Prospective observation of neurological symptoms attributable to cerebral hyperfusion syndrome after CEA and CAS

A 64-year-old man with a past medical history of diabetes mellitus, hyperlipidemia, and hypertension presented with acute-onset left hemiparesis, hemisensory loss, and dysarthria. He was diagnosed with a right middle cerebral artery stroke and treated with systemic thrombolysis. His poststroke workup included a carotid duplex ultrasound and computed tomographic angiogram of the carotid arteries (Figure 1), which confirmed a severe (70%–99%) stenosis in the right internal carotid artery (ICA) secondary to a 20-mm-long atherosclerotic plaque extending from the carotid bifurcation to the level of C2-C3 disc space. The left ICA showed moderate (50%–69%) stenosis. Should this patient be recommended for carotid artery revascularization, and, if so, by which method? Figure 1. Computed tomographic angiogram of the 64-year-old patient presented in this case, showing severe right internal carotid artery stenosis (arrow) in coronal ( A ) and sagittal ( B ) views. Stroke, defined as acute development of a focal neurological deficit attributable to the disruption of blood flow to the brain, is caused by 1 of 2 main causes: ischemia or hemorrhage. The majority (>80%) of strokes are of ischemic etiology, of which ≈15% to 20% are attributable to atherosclerosis of the extracranial carotid arteries. The risk of death and recurrent stroke increases following an ischemic stroke. Transient ischemic attacks, or strokelike symptoms that last <24 hours, are also associated with an increased risk of early recurrent stroke, particularly in patients with carotid artery atherosclerosis. The bifurcation point of the common carotid artery, or carotid bulb, is predisposed to the development of atherosclerosis owing to low wall shear stress and resulting flow stagnation. Narrowing or stenosis of the carotid bulb and ICA because of atherosclerosis can lead to ischemic stroke secondary to plaque embolization or hypoperfusion. The prevalence of ICA stenosis is estimated to be 2% to 3% in the general population, with increased prevalence noted …

P rimarily on the basis of data derived from the Stenting and Angioplasty With Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial, 1 the US Food and Drug Administration (FDA) has approved the use of carotid stents (CASs) in high-risk patients.The SAPPHIRE trial was published and much heralded as a randomized trial demonstrating that CASs were not inferior to carotid endarterectomy (CEA).Yet, the more recent Endarterectomy Versus Angioplasty in Patients with Symptomatic Carotid Stenosis randomized trial of CASs compared with CEA had to be stopped because the stroke rate with stents was so high that it triggered the safety guidelines of the study design. 2How can we explain the striking difference in outcome between these 2 studies, and how did it happen that the FDA was so convinced of the quality and validity of the SAPPHIRE trial that it granted approval for CASs?An examination of the SAPPHIRE trial-its conduct, data collection and analysis, the circumstances of publication, the presentation to the FDA Advisory Panel, and its consequent approval-is the primary focus of this article.This is a case study of the flaws in our system for the evaluation and approval of medical devices that warrant serious reflection on our ability to properly create and act on accurate information and live up to our commitment to evidence-based decision making. Response by Samuelson et al p 1601As it now stands, existing studies leave us with the unfortunate but not unreasonable conclusion that no scientific basis exists for the use of CASs as approved by the FDA, and in the absence of change, there is every reason to doubt the capability of our current system to protect the public from unnecessary risk in the future.Although this article focuses on just 1 example of how our systems are flawed at multiple levels to provide a reliable assessment of CASs and other technology, readers seeking further examples can find a wealth of related information.

Cerebral Hyperperfusion Syndrome after Carotid Revascularization; Predictors and Complications.

Cerebral Hyperperfusion Syndrome Risk Comparison between Transcarotid Artery Revascularization and Carotid Artery Stenting with Distal Embolic Protection.

In Brief Cerebral hyperperfusion syndrome (CHS) is a complication that follows carotid artery revascularization by either carotid endarterectomy or carotid artery stenting. CHS typically presents with a triad of signs and symptoms including throbbing headache; focal neurologic deficits such as unilateral paresis, visual disturbance, or dysarthria; and seizures. Because CHS can result in significant morbidity and mortality, anticipation, early recognition, and aggressive management are essential to prevent disastrous complications such as intracerebral hemorrhage.1 Cerebral hyperperfusion syndrome (CHS) is a complication that follows carotid artery revascularization by either carotid endarterectomy or carotid artery stenting. Anticipation, early recognition, and aggressive management of CHS are essential to prevent disastrous complications.

