Symptomatic Atherosclerosis Research Articles

PCSK9 Inhibitor with Statin Therapy for Intracranial Artery Stenosis ( PISTIAS): Rationale and design of a multicenter randomized controlled trial.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors enable an additional 54-75% reduction in low-density lipoprotein cholesterol (LDL-C) in statin-treated patients, demonstrating plaque regression in coronary artery disease. However, the impact of achieving an extremely low level of LDL-C with PCSK9 inhibitors (e.g. Evolocumab) on symptomatic intracranial atherosclerosis remains unexplored. To determine whether combining Evolocumab and statins achieves a more significant symptomatic intracranial plaque regression than statin therapy alone. With a sample size of 1000 subjects, a two-sided α of 0.05, and 20% lost to follow-up, the study will have 83.3% power to detect the difference in intracranial plaque burden. This is an investigator-initiated multicenter, randomized, open-label, outcome assessor-blinded trial, evaluating the impact of combining Evolocumab and statins on intracranial plaque burden assessed by high-resolution magnetic resonance imaging at baseline in patients undergoing a clinically indicated acute stroke or transient ischemic attack due to intracranial artery stenosis, and after 24 weeks of treatment. Subjects (n = 1000) were randomized 1:1 into two groups to receive either Evolocumab 140 mg every 2 weeks with statin therapy or statin therapy alone. The primary endpoint is the change in intracranial plaque burden assessed by high-resolution magnetic resonance imaging, performed at baseline and at the end of the 24-week treatment period. This trial will explore whether more significant intracranial plaque regression is achievable with the treatment of combining Evolocumab and statins, providing information about efficacy and safety data. ChiCTR2300068868; https://www.chictr.org.cn/.

Application of high-resolution MRI in evaluating statin efficacy on symptomatic intracranial atherosclerosis.

To investigate the efficacy of statins on symptomatic intracranial atherosclerotic plaques using high-resolution 3.0 T MR vessel wall imaging (HR-MRI). Patients with symptomatic intracranial atherosclerotic plaques (cerebral ischemic events within the last three months) confirmed by HR-MRI from July 2017 to August 2022 were retrospectively included in this study. The enrolled patients started statin therapy at baseline. All the patients underwent the follow-up HR-MRI examination after statin therapy for at least 3 months. A paired sample t-test and Wilcoxon rank sum test were used to evaluate the changes in plaque characteristics after statin therapy. Multivariate linear regression was further used to investigate the clinical factors associated with statin efficacy. A total of 48 patients (37 males; overall mean age = 60.2 ± 11.7 years) were included in this study. The follow-up time was 7.0 (5.6-12.0) months. In patients treated with statins for > 6 months (n = 31), plaque length, wall thickness, plaque burden, luminal stenosis and plaque enhancement were significantly reduced. Similar results were found in patients with good lipid control (n = 21). Younger age, lower BMI and hypertension were associated with decreased plaque burden. Lower BMI, hypertension and longer duration of statin therapy were associated with decreased plaque enhancement. Younger age and hypertension were associated with decreased luminal stenosis (all p < 0.05). HR-MRI can effectively evaluate plaques changes after statin therapy. Statins can reduce plaque burden and stabilize plaques. The effect of statin may have a relationship with age, BMI, hypertension, and duration of statin therapy. High-resolution MRI can be applied to evaluate the efficacy of statins on symptomatic intracranial atherosclerotic plaques. Long-term statin use and well-controlled blood lipid levels can help reduce plaque burden and stabilize plaques. High-resolution MRI provides great help evaluating the changes of plaque characteristics after statin therapy. Efficacy of statins is associated with duration of use, controlled lipid levels, and clinical factors. High-resolution MRI can serve as an effective method for following-up symptomatic intracranial atherosclerosis.

Diagnostics Accuracy of Magnetic Resonance Imaging in Detection of Atherosclerotic Plaque Characteristics in Carotid Arteries Compared to Histology: A Systematic Review.

Carotid plaque composition represents one of the main risk factors of future ischemic stroke. MRI provides excellent soft tissue contrast that can distinguish plaque characteristics. Our objective was to analyze the diagnostic accuracy of MRI imaging in the detection of carotid plaque characteristics compared to histology in patients with symptomatic and asymptomatic carotid atherosclerosis through a systematic review. After prospective registration in PROSPERO (ID CRD42022329690), Medline Ovid, Embase.com, Cochrane Library, and Web of Science Core were searched without any search limitation up to May 27, 2022 to identify eligible articles. Of the 8168 studies, 53 (37 × 1.5 T MRI, 17 × 3 T MRI) evaluated MRI accuracy in the detection of 13 specific carotid plaque characteristics in 169 comparisons. MRI demonstrated high diagnostic accuracy for detection of calcification (3 T MRI: mean sensitivity 92%/mean specificity 90%; 1.5 T MRI: mean sensitivity 81%/mean specificity 91%), fibrous cap (1.5 T: 89%/87%), unstable plaque (1.5 T: 89%/87%), intraplaque hemorrhage (1.5 T: 86%/88%), and lipid-rich necrotic core (1.5 T: 89%/79%). MRI also proved to have a high level of tissue discrimination for the carotid plaque characteristics investigated, allowing potentially for a better risk assessment and follow-up of patients who may benefit from more aggressive treatments. These results emphasize the role of MRI as the first-line imaging modality for comprehensive assessment of carotid plaque morphology, particularly for unstable plaque. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Diagnostic accuracy of carotid plaque instability by noninvasive imaging: a systematic review and meta-analysis.

