Plaque Hemorrhage Research Articles

Characterization of plaque hemorrhage with optical coherence tomography imaging in statin-treated patients with coronary artery disease: comparison with noncontrast T1-weighted MRI

Abstract Background Plaque hemorrhage is a phenotypic feature of coronary lesions associated with future coronary events. Noncontrast T1-weighted MRI has a potential to non-invasively identify plaque hemorrhage. Plaque to myocardium ratio (PMR) evaluated by noncontrast T1-weighted MRI has been shown to pathohistologically correspond to plaque hemorrhage. In several case reports comparing OCT images with coronary specimens, low intensity area without its attenuation was observed at lesions presenting plaque hemorrhage. However, whether the association of this OCT-derived feature with PMR remains to be elucidated yet. Purpose To characterize plaque hemorrhage in vivo by comparing with OCT and noncontrast T1-weighted MRI. Methods The current study prospectively enrolled 80 statin-treated patients with coronary artery disease requiring elective PCI. A total of 103 target lesions were imaged by both noncontrast T1-weighted MRI and OCT prior to PCI. Plaque hemorrhage on noncontrast T1-weighted MRI was defined as PMR>1.0. On OCT imaging analysis, low intensity area without attenuation (LIA) was defined according to the following criteria; (1) area presenting homogeneous low intensity signals, (2) clear border and (3) no signal attenuation behind its area. The maximum arc of LIA was manually measured. OCT-derived plaque features were compared in lesions with and without PMR>1.0. Results PMR>1.0 was observed at 49.5% of analyzed lesions. Patients with PMR>1.0 were more likely older (72 vs. 66 years, p=0.02), whereas there was no significant difference in on-treatment LDL-C levels (median: 80 vs. 77 mg/dL, p=0.62) (Table). On lesion-based analysis, while fibrous cap thickness was similar between the two groups (80 vs. 100um, p=0.10), a larger lipid arc (270 vs. 230º, p=0.02) and a greater frequency of macrophage (90.2 vs. 53.9%, p<0.01), layered plaque (62.8 vs. 32.7%, p=0.003) and cholesterol crystal (70.6 vs. 30.8%, p<0.001) were observed at lesions with PMR>1.0. Furthermore, lesions with PMR>1.0 more frequently exhibited LIA (66.7 vs. 19.2%, p<0.001) and its greater maximum arc (33 vs. 0º, p<0.001) (Figure). Of note, PMR was significantly correlated to the maximum arc of LIA (r=0.51, p<0.001) (Figure). Multivariate analysis demonstrated LIA and cholesterol crystal as independent OCT-derived features associated with PMR>1.0 (Table). Conclusion In statin-treated patients, 49.5% of analyzed lesions presented PMR>1.0. Coronary lesions with PMR>1.0 more frequently harbored LIA and cholesterol crystals, in addition to other vulnerable OCT features. Our findings suggest OCT-derived LIA as a potential signature of plaque hemorrhage. Given that cholesterol crystal was another feature of PMR>1.0, plaque inflammation driven by cholesterol crystallization may exist at plaque hemorrhage despite statin use. Whether anti-inflammation agent could modulate plaque hemorrhage requires future investigation.

Intraplaque hemorrhage in carotid atherosclerotic plaques is associated with a local increase in inflammatory cytokines

Abstract Background One of the main features of vulnerability in atherosclerotic carotid plaques is intraplaque hemorrhage (IPH), which is related to a higher incidence of cerebrovascular events in patients with carotid artery disease. Additionally, inflammation plays a pivotal role in the progression of atherosclerotic disease. Purpose We aimed to determine plasma and tissue levels of inflammatory cytokines in patients with carotid artery disease hypothesizing that plaques with IPH are characterized by the presence of a more inflamed environment. Methods We retrospectively enrolled 104 consecutive patients undergoing carotid endarterectomy (CEA) with symptomatic (ischemic stroke, TIA, amaurosis fugax) or asymptomatic ipsilateral carotid artery disease. Plasma and carotid plaque specimens were collected at CEA. The tissue samples were stained with H&E to identify IPH and classified as specimens with and without IPH. Frozen homogenates of both plasma and tissue were analyzed using a customized 10-plex Luminex assay to determine the levels of inflammatory cytokines such as MCP-1/CCL2, IL-8/CXCL8, IFN-gamma, IL-10, IL-1beta/IL-1F2, IL-6, PDGF-AA, PDGF-AB/BB, TNF-alpha, and VEGF. Results IPH was identified in 53 patients (51.0 %). Cytokine levels in plasma and tissue from patients with and without IPH are reported in Table 1. In the univariate logistic regression MCP-1/CCL2, IL-8/CXCL8, IFN-gamma, IL-10, IL6, PDGF-AA, and PDGF-AB/BB were associated with IPH (Table 2). In the multivariate logistic regression, IL-6 was an independent predictor of IPH (HR 1.026 [95% CI 1.005-1.047]; p=0.014) after adjusting for cardiovascular risk factors such as age, BMI, sex, hypertension, diabetes mellitus, hyperlipidemia, ipsilateral carotid stenosis %. Conclusions Carotid plaques with IPH have an elevated inflammatory burden, potentially impacting adverse outcomes in this patient cohort. The local inflammatory cytokines in carotid plaques with IPH might serve as biomarkers and therapeutic targets in patients with carotid artery disease.