One of the great achievements of modern medicine is the successful prevention of stroke and other cardiovascular diseases. Although the incidence of stroke has substantially declined over the last 30 years, ≈200 000 preventable stroke deaths still occur annually in the United States. According to a recent study based on the Greater Cincinnati/Northern Kentucky Stroke Study, annually ≈41 000 strokes in the United States are attributed to extracranial internal carotid artery stenosis. Early revascularization for symptomatic carotid stenosis—that is, in patients with recent ipsilateral stroke or TIA—is well established as effective at preventing ipsilateral stroke. Carotid stenosis in the absence of symptoms is extremely common, but the best treatment is unclear. While 2 randomized trials showed a benefit of carotid endarterectomy (CEA) over antiplatelet therapy with aspirin, the number needed to treat approaches 200. Does aggressive risk factor control change that balance? Population screening for carotid stenosis followed by revascularization is considered to cause net harm. Are complication rates from endarterectomy and stenting now low enough to justify expanding their indications in asymptomatic patients? The National Institute of Neurological Disorders and Stroke (NINDS)–funded CREST-2 trial (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial) is an ambitious attempt to further refine the treatment of asymptomatic carotid stenosis. As one of the largest randomized stroke prevention trials, the first CREST (Carotid Revascularization Endarterectomy Versus Stenting Trial) was designed to compare the safety and efficacy of 2 stroke prevention procedures for carotid artery narrowing—CEA and carotid artery stenting (CAS)—in symptomatic and asymptomatic individuals. Starting in December 2000, this NINDS-funded trial enrolled >2500 patients at 117 sites in the United States and Canada. Because of slow enrollment, the trial took 9 years to complete. In 2010, the results of CREST indicated that the 2 revascularization procedures were equivalent for …

Carotid artery disease is a major cause of ischemic stroke, the risk of which is directly related to the severity of stenosis and presence of symptoms.1,2 Stroke is the third leading cause of death in the United States, with approximately three quarters of a million strokes per year. Stroke is the leading cause of functional impairment, with more than 20% of survivors requiring institutional care and up to one third having a permanent disability.3 More worrisome, however, is the fact that as the population ages, the number of patients having strokes appears to be increasing.4 The pathophysiology of stroke may be broadly classified as hemorrhagic, embolic, or ischemic. The majority of strokes are caused by embolic events due to atheroemboli from the carotid artery, the ascending aorta, and arch vessels or cardiac thromboembolism from the left atrium or ventricle. It is estimated that carotid artery stenosis is responsible for 15% to 20% of all strokes.5 As percutaneous treatment options expand, there is uncertainty about appropriate therapy for carotid disease. This document will focus on 3 current controversies: (1) carotid artery revascularization in asymptomatic patients, (2) carotid artery stenting (CAS) in patients who are considered to be at increased surgical risk for carotid endarterectomy (CEA), and (3) the current role for CAS in patients at average surgical risk. ### Prevalence and Natural History The prevalence of asymptomatic extracranial carotid stenosis (≥50%) in persons >65 years of age is estimated to be between 5% and 10%, whereas ≤1% of patients are estimated to have a severe narrowing (>80%).6 In asymptomatic patients with ≥50% carotid artery stenoses, the annual risk of stroke is between 1% and 4.3%.2,7 Long-term (10- to 15-year) cohort studies in asymptomatic patients with moderate to severe carotid stenosis demonstrate an ipsilateral stroke rate between 0.9% and 1.1% per …

OBJECTIVEIntracranial hemorrhage (ICH) associated with cerebral hyperperfusion syndrome is a rare but major complication of carotid artery revascularization. The objective of this study was to compare the rate of ICH after carotid artery stenting (CAS) with that after endarterectomy (CEA).METHODSThe authors performed a retrospective population-based cohort study of patients who underwent carotid artery revascularization in the province of Ontario, Canada, between 2002 and 2015. The primary outcome was the rate of ICH that occurred within 90 days after carotid artery intervention among patients who underwent CAS versus that of those who underwent CEA. The authors used inverse probability of treatment weighting and propensity scores to account for selection bias. In sensitivity analyses, patients who had postprocedure ischemic stroke were excluded, and the following subgroups were examined: patients with symptomatic and asymptomatic carotid artery stenosis, patients treated between 2010 and 2015, and patients aged ≥ 66 years (to account for antiplatelet and anticoagulant use).RESULTSA total of 16,688 patients underwent carotid artery revascularization (14% CAS, 86% CEA). Patients with more comorbid illnesses, symptomatic carotid artery stenosis, or cardiac disease and those who were taking antiplatelet agents or warfarin before surgery were more likely to undergo CAS. Among the overall cohort, 80 (0.48%) patients developed ICH within 90 days (0.85% after CAS, 0.42% after CEA). The 180-day mortality rate after ICH in the overall cohort was 2.7%, whereas the 180-day mortality rate among patients who suffered ICH was 42.5% (40% for CAS-treated patients, 43.3% for CEA-treated patients). In the adjusted analysis, patients who underwent CAS were significantly more likely to have ICH than those who underwent CEA (adjusted OR 1.77; 95% CI 1.32-2.36; p < 0.001). These results were consistent after excluding patients who developed postprocedure ischemic stroke (adjusted OR 1.90; 95% CI 1.41-2.56) and consistent among symptomatic (adjusted OR 1.74; 95% CI 1.16-2.63) and asymptomatic (adjusted OR 1.75; 95% CI 1.16-2.63) patients with carotid artery stenosis, among patients treated between 2010 and 2015 (adjusted OR 2.21; 95% CI 1.45-3.38), and among the subgroup of patients aged ≥ 66 years (adjusted OR 1.53; 95% CI 1.05-2.24) after adjusting for medication use.CONCLUSIONSCAS is associated with a rare but higher risk of ICH relative to CEA. Future research is needed to devise strategies that minimize the risk of this serious complication after carotid artery revascularization.

