An International, Expert-Based Delphi Consensus Document on Controversial Issues about TransCarotid Artery Revascularization (TCAR).

OBJECTIVE: TransCarotid Artery Revascularization (TCAR) has emerged as an alternative therapeutic modality to carotid endarterectomy (CEA) and transfemoral carotid artery stenting (TFCAS) for the management of patients with carotid artery stenosis. However, certain issues regarding the indications and contraindications of TCAR remain unanswered or unresolved. The aim of this international, expert-based Delphi Consensus document was to attempt to provide some guidance on these topics. METHODS: A 3-Round Delphi Consensus process was performed including 29 experts. The aim of Round 1 was to investigate the differing views and opinions of the participants. Round 2 was carried out after the results from the literature on each topic were provided to the participants. During Round 3, the participants had the opportunity to finalize their vote. RESULTS: Most participants agreed that TCAR can/can probably/possibly be performed within 14 days of a cerebrovascular event, but it is best to avoid it in the first 48 hours. It was felt that TCAR cannot/should not replace TFCAS or CEA, as each procedure has specific indications and contraindications. Symptomatic patients >80 years should probably be treated with TCAR rather than with TFCAS. TCAR can/can probably be used for the treatment of restenosis following CEA/TFCAS. Finally, there is a need for a randomized controlled trial to provide better evidence for the unresolved issues. CONCLUSIONS: This Delphi Consensus document attempted to assist the decision-making of physicians/interventionalists/vascular surgeons involved in the management of carotid stenosis patients. Furthermore, areas requiring additional research were identified. Future studies and randomized controlled trials should provide more evidence to address the unanswered questions regarding TCAR.

Diet and exercise in relation to lower extremity artery disease.

Adherence to the Mediterranean diet (MeD) has been associated with a reduced incidence of peripheral arterial disease (PAD)/lower extremity arterial disease (LEAD) in observational trials and in a randomized trial. In secondary prevention, a lower hazard ratio for composite major adverse cardiovascular events has been associated with better adherence to MeD in a relatively small, randomized trial. This has not been confirmed in a sub-analysis of a large interventional trial of dual antithrombotic treatment. The effects of vegetarian, vegan or low carbohydrate/ketogenic diets on the incidence and outcomes of PAD/LEAD are not known. While abdominal obesity is associated with diabetes mellitus and PAD/LEAD, the lowest incidence of PAD/LEAD has been found in subjects with a body mass index 25-29.9 kg/m2. Malnutrition is a negative prognostic factor for survival of patients with chronic limb threatening ischemia. Physical activity (PA) is an acute stressor, but habitual recreational PA results in beneficial adaptations and improved health. In observational studies, lower levels of exercise and lower physical fitness have been associated with more prevalent PAD/LEAD. In contrast to coronary artery disease, that shows a reverse J-shaped relationship between long-term endurance exercise and coronary atherosclerosis, such a relationship is not known for PAD/LEAD. A general recommendation for maintaining cardiovascular health is performing regular moderate-intensity exercise with some vigorous-intensity aerobic PA, and resistance exercise at least twice a week. Combinations of healthy behaviors are more effective in preventing PAD/LEAD than a single behavioral component. In treatment of PAD/LEAD causing intermittent claudication, supervised walking training is recommended among measures of first-line treatment, while unsupervised walking training should be considered as an alternative.

STABILISE for acute type B aortic dissection.