There is increasing evidence that plaque instability in the extracranial carotid artery may lead to an increased stroke risk independently of the degree of stenosis. We aimed to determine diagnostic accuracy of vulnerable and stable plaque using noninvasive imaging modalities when compared to histology in patients with symptomatic and asymptomatic carotid atherosclerosis. Medline Ovid, Embase, Cochrane Library, and Web of Science were searched for diagnostic accuracy of noninvasive imaging modalities (CT, MRI, US) in the detection of 1) vulnerable/stable plaque, and 2) vulnerable/stable plaque characteristics, compared to histology. The quality of included studies was assessed by QUADAS-2 and univariate and bivariate random-effect meta-analyses were performed. We included 36 vulnerable and 5 stable plaque studies in the meta-analysis, and out of 211 plaque characteristics from remaining studies, we classified 169 as vulnerable and 42 as stable characteristics (28 CT, 120 MRI, 104 US characteristics). We found that MRI had high accuracy [90% (95% CI: 82-95%)] in the detection of vulnerable plaque, similar to CT [86% (95% CI: 76-92%); P > 0.05], whereas US showed less accuracy [80% (95% CI: 75-84%); P = 0.013]. CT showed high diagnostic accuracy in visualizing characteristics of vulnerable or stable plaques (89% and 90%) similar to MRI (86% and 89%; P > 0.05); however, US had lower accuracy (77%, P < 0.001 and 82%, P > 0.05). CT and MRI have a similar, high performance in detecting vulnerable carotid plaques, whereas US showed significantly less diagnostic accuracy. Moreover, MRI visualized all vulnerable plaque characteristics allowing for a better stroke risk assessment. PROSPERO ID CRD42022329690.

Multiplane reconstruction modifies the diagnostic performance of CT angiography in carotid webs

IntroductionCarotid Web (CaW) represents an overlooked stroke etiology and has been associated with high recurrence rates and to be amenable to stenting. We evaluated the diagnostic performance of different computed tomography angiography (CTA) projections in CaW. MethodsConsecutive patients <65 years-old with symptomatic CaW (n=31), carotid atherosclerosis (n=27), or normal carotids (n=49) diagnosed with a thin-cut CTA were included. Deidentified CTAs were independently reviewed by three readers, who recorded the diagnosis and level of certainty after evaluating the axial plane alone, after adding sagittal/coronal maximum intensity projection (MIP), then after oblique MPR reformats. ResultsThere were 93 total CaW, 81 atherosclerosis, and 147 normal carotid reads. With CTA axial projection alone, less CaW cases (44.1 %) were appropriately diagnosed as compared to atherosclerosis (87.7 %; p<0.001) and normal carotid (83 %; p<0.001) cases. Sagittal/coronal MIPS increased the rate of accurate CaW diagnosis (44.1–76.3 %; p<0.001). Inter-rater agreement in CaW detection increased from k= 0.46 (0.35–0.57) using axial to k= 0.80 (0.69–0.91) with sagittal/coronal planes. The axial projection alone had lower sensitivity (44 % vs. 76 %) but similar specificity (95 % vs. 96 %) in CaW detection compared to axial+ sagittal/coronal MIPS. The accuracy in detecting atherosclerosis or normal carotids did not increase after adding sagittal/coronal MIPS and oblique MPRs. The certainty level for CaW diagnosis was lower when compared to atherosclerosis and normal carotids using axial alone (3.0 [3.0–4.0] vs. 4.0 [3.0–5.0]; p<0.001 and 4.0 [3.0–5.0]; p<0.001) as well as after adding sagittal/coronal MIPS (4.0 [3.0–5.0] vs. 5.0[4.0–5.0]; p=0.01 and 4.0 [4.0–5.0]; p<0.001). ConclusionCTA axial plane alone was insufficient for CaW detection. CTA sagittal/coronal MIP reconstructions as well as oblique MPR reformats enhanced the accuracy and confidence related to CaW diagnosis.

Carotid atherosclerotic plaque microcalcification is independently associated with recurrent neurovascular events: A pilot study.

