Symptomatic Carotid Stenosis Patients Research Articles

Frequency of inter-specialty consensus decisions and adherence to advice following discussion at a weekly neurovascular multidisciplinary meeting

Background/aimsData are limited on the frequency of ‘consensus decisions’ between sub-specialists attending a neurovascular multidisciplinary meeting (MDM) regarding management of patients with extracranial carotid/vertebral stenoses and post-MDM ‘adherence’ to such advice.MethodsThis prospective audit/quality improvement project collated prospectively-recorded data from a weekly Neurovascular/Stroke Centre MDM documenting the proportion of extracranial carotid/vertebral stenosis patients in whom ‘consensus management decisions’ were reached by neurologists, vascular surgeons, stroke physicians-geriatricians and neuroradiologists. Adherence to MDM advice was analysed in asymptomatic carotid stenosis (ACS), symptomatic carotid stenosis (SCS), ‘indeterminate symptomatic status stenosis’ (ISS) and vertebral artery stenosis (VAS) patients, including intervals between index event to MDM + / − intervention.ResultsOne hundred fifteen patients were discussed: 108 with carotid stenosis and 7 with VAS. Consensus regarding management was noted in 96.5% (111/115): 100% with ACS and VAS, 96.2% with SCS and 92.9% with ISS. Adherence to MDM management advice was 96.4% (107/111): 100% in ACS, ISS and VAS patients; 92% (46/50) in SCS patients. The median interval from index symptoms to revascularisation in 50–99% SCS patients was 12.5 days (IQR: 9–18.3 days; N = 26), with a median interval from MDM to revascularisation of 5.5 days (IQR: 1–7 days). Thirty patients underwent revascularisation. Two out of twenty-nine patients (6.9%) with either SCS or ISS had a peri-procedural ipsilateral ischaemic stroke, with no further strokes/deaths during 3-months follow-up.ConclusionsThe high frequency of inter-specialty consensus regarding management and adherence to proposed treatment supports a collaborative/multidisciplinary model of care in patients with extracranial arterial stenoses. Service development should aim to shorten times between MDM discussion-intervention and optimise prevention of stroke/death.

Simple CaroTID-VasC score to predict one-year risk of stroke in symptomatic carotid stenosis patients

BackgroundA subset of extracranial symptomatic carotid stenosis (ESCS) patients may fare well on current optimal medical therapy (OMT), and surgery may be avoided in these patients. Therefore, we aimed to develop and validate a stroke risk prediction model to stratify the risk among ESCS patients. MethodsAdult ESCS patients who denied revascularization procedures were enrolled prospectively and prescribed OMT. Patients were followed-up for twelve months after assessing the clinical, imaging, and hemodynamics-based risk predictors at baseline. Cox regression analysis was performed on predictors which were significant in univariate analysis. Beta coefficients of significant predictors in Cox regression were used to generate a numeric score. The model was internally validated using bootstrapping. ResultsA total of 20 (20.2%) out of 99 patients had event recurrence during the follow-up. Transient ischemic attack index event (P = 0.014), diabetes mellitus (P = 0.018), contralateral significant stenosis (P = 0.007), echolucent plaque (P = 0.011), and impaired vasomotor reactivity (P = 0.006) were significant predictors in Cox regression analysis. A points score (0–6) was derived from regression coefficients of the significant predictors. The area under ROC was 0.884 for the developed model and 0.832 for the bootstrapped model. Youden's index divided the score into low-risk (2.2%) and high-risk (35.8%) groups, and the difference in risk was significant (P < 0.001). ConclusionsMost ESCS patients benefited from OMT, and the CaroTID-VasC score was effective in stratifying patients for risk of endpoint occurrence. The developed model may help identify high-risk subgroups of ESCS patients and assist the decision-making of carotid interventions.

Comparing carotid endarterectomies with or without shunting in symptomatic and asymptomatic patients

BackgroundRecent research shows that placement of an intraluminal shunt during a carotid endarterectomy (CEA) can be associated with postoperative complications. Therefore, we compared CEA operations with or without shunting to further analyze their clinical outcomes. MethodsFrom the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database, 13,736 cases between 2016 and 2019 were analyzed to compare adult symptomatic and asymptomatic carotid stenosis patients who underwent a CEA operation, with or without shunt placement. ResultsRates of stroke with a neurological deficit (p = 0.012), myocardial infarction (p = 0.021), and urinary tract infection (p = 0.030) were higher among symptomatic patients with shunting. Multivariate logistic regression revealed that risk of CNI was higher among both symptomatic (93.63%, p < 0.001) and asymptomatic (69.58%, p = 0.001) patients with shunting, irrespective of confounding variables. ConclusionShunting was found to be associated with higher rates of postoperative complications in both symptomatic and asymptomatic patient populations.

