Implications of the Centers for Medicare and Medicaid Services (CMS) decision to expand indications for carotid artery stenting.

OBJECTIVE: On October 11, 2023, the Centers for Medicare and Medicaid Services (CMS) expanded the indications for carotid artery stenting (CAS) to include patients with ≥50% symptomatic or ≥70% asymptomatic carotid stenosis. The aim of this article was to investigate the implications of this decision. METHODS: The reasons behind the increased coverage for CAS are analyzed and discussed, as well as the various Societies supporting or opposing the expansion of indications for CAS. RESULTS: The benefits associated with expanding CAS indications include providing an additional therapeutic option to patients and enabling individualization of treatment according to patient-specific characteristics. The drawbacks of expanding CAS indications include a possible bias in decision-making and an increase in inappropriate CAS procedures. CONCLUSIONS: The purpose of the CMS recommendation to expand indications for CAS is to improve the available therapeutic options for patients. Hopefully this decision will not be misinterpreted and will be used to improve patient options and patient outcomes.

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.

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.

Exploring vertebral artery stump syndrome: An overlooked cause of posterior ischemic strokes. A narrative review of current management options.

INTRODUCTION: Stump syndrome is defined as a clinical syndrome resulting from a distal intracranial vessel embolic stroke due to an extracranial vessel occlusion. Similar to the anterior circulation, the recurrence of ischemic strokes in territories supplied by the posterior circulation in the presence of vertebral artery occlusion is termed Vertebral Artery Stump Syndrome (VASS). MATERIAL AND METHODS: We conducted a literature review, identifying 72 patients with transient ischemic attacks (TIAs) or ischemic strokes attributed to VASS, according to Kawano criteria. We categorized all patients in two groups focusing on the therapeutic management those who underwent primary medical treatment and those who received endovascular or surgical treatment either in acute or chronic phase. RESULTS: In the anticoagulant therapy group, only 1 patient had a stroke recurrence. Among the 4 on antiplatelets, all had recurrences, but 3 benefited from switching to anticoagulants or endovascular therapy. In the endovascular therapy group, worse outcomes were linked to acute large vessel occlusion. Endovascular treatment of the vertebral artery, in a chronic phase, was explored in literature for recurrent TIAs or minor strokes suggesting that this could be a viable therapeutic alternative when medical treatment failed in preventing recurrence of ischemic stroke. CONCLUSIONS: Some studies suggest that anticoagulant medical therapy may be beneficial for VASS and endovascular therapy has also been reported for selected patients. However, data on treatment outcomes and prognosis are still underreported, making treatment decisions challenging. Randomized Controlled Trials are needed to establish the optimal treatment approach.

Polygenic Risk Score for Cardiovascular Diseases in Artificial Intelligence Paradigm: A Review.

Cardiovascular disease (CVD) related mortality and morbidity heavily strain society. The relationship between external risk factors and our genetics have not been well established. It is widely acknowledged that environmental influence and individual behaviours play a significant role in CVD vulnerability, leading to the development of polygenic risk scores (PRS). We employed the PRISMA search method to locate pertinent research and literature to extensively review artificial intelligence (AI)-based PRS models for CVD risk prediction. Furthermore, we analyzed and compared conventional vs. AI-based solutions for PRS. We summarized the recent advances in our understanding of the use of AI-based PRS for risk prediction of CVD. Our study proposes three hypotheses: i) Multiple genetic variations and risk factors can be incorporated into AI-based PRS to improve the accuracy of CVD risk predicting. ii) AI-based PRS for CVD circumvents the drawbacks of conventional PRS calculators by incorporating a larger variety of genetic and non-genetic components, allowing for more precise and individualised risk estimations. iii) Using AI approaches, it is possible to significantly reduce the dimensionality of huge genomic datasets, resulting in more accurate and effective disease risk prediction models. Our study highlighted that the AI-PRS model outperformed traditional PRS calculators in predicting CVD risk. Furthermore, using AI-based methods to calculate PRS may increase the precision of risk predictions for CVD and have significant ramifications for individualized prevention and treatment plans.

A systematic review and meta-analysis of the occurrence of spinal cord ischemia after endovascular repair of thoracoabdominal aortic aneurysms.