Microcalcification and macrocalcification are critical processes in atherosclerotic plaque progression, though how these processes relate to the risk of stroke recurrence in symptomatic carotid atherosclerosis is poorly understood. We performed a post hoc analysis of data from the ICARUSS (Imaging Carotid Atherosclerosis in the Recovery and Understanding of Stroke Severity) study, where individuals with acute ischemic stroke originating from ipsilateral carotid stenosis of ⩾ 50% underwent 18F-sodium fluoride positron emission tomography (NaF-PET) to measure microcalcification. Tracer uptake was quantified using maximum tissue-to-background ratio (TBRmax). Macrocalcification was measured on computed tomography (CT) using Agatston scoring. Patients were followed up for 6 months for recurrent ipsilateral neurovascular events. Five (27.8%) of 18 individuals had a recurrent ischemic stroke or transient ischemic attack. Ipsilateral carotid plaque NaF uptake at baseline was higher in those with recurrent events compared to those without, and this association remained after adjustment for other vascular risk factors (adjusted odds ratio (aOR) = 1.24, 1.03-1.50). Macrocalcification score in the symptomatic artery was also significantly independently associated with ipsilateral recurrence, but the effect size was relatively smaller (aOR = 1.12, 1.06-1.17 for each 100 unit increase). Our findings indicate that microcalcification in symptomatic carotid plaques is independently associated with ipsilateral ischemic stroke recurrence. Furthermore, differences in the extent of active microcalcification in macrocalcified plaques may help explain variation in the relationship between calcified carotid plaques and stroke recurrence reported in the literature. Our pilot study indicates that evaluation of carotid artery microcalcification using NaF-PET may be a useful method for risk-stratification of carotid atherosclerosis, though our findings require confirmation in larger cohorts.

Machine Learning Detects Symptomatic Plaques in Patients With Carotid Atherosclerosis on CT Angiography.

This study aimed to develop and validate a computed tomography angiography based machine learning model that uses plaque composition data and degree of carotid stenosis to detect symptomatic carotid plaques in patients with carotid atherosclerosis. The machine learning based model was trained using degree of stenosis and the volumes of 13 computed tomography angiography derived intracarotid plaque subcomponents (eg, lipid, intraplaque hemorrhage, calcium) to identify plaques associated with cerebrovascular events. The model was internally validated through repeated 10-fold cross-validation and tested on a dedicated testing cohort according to discrimination and calibration. This retrospective, single-center study evaluated computed tomography angiography scans of 268 patients with both symptomatic and asymptomatic carotid atherosclerosis (163 for the derivation set and 106 for the testing set) performed between March 2013 and October 2019. The area-under-receiver-operating characteristics curve by machine learning on the testing cohort (0.89) was significantly higher than the areas under the curve of traditional logit analysis based on the degree of stenosis (0.51, P<0.001), presence of intraplaque hemorrhage (0.69, P<0.001), and plaque composition (0.78, P<0.001), respectively. Comparable performance was obtained on internal validation. The identified plaque components and associated cutoff values that were significantly associated with a higher likelihood of symptomatic status after adjustment were the ratio of intraplaque hemorrhage to lipid volume (≥50%, 38.5 [10.1-205.1]; odds ratio, 95% CI) and percentage of intraplaque hemorrhage volume (≥10%, 18.5 [5.7-69.4]; odds ratio, 95% CI). This study presented an interpretable machine learning model that accurately identifies symptomatic carotid plaques using computed tomography angiography derived plaque composition features, aiding clinical decision-making.

Abstract 143: Multi-omics Integration From A Large Human Biobank Identifies Key Molecular Mechanisms And Signatures Of Atherosclerotic Plaque Instability

Understanding the pathophysiology of unstable atherosclerosis, the underlying cause of myocardial infarction and ischemic stroke, is imperative to catalyze novel translational strategies. Our objective was to identify key mechanisms and signatures of atherosclerotic instability, by leveraging the power of multi-omics integration from a large biobank. Biobank of Karolinska Endarterectomies (BiKE), with biomaterial and data from patients with symptomatic (S) and asymptomatic (AS) carotid atherosclerosis, was the main resource in this study. Matched plaques, PBMCs, plasma sampled locally around the plaque and from the periphery in n&gt;600 individuals, were profiled by orthogonal genomic, transcriptomic, proteomic and metabolomic technologies. Single-omics analyses were performed for differential expression, pathway and network studies in S vs. AS comparisons. Multi-omics integration was performed using a benchmarked method DIABLO, across local and peripheral disease sites and their intersection. Top targets were investigated further using scRNAseq, patient clinical and outcome data, as well as QTL analyses coupling target genetics with transcript, protein, and metabolite levels. Plaque and PBMC transcriptomics showed that inflammatory signalling, hypoxia, angiogenesis, ECM reorganisation, bone remodelling, cholesterol homeostasis, glycolysis were enriched pathways. In proteomics, chemokine signalling upregulation was found in both peripheral and local plasma, while IL17 pathway was enriched in local plasma from S patients. In plasma metabolomics, Bilirubin degradation products were downregulated, while Sphingomyelins were upregulated. Multi-omics integrations revealed coagulation, necroptosis, immune activation and cholesterol metabolism as key pathways determining instability. Extended analyses of the top analytes FABP4, ICOSLG, ANGPTL3, Bilirubin and Sphingomyelins, generated an insight into their association with survival, clinical and genetic risk in patients. Using an innovative framework, this study brings novel information about atherosclerosis vulnerability, opening avenues for drug target and biomarker discoveries, but also improving personalised treatment options and risk stratifications.

