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.

Clinical Outcomes of Extracranial Carotid Artery-Related Stroke Eligible for Mechanical Reperfusion on Top of Per-Guidelines Thrombolytic Therapy: Analysis from a 6-Month Consecutive Patient Sample in 2 Centers.

BACKGROUND Systemic intravenous thrombolysis and mechanical thrombectomy (MT) are guideline-recommended reperfusion therapies in large-vessel-occlusion ischemic stroke. However, for acute ischemic stroke of extracranial carotid artery origin (AIS-CA) there have been no specific trials, resulting in a data gap. MATERIAL AND METHODS We evaluated referral/treatment pathways, serial imaging, and neurologic 90-day outcomes in consecutive patients, presenting in a real-life series in 2 stroke centers over a period of 6 months, with AIS-CA eligible for emergency mechanical reperfusion (EMR) on top of thrombolysis as per guideline criteria. RESULTS Of 30 EMR-eligible patients (33.3% in-window for thrombolysis and thrombolysed, 73.3% male, age 39-87 years, median Alberta Stroke Program Early Computed Tomography Score (ASPECTS) 10, pre-stroke mRS 0-1 in all, tandem lesions 26.7%), 20 (66.7%) were EMR-referred (60% - endovascular, 6.7% - surgery referrals). Only 40% received EMR, nearly exclusively in stroke centers with carotid artery stenting (CAS) expertise (100% eligible patient acceptance rate, 100% treatment delivery involving CAS±MT with culprit lesion sequestration using micronet-covered stents). The emergency surgery rate was 0%. Baseline clinical and imaging characteristics did not differ between EMR-treated and EMR-untreated patients. Ninety-day neurologic status was profoundly better in EMR-treated patients: mRS 0-2 (91.7% vs 0%; P<0.001); mRS 3-5 (8.3% vs 88.9%; P<0.001), mRS 6 (0% vs 11.1%; P<0.001). CONCLUSIONS In a real-life AIS-CA setting, the referral rate of EMR-eligible patients for EMR was low, and the treatment rate was even lower. AIS-CA revascularization was delivered predominantly in stroke thrombectomy-capable cardioangiology centers, resulting in overwhelmingly superior patient outcome. Large vessel occlusion stroke referral and management pathways should involve centers with proximal-protected CAS expertise. AIS-CA, irrespective of any thrombolysis administration, is a hyperacute cerebral emergency and EMR-eligible patients should be immediately referred for mechanical reperfusion.

Randomized Clinical Trial of Surgical vs. Percutaneous vs. Hybrid Revascularization in Multivessel Coronary Artery Disease: Residual Myocardial Ischemia and Clinical Outcomes at One Year-Hybrid coronary REvascularization Versus Stenting or Surgery (HREVS).

AIM: Optimal revascularization strategy in multivessel (MV) coronary artery disease (CAD) eligible for percutaneous management (PCI) and surgery remains unresolved. We evaluated, in a randomized clinical trial, residual myocardial ischemia (RI) and clinical outcomes of MV-CAD revascularization using coronary artery bypass grafting (CABG), hybrid coronary revascularization (HCR), or MV-PCI. METHODS: Consecutive MV-CAD patients (n = 155) were randomized (1 : 1 : 1) to conventional CABG (LIMA-LAD plus venous grafts) or HCR (MIDCAB LIMA-LAD followed by PCI for remaining vessels) or MV-PCI (everolimus-eluting CoCr stents) under Heart Team agreement on equal technical and clinical feasibility of each strategy. SPECT at 12 months (primary endpoint of RI that the trial was powered for; a measure of revascularization midterm efficacy and an independent predictor of long-term prognosis) preceded routine angiographic control. RESULTS: Data are given, respectively, for the CABG, HCR, and MV-PCI arms. Incomplete revascularization rate was 8.0% vs. 7.7% vs. 5.7% (p=0.71). Hospital stay was 13.8 vs. 13.5 vs. 4.5 days (p < 0.001), and sick-leave duration was 23 vs. 16 vs. 8 weeks (p < 0.001). At 12 months, RI was 5 (2, 9)% vs. 5 (3, 7)% vs. 6 (3, 10)% (median; Q1, Q3) with noninferiority p values of 0.0006 (HCR vs. CABG) and 0.016 (MV-PCI vs. CABG). Rates of angiographic graft stenosis/occlusion or in-segment restenosis were 20.4% vs. 8.2% vs. 5.9% (p=0.05). Clinical target vessel/graft failure occurred in 12.0% vs. 11.5% vs. 11.3% (p=0.62). Major adverse cardiac and cerebral event (MACCE) rate was similar (12% vs. 13.4% vs. 13.2%; p=0.83). CONCLUSION: In this first randomized controlled study comparing CABG, HCR, and MV-PCI, residual myocardial ischemia and MACCE were similar at 12 months. There was no midterm indication of any added value of HCR. Hospital stay and sick-leave duration were shortest with MV-PCI. While longer-term follow-up is warranted, these findings may impact patient and physician choices and healthcare resources utilization. This trial is registered with NCT01699048.