Acute Vision Impairment Caused by Internal Carotid Artery Plaque Hemorrhage Combined With Thrombosis.

Atherosclerosis (As) is an important pathologic basis for ischemic cerebrovascular disease and easily causes stenosis of the origin of the internal carotid artery (ICA). As the main source of intracranial blood supply, the ICA accounts for 70% to 80% of blood flow. This stenosis can cause various ocular symptoms in patients. In the existing literature, it is rare to report cases with only acute vision loss caused by ICA plaque hemorrhage combined with thrombosis. The authors report a case of acute vision impairment caused by ICA plaque hemorrhage. The clinical manifestations, imaging characteristics, differential diagnosis, and treatment methods were discussed based on relevant literature, and the diagnosis and differentiation of the disease were considered to deepen the understanding of the disease.

Proteomic profiling reveals higher presence of glycolytic enzymes in vulnerable atherosclerotic lesions

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Leducq PlaqOmics Background Our definition of vulnerable plaques is predominantly driven by histological analysis. The molecular mechanisms behind the vulnerable histological characteristics are not fully understood. Here we use mass spectrometry-based proteomics data, to identify molecular mechanisms linked to vulnerable plaques. Methods Atherosclerotic lesions from two hundred patients undergoing endarterectomy surgery were collected (149 male and 51 female plaques). From a total of two hundred plaque samples, extracellular matrix proteins were extracted and processed for untargeted proteomics analysis. The resulting protein levels were linked to existing histological characteristics, transcriptomic, and clinical data. Results We detected 1499 proteins in atherosclerotic lesions, which were mostly affiliated with biological processes including extracellular matrix organization, coagulation, and peptidase activity. Linear regression identified 240 proteins associated with plaque vulnerability index (a semi-quantitative score summarizing the presence of SMC cells, macrophages, plaque hemorrhage, and fat in the plaque). Among the proteins associated with high plaque vulnerability index we identified an overrepresentation of enzymes involved in glycolysis – including the rate limiting enzymes HK3 (beta =0.40 p =0.003) and PKM (beta =0.19 p =0.009). This was driven by macrophage numbers and fat content in the plaque. Furthermore, data from a validation cohort of 120 patients from the Medical University of Vienna, Austria, revealed that HK3 and PKM were associated with plaque progression (p =<0.001, p =0.017) and clinical symptoms (p = <0.001, p = <0.001). Conclusion Enzymes involved in the glycolysis process show higher presence in vulnerable plaques. This suggests an important role for energy metabolism in plaque vulnerability.

Atherosclerotic Plaque Epigenetic Age Acceleration Predicts a Poor Prognosis and Is Associated With Endothelial-to-Mesenchymal Transition in Humans.

