Carotid-related Stroke Research Articles

TCT-313 A Multicenter Study of the Micronet-Covered Stent in Consecutive Patients With Acute Carotid-Related Stroke: SAFEGUARD-STROKE

TCT-313 A Multicenter Study of the Micronet-Covered Stent in Consecutive Patients With Acute Carotid-Related Stroke: SAFEGUARD-STROKE

Outcomes in acute carotid-related stroke eligible for mechanical reperfusion: SAFEGUARD-STROKE Registry.

Carotid-related strokes (CRS) are largely unresponsive to intravenous thrombolysis and are often large and disabling. Little is known about contemporary CRS referral pathways and proportion of eligible patients who receive emergency mechanical reperfusion (EMR). Referral pathways, serial imaging, treatment data, and neurologic outcomes were evaluated in consecutive CRS patients presenting over 18 months in catchment area of a major carotid disease referral center with proximal-protected CAS expertise, on-site neurology, and stroke thrombectomy capability (Acute Stroke of CArotid Artery Bifurcation Origin Treated With Use oF the MicronEt-covered CGUARD Stent - SAFEGUARD-STROKE Registry; companion to SAFEGUARD-STROKE Study NCT05195658). Of 101 EMR-eligible patients (31% i.v.-thrombolyzed, 39.5% women, age 39-89 years, 94.1% ASPECTS 9-10, 90.1% pre-stroke mRS 0-1), 57 (56.4%) were EMR-referred. Referrals were either endovascular (Comprehensive Stroke Centre, CSC, 21.0%; Stroke Thrombectomy-Capable CAS Centre, STCC, 70.2%) or to vascular surgery (VS, 1.8%), with >1 referral attempt in 7.0% patients (CSC/VS or VS/CSC or CSC/VS/STCC). Baseline clinical and imaging characteristics were not different between EMR-treated and EMR-untreated patients. EMR was delivered to 42.6% eligible patients (emergency carotid surgery 0%; STCC rejections 0%). On multivariable analysis, non-tandem CRS was a predictor of not getting referred for EMR (OR 0.36; 95%CI 0.14-0.93, P=0.03). Ninety-day neurologic status was profoundly better in EMR-treated patients; mRS 0-2 (83.7% vs. 34.5%); mRS 3-5 (11.6% vs. 53.4%), mRS 6 (4.6% vs. 12.1%); P<0.001 for all. EMR-treatment substantially improves CRS neurologic outcomes but only a minority of EMR-eligible patients receive EMR. To increase the likelihood of brain-saving treatment, EMR-eligible stroke referral and management pathways, including those for CSC/VS-rejected patients, should involve stroke thrombectomy-capable centres with endovascular carotid treatment expertise.

A multi-center study of the MicroNET-covered stent in consecutive patients with acute carotid-related stroke: SAFEGUARD-STROKE.

Acute carotid-related stroke (CRS), with its large thrombo-embolic load and large volume of affected brain tissue, poses significant management challenges. First generation (single-layer) carotid stents fail to insulate the athero-thrombotic material; thus they are often non-optimized (increasing thrombosis risk), yet their use is associated with a significant (20-30%) risk of new cerebral embolism. To evaluate, in a multi-center multi-specialty investigator-initiated study, outcomes of the MicroNET-covered (cell area ≈ 0.02-0.03 mm2) carotid stent (CGuard, InspireMD) in consecutive CRS patients eligible for emergency recanalization. Treatment, other than study device use, was according to center/operator routine. Seventy-five patients (age 40-89 years, 26.7% women) were enrolled in 7 interventional stroke centers. The median Alberta Stroke Program Early CT Score (ASPECTS) was 9 (6-10). Study stent use was 100% (no other stent types implanted); retrograde strategy predominated (69.2%) in tandem lesions. Technical success was 100%. Post-dilatation balloon diameter was 4.0 to 8.0 mm. 89% of patients achieved final modified Thrombolysis in Cerebral Infarction (mTICI) 2b-c/3. Glycoprotein IIb/IIIa inhibitor use as intraarterial (IA) bolus + intravenous (IV) infusion was an independent predictor of symptomatic intracranial hemorrhage (OR = 13.9, 95% CI: 5.1-84.5, p < 0.001). The mortality rate was 9.4% in-hospital and 12.2% at 90 days. Ninety-day mRS0-2 was 74.3%, mRS3-5 13.5%; stent patency was 93.2%. Heparin-limited-to-flush predicted patency loss on univariate (OR = 14.3, 95% CI: 1.5-53.1, p < 0.007) but not on multivariate analysis. Small-diameter balloon/absent post-dilatation was an independent predictor of stent patency loss (OR = 15.2, 95% CI: 5.7-73.2, p < 0.001). This largest to-date study of the MicroNET-covered stent in consecutive CRS patients demonstrated a high acute angiographic success rate, high 90-day patency and favorable clinical outcomes despite variability in procedural strategies and pharmacotherapy (SAFEGUARD-STROKE NCT05195658).