Highly-calcific carotid lesions endovascular management in symptomatic and increased-stroke-risk asymptomatic patients using the CGuard™ dual-layer carotid stent system: Analysis from the PARADIGM study.

OBJECTIVES: To assess feasibility, safety, angiographic, and clinical outcome of highly-calcific carotid stenosis (HCCS) endovascular management using CGuard™ dual-layer carotid stents. BACKGROUND: HCCS has been a challenge to carotid artery stenting (CAS) using conventional stents. CGuard combines a high-radial-force open-cell frame conformability with MicroNet sealing properties. METHODS: The PARADIGM study is prospectively assessing routine CGuard use in all-comer carotid revascularization patients; the focus of the present analysis is HCCS versus non-HCCS lesions. Angiographic HCCS (core laboratory evaluation) required calcific segment length to lesion length ≥2/3, minimal calcification thickness ≥3 mm, circularity (≥3 quadrants), and calcification severity grade ≥3 (carotid calcification severity scoring system [CCSS]; G0-G4). RESULTS: One hundred and one consecutive patients (51-86 years, 54.4% symptomatic; 106 lesions) received CAS (16 HCCS and 90 non-HCCS); eight others (two HCCS) were treated surgically. CCSS evaluation was reproducible, with weighted kappa (95% CI) of 0.73 (0.58-0.88) and 0.83 (0.71-0.94) for inter- and intra-observer reproducibility respectively. HCCS postdilatation pressures were higher than those in non-HCCS; 22 (20-24) versus 20 (18-24) atm, p = .028; median (Q1-Q3). Angiography-optimized HCCS-CAS was feasible and free of contrast extravasation or clinical complications. Overall residual diameter stenosis was single-digit but it was higher in HCCS; 9 (4-17) versus 3 (1-7) %, p = .002. At 30 days and 12 months HCCS in-stent velocities were normal and there were no adverse clinical events. CONCLUSION: CGuard HCCS endovascular management was feasible and safe. A novel algorithm to grade carotid artery calcification severity was reproducible and applicable in clinical study setting. Larger HCCS series and longer-term follow-up are warranted.

One-day, sequential carotid artery stenting followed by cardiac surgery in patients with severe carotid and cardiac disease.

Optimal management of patients with internal carotid artery (ICA) stenosis concurrent with severe cardiac disease remains undefined. The aim of this study is to evaluate the safety and feasibility of the one-day, sequential approach by carotid artery stenting (CAS) immediately followed by cardiac surgery. The study included 70 consecutive patients with symptomatic > 50% or ⩾ 80% asymptomatic ICA stenosis coexisting with severe coronary/valve disease, who underwent one-day, sequential CAS + cardiac surgery. The majority of patients (85.7%) had CSS class III or IV angina and 10% had non-ST elevation myocardial infarction. The EuroSCORE II risk was 2.4% (IQR 1.69-3.19%). All CAS procedures were performed according to the 'tailored' algorithm with a substantial use of proximal neuroprotection devices of 44.3%. Closed-cell (75.7%) and mesh-covered (18.6%) stents were implanted in most cases. The majority of patients underwent isolated coronary artery bypass grafting (88.6%) or isolated valve replacement (7.1%). No major adverse cardiac and cerebrovascular events (MACCE) occurred at the CAS stage. There were three (4.3%) perioperative MACCE: one myocardial infarction and two deaths. All MACCE were related to cardiac surgery and were due to the high surgical risk profile of the patients. Up to 30 days, no further MACCE were observed. No perioperative or 30-day neurological complications occurred. In this patient series, one-day, sequential CAS and cardiac surgery was relatively safe and did not result in neurological complications. Thus, a strategy of preoperative CAS could be considered for patients with severe or symptomatic ICA stenosis who require urgent cardiac surgery.

