Undergoing Carotid Endarterectomy Research Articles

Comparing the Surgical Outcomes of Carotid Endarterectomy: Assessing the Impact of Consultant vs. Trainee Cases on Patient Care and Surgical Training

ObjectiveThis study assesses the impact of having a surgical trainee performing a carotid endarterectomy procedure on the post-operative rates of stroke and death. DesignObservational Retrospective study MethodsConsecutive patients, who underwent carotid endarterectomy between 01/05/2016 and 31/7/2022, were entered into a retrospectively collected database. Patients were stratified into two categories – consultant-led cases and trainees-led cases. Primary outcomes were 30- day stroke rate, and 30-day morbimortality. A sub analysis was performed after grouping the patients in whether there was a neurological event in the previous six months – symptomatic or asymptomatic. Results/ConclusionsTrainees-led cases had significantly longer clamping times and higher rates of stroke in asymptomatic patients compared with consultant-led cases. Patient’s safety should be our top priority. Any practice leading to a significantly increased rate of post-operative stroke must be discontinued. Training protocols and adequate supervision must ensure that trainees possess the necessary skills and knowledge to safely and effectively perform carotid endarterectomy (CEA) procedures, thereby prioritizing patient safety.

Cross-species single-cell RNA sequencing reveals divergent phenotypes and activation states of adaptive immunity in human carotid and experimental murine atherosclerosis.

The distinct functions of immune cells in atherosclerosis have been mostly defined by preclinical mouse studies. Contrastingly, the immune cell composition of human atherosclerotic plaques and their contribution to disease progression is only poorly understood. It remains uncertain whether genetic animal models allow for valuable translational approaches. Single cell RNA-sequencing (scRNA-seq) was performed to define the immune cell landscape in human carotid atherosclerotic plaques. The human immune cell repertoire demonstrated an unexpectedly high heterogeneity and was dominated by cells of the T-cell lineage, a finding confirmed by immunohistochemistry. Bioinformatical integration with 7 mouse scRNA-seq data sets from adventitial and atherosclerotic vascular tissue revealed a total of 51 identities of cell types and differentiation states, of which some were only poorly conserved between species and exclusively found in humans. Locations, frequencies, and transcriptional programs of immune cells in mouse models did not resemble the immune cell landscape in human carotid atherosclerosis. In contrast to standard mouse models of atherosclerosis, human plaque leukocytes were dominated by several T-cell phenotypes with transcriptional hallmarks of T-cell activation and memory formation, T-cell receptor-, and pro-inflammatory signaling. Only mice at the age of 22 months partially resembled the activated T-cell phenotype. In a validation cohort of 43 patients undergoing carotid endarterectomy, the abundance of activated immune cell subsets in the plaque defined by multi-color flow cytometry associated with the extend of clinical atherosclerosis. Integrative scRNA-seq reveals a substantial difference in the immune cell composition of murine and human carotid atherosclerosis - a finding that questions the translational value of standard mouse models for adaptive immune cell studies. Clinical associations suggest a specific role for T-cell driven (auto-) immunity in human plaque formation and -instability.

Predictors of the dynamics of changes in cognitive functions in patients 6 months after carotid endarterectomy

Background. Carotid atherosclerosis is one of the urgent problems due to the high risk of developing ischemic stroke and cognitive impairment. The dynamics of clinical disorders in patients with carotid stenosis is determined by a complex of neurophysiological, angiological, tissue and biomolecular reactions, the characteristics of which can act as predictors of the course of the pathology.The aim of the work. To determine the neurophysiological parameters and predictors of cognitive dysfunction in patients who underwent carotid endarterectomy.Materials and methods. The study included 59 people with carotid atherosclerotic disease. All included patients underwent carotid endarterectomy. We assessed the degree of stenosis of the internal carotid artery and cognitive status using the FAB (Frontal Assessment Battery) scale and MoCA (Montreal Cognitive Assessment) Test and recorded electroencephalogram (EEG), P300 cognitive evoked potentials and heart rate variability in patients at various terms (before surgery, 6 months after the surgery). Patients were divided into groups based on the dynamics of cognitive tests using cluster analysis (k-means) with identification of elements included in the clusters: patients of cluster 1 had a “preserved” profile of cognitive status; patients of cluster 2 – moderate cognitive dysfunction.Results. Patients of cluster 1 had a higher power of beta oscillations in the frontal lead, a higher amplitude of the P3 component of the P300 potential, and a greater variability of R-R intervals in terms of the total indicator and high-frequency power. We proposed a model that allows us to classify patients into groups according to the dynamics of cognitive function scores. According to the data obtained, the most significant predictors of the dynamics of cognitive status were the initial characteristics of the EEG and the P300 cognitive evoked potential.Conclusions. We determined the clinical and neurophysiological correlates of cognitive dysfunction: an association with greater preservation of activating effects on the EEG, processes of recognition and decision-making in the associative zones of the cortex, and less pronounced activity of stress-implementing mechanisms. Indicators of EEG spectral analysis and characteristics of the P300 cognitive evoked potential are predictors of the cognitive status dynamics.