Localized Elevation of Wall Shear Stress Is Linked to Recent Symptoms in Patients with Carotid Stenosis

Background: Estimation of symptomatic and asymptomatic carotid atherosclerosis differences can be the basis for prevention and management of carotid artery stenosis disease. In clinical practice, carotid plaque vulnerability is assessed only on the basis of luminal stenosis. However, the evolution of carotid plaque from an asymptomatic state to a symptomatic one is a complex process and the underlying hemodynamic mechanisms are unknown. We aimed to investigate the differences in hemodynamic parameters between patients with recently symptomatic carotid stenosis and asymptomatic ones. Methods: Hemodynamic simulations were performed on 26 carotid plaques from 25 patients with carotid artery stenosis ≥50%, 16 of whom had recent cerebrovascular ischemic events. Using human-specific flow parameters and 3D reconstruction of carotid computed tomography angiography images, we assessed hemodynamic characteristics such as wall shear stress (WSS), time-averaged WSS (TAWSS), oscillatory shear index, and relative residence time (RRT) during the cardiac cycle in patients with and without symptoms. Results: We found that symptomatic carotid stenosis patients had greater local TAWSS (99.59 ± 26.29 vs. 60.40 ± 20.46 dyn/cm², p = 0.0007) and maximal WSS (116.65 ± 39.11 vs. 68.28 ± 23.67 dyn/cm², p = 0.003), but lower RRT (0.019 ± 0.006 vs. 0.013 ± 0.069 s, p = 0.049), than asymptomatic patients, but this hemodynamic difference was not associated with carotid stenosis severity (p = 0.70). Patients with transient ischemic attack (TIA) or stroke had higher local TAWSS and WSSmax than patients with asymptomatic stenosis (p < 0.05). Subgroup analysis showed that there was no statistical difference in local hemodynamic variables between TIA and stroke patients with carotid artery stenosis. Conclusions: Patients with carotid artery stenosis are more likely to experience acute ischemic cerebrovascular accidents if they have higher WSS. Simultaneous assessment with hemodynamic parameters like WSS along with stenosis severity may aid risk stratification in patients with asymptomatic carotid artery stenosis.

Clinical risk scores for stroke correlate with molecular signatures of vulnerability in symptomatic carotid patients

SummaryUnstable carotid stenosis is an important cause of ischemic stroke, yet the basis of disease pathophysiology remains largely unknown. We hypothesized that integrated analyses of symptomatic carotid stenosis patients at increased stroke risk stratified by clinical scores, CAR and ABCD2, with transcriptomic and clinical data could improve identification of molecular pathways and targets for instability. We show that high CAR score reflects plaque instability processes related to intra-plaque hemorrhage, angiogenesis, inflammation, and foam cell differentiation, whereas ABCD2 associates with neutrophil-mediated immunity, foam cell differentiation, cholesterol transport, and coagulation. Repressed processes in plaques from high-risk patients were ossification, chondrocyte differentiation, SMC migration, and ECM organization. ABCB5 gene was found as the top upregulated in high-risk patient’s plaques, localized to macrophages in areas with neovascularization and intra-plaque hemorrhage. The link between ABCB5 and intra-plaque hemorrhage suggests its key role for plaque instability that warrants further exploration.

Increased Regional Market Competition Lowers Threshold For Revascularization In Asymptomatic Carotid Artery Stenosis

INTRODUCTION AND OBJECTIVES Revascularization practices for asymptomatic carotid stenosis(ACAS) vary widely among physicians. Our study examines the association of regional market competition with ACAS revascularization thresholds. METHODS We included all patients undergoing carotid revascularization in the VQI endarterectomy and stenting databases(2016-2020). High-grade stenosis was defined as ≥80%. We calculated the Herfindahl-Hirschman Index(HHI; measuring physician market competition) for US regions. Logistic regression was used to examine the association between degree of stenosis at revascularization with HHI stratified by symptomatology, adjusting for revascularization modality and traditional risk factors. RESULTS Of 92,243 carotid interventions, 61.9% were performed for ACAS and 38.1% for symptomatic carotid stenosis(SCAS). Patients undergoing revascularization for moderate-grade ACAS(vs. high-grade) were less likely to be on aspirin(85.6% vs. 86.3%) and clopidogrel(41.3% vs. 45.1%, both p<0.05), but equally likely to be on statins (85.6% vs. 85.7%, p=0.70). There were significant regional differences in the proportion of carotid revascularization procedures performed for moderate-grade ACAS(Figure). After adjusting for baseline differences between groups, market competition was independently associated with higher odds of revascularization for moderate versus high-grade ACAS(OR:1.02 per 10pt ΔHHI, 95%CI:1.01-1.03). There was no association of market competition with degree of carotid stenosis at time of revascularization among SCAS patients(OR:1.00 per 10pt ΔHHI, 95%CI:1.00-1.01). ACAS patients with moderate-grade stenosis had higher odds of in-hospital stroke or death compared to high-grade stenosis patients(OR:1.28, 95%CI:1.05-1.56). CONCLUSIONS Increased local market competition is associated with a lower revascularization threshold for ACAS but not SCAS. These findings, combined with the increased risk of perioperative stroke/death among moderate-grade ACAS patients, suggest that competition among physicians may result in a higher tolerance for increased operative risk in patients who might otherwise be reasonable candidates for surveillance. Revascularization practices for asymptomatic carotid stenosis(ACAS) vary widely among physicians. Our study examines the association of regional market competition with ACAS revascularization thresholds. We included all patients undergoing carotid revascularization in the VQI endarterectomy and stenting databases(2016-2020). High-grade stenosis was defined as ≥80%. We calculated the Herfindahl-Hirschman Index(HHI; measuring physician market competition) for US regions. Logistic regression was used to examine the association between degree of stenosis at revascularization with HHI stratified by symptomatology, adjusting for revascularization modality and traditional risk factors. Of 92,243 carotid interventions, 61.9% were performed for ACAS and 38.1% for symptomatic carotid stenosis(SCAS). Patients undergoing revascularization for moderate-grade ACAS(vs. high-grade) were less likely to be on aspirin(85.6% vs. 86.3%) and clopidogrel(41.3% vs. 45.1%, both p<0.05), but equally likely to be on statins (85.6% vs. 85.7%, p=0.70). There were significant regional differences in the proportion of carotid revascularization procedures performed for moderate-grade ACAS(Figure). After adjusting for baseline differences between groups, market competition was independently associated with higher odds of revascularization for moderate versus high-grade ACAS(OR:1.02 per 10pt ΔHHI, 95%CI:1.01-1.03). There was no association of market competition with degree of carotid stenosis at time of revascularization among SCAS patients(OR:1.00 per 10pt ΔHHI, 95%CI:1.00-1.01). ACAS patients with moderate-grade stenosis had higher odds of in-hospital stroke or death compared to high-grade stenosis patients(OR:1.28, 95%CI:1.05-1.56). Increased local market competition is associated with a lower revascularization threshold for ACAS but not SCAS. These findings, combined with the increased risk of perioperative stroke/death among moderate-grade ACAS patients, suggest that competition among physicians may result in a higher tolerance for increased operative risk in patients who might otherwise be reasonable candidates for surveillance.