Single-Cell Gene-Regulatory Networks of Advanced Symptomatic Atherosclerosis.

While our understanding of the single-cell gene expression patterns underlying the transformation of vascular cell types during the progression of atherosclerosis is rapidly improving, the clinical and pathophysiological relevance of these changes remains poorly understood. Single-cell RNA sequencing data generated with SmartSeq2 (≈8000 genes/cell) in 16 588 single cells isolated during atherosclerosis progression in Ldlr-/-Apob100/100 mice with human-like plasma lipoproteins and from humans with asymptomatic and symptomatic carotid plaques was clustered into multiple subtypes. For clinical and pathophysiological context, the advanced-stage and symptomatic subtype clusters were integrated with 135 tissue-specific (atherosclerotic aortic wall, mammary artery, liver, skeletal muscle, and visceral and subcutaneous, fat) gene-regulatory networks (GRNs) inferred from 600 coronary artery disease patients in the STARNET (Stockholm-Tartu Atherosclerosis Reverse Network Engineering Task) study. Advanced stages of atherosclerosis progression and symptomatic carotid plaques were largely characterized by 3 smooth muscle cells (SMCs), and 3 macrophage subtype clusters with extracellular matrix organization/osteogenic (SMC), and M1-type proinflammatory/Trem2-high lipid-associated (macrophage) phenotypes. Integrative analysis of these 6 clusters with STARNET revealed significant enrichments of 3 arterial wall GRNs: GRN33 (macrophage), GRN39 (SMC), and GRN122 (macrophage) with major contributions to coronary artery disease heritability and strong associations with clinical scores of coronary atherosclerosis severity. The presence and pathophysiological relevance of GRN39 were verified in 5 independent RNAseq data sets obtained from the human coronary and aortic artery, and primary SMCs and by targeting its top-key drivers, FRZB and ALCAM in cultured human coronary artery SMCs. By identifying and integrating the most gene-rich single-cell subclusters of atherosclerosis to date with a coronary artery disease framework of GRNs, GRN39 was identified and independently validated as being critical for the transformation of contractile SMCs into an osteogenic phenotype promoting advanced, symptomatic atherosclerosis.

Clinical experience in intracranial stenting of Wingspan stent system under local anesthesia.

The use of endovascular treatments for symptomatic intracranial atherosclerosis disease (ICAD) remains contentious due to high periprocedural complications. Many centers resort to general anesthesia for airway protection and optimal periprocedural conditions; however, this approach lacks real-time monitoring of patients' neurological status during procedures. In this study, we employed intracranial stenting with the Wingspan system under local anesthesia to address this challenge. We conducted a retrospective study of 45 consecutive ICAD patients who underwent intracranial stenting with the Wingspan system at our hospital from August 2013 to May 2021. These stenting procedures were performed under local anesthesia in a hybrid operation room. Neurological assessments were conducted during the procedure. The patients with periprocedural complications were analyzed for the risk factors. The study included 45 ICAD patients (median age 62 years; 35 male and 10 female individuals). Among them, 30 patients had anterior circulation ICAD, and 15 had posterior circulation ICAD. The periprocedural complication rate was 8.9% (4/45), with an overall mortality rate of 2.2% (1/45). Notably, no procedure-related perforation complications were found, and all ischemic complications occurred in the perforating bearing artery, specifically in patients with stents placed in the middle cerebral artery or basilar artery, while no complications were observed in the non-perforating bearing artery of the internal carotid artery and vertebral artery (p = 0.04). Our study demonstrates the safety and efficacy of the Wingspan stent system when performed on selected patients under local anesthesia. This approach seems to reduce procedural-related morbidity and be a safe intervention. In addition, it is crucial for surgeons to be aware that patients with perforator-bearing artery stenosis may be at a higher risk of complications.

The Prepetrous Segment of the Internal Carotid Artery as a Neglected Site of Symptomatic Atherosclerosis: A Single-Center Series.