Gray-Scale Median in Patients with Symptomatic and Asymptomatic Carotid Atherosclerosis-Risk Factors and Diagnostic Potential.

The identification of clinical factors affecting the gray-scale median (GSM) and determination of GSM diagnostic utility for differentiating between symptomatic and asymptomatic internal carotid artery (ICA) stenosis. This study included 45 patients with asymptomatic and 40 patients with symptomatic ICA stenosis undergoing carotid endarterectomy (CEA). Echolucency of carotid plaque was determined using computerized techniques for the GSM analysis. Study groups were compared in terms of clinical risk factors, coexisting comorbidities, and used pharmacotherapy. Mean GSM values in the symptomatic group were significantly lower than in the asymptomatic group (p < 0.001). Both in the univariate as well as in the multiple regression analysis, GSM was significantly correlated with D-dimers and fasting plasma glucose levels and tended to correlate with β-adrenoceptor antagonist use in the symptomatic group. In asymptomatic patients, GSM was associated with the presence of grade 2 and grade 3 hypertension, and tended to correlate with the use of metformin, sulfonylureas, and statin. Independent factors for GSM in this group remained as grade 3 hypertension and statin's therapy. The receiver operating characteristic (ROC) analysis revealed that GSM differentiated symptomatic from asymptomatic ICA stenosis with sensitivity and specificity of 73% and 80%, respectively. The completely diverse clinical parameters may affect GSM in symptomatic and asymptomatic patients undergoing CEA, whose clinical characteristics were similar in terms of most of the compared parameters. GSM may be a clinically useful parameter for differentiating between symptomatic and asymptomatic ICA stenosis.

Amyloid beta is associated with carotid wall echolucency and atherosclerotic plaque composition

Circulating amyloid-beta 1–40 (Αb40) has pro-atherogenic properties and could serve as a biomarker in atherosclerotic cardiovascular disease (ASCVD). However, the association of Ab40 levels with morphological characteristics reflecting atherosclerotic plaque echolucency and composition is not available. Carotid atherosclerosis was assessed in consecutively recruited individuals without ASCVD (n = 342) by ultrasonography. The primary endpoint was grey scale median (GSM) of intima-media complex (IMC) and plaques, analysed using dedicated software. Vascular markers were assessed at two time-points (median follow-up 35.5 months). In n = 56 patients undergoing carotid endarterectomy, histological plaque features were analysed. Plasma Αb40 levels were measured at baseline. Ab40 was associated with lower IMC GSM and plaque GSM and higher plaque area at baseline after multivariable adjustment. Increased Ab40 levels were also longitudinally associated with decreasing or persistently low IMC and plaque GSM after multivariable adjustment (p < 0.05). In the histological analysis, Ab40 levels were associated with lower incidence of calcified plaques and plaques without high-risk features. Ab40 levels are associated with ultrasonographic and histological markers of carotid wall composition both in the non-stenotic arterial wall and in severely stenotic plaques. These findings support experimental evidence linking Ab40 with plaque vulnerability, possibly mediating its established association with major adverse cardiovascular events.

Perioperative platelet reactivityover time inpatients undergoing vascular surgery: An observational pilot study.

Despite Antiplatelet therapy (APT), cardiovascular patients undergoing revascularisation remain at high risk for thrombotic events. Individual response to APT varies substantially, resulting in insufficient protection from thrombotic events due to high on-treatment platelet reactivity (HTPR) in ≤40% of patients. Individual variation in platelet response impairs APT guidance on a single patient level. Unfortunately, little is known about individual platelet response to APT over time, timing for accurate residual platelet reactivity measurement, or the optimal test to monitor residual platelet reactivity. To investigate residual platelet reactivity variability over time in individual patients undergoing carotid endarterectomy (CEA) treated with clopidogrel. Platelet reactivity was determined in patients undergoing CEA in a prospective, single-centre, observational study using the VerifyNow (change in turbidity from ADP-induced binding to fibrinogen-coated beads), the VASP assay (quantification of phosphorylation of vasodilator-stimulated phosphoprotein), and a flow-cytometry-based assay (PACT) at four perioperative time points. Genotyping identified slow (CYP2C19*2 and CYP2C19*3) and fast (CYP2C19*17) metabolisers. Between December 2017 and November 2019, 50 patients undergoing CEA were included. Platelet reactivity measured with the VerifyNow (p = < .001) and VASP (p = .029) changed over time, while the PACT did not. The VerifyNow identified patients changing HTRP status after surgery. The VASP identified patients changing HTPR status after eight weeks (p = .018). CYP2C19 genotyping identified 13 slow metabolisers. In patients undergoing CEA, perioperative platelet reactivity measurements fluctuate over time with little agreement between platelet reactivity assays. Consequently, HTPR status of individual patients measured with the VerifyNow and VASP assay changed over time. Therefore, generally used perioperative platelet reactivity measurements seem unreliable for adjusting perioperative APT strategy.