Factors Affecting the Outcome of Symptomatic Carotid Stenosis Surgical Treatment in a Single Center Series

The aim of this study is to evaluate the role of preoperative ischemic brain lesion (IBL) volume, assessed by Diffusion-weighted magnetic resonance brain imaging (DW-MRI) with RAPID® processing, and surgery timing in predicting post-operative neurological outcomes in symptomatic carotid stenosis (SCS) patients treated with carotid endarterectomy (CEA). All patients with SCS who underwent CEA between January 2010 and June 2020 were considered. IBLs ipsilateral to the stenosis were identified in the preoperative magnetic resonance brain (MRI). The volume was quantified in mL and correlated with 30-day rates of stroke and stroke/death by χ2 and receiver operating characteristic (ROC) curve. One hundred thirty-four patients were surgically treated for SCS during the entire study period. CEA procedures were defined as emergent, urgent, or elective if performed within 48 hr, between 48 hr and 14 days, or after 14 days from symptoms onset, respectively. Cumulative new ipsilateral stroke rate was 4,5%, with a statistically higher neurological complications in emergent patients compared to urgent and elective patients (10,6%, 1,47% and 0% respectively, P 0,039). ROC curve analysis showed a volume of 10 mL was predictive of postoperative stroke with 100% sensitivity and 80% specificity. An IBL volume >10 mL was an independent risk factor for postoperative stroke. In fact, the perioperative neurological complication rate was significantly different in high-IBL volume patients (>10 mL) compared with low-IBL volume patients (<10 mL) (P 0,003) CONCLUSIONS: The present study suggests that the optimal timing for CEA is between 48 hr and 14 days. Furthermore, the present study suggests that the presence of the IBL, by itself, is not definitively related with an unsatisfactory neurological outcome. However, an IBL higher than 10 mL should be as a reliable threshold value adverse neurological result in SCS patients.

Abstract 11729: Elevated Procoagulant Platelets Predict Myocardial Infarction or Cardiac Death at 10 Months in Symptomatic Carotid Stenosis

Background: Symptomatic carotid stenosis is associated with elevated myocardial infarction (MI) risk. Better risk prediction and intervention targets may help reduce adverse cardiac events. Coated-platelets, a subset of procoagulant platelets observed upon dual agonist stimulation with collagen and thrombin, predict stroke recurrence in symptomatic carotid disease, but the association with MI risk is unknown. Here we assess whether coated-platelets predict MI or sudden cardiac death (SCD) in symptomatic carotid stenosis. Methods: Patients with symptomatic ≥50% carotid artery stenosis were enrolled and coated-platelet levels assayed within 92 hours of stroke onset. Demographics, comorbidities and interventions were recorded. MI (4 th universal definition) and SCD (death from MI or arrhythmia) were determined by chart review and confirmed by blinded adjudication. The Area Under the Curve (AUC) was calculated for coated-platelet levels for predicting MI or SCD and the most sensitive and specific cutoff identified using Youdon’s Index. Predictors of MI or SCD were determined by Cox Proportional Hazards analysis. Results: We enrolled 179 patients (mean age 67, 85% male, 43% diabetic, 44% smokers, 45% with coronary disease, 26% with carotid revascularization at discharge). Eleven MI’s (5 fatal) and 4 SCD’s without MI (8.4%) occurred over 10.1±3.6 months. Baseline coated-platelets ≥54.6% were associated with risk of MI or SCD (AUC, 0.687±0.0842, p=0.0265, 53% sensitivity, 85% specificity). Age (HR=1.074, p=0.0187) and the interaction between elevated coated-platelets and carotid revascularization at discharge (HR=37.6, p=0.0182) were retained as significant on multivariate analysis. Conclusions: Our findings revealed a 37.6 increased hazard of MI or SCD among revascularized symptomatic carotid stenosis patients with ≥54.6% coated-platelets. A high rate of often fatal MI was also noted after revascularization, supporting the need to optimize cardiovascular risk management. Our results suggest a role for coated-platelets as biomarkers of perioperative cardiovascular risk and as potential novel treatment targets to reduce perioperative adverse cardiac events in symptomatic carotid stenosis.

