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Carotid atherosclerotic plaque composition influences plaque rupture risk and may be used to better stratify patients based on ischemic stroke risk than degree of luminal stenosis alone. The goal of this review is to critically evaluate the ability of both conventional and advanced noninvasive vascular imaging techniques to identify and characterize vulnerable carotid plaques. Advanced noninvasive vascular imaging techniques include contrast-enhanced vascular ultrasound, dual-energy CT, and MR vessel wall imaging (VWI). Each of these modalities has unique strengths with the ability to evaluate the degree of luminal stenosis and provide insight into carotid atherosclerotic plaque composition. MR VWI has proven superior to other imaging modalities in terms of its ability to accurately characterize and quantify components of carotid plaque including intraplaque hemorrhage, lipid-rich necrotic core, dystrophic calcification, and the integrity of the plaque fibrous cap. Advanced noninvasive vascular imaging techniques such as MR VWI offer important insights into carotid atherosclerotic plaque composition and have the potential to dramatically improve the quality of care delivered to patients with carotid atherosclerosis.

Inflammation has a central role in atherosclerotic plaque formation and rupture. Intense macrophage inflammatory activity results in microcalcifications which are strongly associated with plaque vulnerability. Microcalcifications with specific critical size between 5 and 65 μ, located in the fibrous cap producing local mechanical stress on the plaque surface and may directly contribute to plaque rupture. Hence, accurate assessment of microcalcifications size and dimension has significant clinical importance. Current invasive and noninvasive plaque imaging has limited spatial resolution which limits accurate definition of microcalcifications in the atherosclerotic plaques. We describe a new imaging technique with high spatial resolution, based on confocal microscopic analysis, using a dedicated software which allows automatic characterization of microcalcifications and quantitative assessment of their extent and localization.

BackgroundPlaque rupture (PR) and plaque erosion (PE) are main causes of acute myocardial infarction with different demographic and histology characteristics and need different treatment strategy. PR and PE can be identified with optical coherence tomography (OCT) accurately, but convenient and effective noninvasive markers for them are rarely found. History of diabetes mellitus (DM) was reported to be a potential predictor of PR in ST-segment elevated myocardial infarction (STEMI) patients, but the predictive value of other glucose-related variables for it is still uncertain. Present study aimed to clear the relationship between some glucose-related variables and plaque morphology in patients with STEMI.MethodsWe consecutively enrolled 872 STEMI patients and divided them into PR group (n = 616) and PE group (n = 256) based on OCT diagnostic criteria. The relationship of glucose-related variables, including random plasma glucose on admission (ARPG), glycosylated hemoglobin (HbA1c), post-PCI fasting plasma glucose (PFPG), DM history, glucose variable tendency (GVT) and the acute-to-chronic glycemic ratio (A/C), to the PR risk of STEMI patients was analyzed. The correlation between the glucose-related variables and plaque morphology was analyzed meanwhile.ResultsAmong the glucose-related variables, ARPG and GVT were confirmed to be independent predictors for PR after adjusting for other traditional risk factors in nondiabetic patients. The higher the ARPG level, the more PR risk the STEMI patients had. And high HbA1c and APPG were demonstrated to have a weak and positive correlation with lipid constituents and stenosis degree of culprit vessel.ConclusionsCompared to HbA1c, DM history, and some other glucose-related variables, ARPG and GVT were risk factors for PR in STEMI patients, especially those without DM. And high HbA1c and ARPG were positively correlated with the development of vulnerable plaque in culprit vessels.Trial registrationPresent study is a retrospective one and the population came from the EROSION study of our center previously. It was approved by the Ethics Committee of the Second Affiliated Hospital of Harbin Medical University (Approval reference number, KY2017-249), and all patients provided written informed consent prior to the inclusion in the study and the investigation conformed to the principles outlined in the Declaration of Helsinki.

Background Seasonal variations in acute coronary syndromes ( ACS ) have been reported, with incidence and mortality peaking in the winter. However, the underlying pathophysiology for these variations remain speculative. Methods and Results Patients with ACS who underwent optical coherence tomography were recruited from 6 countries. The prevalence of the 3 most common pathologies (plaque rupture, plaque erosion, and calcified plaque) were compared between the 4 seasons. In 1113 patients with ACS (885 male; mean age, 65.8±11.6 years), the rates of plaque rupture, plaque erosion, and calcified plaque were 50%, 39%, and 11% in spring; 44%, 43%, and 13% in summer; 49%, 39%, and 12% in autumn; and 57%, 30%, and 13% in winter ( P =0.039). After adjusting for age, sex, and other coronary risk factors, winter was significantly associated with increased risk of plaque rupture (odds ratio [OR], 1.652; 95% CI, 1.157–2.359; P =0.006) and decreased risk of plaque erosion (OR, 0.623; 95% CI, 0.429–0.905; P =0.013), compared with summer as a reference. Among patients with rupture, the prevalence of hypertension was significantly higher in winter ( P =0.010), whereas no significant difference was observed in the other 2 groups. Conclusions Seasonal variations in the incidence of ACS reflect differences in the underlying pathobiology. The proportion of plaque rupture is highest in winter, whereas that of plaque erosion is highest in summer. A different approach may be needed for the prevention and treatment of ACS depending on the season of its occurrence. Registration URL : https://www.clini​caltr​ials.gov . Unique identifier: NCT 03479723.