Reversible cerebral vasoconstriction syndrome following carotid artery revascularization: About three case reports and review of literature

BackgroundOcular ischemic syndrome (OIS) and subsequent neovascular glaucoma (NVG) lead to irreversible visual impairment. This study aimed to investigate the association of carotid artery revascularization and the collateral circulation types...

Several randomized trials have emerged with conflicting data on the overall safety of carotid artery stenting (CAS) in comparison with carotid endarterectomy (CEA). The authors hypothesize that changes in national trends correspond to publication of randomized trials, including an increase in utilization of CAS after publication of trials favorable to CAS (for example, Carotid and Vertebral Artery Transluminal Angioplasty Study [CAVATAS] and Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy [SAPPHIRE]) and decrease in utilization of CAS after publication of trials favorable to CEA (for example, Endarterectomy versus Stenting in Patients with Symptomatic Severe Carotid Stenosis [EVA3-S] and Stent-Supported Percutaneous Angioplasty of the Carotid Artery versus Endarterectomy [SPACE]). The Nationwide Inpatient Sample was obtained for the years 1998-2008. Individual cases were isolated for principal diagnosis of unilateral or bilateral carotid artery stenosis or occlusion undergoing CEA or CAS. The percentage of CAS for all carotid revascularization procedures was calculated for each year. Perioperative inpatient morbidity, including stroke or death, were calculated and compared. The percentage of patients undergoing CAS increased yearly from the start of the observed period to the end, with the exception of a decrease in 2007. The peak utilization of CAS for carotid artery revascularization procedures was 15% of all cases in 2006. The stroke or death rate was consistent at 5% among all patients undergoing CEA for all years, while the incidence of stroke or death decreased among patients undergoing CAS from 9% in 1998 to 5% in 2008. The practice of CAS in the US is expanding, from less than 3% of all carotid artery revascularization procedures to 13% in 2008. The utilization of CAS was seen to correlate with publication of randomized trials. Utilization nearly doubled in 2005 after publication of the CAS-favorable SAPPHIRE in 2004, and decreased by 22% after publication of the CEA-favorable EVA-3S and SPACE in 2007. With the publication of Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST), the authors predict a resultant increase in the rate of CAS for carotid artery disease in the upcoming years.

Carotid artery revascularization can result in new ischemic brain lesions on diffusion-weighted magnetic resonance imaging. This study aimed to investigate the relationship between periprocedural ischemic diffusion-weighted imaging (DWI) lesions after carotid artery revascularization and recurrent long-term cerebrovascular events. A secondary observational prospective cohort analysis of existing clinical trial data was performed on 162 patients with symptomatic carotid stenosis that were previously randomized to carotid artery stenting or carotid endarterectomy in the ICSS (International Carotid Stenting Study) and included in the magnetic resonance imaging substudy. Magnetic resonance imagings were performed 1 to 7 days before and 1 to 3 days after treatment. The primary composite clinical outcome was the time to any stroke or transient ischemic attack during follow-up. Patients with new diffusion-weighted imaging (DWI) lesions on posttreatment magnetic resonance imaging scan (DWI+) were compared with patients without new lesions (DWI-). The median time of follow-up was 8.6 years (interquartile range, 5.0-12.5). Kaplan-Meier cumulative incidence for the primary outcome after 12.5-year follow-up was 35.3% (SE, 8.9%) in DWI+ patients and 31.1% (SE, 5.6%) in DWI- patients. Uni- and multivariable regression analyses did not show significant differences (hazard ratio, 1.50 [95% CI, 0.76-2.94] and hazard ratio, 1.30 [95% CI, 0.10-1.02], respectively). Higher event rate of the primary outcome in DWI+ patients in the overall cohort was mainly caused by events in the carotid artery stenting group. Based on our outcome analysis within the ICSS magnetic resonance imaging substudy, DWI lesions following carotid revascularization did not seem to have a relationship with long-term stroke risk. URL: https://www. gov; Unique identifier: ISRCTN 25337470.