Cerebrovascular dysregulation and postoperative cognitive alterations after carotid endarterectomy.

There are controversial data about the effect of carotid endarterectomy regarding postoperative cognitive function. Our aim was to analyze the effect of cerebral tissue saturation monitored by near-infrared spectroscopy (NIRS) on cognitive function. Perioperative data of 103 asymptomatic patients undergoing elective carotid surgery under general anesthesia were analyzed. Preoperatively and 3months after the operation, MMSE (Mini Mental State Examination) and MoCA (Montreal Cognitive Assessment) tests were conducted. For cerebral monitoring, NIRS was used, and the lowest rSO2 value and the degree of desaturation were calculated. Cognitive changes were defined as one standard deviation change from the preoperative test scores, defined as postoperative neurocognitive decline (PNCD) and cognitive improvement (POCI). PNCD was found in 37 patients (35.92%), and POCI was found in 18 patients (17.47%). Female gender, patients with diabetes, and the degree of desaturation were independently associated with PNCD. The degree of desaturation during the cross-clamp period negatively correlated with the change in the MoCA scores (R = - 0.707, p = 0.001). The 15.5% desaturation ratio had 86.5% sensitivity and 78.8% specificity for discrimination. For POCI, a desaturation of less than 12.65% had 72.2% sensitivity and 67.1% specificity. POCI was associated with lower preoperative MOCA scores and a lower degree of desaturation. We found a significant relation between the change of postoperative cognitive function proven by the MoCA test and cerebral tissue saturation during the clamping period in patients undergoing carotid endarterectomy.

Locoregional Anesthesia Is Associated with Decreased Cardiac Complications in Symptomatic Heart Failure Patients Undergoing Carotid Endarterectomy

ObjectiveWhile current literature reports no advantage for locoregional anesthesia (LRA) over general anesthesia (GA) in patients undergoing carotid endarterectomy (CEA), there remains a gap in understanding the impact of LRA on individuals with congestive heart failure (CHF). This study aims to assess whether the choice of anesthesia influences the rates of perioperative complications within this patient population. MethodsUsing the Vascular Quality Initiative (VQI) carotid endarterectomy module, all patients undergoing CEA between 2013-2023 were identified. The subset of patients with CHF was included, and patients were divided based on the type of anesthesia received. Patient characteristics and outcomes were compared using χ2 or Fischer’s exact test as appropriate for categorical variables and the independent t-test or Mann-Whitney U test as appropriate for continuous variables. A sensitivity analysis was performed based on the symptomatic status of CHF, and the association between anesthesia modality and post-operative outcomes was studied using multivariable logistic regression analysis. The primary outcomes of this study included perioperative stroke, MI, acute heart failure (HF), and the combination of MI and acute HF defined as major cardiac complications. ResultsA total of 21,292 patients (19,730 receiving GA, 1,562 receiving LRA) with a diagnosis of CHF undergoing CEA were identified. On multivariable logistic regression analysis, LRA was independently associated with lower MI (OR 0.35, 95% CI 0.13–0.96), acute HF (OR 0.27, 95% CI 0.09-0.87), major cardiac complications (OR 0.30, 95% CI 0.13-0.67), hemodynamic instability (OR 0.64, 95% CI 0.53-0.78), cranial nerve injury (OR 0.40, 95% CI 0.19-0.81), shunt use (OR 0.25, 95% CI 0.20-0.31), and neuromonitoring device use (OR 0.20, 95% CI 0.17-0.24) compared to GA in symptomatic CHF patients. No difference in MI, acute HF, and major cardiac complications was seen in asymptomatic CHF patients. ConclusionCEA can be safely performed in patients with CHF. Utilizing LRA is associated with a decreased incidence of perioperative cardiac complications in patients with symptomatic heart failure undergoing CEA.

In Patients with Heart Failure Undergoing Carotid Endarterectomy, Locoregional Anesthesia is Not Associated with Decreased Mortality, Stroke, or Myocardial Infarction Compared to General Anesthesia