INTRODUCTION: Stent-assisted, balloon-induced intimal disruption and relamination of aortic dissection (STABILISE) is an extended downstream endovascular management technique for acute type B aortic dissection (TBAD), that aimed to achieve complete aortic remodeling. This systematic review aimed to assess the early and mid-term clinical outcomes with STABILISE in the management of TBAD. EVIDENCE ACQUISITION: A literature search was performed on the Medline, Web of Science, Scopus, and SciELO databases, which returned 195 studies. Five studies were included. Data were extracted using predefined forms. EVIDENCE SYNTHESIS: In total, one hundred patients with acute or subacute TBAD managed with STABILISE were included. All studies reported a technical success of 100%. Thirty-day mortality was estimated at 4% (4/100) with no further deaths documented during an estimated mean follow-up of 12.7 months (range 12-15 months). Five percent developed spinal cord ischemia and another 5% developed visceral artery occlusions. One case of aortic rupture during time of balloon inflation was reported. Rare complications included delayed retrograde dissection (1%), aortobronchial fistula (1%), and renal failure (1%). One case of disconnection between stent-graft and bare stent was documented. Six percent of patients developed endoleak, predominately type I. Overall re-intervention rate was 21%, as reported in all studies. Complete obliteration of the false lumen in the thoracic aorta was achieved in 99% of patients and in the abdominal aorta in 96% of patients. CONCLUSIONS: STABILISE technique carries promising early and mid-term outcomes with high technical success and low mortality and morbidity. Excellent results on complete false lumen obliteration were observed. However, the heterogeneity among available studies' methodology does not permit firm conclusions, and further prospective analyses are needed to study the long-term outcomes of STABILISE.

Dyslipidemia and lower extremity arterial disease.

INTRODUCTION: Dyslipidemia is an established risk factor for cardiovascular diseases. We aimed to review its role in the pathogenesis of lower extremity arterial disease (LEAD), as well as the effect of lipid-lowering treatment on the progression of LEAD. EVIDENCE ACQUISITION: PubMed/MedLine, EMBASE and Scopus were searched between January 1990 and January 2024 for articles investigating the role of dyslipidemias and hyperlipidemias in the pathogenesis of LEAD. A separate search focused on the effects of lipid-lowering therapy on patients with LEAD. EVIDENCE SYNTHESIS: There is evidence that dyslipidemias play a major role in the development of LEAD. All patients with LEAD should receive intensive lipid-lowering therapy for the reduction not only of claudication symptoms and amputation rates, but also of myocardial infarction and cardiovascular event rates. CONCLUSIONS: Vascular specialists should keep in mind the pivotal role of dyslipidemia in the pathogenesis and progression of LEAD.

Collapse of a cephalic arch stent: An atypical complication of hemodialysis vascular access.

Access dysfunction is a significant contributor to morbidity in hemodialysis patients. The cephalic arch is a common location of vascular stenosis, with a considerable risk of relapse. While covered stents demonstrated a higher patency rate when compared to percutaneous transluminal angioplasty, their placement has some issues. Stent collapse and guttering are well-documented in arteries but not in arteriovenous fistulas. This report describes an unusual case of a cephalic arch stent collapsing 1 month after its positioning, as evidenced by access dysfunction.

An international, expert-based, Delphi consensus document on controversial issues in the management of abdominal aortic aneurysms.

OBJECTIVE: As a result of conflicting, inadequate or controversial data in the literature, several issues concerning the management of patients with abdominal aortic aneurysms (AAAs) remain unanswered. The aim of this international, expert-based Delphi consensus document was to provide some guidance for clinicians on these controversial topics. METHODS: A three-round Delphi consensus document was produced with 44 experts on 6 prespecified topics regarding the management of AAAs. All answers were provided anonymously. The response rate for each round was 100%. RESULTS: Most participants (42 of 44 [95.4%]) agreed that a minimum case volume per year is essential (or probably essential) for a center to offer open or endovascular AAA repair (EVAR). Furthermore, 33 of 44 (75.0%) believed that AAA screening programs are (probably) still clinically effective and cost effective. Additionally, most panelists (36 of 44 [81.9%]) voted that surveillance after EVAR should be (or should probably be) lifelong. Finally, 35 of 44 participants (79.7%) thought that women smokers should (or should probably/possibly) be considered for screening at 65 years of age, similar to men. No consensus was achieved regarding lowering the threshold for AAA repair and the need for deep venous thrombosis prophylaxis in patients undergoing EVAR. CONCLUSIONS: This expert-based Delphi consensus document provides guidance for clinicians regarding specific unresolved issues. Consensus could not be achieved on some topics, highlighting the need for further research in those areas.