(1) Background: Non-stenotic complicated plaques are a neglected cause of stroke, in particular in young patients. Atherosclerosis has some preferential sites in extracranial arteries and the prepetrous segment of the internal carotid artery has been rarely described as site of atheroma in general and of complicated atheroma in stroke patients. The aim of this study is to describe the rate of the prepetrous internal carotid artery's (ICA) involvement in a single-center case series of young stroke patients. (2) Methods: All patients < 50 years old with acute ischemic stroke admitted to a single-center Stroke Unit during two time periods (the first one from 1 January 2018 to 31 December 2019, and the second one from 1 January 2021 to 30 June 2022), were prospectively investigated as part of a screening protocol of the Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO) study [ClinicalTrials.gov ID NCT01934725], including extracranial vascular examination by using computed tomography (CT) or magnetic resonance imaging (MRI). (3) Results: Two out of ninety-three consecutive patients (2.15%) had a complicated atheroma in the prepetrous ICA as the cause of stroke and both CT angiography and high-resolution vessel wall MRI were applied to document the main features of positive remodeling, cap rupture, ulceration, intraplaque hemorrhage, and a transient thrombus superimposed on the atheroma. The two patients had a different evolution of healing in the first case and a persisting ulceration at 12 months in the second case. (4) Conclusions: The prepetrous ICA is a rarely described location of complicated atheroma in stroke patients at all ages and it represents roughly 2% of causes of acute stroke in this single-center case series in young people.

Characteristics of the gut microbiota of patients with symptomatic carotid atherosclerotic plaques positive for bacterial genetic material.

The gut microbiota (GM) is believed to be closely associated with symptomatic carotid atherosclerosis (SCAS), yet more evidence is needed to substantiate the significant role of GM in SCAS. This study, based on the detection of bacterial DNA in carotid plaques, explores the characteristics of GM in SCAS patients with plaque bacterial genetic material positivity, aiming to provide a reference for subsequent research. We enrolled 27 healthy individuals (NHF group) and 23 SCAS patients (PFBS group). We utilized 16S rDNA V3-V4 region gene sequencing to analyze the microbiota in fecal samples from both groups, as well as in plaque samples from the carotid bifurcation extending to the origin of the internal carotid artery in all patients. Our results indicate significant differences in the gut microbiota (GM) between SCAS patients and healthy individuals. The detection rate of bacterial DNA in plaque samples was approximately 26%. Compared to patients with negative plaques (PRSOPWNP group), those with positive plaques (PRSOPWPP group) exhibited significant alterations in their GM, particularly an upregulation of 11 bacterial genera (such as Klebsiella and Streptococcus) in the gut, which were also present in the plaques. In terms of microbial gene function prediction, pathways such as Fluorobenzoate degradation were significantly upregulated in the GM of patients with positive plaques. In summary, our study is the first to identify significant alterations in the gut microbiota of patients with positive plaques, providing crucial microbial evidence for further exploration of the pathogenesis of SCAS.

Triglyceride-Related Parameters and Symptomatic Atherosclerotic Lesions in Patients With Ischemic Stroke.

Recently, evidence has suggested that the pathophysiology and risk factors of intracranial atherosclerosis (ICAS) differs from those of extracranial atherosclerosis (ECAS). In addition, novel parameters reflecting metabolic conditions, such as insulin resistance or atherogenic dyslipidemia, based on triglycerides (TG) and other biomarkers, have emerged. In this study, we evaluated the association between TG-related parameters and symptomatic cerebral atherosclerosis in patients with acute ischemic stroke resulting from large artery atherosclerosis (LAA). We assessed consecutive acute LAA-stroke patients between January 2010 and December 2020. Based on the radiological findings, we classified the relevant symptomatic arteries that caused the index stroke into LAA-ICAS and LAA-ECAS. As TG-related parameters, the atherogenic index of plasma (AIP) and TG-glucose (TyG) index were calculated according to the following formulas: AIP = log10 (TG Level/High-density Lipoprotein Cholesterol Level), TyG Index = Ln (TG Level × Glucose Level/2). A total of 519 patients with LAA-stroke were evaluated. In multivariable logistic regression analysis to identify predictors of LAA-ICAS, AIP was significantly associated with LAA-ICAS (adjusted odds ratio [aOR], 3.60; 95% confidence interval [CI], 1.60-8.06). TyG index also showed a statistically significant relationship with LAA-ICAS (aOR, 1.60; 95% CI, 1.11-2.32). However, TG per se did not show a statistical association with LAA-ECAS. TG-related parameters were more closely associated with stroke by ICAS than by ECAS. The metabolic conditions reflected by the AIP or TyG index, rather than hypertriglyceridemia itself, may play a greater role in determining the relevant vessel causally involved in a stroke.

Cost-effectiveness analysis of intravascular ultrasound-guided peripheral vascular interventions in patients with femoropopliteal peripheral artery disease.

