High-grade Carotid Artery Stenosis Research Articles

Association Between Total Cholesterol and 5 year Mortality in Patients with Carotid Artery Stenosis and Poststroke Functional Dependence

Background: Aggressive lipid-lowering treatment reduces the risk of cardiovascular events, but remains controversial in stroke patients. We investigate the influence of total cholesterol level on 5-year outcomes of ischemic stroke patients with high-grade internal carotid artery (ICA) stenosis and poststroke functional dependence.Methods: One-hundred and ninety-six acute ischemic stroke patients with high-grade ICA stenosis and modified Rankin Scale score ≥ 3 upon discharge were enrolled and prospectively observed for 5 years. Patients were divided into 2 groups according to total cholesterol level at admission: ≥200 mg/dL or <200 mg/dL. Demographic features, vascular risk factors, co-morbidities, and outcomes were compared between the 2 groups. Results: 117 (59.7%) patients had higher and 79 (40.3%) patients had lower total cholesterol levels. The prevalence of older age and atrial fibrillation was significantly higher in patients with lower total cholesterol; the prevalence of diabetes mellitus was higher in patients with higher total cholesterol. After adjusting for the established clinical predictors of adverse outcomes, the multivariate Cox regression revealed that lower total cholesterol level is a significant predictor of 5-year mortality (HR (hazard ratio) = 1.88, 95% CI (confidence interval) = 1.09-3.23, P = .023). Conclusions: Lower total cholesterol level is associated with increased risk of 5-year mortality in ischemic stroke patients with high-grade ICA stenosis and post-stroke functional dependence. Aggressive treatment of hyperlipidemia should be carefully considered in these patients although it could reduce the risk of atherosclerotic cardiovascular diseases and stroke recurrence in some stroke patients.

Dynamics of brain perfusion and cognitive performance in revascularization of carotid artery stenosis.

IntroductionThere is evidence suggesting a detrimental effect of asymptomatic carotid artery stenosis on cognitive function even in the absence of ischemic cerebral lesions. Hypoperfusion has been suggested as pathophysiological mechanism causing cognitive impairment. We aimed to assess cognitive performance and cerebral perfusion changes in patients with carotid artery stenosis without ischemic lesions by arterial spin labeling (ASL) and contrast enhanced (CE) perfusion MRI before and after revascularization therapy.Methods17 asymptomatic patients with unilateral high-grade (≥70%) carotid artery stenosis without evidence of structural brain lesions underwent ASL and CE perfusion MRI and cognitive testing (MMSE, DemTect, Clock-Drawing Test, Trail-Making Test, Stroop Test) before and 6–8 weeks after revascularization therapy by endarterectomy or stenting. Multiparametric perfusion maps (ASL: cerebral blood flow (ASL-CBF), bolus arrival time (ASL-BAT); CE: cerebral blood flow (CE-CBF), mean transit time (CE-MTT), cerebral blood volume (CE-CBV)) were calculated and analyzed by vascular territory. Relative perfusion values were calculated.ResultsMultivariate analysis revealed a significant impact of revascularization therapy on all perfusion measures analyzed. At baseline post-hoc testing showed significant hypoperfusion in MCA borderzones as assessed by ASL-CBF, ASL-BAT, CE-MTT and CE-CBV. All perfusion alterations normalized after revascularization. We did not observe any significant correlation of cognitive test results with perfusion parameters. There was no significant change in cognitive performance after revascularization.ConclusionWe found evidence of traceable perfusion alterations in patients with high grade carotid artery stenosis in the absence of structural brain lesions, which proved fully reversible after revascularization therapy. In this cohort of asymptomatic patients we did not observe an association of hypoperfusion with cognitive performance.

Severe, recurrent in-stent carotid restenosis: endovascular approach, risk factors. Results from a prospective academic registry of 2637 consecutive carotid artery stenting procedures (TARGET-CAS).