Contemporary open surgical approaches for the management of carotid stenosis: a comprehensive review.

This study aims to provide an overview on contemporary open surgical approaches for the management of carotid artery stenosis. A comprehensive literature search was performed to identify and categorize open surgery intervention techniques for the management of carotid artery stenosis, focusing on the benefits and drawbacks of each technique. Five surgical techniques for carotid endarterectomy (CEA) have been described: CEA with primary closure, CEA with patch closure, CEA by eversion technique, CEA by modified eversion technique and CEA by partial eversion. Evidence has reported significantly higher rates of perioperative complications after CEA with primary closure, including 30-days stroke rate and late restenosis. Although more recent techniques have been reported to provide superior outcomes, electing the best surgical technique is still a matter of debate. Also, CEA using a mini-skin incision has been associated to lower risk of cranial/cervical nerve injury and shorter length of hospital stay. The selection of the surgical intervention should be tailored and have into consideration individual patient characteristics, clinical considerations, surgeon preference and surgical team expertise. Further large-scale randomized clinical trials are needed to support more robust decisions on the choice of contemporary open surgical approaches to manage carotid stenosis.

Specificities of primary and secondary prevention of lower extremity artery disease in patients with diabetes mellitus.

Diabetes mellitus (DM) is a major risk factor for lower extremity arterial disease (LEAD) and about 20% of symptomatic patients with LEAD have DM. In subjects with DM, LEAD is a cause of morbidity and mortality. DM typically causes complications in the form of macro- and microangiopathy. In these patients, macroangiopathy manifests as atherosclerosis like in non-diabetic patients. However, its course is accelerated due to accompanying risk factors like hyperlipidemia and hypertension, with cumulative effects. Other factors are also relevant such as inflammation, endothelial dysfunction, platelet activation, blood rheological properties, hypercoagulability, and factors stimulating vascular smooth muscle cell proliferation. Additionally, DM is a risk factor for restenosis and amputation. DM is strongly associated with femoral-popliteal and tibial LEAD, which manifests earlier in patients with DM and may progress more rapidly to critical limb ischemia. Diabetic microangiopathy is characterized by arteriolosclerosis and interstitial fibrosis which additionally affects progression and outcomes of angiopathy of lower limbs. Glycemic control particularly decreases microangiopathic complications, while prevention of macrovascular complications requires treatment of accompanying risk factors like hypertension and dyslipidemia.

Higher Levels of Cytokines in Patients with Chronic Limb-Threatening Ischemia.

BACKGROUND: Inflammation is a key element in the initiation and progression of peripheral arterial disease (PAD). Understanding the impact of inflammatory molecules, as cytokines in PAD could help us to improve the prognosis of these patients. The main goal of this study was to compare the serum level of cytokines between patients with claudication to those with chronic limb-threatening ischemia (CLTI). The second objective was to evaluate the relationship between the levels of cytokines and death or amputation rate. METHODS: An observational, single-center, and prospective study was conducted from January 2018 to July 2022. The study was approved by the ethical commission of the Local Hospital (75/2017). Patients with PAD, suggested by the clinical history and objective examination and confirmed with ankle-brachial index, attending vascular surgery consultations of the first author were included. The following exclusion criteria were applied: i) bedridden individuals or subjects who refused to participate in the protocol; ii) diseases responsible for body composition changes or proinflammatory state; iii) recent diet change, iv) active malignancy, v) autoimmune disease, vi) active infection, vii) chronic renal failure (glomerular filtration rate <30 mL/min/1.73 m2), or viii) heart failure in the past 3 months. This cohort was observed at admission, 3, 6, and 12 months. A panel of 27 cytokines was determined with ELISA, at baseline. RESULTS: We included 119 subjects (mean age: 67.58 ± 9.60 years old; 79.80% males), 65 patients with claudication and 54 with CLTI. From the 27 cytokines analyzed, patients with CLTI, when compared to those with claudication, had a higher serum level of 11 cytokines: IL1ra, IL-6, IL-8, IL12 p70, G-CSF, IP-10, MCP-1, MIP-1α, PDGF-ß, RANTES, and TNF-α. From the group of patients with CLTI those who underwent a major amputation had a higher serum level of FGF-basic [median = 49.04; interquartile range = 37.03-52.49; versus median = 33.04; interquartile range = 28.60-38.98; P = 0.001]. CONCLUSIONS: Patients with CLTI have higher serum level of inflammatory cytokines, which may have role in the prognosis of these patients.