Endovascular carotid revascularization under open-chest extracorporeal circulation combined with cardiac surgery in unstable patients at increased risk of carotid-related stroke: SIMultaneous urgent cardiac surgery and MicroNet-covered stent carotid revascularization in extreme-risk patients-SIMGUARD Study.

In patients at urgent need for cardiac surgery coexisting with increased-stroke-risk carotid stenosis, any staged intervention increases the risk of complications from the primarily unaddressed pathology. In this challenging cohort, we assessed safety and feasibility of endovascular carotid revascularization under open-chest extracorporeal circulation (ECC) combined with cardiac surgery (hybrid-room true simultaneous treatment). Per-protocol (PP), after general anesthesia induction, chest-opening and ECC stand-by installation, carotid stenting (CAS) was performed (femoral/radial or direct carotid access) with ad-hoc/on-hand switch to ECC cardiac surgery. Over 78 months, 60 patients (70.7±6.9years, 85% male, all American Society of Anesthesiology grade IV) were enrolled. All were at increased carotid-related stroke risk (ipsilateral recent stroke/transient ischemick attack, asymptomatic cerebral infarct, increased-risk lesion morphology, bilateral severe stenosis). Majority of study procedures involved CAS+coronary bypass surgery or CAS+valve replacement±coronary bypass. 45 (75%) patients were PP- and 15 (25%) not-PP (NPP-) managed (context therapy). CAS was 100% neuroprotected (transient flow reversal-64.4%, filters-35.6%) and employed micronet-covered plaque-sequestrating stents with routine post-dilatation optimization/embedding. 4 deaths (6.7%) and 7 strokes (11.7%) occurred by 30-days. Despite CAS+surgery performed on aspirin and unfractionated heparin-only (delayed clopidogrel-loading), no thrombosis occurred in the stented arteries, and 30-days stent patency was 100%. NPP-management significantly increased the risk of death/ipsilateral stroke (OR 38.5; P<0.001) and death/any stroke (OR 12.3; P=0.002) by 30-days. In cardiac unstable patients at increased carotid-related stroke risk who require urgent cardiac surgery, simultaneous cardiac surgery and CAS with micronet-covered stent lesion sequestration is feasible and safe and shows efficacy in minimizing stroke risk. Larger-scale, multicentric evaluation is warranted. (SIMGUARD NCT04973579).

12-Month Outcomes of Carotid Artery Stenting With CGuard MicroNET-Covered Stent: A Single-Center Study in 113 Patients.

Dual layer mesh stents constitute a novel treatment option for patients who undergo carotid artery stenting (CAS). The aim of this prospective study is to report 12month outcomes of patients who underwent CAS with CGuard (Inspire MD, Tel Aviv, Israel) microNET self-expanding stent with embolic protection system in a tertiary center from October 2018 to March 2022. Primary endpoints included in-stent restenosis >70% verified by ultrasound (DUS), ipsilateral transient ischemic attack (TIA), and stroke at 12months. Secondary endpoints included cardiovascular-related mortality (stroke, myocardial infarction, heart failure) and all-cause mortality during follow-up. One hundred thirteen patients were included in the study (male 72.5%), symptomatic 47.8%. Median follow-up was 25months (2-48). By 12months, there was one in-stent occlusion that manifested as stroke (1/113, 0.8%) but no other forms of in-stent restenosis. Two patients experienced contralateral TIA (1.7%). CVRM was 3.5% (4 MI) and all-cause mortality was 6% at follow-up. This prospective study shows that CAS with CGuard MicroNET-covered stent is safe with minimal neurological adverse events at 12months follow-up. Larger, and longer-term studies are necessary to define CGuard long-term safety and protection against carotid-related stroke.

Stroke risk management in carotid atherosclerotic disease: A Clinical Consensus Statement of the ESC Council on Stroke and the ESC Working Group on Aorta and Peripheral Vascular Diseases.