Epigenetic age estimators (clocks) are predictive of human mortality risk. However, it is not yet known whether the epigenetic age of atherosclerotic plaques is predictive for the risk of cardiovascular events. Whole-genome DNA methylation of human carotid atherosclerotic plaques (n=485) and of blood (n=93) from the Athero-Express endarterectomy cohort was used to calculate epigenetic age acceleration (EAA). EAA was linked to clinical characteristics, plaque histology, and future cardiovascular events (n=136). We studied whole-genome DNA methylation and bulk and single-cell transcriptomics to uncover molecular mechanisms of plaque EAA. We experimentally confirmed our in silico findings using in vitro experiments in primary human coronary endothelial cells. Male and female patients with severe atherosclerosis had a median chronological age of 69 years. The median epigenetic age was 65 years in females (median EAA, -2.2 [interquartile range, -4.3 to 2.2] years) and 68 years in males (median EAA, -0.3 [interquartile range, -2.9 to 3.8] years). Patients with diabetes and a high body mass index had higher plaque EAA. Increased EAA of plaque predicted future events in a 3-year follow-up in a Cox regression model (univariate hazard ratio, 1.7; P=0.0034) and adjusted multivariate model (hazard ratio, 1.56; P=0.02). Plaque EAA predicted outcome independent of blood EAA (hazard ratio, 1.3; P=0.018) and of plaque hemorrhage (hazard ratio, 1.7; P=0.02). Single-cell RNA sequencing in plaque samples from 46 patients in the same cohort revealed smooth muscle and endothelial cells as important cell types in plaque EAA. Endothelial-to-mesenchymal transition was associated with EAA, which was experimentally confirmed by TGFβ-triggered endothelial-to-mesenchymal transition inducing rapid epigenetic aging in coronary endothelial cells. Plaque EAA is a strong and independent marker of poor outcome in patients with severe atherosclerosis. Plaque EAA was linked to mesenchymal endothelial and smooth muscle cells. Endothelial-to-mesenchymal transition was associated with EAA, which was experimentally validated. Epigenetic aging mechanisms may provide new targets for treatments that reduce atherosclerosis complications.

Emerging Trends in Atherosclerosis: Time to Address Atherosclerosis From a Younger Age.

Over the past two decades, research efforts into cardiovascular disease (CVD) have uncovered findings that fundamentally challenge our understanding of CVD, particularly atherosclerosis. Atherosclerosis was primarily attributed to the well-described abnormal lipid accumulation theory, involving plaque growth with subsequent plaque hemorrhage resulting in acute vessel thrombosis that may or may not rupture. This perspective has now evolved to encompass more complex pathways, wherein the accumulation of abnormal products of oxidation and inflammation is the most likely factor mediating atherosclerotic plaque growth. Furthermore, atherosclerosis was traditionally thought of as a disease in patients aged 40 and older. However, mounting evidence has demonstrated that significant atherosclerosis and CVD events are more prevalent in younger patients than previously realized and accelerating in incidence. With this alarming trend among younger individuals, our review sought to explore why this trend may be happening and what can be done about this developing problem.

Circulating Sex-Specific Markers of Plaque Instability in Women and Men With Severe Carotid Atherosclerosis.

Sex-specific differences in plaque composition and instability underscore the need to explore circulating markers for better prediction of high-risk plaques. This cross-sectional study aims to (1) investigate differences in lipid, immune, and adipokine circulating profiles between men and women with stable versus unstable plaques and (2) identify circulating markers that can better classify men and women according to plaque instability. Preoperative blood samples and plaque specimens were collected from consecutive men and women with carotid artery stenosis ≥50% and who underwent a carotid endarterectomy between 2009 and 2018. Adipokine, lipid, and immune profiling was conducted. Plaque stability was determined by gold-standard histological classifications. Statistical analyses, including χ2, ANOVA, Kruskal-Wallis, and logistic regression, assessed differences in plaque features and blood parameters between men and women with stable and unstable plaques. Of 470 recruited patients (aged 70.8±9.2 years), the final study analyses included 317 men and 143 women (aged 71.0±9.0 years). Men exhibited more unstable plaques (P<0.001), characterized by increased plaque hemorrhage, larger lipid core, and inflammation (P<0.001), along with less favorable circulating profiles. Antagonistic interactions between sex and white blood cell (WBC) counts, basophil-to-WBC ratio, and platelet counts influenced plaque instability. In men, low WBC counts, high monocyte-to-WBC ratio, low basophil-to-WBC ratio, and high LDL-C (low-density lipoprotein cholesterol) levels were associated with greater plaque instability (odds ratio, 0.827 [95% CI, 0.713-0.926], 1.158 [95% CI, 1.027-1.305], 0.495 [95% CI, 0.281-0.871], and 1.564 [95% CI, 1.001-2.443], respectively) and more unstable features (ie, inflammation, foam cells, and neovascularization). In women, a high basophil-to-WBC ratio was associated with greater plaque instability (3.142 [95% CI, 1.220-8.093]), hemorrhage, and thrombosis, while a high molecular weight-to-total adiponectin ratio was associated with decreased instability (0.014 [95% CI, 0.000-0.646]) and inflammation. Our findings demonstrated sex-specific differences, with women displaying more stable plaque phenotypes and favorable circulating profiles compared with men. This proof-of-concept study was also designed as the key first step in exploring novel sex-specific associations between circulating lipid, immune, and adipokine profiles and carotid plaque instability.

