/MI among all patients undergoing CEA (odds ratio, 2.1; 95% confidence interval, 1.3-3.5). No difference in cranial nerve injury was identified between redo CEA and primary CEA (5.2% vs 4.7%; P = .8). CONCLUSIONS In the VSGNE, CEA and CAS showed statistically equivalent outcomes in asymptomatic and symptomatic patients treated for restenosis after prior ipsilateral CEA. However, regardless of symptom status, the risk of reintervention was increased compared with patients undergoing primary CEA.

The impact of the present on admission indicator on the accuracy of administrative data for carotid endarterectomy and stenting

BACKGROUND Administrative data are often hampered by coding errors, absent data, and the difficulty of distinguishing pre-existing conditions from perioperative complications. We evaluated whether the introduction of the present on admission (POA) indicator improved outcome analysis of carotid endarterectomy (CEA) and carotid angioplasty and stenting (CAS) using administrative data. METHODS State inpatient databases from California (2005-2008), New York (2008), and New Jersey (2008) were used to identify patients undergoing CAS and CEA. We first analyzed morbidity data without the POA indicator, using International Classification of Diseases, Ninth Revision complication codes (eg, 997.02, iatrogenic cerebrovascular infarction or hemorrhage, postoperative stroke) and diagnosis codes (eg, 433.11, occlusion and stenosis of the carotid artery with cerebral infarction). Then, we applied the POA indicator to both diagnosis and complication codes and calculated the proportion of events that were labeled POA. Symptom status and perioperative stroke rate were compared using these coding approaches. RESULTS We identified 21,639 patients who underwent CEA and 3688 patients who underwent CAS. Without the POA indicator, the complication code for stroke indicated a postoperative stroke rate of 1.4% for CEA and 2.4% for CAS. After applying the POA indicator, 54% (CEA) and 62% (CAS) of these strokes were labeled POA. These POA strokes were either preoperative or intraoperative events. Proportion of symptomatic patients ranged from 7% to 16% for CEA and from 5% to 22% for CAS. Perioperative stroke rate was the lowest in the POA method (1.1% CEA, 1.8% CAS) compared with two other methods without POA information (1.4% and 9.5% CEA and 2.4% and 16.4% CAS). Kappa indicated a poor (0.2) to fair (0.7) agreement between these approaches. CONCLUSIONS Administrative data has known limitations for assignment of symptom status and nonfatal perioperative outcomes. Given the uncertain timing of POA events as preoperative vs intraoperative and its apparent underestimation of the perioperative stroke rate, the use of administrative data even with the POA indicator for symptom status and non-fatal outcomes after CEA and CAS is hazardous.

Characteristics that define high risk in carotid endarterectomy from the Vascular Study Group of New England

OBJECTIVE The Stenting with Angioplasty and Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial compared carotid endarterectomy (CEA) to carotid artery stenting (CAS) among high-risk patients using a model of risk that has not been validated by previous publications. The objective of our study was to determine the accuracy of this high-risk model and to determine the true risk factors that result in patients being at high risk for CEA. METHODS Prospectively collected data for 3098 CEAs between 2003 and 2011 at 20 Vascular Surgery Group of New England (VSGNE) centers were used. SAPPHIRE general inclusion criteria and primary outcomes were assessed. Factors that were associated with the primary outcome by analysis of variance (P < .10) and not linearly dependent, as determined by a Pearson correlation analysis, were further assessed for an independent association by multivariate logistic regression. A risk index model was developed for these significant predictors to accurately define high-risk CEA. RESULTS The average patient age was 69.9 ± 9.5 years, 60% were male, and 45.7% were asymptomatic. The 1-year composite outcome event rate, defined as postoperative myocardial infarction and stroke or death, was 14.2%. Multivariate analysis (P < .05) found the following independently significant risk factors: age in years (95% confidence interval [CI], 1.0-1.1; P < .001), preadmission living in a nursing home (95% CI, 1.2-6.6; P = .020), congestive heart failure (95% CI, 1.4-2.8; P < .001), diabetes mellitus (DM; 95% CI, 1.1-1.3; P < .001), chronic obstructive pulmonary disease (95% CI, 1.2-1.5; P < .001), any previous cerebrovascular disease (95% CI, 1.1-1.9; P = .003), and contralateral internal carotid artery stenosis (95% CI, 1.0-1.2; P = .001). Three of the SAPPHIRE high-risk criteria-abnormal stress test, recurrent stenosis after CEA, and previous radiotherapy to the neck-were not independently associated with an adverse outcome. Independently significant risk factors not included in the SAPPHIRE criteria are inclusion of ages <80 years, preadmission living in a nursing home, DM, contralateral carotid stenosis, and any previous cerebrovascular accident. The risk index predictors are age in years (40-49: 0 points; 50-59: 2 points; 60-69: 4 points; 70-79: 6 points; 80-89: 8 points), living in a nursing home (4 points), any cardiovascular disease (2 points), congestive heart failure (5 points), chronic obstructive pulmonary disease (3 points), DM (2 points), degree of contralateral stenosis (<50%: 0 points; 50%-69%: 1 point; 70%-near occlusion: 2 points; occlusion: 3 points). High-risk CEA is defined as >13 points, representing adverse outcome rate of 22.5%. CONCLUSIONS SAPPHIRE and other previously reported high-risk CAS inclusion criteria do not include all of the factors found to be independently associated with outcomes. Further studies are required to determine whether CAS is inferior to CEA in high-risk patients using a validated model of risk. In addition, this preoperative assessment includes novel criteria that can be used to stratify risks.