Diffusion weight magnetic resonance imaging analisys with rapid software appication in symptomatic carotid stenosis revascularization

Abstract Objectives The aim of this study was to evaluate whether the extension of preoperative neuroradiological lesions assessed by magnetic resonance imaging (MRI) with Diffusion Weighted sequences (DWI) and Rapid processing of Perfusion and Diffusion software are potentially related to post-operative neurological outcome in patients with symptomatic carotid stenosis (SCS) treated by carotid endarterectomy (CEA). Methods From January 2010 to June 2020, data from 134 consecutive patients affected by SCS, presenting with transient ischemic attack (TIA), and minor or moderate stroke, and submitted to urgent CEA in a single academic center, were prospectively collected and reviewed. All SCS patients underwent independent neurological evaluation, duplex ultrasound scan, computed tomographic angiography, and DW-MRI with RAPID evaluation. RAPID evaluation was performed to assess the volume of acute ischemic brain lesion (IBL); through this method it is possible to obtain the identification of the ischemic core milliliters (mL). According with clinical presentation, and imaging studies analysis CEA endarterectomies were performed within 48 hours, within 14 days or after 14 days from symptoms onset. Outcomes for presented analysis were the post-operative new neurological event, and deathat follow-up. Timing of CEA and IBL volume at RAPID evaluation were considered as risk factor potentially influencing outcomes. Results Among all the 134 enrolled patients, 68 patients (50.7%) presented with TIA, 49 (36.6%) with a minor Stroke, and 17 (12.7%) with a moderate Stroke. No intraoperative death occurred in any group. Overall, 6 (4.4%) new neurological events were noted in this series, 1 minor stroke (0.7%), and 5 TIAs (3.7%). One-hundred-fifteen (86%) underwent surgery within 14 days from neurological symptoms onset (Urgent patients – U), and 19 (14%) after 14 days (Delayed patients – D); U patients were also divided in two subgroups U1 47/115 patients (35%) submitted to CEA within 48 hours from symptoms onset, and U2 68/115 patients (51%) after 48 hours. No neurological complications were noted in group D, while 5 new adverse events occurred in U1, and 1 in U2 (p=0.01). Results from MRI with DWI sequences performed in 100/134 patients (74.6%) showed positive preoperative diffusion in 62 patients. The RAPID processing ascribed a 0 value, for punctiform lesions, and a value from 2 to 77 ml for single acute lesions; average volume lesion volume was 8.6 mL. Patients were then divided into two groups according to IBL volume: 84 &amp;lt;10 ml, and 16≥10 mL. Incidence of new neurological events was significantly higher in &amp;gt;10ml group (18.7% vs 3.6%; p=0.02). Conclusion Our experience seems to suggest that the optimal time for SCS revascularization is between 48 hours and 14 days. Moreover, IBL volume &amp;gt;10ml might greatly increase risk of postoperative adverse events occurrence. Funding Acknowledgement Type of funding sources: None.

Asymptomatic Preoperative Leukocytosis Before Carotid Endarterectomy is Associated With Increased Risk of Stroke: A Study From NSQIP Database

Carotid endarterectomy (CEA) is the gold standard operation for treating carotid artery stenosis in patients with symptomatic carotid stenosis of more than 50% and asymptomatic carotid stenosis of more than 80%. Asymptomatic leukocytosis before CEA represents a clinical dilemma for surgeons about the management options. The objectives of this study are to identify the relationship between asymptomatic preoperative leukocytosis and postoperative complications in patients undergoing CEA and to assess the relationship between asymptomatic preoperative leukocytosis and postoperative complications in the cohort of patients with symptomatic carotid stenosis. The American College of Surgeons National Surgical Quality Improvement Program database for the years 2011-2019 was utilized for this analysis. Patients with preoperative sepsis, septic shock, pneumonia, wound infections, disseminated cancer, renal failure, and history of chronic steroid use were excluded. The remaining patients were sub-grouped based on white blood cell (WBC) count: Normal WBC (<11k/µL) and High WBC (≥11k/µL). Bivariate analysis between the patient characteristics and preoperative WBC levels was performed following simple and multiple regression analysis. A P-value of <0.05 was set as significant. Of the 26,332 patients in the study cohort, 7.4% (n =1,946) had preoperative leukocytosis. Patients with preoperative leukocytosis were relatively younger (mean age: 41.5 +/- 9.7 vs 44.3 +/- 9.1; P< 0.001) and more likely to be females (43% vs. 38.5; P< 0.001) than patients with normal WBC count. Patients with preoperative leukocytosis were also more likely to have DM, COPD, a bleeding disorder, be smokers, and be functionally dependent. The analysis revealed that patients with preoperative leukocytosis had a significantly higher rate of stroke, length of stay (LOS)>1- week, acute occlusion or revision, acute renal failure, and return to OR when compared to patients with normal WBC count. Furthermore, patients with high WBC count also experienced higher occurrences of infectious complications, such as wound dehiscence, wound infections, pneumonia, and sepsis. However, there was no difference in the overall 30-day mortality. Multivariate regression analysis showed patients with preoperative leukocytosis had anincreased risk of stroke (AOR 1.5, CI: 1.1-1.9, P = 0.009), LOS>1 week (AOR 1.3, CI: 1.1-1.5, P = 0.003), and return to OR (AOR 1.3, CI: 1.0-1.8, P = 0.030). The increased LOS was especially more pronounced in symptomatic carotid stenosis patients with preoperative leukocytosis. The occurrence of LOS>1 week was 4.91% in asymptomatic stenosis patients with high WBC count compared to 21.5% in symptomatic stenosis patients with high WBC count (P< 0.001). Patients with asymptomatic preoperative leukocytosis undergoing CEA have a significantly higher risk of stroke and infectious complications in the postoperative period. Furthermore, patients with symptomatic carotid disease are especially at an increased risk of prolonged LOS. A routine preoperative hematological evaluation may be recommended as a risk assessment tool for patients undergoing CEA, and postponing the elective operation in patients with asymptomatic CEA may be advised unless a thorough preoperative infectious workup is completed.