Carotid atherosclerotic disease continues to be an important cause of stroke, often disabling or fatal. Such strokes could be largely prevented through optimal medical therapy and carotid revascularization. Advancements in discovery research and imaging along with evidence from recent pharmacology and interventional clinical trials and registries and the progress in acute stroke management have markedly expanded knowledge base for clinical decisions in carotid stenosis. Nevertheless, there is variability in carotid-related stroke prevention and management strategies across medical specialities. Optimal patient care can be achieved by (1) establishing a unified knowledge foundation and (2) fostering multi-specialty collaborative guidelines. The emergent Neuro-Vascular Team concept, mirroring the multi-disciplinary Heart Team, embraces diverse specializations, tailores personalized, stratified medicine approaches to individual patient needs, and integrates innovative imaging and risk-assessment biomarkers. Proposed approach integrates collaboration of multiple specialists central to carotid artery stenosis management such as neurology, stroke medicine, cardiology, angiology, ophthalmology, vascular surgery, endovascular interventions, neuroradiology and neurosurgery. Moreover, patient education regarding current treatment options, their risks and advantages, is pivotal, promting patient's active role in clinical care decisions. This enables optimization of interventions ranging from lifestyle modification, carotid revascularization by stenting or endarterectomy, as well as pharmacological management encompassing statins, novel lipid-lowering and antithrombotic strategies and targeting inflammation and vascular dysfunction. This consensus document provides a harmonized multi-specialty approach to multimorbidity prevention in carotid stenosis patients, based on comprehensive knowledge review, pinpointing research gaps in an evidence-based medicine approach. It aims to be a foundational tool for interdisciplinary collaboration and prioritized patient-centric decision-making.

Alterungsbedingte Gefäßveränderungen am Beispiel der Arteria carotis

Einer der Hauptrisikofaktoren für das Vorliegen einer Karotisstenose und des karotisbedingten Schlaganfalls ist das Lebensalter. Ziel dieses Übersichtsartikels ist die Darstellung des aktuellen Wissensstands über altersbedingte Veränderungen der Gefäße am Beispiel der Karotisstenose.Die Gefäßalterung (vaskuläre Seneszenz) als Abnahme struktureller und funktioneller Eigenschaften der Gefäßwand spielt sich auf verschiedenen Ebenen ab. Auf multizellulärer Ebene kommt es mit zunehmendem Alter hauptsächlich aufgrund von atherosklerotischen Veränderungen der Gefäßwand zu einer Zunahme von Gefäßvolumen und -durchmesser sowie der Intima-Media-Dicke. Auf zellulärer und extrazellulärer Ebene kommt es zur Abnahme von Elastinfasern, glatten Muskelzellen und der Gesamtzellularität sowie zur Zunahme der Lipid‑, Cholesterin- und Kalziumphosphatablagerungen und der Neovaskularisierung. Ursachen der Gefäßalterung auf molekularer Ebene sind insbesondere oxidativer Stress, chronische Entzündungsreaktion, mitochondriale Dysfunktion, epigenetische Veränderungen, Dysregulation der Expression nicht kodierender RNAs (ncRNAs) und die Zunahme der Seneszenz. Der altersbedingte Verlust der Heilungs- und Reparaturfähigkeit des Gewebes macht die Plaques vulnerabler und im Falle der A. carotis anfälliger für ischämische Schlaganfälle.Zunehmende Erkenntnisse über den Einfluss des Alterns auf die Epigenetik und der ncRNAs in atherosklerotischen Plaques kann zukünftig das individuelle Risiko von Patienten genauer quantifizieren und zur Entwicklung zielgerichteter Therapiestrategien beitragen. Weitere Studien sind auf diesem Gebiet jedoch notwendig, um das gesamte Ausmaß der Gefäßalterung und den damit einhergehenden Erkrankungen zu verstehen, damit diesen dann gezielt entgegenwirkt werden kann.

Important recommendations of the German-Austrian S3 guidelines on management of extracranial carotid artery stenosis

Lesions of the extracranial carotid artery are the cause of 10-15 % of all cases of cerebral ischemia. The aims of the updated S3 guidelines are evidence-based and consensus-based recommendations for action on comprehensive care of patients with extracranial carotid stenosis in Germany and Austria. A systematic literature search (1990-2019) and methodical assessment of existing guidelines and systematic reviews were carried out. Consensus answers to 37 key questions with evidence-based recommendations. The prevalence of extracranial carotid stenosis is approximately 4% and increases after the age of 65 years. The most important examination method is duplex sonography. Randomized controlled studies (RCT) have shown that carotid endarterectomy (CEA) of an asymptomatic 60-99% carotid artery stenosis reduces the absolute risk of stroke (absolute risk reduction, ARR) within 5 years in comparison to drug treatment alone by 4.1%. Due to an improved pharmaceutical prevention of arteriosclerosis, the S3 guidelines recommend a prophylactic CEA of a 60-99% stenosis only for patients without an increased surgical risk. Additionally, one or more clinical or imaging results should be present, which indicate an increased risk of carotid-related stroke in the follow-up. For medium-grade (50-69 %) and high-grade (70-99 %) symptomatic stenoses the ARRs after 5 years are 4.6% and 15.6%, respectively. Systematic reviews of RCTs have shown that CEA is associated with a ca. 50% lower periprocedural risk of stroke compared to carotid artery stenting (CAS). There are no differences in the long-term course. The CEA is recommended for high-grade asymptomatic, medium-grade and high-grade symptomatic carotid stenosis as a standard procedure, alternatively CAS can be considered. For both procedures the periprocedural stroke rate/mortality during hospitalization should be a maximum of 2% (asymptomatic stenosis) or 4% (symptomatic stenosis). Both CEA and CAS necessitate a critical evaluation of the indications and strict quality criteria. Future studies should evaluate even better selection criteria for an individual, optimal, conservative, operative or endovascular treatment.