OBJECTIVES To investigate the non-culprit plaques (NCPs) characteristics in acute coronary syndrome (ACS) patients with calcified plaques (CP). BACKGROUND Recently, a new in vivo classification of calcified culprit plaques in patients with ACS was proposed. Characteristics of NCPs in this group of patients are unknown. METHODS A total of 692 NCPs from 492 ACS patients were retrospectively compared based on the culprit plaque phenotype: 71 from CP patients, 383 from plaque rupture (PR) patients, 238 from plaque erosion (PE) patients. RESULTS NCPs of CP patients had greater maximal calcium thickness, wider calcium arc, longer calcium length, and greater calcium index, compared to PR or PE patients (CP vs. PR: all p

The impact of residual cholesterol risk (RCR) on plaque characteristics is not fully understood. The study aims to explore the relationship between RCR and plaque features in patients presenting with acute coronary syndrome (ACS).All ACS patients undergoing pre-intervention optical coherence tomography (OCT) with high-sensitivity C-reactive protein (hs-CRP)2 mg/L on admission were retrospectively enrolled from January to December 2017, at Beijing Anzhen Hospital, Capital Medical University. RCR was defined as low density lipoprotein cholesterol (LDL-C) ≥1.8 mmol/L. Patients were divided into the RCR and non-RCR groups according to baseline LDL-C.A total of 90 patients (94 vessels) were included, with 50 in the RCR group and 40 in the non-RCR group, respectively. Compared with the non-RCR group, patients in the RCR group were younger (54.0 ± 11.04 vs. 58.4 ± 9.59, p = 0.049) and had a higher incidence of multivessel disease (6.0% vs. 2.5%, p = 0.028). With regard to plaque characteristics, fibrous plaque (0.0% vs 12.5%, p = 0.003) was less and fibroatheroma (79.6% vs. 50.0%, p = 0.028) was more frequently seen in the RCR group. Patients in the RCR group were more prone to present with plaque rupture (24.1% vs 5.0%, p = 0.008). Cholesterol crystal (22.2% vs 12.5%, p = 0.226) and thin-cap fibroatheroma (25.9% vs. 12.5%, p = 0.109) were more common in the RCR group, though without statistical difference. Multivariate logistic regression showed that RCR (odds ratio [OR]: 7.95, p = 0.011) and smoking (OR: 4.08, p = 0.026) were independent risk factors of plaque rupture in our patients.ACS patients with RCR are more likely to have atherosclerotic plaque and plaque rupture, indicating a more vulnerable plaque phenotype.

Background: Plaque rupture is an important etiology for symptomatic carotid stenosis. The role of calcification in the plaque vulnerability has been controversial. We aimed to detect the geometric features of calcifications in carotid plaque and to examine its association with plaque rupture.Methods: Optical coherence tomography assessment of carotid plaque was performed in 88 patients. Calcification shape was evaluated through quantitative measurements of the long and short axis, area size, circumference, calcification arc, and longitudinal length. Calcification location was analyzed through the distance to the lumen. Furthermore, we developed idealized fluid-structure interaction models to investigate the association of calcification shape and plaque stress.Results: A total of 33 ruptured plaques and 30 non-ruptured plaques were recognized. Ruptured plaques had more multiple calcifications and protruded calcifications. The calcifications in the ruptured plaques displayed a remarkably lower long-axis/short-axis (L/S) ratio than in the non-ruptured plaques (p = 0.001). We classified calcification shape into crescentic calcification (L/S > 2.5) and rotund calcification (L/S ≤ 2.5). Rotund-shaped calcifications were more common in ruptured plaques than in non-ruptured plaques (p = 0.02). Superficial calcifications with minimal distance to the lumen ≤ 50 μm accounted for 79.4% of all calcifications in the ruptured plaques, and only 7.7% in the non-ruptured plaques (p < 0.001). Biomechanical analysis showed that the plaque with rotund-shaped calcification developed 7.91-fold higher von Mises stress than the plaque with crescentic calcification.Conclusions: Superficial calcifications and rotund-shaped calcifications are associated with carotid plaque rupture, suggesting that calcification location and shape may play a key role in plaque vulnerability.

COVID‐19 causes significant hypoxia along with an exacerbated inflammatory milieu, which may be a trigger for atherosclerotic plaque rupture and/or thromboembolic events. Herein, we presented a case of COVID‐19 presented with acute coronary syndrome followed by pulmonary thromboembolism and cerebrovascular accident.

Myocardial infarction (MI) can be secondary to atherosclerotic coronary artery disease (ACAD) and non-atherosclerotic coronary artery disease (NACAD). The common cause of NACAD in young females is spontaneous coronary artery dissection (SCAD). We present a case of SCAD and plaque rupture leading to MI.

BackgroundPostprandial hyperglycemia was reported to play a key role in established risk factors of coronary artery diseases (CAD) and cardiovascular events. Serum 1,5-anhydroglucitol (1,5-AG) levels are known to be a clinical marker of short-term postprandial glucose (PPG) excursions. Low serum 1,5-AG levels have been associated with occurrence of CAD. However, the relationship between 1,5-AG levels and coronary plaque rupture has not been fully elucidated. The aim of this study was to evaluate 1,5-AG as a predictor of coronary plaque rupture in diabetic patients with acute coronary syndrome (ACS).MethodsA total of 144 diabetic patients with ACS were included in this study. All patients underwent intravascular ultrasound examination, which revealed 49 patients with plaque rupture and 95 patients without plaque rupture in the culprit lesion. Fasting blood glucose (FBG), hemoglobin A1c(HbA1c) and 1,5-AG levels were measured before coronary angiography. Fasting urinary 8-iso-prostaglandin F2α(8-iso-PGF2α) level was measured and corrected by creatinine clearance.ResultsPatients with ruptured plaque had significantly lower serum 1,5-AG levels, longer duration of diabetes, higher HbA1cand FBG levels than patients without ruptured plaque in our study population. In multivariate analysis, low 1,5-AG levels were an independent predictor of plaque rupture (odds ratio 3.421; P = 0.005) in diabetic patients with ACS. The area under the receiver-operating characteristic curve for 1,5-AG (0.658, P = 0.002) to predict plaque rupture was superior to that for HbA1c(0.587, P = 0.087). Levels of 1,5-AG were significantly correlated with urinary 8-iso-prostaglandin F2αlevels (r = − 0.234, P = 0.005).ConclusionsSerum 1,5-AG may identify high risk for coronary plaque rupture in diabetic patients with ACS, which suggests PPG excursions are related to the pathogenesis of plaque rupture in diabetes.