ObjectiveWhile existing literature reports no benefit of locoregional anesthesia (LRA) over general anesthesia (GA) in patients undergoing carotid endarterectomy (CEA), the effect of LRA on patients with congestive heart failure (CHF) has not been explored. This study aims to assess whether the choice of anesthesia plays a role in influencing outcomes within this population. MethodsUsing the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) files between 2005-2022 and the procedural targeted ACS-NSQIP database for CEA between 2011-2022, all patients receiving CEA were identified, and the subset of patients with CHF was included. Patient characteristics and 30-day outcomes were compared using χ2 or Fischer’s exact test as appropriate for categorical variables and the independent t-test or Mann-Whitney U test as appropriate for continuous variables. Mortality, stroke, myocardial infarction (MI), and major adverse cardiac events (MACE) were compared between patients receiving general anesthesia (GA) and locoregional anesthesia (LRA) using univariate analysis. ResultsA total of 3,040 patients (2,733 undergoing GA, 307 undergoing LRA) with a diagnosis of CHF undergoing CEA were identified. No difference in mortality (GA 3.1% vs LRA 4.6%, p=0.162), MI (GA 3.0% vs LRA 2.3%, p=0.478), stroke (2.4% vs 2.6%, p=0.805) or MACE (GA 7.4% vs LRA 8.1%, p=0.654) was observed. LRA patients had a significantly lower hospital stay compared to GA patients (1 day [IQR 1-3] vs 2 days [IQR 1-4], p<0.001). Shunt was more commonly used in patients receiving GA (32.9% vs 12.5%, p<0.001) compared to LRA. ConclusionWhile utilizing LRA compared to GA during carotid endarterectomy in patients with CHF is associated with a shorter hospital stay and less intraoperative shunting, the choice of anesthesia did not impact the outcomes of mortality, MI or stroke. Further research is needed to determine the effect of LRA on the outcomes of CEA among patients with different stages of heart failure.

Diagnostic accuracy of preoperative quantitative susceptibility mapping for detecting histologic intraplaque hemorrhage in cervical ICA stenosis in patients undergoing carotid endarterectomy.

Quantitative susceptibility mapping (QSM) has been proposed to assess intraplaque hemorrhage (IPH) in the carotid artery. The purpose of this study was to compare the diagnostic accuracy of preoperative QSM with that of the conventional T1-weighed (T1W) three-dimensional (3D)-FSE sequence for detecting IPH in cervical ICA stenosis in patients undergoing carotid endarterectomy (CEA) using histology as the reference standard. Carotid T1W 3D-FSE and QSM images were obtained from 16 patients with cervical ICA stenosis before CEA. Relative signal intensity (RSI) and susceptibility of the ICA were measured on three axial images including the location of most severe stenosis on T1W 3D-FSE and QSM images, respectively. Three transverse sections of carotid plaques excised by CEA, which corresponded with images on MRI, were stained with H&E, antibody against glycophorin A and Prussian blue, and the relative area (RA) of histologic IPH was calculated. The correlation coefficient was significantly greater between susceptibility and RA-histologic IPH (ρ = 0.691) than between RSI and RA-histologic IPH (ρ = 0.413; P = .0259). The areas under the receiver operating characteristic curves for detecting histologic sections consisting primarily of IPH (RA-histologic IPH > 40.7%) tended to be greater for susceptibility (0.964) than for T1WI FSE-RSI (0.811). Marginal homogeneity was observed between susceptibility and histologic sections consisting primarily of IPH (P = .0412) but not between T1W FSE-RSI and histologic sections consisting primarily of IPH (P = .1824). Pre-CEA QSM detects histologic IPH in cervical ICA stenosis more accurately than preoperative T1W 3D-FSE imaging. QSM = quantitative susceptibility mapping; IPH = intraplaque hemorrhage; T1W = T1-weighed; 3D = three-dimensional; CEA = carotid endarterectomy; RSI = relative signal intensity; RA = relative area.

African American Women Are More Likely to Undergo Carotid Endarterectomy for a Higher Degree of Stenosis and Have Increased Risk of Return to the Operating Room as Compared With White Women

African American Women Are More Likely to Undergo Carotid Endarterectomy for a Higher Degree of Stenosis and Have Increased Risk of Return to the Operating Room as Compared With White Women

Abstract 2079: Single-cell And Spatially Resolved Transcriptome Analysis Reveals A Novel Lncrna Regulator Of Human Atherosclerosis