Ischemic Versus Non-Ischemic (Neurogenic) Myocardial Contractility Impairment in Acute Coronary Syndromes: Prevalence and Impact on Left Ventricular Systolic Function Recovery.

BACKGROUND Neurogenic mechanism is believed to contribute to left ventricular (LV) systolic dysfunction in acute coronary syndromes (ACS); its extreme form is known as takotsubo cardiomyopathy. However, the magnitude of neurogenic contribution to LV dysfunction in all-comer first-time ACS remains unknown. MATERIAL AND METHODS In 120 consecutive patients with first-time ACS (age 66.3±12.3years, 40 women) coronary angiograms were individually matched to the echocardiographic left ventricular (LV) segments (17-segment model). Baseline contractility impairment was classified as ischemic (I): confined to the stenotic artery(ies) supply area(s), neurogenic (N): in absence of attributable coronary stenosis, or partially ischemic/partially neurogenic (I&N). Echocardiography was repeated at 6 months to determine LV systolic function recovery. RESULTS Neurogenic component (NC) contribution to myocardial contractility impairment was present in 24.2% of ACS patients, with pure N in 6.7% and I&N in 17.5%. Diabetes/pre-diabetes was present in 38.5% vs. 33.5% vs. 0% (I vs. I&N vs. N; p=0.02). Major stressor preceding symptom onset was reported in 3.3% in I, 9.5% in I&N, and 25.0% in N (p=0.03). The number of LV segments with contractility impairment was 2±4 in I, 17±11 in I&N, and 3±16 in N (p<0.05). NC presence was independently associated with better recovery of global LV systolic function (OR 2.99, 95% CI: 1.16-7.76; p=0.024). CONCLUSIONS Novel findings from this study are: (1) NC may contribute to myocardial contractility impairment in 1 in every 4 first-time ACS patients, (2) NC contribution to contractility impairment in ACS is blunted in diabetes or pre-diabetes, and (3) LV systolic function recovery is better in patients with NC.

Cardiopoietic cell therapy for advanced ischaemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial.

AIMS: Cardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort. METHODS AND RESULTS: This multinational, randomized, double-blind, sham-controlled study was conducted in 39 hospitals. Patients with symptomatic ischaemic heart failure on guideline-directed therapy (n = 484) were screened; n = 348 underwent bone marrow harvest and mesenchymal stem cell expansion. Those achieving > 24 million mesenchymal stem cells (n = 315) were randomized to cardiopoietic cells delivered endomyocardially with a retention-enhanced catheter (n = 157) or sham procedure (n = 158). Procedures were performed as randomized in 271 patients (n = 120 cardiopoietic cells, n = 151 sham). The primary efficacy endpoint was a Finkelstein-Schoenfeld hierarchical composite (all-cause mortality, worsening heart failure, Minnesota Living with Heart Failure Questionnaire score, 6-min walk distance, left ventricular end-systolic volume, and ejection fraction) at 39 weeks. The primary outcome was neutral (Mann-Whitney estimator 0.54, 95% confidence interval [CI] 0.47-0.61 [value > 0.5 favours cell treatment], P = 0.27). Exploratory analyses suggested a benefit of cell treatment on the primary composite in patients with baseline left ventricular end-diastolic volume 200-370 mL (60% of patients) (Mann-Whitney estimator 0.61, 95% CI 0.52-0.70, P = 0.015). No difference was observed in serious adverse events. One (0.9%) cardiopoietic cell patient and 9 (5.4%) sham patients experienced aborted or sudden cardiac death. CONCLUSION: The primary endpoint was neutral, with safety demonstrated across the cohort. Further evaluation of cardiopoietic cell therapy in patients with elevated end-diastolic volume is warranted.

Resolution of ischemic symptoms after percutaneous angioplasty for a symptomatic subclavian artery stenosis.