Free floating thrombus is uncommon in the carotid arteries, and it is defined as an elongated thrombus attached to the arterial wall with circumferential blood flow at its distal most aspect. The majority of patients present with acute neurological deficits and usually have an underlying unstable atherosclerotic plaque. We present two cases of carotid stenosis associated with free floating thrombus. Both patients shared similar clinical presentation and were managed according to the standard workflow for suspected ischemic strokes from our institution. Conservative management was decided based on a multidisciplinary decision that intervention of any kind would be associated with high risk of periprocedural complications. Complete resolution of the atherosclerotic plaque and free floating thrombus in a short period occurred. We further discuss the mechanism behind such a dramatic radiographic and clinical improvement with medical therapy, hypothesizing that plaque erosion is a plausible explanation, based on pathology studies.

Background Macrophages play a key role in coronary plaque destabilization. In-vitro human monocyte-derived macrophages (MDMs) are used to study macrophages infiltrating tissue. Optical coherence tomography (OCT) provides an in-vivo insight of the coronary arteries. We compared the MDMs morpho-phenotype and culprit plaque features at OCT in acute coronary syndrome (ACS) patients according to the underlying plaque pathobiology. Methods Sixty-six patients undergoing coronary angiography and pre-angioplasty OCT of the culprit vessel were allocated to three groups according to mechanism of ACS at OCT and C-reactive protein levels (cut-off: 2 mg/Ll): 1) plaque rupture with systemic inflammation; 2) plaque rupture without systemic inflammation, 3) plaque with intact fibrous cap. A blood sample was collected to obtain MDMs, categorized as having “round” or “spindle” morphology. Results Thirty-two patients (48.5%) were assigned to Group 1, 10 (15.2%) to Group 2 and 24 (36.4%) to Group 3. The “round” MDMs were significantly more frequent in Group 1 (39.25 ± 4.98%) than in Group 2 (23.89 ± 3.10%) and Group 3 (23.02 ± 7.89%), p = 0.008. MDMs in Group 1 as compared to Groups 2 and 3 showed lower efferocytosis (8.74 ± 1.38 vs 9.74 ± 2.15 vs 11.41 ± 2.41; p = 0.012), higher tissue factor levels (369.84 ± 101.13 vs 301.89 ± 59.78 vs 231.74 ± 111.47; p = 0.001) and higher heme oxygenase-1 expression (678.78 ± 145.43 vs 419.12 ± 74.44 vs 409.78 ± 64.33; p = 0.008). Conclusions MDMs of ACS patients show morpho-phenotypic heterogeneity with prevalence of pro-thrombotic and pro-oxidative properties in case of plaque rupture and systemic inflammation. Such MDMs subpopulation may take part to the cellular pathways leading to fibrous cap rupture with the subsequent thrombus formation.

The etiology of ST-elevation myocardial infarction (STEMI) is either rupture or erosion of unstable plaque with subsequent thrombosis. With the widespread use of plaque-stabilizing lipid-lowering therapies (statins), plaque erosion, rather than rupture, now accounts for most cases of acute coronary syndromes (ACS). In the spectrum of ACS, STEMI usually results from the total occlusion of the culprit epicardial coronary artery, leading to the occlusion of blood flow to the affected myocardium. The differential diagnosis of ST-elevations on electrocardiograms are broad. However, an elevated cardiac marker, evidence of wall motion abnormality on echocardiogram or positive stress testing makes an alternate diagnosis less likely. This prompts emergent coronary angiography with an intent to fix the underlying cause. In some cases like ours, when the clinical suspicion of STEMI is high, the coronary angiography may be unrevealing of the diagnosis.

Atherosclerosis is a lipoprotein-driven inflammatory disorder leading to a plaque formation at specific sites of the arterial tree. After decades of slow progression, atherosclerotic plaque rupture and formation of thrombi are the major factors responsible for the development of acute coronary syndromes (ACSs). In this regard, the detection of high-risk (vulnerable) plaques is an ultimate goal in the management of atherosclerosis and cardiovascular diseases (CVDs). Vulnerable plaques have specific morphological features that make their detection possible, hence allowing for identification of high-risk patients and the tailoring of therapy. Plaque ruptures predominantly occur amongst lesions characterized as thin-cap fibroatheromas (TCFA). Plaques without a rupture, such as plaque erosions, are also thrombi-forming lesions on the most frequent pathological intimal thickening or fibroatheromas. Many attempts to comprehensively identify vulnerable plaque constituents with different invasive and non-invasive imaging technologies have been made. In this review, advantages and limitations of invasive and non-invasive imaging modalities currently available for the identification of plaque components and morphologic features associated with plaque vulnerability, as well as their clinical diagnostic and prognostic value, were discussed.