Cardiovascular diseases, such as atherosclerosis, are the major cause of death in Western societies. Still, molecular mechanisms of plaque destabilization remain unclear. Vascular Smooth Muscle Cells (VSMCs) are the most abundant cell type in atherosclerotic lesions. These cells keep their plasticity also with disease progression and are, therefore, an ideal target cell type for potential therapies. Long non-coding RNAs (lncRNAs) are one example of highly cell type- and disease-state-specific novel molecular modulators. We utilized combined total (bulk) RNA and single cell (sc) RNA sequencing of advanced human carotid artery lesions (patients who underwent carotid endarterectomy in our vascular surgery clinic) to discover novel regulators. Additionally, we performed hybridization-based RNA in situ sequencing (HybRISS, Xenium) to indicate where these genes are located within the plaques. We also performed scSeq in our inducible carotid artery plaque rupture mice ( ApoE-/- ). In vivo and in vitro modulation (KD; knock-down) of the newly identified lncRNA DLX6-AS1 ( D istal- L ess Homeobo x 6 A nti s ense 1 ) using Antisense LNA (Locked nucleic acid) GapmeRs is performed in this mouse model as well as in primary human VSMC culture. DLX6-AS1 shows a highly specific expression pattern in a distinct sub-cluster of VSMCs, as well as a striking location within human atherosclerotic lesions shown by spatial transcriptomics in advanced plaques. DLX6-AS1 is mainly expressed in the nucleus of cells, and KD of this lncRNA leads to changes in VSMC behavior in vitro and in vivo . The KD also has only little effect on the other genes of this locus, DLX6 and DLX5 ( D istal- L ess Homeobo x 6 and 5 ) We found Dlx6os1 ( D istal- l ess homeobo x 6, o pposite s trand 1 ) in our scRNA-seq dataset of the inducible carotid artery plaque rupture mice ( ApoE-/- ) where the KD leads to an increased plaque rupture rate. Taken together, our datasets, methods, and animal models demonstrate that utilizing bulk- and scRNA-seq data, together with spatially resolved sequencing methods, are powerful tools to identify and characterize novel lncRNA regulators that can facilitate fate decisions in VSMCs in atherosclerosis. DLX6-AS1 is one of these novel regulators and will be further analyzed in vivo and in vitro .

Abstract 1028: Cytotoxic CD4+ T Cells: Unraveling The Residual Risk In Lipid Lowering For Type 2 Diabetes Patients

Type 2 Diabetes (T2D) significantly increases the risk of cardiovascular diseases (CVDs), marked by severe plaque pathology resistant to standard cholesterol-lowering treatments. While the roles of the innate immune system and macrophages in CVDs are well-established, T cell alterations, particularly involving cytotoxic CD4 T cells (CD4 CTLs), remain unexplored in human atherosclerotic plaques. In our study, we aimed to identify the phenotype and function of CD4 CTLs in blood &amp; plaque tissue, in the context of T2D. Using unbiased single-cell RNA sequencing (scRNA-seq) analysis, we examined over 70,000 immune cells from 22 plaques of patients undergoing carotid endarterectomy (T2D: n=12, Non-Diabetic (ND): n=10), &amp; peripheral blood mononuclear cells (PBMCs) from the CHORD study (NCT04369664) (T2D: n=12, ND: n=4). scRNA-seq analysis revealed a diverse population of CD4 T cells, like naïve, central memory (CM), effector memory (EM), tissue resident memory (Trm), T regulatory (Tregs), &amp; two clusters of cytotoxic (CTL) T cells expressing canonical cytotoxicity-related genes. Cluster 5 expressed GZMB, GNLY, PRF1 , whereas Cluster 10 expressed GZMA, GZMK . Cell-cell communication analysis demonstrated that both CTL clusters received signaling from dendritic cells and macrophages, including TREM2+ macrophages. CTL T cells reciprocally communicated with clusters of EM and EMRA CD8 T cells, underscoring their central role in plaque cell-cell communication. Notably, Cluster 5, one of these two CTL clusters, was expanded in T2D plaque samples (p=0.032) and expressed genes involved in chemotaxis, IL-2 signaling, &amp; transcription factors (e.g., RUNX3, TBX21 ) involved in T cell activation. The equivalent of CD4 CTL phenotype was found to be expanded in T2D individuals compared to controls, &amp; these elevated levels persisted in T2D patients following intensive lipid-lowering therapy, indicating resistance to the treatment regimen. In summary, our study emphasizes the crucial role of CD4 CTLs in the immune dynamics of atherosclerotic plaques. The observed resistance of CTLs to lipid-lowering interventions underscores the necessity for targeted therapeutic strategies to address the distinctive immune changes in T2D-associated cardiovascular diseases.

Predictors of prolonged length of stay after elective carotid revascularization

ObjectivePostoperative day-one discharge is used as a quality-of-care indicator after carotid revascularization. This study identifies predictors of prolonged length of stay (pLOS), defined as a postprocedural LOS of >1 day, after elective carotid revascularization. MethodsPatients undergoing carotid endarterectomy (CEA), transcarotid artery revascularization (TCAR), and transfemoral carotid artery stenting (TFCAS) in the Vascular Quality Initiative between 2016 and 2022 were included in this analysis. Multivariable logistic regression analysis was used to identify predictors of pLOS, defined as a postprocedural LOS of >1 day, after each procedure. ResultsA total of 118,625 elective cases were included. pLOS was observed in nearly 23.2% of patients undergoing carotid revascularization. Major adverse events, including neurological, cardiac, infectious, and bleeding complications, occurred in 5.2% of patients and were the most significant contributor to pLOS after the three procedures. Age, female sex, non-White race, insurance status, high comorbidity index, prior ipsilateral CEA, non-ambulatory status, symptomatic presentation, surgeries occurring on Friday, and postoperative hypo- or hypertension were significantly associated with pLOS across all three procedures. For CEA, additional predictors included contralateral carotid artery occlusion, preoperative use of dual antiplatelets and anticoagulation, low physician volume (<11 cases/year), and drain use. For TCAR, preoperative anticoagulation use, low physician case volume (<6 cases/year), no protamine use, and post-stent dilatation intraoperatively were associated with pLOS. One-year analysis showed a significant association between pLOS and increased mortality for all three procedures; CEA (hazard ratio [HR],1.64; 95% confidence interval [CI], 1.49-1.82), TCAR (HR,1.56; 95% CI, 1.35-1.80), and TFCAS (HR, 1.33; 95%CI, 1.08-1.64) (all P < .05). ConclusionsA postoperative LOS of more than 1 day is not uncommon after carotid revascularization. Procedure-related complications are the most common drivers of pLOS. Identifying patients who are risk for pLOS highlights quality improvement strategies that can optimize short and 1-year outcomes of patients undergoing carotid revascularization.