Reversion of the Inflammatory Markers in Patients With Chronic Limb-Threatening Ischemia.

BACKGROUND: Peripheral artery disease is characterized by an intense inflammatory process that can be associated with a higher mortality rate, particularly in chronic limb-threatening ischemia (CLTI). This study aims to compare the evolution of inflammatory markers between patients with claudication with those with CLTI at 3, 6, and 12 months. METHODS AND RESULTS: An observational, single-center, and prospective study was conducted. A total of 119 patients with peripheral artery disease (65 with claudication and 54 with CLTI) were observed and inflammatory markers collected at admission and 3, 6, and 12 months. At admission, patients with CLTI, when compared with patients with claudication, had significantly higher serum levels of C-reactive protein and fibrinogen (positive acute-phase proteins) and lower serum level of albumin, total cholesterol, and high-density lipoprotein (negative acute-phase proteins): C-reactive protein (g/dL), 2.90 (25th-75th percentile, 2.90-4.90) versus 6.80 (25th-75th percentile, 2.90-53.26) (P=0.000); fibrinogen (mg/dL), 293.00 (25th-75th percentile, 269.25-349.00) versus 415.50 (25th-75th percentile, 312.00-615.75) (P=0.000); total cholesterol (mg/dL), 161.79±95% [152.74-170.85] versus 146.42%±95% [135.30-157.53] (P=0.034); high-density lipoprotein (mg/dL), 50.00 (25th-75th percentile, 41.00-60.00) versus 37.00 (25th-75th percentile, 30.00-45.50) (P=0.000); albumin (g/dL): 4.00 (25th-75th percentile, 3.70-4.20) versus 3.60 (25th-75th percentile, 3.10-4.00) (P=0.003). The association between CLTI and total cholesterol was lost after adjusting for confounders. Three months after the resolution of the CLTI, there was an increase in the levels of negative acute-phase proteins and a decrease in positive acute-phase proteins. These inflammatory proteins did not register an evolution in patients with claudication. The differences in the inflammatory proteins between groups disappeared at 6 months. CONCLUSIONS: CLTI has an inflammatory environment that can be partially reverted after resolution of the ischemic process, emphasizing the importance of timely intervention.

Inflammatory Cells in Adipose Tissue and Skeletal Muscle of Patients with Peripheral Arterial Disease or Chronic Venous Disease: A Prospective, Observational, and Histological Study.

The main goal of this study was to assess whether the presence of peripheral arterial disease (PAD) correlates with increased inflammatory cell infiltration. An observational, single-centre, and prospective study was conducted from January 2018 to July 2022. Clinical characteristics and anthropometric measures were registered. Consecutive PAD patients with surgical indications for a common femoral artery approach and patients with varicose veins with an indication for surgical ligation of the saphenofemoral junction were included. In both groups, samples of sartorius skeletal muscle, subcutaneous adipose tissue (SAT), and perivascular adipose tissue (PVAT) were collected from the femoral region. We analysed the characteristics of adipocytes and the presence of haemorrhage and inflammatory cells in the samples of PVAT and SAT via haematoxylin-eosin staining. We found that patients with PAD had significantly more inflammatory cells in PVAT [16 (43.24%) vs. 0 (0%) p = 0.008]. Analysing SAT histology, we observed that patients with PAD had significantly more CD45+ leucocytes upon immunohistochemical staining [32 (72.73%) vs. 3 (27.27%) p = 0.005]. Upon analysing skeletal muscle histology with haematoxylin-eosin staining, we evaluated skeletal fibre preservation, as well as the presence of trauma, haemorrhage, and inflammatory cells. We registered a significantly higher number of inflammatory cells in patients with PAD [well-preserved skeletal fibres: PAD = 26 (63.41%) vs. varicose veins = 3 (37.50%) p = 0.173; trauma: PAD = 4 (9.76%) vs. varicose veins = 2 (25.00%) p = 0.229; haemorrhage: PAD = 6 (14.63%) vs. varicose veins = 0 (0%) p = 0.248; inflammatory cells: PAD = 18 (43.90%) vs. varicose veins = 0 (0%) p = 0.018]. Patients with PAD had a higher number of inflammatory cells in skeletal muscle and adipose tissue (PVAT and SAT) when compared with those with varicose veins, emphasizing the role of inflammation in this group of patients.