Objectives This study sought to investigate the ability of combined near-infrared spectroscopy and intravascular ultrasound (NIRS-IVUS) to differentiate plaque rupture (PR), plaque erosion (PE), or calcified nodule (CN) in acute myocardial infarction (AMI). Background Most acute coronary syndromes occur from coronary thrombosis based on PR, PE, or CN. In vivo differentiation among PR, PE, and CN is a major challenge for intravascular imaging. Methods The study enrolled 244 patients with AMI who had a de novo culprit lesion in a native coronary artery. The culprit lesions were assessed by both NIRS-IVUS and optical coherence tomography (OCT). Maximum lipid core burden index in 4 mm (maxLCBI4mm) was measured by NIRS. Plaque cavity and convex calcium was detected by IVUS. The OCT diagnosis of PR (n = 175), PE (n = 44), and CN (n = 25) was used as a reference standard. Results In the development cohort, IVUS-detected plaque cavity showed a high specificity (100%) and intermediate sensitivity (62%) for identifying OCT-PR. IVUS-detected convex calcium showed a high sensitivity (93%) and specificity (100%) for identifying OCT-CN. NIRS-measured maxLCBI4mm was largest in OCT-PR (705 [interquartile range (IQR): 545 to 854]), followed by OCT-CN (355 [IQR: 303 to 478]) and OCT-PE (300 [IQR: 126 to 357]) (p Conclusions By evaluating plaque cavity, convex calcium, and maxLCBI4mm, NIRS-IVUS can accurately differentiate PR, PE, and CN.

Background Postprandial hyperglycemia was reported to play a key role in established risk factors of coronary artery diseases (CAD) and cardiovascular events. Serum 1,5-anhydroglucitol (1,5-AG) levels are known to be a clinical marker of short-term postprandial glucose (PPG) excursions. Low serum 1,5-AG levels have been associated with occurrence of CAD; however, the relationship between 1,5-AG levels and coronary plaque rupture has not been fully elucidated. The aim of this study was to evaluate 1,5-AG as a predictor of coronary plaque rupture in diabetic patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS).Methods A total of 132 diabetic patients with NSTE-ACS were included in this study. All patients underwent intravascular ultrasound examination, which revealed 38 patients with plaque rupture and 94 patients without plaque rupture in the culprit lesion. Fasting blood glucose (FBS), hemoglobin A1c (HbA1c) and 1,5-AG levels were measured before coronary angiography. Fasting urinary 8-iso-prostaglandin F2α (8-iso-PGF2α) level was measured and corrected by creatinine clearance. Results Patients with ruptured plaque had significantly lower serum 1,5-AG levels and a tendency of higher HbA1c levels than patients without ruptured plaque in our study population. In multivariate analysis, low 1,5-AG levels were an independent predictor of plaque rupture (odds ratio 3.3; p = 0.006) in diabetic patients with NSTE-ACS, but HbA1c was not. The area under the receiver-operating characteristic curve for 1,5-AG (0.678, p = 0.001) to predict plaque rupture was superior to that for HbA1c (0.618, p = 0.034). Levels of 1,5-AG were significantly correlated with urinary 8-iso-PGF2α levels (r=-0.224, p = 0.010).Conclusions Serum 1,5-AG may identify high risk for coronary plaque rupture in diabetic patients with NSTE-ACS, which suggests PPG excursions are related to the pathogenesis of plaque rupture in diabetes.

OBJECTIVES The purpose of this study was to derive a biomechanical stress metric that was based on the multifactorial assessment of coronary plaque morphology, likely related to the propensity of plaque rupture in patients.BACKGROUND Plaque rupture, the most frequent cause of coronary thrombosis, occurs at locations of elevated tensile stress in necrotic core fibroatheromas (NCFAs). Finite element modeling (FEM), typically used to calculate tensile stress, is computationally intensive and impractical as a clinical tool for locating rupture-prone plaques. This study derived a multifactorial stress equation (MSE) that accurately computes peak stress in NCFAs by combining the influence of several morphological parameters.METHODS Intravascular ultrasound and optical frequency domain imaging were conducted in 30 patients, and plaque morphological parameters were defined in 61 NCFAs. Multivariate regression analysis was applied to derive the MSE and compute a peak stress metric (PSM) that was based on the analysis of plaque morphological parameters. The accuracy of the MSE was determined by comparing PSM with FEM-derived peak stress values. The ability of the PSM in locating plaque rupture sites was tested in 3 additional patients.RESULTS The following parameters were found to be independently associated with peak stress: fibrous cap thickness (p < 0.0001), necrotic core angle (p = 0.024), necrotic core thickness (p < 0.0001), lumen area (p < 0.0001), necrotic core including calcium areas (p = 0.017), and plaque area (p = 0.003). The PSM showed excellent correlation (R = 0.85; p < 0.0001) with FEM-derived peak stress, thus confirming the accuracy of the MSE. In only 56% (n = 34) of plaques, the thinnest fibrous cap thickness was a determining parameter in identifying the cross section with highest PSM. In coronary segments with plaque ruptures, the MSE precisely located the rupture site.CONCLUSIONS The MSE shows potential to calculate the PSM in coronary lesions rapidly. However, further studies are warranted to investigate the use of biomechanical stress profiling for the prognostic evaluation of patients with atherosclerosis. (C) 2020 by the American College of Cardiology Foundation.