OBJECTIVE: A minor part of patients with subclavian or innominate artery occlusive disease (subclavian artery stenosis [SAS]) experience symptoms of vertebrobasilar insufficiency, upper extremity exertional ischemia (UEEI), or cardiac ischemia owing to subclavian-coronary steal (SCS) in some instances. The study aimed to assess the impact of percutaneous transluminal angioplasty (PTA) of symptomatic SAS on symptom resolution and to determine factors related with SAS recurrence. METHODS: Symptom resolution and incidence of restenosis (RS) were evaluated for up to 15 years in patients who had undergone successful PTA of SAS. RESULTS: The study group comprised 232 consecutive subjects after successful PTA of SAS (61.9 ± 8.4 years old 53.4% men). The mean follow-up time was 101 ± 40 months (range, 5-188 months). One month after PTA, 85.4% of the study participants were free from dizziness, 94.4% from imbalance, 97.1% from visual disturbances, 97.8% from syncope, 98.7% from UEEI, and 100% from SCS. RS was found in 37 patients (15.9%) in long-term observation. UEEI, dizziness, imbalance, and SCS were significantly more frequent in patients with SAS recurrence, as compared with patients with patent artery (65.9% vs 3.1% [P < .001] 63.4% vs 19.4% [P < .001]; 26.8% vs 9.4% [P = .005]; and 100% vs 15.4% [P = .018], respectively). Smaller stent diameter (odds ratio [OR], 0.87; 95% confidence interval [CI], 0.79-0.96; P = .004), implantation of ≥2 stents for a lesion (OR, 1.15; 95% CI, 1.05-1.26; P = .003), concomitant stenosis in the carotid or vertebral artery (OR, 1.10; 95% CI, 1.01-1.21; P = .036), high-sensitivity C-reactive protein level (OR, 1.20; 95% CI, 1.09-1.31; P < .001), and high-density lipoprotein level (OR, 0.91; 95% CI, 0.82-0.98; P = .021) were associated independently with risk of RS, whereas recurrence of UEEI (relative risk, 1.71; 95% CI, 1.55-1.90; P < .001), dizziness (OR, 1.26; 95% CI, 1.14-1.39; P < .001), limb paresthesia (OR, 1.14; 95% CI, 1.04-1.25; P = .005), and angina in subjects after coronary artery bypass grafting (OR, 1.11; 95% CI, 1.01-1.21; P = .024) were associated with RS/SAS progression after PTA. CONCLUSIONS: Angioplasty of SAS leads to symptom resolution in most patients. UEEI, dizziness, and angina recurrence are predictors of RS or SAS progression; high-sensitivity C-reactive protein, smaller stent diameter, and number of implanted stents predict RS.

Next-generation transcarotid artery revascularization: TransCarotid flOw Reversal Cerebral Protection And CGUARD MicroNET-Covered Embolic Prevention Stent System To Reduce Strokes - TOPGUARD Study.

BACKGROUND: Stent-assisted carotid artery revascularization employing surgical cutdown for transcervical access and dynamic flow reversal (TCAR) is gaining popularity. TCAR, despite maximized intra-procedural cerebral protection, shows a marked excess of 30-day neurologic complications in symptomatic vs. asymptomatic stenoses. The TCAR conventional single-layer stent (free-cell area 5.89mm2) inability to seal embologenic lesions may be particularly relevant after the flow reversal neuroprotection is terminated. METHODS: We evaluated peri-procedural and 30-day major adverse cerebral and cardiac events (MACCE) of TCAR (ENROUTE, SilkRoad Medical) paired with MicroNET-covered neuroprotective stent (CGuard, InspireMD) in consecutive patients at elevated risk of complications with transfemoral/transradial filter-protected stenting (increased lesion-related and/or access-related risk). CGuard (MicroNET free cell area ≈0.02-0.03 mm2) has level-1 evidence for reducing intra- and abolishing post-procedural lesion-related cerebral embolism. RESULTS: One hundred and six increased-risk patients (age 72 [61-76] years, median [Q1-Q3]; 60.4% symptomatic, 49.1% diabetic, 36.8% women, 61.3% left-sided index lesion) were enrolled in three vascular surgery centers. Angiographic stenosis severity was 81 (75-91)%, lesion length 21 (15-26)mm, increased-risk lesional characteristics 87.7%. Study stent use was 100% (no other stent types). 74.5% lesions were predilated; post-dilatation rate was 90.6%. Flow reversal duration was 8 (5-11)min. One stroke (0.9%) occurred in an asymptomatic patient prior to establishing neuroprotection (index lesion disruption with the sheath insertion wire); there were no other peri-procedural MACCE. No further adverse events occurred by 30-days. 30-day stent patency was 100% with normal velocities and absence of any in-stent material by Duplex Doppler. CONCLUSIONS: Despite a high proportion of increased-risk lesions and clinically symptomatic patients in this study, TCAR employing the MicroNET-covered anti-embolic stent showed 30-day MACCE rate <1%. This suggests a clinical role for combining maximized intra-procedural prevention of cerebral embolism by dynamic flow reversal with anti-embolic stent prevention of peri- and post-procedural cerebral embolism (TOPGUARD NCT04547387).