IntroductionOptimal management of severe carotid in-stent restenosis remains unknown. Prevalence and risk factors of first and recurrent carotid in-stent restenosis in the multi-stent approach have not been established yet.AimTo evaluate the safety of different methods of endovascular treatment of carotid in-stent restenosis/recurrent restenosis and to establish its rate and risk factors.Material and methodsBetween January 2001 and June 2016, 2637 neuroprotected carotid artery stenting (CAS) procedures were performed in 2443 patients (men: 67.0%; mean age: 67.9 ±8.8 years, symptomatic: 45.5%). Doppler ultrasound (DUS) evaluation was performed at discharge, after 3–6 months, 12 months, and then annually. Peak systolic velocity of 2–3 and > 3.0 m/s as well as end diastolic velocity of 0.5–0.9 and > 0.9 m/s were DUS criteria for 50–69% and ≥ 70% carotid in-stent restenosis (ISR) respectively. For angiographically confirmed ≥ 70% stenosis balloon re-angioplasty was first line treatment.ResultsOut of 95 DUS detected > 50% ISR (95/2637; 3.6%), 53 were confirmed in angiography as ≥ 70% (53/2637; 2.0%, one total occlusion). All patients were treated with bare balloon (n = 19), drug-eluting balloon (n = 27) or stent-supported (n = 6) angioplasty. One procedure was complicated with stroke (1.9%). Angiographic diameter stenosis (DS) was reduced from 83 ±8.3% to 13 ±7.6% (p < 0.001). There were 13 cases of ≥ 70% recurrent ISR. Bilateral and high-grade stenosis were independent risk factors of restenosis. Initial Carotid Wallstent implantation was a risk factor of first and recurrent in-stent restenosis.ConclusionsEndovascular treatment of carotid in-stent restenosis is safe. Bilateral and high-grade carotid artery stenosis may increase the risk of restenosis. Initial Carotid Wallstent implantation may increase the risk of first and recurrent restenosis.

The stronger one-sided relative hypoperfusion, the more pronounced ipsilateral spatial attentional bias in patients with asymptomatic carotid stenosis

Patients with asymptomatic, high-grade internal carotid artery stenosis often suffer from subtle cognitive impairments with unclear underlying neuro-cognitive mechanisms. Thus, we hypothesized that stenosis-related unilateral cerebral hypoperfusion leads to an ipsilateral attentional bias; 22 patients with asymptomatic, one-sided high-grade carotid stenosis and 24 age-matched healthy controls underwent pseudo-continuous arterial spin labeling to assess brain perfusion in the territory of the carotid arteries. Furthermore, a parametric assessment of attention functions was carried out on the basis of the computational Theory of Visual Attention. Both patients' perfusion and spatial attention were significantly more lateralized than those of healthy controls. Critically, both asymmetry indices were significantly correlated in patients, i.e. the stronger one-sided relative hypoperfusion, the stronger ipsilateral bias of attention. This association was specifically pronounced in parietal cortices and independent of white matter hyperintensities as a surrogate for cerebrovascular brain damage. Results provide evidence for a link between lateralized hypoperfusion and lateralized attentional weighting in asymptomatic, high-grade carotid stenosis. Data suggest that lateralized hypoperfusion with simultaneous spatial attentional bias might serve as a potential therapeutic target in one-sided carotid stenosis.

Association between Circulatory and Plaque Resistin Levels with Carotid Plaque Instability and Ischemic Stroke Events.

40 patients with ischemic stroke events and 38 neurologically asymptomatic patients scheduled for carotid endarterectomy were recruited for this study. Fasting blood samples for laboratory analysis were collected preoperatively and serum resistin levels were measured by enzyme-linked immunosorbent assays. Carotid endarterectomy specimens were analyzed according to the gold-standard procedure of histological classification. Plaque resistin expression was determined by standard immunohistochemical procedure. Serum resistin levels and resistin plaque expression were found to be significantly higher in subjects with unstable carotid plaque (P < .001) while significantly higher serum resistin levels were also present in patients with ischemic stroke events (P < .001). In univariate stepwise logistic regression analysis, higher serum resistin levels were significantly associated with plaque instability (OR 2.223, 95% CI 1.488-3.320, P < .0001) and ischemic stroke events (OR 1.237, 95% CI 1.079-1.420, P = .002). There was also a significant association between higher serum and plaque resistin expression (OR 1.663, 95% CI1.332-2.077, P < .0001). These associations remained significant in all models of multivariate logistic regression analysis. High serum and plaque resistin levels were also significantly associated with specific histological features of plaque instability. The results suggests that serum resistin levels may be used as a potential biomarker of plaque vulnerability and ischemic stroke events in patients with moderate- to high-grade carotid artery stenosis and highlight the possible relationship that plaque resistin expression has with histological features of plaque vulnerability.