Ceramides (Cer) are an atherogenic substance. However, the associations between specific plasma Cer levels and culprit plaque morphology in ST-segment elevation myocardial infarction (STEMI) patients are unclear.The study consisted of two parallel cohorts. 100 consecutive patients with STEMI were screened as discovery cohort. In the validation cohort, we separately screened 30 normal donors, 30 stable angina pectoris (SAP) and 315 STEMI patients. All STEMI patients underwent emergency percutaneous intervention (PCI) and optical coherence tomography (OCT) examination for culprit plaque. Based on established diagnostic criteria, STEMI patients were classified into plaque rupture (PR) and plaque erosion (PE) group, respectively. Rapid resolution liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (RRLC-Q-TOF/MS) was used to evaluate plasma Cer levels of the screened patients.STEMI patients had higher plasma Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:1) and Cer(d18:1/24:0) levels than normal donors and SAP patients (p 0.001, p 0.001, p 0.001, p 0.001, respectively). Plasma Cer levels were significantly higher in STEMI patients with PR than with PE (p 0.001, p 0.001, p = 0.008 and p = 0.006, respectively). The frequency of PR increased with increasing tertiles of plasma Cer (adjusted p for trend = 0.004, 0.044, 0.021 and 0.133, respectively). The fully adjusted per SD odds ratios (95% confidence interval) for PR were 9.375 (2.496-35.215) for Cer(d18:1/16:0), 3.586 (1.588-8.089) for Cer(d18:1/18:0), 8.171 (1.764-37.857) for Cer(d18:1/24:1), and 3.831 (1.288-11.289) for Cer(d18:1/24:10).The study documented novel, positive and independent associations between plasma Cer concentrations and the presence of PR, suggesting plasma Cer may act as potential biomarkers for PR to improve risk stratification.

Atherosclerosis remains the leading cause of ischemic syndromes such as myocardial infarction or brain stroke, mainly promoted by plaque rupture and subsequent arterial blockade. Identification of vulnerable or high-risk plaques constitutes a major challenge, being necessary to identify patients at risk of occlusive events in order to provide them with appropriate therapies. Clinical imaging tools have allowed the identification of certain structural indicators of prone-rupture plaques, including a necrotic lipidic core, intimal and adventitial inflammation, extracellular matrix dysregulation, and smooth muscle cell depletion and micro-calcification. Additionally, alternative approaches focused on identifying molecular biomarkers of atherosclerosis have also been applied. Among them, proteomics has provided numerous protein markers currently investigated in clinical practice. In this regard, it is quite uncertain that a single molecule can describe plaque rupture, due to the complexity of the process itself. Therefore, it should be more accurate to consider a set of markers to define plaques at risk. Herein, we propose a selection of 76 proteins, from classical inflammatory to recently related markers, all of them identified in at least two proteomic studies analyzing unstable atherosclerotic plaques. Such panel could be used as a prognostic signature of plaque instability.

Carotid atherosclerosis treatments involve endovascular intervention. Predicting the mechanical behavior of carotid artery with calcified plaques can decrease the high risk for endovascular procedures. The aim of this research is to study the impact of morphological changes in calcification on the mechanical behavior of plaques. Fluid structure interaction simulations were applied to four 3D carotid artery models, with different calcification patterns, using the FEM. Results show that the magnitude and the spatial distribution of the circumferential strain is greatly affected by geometrical plaque morphology. The highest strain of 0.08 was observed for the diffused calcification with lipid model as compared to the strain in other plaque models (0.042, 0.031). The presence of a calcification region surrounding the lipid lowered the first principal stress value from 80KPa to 60KPa for the diffused calcification with lipid model. The morphological features of calcified plaques may play an important role in assessing plaque rupture and the choice of treatment plan.

Background: The rupture of atherosclerotic plaques could cause serious clinical events. The wall shear stress (WSS) and axial plaque stress (APS) could reflect the risk of plaque rupture. This study aimed to quantitatively investigate the geometric effects on WSS and APS using computational fluid dynamics (CFD).Methods: 63 plaque models were developed from three severities (75%, 82%, and 89% in area), three eccentricities (the deviation of plaque throat from the arterial centerline: 0, 0.375 and 0.75mm), and 7 different length combinations of the proximal and distal stenotic segments (2mm-5mm, 3mm-5mm, 4mm-5mm, 5mm-5mm, 5mm-4mm, 5mm-3mm, 5mm-2mm). For each model, CFD simulation was performed to calculate the maximum and area-averaged WSS and APS on the proximal and distal stenotic segments. The multivariate analysis of variance and linear regression analysis were performed to quantitatively investigate the geometry-stress relationship.The results showed that, the severity and eccentricity of a plaque were linearly related to its WSS and APS. APS value on a segment (proximal or distal) of the plaque depended on the segmental length It was also shown that the difference of APS between proximal and distal segments depended exclusively on the difference of length between segments (all p

Myocardial infarction (MI) is a serious and time-sensitive condition. MIs are typically seen in patients with coronary artery disease (CAD) and are caused by the rupture of an atherosclerotic plaque due to factors contributing to plaque instability. However, this case illustrates that plaque rupture can also be caused by blunt trauma to the chest. Considering MI as a possible result of chest trauma may decrease time from presentation to diagnosis and treatment and, therefore, improve outcomes in similar cases, particularly when patients presents unusually or with very few risk factors for MI.

Cardiovascular diseases related to atherosclerosis are the first cause of death in the western world. This relevant fact has motivated the development of numerical models for arterial behavior in order to understand better cardiovascular pathologies. This chapter provides a parametric tool, using Machine Learning Techniques (MLTs), to assist the clinicians on decisions of the vulnerability of the atheroma plaque, especially when an instantaneous response is needed. The MLTs use an intelligent algorithm to model the atheroma plaque rupture in terms of four of the most influential geometrical factors in the plaque rupture: (i) fibrous cap thickness; (ii) stenosis ratio; (iii) lipid core width, and (iv) lipid core length. The output predicted is the maximum maximal principal stress occurred in an atherosclerotic coronary vessel with the input dimensions. For this purpose, an idealized and parametric coronary vessel model has been performed using finite element methods in order to train the machine learning.