Low Risk of Neurological Recurrence while Awaiting Carotid Endarterectomy: Results From a Danish Multicentre Study

The risk of ipsilateral neurological recurrence (NR) was assessed in patients awaiting carotid endarterectomy (CEA) due to symptomatic carotid artery stenosis and whether current national guidelines of performing CEA within 14 days are adequate in present day practice. This was a retrospective multicentre observational cohort study. Patients scheduled for CEA due to symptomatic carotid artery stenosis in a five year period, 1 January 2014 to 31 December 2018, from four centres were included. Data from the Danish Vascular Registry (www.karbase.dk), operative managing systems, and electronic medical records were reviewed. In total, 1 125 patients scheduled for CEA were included and 1 095 (97%) underwent the planned surgery. During a median delay from index event to CEA of 11 days (interquartile range 8-16 days), 40 patients (3.6%; 95% confidence interval [CI] 2.5%-5%) experienced a NR. One third were minor strokes (n=12, 30%); half were transient ischaemic attacks (TIA) (n=22, 55%); and amaurosis fugax accounted for 15% (n=6). Twenty-six (2%) CEA procedures was cancelled, of which one was due to a disabling recurrent ischaemic event (aphasia). There were no deaths or major strokes in the waiting time for CEA. Best medical treatment (BMT) with platelet inhibitory or anticoagulation drugs and a statin was initiated in nearly all patients (98%) at first assessment. The overall 30 day risk of a post-operative major event (death or stroke) was (Kaplan-Meier [KM] estimate) 2.7% (95% CI 1.8-3.8), and not significantly correlated with the timing of surgery. Most (69%) occurred within the first three days. One, two, and three year mortality rate for CEA patients was (KM estimate) 4.8%, 7.8%, and 11.5% respectively. In symptomatic carotid artery stenosis patients awaiting CEA, very few NRs occurred within 14 days. Institution of immediate BMT in specialised TIA/stroke units followed by early, but not necessarily urgent, CEA is a reasonable course of action in patients with high grade symptomatic carotid artery stenosis.

Neutrophil extracellular traps induce thrombogenicity in severe carotid stenosis.

BackgroundSevere carotid stenosis is a common cause of stroke. In addition, previous clinical studies revealed that patients symptomatic of carotid stenosis suffer from increased episodes of stroke compared with their asymptomatic counterparts. However, the mechanism underlying these differences in the recurrence of stroke remains unclear.ObjectiveThe present study aimed to evaluate the levels of neutrophil extracellular traps (NETs) in the plasma of patients with severe carotid stenosis and investigate whether NETs induced procoagulant activity (PCA) in severe carotid stenosis. The study also sought to investigate the interactions between platelets or endothelial cells (ECs) and NETs.MethodsThe levels of NETs in plasma were quantified using enzyme‐linked immunosorbent assay (ELISA). In addition, NETting neutrophils and neutrophil‐platelet aggregates were detected through flow cytometry. On the other hand, the morphology of NETs formation and endothelial cells were analyzed through confocal microscopy. Finally, the procoagulant activity (PCA) of NETs and endothelial cells were assessed through ELISA and fibrin formation.ResultsPatients with symptomatic carotid stenosis patients had significantly higher levels of NETs markers compared with their asymptomatic counterparts and healthy subjects. In addition, increased levels of neutrophil‐platelet aggregates induced the generation of NETs in patients with symptomatic carotid stenosis. Moreover, NETs contributed to PCA through tissue factor (TF), in patients with carotid stenosis. Furthermore, NETs disrupted the endothelial barrier and converted endothelial cells (ECs) into PCA to enhance the PCA in patients with carotid stenosis.ConclusionsThe current study revealed differences in the levels of NETs in the plasma of symptomatic and asymptomatic patients suffering from carotid stenosis. The study also uncovered the interaction between NETs and thrombogenicity in carotid stenosis. Therefore, inhibiting NETs may be a potential biomarker and therapeutic target for recurring stroke in severe carotid stenosis.

Von Willebrand Factor Antigen, von Willebrand Factor Propeptide, and ADAMTS13 in Carotid Stenosis and Their Relationship with Cerebral Microemboli.