The effect of controlled vs uncontrolled hypertension on outcomes of carotid revascularization procedures

BackgroundHypertension (HTN) has been implicated as a strong predictive factor for poorer outcomes in patients undergoing various vascular procedures. However, limited research is available that examines the effect of uncontrolled HTN (uHTN) on outcomes after carotid revascularization. We aimed to determine which carotid revascularization procedure yields the best outcome in this patient population. MethodsWe studied patients undergoing carotid endarterectomy (CEA), transfemoral carotid artery stenting (TFCAS), or transcarotid artery revascularization (TCAR) from April 2020 to June 2022 using data from the Vascular Quality Initiative. Patients were stratified into two groups: those with cHTN and those with uHTN. Patients with cHTN were those with HTN treated with medication and a blood pressure of <130/80 mm Hg. Patients with uHTN had a blood pressure of ≥130/80 mm Hg. Our primary outcomes were in-hospital stroke, death, myocardial infarction (MI), and 30-day mortality. Our secondary outcomes were postoperative hypotension or HTN, reperfusion syndrome, prolonged length of stay (LOS) (>1 day), stroke/death, and stroke/death/MI. We used logistic regression models for the multivariate analysis. ResultsA total of 34,653 CEA (uHTN, 11,347 [32.7%]), 8199 TFCAS (uHTN, 2307 [28.1%]), and 17,309 TCAR (uHTN, 4990 [28.8%]) patients were included in this study. There was no significant difference in age between patients with cHTN and patients with uHTN for each carotid revascularization procedure. However, compared with patients with cHTN, patients with uHTN had significantly more comorbidities. uHTN was associated with an increased risk of combined in-hospital stroke/death/MI after CEA (adjusted odds ratio [aOR], 1.56; 95% confidence interval [CI], 1.30-1.87; P < .001), TFCAS (aOR, 1.59; 95% CI, 1.21-2.08; P < .001), and TCAR (aOR, 1.39; 95% CI, 1.12-1.73; P = .003) compared with cHTN. Additionally, uHTN was associated with a prolonged LOS after all carotid revascularization methods. For the subanalysis of patients with uHTN, TFCAS was associated with an increased risk of stroke (aOR, 1.82; 95% CI, 1.39-2.37; P < .001), in-hospital death (aOR, 3.73; 95% CI, 2.25-6.19; P < .001), reperfusion syndrome (aOR, 6.24; 95% CI, 3.57-10.93; P < .001), and extended LOS (aOR, 1.87; 95% CI, 1.51-2.32; P < .001) compared with CEA. There was no statistically significant difference between the outcomes of TCAR compared with CEA. ConclusionsThe results from this study show that patients with uHTN are at a higher risk of stroke and death postoperatively compared with patients with cHTN, highlighting the importance of treating HTN before undergoing elective carotid revascularization. Additionally, in patients with uHTN, TFCAS yields the worst outcomes, whereas CEA and TCAR proved to be safer interventions. Patients with uTHN with symptomatic carotid disease treated with CEA or TCAR have better outcomes compared with those treated with TFCAS.

Optimization of cerebral oxygenation based on regional cerebral oxygen saturation monitoring during carotid endarterectomy: a Phase III multicenter, double-blind randomized controlled trial