Progress in biophysical modeling has recently identified several key plaque morphology features that play an important mechanistic role in plaque rupture, leading to often devastating clinical symptoms of the organ ischemia (stroke—in case of carotid artery atherosclerosis or myocardial infarction—in coronary atherosclerosis). Importantly, identification of these biophysics-relevant plaque features has been so far based on conventional (ex vivo) histological analyses while histological tissue processing affects both biological and biophysical characteristics of the atherosclerotic plaque components. Therefore, accurate (in situ), precise quantification of the key players that determine plaque biophysics and rupture risk is fundamental for increased precision of modeling in relation to better understanding the biologic processes and enhancing risk stratification.

Atherosclerotic Plaque Healing Atherosclerotic plaque rupture and erosion result in acute coronary syndromes. Plaque healing after initial disruption has been less extensively studied. Reviewed are...

Atherosclerotic disease is the leading cause of death worldwide. Plaque rupture and erosion lead to superimposed thrombosis and are responsible for the vast majority of acute ischaemic syndromes. Vulnerable plaques, plaques that are at increased risk of rupture, pose certain high-risk morphological features that can be imaged. Key processes include thin-cap fibroatheromas, larger plaque volume, larger lipid-rich necrotic core, neovascularization, intraplaque haemorrhage and spotty microcalcification. Various non-invasive and invasive imaging modalities have been developed with the aim to identify vulnerable plaque features in vivo and stratify patients at a higher risk of future cardiovascular events.

The aim of this study was to investigate whether CD74 levels in atherosclerotic lesions are associated with inflammation, apoptosis, plaque severity, and clinical symptoms among patients with carotid atherosclerosis. We further studied whether CD74 expression is associated with apoptosis in macrophages induced by 7ketocholesterol (7keto). Sixty-one carotid samples (39 males and 22 females) were immunostained with macrophages, smooth muscle cells, CD74, ferritin, TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling), and thrombin receptors. Double immunocytochemistry of CD74 and caspase 3 or CD74 and Annexin V was performed on THP-1 macrophages exposed to 7keto. In human carotid plaques, CD74 expression is lesion-dependently increased and is associated with necrotic core formation and plaque rupture, clinical symptoms, macrophage apoptosis, ferritin, and thrombin receptors. CD74 levels were inversely correlated to high-density lipoproteins and statin treatment, and positively correlated to triglycerides. In THP-1 macrophages, 7keto induced a significant increase in levels of CD74, ferritin, and apoptotic cell death. This study suggests that CD74 in apoptotic macrophages is linked to inflammation and thrombosis in progression of human atherosclerotic plaques, lipid metabolism, and clinical manifestation in atherosclerosis. Surface CD74 in apoptotic macrophages and ferritin production induced by oxidized lipids may contribute to inflammation and plaque vulnerability in atherosclerosis. Funding Agencies: Swedish Heart Lung Foundation[20060382, 20070488, 20100496]; Torsten and Ragnar Söderbergs Foundation [MT 13/06, MN 130/08]; Stroke Foundation; Olle Engkvist Foundation; Swedish Gamla Tjänarinnor Foundation; Linköping University; Linköping University Hospital Research Fund (ALF)

In den letzten Jahren wurde mit zunehmendem Interesse beobachtet, dass bei einem Teil der Myokardinfarktpatienten keine obstruktive Koronarsklerose vorliegt. Hierfur wurde der Begriff „MINOCA“ („myocardial infarction with non-obstructive coronary arteries“) eingefuhrt. Die Pravalenz von MINOCA wird auf 6–9 % aller Myokardinfarkte geschatzt. Bei Patienten mit NSTEMI wird ein hoherer Anteil an MINOCA-Patienten beobachtet als bei Patienten mit STEMI, auserdem sind haufiger weibliche als mannliche Patienten betroffen. MINOCA ist eine Arbeitsdiagnose, die weitere diagnostische Abklarung mittels invasiver Techniken (intravaskularer Ultraschall [IVUS], optische Koharenztomographie [OCT]) oder nicht-invasiver Bildgebung mit kardialer Magnetresonanztomographie (CMR) erfordert. Wenn koronare Verschlusse sicher nicht ubersehen wurden, mussen andere koronare Ursachen wie Plaqueruptur, oder -erosion, Thrombosen, Dissektion, Spasmus oder mikrovaskulare Dysfunktion evaluiert werden. Auserdem ist als nichtkoronare Ursache eine Myokarditis oder Tako-Tsubo-Kardiomyopathie mittels CMR auszuschliesen. Die weitere Behandlung und Prognose richten sich nach der endgultigen Diagnose.