NESVS16. Carotid Duplex Velocity Criteria Recommended by the Society of Radiologists in Ultrasound and Endorsed by the Intersocietal Accreditation Commission Lack Predictive Ability for Identifying High-Grade Carotid Artery Stenosis

Carotid duplex ultrasound is the first-line imaging modality for characterizing degree of carotid artery stenosis. The Intersocietal Accreditation Commission, in published guideline documents, has endorsed use of the Society of Radiologists in Ultrasound (SRU) criteria to characterize ≥70% stenosis: peak systolic velocity (PSV) ≥230 cm/s. We sought to perform a validation of the SRU criteria using computed tomography (CT) angiography as a “gold standard” imaging modality and to perform a sensitivity analysis to determine optimal velocity criteria for identifying ≥80% stenosis. We queried all carotid duplex ultrasound examinations performed at our institution between 2008 and 2017. Patients with ≥70% carotid stenosis, based on previous criteria, and further narrowed to those with minimum PSV ≥300 cm/s or end-diastolic velocity (EDV) ≥100 cm/s were identified. Of these patients, those who also had CT angiography of the neck within 1 year formed the study cohort. Patients who underwent carotid revascularization between the two imaging dates were excluded. Degree of stenosis, as reported from the CT angiogram, was considered the true degree of stenosis. Receiver operating characteristic curves were generated to evaluate the SRU criteria and to identify the optimal discrimination threshold for high-grade carotid stenosis. Of 37,204 carotid duplex ultrasound examinations, 3478 arteries met criteria for ≥70% stenosis. Of these, 344 patients had CT angiography within 1 year of the carotid duplex ultrasound examination (mean time between studies, 55 days; standard deviation, 6.5), and 240 (69.8%) were consistent with ≥80% carotid stenosis. The predictive ability of the SRU criteria to identify ≥70% stenosis was poor, with an area under the curve of 0.51. A sensitivity analysis to identify ≥80% stenosis demonstrated the optimal discrimination threshold to be PSV ≥450 cm/s or EDV ≥120 cm/s, with an area under the curve of 0.66 (Fig). In this validation study, the SRU criteria, endorsed by the Intersocietal Accreditation Commission, to identify ≥70% carotid stenosis have no predictive value. For detection of ≥80% stenosis, the optimal criteria are PSV ≥450 cm/s and EDV ≥120 cm/s. This study demonstrates the critical importance of carotid duplex ultrasound examination validation.

Temporary Reversal of Blood Flow During Transcarotid Artery Revascularization Does Not Change Brain Electrical Activity in Lead-In Cases of the ROADSTER 1 Multicenter Trial

Purpose: To evaluate any intraoperative electroencephalographic (EEG) changes accompanying reversed flow with the ENROUTE Transcarotid Neuroprotection System during transcarotid artery revascularization (TCAR). Methods: A post hoc analysis was performed of the first 81 consecutive lead-in patients (mean age 72.8±8 years; 61 men) enrolled in the ROADSTER 1 trial at 5 participating institutions. All patients had high-grade carotid artery stenosis [53 (59.3%) left sided; 12 (14.8%) contralateral occlusions] and high-risk criteria for carotid endarterectomy. A third had symptoms of either stroke (13, 16.0%) or transient ischemic attack (14, 17.3%). This subset of early patients underwent EEG monitoring to detect any cerebral changes during reversed flow as an added safety measure mandated by the ROADSTER 1 trial protocol. Results: Mean flow reversal time was 12.9±8.2 minutes. The goal mean arterial pressure during reversed flow was 100 mm Hg, but 7 (8.6%) patients suffered hypotension. One (1.2%) patient had slight EEG changes secondary to blood pressure fluctuation; these resolved with blood pressure elevation. No other EEG changes were noted. One (1.2%) patient had a postoperative stroke and another (1.2%) had postoperative myocardial infarction (MI), leading to 2.5% 30-day stroke/death/MI rate. Conclusion: Temporary reversal of blood flow during TCAR is a safe maneuver and does not cause cerebral ischemia in the vast majority of patients, including those with contralateral carotid occlusion. Carotid stenting performed with reversed blood flow mitigates cerebral embolization and periprocedural stroke without concern for brain ischemia.