The burden of carotid-related strokes

The burden of carotid-related strokes

The Natural History and Stroke Risk of Carotid Artery Occlusion

Limited available data suggests the incidence of carotid artery occlusion (CAO) is declining, and if detected, the association with acute stroke is very low. We report our long-term stroke outcomes in patients with CAO in an integrated health system. We identified adult patients with evidence of CAO at initial imaging from 2008 to 2012 or identified during follow-up through 2017 without prior carotid intervention. The primary outcome was acute ischemic stroke (AIS) attributed to the carotid artery (any ipsilateral stroke within the anterior circulation, including internal capsule, basal ganglia, and thalamus). Timing of stroke was assessed in three intervals: >6 months prior to CAO imaging, within 6 months of CAO including the time of imaging study acquisition, and in follow-up until study endpoint. Secondary outcomes include ischemic stroke of other etiology and/or location, and survival. Among over 94,800 eligible patients with carotid imaging, 2084 arteries in 2044 patients were identified with CAO, including 1787 arteries (85.8%) occluded at baseline and 297 arteries (14.3%) that occluded in follow-up. The mean age was 71 ± 11 years, and 35.6% of patients were female. The mean maximal follow-up was 4.8 ± 3.1 years. Of patients that occluded in follow-up, 37, 60, and 189 CAO were seen with baseline arteries with mild/none, moderate, and severe stenosis, respectively. The mean time of progression to occlusion (without interceding intervention) was 3.2 ± 2.2 years for arteries with no/mild stenosis, 3.5 ± 2.4 years for arteries with moderate stenosis, and 1.5 ± 2.0 years for arteries with severe stenosis. In total, 366 ipsilateral AIS events (17.6%) occurred in 346 arteries, with 297 strokes in arteries occluded at baseline and 69 in arteries that occluded in follow-up. The majority of carotid-related strokes (79.2%) occurred within 6 months prior to CAO (Table). After ipsilateral AIS, 5 patients (11.6%) died within 30 days, an additional 8 patients (18.6%) within 1 year, and 16 patients (37.2%) were alive at the end of follow-up. The overall mortality rate was 43.5%, with 13.9% of patients lost to follow-up. There were 370 other strokes (17.8%) observed in 350 arteries, including 308 contralateral strokes in 288 arteries and 62 ipsilateral strokes not attributable to carotid disease. The observed incidence of CAO is low in this select cohort of patients; however, the incidence of carotid-related stroke and associated short- and long-term mortality is high. Further investigation is needed to identify patients at risk of progression to CAO to prevent the associated morbidity and mortality of stroke.TableCharacteristics of occlusion and stroke outcomes by initial artery statusTotalN = 2084, No. (%)Occlusion at baseline n = 1787, No. (%)Occluded during follow-up n = 297, No. (%)Ipsilateral carotid-related stroke366 (17.6)297 (16.6)69 (23.2) >6 months prior to occlusiona30 (8.2)20 (6.7)10 (14.5) ≤6 months prior to occlusiona290 (79.2)243 (81.8)47 (68.1)In follow-up (after occlusion)a46 (12.6)34 (11.4)12 (17.4)aPercentages derived from the total number of ipsilateral carotid-related strokes in each column. Open table in a new tab

Abstract WMP39: Laser Angioscopy in Carotid Artery Disease: Imaging Findings and Histopathological Correlation

Our understanding and management of carotid artery disease has largely relied on angiography, US and MR. However, existing modalities cannot accurately identify the spectrum of thrombogenic lesions on the vascular surface or reliably detect structural markers of instability. Thus, the natural history of the different histopathological hallmarks of advanced or complicated plaques is unknown, and many patients with culprit substenotic plaques are misdiagnosed with cryptogenic stroke. An intraluminal approach to directly inspect the endovascular surfaces at unprecedented resolutions would enable detailed structural analysis of carotid plaques and the identification of the root cause of carotid-related strokes. A scanning fiber angioscope (SFA), a high-definition 1.2-mm forward-viewing camera that generates videos by spirally scanning low-power laser beams, was developed for clinical use and employed to analyze the endovascular surfaces of ex vivo human carotid arteries (n=95) and endarterectomized plaques (n=20). Specimens were then imaged with US and micro-CT, and all vascular diagnostic tests obtained in the patients undergoing carotid revascularization were accessed. Imaging findings in the vascular surfaces were then validated by histomorphological analysis of &gt;300 lesions, and an angioscopic classifier for atherosclerosis was generated. Full-color videos at 30Hz and at a resolution &gt;200,000 pixels were generated from the entire endovascular circumference in all specimens with depth-of-focus larger than 5cm in saline solution. The ability to analyze the surface anatomy with unparalleled detail allowed the identification of early, intermediate, advanced and complex atherosclerotic lesions, including ulceration of fibrotic cap, excavation of the necrotic core leading to pseudolumens, intimal flaps, exposed necrotic core to the lumen, erosions, recent and remote intimal hemorrhages, luminal thrombus, eruptive calcified nodules and calcified intimal sheaths and plates. SFA offers a direct view of the endoluminal surfaces with unparalleled resolution and has the potential to revolutionize research, diagnosis, prognosis and image-guided therapy in carotid atherosclerosis.