Calcification morphology can determine atherosclerotic plaque stability and is associated with increased failures rates for endovascular interventions. Computational efforts have sought to elucidate the relationship between calcification and plaque rupture in addition to predicting tissue response during aggressive revascularisation techniques. However, calcified material properties are currently estimated and may not reflect real tissue conditions. The objective of this study is to correlate calcification mechanical properties with three radiographic density groups obtained from corresponding Computed Tomography (CT) images. Seventeen human plaques extracted from carotid (n = 10) and peripheral lower limb (n = 7) arteries were examined using micro-computed tomography (µCT), simultaneously locating the calcified deposits within their internal structure and quantifying their densities. Three radiographic density groups were defined based on the sample density distribution: (A) 130-299.99 Hounsfield Units (HU), (B) 300-449.99 HU and (C)450 HU. Nanoindentation was employed to determine the Elastic Modulus (E) and Hardness (H) values within the three density groups. Results reveal a clear distinction between mechanical properties with respect to radiographic density groups (p 0.0005). No significant differences exist in the density-specific behaviours observed between carotid and peripheral samples. Previously defined calcification classifications indicate an association with specific radiographic density patterns. Scanning Electron Microscopy (SEM) examination revealed that density group A regions consist of both calcified and non-calcified tissues. Further research is required to define the radiographic thresholds which identify varying degrees of tissue calcification. This study demonstrates that the mechanical properties of fully mineralised atherosclerotic calcification emulate that of bone tissues (17-25 GPa), affording computational models with accurate material parameters. STATEMENT OF SIGNIFICANCE: Global mechanical characterisation techniques disregard the heterogeneous nature of atherosclerotic lesions. Previous nanoindentation results for carotid calcifications have displayed a wide range. This study evaluates calcification properties with respect to radiographic density obtained from Micro-CT images. This is the first work to characterise calcifications from peripheral lower limb arteries using nanoindentation. Results demonstrate a strong positive correlation between radiographic density and calcification mechanical properties. Characterising calcifications using their density values provides clarity on the variation in published properties for calcified tissues. Furthermore, this study confirms the hypothesis that fully calcified plaque tissue behaviour similar to that of bone. Appropriate material parameters for calcified tissues can now be employed in computational simulations.

Atherosclerosis is a complex process with strong inflammatory component. We developed a straightforward sevenfold staining protocol for simultaneous assessment of dominant leukocyte classes, vascularization, and expression of the putative foam cell maker CD36. The method was applied on human coronaries covering the full spectrum of atherosclerotic disease. Results confirm the progressive association of macrophages and T cells with the process and a global presence of mast cells. B cells are exclusively present in adventitial follicles that accompany the process plaque destabilization (thin cap and ruptured lesions) and are otherwise absent. Neutrophils are only present as part of the hemorrhage that accompanies plaque rupture. This study does not classify CD36 as a key factor in foam cell formation. Observed macrophage accumulation in the neointima of stabilized fibrous calcified plaques is consistent with a process of neoatherosclerosis. This study on human coronaries shows a progressive association of macrophage and T-cell abundance with plaque progression. Follicle-like structures are transiently present during the process of plaque destabilization. Plaque healing is accompanied by cessation of the inflammatory response but followed by a new cycle of atherosclerosis.

Two-dimensional numerical models of arterial plaque are used to determine the effects of the geometrical characteristics of the lumen on the stress gradient and stress distribution. Three parameters with three levels that form the plaque lumen, stenosis rate by diameter, eccentricity, and ellipticity, were analyzed based on experimental design. A review of 27 cases confirmed that the stress and stress gradient tended to increase with a decreasing stenosis rate by diameter, and the eccentricity and ellipticity ratio also increased. Eccentricity had the greatest influence on the mechanical behavior of the plaque, and it was confirmed that even the same types of plaques varied in magnitude of influence depending on the geometrical characteristics of the lumen.

Atherosclerotic plaque rupture or erosion and subsequent development of platelet-containing thrombus formation is the fundamental cause of cardiovascular disease, which is the most common cause of death and disability worldwide. Here we show the high sensitivity of 200–270 GHz T-ray to distinguish thrombus formation at its early stage from uncoagulated blood. A clinical observational study was conducted to longitudinally monitor the T-ray absorption constant of ex-vivo human blood during the thrombus formation from 29 subjects. Compared with the control group (28 subjects) with uncoagulated blood samples, our analysis indicates the high sensitivity of 200–270 GHz T-Ray to detect thrombus with a low p-value −5. Further analysis supports the significant role of platelet-activated thrombotic cascade, which modified the solvation dynamics of blood and occurred during the early coagulation stage, on the measured T-Ray absorption change. The ability to sense the thrombus formation at its early stage would hold promise for timely identification of patients at risk of various atherothrombotic disorders and save billions of lives.

Pathology and in vivo imaging studies have identified superficial plaque erosion as a frequent and important mechanism underlying acute coronary syndromes (ACS). In contrast with plaque rupture, the pathophysiological mechanisms leading to plaque erosion remain poorly understood. The advent of intravascular imaging techniques, particularly optical coherence tomography, has aided understanding of this mode of ACS in vivo by complementing previous insights from pathology studies. Appreciation of the distinct biological and clinical mechanisms of plaque erosion points to the possibility of tailored management strategies for patients presenting with ACS.

Background and purpose Carotid plaques are a strong risk factor for ischemic stroke, and plaque rupture poses an even higher risk. Although many studies have investigated the pathogenic mechanisms of carotid plaque formation, few have studied the differences in molecular mechanisms underlying the rupture and non-rupture of carotid plaques. In addition, since early diagnosis and treatment of carotid plaque rupture are critical for the prevention of ischemic stroke, many studies have sought to identify the important target molecules involved in the rupture. However, a target molecule critical in symptomatic ruptured plaques is yet to be identified. Methods A total of 79 carotid plaques were consecutively collected, and microscopically divided into ruptured and non-ruptured groups. Quantitative polymerase chain reaction array, proteomics, and immunohistochemistry were performed to compare the differences in molecular mechanisms between ruptured and non-ruptured plaques. Enzyme-linked immunosorbent assay was used to measure the differences in ATP-binding cassette subfamily A member 1 (ABCA1) levels in the serum. Results The expression of several mRNAs and proteins, including ABCA1, was higher in ruptured plaques than non-ruptured plaques. In contrast, the expression of other proteins, including β-actin, was lower in ruptured plaques than non-ruptured plaques. The increased expression of ABCA1 was consistent across several experiments, ABCA1 was positive only in the serum of patients with symptomatic ruptured plaques. Conclusions This study introduces a plausible molecular mechanism underlying carotid plaque rupture, suggesting that ABCA1 plays a role in symptomatic rupture. Further study of ABCA1 is needed to confirm this hypothesis.

