Search

Carotid atherosclerosis has a relevant impact on cerebral blood flow regulation. There is accruing evidence that hemodynamic impairment related to the presence of a significant carotid lumen narrowing may predispose to the development of cerebral dysfunctions, including a reduction in cognitive abilities. In the last years an increasing number of findings showed that carotid stenosis did contribute to cognitive impairment not only in relation to the occurrence of cerebral ischemic lesions, but also as an independent risk factor. The principal mechanisms involved are chronic hypoperfusion, microembolization and cerebrovascular reactivity impairment. Moreover, more recent studies showed alterations of regional functional connectivity. In this narrative review, we analyzed the relationships between carotid stenosis, cerebral hemodynamic derangement and cognitive impairment onset and progression, and underlined that cognitive impairment is the final result of the complex interaction between different elements, including also collateral circulation, cerebral hemodynamic status, brain connectivity and pro-inflammatory state. Further, therapeutic approaches, with a specific focus on vascular risk factors correction and on the effectiveness of surgical or endovascular interventions were discussed. We particularly focused our attention on the concept of "asymptomatic carotid stenosis", and how could a cognitive impairment improve after an intervention, and how this could change the indications to surgical approach. Larger studies and randomized controlled trials are urgently required to better define time, characteristics and effectiveness of both medical and surgical/endovascular approaches.

Indications for intervention in hemodynamically relevant carotid artery stenosis (carotid endarterectomy or stenting) are primarily based on a degree of stenosis and symptomatology. To date the plaque vulnerability is rarely taken into account in clinical decision making although development of molecular imaging allows a better understanding of plaque biology and provides new techniques detecting potentially vulnerable plaque at risk. A significant number of reports describing the mechanisms of unstable plaque formation suggest that it is a multifactorial process. Inflammation, lipid accumulation, apoptosis, proteolysis, the thrombotic process and angiogenesis are among the main factors of carotid plaque destabilization. Although inflammation is a key process in development of plaque vulnerability, the hemostasis and neoangiogenesis should be regarded as equally important. Only a small group of asymptomatic patients may benefit from the invasive treatment and it remains a challenge to determine whether initially asymptomatic carotid plaque become unstable or vulnerable. Currently, the main task of research on atherosclerotic lesion imaging is focused on functional state of the plaque. The presence of one or more features such as stenosis progression, large plaque area, large juxta-luminal black area, plaque echolucency, intra-plaque hemorrhage, impaired cerebral vascular reserve and spontaneous embolization may indicate patients at higher risk for stroke suitable for revascularization. Treatment of carotid stenosis as one of the manifestations of generalized atherosclerosis requires a broad approach. Nowadays pharmacological treatment options for the atherosclerotic process are largely aimed at stimulating the plaque stabilization, but in symptomatic patients and selected asymptomatic patients, carotid plaque should be removed as a potential source of embolism.

The management of patients with symptomatic chronic total occlusion (CTO) of the internal carotid artery (ICA) is controversial. The aim of this systematic review was to investigate patient selection, technical success, early and late outcome of endovascular treatment for CTO of the ICA. PubMed/Medline and EMBASE databases were searched until January 2, 2020 for studies on endovascular treatment for CTO of the ICA. A descriptive analysis of demographic, clinical and anatomic data, endovascular technique, perioperative and late outcomes was performed. A total of 1,222 articles were screened, 8 retrospective or prospective cohort studies were reviewed; 276 patients, 18.9% females, mean age: 64.3 years, underwent attempt at endovascular treatment of 278 lesions. Two hundred and thirteen patients (77.2%) had neurological symptoms; the others had evidence of ipsilateral cerebral hypoperfusion. Two hundred and thirty-eight lesions (91.2%) were treated >30 days after diagnosis of occlusion. Technical success was 66.9%. Perioperative mortality was 1.64% (4/243), early stroke rate was 3.3%. Follow-up averaged 23.4 months (range, 0.25-84 months), late mortality was 1.89% (5/265), stroke rate was 3.4% (9/265). Stroke rate was similar after successful stenting (3.57%, 4/112) vs. failed stenting (3.61%, 2/61; P=1.00), stroke/death rates were also similar after successful stenting (5.36%, 6/112) than after failed stenting (3.28%, 2/61; P=0.71). Endovascular treatment of CTO of the ICA in eight cohort studies was safe and feasible with a technical success of 67% and a low rate of early and late neurological complications. Pooled data in this review failed to confirm the benefit of successful stenting on stroke and mortality, but some of the included studies suggest benefit and some also supported improvement in neurocognitive function after successful stenting. Prospective randomized trials to investigate the benefit of endovascular treatment in addition to best medical therapy for symptomatic CTO of the ICA are urgently needed.