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

BACKGROUND: 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). METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Introduction: 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. Aim: 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. Material and methods: Seventy-five patients (age 40-89 years, 26.7% women) were enrolled in 7 interventional stroke centers. Results: 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). Conclusions: 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).

Carotid artery stenting according to the "tailored CAS" algorithm performed in the very elderly patients: the thirty day outcome.

OBJECTIVES: To assess safety and efficacy of carotid artery stenting (CAS) according to "tailored-CAS" algorithm in the elderly (≥75 years) in relation to younger patients. BACKGROUND: Although CAS has grown as an alternative to carotid endarterectomy the data on safety of CAS in the very elderly are inconsistent. MATERIAL AND METHODS: 1,139 patients with significant carotid stenosis underwent 1,252 CAS procedures in one high-volume center between years 2001-2011. CAS procedures were performed with lesion and patient dependent selection of neuroprotection type ("tailored-CAS"). There were 193 subjects ≥75-years-old (17%) and 946 <75-years-old. No major differences in atherosclerosis risk factors and comorbidities between groups were noted. In both groups the majority of patients were male (70.4% vs. 68.6%, P = NS) and half of the patients were symptomatic (50.2% vs. 55.2%, P = NS). Bilateral carotid stenosis was present in 25% of patients from CAS ≥75 group and 22% from CAS< 75 group, P = NS. Proximal neuroprotection devices use for high risk or symptomatic lesions accounted for 31% in CAS≥ 75 group and 32% in CAS<75 group, P = NS. RESULTS: In symptomatic patients aged ≥75 years 30-day stroke and death rate was 7% versus 1.9% in symptomatic patients aged <75; P = 0.01 and vs. 1.8% in asymptomatic elderly, P = 0.09. No myocardial infarcts were noted. CONCLUSIONS: Symptomatic elderly is a group of highest CAS risk and the use of "tailored CAS" algorithm does not equalize CAS risk in this patients' group. "Tailored CAS" remains a safe procedure for asymptomatic elderly as well as symptomatic and asymptomatic young patients.

Imaging modality-dependent carotid stenosis severity variations against intravascular ultrasound as a reference: Carotid Artery intravasculaR Ultrasound Study (CARUS).

PURPOSE: Different non-invasive and invasive imaging modalities are used to determine carotid artery stenosis severity that remains a principal parameter in clinical decision-making. We compared stenosis degree obtained with different modalities against vascular imaging gold standard, intravascular ultrasound, IVUS. METHODS: 300 consecutive patients (age 47-83 years, 192 men, 64% asymptomatic) with carotid artery stenosis of " ≥ 50%" referred for potential revascularization received as per study protocol (i) duplex ultrasound (DUS), (ii) computed tomography angiography (CTA), (iii) intraarterial quantitative angiography (iQA) and (iv) and (iv) IVUS. Correlation of measurements with IVUS (r), proportion of those concordant (within 10%) and proportion of under/overestimated were calculated along with recipient-operating-characteristics (ROC). RESULTS: For IVUS area stenosis (AS) and IVUS minimal lumen area (MLA), there was only a moderate correlation with DUS velocities (peak-systolic, PSV; end-diastolic, EDV; r values of 0.42-0.51, p < 0.001 for all). CTA systematically underestimated both reference area and MLA (80.4% and 92.3% cases) but CTA error was lesser for AS (proportion concordant-57.4%; CTA under/overestimation-12.5%/30.1%). iQA diameter stenosis (DS) was found concordant with IVUS in 41.1% measurements (iQA under/overestimation 7.9%/51.0%). By univariate model, PSV (ROC area-under-the-curve, AUC, 0.77, cutoff 2.6 m/s), EDV (AUC 0.72, cutoff 0.71 m/s) and CTA-DS (AUC 0.83, cutoff 59.6%) were predictors of ≥ 50% DS by IVUS (p < 0.001 for all). Best predictor, however, of ≥ 50% DS by IVUS was stenosis severity evaluation by automated contrast column density measurement on iQA (AUC 0.87, cutoff 68%, p < 0.001). Regarding non-invasive techniques, CTA was the only independent diagnostic modality against IVUS on multivariate model (p = 0.008). CONCLUSION: IVUS validation shows significant imaging modality-dependent variations in carotid stenosis severity determination.