Coronary plaque morphology, including plaque size and fibrous cap thickness, is thought to contribute to the risk of plaque rupture and future cardiac events. Dual-frequency intravascular ultrasound has been proposed as a possible technique to visualize both large-scale features and superficial detail of coronary plaque; however, it has not been found to be feasible within the constraints of a clinically functional intravascular ultrasound catheter. In this study, we describe the design and fabrication of a dual-frequency catheter using a bidirectional transducer stack with center frequencies of approximately 30 and 80 MHz. We describe how the high-frequency transducer achieves significantly improved axial and lateral resolution (16 and 120 µm, respectively, vs. 50 and 220 µm) at the expense of penetration depth. Finally, imaging of ex vivo human coronary artery segments reveals that the catheter can provide complementary images of the deeper arterial wall and superficial plaque features.

While primary percutaneous coronary intervention (PCI) has significantly contributed to improve the mortality in patients with ST segment elevation myocardial infarction even in cardiogenic shock, primary PCI is a standard of care in most of Japanese institutions. Whereas there are high numbers of available facilities providing primary PCI in Japan, there are no clear guidelines focusing on procedural aspect of the standardized care. Whilst updated guidelines for the management of acute myocardial infarction were recently published by European Society of Cardiology, the following major changes are indicated; (1) radial access and drug-eluting stent over bare metal stent were recommended as Class I indication, and (2) complete revascularization before hospital discharge (either immediate or staged) is now considered as Class IIa recommendation. Although the primary PCI is consistently recommended in recent and previous guidelines, the device lag from Europe, the frequent usage of coronary imaging modalities in Japan, and the difference in available medical therapy or mechanical support may prevent direct application of European guidelines to Japanese population. The Task Force on Primary Percutaneous Coronary Intervention of the Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT) has now proposed the expert consensus document for the management of acute myocardial infarction focusing on procedural aspect of primary PCI.

Recent studies have shown that plaque composition and type of plaque rupture (PR) might cause different clinical presentations in coronary artery disease [(1)][1], indicating that multiple mechanisms were involved in PR. The aim of the current study was to evaluate the morphological characteristics

Mobile plaque in the innominate artery is extremely rare and difficult to diagnose, especially in its acute stage. Its diagnosis is often delayed in many cases, resulting in delayed treatment and poor prognosis. Herein, we report the case of a 69-year-old patient with multiple cerebral infarction only in the right internal carotid artery and vertebrobasilar territories. No embolic sources were found until arterial ultrasonography detected a large balloon-like mobile plaque in the IA. Mobile plaque consisted of high-and low-echoic components and showed balloon-like plaque. Despite sufficient antiplatelet therapy, recurrence of cerebral embolism could not be prevented. IA replacement was eventually performed by cardiac surgeons. Pathological examinations showed that organized mobile plaque could have existed previously and acute thrombi, generated after the atheromatous plaque rupture caused by the mechanical burden of organized mobile plaque, could expand along with the organized mobile plaque and caused balloon-like plaque and related with repeated embolism. The IA should be explored immediately in cases of repetitive right-sided cerebral embolisms to prevent further recurrence.

Highlights • Surgical resection of tumors invading the aorta is a challenging procedure. • Thoracic aorta endografts facilitate en bloc resection of tumor infiltrating the aortic wall. • The best treatment option is to keep the procedure separated before lung resection. • Aortic stent placement is not mandatory with no clear signs of plaque infiltrating. • The aortic stent placement is possible in emergency, even during another operation., Background Surgical resection of tumors invading the aorta is a challenging procedure. More recently, the use of thoracic aortic endografts has been reported to facilitate en bloc resection of tumors invading the aortic wall. The best treatment option is to keep the procedure separated before lung resection to reduce the risks of bleeding, therefore avoiding adverse consequences for the patient. However, an aortic stent placement before surgery is not mandatory with no clear signs of tumor or atherosclerotic plaque infiltrating the entire aortic wall. Case presentation A 72-year-old man came to our Department for a persistent cough. Computed tomography (CT) scan with enhancement showed a mass located in the left upper lobe of the lung with no clear sign of infiltration or calcified plaques along the entire vascular wall. A positron emission tomography with 2-deoxy-2-[fluorine-18] fluoro-d-glucose integrated with computed tomography (PET/CT with 18F-FDG) was positive for hypermetabolic mass with negative lymph node stations bilaterally. Patient was undergone surgery for major lung resection by left thoracotomy. For an unexpected intraoperative bleeding due to the rupture of a calcified plaque, a stent was placed before proceeding with lung surgery. Patient was persistently stable, discharged after six days from surgery with no morbidities. Conclusions In our case, no signs of the atherosclerotic plaque infiltration as well as no tumor infiltration were shown. In these situations, the aortic stent placement is possible in emergency, even during another operation. Nevertheless, surgeon experience and the good coordination among specialists is mandatory to yield a satisfying solution.