Why selective screening for asymptomatic carotid stenosis is currently appropriate: a special report.

INTRODUCTION: Two of the main reasons recent guidelines do not recommend routine population-wide screening programs for asymptomatic carotid artery stenosis (AsxCS) is that screening could lead to an increase of carotid revascularization procedures and that such mass screening programs may not be cost-effective. Nevertheless, selective screening for AsxCS could have several benefits. This article presents the rationale for such a program. AREAS COVERED: The benefits of selective screening for AsxCS include early recognition of AsxCS allowing timely initiation of preventive measures to reduce future myocardial infarction (MI), stroke, cardiac death and cardiovascular (CV) event rates. EXPERT OPINION: Mass screening programs for AsxCS are neither clinically effective nor cost-effective. Nevertheless, targeted screening of populations at high risk for AsxCS provides an opportunity to identify these individuals earlier rather than later and to initiate a number of lifestyle measures, risk factor modifications, and intensive medical therapy in order to prevent future strokes and CV events. For patients at 'higher risk of stroke' on best medical treatment, a prophylactic carotid intervention may be considered.

Peri-Carotid Adipose Tissue and Atherosclerosis at Carotid Bifurcation.

Vulnerable carotid plaques are responsible for 20% of the ischemic strokes. The identification of these asymptomatic carotid plaques that will become symptomatic is essential but remains unclear. Our main goal was to investigate whether the amount of the peri-carotid adipose tissue, estimated by the extra-media thickness (EMT), is associated with the atherosclerotic characteristics at the carotid bifurcation in patients with PAD. An observational, prospective, single-center, longitudinal study was conducted. Overall, 177 patients were subjected to carotid Doppler ultrasound at the study admission. The following data were collected: EMT, intima-media thickness (IMT), the presence of carotid plaques, the area of the highest plaque, the presence of "acute culprit" carotid stenosis, and the grade of internal carotid stenosis. "Acute culprit" carotid stenosis was defined as a significant atherosclerotic plaque that leads to a neurologic event within 15 days. From each carotid bifurcation, a right and a left EMT were determined. We analyzed both the mean EMTs (calculated as the mean between the right and the left EMT) and the EMT ipsilateral to the carotid bifurcation. The presence of carotid plaques was associated with a higher mean EMT [Median = 1.14; IQR = 0.66 versus Median = 0.97; IQR = 0.40; p = 0.001]. A positive correlation was found between the mean EMT and IMT (right: ρ = 0.20; p = 0.010; left: ρ = 0.21; p = 0.007) and between the mean EMT and the area of the largest carotid plaque (right: ρ = 0.17; p = 0.036; left: ρ = 0.22; p = 0.004). Left carotid stenosis ≥ 70% was associated with higher ipsilateral EMT [Median = 1.56; IQR = 0.70 versus Median = 0.94; IQR = 0.42; p = 0.009]. Patients with "acute culprit" carotid stenosis had a higher ipsilateral EMT [left ipsilateral EMT: Median = 1.46; IQR = 0.63; "non-acute": Median = 0.94; IQR = 0.43; p = 0.009; right ipsilateral EMT: Median = 2.25; IQR = 0.62; "non-acute": Median = 1.00; IQR = 0.51; p = 0.015]. This difference was not found in the contra-lateral EMT. Six months after the neurologic event, EMT ipsilateral to an "acute culprit" carotid stenosis decreased (p = 0.036). The amount of peri-carotid adipose tissue, estimated with EMT, was associated with atherosclerosis at the carotid arteries. The mean EMT was associated with the features of chronic atherosclerosis lesions: the presence of carotid plaques, IMT, and the area of the highest plaque. Ipsilateral EMT was linked with "acute culprit" atherosclerotic plaque.