Patients with chronic kidney disease (CKD) have an increased cardiovascular (CV) risk that is only in part explained by established risk factors. Carotid arteriosclerosis and atherosclerosis are increased in CKD, play a role in the causation of CV disease in these patients and can affect the progression of renal disease. The arterial stiffening process is evident even in CKD patients with a very mild reduction of glomerular filtration rate (GFR) whereas arterial thickening is evident in more advanced stages. Possible mechanisms include functional and structural alterations of the arterial wall. Arterial stiffness can mediate the effect of CKD on target organs (i.e., brain, kidney and heart). In this review we discuss the arterial phenotype of patients with CKD. This is characterized by increased common carotid artery stiffness and outward remodeling (enlargement and thickening of the arterial wall) and a normal/reduced stiffness paired with an inward remodeling (narrowing of the arterial wall) of muscular arteries. We also discuss the consequences of carotid dysfunction, including the involvement of large elastic arteries stiffness on ventricular-vascular coupling, the mechanisms linking carotid stiffening and increased cardio- and cerebrovascular risk in CKD patients, and the therapeutic options to improve carotid function.

Atherosclerotic carotid artery stenosis causes about 10-20% of all ischemic strokes through two main mechanisms: hemodynamic impairment in case of significant stenosis and thromboembolism from an atherosclerotic plaque regardless of the degree of stenosis. The latter is the most frequent mechanism and appear to result from embolization from a vulnerable atherosclerotic plaque or acute occlusion of the carotid artery and propagation of thrombus distally. Downstream infarcts may occur in a territory of major cerebral artery or at the most distal areas between two territories of major cerebral arteries, the so-called watershed (WS), or border zone area. Although WS infarcts, especially deep WS infarct, were historically thought to be due to hemodynamic compromise, the role of microembolism has also been documented, both mechanisms may act synergistically to promote WS infarcts. Routine and more advanced imaging techniques may provide information on the underlying mechanism involved in ipsilateral ischemic stroke. A better understanding of ischemic stroke pathogenesis in carotid stenosis may limit the use of routine non-selective shunt, whose benefit-risk balance is debated, to patients with hemodynamic impairment. After reviewing existing evidence underpinning the contribution of the two mechanisms in downstream ischemic stroke and the various imaging techniques available to investigate them, we will focus on the pathogenesis of WS infarcts that remains debated.

Cardiovascular disease (CVD) is one of the leading causes of morbidity and mortality in the United States of America and globally. Carotid arterial plaque, a cause and also a marker of such CVD, can be detected by various non-invasive imaging modalities such as magnetic resonance imaging (MRI), computer tomography (CT), and ultrasound (US). Characterization and classification of carotid plaque-type in these imaging modalities, especially into symptomatic and asymptomatic plaque, helps in the planning of carotid endarterectomy or stenting. It can be challenging to characterize plaque components due to (I) partial volume effect in magnetic resonance imaging (MRI) or (II) varying Hausdorff values in plaque regions in CT, and (III) attenuation of echoes reflected by the plaque during US causing acoustic shadowing. Artificial intelligence (AI) methods have become an indispensable part of healthcare and their applications to the non- invasive imaging technologies such as MRI, CT, and the US. In this narrative review, three main types of AI models (machine learning, deep learning, and transfer learning) are analyzed when applied to MRI, CT, and the US. A link between carotid plaque characteristics and the risk of coronary artery disease is presented. With regard to characterization, we review tools and techniques that use AI models to distinguish carotid plaque types based on signal processing and feature strengths. We conclude that AI-based solutions offer an accurate and robust path for tissue characterization and classification for carotid artery plaque imaging in all three imaging modalities. Due to cost, user-friendliness, and clinical effectiveness, AI in the US has dominated the most.