Intraplaque Neovascularization, CD68+ and iNOS2+ Macrophage Infiltrate Intensity Are Associated with Atherothrombosis and Intraplaque Hemorrhage in Severe Carotid Atherosclerosis.

Atherosclerosis is a progressive disease that results from endothelial dysfunction, inflammatory arterial wall disorder and the formation of the atheromatous plaque. This results in carotid artery stenosis and is responsible for atherothrombotic stroke and ischemic injury. Low-grade plaque inflammation determines biological stability and lesion progression. Sixty-seven cases with active perilesional inflammatory cell infiltrate were selected from a larger cohort of patients undergoing carotid endarterectomy. CD68+, iNOS2+ and Arg1+ macrophages and CD31+ endothelial cells were quantified around the atheroma lipid core using digital morphometry, and expression levels were correlated with determinants of instability: ulceration, thrombosis, plaque hemorrhage, calcification patterns and neovessel formation. Patients with intraplaque hemorrhage had greater CD68+ macrophage infiltration (p = 0.003). In 12 cases where iNOS2 predominated over Arg1 positivity, the occurrence of atherothrombotic events was significantly more frequent (p = 0.046). CD31 expression, representing neovessel formation, correlated positively with atherothrombosis (p = 0.020). Intraplaque hemorrhage is often described against the background of an intense inflammatory cell infiltrate. Atherothrombosis is associated with the presence of neovessels and pro-inflammatory macrophages expressing iNOS2. Modulating macrophage polarization may be a successful therapeutic approach to prevent plaque destabilization.

Diagnostic accuracy of non-invasive imaging methods in detection of intraplaque hemorrhage in carotid atherosclerotic plaques: A systematic review and meta-analysis

Diagnostic accuracy of non-invasive imaging methods in detection of intraplaque hemorrhage in carotid atherosclerotic plaques: A systematic review and meta-analysis

Abstract 17231: Importance of Intra Plaque Hemorrhage During Carotid Artery Revascularization

Introduction: The American Heart Association currently estimates that every 3 minutes a person dies from a stroke. Carotid artery stenosis, a major risk factor for new and recurrent strokes, can be treated with carotid artery revascularization. Vascular emboli released during this procedure are non-invasively detected by transcranial doppler (TCD) ultrasound as micro embolic signals (MES). In this study we aim to show the relationship between carotid plaque characteristics and MES rates that were detected by TCD-monitoring throughout the stages of the carotid artery revascularization procedures. Methods: Before elective carotid revascularization 30 patients (mean age 72±8 years; 16 males, 14 females) underwent 3-T MRI. After localization of the carotid bifurcation using phase contrast imaging, Time-of-Flight, 3D T1 weighting, transverse T1 and T2 weightings and proton density sequences were acquired. The different plaque components: lipid core, intraplaque hemorrhage, calcification and the characterization of the fibrous cap were assessed. While 20 patients underwent carotid endarterectomy (CEA), 10 patients had carotid artery stenting (CAS). CES was divided into 9 stages: 1- Pre-procedure, 2- Dissection, 3- IC clamp, 4- Shunt placement, 5- Shunt open, 6- Endarterectomy, 7- Clamped, 8- IC opened, 9- Post-procedure. Similarly, CAS was divided into 9 stages: 1- Pre-procedure, 2- Arch-carotid angiography, 3- Wire insertion, 4- Filter deployment, 5- Pre-dilation, 6- Stent deployment, 7- Post-dilation, 8- Final angiography, 9- Post-procedure. Patients were monitored continuously with TCD to detect pre-procedural, intra-procedural and post-procedural MES rates. Results: Intraplaque hemorrhage was observed in 18 patients (60%). Patients with intra plaque hemorrhage had more MES during carotid artery dissection/arch-carotid angiography (p=0.028) and IC clamping/wire insertion (p=0.009) compared to patients without intra plaque hemorrhage in the pre-procedural stage. Conclusions: Carotid plaques with intra plaque hemorrhage is associated with higher MES during carotid artery revascularization procedures.