OBJECTIVE: The rate of endovascular repair of thoracoabdominal aortic aneurysms (TAAA-ER) has increased considerably in recent years. Although the mortality and morbidity rates have improved, the incidence of spinal cord ischemia (SCI) has not declined significantly. The aim of the present systematic review and meta-analysis was to examine the SCI rates with respect to the efficacy of the different approaches. METHODS: Cohort studies and case series (>20 patients) reporting SCI rates after TAAA-ER were eligible for inclusion. The primary outcome measure was the evaluation of SCI. The moderators considered were primarily the staged vs nonstaged approach, the use of cerebrospinal fluid drainage (CSFD), and TAAA extension. The permanent SCI and mortality rates were extracted. RESULTS: A total of 27 studies with 2333 patients were included in the meta-analysis. The pooled estimate for SCI was 11% (95% confidence interval [CI], 8%-15%; I2, 79%). For extent I, II, III, and V TAAA, the pooled SCI rate was 13% (95% CI, 10%-17%; I2, 69%). For extent IV TAAA, the pooled SCI rate was 6% (95% CI, 3%-10%; I2, 62%). A staged TAAA-ER approach was used in 20 studies and a nonstaged approach in 8 (1 study had included both). A lower pooled SCI rate was identified after staged than after nonstaged TAAA-ER (9% vs 18%, respectively; P = .02). Staging was accomplished in >1 month in nine studies and ≤1 month in two studies, leading to similar SCI rates (7% vs 11%, respectively; P = .26). The method of staging (thoracic endoprosthesis or temporary aortic sac perfusion) did not affect the SCI rates. Symptomatic CSFD was associated with a similar pooled rate of SCI compared with prophylactic CSFD (10% vs 10%, respectively; P = .99). The pooled permanent SCI rate was 6% (6% for extent I, II, III, and V TAAA; and 3% for extent IV TAAA). The pooled rate of 30-day mortality was 7%, with a similar incidence for the staged and nonstaged approaches (6% vs 9%, respectively). Interstage mortality was reported in 9 studies, with a pooled estimate rate of 1.6%. CONCLUSIONS: SCI had occurred in 11% of TAAA-ER, and one half of these cases were permanent. A staged approach can reduce SCI rates independently of the timing and method adopted. The overall mortality rate for staged TAAA-ER was 7%, with one fifth of the deaths (1.6%) occurring between stages.

Carotid Artery Stenting With Double-Layer Stent: A Systematic Review and Meta-Analysis.

BACKGROUND: Carotid artery stenting (CAS) in the treatment of significant stenosis is a cause of stroke due to both plaque prolapse and cerebral embolization. New types of stents with a double-layer structure have been designed to minimize plaque prolapse and embolization; these double-layer stents (DLSs) should be able to reduce the stroke risk; however, definite data on their performance are scarce in the literature. METHODS: A systematic search was performed through PubMed, Scopus, and Cochrane Library, according to PRISMA guidelines; all studies on CAS with DLS (Roadsaver/Casper or CGuard) up to January 1, 2022, with a cohort of at least 20 patients were considered eligible. The present meta-analysis was approved and registered on PROSPERO register (CRD42022297512). Patients with tandem lesions or complete carotid occlusion were excluded from the study. The 30-day stroke rate after CAS was analyzed evaluating the preoperative symptomatic status and DLS occlusion. The estimated pooled rate of events was calculated by random effect model and moderators were evaluated. RESULTS: A total of 14 studies were included in the meta-analysis for a total of 1955 patients. The estimated overall (95% confidence interval [CI]) stroke rate was 1.4% (0.9%-2.2%, I2 = 0%), which was not influenced by the type of DLS used: CGuard 0.8% (0.4%-1.8%, I2 = 0%) versus Roadsaver/Casper 1.5% (0.7%-3.2%, I2 = 0%), p=0.30. The 30-day estimated stroke rate was 1.5% (0.8%-2.9%, I2 = 0%) in asymptomatic and 1.9% (1.0%-3.6%, I2 = 0%) in symptomatic patients, with no influence by moderators. The 30-day DLS occlusion rate was 0.8% (0.4%-1.8%, I2 = 0%). The publication bias assessment identified asymmetry in the asymptomatic populations. CONCLUSION: The overall 30-day stroke rate in CAS with DLS is low (1.4%), with similar results in symptomatic and asymptomatic patients. Acute occlusion of DLS is rare (0.8%). Further studies are necessary to reduce the publication bias for asymptomatic patients. CLINICAL IMPACT: CAS with DLS is associated to a low rate of 30-day stroke in both symptomatic (1.9%) and asymptomatic (1.5%) patients. The type of DLS (CGuard or Roadsaver/Casper) did not affect the 30-day stroke rate.