Invited commentary

In laminar flow situations, shear occurs in the zone between the blood vessel wall (velocity = zero) and the central column of flow. In vitro measurement of shear, sometimes difficult, has been achieved with laser Doppler sensors and with magnetic resonance techniques.1Yap C.H. Saikrishnan N. Tamilselvan G. Yoganathan A.P. Experimental technique of measuring dynamic fluid shear stress on the aortic surface of the aortic valve leaflet.J Biomech Eng. 2011; 133: 061007Crossref PubMed Scopus (27) Google Scholar, 2Campagnolo L. Nikolić M. Perchoux J. Lim Y.L. Bertling K. Loubiere K. et al.Flow profile measurement in microchannel using the optical feedback interferometry sensing technique.Microfluidics Nanofluidics. 2013; 14: 113-119Crossref Scopus (54) Google Scholar Casa et al diagrammed the cross section of flow velocity as parabolic for laminar flow and showed how platelets and blood clotting factors can be activated in the shear zone, the region where the velocity curve becomes asymptotic with the wall (Casa Fig 1). The thickness of this zone is related to many parameters, including viscosity. Shear forces are not uniform in the proximal internal carotid artery: under physiologic conditions, the zone of abnormal shear can vary longitudinally as well as along the circumference, as measurements with magnetic resonance techniques have demonstrated.3Markl M. Wegent F. Zech T. Bauer S. Strecker C. Schumacher M. et al.In vivo wall shear stress distribution in the carotid artery: effect of bifurcation geometry, internal carotid artery stenosis, and recanalization therapy.Circ Cardiovasc Imaging. 2010; 3: 647-655Crossref PubMed Scopus (160) Google Scholar The biologic behavior of artery walls in zones of severe stenosis is more difficult to model. Not only is there the problem of turbulence, but measurement accuracy is difficult because of physical limitations of instrumentation. A normal internal carotid artery diameter ranges from 6 to 8 mm, and a significantly stenotic segment is at or less than 1 mm. The axial gate size used to measure carotid flow velocity by duplex ultrasound is typically 1 to 3 mm. The axial resolution for this measurement is on the order of magnitude 0.1 to 0.2 mm, depending on the frequency selected, typically 9 to 12 MHz. Axial resolution is inversely proportional to frequency.4Kremkau F.W. Sonography principles and instruments.9th edition. Elsevier, St. Louis, MO2016: 66Google Scholar Because the formula for shear stress includes 1/(D3), there is potential for any value to have an inherent error between 30% and 70% based on the physics of ultrasound probes, irrespective of operator-related variability. Velocity measurements in a duplex ultrasound scan are sensitive to the beam angle, which is also operator dependent. If shear is to be used as a parameter for risk, it is therefore necessary that the measurement is conducted at the highest probe frequency and is not in an area of severely eccentric plaque, which may distort the measurements. For any vascular laboratory, the overall reproducibility of velocity measurements is not generally ascertained. Understanding that this is the case, reporting standards therefore mandate ranges, not use of precise velocities. Shear stress criteria may need to be formulated in a similar manner. Shear stress is proportional to blood viscosity. For the purposes of clarity, Casa et al did not factor variability of viscosity in their analysis, but it is well established that blood viscosity can vary significantly in any individual over time.5Wells Jr., R.E. Merrill E.W. The variability of blood viscosity.Am J Med. 1961; 31: 505-509Abstract Full Text PDF PubMed Scopus (26) Google Scholar Some literature indicates that viscosity is not really important in terms of carotid-related stroke risk,6Parkhurst K.L. Lin H.F. Devan A.E. Barnes J.N. Tarumi T. Tanaka H. Contribution of blood viscosity in the assessment of flow-mediated dilation and arterial stiffness.Vasc Med. 2012; 17: 231-234Crossref PubMed Scopus (21) Google Scholar but this should be validated in the context of the present study. Therefore, before translating from Casa to clinical utility, as proposed in this paper, it will be necessary for some significant research to occur. In particular, standards for precise vascular laboratory measurement will need to be redefined. The opinions or views expressed in this commentary are those of the author and do not necessarily reflect the opinions or recommendations of the Journal of Vascular Surgery or the Society for Vascular Surgery. Shear rate is a better marker of symptomatic ischemic cerebrovascular events than velocity or diameter in severe carotid artery stenosisJournal of Vascular SurgeryVol. 69Issue 2PreviewThis study was designed to test the hypothesis that the high shear rate of flow in the area of carotid stenosis is associated with the incidence of ischemic symptoms in patients with a high degree of carotid stenosis. Full-Text PDF Open Archive