Cervical artery dissection (CeAD) with an intramural haematoma can lead to stroke risk, especially in young patients. We performed comprehensive searches of the Cochrane Stroke Group Trials Register, the CENTRAL, MEDLINE and EMBASE to review the effectiveness of surgical and endovascular interventions versus best medical treatment alone for symptomatic CeAD. Furthermore, we aim to elaborate on the phenotypic individual disease manifestations of spontaneous Cervical Artery Dissection (sCAD) and how they translate into stroke and risk of dissection recurrence. Primary outcomes were ipsilateral stroke and disability. Secondary outcomes were death, any stroke, or transient ischaemic attack, residual stenosis >50%, recurrence of CeAD, expanding pseudo-aneurysm or major bleeding. Our search yielded no randomised controlled trials and/or controlled clinical trials (CCTs) comparing either carotid surgery or endovascular therapy with optimal medical management; thus there was no evidence to support the use of any specific method for management of extracranial CeAD in patients who fail antithrombotic therapy. However, despite the absence of controlled studies to compare surgery or endovascular therapy in patients who fail antithrombotic therapy, carotid surgery in young patients can be justified as a personalized precision approach given the high morbidity and mortality in this age group.

Carotid endarterectomy (CEA) is a surgical treatment option to prevent ischemic cerebrovascular accidents. Patients that present with pre-operative frailty might have an elevated risk for unfavorable outcomes after the CEA. A systematic search, using Medline, Embase, Web of Science and Cochrane Database, was performed for relevant literature on frailty in patients undergoing CEA. The study protocol was registered with PROSPERO (CRD42020190345). Eight articles were included. The pooled prevalence for pre-operative frailty was 23.9% (95% CI: 12.98–34.82). A difference in the incidence of complications between frail and non-frail patients (6.4% vs. 5.2%, respectively) and a difference in hospital length of stay [2 (IQR: 2–3) days vs. 1 (IQR: 1–2) day, respectively] were described. The 30-day mortality after CEA was 0.6% for non-frail patients, 2.6% for frail patients, and 4.9% for very frail patients (P1.5-fold increased risk was found for frail patients (OR 1.7, 95% CI: 1.4–2.0) and a >2.5-fold increased risk for very frail patients (OR 2.6, 95% CI: 2.2–3.1). In conclusion, this review shows the impact of frailty on outcome after CEA. Pre-operative frailty assessment with a validated, multi-domain tool should be implemented in the clinical setting as it will provide information on post-operative surgical outcomes and mortality risk but also frailty trajectory and cognitive decline.

Dual antiplatelet therapy is frequently prescribed for patients undergoing carotid artery stenting (CAS), however clopidogrel resistance might cause thromboembolic complications. The role of testing for clopidogrel resistance in patients undergoing CAS is unclear. In this study, we aimed to review the periprocedural thromboembolic outcomes in clopidogrel resistant patients who underwent CAS. We conducted a review of PubMed, EMBASE, and the Cochrane Library up to October 7, 2020. Studies were included that investigated at least ten patients aged 18 years or older with a symptomatic carotid artery stenosis requiring CAS. Studies were excluded that investigated patients with a carotid artery dissection, case reports, case series of less than ten patients, reviews, commentaries, letters to the editors, and conference abstracts. The primary endpoint was the incidence of thromboembolic events. One hundred seventy-seven unique articles were identified of which three studies were included in our systematic review. The sample sizes ranged from 76 to 449 patients and the follow-up duration from 24 hours to 2 years postprocedural. Two retrospective observational studies determined clopidogrel resistance using measurement of P2Y12 reaction units, and one historical cohort study used genetic testing. Two studies concluded that clopidogrel resistance was a risk factor for thromboembolic complications, the other found higher values of P2Y12 reaction units in patients with thromboembolic events compared to those without. In conclusion, current literature supports a possible relationship between clopidogrel resistance and thromboembolic complications in patients who underwent CAS. Preprocedural testing for clopidogrel resistance might therefore be of additional value. Randomized studies using a valid, reliable clopidogrel resistance test and clinical endpoints, are however required to make a definitive statement and to determine the impact of the thromboembolic complications. This study was registered within PROSPERO (CRD42020197318).