Inflammatory and Prothrombotic Biomarkers, DNA Polymorphisms, MicroRNAs and Personalized Medicine for Patients with Peripheral Arterial Disease.

Classical risk factors play a major role in the initiation and development of atherosclerosis. However, the estimation of risk for cardiovascular events based only on risk factors is often insufficient. Efforts have been made to identify biomarkers that indicate ongoing atherosclerosis. Among important circulating biomarkers associated with peripheral arterial disease (PAD) are inflammatory markers which are determined by the expression of different genes and epigenetic processes. Among these proinflammatory molecules, interleukin-6, C-reactive protein, several adhesion molecules, CD40 ligand, osteoprotegerin and others are associated with the presence and progression of PAD. Additionally, several circulating prothrombotic markers have a predictive value in PAD. Genetic polymorphisms significantly, albeit moderately, affect risk factors for PAD via altered lipoprotein metabolism, diabetes, arterial hypertension, smoking, inflammation and thrombosis. However, most of the risk variants for PAD are located in noncoding regions of the genome and their influence on gene expression remains to be explored. MicroRNAs (miRNAs) are single-stranded, noncoding RNAs that modulate gene expression at the post-transcriptional level. Patterns of miRNA expression, to some extent, vary in different atherosclerotic cardiovascular diseases. miRNAs appear to be useful in the detection of PAD and the prediction of progression and revascularization outcomes. In conclusion, taking into account one's predisposition to PAD, i.e., DNA polymorphisms and miRNAs, together with circulating inflammatory and coagulation markers, holds promise for more accurate prediction models and personalized therapeutic options.

Optimal Management of Asymptomatic Carotid Stenosis in 2021: The Jury is Still Out. An International, Multispecialty, Expert Review and Position Statement.

OBJECTIVES: The recommendations of international guidelines for the management of asymptomatic carotid stenosis (ACS) often vary considerably and extend from a conservative approach with risk factor modification and best medical treatment (BMT) alone, to a more aggressive approach with a carotid intervention plus BMT. The aim of the current multispecialty position statement is to reconcile the conflicting views on the topic. MATERIALS AND METHODS: A literature review was performed with a focus on data from recent studies. RESULTS: Several clinical and imaging high-risk features have been identified that are associated with an increased long-term ipsilateral ischemic stroke risk in patients with ACS. Such high-risk clinical/imaging features include intraplaque hemorrhage, impaired cerebrovascular reserve, carotid plaque echolucency/ulceration/ neovascularization, a lipid-rich necrotic core, a thin or ruptured fibrous cap, silent brain infarction, a contralateral transient ischemic attack/stroke episode, male patients < 75 years and microembolic signals on transcranial Doppler. There is growing evidence that 80-99% ACS indicate a higher stroke risk than 50-79% stenoses. CONCLUSIONS: Although aggressive risk factor control and BMT should be implemented in all ACS patients, several high-risk features that may increase the risk of a future cerebrovascular event are now documented. Consequently, some guidelines recommend a prophylactic carotid intervention in high-risk patients to prevent future cerebrovascular events. Until the results of the much-anticipated randomized controlled trials emerge, the jury is still out regarding the optimal management of ACS patients.

Editor's Choice - Effect of Carotid Interventions on Cognitive Function in Patients With Asymptomatic Carotid Stenosis: A Systematic Review.