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.

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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).

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.

World Federation for Interventional Stroke Treatment (WIST) multispecialty training guidelines for endovascular stroke intervention.

Introduction: Today, endovascular treatment (EVT) is the therapy of choice for strokes due to acute large vessel occlusion, irrespective of prior thrombolysis. This necessitates fast, coordinated multi-specialty collaboration. Currently, in most countries, the number of physicians and centres with expertise in EVT is limited. Thus, only a small proportion of eligible patients receive this potentially life-saving therapy, often after significant delays. Hence, there is an unmet need to train a sufficient number of physicians and centres in acute stroke intervention in order to allow widespread and timely access to EVT. Aim: To provide multi-specialty training guidelines for competency, accreditation and certification of centres and physicians in EVT for acute large vessel occlusion strokes. Material and methods: The World Federation for Interventional Stroke Treatment (WIST) consists of experts in the field of endovascular stroke treatment. This interdisciplinary working group developed competency - rather than time-based - guidelines for operator training, taking into consideration trainees' previous skillsets and experience. Existing training concepts from mostly single specialty organizations were analysed and incorporated. Results: The WIST establishes an individualized approach to acquiring clinical knowledge and procedural skills to meet the competency requirements for certification of interventionalists of various disciplines and stroke centres in EVT. WIST guidelines encourage acquisition of skills using innovative training methods such as structured supervised high-fidelity simulation and procedural performance on human perfused cadaveric models. Conclusions: WIST multispecialty guidelines outline competency and quality standards for physicians and centres to perform safe and effective EVT. The role of quality control and quality assurance is highlighted.

World Federation for Interventional Stroke Treatment (WIST) Multispecialty Training Guidelines for Endovascular Stroke Intervention.

INTRODUCTION: Today, endovascular treatment (EVT) is the therapy of choice for strokes due to acute large vessel occlusion, irrespective of prior thrombolysis. This necessitates fast, coordinated multi-specialty collaboration. Currently, in most countries, the number of physicians and centres with expertise in EVT is limited. Thus, only a small proportion of eligible patients receive this potentially life-saving therapy, often after significant delays. Hence, there is an unmet need to train a sufficient number of physicians and centres in acute stroke intervention in order to allow widespread and timely access to EVT. AIM: To provide multi-specialty training guidelines for competency, accreditation and certification of centres and physicians in EVT for acute large vessel occlusion strokes. MATERIAL AND METHODS: The World Federation for Interventional Stroke Treatment (WIST) consists of experts in the field of endovascular stroke treatment. This interdisciplinary working group developed competency - rather than time-based - guidelines for operator training, taking into consideration trainees' previous skillsets and experience. Existing training concepts from mostly single specialty organizations were analysed and incorporated. RESULTS: The WIST establishes an individualized approach to acquiring clinical knowledge and procedural skills to meet the competency requirements for certification of interventionalists of various disciplines and stroke centres in EVT. WIST guidelines encourage acquisition of skills using innovative training methods such as structured supervised high-fidelity simulation and procedural performance on human perfused cadaveric models. CONCLUSIONS: WIST multispecialty guidelines outline competency and quality standards for physicians and centres to perform safe and effective EVT. The role of quality control and quality assurance is highlighted. SUMMARY: The World Federation for Interventional Stroke Treatment (WIST) establishes an individualized approach to acquiring clinical knowledge and procedural skills to meet the competency requirements for certification of interventionalists of various disciplines and stroke centres in endovascular treatment (EVT). WIST guidelines encourage acquisition of skills using innovative training methods such as structured supervised high-fidelity simulation and procedural performance on human perfused cadaveric models. WIST multispecialty guidelines outline competency and quality standards for physicians and centers to perform safe and effective EVT. The role of quality control and quality assurance is highlighted. SIMULTANEOUS PUBLICATION: The WIST 2023 Guidelines are published simultaneously in Europe (Adv Interv Cardiol 2023).