Background: Intravascular ultrasound (IVUS)-guided percutaneous transluminal angioplasty (PTA) might offer clinical benefits compared to angiography-guided PTA in patients with peripheral artery disease (PAD). A cost-effectiveness model was developed to examine the benefits and costs of IVUS-guided PTA versus angiography-guided PTA in PAD patients with femoropopliteal (FP) occlusive disease. Methods: A two-step model (a one-year decision tree followed by a lifetime semi-Markov model) was developed from a German healthcare payer perspective to estimate the costs and outcomes over a one-year and lifetime horizon. Clinical events included target lesion revascularization (TLR), amputation, and death. Transition probabilities and utility values were derived from published literature. Healthcare costs were based on German Diagnosis Related Groups (DRG) codes. Costs and outcomes were discounted at a rate of 3% per year. The incremental cost-effectiveness ratio (ICER) was calculated, and sensitivity analyses were performed to assess the robustness of the results. Results: In the one-year horizon, IVUS-guided PTA resulted in incremental quality-adjusted life-years (QALY) and costs of 0.02 and €919 per patient respectively, with a corresponding ICER of €45,195/QALY gained versus angiography-guided PTA. In the lifetime horizon, IVUS-guided PTA outperforms angiography-guided PTA; it was associated with a cost saving of €46 per patient and incremental QALY of 0.22. Utility value for post-TLR, as well as probabilities of death and TLR had the greatest impact on the one-year ICER, while cost of TLR and probabilities of TLR and amputation influenced the lifetime ICER most. The probability of IVUS-guided PTA being cost-effective at a willingness-to-pay (WTP) threshold of €50,000/QALY was 50.4% in the one-year horizon and increased to 85.9% in the lifetime horizon. Conclusions: In this analysis IVUS-guided PTA among patients with symptomatic FP atherosclerosis was cost-saving in a lifetime horizon from the German healthcare payer perspective.

Vessel shrinkage is associated with stroke recurrence in patients with symptomatic intracranial atherosclerosis

Vessel shrinkage is associated with stroke recurrence in patients with symptomatic intracranial atherosclerosis

Trapdoor endarterectomy for coral reef plaque of the paravisceral aorta in the modern era

Coral reef atherosclerosis of the paravisceral aorta is a rare disease whose description is confined to before contemporary vascular surgical techniques. This study aims to describe the characteristics and outcomes of patients with coral reef aorta treated with trapdoor endarterectomy at a single high-volume quaternary referral center since 2010. From 2010 to 2022, 14 patients with coral reef aorta were treated with trapdoor endarterectomy. The patient data were obtained via a retrospective medical record review. The patients were predominantly women (79%) with a median age of 65 years (interquartile range [IQR], 60-70 years). The patients universally had a tobacco smoking history and hypertension. More than 85% had previously diagnosed carotid stenosis. Two patients (14%) had undergone prior aortofemoral reconstruction, and one patient (7%) had undergone prior axillobifemoral bypass. The most common presenting symptoms were claudication (71%), chronic mesenteric ischemia (50%), and renovascular hypertension (43%). Of the 14 patients, 8 (57%) underwent isolated endarterectomy and 6 (43%) underwent concomitant aortobifemoral bypass. In addition, 13 patients (93%) required a supraceliac aortic clamp position with a median clamp time of 23 minutes (IQR, 20-30 minutes). The median estimated blood loss was 1650 mL (IQR, 1025-3000 mL). A cell saver was used in 13 procedures (93%), with a median transfusion of 563 mL (IQR, 231-900 mL). The median operative time was 341 minutes (IQR, 315-416 minutes). Eight patients (57%) experienced acute kidney injury in the postoperative period with a peak creatinine of 1.96 mg/dL (IQR, 1.50-2.84 mg/dL). The median length of stay was 11 days (IQR, 6-16 days), with an intensive care unit stay of 4 days (IQR, 2-7 days). One patient (7%) required reoperation in the immediate perioperative period for a retroperitoneal hematoma. The postoperative ankle brachial index increased from a median of 0.58 (right) and 0.57 (left) bilaterally in the preoperative period to 1.09 (right) and 1.10 (left) postoperatively. Eight patients (57%) had follow-up data available for >2 years postoperatively, with five patients (36%) having follow-up data available for >3 years. Two major adverse cardiac events were reported at the last follow-up. One patient reported mild recurrent symptoms of chronic mesenteric ischemia during 3 years of postoperatively, with no concurrent imaging findings or loss of patency found on computed tomography angiography. Symptomatic coral reef atherosclerosis of the paravisceral aorta is a complex disease rarely encountered even at high-volume referral centers. These patients can be expected to experience short-term postoperative morbidity and require intensive care. Despite these challenges, trapdoor endarterectomy is a safe and effective procedure for coral reef aorta, and most patients achieve dramatic symptomatic improvement with durable results.