Inflammation Is a Histological Characteristic of Skeletal Muscle in Chronic Limb Threatening Ischemia.

BACKGROUND: The loss of skeletal muscle is a prognostic factor in several diseases including in patients with chronic limb threatening ischemia (CLTI). Patients with CLTI also have a lower skeletal mass and area when compared to those with claudication. However, there are no currently available data regarding the histological characteristics of core muscles in patients with CLTI. This study aims to determine the differences in core skeletal muscles between patients with claudication and those with CLTI. The second aim is to evaluate the differences in myokines, which are molecules secreted by skeletal muscle, between patients with claudication and those with CLTI. METHODS: An observational, prospective study was conducted from January 2018 to July 2022 involving consecutive patients with peripheral arterial disease (PAD). The clinical characteristics were registered. In PAD patients with surgical indication for common femoral artery approach, samples of sartorius skeletal muscle (and not from the limb muscles directly involved in the ischemic process) were collected. The samples were submitted to histological characterization on hematoxylin-eosin and to immunohistochemical analysis to detect CD45+ leukocytes and CD163+ macrophages. The extent of the inflammatory cells (leukocytes and macrophages) was semiquantitatively assessed using a 0-to-4 grade scale as follows: absent (0†), mild (†), moderate (††), severe (†††), and very severe (††††). Serum levels of myokines: irisin, myostatin, IL-8, and lL-6 were determined with multiplex bead-based immunoassay. RESULTS: 119 patients (mean age: 67.58 ± 9.60 years old, 79.80% males) 64 with claudication and 54 with CLTI were enrolled in the study. No differences were registered between patients with claudication and those with CLTI on age, gender, cardiovascular risk factors, and medication, except on smoking habits. There was a significantly higher prevalence of smokers and a higher smoking load in the claudication group. Samples of sartorius skeletal muscle from 40 patients (14 with claudication and 26 with CLTI) were submitted to histological analysis. No differences were found in skeletal muscle fibers preservation, trauma, or hemorrhage (on hematoxylin-eosin staining). However, in the immunohistochemistry study, we found more inflammatory cells CD45+ leukocytes in patients with CLTI when compared to those with claudication [CD45+ ≥ moderate (††): claudication (n = 14): 4; 28.57%; CLTI (n = 25): 16; 64.00%; P = 0.034]. Patients with CLTI also had higher tissue levels of CD163+ macrophages, but this difference was not significant [CD163+ ≥ moderate (††): claudication (n = 13): 7; 53.85%; CLTI (n = 27): 21; 77.78%; P = 0.122]. The serum levels of the myokines, irisin, and myostatin were below the lower limit of detection, in the majority of patients, so no valid results were obtained. However, patients with CLTI had a higher serum level of Interleukin (IL)-6 and IL-8. CONCLUSIONS: CLTI patients exhibit increased quantities of leukocytes in their sartorius muscle, as well as elevated serum levels of myokines IL-8 and IL-6. Inflamed skeletal muscle can contribute to the loss of muscle mass and account for the lower density of skeletal muscle observed in CLTI. Additionally, inflamed skeletal muscle may contribute to the development of systemic inflammation through the secretion of pro-inflammatory cytokines into the systemic circulation. Halting the inflammatory process could eventually improve the prognosis of CLTI patients.

An international, multispecialty, expert-based Delphi Consensus document on controversial issues in the management of patients with asymptomatic and symptomatic carotid stenosis.