Association Between Stroke Severity and 5-Year Mortality in Ischemic Stroke Patients with High-Grade Stenosis of Internal Carotid Artery

BackgroundThe clinical presentations and outcomes of patients with high-grade stenosis of internal carotid artery (ICA) are highly variable. We investigate the influence of different stroke severity on outcomes of ischemic stroke patients with high-grade stenosis of ipsilateral ICA. Methods372 acute first-ever ischemic stroke patients with high-grade stenosis (70%-99%) or occlusion of ipsilateral ICA were enrolled and followed up for 5years. Stroke severities of the enrolled patients were grouped according to the Oxfordshire Community Stroke Project classification system as total anterior circulation infarcts (TACI) or non-TACI. Demographic features, vascular risk factors, comorbidities, and outcomes were compared between the 2 groups. ResultsA total of 71 patients (19.1%) were presented with TACI. Of laboratory data, the values of white blood cell count and high-sensitivity C-reactive protein were significantly higher in patients with TACI (P = .008 and P = .003, respectively). Of clinical course, the occurrence of initial impaired conscious, stroke-in-evolution, pneumonia, gastrointestinal bleeding, and urinary tract infection were significantly higher in patients with TACI. The prevalence of dependent functional status was higher in patients with TACI. Multivariate Cox regression revealed that TACI is a significant predictor of 5-year all-cause mortality in first-ever ischemic stroke patients with high-grade stenosis of ipsilateral ICA (HR [hazard ratio] = 3.66, 95% confidence interval = 2.23-6.00, P < .001). ConclusionsTACI is associated with increased risk of 5-year mortality in ischemic stroke patients with high-grade stenosis of ipsilateral ICA. Intensive medical treatment for stroke prevention in patients with severe carotid artery stenosis is warranted.

Early carotid artery stenting after onset neurologic symptoms

Multicenter clinical trials level 1 evidence favors the application of carotid endarterectomy in symptomatic patients, especially the in the elderly cohort. Carotid artery stenting has been proposed as a possible early alternative in selected patients after onset of ipsilateral neurologic symptoms. It is well known that treatment of acute stroke is time-dependent in patients with acute ischemic stroke caused by high-grade stenosis of the internal carotid artery, but intensive medical treatment in conjunction with intervention to improve stroke severity and clinical outcomes has not been established. Two major clinical concerns exist: (1) the risk of hemorrhagic infarction after cerebral revascularization in the acute stage and (2) application of carotid stenting in the acute embolic stage, which may be associated with continued embolic risk after carotid artery stenting compared to carotid endarterectomy, which removes the symptomatic plaque. This review summarizes the indications and results of early carotid artery stenting after onset of neurologic symptoms, considering the new carotid stents and cerebral protection systems available for clinical use and enhanced stenting techniques.

Safety and effectiveness of selective carotid angioplasty prior to cardiac surgery: a single-centre matched case-control study.