Impact of diabetes on carotid artery revascularization

The aim of this study was to assess the association of kidney function with carotid artery revascularization outcomes in a large contemporary database. Chronic kidney disease (CKD) is associated with increased mortality and adverse cardiovascular events after coronary intervention. There are limited data evaluating the association between CKD and adverse events among patients undergoing carotid artery revascularization procedures. The Carotid Artery Revascularization and Endarterectomy (CARE) Registry is a voluntary registry of 168 hospitals. Using data from the CARE Registry, we examined registry patients undergoing carotid artery revascularization by either carotid endarterectomy (CEA) or carotid artery stenting (CAS) from May 2005 through March 2010. Patients were divided into four groups according to their glomerular filtration rate (GFR), as estimated by the Modification of Diet in Renal Disease Study Group equation using preprocedural serum creatinine levels. The analysis included 11,832 patients who underwent carotid revascularization (6,899 CAS and 4,933 CEA). Patients with lower GFR were older, more frequently female, had more comorbidities, including hypertension, dyslipidemia, peripheral arterial disease, diabetes mellitus, chronic lung disease, ischemic heart disease, heart failure, and reduced left ventricular function, and were more likely to undergo CAS than CEA. In the overall population, CKD was associated with higher unadjusted in-hospital and 30-day rates of the combined endpoint of death, stroke, and myocardial infarction and the individual endpoint of stroke. After adjustment for baseline and preprocedural characteristics, CKD was not an independent predictor of adverse events in either CAS or CEA. Patients with CKD have a greater number of comorbidities and worse unadjusted in-hospital and 30-day outcomes; CKD was not, however, an independent predictor of in-hospital and 30-day outcomes after carotid artery revascularization.

The baroreceptor at the carotid body plays an important role in hemodynamic autoregulation. Manipulation of the baroreceptor during carotid endarterectomy (CEA) or radial force from carotid artery angioplasty and/or stenting (CAS) may cause both intraoperative and postoperative hemodynamic instability. The purpose of this study is to evaluate the long-term effects of CEA and CAS on blood pressure (BP), heart rate (HR), and subsequent changes on antihypertensive medications. A retrospective chart review was performed to identify patients who underwent CEA or CAS between 2009 and 2015 at a single tertiary care institution. Baseline demographics and comorbidities were recorded. Operative details of the carotid artery endarterectomy and the use of balloon angioplasty during the CAS were analyzed. Hemodynamic parameters such as BP, HR, and antihypertensive medication requirement were evaluated at 3, 6, 12, 24, and 36 months. A total of 289 patients were identified. The average age was 70.6 years old, and males constituted 64.0%. All patients had moderate (>50%) to severe (>70%) carotid stenosis. Of those, 111 (40.5%) patients were symptomatic. Systolic BP (mm Hg) of CAS and CEA were similar over the entire follow-up period. Heart rate (beats/min) remained stable postoperatively. A reduced number of antihypertensive medications was observed in the CAS cohort during the first postoperative year when compared to the preoperative baseline: 2.03 at preop, 1.77 ( P < .01) at 3 months, 1.78 ( P = .02) at 6 months, 1.77 ( P = .02) at 12 months, 1.86 ( P = .09) at 24 months, and 2.03 ( P = =.50) at 36 months. Logistic regression analysis identified that CAS (odds ratio [OR]: 2.52, confidence interval [CI]: 1.09-5.83) and multiple (>2) antihypertensive medication use at baseline (OR: 5.89, CI: 2.62-13.26) were predictors for a reduction in the number of antihypertensive medications following carotid revascularization. Surgical intervention for carotid stenosis poses a risk of postoperative hemodynamic dysregulation. Although postoperative BP and HR remained relatively stable after both CAS and CEA, the number of postoperative antihypertensive medications was reduced in the CAS cohort for the first postoperative year when compared to baseline. Patients with multiple antihypertensive agents undergoing CAS should have close postoperative BP monitoring and should be monitored for a possible reduction in their antihypertensive medication regimen.