Invited commentary

Invited commentary

CAD 2. Perioperative Complication Risk Prediction According to Carotid Plaque Ulceration in 964 Consecutive Carotid Endarterectomies

The role of the carotid plaque fibrous cap in carotid-related stroke risk has been demonstrated in many studies. The aim of this study was to evaluate the relationship between the presence of a carotid plaque ulcer and the perioperative complication risk in a consecutive series/cohort of patients submitted to carotid endarterectomy (CEA) at our academic tertiary hospital. A retrospective review of a prospectively collected database on consecutive CEAs performed between January 2009 and December 2017 was performed. All patients with a carotid plaque ulcer (defined as a discontinuation in the carotid fibrous cap of >2 mm) at carotid duplex ultrasound were analyzed. Perioperative (30-day) complications considered for analysis were transient ischemic attack, minor and major stroke, death, myocardial infarction, hemodynamic instability, cervical hematoma, and cranial nerve palsy. The prognostic value of plaque ulcer on the development of perioperative complications was assessed by odds ratio (OR) estimation. Among 964 CEAs (158 symptomatic, 806 asymptomatic), a carotid plaque ulcer was detected in 207 patients. Complications are listed in the Table. Plaque ulcer was significantly associated with preoperative neurologic symptoms (OR, 1.51; 95% confidence interval [CI], 1.02-2.22; P = .03), but it was not significantly associated with an increase in total number of complications in the whole cohort (OR, 1.37; 95% CI, 0.86-2.17; P = 0.17) or in the symptomatic (OR, 1.47; 95% CI, 0.51-4.27; P = .46) or asymptomatic (OR, 1.36; 95% CI, 0.81-2.28; P = .23) groups. The presence of an ulcer was not able to predict the development of neurologic complications (transient ischemic attack, minor and major stroke, neurologic death) in symptomatic (OR, 1.30; 95% CI, 0.23-7.41; P = .75) and asymptomatic (OR, 1.50; 95% CI, 0.68-3.30; P = .30) patients. In our experience, a carotid plaque ulcer is significantly associated with preoperative carotid-related neurologic symptoms, but it is not able to predict an increase in neurologic or total complications. Its presence demands a prompt intervention to reduce the risk of carotid-related embolism.TableComplications in 964 carotid endarterectomies (CEAs)Ulcerated plaque (n = 207), No.Nonulcerated plaque (n = 757), No.Total (N = 964), No. (%)Neurologic death123 (0.31)Cardiac death112 (0.20)Major stroke2810 (1.03)Minor stroke4913 (1.34)TIA4913 (1.34)Asymptomatic CEA thrombosis033 (0.31)Cervical hematoma71825 (2.56)Hemodynamic instability347 (0.72)Cervical nerve palsy61723 (2.38)Myocardial infarction066 (0.62)Total2877105 (10.89)TIA, Transient ischemic attack. Open table in a new tab

Risk factor profile and anatomic features of previously asymptomatic patients presenting with carotid-related stroke

ObjectiveAlthough carotid atherosclerotic-mediated stroke remains a major cause of morbidity and mortality, some have suggested intervention in carotid stenosis should be limited to symptomatic patients given the advances in medical therapy. The present study was conducted to assess the atherosclerotic risk factor profiles, anatomic features, and clinical outcomes of previously asymptomatic patients admitted with stroke of carotid etiology. MethodsWe reviewed the data from 3382 patients admitted to a tertiary referral center with an ischemic stroke during 2005 to 2015. We focused on patients admitted with a radiographically confirmed infarct ipsilateral to a documented carotid artery stenosis ≥50%, with the admitting neurology team adjudicating the stroke etiology as carotid related. Patients were excluded if they had had a previous transient ischemic attack, previous infarct ipsilateral to any carotid lesion, or previous carotid revascularization, intracranial hemorrhage, or malignancy. Patient demographic data, medical treatments before stroke, stroke admission carotid imaging, and stroke treatments and outcomes were assessed. ResultsA total of 219 carotid stroke patients (7% of all strokes) were identified, of whom 61% were white and 66% were men, with a mean age of 68 ± 12 years. Hypertension (79%) and smoking (33% current; 29% former) were predominant risk factors. On admission, 50% were receiving antiplatelet therapy (aspirin, n = 92 [41%]; clopidogrel, n = 9 [4%]; dual therapy, n = 11 [5%]) and 55% were receiving lipid-lowering agents (statin, n = 115 [53%]; other, n = 6 [2%]); 77 patients (35%) were receiving both antiplatelet and lipid-lowering therapy. Of the 219 patients, 156 (71%) presented with a moderate or severe stroke (National Institutes of Health stroke scale ≥5 at admission), 54 (25%) received lytic therapy, 96 (43%) presented with an occluded ipsilateral internal carotid artery, and 117 (53%) ultimately underwent carotid revascularization at a median of 4 days. Individuals receiving both antiplatelet and lipid-lowering therapy were significantly less likely to experience a moderate or severe stroke (44% vs 78%; P = .006). ConclusionsInternal carotid artery occlusion is the culprit lesion in 43% of carotid-related strokes in those without previous symptoms. Previously asymptomatic patients not receiving combined antiplatelet and lipid-lowering medical therapy presenting with carotid-related stroke are significantly more likely to experience a severe, debilitating stroke. However, those receiving appropriate risk-reduction medical therapy are still at risk of carotid-mediated stroke. These results suggest medical therapy alone is unlikely to be sufficient stroke prevention for patients with significant carotid stenosis.