Reducing the rate of postoperative stroke after cardiac surgery remains challenging, especially in patients with occlusive cerebrovascular disease. Angioplasty in all patients with high-grade carotid artery stenosis has not been shown to be effective in reducing the post-surgical stroke rate. In this study, we present the initial results of a different approach using selective carotid angioplasty only in patients with poor intracranial collaterals. We conducted a single-centre study to assess the safety of this procedure. The postangioplasty complication rate of the study group was compared to that of patients who were scheduled for symptomatic carotid artery angioplasty. To determine the effectiveness of this procedure, the post-cardiac surgery complication rate of the study group was compared with that of the matched case controls. Twenty-two patients were treated with selective carotid angioplasty without developing persistent major neurological complications. All patients except 1 patient subsequently underwent surgery without developing persistent major neurological disabilities. Two patients died of cardiogenic shock within 30 days. Selective carotid angioplasty prior to cardiac surgery in patients with a presumed high risk of stroke was relatively safe and effective in this study group. Although this strategy does not prevent stroke in these high-risk patients, data suggest that this approach shifts the postoperative type of stroke from a severe haemodynamic stroke towards a minor embolic stroke with favourable neurological outcomes. Larger studies are needed to determine whether this strategy can effectively eliminate the occurrence of haemodynamic stroke after cardiac surgery.

Coexistent Ipsilateral Internal Carotid Artery Occlusion and Cerebral Venous Thrombosis in Hepatitis C.

A 58-year-old male, known to have hepatitis C virus (HCV), presented with intermittent headaches and left-sided sensorimotor symptoms. There were no focal neurological deficits on examination. Electrocardiogram was unremarkable. Computed tomography angiography head and neck displayed extracranial right internal carotid artery occlusion. Magnetic resonance imaging showed right cortical vein thrombosis, with hemorrhagic infarction. Echocardiography with bubble study was unremarkable. Hypercoagulable workup was significant for protein S deficiency. He was treated with warfarin for 6 months. Repeat protein S levels remained low 9 months later. The coexistence of arterial and venous thrombotic events gives rise to a limited differential. In this case, it may be related to chronic HCV infection. The underlying pathogenesis is not clear; however, it is possible the patient had chronic high-grade internal carotid artery stenosis, which occluded leading to his presenting symptoms. The cortical vein thrombosis is likely an incidental finding here. The extent by which HCV contributed to the cerebral thrombosis and carotid artery occlusion in our case is not clear; however, the hypercoagulable and atherosclerotic properties of the virus cannot be disregarded. The virus can promote carotid atherosclerosis and cerebral venous thrombosis as well as other venous and arterial thromboembolic events. Furthermore, HCV is associated with impaired venous flow and procoagulant properties, which can fuel a hypercoagulable state. Also of note cirrhosis is associated with protein S deficiency. We recommend considering an underlying hypercoagulable state including both arterial and venous thrombosis in HCV infection.

Neurocognitive functioning and cerebrovascular reactivity after carotid endarterectomy.

To evaluate in patients with TIA and ipsilateral high-grade internal carotid artery (ICA) stenosis whether changes in cognitive performance and cerebral hemodynamics occurred after carotid endarterectomy (CEA) and to explore their relationship. Participants were patients who underwent CEA, had TIA within the last 6 months, and had an ipsilateral severe ICA stenosis. Coloured Progressive Matrices (CPM) plus Complex Figure Copy Test (CFCT) and phonemic (ph) plus categorical (ca) Verbal Fluency (VF) tests were performed to assess right and left hemisphere cognitive functions, respectively. Hemodynamics was assessed with transcranial Doppler ultrasonography by means of the cerebral vasomotor reactivity (CVR) to hypercapnia. A total of 137 patients were included. Before CEA, patients with right ICA obtained lower scores on the CPM and CFCT; patients with left ICA stenosis performed worse on the phonemic and categorical VF tests. The CVR was decreased on the side of the stenosis. At 6 months from CEA, CVR and cognitive performance were significantly improved. The performance change in cognitive tests exploring the revascularized hemisphere was positively associated with the ipsilateral CVR variation (CPM: R2 for linear regression = 0.759, adjR2 = 0.737; CFCT: R2 = 0.734, adjR2 = 0.710; (ph)VF: R2 = 0.774, adjR2 = 0.749; (ca)VF: R2 = 0.732, adjR2 = 0.703). Cognitive performance was enhanced at 6 months since CEA, and the improvement was related to the CVR increase. Cerebral hemodynamics may be an independent and potentially reversible determinant of cognitive dysfunction in severe carotid artery disease.

Predictive Value of Dynamic Cerebral Autoregulation Assessment in Surgical Management of Patients with High-Grade Carotid Artery Stenosis.