Intralesional interleukin 6 is associated with intraplaque hemorrhage in carotid atherosclerotic plaques

Intralesional interleukin 6 is associated with intraplaque hemorrhage in carotid atherosclerotic plaques

Predictors of Inappropriately Rapid Coronary Lesion Progression in Patients Undergoing Percutaneous Coronary Interventions

BackgroundPatients undergoing percutaneous coronary intervention (PCI) may experience rapid atherosclerotic plaque progression in nontreated vessels that is unlikely to result from natural de novo atherosclerosis. We hypothesize that intra-lesion bleeding plays a central role in this process. The aim of this study is to investigate the factors that may contribute to accelerated narrowing in coronary diameter. MethodsWe reviewed 65 interventional procedures and their consequent staged PCIs and mapped the coronary tree into 16 segments (as divided by the American Heart Association), grading the percentage of stenosis in each segment and spotting the rapidly progressing lesions. Demographic, procedural, and laboratory data were recorded and analyzed. ResultsFor the lesions that progressed rapidly in the time period between angiographies, the administration of eptifibatide intra-procedurally was associated with rapid progression of coronary lesions. Moreover, an increased white blood cell count prior to the index procedure was also associated with a trend toward rapid plaque progression. ConclusionsIn this hypothesis-generating study, treatment with a IIb/IIIa inhibitor in the index PCI was associated with an accelerated short-term progression of some of the nontreated lesions, suggesting that this mode of anti-aggregation therapy could facilitate plaque hemorrhage and consequent acceleration of coronary atherosclerosis in eroded plaques.

X chromosome inactivation skewing is common in advanced carotid atherosclerotic lesions in females and predicts secondary peripheral artery events

Background and aimSex differences in atherosclerosis have been described with female plaques being mostly perceived as stable and fibrous. Sex-specific mechanisms such as mosaic loss of the Y chromosome in men have been linked to cardiovascular health. In women, X-linked mechanisms such as X chromosome inactivation (XCI) skewing is common in several tissues. Yet, information on the role of XCI in female atherosclerotic plaques is lacking. Here, we investigated the presence of XCI skewing in advanced atherosclerotic lesions and its association with cardiovascular risk factors, histological plaque data, and clinical data.MethodsXCI skewing was quantified in 154 atherosclerotic plaque and 55 blood DNA samples of women included in the Athero-Express study. The skewing status was determined performing the HUMARA assay. Then, we studied the relationship of XCI skewing in female plaque and cardiovascular risk factors using regression models. In addition, we studied if plaque XCI predicted plaque composition, and adverse events during 3-years follow-up using Cox proportional hazard models.ResultsXCI skewing was detected in 76 of 154 (49.4%) plaques and in 27 of 55 (67%) blood samples. None of the clinical risk factors were associated with plaque skewing. Plaque skewing was more often detected in plaques with a plaque hemorrhage (OR [95% CI]: 1.44 [1.06–1.98], P = 0.02). Moreover, skewed plaques were not associated with a higher incidence of composite and major events but were specifically associated with peripheral artery events during a 3-year follow-up period in a multivariate model (HR [95%CI]: 1.46 [1.09–1.97]; P = 0.007).ConclusionsXCI skewing is common in carotid plaques of females and is predictive for the occurrence of peripheral artery events within 3 years after carotid endarterectomy.

Relationship between carotid atherosclerotic plaque characteristics in magnetic resonance imaging and perioperative hemodynamic instability