OBJECTIVE: To determine the effect of carotid endarterectomy (CEA) and carotid artery stenting (CAS) on early (baseline vs. maximum three months) and late (baseline vs. at least five months) cognitive function in patients with exclusively asymptomatic carotid stenoses (ACS). METHOD: Searches were conducted in PubMed/Medline, Embase, Scopus, and the Cochrane library. This systematic review includes 31 non-randomised studies. RESULTS: Early post-operative period: In 24 CEA/CAS/CEA+CAS cohorts (n = 2 059), two cohorts (representing 91/2 059, 4.4% of the overall study population) reported significant improvement in cognitive function, while one (28/2 059, 1%) reported significant decline. Three cohorts (250/2 059, 12.5% reported "mixed findings" where some cognitive scores significantly improved, and a similar proportion declined. The majority (nine cohorts; 1 086/2 059, 53%) reported no change. Seven cohorts (250/2 059, 12.1%) were mostly unchanged but one to two individual test scores improved, while two cohorts (347/2 059, 16.8%) were mostly unchanged with one to two individual test scores worse. Late post-operative period: In 21 cohorts (n = 1 554), one (28/1 554, 1.8%) reported significantly worse cognitive function, one reported significant improvement (24/1 554, 1.5%), while a third (19/1 554, 1.2%) reported "mixed findings". The majority were unchanged (six cohorts; 1 073/1 554, 69%) or mostly unchanged, but with one to two cognitive tests showing significant improvement (11 cohorts; 386/1 554, 24.8%). Overall, there was a similar distribution of findings in small, medium, and large studies, in studies with controls vs. no controls, in studies comparing CEA vs. CAS, and in studies with shorter/longer late follow up. CONCLUSION: Notwithstanding accepted limitations regarding heterogeneity within non-randomised studies, CEA/CAS rarely improved overall late cognitive function in ACS patients (< 2%) and the risk of significant cognitive decline was equally low (< 2%). In the long term, the majority were either unchanged (69%) or mostly unchanged with one to two test scores improved (24.8%). Until new research identifies vulnerable ACS subgroups (e.g., impaired cerebral vascular reserve) or provides evidence that silent embolisation from ACS causes cognitive impairment, evidence supporting intervention in ACS patients to prevent/reverse cognitive decline is lacking.

Editor's Choice - Asymptomatic Carotid Stenosis and Cognitive Impairment: A Systematic Review.

OBJECTIVE: The aim was to evaluate the relationship between asymptomatic carotid stenosis (ACS) of any severity and cognitive impairment and to determine whether there is evidence supporting an aetiological role for ACS in the pathophysiology of cognitive impairment. DATA SOURCES: PubMed/Medline, Embase, Scopus, and the Cochrane library. REVIEW METHODS: This was a systematic review (35 cross sectional or longitudinal studies) RESULTS: Study heterogeneity confounded data interpretation, largely because of no standardisation regarding cognitive testing. In the 30 cross sectional and six longitudinal studies (one included both), 33/35 (94%) reported an association between any degree of ACS and one or more tests of impaired cognitive function (20 reported one to three tests with poorer cognition; 11 reported four to six tests with poorer cognition, while three studies reported seven or more tests with poorer cognition). There was no evidence that ACS caused cognitive impairment via silent cortical infarction, or via involvement in the pathophysiology of lacunar infarction or white matter hyperintensities. However, nine of 10 studies evaluating cerebral vascular reserve (CVR) reported that ACS patients with impaired CVR were significantly more likely to have cognitive impairment and that impaired CVR was associated with worsening cognition over time. Patients with severe ACS but normal CVR had cognitive scores similar to controls. CONCLUSION: Notwithstanding significant heterogeneity within the constituent studies, which compromised overall interpretation, 94% of studies reported an association between ACS and one or more tests of cognitive impairment. However, "significant association" does not automatically imply an aetiological relationship. At present, there is no clear evidence that ACS causes cognitive impairment via silent cortical infarction (but very few studies have addressed this question) and no evidence of ACS involvement in the pathophysiology of white matter hyperintensities or lacunar infarction. There is, however, better evidence that patients with severe ACS and impaired CVR are more likely to have cognitive impairment and to suffer further cognitive decline with time.

An updated systematic review and meta-analysis of results of transcervical carotid artery stenting with flow reversal.