Dynamic cerebral autoregulation (DCA) capacity along with the degree of internal carotid artery (ICA) stenosis and characteristics of the plaque can also play an important role in selection of appropriate treatment strategy. This study aims to classify the patients with severe ICA stenosis according to preoperative state of DCA and to assess its dynamics after surgery. Thirty-five patients with severe ICA stenosis having different clinical type of disease underwent reconstructive surgery. DCA was assessed with transfer function analysis (TFA) by calculating phase shift (PS) between Mayer waves of blood flow velocity (BFV) and blood pressure (BP) before and after operation. In 18 cases, regardless of clinical type, preoperative PS on ipsilateral side was within the normal range and did not change considerably after surgery. In other 17 cases preoperative PS was reliably lower both in patients with symptomatic and asymptomatic stenosis. Surgical reconstruction led to restoration of impaired DCA evidenced by significant increase of PS in postoperative period. Our data suggest that regardless clinical type of disease various state of DCA may be present in patients with severe ICA stenosis. This finding can contribute to establishing the optimal treatment strategy, and first of all for asymptomatic patients. Patients with compromised DCA should be considered as ones with higher risk of stroke and first candidates for reconstructive surgery.

170 Vasa Vasorum Activities in Human Carotid Atherosclerosis is Associated with Plaque Development and Vulnerability

Abstract INTRODUCTION Carotid endarterectomy (CEA) has been shown to be beneficial in patients with high-grade symptomatic carotid artery stenosis. Subintimal and intraplaque hemorrhages are frequently seen during CEA in the absence of any visible breach in the intima, as these changes are derived from the vasa vasorum system rather than from blood in the vessel lumen. Imaging modalities to characterize unstable, vulnerable plaques are strongly needed for better risk stratification in these patients. The aim of this study was to investigate the correlation between the activities of the carotid vasa vasorum and carotid plaque vulnerability using indocyanine green-video angiography (ICG-VA) during CEA, focusing on how the carotid artery vasa vasorum is depicted. METHODS Sixty-nine patients (mean age, 68.5 ± 2.5 years; mean degree of stenosis, 78.9 ± 3.8) who underwent CEA were enrolled prospectively from September 2013 to December 2014. ICG was injected intravenously as a bolus before and after resecting the atheroma during CEA. We also performed immunohistochemistry using CD68 (macrophage), CD117 (mast cell), CD4 (T-cell), and CD8 (T-cell) antibodies for resected plaque specimens. RESULTS &gt;Active vasa vasorum density was observed in all patients on ICG-VA (n = 69). The vasa vasorum externa (VVE) and interna (VVI) were seen in 11 (16%) and 57 patients (82.6%), respectively. The types of VVE were strongly associated with preoperative angiographic instability (90.0%, P = 0.005) and carotid plaque vulnerability (100%, P = 0.007) macroscopically. In contrast, the types of VVI were less associated with angiographic instability (36.1%) and plaque vulnerability (49.1%, P = 0.003). CD86- and CD117-stained macrophages and mast cells were observed more frequently in unstable plaque, compared to those in stable plaque (P &lt; 0.0001, P = 0.002, respectively). CONCLUSION The early appearance of VVE on ICG-VA was strongly associated with unstable carotid plaque and many microvessel channels that provided nutrients to the developing and expanding intima and potentially created an unstable hemorrhagic environment prone to rupture. Macrophages and mast cells were involved in the formation of microvessels in the atherogenic plaque and accelerated plaque progression into an unstable plaque phenotype.

Stent-induced flow disturbances in the ipsilateral external carotid artery following internal carotid artery stenting: atemporary cause of jaw claudication.