Objective: To analyze the relationship between carotid atherosclerotic plaque characteristics in magnetic resonance imaging (MRI) and perioperative hemodynamic instability in patients with severe carotid artery stenosis undergoing carotid artery stenting (CAS). Methods: A total of 89 patients with carotid artery stenosis who underwent CAS treatment at Beijing Tsinghua Changgung Hospital affiliated to Tsinghua University from January 1, 2017, to December 31, 2021, were prospectively included. Among them, 74 were male and 15 were female, with an age range of 43 to 87 years (mean age: 67.8±8.2 years). Preoperative examinations included carotid artery MRI vessel wall imaging to analyze the existence of large lipid-rich necrotic core (LRNC), intraplaque hemorrhage (IPH), and fibrous cap rupture in carotid artery plaques. Plaques without the above-mentioned risk factors were defined as stable plaque group (34 cases), while those with such risk factors were defined as vulnerable plaque group (55 cases). The number of risk factors present in each plaque was also calculated. Intraoperative changes in blood pressure and heart rate were recorded, and the use of dopamine postoperatively was noted. Using the risk factors that the plaque has as independent variables and the clinical outcomes as dependent variables, the RR values were calculated, and the differences in clinical outcomes of patients with different risk factors were compared. Results: The incidence rates of hypotension and bradycardia were higher in patients with vulnerable plaques than those with stable plaques (60.0% (33/55) vs 14.7%(5/34) and 38.2%(21/55) vs 14.7%(5/34), respectively; both P<0.05). Based on MRI imaging features, the large LRNC was present in 45 cases, with RR values for hypotension and bradycardia of 3.15 (1.69-5.87) and 2.20 (1.07-4.53), respectively; IPH was present in 37 cases, with RR values for hypotension and bradycardia of 2.70 (1.61-4.55) and 2.25 (1.15-4.39), respectively; and fibrous cap rupture was present in 29 cases, with RR values for hypotension and bradycardia of 1.50 (0.94-2.40) and 1.29 (0.67-2.49), respectively. The higher the number of risk factors in vulnerable plaques, the higher the incidence of intraoperative blood pressure and heart rate decrease: when the number of risk factors ranged from 0 to 3, the incidence of blood pressure decrease was 14.7% (5/34), 9/18, 11/18, and 13/19, respectively (P<0.001), and the incidence of heart rate decrease was 14.7% (5/34), 6/18, 7/18, and 8/19, respectively (P=0.022). There was no significant difference in the number of cases of dopamine use between the two groups (P>0.05). Conclusion: Patients with a higher number of risk factors for vulnerable carotid plaques, as indicated by carotid artery MRI vessel wall imaging, are at a higher risk of experiencing blood pressure and heart rate decrease during CAS surgery.

Clinical results of the Physical Activity and Carotid Atherosclerotic Plaque hemorrhage (PACAPh) study

Intraplaque hemorrhage (IPH) and intercurrent inflammatory processes cause carotid plaque instability. IPH is the instability factor that better predicts plaque rupture. In two previous cross-sectional prospective study, our team demonstrated that patients practicing moderate physical activity (PA) had lower rates of IPH and pro-inflammatory monocytes. We hypothesized that an individualized home-based PA intervention can reduce IPH and modulate inflammation, as well as monocyte phenotype in asymptomatic patients with a non-endarterectomized carotid atherosclerotic plaque. Fifty-seven patients had been included at Louis Pradel hospital in Lyon. Patients should have been asymptomatic of ischemic events for more than 6 months and present a carotid stenosis > 50%. At inclusion and after 6 months, IPH was measured with a high-resolution MRI, a blood sample was used to quantify the inflammation state and determine the circulation monocytes phenotype, moreover, PA was quantified with a 6 minutes walking test, a test of isometric contraction of the quadriceps and finally, sedentary behavior and PA levels were assessed by questionnaire. Patients were randomly allocated to the control or to the PA intervention group. In the PA group, patients should reach daily goals of steps, measured by a connected watch. Dailly steps goal was reevaluated twice a month, in order to encourage patients to increase their walking habits. Patients in the control group receive their usual care during the protocol. Fifty-two patients finished the study, 26 where randomized in each group. At inclusion, blood test, frequency of comorbidities, associated treatments and risk factors were equivalents between groups. The intervention in PA did improve the physical activity capacity. Indeed, the distance walked during the 6 minutes’ walk test was significantly improved in the PA group. On the clinical side, the PA intervention did allow a 43% reduction in the IPH rates, measured by MRI. IPH is a well-known risk factor of plaque rupture. Thus, MRI is a reliable tool to follow the evolution of IPH and is sensible enough to measure IHP variations du to PA. Moreover, the PA intervention did stabilize the rates of classical pro-inflammatory monocytes, while it increased in the control group, according to the evolution of atherosclerosis.