Risks and benefits of antiplatelet therapy in patients with abdominal aortic aneurysm without symptomatic atherosclerotic disease: a nationwide cohort study

Abstract Background Patients with abdominal aortic aneurysm (AAA) suffer a high risk of ischemic events associated with concomitant atherosclerotic cardiovascular disease, and current clinical practice guidelines recommend antiplatelet therapies to mitigate this risk. However, in patients with AAA and no symptomatic atherosclerosis, the benefit of antiplatelet is sparsely investigated. Purpose To assess the effectiveness of antiplatelets vs no antiplatelets on the risk of ischemic events (composite of myocardial infarction and ischemic stroke) and bleeding in individuals with AAA who had no concomitant atherosclerotic vascular disease. Methods We designed a target trial to compare outcomes among treatment initiators and non-initiators and emulated the trial contingent on patient eligibility at time of inclusion, utilizing Danish nationwide observational data from January 2010 through August 2021. Confounding was handled by means of inverse probability treatment weighting based on the propensity score. The emulated sequential trial results for all possible trial months were pooled by means of pooled logistic regression models to estimate the intention-to-treat average treatment effects, and the 5-year associated treatment differences were expressed as hazard ratio (HR) with 95% confidence intervals (CI) and estimated event-free survival. Results A total of 6,344 patients provided 131,047 trial participants: 3,363 of these were new initiators of antiplatelet therapy, while 127,684 were non-initiators. During a median follow-up of 24 months, 173 and 369 ischemic events occurred among initiators and non-initiators, respectively. The corresponding HR of 0.91 (CI 95% 0.73 to 1.17) and an estimated absolute event-free survival difference of -0.6% (Figure 1). For bleeding, the HR was 1.26 (CI 0.97 to 1.58) and the event-free survival difference was 1.0%. Conclusion This target trial emulation, using nationwide observational data on all patients with AAA and no record of symptomatic atherosclerotic disease, did not find evidence of antiplatelets to lower the risk of ischemic events, but also no evidence of substantial higher bleeding risk. The observed differences between the treatment groups were minimal, suggesting limited clinically relevance of this treatment.ischemia- and bleeding free survival

Abstract 188: Rescue Left Middle Cerebral Artery Stenting With Xience Skypoint Everolimus‐Eluting Stent: Technical Report

Introduction Drug‐eluting stent (DES) use in symptomatic intracranial atherosclerosis disease (ICAD) has been described in the literature using different guiding and distal access catheters. We describe a case of deployment of a Xience Skypoint everolimus‐eluting stent (EES) (Abbott Vascular, Abbott Park, Illinois) into a symptomatic stenosed left M1 segment using Armadillo catheter (Q'Apel, Fremont, CA) with a successful result. Methods Case report and review of literature Results 67‐year‐old woman with type II diabetes mellitus, hypertension, hyperlipidemia, and recent admission for transient ischemic attack (resolving right hemiparesis and mild dysnomia in the setting of severe left M1 segment stenosis with discharge on Aspirin, Clopidogrel and Atorvastatin), presented with recurrence of symptoms, and MRI brain showing left basal ganglia acute infarction. No tPA was given low NIHSS and resolution of symptoms. Patient’s aphasia and hemiparesis worsened with segmental hypoperfusion which resolved by maintaining high blood pressures with norepinephrine drip. Decision was made to deploy a drug eluting stent into the stenosed M1 segment. Through femoral access, a 7F long destination sheath was inserted to the left common carotid origin. A 7F Armadillo catheter was then inserted into the left internal carotid artery (ICA) terminus. ASAHI Prowater coronary guidewire was inserted over which Xience Skypoint EES deployment was attempted but was unsuccessful given difficulty traversing the ICA ophthalmic segment. Ultimately, Armadillo catheter was advanced over a Phenom catheter (Medtronic) with good access into the distal M1 segment. The Phenom intermediate catheter was then removed, and the 2.25 mm x 12 mm stent was introduced through the Prowater guidewire into the segment and inflated to a pressure of 8 atm, with restoration of blood flow. Postoperatively, SBP was lowered to prevent reperfusion injury. Patient’s exam stabilized with mild dysnomia and right hemiparesis without any elevated blood pressure requirements. At 5‐months follow‐up, patient’s exam was non‐focal with NIHSS 0 and repeat DSA showed no evidence of stent occlusion and patent M1 segment. Conclusion Xience Skypoint EES can be successful in treating symptomatic MCA stenosis refractory to maximal medical therapy with good long term results.

Abstract 190: Patient Selection for Intracranial Stenting: Impact on Clinical Outcomes and Procedural Success Rates