SummaryBackgroundWe hypothesize that stenting of the internal carotid artery can immediately impede blood flow to the external carotid artery by either plaque shift or stent coverage of the ostium, and thereby cause ischemic symptoms like ipsilateral jaw claudication.MethodsThirty-three patients with high-grade asymptomatic stenosis of the internal carotid artery who underwent endovascular treatment were examined by ultrasound of the external carotid artery and performed an exercise test by chewing chewing gum synchronously to an electronic metronome for 3 min. Tests were performed before, the day after, and 1 week after the stenting procedure. Claudication time was defined as the timespan until occurrence of pain of the masseter muscle and/or chewing dyssynchrony to the metronome for more than 15 s. Ten patients with an isolated, atherosclerotic stenosis of the external carotid artery served as controls.ResultsA significantly reduced claudication time (in seconds) was recorded in patients who underwent carotid artery stenting compared to baseline values; median 89 (interquartile range, IQR, 57 to 124) vs. median 180 (IQR 153 to 180; p < 0.001). By categorization of the flow velocity at the external carotid artery into faster or slower as 200 cm/sec, the effect was even accentuated. Stenting values showed improvement 1 week after but did not return to baseline levels. No respective changes were found in controls.ConclusionStenting of the internal carotid artery lead to ipsilateral flow deterioration at the external carotid artery resulting in temporary jaw claudication. This impairment attenuated over the time and was significantly reduced after 1 week.

Intracranial Blood Flow Changes in Patients with High-Grade Severe Carotid Artery Stenosis After Stenting

We investigated whether the cerebral hemodynamic changes of pre- and poststenting in patients with severe carotid stenosis differ by stenosis grades. We prospectively recruited patients who underwent carotid artery stenting (CAS) after acute ischemic stroke from June 2014 to December 2015. We compared the mean relative cerebral blood flow (rCBF) changes (measured by whole-brain computed tomography perfusion) pre- and poststenting in patients with high-grade severe stenosis (HGSS) (90%-99%) versus patients with low-grade severe stenosis (LGSS) (70%-89%). Among 24 patients included in the study (mean age, 66.2 ± 7.2 years; 91.7% men), 62.5% (15/24) were in the HGSS group and 37.5% (9/24) were in the LGSS group. In the HGSS group, rCBF increased in territories of the anterior cerebral artery (P= 0.021), middle cerebral artery (P<0.001), posterior cerebral artery (P=0.001), and basil ganglia (P= 0.003) after stenting. Of the patients with HGSS, 53.3% (8/15) had collateral flow through anterior communicating artery (AcomA) prestenting. After stenting, all the AcomA collaterals in HGSS reverted to normal (P= 0.002). The improvement of brain perfusion combined with the normalization of collateral flow through the circle of Willis after CAS was observed only in patients with HGSS.

Abstract 95: MiRNA-210 Enhances Fibrous Cap Stability in Advanced Atherosclerotic Lesions

In the search for markers and modulators of vascular disease, miRNAs have emerged as potent therapeutic targets. We investigated miRNAs of clinical interest in patients with unstable carotid stenosis at risk of stroke. Utilizing patient material from the Biobank of Karolinska Endarterectomies (BiKE), we profiled miRNA expression in symptomatic versus asymptomatic patients with high-grade carotid artery stenosis. A PCR-based miRNA of plasma, sampled at the carotid lesion site, identified eight deregulated miRNAs (miR-15b, -29c, -30c/d, -150, -191, -210 and -500). miR-210 was the most significantly downregulated miRNA in local plasma material. Laser-capture microdissection as well as in situ hybridization revealed a distinct localization of miR-210 in the fibrous caps of atherosclerotic lesions and showed reduced miR-210 expression in the unstable fibrous cap. We confirmed that miR-210 directly targets the tumor suppressor gene adenomatous polyposis coli (APC), thereby affecting Wnt signaling and regulating vascular smooth muscle cell survival, as well as differentiation, in advanced atherosclerotic lesions. Substantial changes in arterial miR-210 were detectable in two rodent models of vascular remodeling and plaque rupture. Modulating miR-210 in vitro and in vivo improved fibrous cap stability with implications for vascular disease. We discovered that an unstable carotid plaque at risk of stroke is characterized by low expression of miR-210. miR-210 contributes to stabilizing carotid plaques through inhibition of APC, ensuring vascular smooth muscle cell survival. We present local delivery of miR-210 as a therapeutic approach for prevention of atherothrombotic disease.