Recanalized paramedian thalamoperforators after intraarterial tirofiban treatment in a patient with bilateral fetal-type PCAs (P8-5.028)

<h3>Objective:</h3> NA <h3>Background:</h3> There are increasing evidence that support the treatment effect of intraarterial tirofiban during endovascular thrombectomy in acute ischemic stroke. Here, we report a patient with bilateral fetal-type PCAs, whose paramedian perforating thalamic-mesencephalic arteries were recanalized after intraarterial tirofiban treatment during thrombectomy. <h3>Design/Methods:</h3> NA <h3>Results:</h3> A 78-year-old woman presented to the emergency room with acute onset of drowsy mentality, gaze palsy and quadriplegia (NIHSS 9). She had a history of hypertension and diabetes. Brain CT scan revealed no definite early ischemic damage and CTA showed steno-occlusion at the left distal VA and bilateral fetal type PCAs. Brain perfusion CT showed perfusion delay in posterior circulation territory. Under local anesthesia, an 6F Envoy^® catheter (Codman) was placed in the left distal VA of distal V2 segment. The angiography revealed the distal VA occlusion (V4 segment) (Fig. 1A). Suction thrombectomy was performed twice using 5F Sofia^® catheter (Microvention), and no clot was extracted (Fig. 1B). Recanalization of left distal VA with underlying severe ICAS at the occlusion site (Fig. 1C). Delayed angiogram showed subtle re-occlusion tendency of left distal VA, 0.5mg of intraarterial tirofiban was injected. Successful recanalization (mTICI 2C) with further recanalized paramedian perforating thalamic-mesencephalic arteries on distal BA after SCA branches was achieved (Fig. 1D). Follow-up brain MRI showed acute infarction at the posterior circulation territory including bilateral thalami. MRA showed patent left distal VA with underlying severe ICAS, and vessel wall MRI showed eccentric wall thickening without contrast enhancement or plaque hemorrhage. The patient recovered well at 1 week (NIHSS 0). <h3>Conclusions:</h3> In a patient with bilateral fetal type PCAs, distal BA could end after SCA branches and this site should be evaluated cautiously, because thalamoperforators could originate. Intraarterial tirofiban could be helpful to recanalize perforating arteries during thrombectomy. <b>Disclosure:</b> Dr. Baik has nothing to disclose.

Sudden cardiac death in ischaemic heart disease: coronary thrombosis or myocardial fibrosis?

The mechanisms underlying sudden cardiac death (SCD) in patients with ischaemic heart disease (IHD) caused by coronary atherosclerosis are not yet clarified. For decades, acute coronary causes have been sought as the main triggers of SCD in these patients. In fact, angiographic and pathological studies in cardiac arrest survivors and SCD victims, respectively, consistently show that acute plaque events occur in ∼50% of SCD of patients with IHD. Among the acute events, plaque rupture and erosion triggering acute coronary thrombosis remain the main substrates; however, a significant percentage of plaque haemorrhage (20%) is identified by pathological studies. Its role in acute coronary thrombosis is unknown and deserves future intravascular imaging developments. In the remaining 50% of SCD, the atherosclerotic coronary disease shows the characteristics of structural stability. More recent studies have focused attention not only on the coronary tree and on the search for acute complications of atherosclerotic plaques but also on myocardial tissue, identifying replacement and patchy fibrosis as the most frequent findings in the post-mortem hearts of these patients, a feature followed by cardiac hypertrophy, as assessed by the heart weight, usually associated with fibrosis. The possibility of characterizing myocardial fibrosis in vivo, besides confirming the pathological data, now offers new risk stratification perspectives to prevent SCD in IHD, alongside the consolidated secondary prevention criteria based on left ventricular dysfunction.

A Clinical Study of 50 Partially Edentulous Patients with Fixed Partial Denture Restorations to Compare Clinical Parameters and Changes in Gingival Sulcus Width After Displacement with 2 Different Gingival Retraction Cord Materials (Cotton and Polymer).