Introduction Intracranial atherosclerosis (ICAS) is a leading global cause of stroke. The role of intracranial stenting in ICAS remains uncertain. In the SAMMPRIS trial, patients who had experienced recent TIA/CVA secondary to 70‐99% ICAS demonstrated an increased risk of recurrent stroke when treated with angioplasty and stenting compared to medical therapy alone [1]. The VISSIT trial found an increased 12‐month risk of TIA/CVA in the same territory, as well as an increased 30‐day risk of any TIA/CVA, when a stenting was used in patients with ICAS [2]. Additionally, the recent CASSISS trial demonstrated that adding percutaneous transluminal angioplasty and stenting (PTAS) to medical therapy did not significantly affect the risk of stroke or death within 30 days or stroke beyond 30 days through 1 year in patients TIA/CVA secondary to symptomatic ICAS [3]. However, the WEAVE trial demonstrated that using the Wingspan stent for ICAS resulted in a low periprocedural complication rate and excellent safety profile [4]. Subsequently, the WOVEN study provided a 1‐year follow‐up to WEAVE. It presented a more homogeneous patient group than in prior studies, and demonstrated a relatively low 8.5% 1‐year rate of stroke and death in stented patients [5]. Currently underway, the Angioplasty and Stenting for Patients With Symptomatic Intracranial Atherosclerosis Clinical trial (NCT02689037) aims to determine whether PTAS combined with medical treatment is superior to medical treatment alone in preventing stroke and death events in patients with symptomatic ICAS [6]. The purpose of this case series is to provide an overview of the procedural and clinical outcomes of patients who underwent stenting for symptomatic ICAS. Methods We reviewed a database of all interventional procedures conducted at our institution to identify patients who underwent intracranial stenting from 2013 and 2022 for symptomatic ICAS. Electronic medical records were assessed, and data on patient demographics, comorbidities, lesion characteristics, and clinical outcomes were extracted. The outcomes of interest included successful stent placement, restoration of blood flow, procedural complications, symptomatic improvement, change in NIHSS, and mortality and stroke within one year. Descriptive statistics were used, summarizing continuous variables as means and standard deviations, and categorical variables as frequencies and ranges. Results Between 2013 and 2022, 35 patients underwent intracranial stenting for symptomatic ICAS. Procedurally, all patients had successful stent placement and restoration of blood flow. Six patients (17.1%) experienced perioperative complications including stent occlusion, bradycardia, and hematoma. Regarding clinical outcomes, 25 patients (71.4%) showed improvement in their TIA/CVA symptoms, including dizziness, weakness, and speech difficulties. Furthermore, 21 patients (60%) had improved NIHSS scores by discharge, 9 patients (25.7%) remained stable, and 4 patients (11.4%) deteriorated. One unrelated mortality was recorded at 1‐year post‐procedure. Conclusion This case series demonstrates the successful and effective restoration of distal blood flow through intracranial stenting for symptomatic ICAS. The low rates of perioperative complications and potential improvements in patients' clinical outcomes suggest the need for further investigation into the patient selection, safety, and effectiveness of intracranial stenting for managing symptomatic ICAS.

Antiplatelet Therapy in Patients With Abdominal Aortic Aneurysm Without Symptomatic Atherosclerotic Disease

Patients with abdominal aortic aneurysm have a high risk of ischemic events associated with concomitant atherosclerotic cardiovascular disease, and current clinical practice guidelines recommend antiplatelet therapy to mitigate this risk. However, in patients with aneurysms without symptomatic atherosclerosis, the benefit of antiplatelet therapy has been sparsely investigated. To estimate the effect of antiplatelets on the risk of ischemic events and bleeding in individuals with abdominal aneurysms with no symptomatic atherosclerotic vascular disease. A comparative effectiveness research study using a target trial emulation framework was performed. Population-based, cross-linked observational data from Danish national health registries containing comprehensive, individual-level information on all Danish citizens were used to evaluate patients who were antiplatelet-naive and diagnosed with abdominal aortic aneurysms, with no record of symptomatic atherosclerotic vascular disease, from January 1, 2010, through August 21, 2021. Prescription filled for aspirin or clopidogrel. Risk of ischemic events (myocardial infarction and/or ischemic stroke) and risk of major bleeding. For target trial emulation, trials were emulated as sequential, contingent on patient eligibility at the time of inclusion, and were evaluated by means of pooled logistic regression models to estimate the intention-to-treat and as-treated effects, expressed as hazard ratio (HR) and event-free survival. A total of 6344 patients (65.2% men; age, 72 [IQR, 64-78] years) provided 131 047 trial cases; 3363 of these cases involved initiation of antiplatelet therapy and 127 684 did not. A total of 182 ischemic events occurred among initiators and 5602 ischemic events occurred among noninitiators, corresponding to an intention-to-treat HR of 0.91 (95% CI, 0.73-1.17) and an estimated absolute event-free survival difference of -0.6% (95% CI, -1.7% to 0.5%). After censoring nonadherent person-time, the treatment HR was 0.90 (95% CI, 0.68-1.20), with similar risk difference. For bleeding, the intention-to-treat HR was 1.26 (95% CI, 0.97-1.58) and the event-free survival difference was 1.0%. The treatment HR was 1.21 (95% CI, 0.82-1.72); the risk difference was similar. In this study, no evidence of effectiveness of antiplatelet therapy to lower the risk of ischemic events and a trend toward higher bleeding risk was noted. The observed differences between the treatment groups were minimal, suggesting limited clinical relevance of antiplatelet treatment.