BackgroundWhether the optimization of cerebral oxygenation based on regional cerebral oxygen saturation (rSO2) monitoring reduces the occurrence of cerebral ischemic lesions is unknown. MethodsThis multicenter, randomized, controlled trial recruited adults admitted for scheduled carotid endarterectomy. Patients were randomized between the standard of care or optimization of cerebral oxygenation based on rSO2 monitoring using near-infrared spectroscopy. In the intervention group, in case of a decrease in rSO2 in the intervention, the following treatments were sequentially recommended: (1) increasing oxygenotherapy, (2) reducing the tidal volume, (3) legs up-raising, (4) performing a fluid challenge and (5) initiating vasopressor support. The primary endpoint was the number of new cerebral ischemic lesions detected using magnetic resonance imaging pre- and postoperatively. Secondary endpoints included new neurological deficits and mortality on day 120 after surgery. ResultsAmong the 879 patients who were randomized, 665 (75.7%) were men. There was no statistically significant difference between groups for the mean number of new cerebral ischemic lesions per patient up to 3 days after surgery: 0.35 (±1.05) in the standard group vs. 0.58 (±2.83), in the NIRS group; mean difference, 0.23 [95% CI, −0.06 to 0.52]; estimate, 0.22 [95% CI, −0.06 to 0.50]. New neurological deficits up to day 120 after hospital discharge were not different between the groups: 15 (3,39%) in the standard group vs. 42 (5,49%) in the NIRS group; absolute difference, 2,10 [95% CI, −0,62 to 4,82]. There was no significant difference between groups for the median [IQR] hospital length of stay: 4.0 [4.0–6.0] in the standard group vs. 5.0 [4.0–6.0] in the NIRS group; mean difference, −0.11 [95% CI, −0.65 to 0.44]. The mortality rate on day 120 was not different between the standard group (0.68%) vs. the NIRS group (0.92%); absolute difference = 0.24% [95% CI, −0.94 to 1.41]. ConclusionsAmong patients undergoing carotid endarterectomy, optimization of cerebral oxygenation based on rSO2 did not reduce the occurrence of cerebral ischemic lesions postoperatively compared with controlled hypertensive therapy. Trial registrationClinicalTrials.gov identifier: NCT01415648.

Abstract 141: Lesion Site-specific Mass Spectrometry Analysis Of Human Carotid Plaques Reveals Strongest Association Of The Necrotic Core And Fibrous Cap Proteome With Plaque Stability

The spatial impact of the plaque proteome on atherosclerotic plaque stability remains largely unknown. In this study, we performed mass spectrometry-based proteomics of various carotid plaque subregions (media, necrotic core, fibrous cap), using guided laser capture micro-dissections (LCM) of FFPE tissue in a matched cohort of 112 patients undergoing carotid endarterectomy (CEA) to study the impact of the plaque proteome, not only on lesion stability, but also on subregional changes of expression. Further, we performed a histological analysis according to the AHA classification and combined the data with clinical information on risk factors, comorbidities, and patient symptoms. Our LCM mass spectrometry analysis yielded over 3000 proteins for each plaque subregion. Gene set enrichment analysis revealed a high abundance of extracellular proteins and vice versa for cellular proteins. Subregion analysis identified the necrotic core and the fibrous cap to display the most significant changes in proteins associated with the stability status, whereas the media proteome remained largely unaffected. Primary and secondary enrichment analysis revealed synthetic vascular smooth muscle cells as the major source of these proteins. In addition, we analyzed the serum proteome of more than 500 patients (including non-athero control patients) with overlap from the tissue cohort. We combined these with histological evaluation and a complete set of clinical data. We used these two datasets for developing tissue and serological markers associated with plaque stability. In summary, our approach utilized LCM mass spectrometry, histological evaluation, and clinical data to analyze the association of different lesion subregions on plaque stability. We are able to demonstrate a high through-put method to identify potential protein markers relevant to atherosclerotic plaque stability.

Polyvascular disease is common in patients undergoing carotid endarterectomy and lower extremity bypass and is associated with worse outcomes

BackgroundPolyvascular disease is strongly associated with increased risk of cardiovascular morbidity and mortality. However, its prevalence in patients undergoing carotid and lower extremity surgical revascularization and its impact on outcomes are unknown. MethodsThe Vascular Quality Initiative was queried for carotid endarterectomy (CEA) or infrainguinal lower extremity bypass (LEB), 2013-2019. Polyvascular disease was defined as presence of atherosclerotic occlusive disease in more than one arterial bed: carotid, coronary, and infrainguinal. Primary outcomes were (1) composite perioperative myocardial infarction (MI) or death and (2) 5-year survival. Patient characteristics and perioperative outcomes were evaluated using the χ2 test and multivariable logistic regression. Survival was analyzed using Kaplan-Meier method and Cox proportional hazards multivariable models. ResultsPolyvascular disease was identified in 47% of CEA (39.0% in 2 arterial beds, 7.6% in 3 arterial beds; n = 93,736) and 47% of LEB (41.0% in 2 arterial beds, 5.7% in 3 arterial beds; n = 25,223). For both CEA and LEB, patients with polyvascular disease had more comorbidities including hypertension, congestive heart disease, chronic obstructive pulmonary disease, smoking, diabetes mellitus, and end-stage renal disease (P < .0001). Perioperative MI/death rates increased with increasing number of vascular beds affected following CEA (0.9% in 1 bed vs 1.5% in 2 beds vs 2.7% in 3 beds; P < .001) and LEB (2.2% in 1 bed vs 5.3% in 2 beds vs 6.6% in 3 beds; P < .001). Polyvascular disease was associated independently with perioperative MI/death after CEA (odds ratio, 1.59; 95% confidence interval [CI], 1.40-1.81;P < .0001) and LEB (odds ratio, 1.78; 95% CI, 1.52-2.08; P < .0001). Five-year survival was decreased in patients with polyvascular disease after CEA (82% in 3 beds vs 88% in 2 beds vs 92% in 1 bed; P < .01) and LEB (72% in 3 beds vs 75% in 2 beds vs 84% in 1 bed; P < .01) in a dose-dependent manner, with the lowest 5-year survival observed in those with three arterial beds involved. Polyvascular disease was independently associated with 5-year mortality after CEA (hazard ratio, 1.33; 95% CI, 1.24-1.40; P = .0001) and LEB (hazard ratio, 1.30; 95% CI, 1.20-1.41; P = .0001). ConclusionsPolyvascular disease is common in patients undergoing CEA and LEB and is associated with a higher risk of perioperative MI/death and decreased long-term survival. After revascularization, patients with polyvascular disease should be considered for more aggressive cardioprotective medications and closer follow-up.