BACKGROUND The present study aimed to compare the clinical performance and gingival sulcus width changes in partially edentulous patients using cotton and polymer gingival retraction cords. MATERIAL AND METHODS Fifty partially edentulous patients were divided into 2 groups (Gp C and Gp P) and were subjected to single crown/fixed partial denture treatment. Clinical parameters, including plaque index scores, placement time, and hemorrhage control scores, were assessed. Gingival sulcus width changes before and after retraction were evaluated using individual type 4 dental stone dies observed under an optical microscope. Statistical analysis was performed using dependent/independent t tests. RESULTS The mean placement time, hemorrhage control time, and hemorrhagic scores were lower in Gp P than in Gp C, indicating better clinical performance of polymer-based retraction cord. Both groups showed an increase in sulcus width after retraction, but Gp P had a significantly higher sulcus width (690.03±45.37) compared to Gp C (471.38±28.13). The mean difference in sulcus width between baseline and after retraction was also significantly higher in Gp P (525.84 micrometers) than in Gp C (309.11 micrometers). CONCLUSIONS The present study shows that polymer-based cords produce more sulcus width and have better clinical performance compared to cotton-based gingival retraction cords. These results suggest that the use of polymer-based retraction cords can improve the quality of dental impressions in partially edentulous patients.

Erythropoietin promoted intraplaque angiogenesis by PI3K/AKT/mTOR signaling pathway in atherosclerosis

BackgroundThis study aimed to investigate role of erythropoietin in atherosclerosis and explore whether underlying mechanism is associated with PI3K/AKT/mTOR pathway. MethodsHigh-fat-diet-induced atherosclerosis model was established in apolipoprotein E knockout mice (C57BL/6 genetic background). Mice were randomly divided into the control group and the EPO group. Hematoxylin-eosin was performed for the determination of atherosclerotic lesions. The expression levels of related proteins were detected by western blot analysis. ResultsErythropoietin significantly enhanced the incidence of hemorrhage in atherosclerotic plaques compared with the control group. The proteins’ expression signaling pathways (including PI3K, AKT, and mTOR) and angiogenesis-related proteins (VEGF, COX-2, and HIF-1α) were proved to be up-regulated by erythropoietin. Additionally, erythropoietin significantly enhanced the incidence of hemorrhage in the atherosclerotic plaques compared with the control group. The vitro experiments were conducted in macrophages at 21% O2 or 1% O2. The data showed that expression of p-PI3K, p-AKT, p-mTOR, VEGF, COX-2, and HIF-1α related proteins increased in 1% O2 group than 21% O2 group. Moreover, compared with control group, protein expression including p-PI3K, p-AKT, p-mTOR, VEGF, COX-2, and HIF-1α was markedly increased in EPO group, decreased in inhibitors group, and similar results were observed in EPO+ inhibitors group. ConclusionThe present study demonstrated that erythropoietin might promote angiogenesis in atherosclerotic vulnerable by activating PI3K/AKT/mTOR signaling pathway in atherosclerotic, providing a novel therapeutic target for atherosclerotic targeted therapy.

392 A Morphological Study of Non-Stenotic Carotid Atheromas Causing Recurrent Strokes: Chronicle of Disruption and Stabilization

INTRODUCTION: Symptomatic non-stenotic carotid (SyNC) artery disease is a recognized etiology of ischemic strokes with a putative thromboembolic mechanism. To date, the structural phenotypes expressed at the lumen/wall interface of these lesions are not completely understood resulting in misdiagnosis and hindering the development of targeted therapies. METHODS: After IRB approval, en block endarterectomy specimen were obtained from patients with recurrent strokes from SyNC (n=9). Additionally, segments of superficial temporal artery (STA) of patients undergoing cerebral artery bypass surgeries were obtained as controls (n=3). The endovascular surfaces of the samples were imaged with laser microangioscopy and scanning electron microscopy (SEM). Images were benchmarked with histological sections and immunohistochemistry (IHC). RESULTS: Normal endothelial surfaces in STA were light pink, smooth and homogenous by angioscopy with typical cobblestone endothelial pattern. Features recognized as those associated with plaque disruption and thrombosis were de-endothelialization, inflammatory infiltrates within and under the endothelium, delamination (flaps oriented to the flow) with superficial intimal hemorrhages, plaque erosion and disruption of the fibrous cap with fissuring, ulceration, excavation and plaque hemorrhage. Additionally, cellular and acellular structures actively involved in plaque stabilization, seen on SEM and confirmed with histology and IHC, were also identified including activated platelets, fibrin band, bridges and webs, neutrophil extracellular traps and endothelial progenitor cells. CONCLUSIONS: This ultrastructural study of the vascular surface of SyNC specimens reveals concurrent phenotypes of flow-dependent disruption and stabilization that could become new imaging biomarkers and enable the development of targeted therapies.