The relationship between von Willebrand factor antigen (VWF:Ag), VWF propeptide (VWFpp), VWFpp/VWF:Ag ratio, ADAMTS13 activity, and microembolic signal (MES) status in carotid stenosis is unknown. This prospective, multicenter study simultaneously assessed plasma VWF:Ag levels, VWFpp levels and ADAMTS13 activity, and their relationship with MES in asymptomatic versus symptomatic moderate-to-severe (≥50-99%) carotid stenosis patients. One-hour transcranial Doppler ultrasound of the middle cerebral arteries classified patients as MES+ve or MES-ve. Data from 34 asymptomatic patients were compared with 43 symptomatic patients in the "early phase" (≤4 weeks) and 37 patients in the "late phase" (≥3 months) after transient ischemic attack (TIA)/ischemic stroke. VWF:Ag levels were higher (p = 0.049) and VWFpp/VWF:Ag ratios lower (p = 0.006) in early symptomatic than in asymptomatic patients overall, and in early symptomatic versus asymptomatic MES-ve subgroups (p ≤0.02). There were no intergroup differences in VWFpp expression or ADAMTS13 activity (p ≥0.05). VWF:Ag levels and ADAMTS13 activity decreased (p ≤ 0.048) and VWFpp/VWF:Ag ratios increased (p = 0.03) in symptomatic patients followed up from the early to late phases after TIA/stroke. Although there were no differences in the proportions of symptomatic and asymptomatic patients with blood group O, a combined analysis of early symptomatic and asymptomatic patients revealed lower median VWF:Ag levels in patients with blood group O versus those without blood group O (9.59 vs. 12.32 µg/mL, p = 0.035). VWF:Ag expression, a marker of endothelial ± platelet activation, is enhanced in recently symptomatic versus asymptomatic carotid stenosis patients, including in MES-ve patients, and decreases with ADAMTS13 activity over time following atherosclerotic TIA/ischemic stroke.

Abstract WP6: Safety of Acute Carotid Stenting Treatment in Acute Symptomatic Patients

Carotid stenting (CAS) has been shown to be equivalent to carotid endarterectomy in symptomatic patients; however its optimal timing remains unclear. In this study, we aim to evaluate the safety of CAS when performed within the first 48 hours of symptom onset. We performed a retrospective analysis of a prospectively collected database of consecutive CAS patients admitted to our comprehensive stroke center with TIA/stroke and ipsilateral symptomatic carotid stenosis &gt;50% from 2014 to 2019. Medical records were retrospectively reviewed for demographic, clinical and procedural data and outcomes. Acute and delayed treatment were defined as ≤48 and &gt;48 hours from last known well (LKW) respectively. The primary endpoint was procedure-related major complications (stroke with NIHSS increase of ≥4, myocardial infarction, parenchymal hemorrhage type 2 or death) ≤30 days after CAS. Secondary endpoints were procedure-related minor neurological (stroke with NIHSS increase of &lt;4 and reperfusion injury) and non-neurological (groin puncture hematoma, acute anemia and arrhythmia) complications. Functional outcome was assessed by discharge and 90 days mRS, dichotomized as good (0-2) and bad (3-6). A total of 72 patients were included in the analysis, 36 in each group. There was no difference in age, NIHSS at presentation, gender, incidence of TIA as presentation or percentage of TPA received. The acute group differed significantly from the delayed group in number of thrombectomies (36.1% vs. 5.6%, p=0.001) and median time from LKW to CAS (15.9 hours vs. 88.0 hours, p&lt;0.001). There were significantly more carotid occlusions in the acute group when compared to the delayed group (37.8% vs. 2.2, p&lt;0.0001). Overall, the acute group did not show significant difference from the delayed group in major (2.8% vs. 5.6%, p=1.0), minor neurological (13.9% vs. 2.8%, p=0.09) and minor non-neurological complication rates (13.9% vs. 8.3%, p=0.7). Rates of good outcomes were not significantly different between the two groups at discharge (52.8% vs. 50%) or 90 days (75% vs. 63%). CAS can be performed safely in acute symptomatic carotid stenosis patients within the first 48 hours from symptom onset.

Intraoperative Hypotension is not Correlated to Perioperative Silent Brain Ischemia After Carotid Endarterectomy

Introduction: Periprocedural ischemic brain lesions on diffusion weighted imaging (DWI) after carotid revascularization have increasingly been used as a surrogate marker for cerebral ischemia and are related to a higher chance of recurrent cerebrovascular events. It is hypothesized that patients undergoing carotid endarterectomy with intraoperative hypotension are at risk for development of new silent ischemic lesions as a result of cerebral hypoperfusion. Therefore, the current study aimed to investigate the relation between intraoperative blood pressure (BP) and the presence of silent ischemic lesions on postoperative MR-DWI in patients undergoing carotid endarterectomy. Methods: A retrospective analysis was performed based on prospectively collected data of symptomatic carotid endarterectomy patients within Utrecht Athero-Express (AE) biobank that were also included in the MRI-substudy of the international carotid stenting study (ICSS). Intraoperative hypotension was defined both as a decrease of ≥20% below baseline intraoperative BP and an absolute drop in systolic blood pressure below 80mmHg. Intraoperative hypertension is defined as an increase of ≥20% compared to baseline values. Variation in blood pressure was expressed by it's standard deviation. Intraoperative BP was measured invasively by radial artery cannula. Intraoperative BP was analyzed from time of anesthesia induction until emergence. The occurrence of intraoperative hypo- and hypertension and the duration of these changes in blood pressure were associated to the presence of ischemic lesions on MR-DWI. Results: A number of 55 symptomatic carotid stenosis patients were included in the study of which 71% male patients, with mean age (68.5 ± 9.4) and a median stenosis grade of 70-90%. A total of eight patients had new DWI-lesions (DWI positive) on postoperative MRI (5 ipsilateral and 3 both ipsi- and contralateral). Median lesion volume was 0.37mL (IQR: 0.076-7.81). Baseline characteristics between DWI-negative and DWI-positive patients did not differ. There was no difference in the median duration of intraoperative BP dropping below 80% of baseline in DWI-negative (41 minutes; IQR: 23-82) compared to DWI-positive patients (43 minutes; IQR: 25-81, p=.935). No difference was found in median duration of absolute hypotension (0 minutes; IQR 0-2 vs. 0 minutes; IQR 0-0, p=.224), and intraoperative hypertension (1 minute; IQR 0-2 vs. 1 minute; IQR 0-4, p=.417). The standard deviation of systolic intraoperative BP measurements was also comparable between the groups (24.5; IQR 21.5-28.8 vs 25.7; IQR 22.7-33.6, p=.459). Conclusion: An intraoperative period of relative hypotension compared to baseline occurred frequently. The duration of intraoperative hypotension does not seem to be related to development of perioperative DWI-lesions. Disclosure: Nothing to disclose