IP117. Perioperative Complication Risk Prediction According to Carotid Plaque Ulceration in 964 Consecutive Carotid Endarterectomies∗

The role of the carotid plaque fibrous cap in carotid-related stroke risk has been demonstrated in many studies. The aim of this study was to evaluate the relationship between the presence of a carotid plaque ulcer and the perioperative complication risk in a consecutive series/cohort of patients submitted to carotid endarterectomy (CEA) at our academic tertiary hospital. A retrospective review of a prospectively collected database on consecutive CEAs performed between January 2009 and December 2017 was performed. All patients with a carotid plaque ulcer (defined as a discontinuation in the carotid fibrous cap of >2 mm) at carotid duplex ultrasound were analyzed. Perioperative (30-day) complications considered for analysis were TIA, minor and major stroke, death, myocardial infarction, hemodynamic instability, cervical hematoma, and cranial nerve palsy. The prognostic value of plaque ulcer on the development of perioperative complications was assessed by odds ratio (OR) estimation. Among 964 CEAs, 158 were performed in symptomatic patients and 806 in asymptomatic patients. A carotid plaque ulcer was detected in 207 patients. Complications are reported in the Table. Plaque ulcer was significantly associated with preoperative presence of neurologic symptoms (OR, 1.51; 95% confidence interval [CI], 1.02-2.22; P = .03), but it was not significantly associated with an increase in total number of complications in the whole cohort (OR, 1.37; 95% CI, 0.86-2.17; P = .17) or in the symptomatic (OR, 1.47; 95% CI, 0.51-4.27; P = .46) or asymptomatic (OR, 1.36; 95% CI, 0.81-2.28; P = .23) groups. The presence of an ulcer was not able to predict the development of neurologic complications (transient ischemic attack, minor and major stroke, neurologic death) in symptomatic (OR, 1.30; 95% CI, 0.23-7.41; P = .75) and asymptomatic (OR, 1.50; 95% CI, 0.68-3.30; P = .30) patients. The presence of a carotid plaque ulcer is significantly associated with the presence of preoperative carotid-related neurologic symptoms, but it is not able to predict an increase in neurologic or total complications in a consecutive series of symptomatic and asymptomatic patients submitted to CEA.TableComplications occurred in 964 carotid endarterectomies (CEAs)Ulcerated plaque (207)Nonulcerated plaque (757)Total (964), No. (%)Neurologic death123 (0.31)Cardiac death112 (0.20)Major stroke2810 (1.03)Minor stroke4913 (1.34)TIA4913 (1.34)Asymptomatic CEA thrombosis033 (0.31)Cervical hematoma71825 (2.56)Hemodynamic instability347 (0.72)Cervical nerve palsy61723 (2.38)Myocardial infarction066 (0.62)Total2877105 (10.89)TIA, Transient ischemic attack. Open table in a new tab

The Involvement of miRNA in Carotid-Related Stroke

Cardiovascular disease is the leading cause of morbidity and mortality in developed countries. Stroke is associated with a marked disability burden and has a major economic impact; this is especially true for carotid artery stroke. Major advances in primary and secondary prevention during the last few decades have helped to tackle this public health problem. However, better knowledge of the physiopathology of stroke and its underlying genetic mechanisms is needed to improve diagnosis and therapy. miRNAs are an important, recently identified class of post-transcriptional regulators of gene expression and are known to be involved in cerebrovascular disease. These endogenous, small, noncoding RNAs may have applications as noninvasive biomarkers and therapeutic tools in practice. Here, we review the involvement of several miRNAs in cell-based and whole-animal models of stroke, with a focus on human miRNA profiling studies of carotid artery stroke. Lastly, we describe the miRNAs' potential role as a biomarker of stroke.