Identification of neovascularization by contrast-enhanced ultrasound to detect unstable carotid stenosis.

BackgroundPlaque neovascularization accompanies local inflammation and critically contributes to plaque instability. Correct identification of intraplaque neovascularization by contrast–enhanced ultrasound (CEUS) may provide an additional risk marker in carotid stenosis. This pilot study investigates the correlation between histological evaluation of carotid plaque specimens and pre-surgery CEUS to identify neovascularization.Methods17 patients with high-grade internal carotid artery (ICA) stenosis were studied. CEUS was performed in all patients shortly before carotid endarterectomy. Neovascularization, infiltration of T cells and macrophages along with intraplaque hemorrhage were studied in excised plaques by immunohistochemistry. Ultrasound-based four-level and two-level classification systems for neovascularization were used. CEUS findings were compared with histological findings.ResultsScores on the CEUS-based four-level and two-level classifications were robustly correlated with the density of intraplaque vessels (r = 0.635, p = 0.006 and r = 0.578, p = 0.015, respectively). Histological evaluation of regions with strong and prolonged intraplaque enhancement typically showed strong intraplaque neovascularization in conjunction with acute intraplaque hemorrhage. Moreover, higher grades of intraplaque neovascularization as determined by ultrasound were associated with a higher percentage of macrophage-rich areas.ConclusionCEUS is a technique well suited to gauge the degree of neovascularization of carotid plaques. Future research will have to define the reliability and validity of CEUS in everyday clinical practice. Further, our study suggests that CEUS may also be useful to pick up features of vulnerable plaques such as acute intraplaque hemorrhages.

Clinical need, design, and goals for the Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis trial

Prior clinical trials produced evidence-based treatment recommendations for patients with asymptomatic carotid stenosis that may not be appropriate for clinical decision-making today. High-quality patient outcomes data to allow informed decision making regarding the optimal management of high-grade asymptomatic internal carotid artery stenosis is lacking. The results of the Asymptomatic Carotid Atherosclerosis Study were published in 1995 based on a randomized patient enrollment in the 1990s. Outcomes after endarterectomy, stenting, and medical treatment for these patients have all improved in the subsequent 2 decades. Therefore, the time has come to test whether contemporary intensive medical therapy is an acceptable alternative to contemporary endarterectomy or stenting and is the rationale for the Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis (CREST-2) trial. This National Institute of Neurological Disorders and Stroke−sponsored prospective, multicenter clinical trial has the investigators, study teams, asymptomatic patients, and robust study design needed to provide these answers. Two randomized clinical trials are planned: carotid revascularization and intensive medical management versus medical management alone in patients with asymptomatic high-grade carotid stenosis randomize in a 1:1 ratio; the other trial will randomize patients in a 1:1 ratio to carotid stenting with embolic protection versus no stenting. ClinicalTrials.gov Identifier: NCT02089217.

Carotid artery stenting by non-femoral arterial approach in patients with difficult anatomy

Background: Carotid endarterectomy (CEA) and carotid artery stenting (CAS) are safe, effective, and standard methods to treat significant carotid artery stenosis. CAS is generally performed through femoral arterial access. We had six patients with significant carotid artery stenosis, who had difficult anatomy prohibiting a trans- femoral CAS. Those patients were given an option for CEA. However, they refused for surgical intervention. Aim: We investigated the feasibility of performing CAS from a non-femoral arterial approach in patients with difficult anatomies like severe aortic/aorto-iliac disease, tortuous aortic arch, and tortuous carotid artery origin. Materials and Methods: Six patients with difficult anatomy presented to us with either transient ischemic attack or stroke with high-grade carotid artery stenosis. Out of the six patients, three had aorto-iliac disease, one had high-grade coarctation of aorta, two had tortuous aortic arch and or tortuous carotid artery origin. All these patients were treated with CAS though non-femoral arterial route. Results: CAS could be done successfully in all these six patients; four of them were done through trans-brachial arterial route and two were done through a direct carotid artery puncture. There were no new neurological deficits seen in any of the patient post -procedure. Conclusion: CAS can be done safely through non-femoral arterial approach in patients with difficult anatomy.