Risk of perioperative neck hematoma in TIA and non-disabling stroke patients with symptomatic carotid artery stenosis undergoing endarterectomy within 14 days from cerebrovascular event.

Backround & purposePerioperative neck hematoma (PNH) requiring re-intervention is an important complication after carotid endarterectomy (CEA). There are limited data regarding the potential risk factors associated with PNH. The aim of this prospective, multicenter study was to document the rate of PNH in symptomatic carotid artery stenosis (sCAS) patients treated with CEA within the first 14 days of cerebrovascular symptom onset and to identify possible predictors of this complication. MethodsPatients with non-disabling (mRS ≤ 2) acute ischemic stroke or transient ischemic attack due to sCAS (≥70%) underwent CEA at three stroke-centers during a seven-year period. PNH requiring surgical re-intervention or transfusion during a 30-day follow-up period was determined by the attending surgeon but was also confirmed by an independent neurologist. ResultsA total of 280 patients with sCAS underwent CEA within 14 days of ictus. PNH occurred in 10 cases (3.6%; 95%CI: 1.4%–5.8%). Pretreatment with therapeutic anticoagulation (TA) and history of atrial fibrillation were more prevalent in patients with PNH (20% vs. 3.1%, p= 0.047 & 30% vs. 8.2%, p = 0.05 respectively). Elapsed time between symptom onset and carotid surgery, pretreatment with dual antiplatelets, intravenous thrombolysis or prophylactic anticoagulation were not related to PNH in univariable analyses. Pretreatment with TA was independently associated with higher likelihood of PNH [OR: 10.69, 95%CI (1.74–65.72), p = 0.011] in multivariate logistic regression models adjusting for potential confounders. ConclusionPNH is uncommon in patients with sCAS that are operated during the first 14 days of ictus. Pretreatment with TA appears to be associated with higher risk of PNH.

Simultaneous assessment of plaque morphology, cerebral micro-embolic signal status and platelet biomarkers in patients with recently symptomatic and asymptomatic carotid stenosis

The relationship between plaque morphology, cerebral micro-embolic signals (MES) and platelet biomarkers in carotid stenosis patients warrants investigation. We combined data from two prospective, observational studies to assess carotid plaque morphology and relationship with cerebral MES and platelet biomarkers in patients with recently symptomatic (≤4 weeks of transient ischaemic attack (TIA)/ischaemic stroke) versus asymptomatic carotid stenosis. Plaque morphology on ultrasound was graded with Grey-Scale Median (GSM) and Gray–Weale (GW) scoring. Bilateral transcranial Doppler ultrasound classified patients as ‘MES+ve’ or ‘MES-ve’. Full blood counts were analysed and flow cytometry quantified CD62P and CD63 expression, leucocyte-platelet complexes and reticulated platelets. Data from 42 recently symptomatic carotid stenosis patients were compared with those from 36 asymptomatic patients. There were no differences in median GSM scores between symptomatic and asymptomatic patients (25 vs. 30; P = 0.31) or between MES+ve vs. MES-ve symptomatic patients (36 vs. 25; P = 0.09). Symptomatic patients with GSM-echodense plaques (GSM ≥25) had higher platelet counts (228 vs. 191 × 109/L), neutrophil–platelet (3.3 vs. 2.7%), monocyte–platelet (6.3 vs. 4.55%) and lymphocyte–platelet complexes (2.91 vs. 2.53%) than ‘asymptomatic patients with GSM-echodense plaques’ (P ≤ 0.03). Recently, symptomatic carotid stenosis patients with ‘GSM-echodense plaques’ have enhanced platelet production/secretion/activation compared with their asymptomatic counterparts. Simultaneous assessment with neurovascular imaging and platelet biomarkers may aid risk-stratification in carotid stenosis.

Relationship between 'on-treatment platelet reactivity', shear stress, and micro-embolic signals in asymptomatic and symptomatic carotid stenosis.