OBJECTIVE: Despite the publication of various national/international guidelines, several questions concerning the management of patients with asymptomatic (AsxCS) and symptomatic (SxCS) carotid stenosis remain unanswered. The aim of this international, multi-specialty, expert-based Delphi Consensus document was to address these issues to help clinicians make decisions when guidelines are unclear. METHODS: Fourteen controversial topics were identified. A three-round Delphi Consensus process was performed including 61 experts. The aim of Round 1 was to investigate the differing views and opinions regarding these unresolved topics. In Round 2, clarifications were asked from each participant. In Round 3, the questionnaire was resent to all participants for their final vote. Consensus was reached when ≥75% of experts agreed on a specific response. RESULTS: Most experts agreed that: (1) the current periprocedural/in-hospital stroke/death thresholds for performing a carotid intervention should be lowered from 6% to 4% in patients with SxCS and from 3% to 2% in patients with AsxCS; (2) the time threshold for a patient being considered "recently symptomatic" should be reduced from the current definition of "6 months" to 3 months or less; (3) 80% to 99% AsxCS carries a higher risk of stroke compared with 60% to 79% AsxCS; (4) factors beyond the grade of stenosis and symptoms should be added to the indications for revascularization in AsxCS patients (eg, plaque features of vulnerability and silent infarctions on brain computed tomography scans); and (5) shunting should be used selectively, rather than always or never. Consensus could not be reached on the remaining topics due to conflicting, inadequate, or controversial evidence. CONCLUSIONS: The present international, multi-specialty expert-based Delphi Consensus document attempted to provide responses to several unanswered/unresolved issues. However, consensus could not be achieved on some topics, highlighting areas requiring future research.

Recent advances and controversial issues in the optimal management of asymptomatic carotid stenosis.

OBJECTIVE: The optimal management of patients with asymptomatic carotid stenosis (AsxCS) is enduringly controversial. We updated our 2021 Expert Review and Position Statement, focusing on recent advances in the diagnosis and management of patients with AsxCS. METHODS: A systematic review of the literature was performed up to August 1, 2023, using PubMed/PubMed Central, EMBASE and Scopus. The following keywords were used in various combinations: "asymptomatic carotid stenosis," "carotid endarterectomy" (CEA), "carotid artery stenting" (CAS), and "transcarotid artery revascularization" (TCAR). Areas covered included (i) improvements in best medical treatment (BMT) for patients with AsxCS and declining stroke risk, (ii) technological advances in surgical/endovascular skills/techniques and outcomes, (iii) risk factors, clinical/imaging characteristics and risk prediction models for the identification of high-risk AsxCS patient subgroups, and (iv) the association between cognitive dysfunction and AsxCS. RESULTS: BMT is essential for all patients with AsxCS, regardless of whether they will eventually be offered CEA, CAS, or TCAR. Specific patient subgroups at high risk for stroke despite BMT should be considered for a carotid revascularization procedure. These patients include those with severe (≥80%) AsxCS, transcranial Doppler-detected microemboli, plaque echolucency on Duplex ultrasound examination, silent infarcts on brain computed tomography or magnetic resonance angiography scans, decreased cerebrovascular reserve, increased size of juxtaluminal hypoechoic area, AsxCS progression, carotid plaque ulceration, and intraplaque hemorrhage. Treatment of patients with AsxCS should be individualized, taking into consideration individual patient preferences and needs, clinical and imaging characteristics, and cultural, ethnic, and social factors. Solid evidence supporting or refuting an association between AsxCS and cognitive dysfunction is lacking. CONCLUSIONS: The optimal management of patients with AsxCS should include BMT for all individuals and a prophylactic carotid revascularization procedure (CEA, CAS, or TCAR) for some asymptomatic patient subgroups, additionally taking into consideration individual patient needs and preference, clinical and imaging characteristics, social and cultural factors, and the available stroke risk prediction models. Future studies should investigate the association between AsxCS with cognitive function and the role of carotid revascularization procedures in the progression or reversal of cognitive dysfunction.