Carotid atherosclerotic lesions are correlated with atherosclerotic deterioration of the arterial wall in other vascular territories and with cardiovascular events. The detection of pre-symptomatic carotid lesions like intima-media thickness (IMT) and asymptomatic carotid plaques is possible by non-invasive ultrasound duplex scanning. Current measurement guidelines suggest an average measurement of IMT within 10 mm of the segment of the common carotid artery. The thickening of intima-media appears in a long subclinical period of atherosclerosis. Therefore, the determination of IMT has emerged as one of the methods for determining early structural deterioration of the arterial wall. A close interrelationship was shown between IMT and risk factors of atherosclerosis, their duration, and intensity. Different studies demonstrated that increased IMT is a powerful predictor of coronary, cerebrovascular, and peripheral arterial occlusive disease and their complication. A recent meta-analysis indicated a minimal improvement in the risk estimation of cardiovascular events after adding IMT to the Framingham Risk Score. These findings influenced the latest ACC/AHA guidelines which again recommend the use of carotid IMT measurement for individual risk assessment. The presence of atherosclerotic plaques indicates that the atherosclerotic process is already ongoing. The findings of different studies are equivocal that carotid plaques independently predict cardiovascular events and improve risk predictions for coronary artery disease when added to the Framingham Risk Score. However, besides the size of plaque and grade of stenosis, the structure of plaque calcification, vascularization, lipid core, and the surface of plaques are important indicators of related risks for cardiovascular events.

There are approximately 800,000 strokes in the United States (U.S.) annually. This number has remained the same for decades despite efforts at prevention. The Center for Disease Control (CDC) estimates that 80% of strokes could be prevented. A prime reason for failure of prevention is that the three immediate modifiable causes of strokes, carotid artery disease (CAD), atrial fibrillation (AFib), and hypertension (HTN) are asymptomatic in 80% of cases prior to the stroke. Strokes occur predominantly in seniors and the only possible means of reducing strokes on a large scale is to screen seniors for the asymptomatic disease so that it can be preemptively managed. We present a quick, accurate and cost-effective method of screening the senior population for asymptomatic carotid disease. The technique is a quick carotid scan (QCS). The QCS is a 1-minute long, image only, rapid, color flow ultrasound scan of the cervical carotid arteries that had a sensitivity of 97% when evaluated at New York University (NYU). Once identified by the QCS the approximately 8% of those screened found to have a positive QCS can then be referred for a full carotid duplex ultrasound (DUS). Those patients with a positive DUS can then be referred for further evaluation and appropriate stroke prevention management. The use of a full carotid DUS for screening widely for carotid disease is too time consuming and too costly. Approximately 160,000 or nearly 20% of the 800,000 strokes that occur annually in the U.S. are due to CAD that could in large part be prevented by screening the senior population with the QCS, finding those with CAD, evaluating them, and preemptively managing them prior to the occurrence of the stroke.

Carotid endarterectomy (CEA) with patch angioplasty is a widely used method for treating carotid artery stenosis. Patch infections are extremely rare, but the consequences may be serious. The current gold standard for treatment is patch excision and reconstruction with autologous material. However, no consensus has been reached and other options may be valuable as well in certain cases. The objective of this study was to evaluate the various treatment options for carotid patch infection after CEA with patch angioplasty on the basis of their outcomes (reinfection, ischemic stroke, and infection-related mortality). This systematic review was conducted in accordance with the PRISMA statement. The electronic bibliographic databases PubMed, Cochrane, and EMBASE were searched. Case series and case reports were included. Studies in languages other than English were excluded. Patients who developed a post-operative patch infection of CEA with patch angioplasty were included. Angioplasty could be performed with any type of patch. Patch infection needed to be confirmed by clinical presentation in combination with imaging, culture, or during the operation. The primary outcome measures were reinfection, ischemic stroke, and infection-related mortality. Eleven retrospective case series, two prospective case series, and seventeen case reports were included. The study size was 165 patients (mean age 69.7 years, M/F ratio 1.75:1). One hundred and seventy-one patches developed a patch infection after CEA with patch angioplasty and needed treatment. Treatment strategies included conservative treatment (14.0%), endovascular treatment (4.7%), and open surgery (81.4%). Mean follow-up was 34.8 months and extended up to 180 months. Reinfection rate was 4.7%, ischemic stroke rate 5.8%, and infection-related mortality rate 2.3%. No statistical comparison between treatment options could be performed, because of the heterogeneity of the included studies. Autologous material should be the primary choice of treatment if patch infection is diagnosed after CEA with patch angioplasty. In emergency situations, endovascular treatment, carotid ligation, or abscess drainage could be considered. Endovascular treatment and abscess drainage are temporary solutions. After the patient has recovered sufficiently, a more durable treatment i.e., open surgery is advised. Endo vacuum assisted closure (EndoVAC) seems to be promising. Further research is needed to determine the applicability of each treatment option.