The MMP-9 promoter genetic variant rs3918242, mRNA and protein expression in advanced carotid plaque tissue.

The MMP-9 is a known player in atherosclerosis, yet associations of the MMP-9 -1562C/T variant (rs3918242) with various atherosclerotic phenotypes and tissue mRNA expression are still contradictory. This study aimed to investigate the MMP-9 -1562C/T variant, its mRNA and protein expression in carotid plaque (CP) tissue, as a risk factor for CP presence and as a marker of different plaque phenotypes (hyperechoic and hypoechoic) in patients undergoing carotid endarterectomy. The MnSOD as an MMP-9 negative regulator was also studied in relation to CP phenotypes. Genotyping of 770 participants (285 controls/485 patients) was done by tetra-primer ARMS PCR. The MMP-9 mRNA expression in 88 human CP tissues was detected by TaqMan® technology. The protein levels of MMP-9 and MnSOD were assessed by Western blot analysis. The MMP-9 -1562C/T variant was not recognized as a risk factor for plaque presence or in predisposing MMP-9 mRNA and protein levels in plaque tissue. Patients with hypoechoic plaques had significantly lower MMP-9 mRNA and protein levels than those with hyperechoic plaque (p = 0.008, p = 0.003, respectively). MnSOD protein level was significantly higher in hypoechoic plaque compared to hyperechoic (p = 0.039). MMP-9 protein expression in CP tissue was significantly affected by sex and plaque type interaction (p = 0.009). Considering the differences of MMP-9 mRNA and protein expression in CP tissue regarding different plaque phenotypes and the observed sex-specific effect, the role of MMP-9 in human atherosclerotic plaques should be further elucidated.

O250: Blood Pressure Homeostasis and Hyper-perfusion Syndrome Following Carotid Surgeries

Abstract Objectives We aim to compare blood pressure homeostasis in patients undergoing bilateral versus unilateral carotid surgeries. Our primary endpoints are the incidence of postoperative hypertension and hyperperfusion syndrome (HPS). Secondary endpoints are major adverse cardiovascular events and all-cause mortality. Methods All patients undergoing carotid endarterectomy (CEA) from 2003 to 2022 were reviewed. We performed 1230 carotid interventions, of which 690 procedures had ten years of follow-up. Results Both the unilateral (512) and bilateral (91) carotid interventions caused a significant acute elevation in blood pressure (p&amp;lt;0.001). In unilateral carotid interventions, the mean SBP was 137 ± 19.90 mmHg preoperatively and 152 ± 25.80 postoperatively (p&amp;lt;0.001). Smoking (p=0.007), hyperfibrinogenemia (p=0.004), emergency admission (p=0.005), ipsilateral carotid stenosis &amp;gt;90% (p=0.022), and previous ipsilateral carotid intervention (p=0.003) were significantly associated with the development of postoperative hypertension. No incidence of HPS occurred in the unilateral group. In bilateral carotid interventions, the mean SBP was 138 ± 20.50 mmHg preoperatively and 159 ± 24.60 mmHg postoperatively (p&amp;lt;0.001). Emergency admission (p=0.012) and plaque morphology (p=0.035) were significantly associated with postoperative hypertension. Three patients with bilateral carotid interventions had HPS (3.3%) and developed hemorrhagic stroke within 30 days. Multivariate analysis found postoperative stage II hypertension following bilateral carotid procedures to be an independent predictor of stroke (p=0.004). However, postoperative hypertension was not an independent predictor of myocardial infarction (p=0.475) and mortality (p=0.608). Conclusion Significant acute elevation in blood pressure occurred following carotid surgeries. We observed HPS post bilateral carotid interventions, with postoperative hypertension being an independent predictor of peri-operative stroke.