Risk Factor Profile of Previously Asymptomatic Patients Presenting With Carotid-Related Stroke

Whereas carotid atherosclerosis-mediated stroke remains a major cause of morbidity and mortality, some have suggested that intervention in carotid stenosis should be limited to symptomatic patients, given advances in medical therapy. This study was conducted to assess atherosclerotic risk factor profiles of those previously asymptomatic patients admitted with stroke of carotid etiology. We reviewed 3382 patients admitted to a tertiary care center diagnosed with an ischemic stroke during 2005 to 2015. This study focused on patients admitted with a radiographically confirmed infarct ipsilateral to a documented carotid artery stenosis ≥50%, with the admitting neurology team adjudicating the stroke etiology as carotid related. Patients were excluded if they had previous transient ischemic attack, prior infarct ipsilateral to any carotid lesion, prior carotid revascularization, intracranial hemorrhage, or malignant disease. A total of 219 (7% of all strokes) carotid stroke patients were identified, of whom 61% were white and 66% were male, with a mean age of 68 ± 12 years. Hypertension (79%) and smoking (33% current; 29% former) were predominant risk factors. On admission, 47% were receiving antiplatelet therapy (aspirin, 42% [n = 92]; clopidogrel, 4% [n = 8]; dual therapy, 5% [n = 11]) and 55% were taking lipid-lowering agents (statin, 53% [n = 115]; other, 2% [n = 6]); 35% (n = 77) were receiving both antiplatelet and lipid-lowering therapy. Of these patients, 80% (n = 177) presented with a moderate or severe stroke (National Institutes of Health Stroke Scale ≥5 at admission), 25% (n = 54) received lytic therapy, 44% (n = 96) presented with an occluded ipsilateral internal carotid artery, and 53% (n = 117) ultimately underwent carotid revascularization at a median of 4 days. Individuals receiving both antiplatelet and lipid-lowering therapy were significantly less likely to experience a moderate or severe stroke event (44% vs 78%; P = .006). Previously asymptomatic patients receiving inadequate medical therapy presenting with carotid-related stroke are significantly more likely to experience a severe, debilitating stroke. However, those receiving appropriate medical therapy are still at risk for carotid-mediated stroke. These data refute the contention that medical therapy alone is sufficient stroke prevention therapy for patients with significant carotid bifurcation atherosclerotic stenosis.

CREST-2: Identifying the Best Method of Stroke Prevention for Carotid Artery Stenosis: National Institute of Neurological Disorders and Stroke Organizational Update.

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 …

Abstract 168: Coated-Platelets Improve TIA/Stroke Prediction in Asymptomatic Internal Carotid Artery Stenosis

Background: Coated-platelets, a subset of procoagulant platelets observed upon dual agonist stimulation with collagen and thrombin, support a robust prothrombinase activity and provide a unique measure of platelet thrombotic potential. Coated-platelet levels are increased in large artery stroke compared to controls, and higher levels are associated with early stroke recurrence. We now examine whether coated-platelet levels predict TIA/stroke in asymptomatic internal carotid artery (ICA) stenosis. Methods: Consecutive patients referred for carotid Doppler evaluation were enrolled. Those taking anticoagulants, with dementia, or TIA/stroke within 6 months before enrollment were excluded. Coated-platelets were determined at baseline and reported as percent of cells converted to coated-platelets. Subjects were followed for up to 3 years for TIA/stroke. A receiver operating characteristic curve (ROC) analysis was conducted to compare performance of two models in predicting incident TIA/stroke. The first model included stenosis severity (&lt;70% or ≥70%) while the second model included stenosis severity (&lt;50% or ≥50%) and coated-platelet level as predictors. Results: We enrolled 343 patients. Follow-up ranged from 4 days to 39.7 months (mean 10.6 months). Fourteen TIA/strokes were observed. Ten were carotid-related. ROC analysis showed significant improvement in the predictive ability of the stenosis (≥50%) plus coated-platelets model compared to the stenosis (≥70%) only model (AUC: 0.88 ± 0.05 versus 0.71 ± 0.08, respectively; p=0.05). A cut-off of 46.5% for coated-platelet levels in combination with stenosis ≥50% yielded a sensitivity of 0.70 (0.42-0.98; 95% CI), specificity of 0.91 (0.88-0.94), positive predictive value of 0.18 (0.06-0.31), and a negative predictive value of 0.99 (0.98-1.0). Coated-platelet levels at 6 months did not significantly differ from baseline (p=0.69). Conclusions: Coated-platelet levels identify asymptomatic ICA stenosis patients at low risk for carotid-related stroke, which suggests a role for coated-platelets in risk stratification prior to revascularization.