OBJECTIVE: Transcervical carotid artery stenting (CAS) has emerged as an alternative to transfemoral CAS. An earlier systematic review from our group (n = 12 studies; 739 transcervical CAS procedures [489/739 with flow reversal]) demonstrated that transcervical CAS is a safe procedure associated with a low incidence of stroke and complications. Since then, new studies have been published adding nearly 1600 patients to the literature. We aimed to update our early systematic review and also to perform a meta-analysis to investigate outcomes specifically after transcervical CAS with flow reversal. METHODS: An electronic search of PubMed/MEDLINE, Embase, and the Cochrane databases was carried out to identify studies reporting outcomes after transcervical CAS with flow reversal. Crude event rates for outcomes of interest were estimated by simple pooling of data. A proportion meta-analysis was also performed to estimate pooled outcome rates. RESULTS: A total of 18 studies (n = 2110 transcervical CAS procedures with flow reversal) were identified. A high technical success (98.25%) and a low mortality rate (0.48%) were recorded. The crude rates of major stroke, minor stroke, transient ischemic attack, and myocardial infarction (MI) were 0.71%, 0.90%, 0.57%, and 0.57%, respectively; a cranial nerve injury occurred in 0.28% of the procedures. A neck hematoma was reported in 1.04% of the procedures, and a carotid artery dissection occurred in 0.76% of the interventions; in 1.09% of the cases, conversion to carotid endarterectomy was required. After a meta-analysis was undertaken, the pooled technical success rate was 98.69% (95% confidence interval [CI], 97.19-99.70). A pooled mortality rate of 0.04% (95% CI, 0.00-0.29) was recorded. The pooled rate of any type of neurologic complications was 1.88 (95% CI, 1.24-2.61), whereas the pooled rates of major stroke, minor stroke, and transient ischemic attack were 0.12% (95% CI, 0.00-0.46), 0.15% (95% CI, 0.00-0.50), and 0.01% (95% CI, 0.00-0.22), respectively. The pooled rate of bradycardia/hypotension was 10.21% (95% CI, 3.99-18.51), whereas the pooled rate of MI was 0.08% (95% CI, 0.00-0.39). A neck hematoma after transcervical CAS was recorded in 1.51% (95% CI, 0.22-3.54) of the procedures; in 0.74% (95% CI, 0.05-1.95) of the interventions, conversion to CEA was required. Finally, a carotid artery dissection during transcervical CAS occurred in 0.47% (95% CI, 0.00-1.38) of the procedures. CONCLUSIONS: This updated systematic review and meta-analysis demonstrated that transcervical CAS with flow reversal is associated with high technical success, almost zero mortality, and low rates of major stroke, minor stroke, MI, and complications.

Why randomized controlled trials do not always reflect reality.

OBJECTIVE: Randomized controlled trials (RCTs) constitute level I evidence and are used as the backbone of guidelines and recommendations for treatment. Although RCTs are theoretically the studies of choice for the assessment of the effectiveness of health care interventions, these trials (and their interpretation) may sometimes result in erroneous conclusions, erroneous therapeutic decisions, and incorrect recommendations. We aimed to check the applicability of the results of RCTs to everyday practice. METHODS: We reviewed the literature for studies comparing the results of RCTs with observational or population-based studies in the field of vascular surgery, focusing on two specific topics: the results of carotid artery stenting vs carotid endarterectomy for the management of carotid artery stenosis; and the results of open surgical repair vs endovascular aneurysm repair for the management of ruptured abdominal aortic aneurysms. RESULTS: We found considerable discrepancy in the results of RCTs with real-life registries and observational studies in both topics. In the management of carotid artery stenosis, observational studies reported worse outcomes after carotid artery stenting compared with carotid endarterectomy. Regarding ruptured abdominal aortic aneurysms, population-based studies reported better results for endovascular aneurysm repair compared with open repair. In contrast, RCTs in both topics reported similar results for the two procedures. CONCLUSIONS: There is evidence that RCTs sometimes do not reflect clinical reality and are therefore potentially misleading to the reader. Every RCT has to be interpreted and applied carefully using complete available evidence and good clinical judgment.