Assessment of 'high on-treatment platelet reactivity (HTPR)' could enhance understanding of the pathophysiology of first or recurrent vascular events in carotid stenosis patients on antiplatelet therapy. This prospective, multi-centre study assessed antiplatelet-HTPR status and its relationship with micro-emboli signals (MES) in asymptomatic vs. symptomatic ≥ 50-99% carotid stenosis. Platelet function/reactivity was assessed under 'moderately high shear stress' with the PFA-100® and 'low shear stress' with VerifyNow® and Multiplate® analysers. Bilateral 1-h transcranial Doppler ultrasound of the middle cerebral arteries classified patients as MES + ve or MES - ve. Data from 34 asymptomatic patients were compared with 43 symptomatic patients in the 'early phase' (≤ 4weeks) and 37 patients in the 'late phase' (≥ 3months) after TIA/ischaemic stroke. Median daily aspirin doses were higher in early symptomatic (225mg; P < 0.001), but not late symptomatic (75mg; P = 0.62) vs. asymptomatic patients (75mg). There was a lower prevalence of aspirin-HTPR in early (28.6%; P = 0.028), but not late symptomatic (38.9%; P = 0.22) compared with asymptomatic patients (56.7%) on the PFA-100®, but not on the VerifyNow® or Multiplate® (P ≤ 0.53). Early symptomatic patients had a higher prevalence of aspirin-HTPR on the PFA-100® (28.6%) vs. VerifyNow® (9.5%; P = 0.049), but not Multiplate® assays (11.9%, P = 0.10). There was no difference in aspirin-HTPR prevalence between any symptomatic vs. asymptomatic MES + ve or MES - ve subgroup. Recently symptomatic moderate-severe carotid stenosis patients had a lower prevalence of aspirin-HTPR than their asymptomatic counterparts on the PFA-100®, likely related to higher aspirin doses. The prevalence of antiplatelet-HTPR was positively influenced by higher shear stress levels, but not MES status.

251Revacept, an inhibitor of platelet adhesion in symptomatic carotid stenosis: Results from a phase II study

Abstract Revacept is a novel lesion-specific inhibitor for platelet adhesion and thrombus formation. The biological drug is based on the platelet GPVI receptor and prevents collagen-mediated platelet activation from the atherosclerotic plaque. The unique characteristic of Revacept is the specific inhibition of plaque-mediated thrombus formation without alteration of hemostasis. To test this concept in patients with plaque-mediated thrombosis we investigated patients with symptomatic carotid artery stenosis (at least 50% cf. ECST) with a recent ischemic cerebral stroke or transient ischemic attack (TIA). 150 patients were evenly randomized in blinded fashion to receive placebo, 40mg or 120 mg Revacept by IV infusion. To investigate anti-thrombotic efficacy, we assessed microemboli in the middle cerebral artery by transcranial Doppler (MES) and micro-infarctions in the brain by diffusion-weighted nuclear magnetic resonance (DWI-NMR) imaging. Ischemic complications such as myocardial infarctions and ischemic stroke were clinically followed up to 3 and 12 months. Bleeding complications were thoroughly monitored according to the RE-LY study group criteria. All patients were on standard anti-platelet therapy and underwent guideline conform treatment with carotid endarterectomy (CEA),carotid artery stent implantation or intensified conservative treatment. The study was conducted in 16 centers in Germany and the UK from May 2013 to September 2018. Due to lost to follow-up investigations the planned patient numbers were slightly exceeded to 158 patients, who were finally included in the study according to intention to treat. Currently data clearance and detailed analysis of unblinded data is going on. 7.6% of patients underwent carotid artery stenting, 11.4% were under intensified conservative treatment and 81.0% were surgically treated with CEA. The safety data of the overall 158 patients which was closely monitored by an independent data safety board are available. In the overall study population (before unblinding for treatment) ischemic strokes and myocardial infarctions were numerically lower compared to previous studies with symptomatic carotid stenosis patients undergoing CEA or stenting (meta analysis from the EVA-3S, SPACE and ICSS study). Despite comparable basal anti-thrombotic therapy addition of Revacept did not increase bleeding complications in the overall study population. The Revacept CS02 study has successfully achieved the aimed patient recruitment. Safety analysis shows a favorable profile. Bleeding complications in these high-risk patients with recent ischemic stroke were not increased compared to historic data from similar control patients. There is a trend for increased anti-thrombotic and anti-ischemic potency with regard to clinical events. Final data will be presented at the congress. Acknowledgement/Funding None

Upregulation of miR-330-5p is associated with carotid plaque\u2019s stability by targeting Talin-1 in symptomatic carotid stenosis patients

BackgroundThe aim of this study was to investigate the relationship between Talin-1 and stability of carotid atherosclerosis plaque and also find out the role of miRNA, as an upstream regulator, in regulating the expression level of Talin-1.MethodsHuman carotid plaques were obtained from 20 symptomatic carotid stenosis patients who underwent carotid endarterectomy (CEA) in our hospital between October 2014 and August 2017. Western blot analysis and immunohistochemistry was carried out to detect the distribution and expression level of Talin-1 in each plaque sample. The content of miRNAs in carotid plaque was decected by quantitative reverse transcription polymerase chain reaction (RT-qPCR), and the relative expression levels were calculated by 2-△△Ct method after the (cycle threshold) Ct value (power amplification knee point) was obtained. Dual-luciferase reporter assays were applied to verify the successful transfections. Finally, we compared all the groups with independent-samples t-test and one-way analysis of variance (ANOVA).ResultsTalin-1 was significantly downregulated in human unstable carotid plaque samples compared with stable carotid plaques (P < 0.05), and the distribution of Talin-1 was mainly found in the fibrous cap of carotid plaque. The overexpression of miRNA-330-5p was found in unstable carotid plaque, which significantly induced the inhibition of expression level of Talin-1.ConclusionUpregulated miR-330-5p may lead to unstable carotid plaques by targeting Talin-1 in symptomatic carotid stenosis patients. This might be a new target for the treatment of atherosclerotic diseases through future studies.