Aortic Atheroma Research Articles

Enhancing Thromboembolic Risk Prediction in Non-valvular Atrial Fibrillation: The Critical Role of Transesophageal Echocardiography (TEE).

Introduction Atrial fibrillation (AF), the most common cardiac arrhythmia, poses challenges in predicting thromboembolic risk. While the CHA2DS2-VASc (congestive heart failure, hypertension, age ≥ 75 years (doubled), type 2 diabetes mellitus, previous stroke, transient ischemic attack, or thromboembolism (doubled), vascular disease, age 65-74 years, and sex category) scoreremains essential, its limitations include failure to identify left atrial (LA) thrombus in some patients. Transesophageal echocardiography (TEE) provides superior detection of LAthrombi and thrombogenic factors compared to transthoracic echocardiography (TTE), improving risk stratification, especially in intermediate-risk groups. Our study highlights the value of TEE in addressing gaps left by clinical scoring systems in certain subgroups of patients. Purpose and methodology This descriptive, prospective study aims to evaluate the role of transthoracic and transesophageal echocardiography in stratifying thromboembolic risk in patients with non-valvular AF. A total of 100 patients, from two hospitals in Morocco, were included. Data were collected through clinical and paraclinical assessments, with echocardiography examining morphological and functional atrial parameters. Results Among the 100 patients, 73% were male, with a mean age of 67 years. AF was permanent in 84.8% of cases, with dyspnea and palpitations being the most common symptoms. Hypertension was the leading underlying cause. Echocardiographic findings showed a correlation between LA enlargement, reduced left atrial appendage (LAA) emptying velocities, and increased thromboembolic risk. In patients with low clinical scores, 30.7% exhibited echocardiographic signs of a thrombogenic environment, while protrusive aortic atheroma was more prevalent in those with higher clinical risk scores. Discussion The findings confirm the utility of echocardiography, particularly transesophageal, in detecting parameters associated with heightened thromboembolic risk, including LAA emptying velocities, spontaneous contrast, and aortic abnormalities. These echocardiographic markers, combined with clinical scores, may enhance the precision of risk stratification and allow for more targeted anticoagulation therapy. Conclusion Atrial fibrillation remains a common and potentially serious arrhythmia. Echocardiography provides valuable information that complements clinical risk stratification, especially for patients at moderate thromboembolic risk. This study highlights the benefit of incorporating echocardiographic parameters into risk assessment to optimize strategies for preventing thromboembolic events in patients with AF.

Fluorescent gold nanoclusters possess multiple actions against atherosclerosis

Atherosclerosis caused major morbidity and mortality worldwide. Molecules possessing lipid-lowering and/or anti-inflammatory properties are potential druggable targets against atherosclerosis. We examined the anti-atherosclerotic effects of fluorescent gold nanoclusters (FANC), which were dihydrolipoic acid (DHLA)-capped 2-nm gold nanoparticles. We evaluated the 8-week effects of FANC in Western-type diet-fed ApoE-deficient mice by either continuous intraperitoneal delivery (20 μM, 50 μl weekly) or via drinking water (300 nM). FANC reduced aortic atheroma burden, serum total cholesterol, and oxidative stress markers malondialdehyde and 4-hydroxynonenal levels. FANC attenuated hepatic lipid deposit, with changed expression of lipid homeostasis-related genes HMGCR, SREBP, PCSK9, and LDLR in a pattern similar to mice treated with ezetimibe. FANC also inhibited intestinal cholesterol absorption, resembling the action of ezetimibe. The lipid-lowering and anti-atherosclerotic effects of FANC reappeared in Western-type diet-fed LDLr-deficient mice. FANC bound insulin receptor β (IRβ) via DHLA, leading to AKT activation. However, unlike insulin, which also bound IRβ to activate AKT to induce HO-1, activation of AKT by FANC was independent of HO-1 expression in human aortic endothelial cells (HAECs). Alternatively, FANC up-regulated NRF2, interfered the binding of KEAP1 to NRF2, and promoted KEAP1 degradation to free NRF2 for nuclear entry to induce HO-1 that suppressed the expression of ICAM-1 and VCAM-1. Consistently, FANC suppressed ox-LDL-induced enhanced attachment of THP-derived macrophages onto HAECs. In macrophages, FANC up-regulated ABCA1, and reversed ox-LDL-induced suppression of cholesterol efflux. FANC effected in vitro at nano moles. In conclusion, our findings showed novel actions and multiple mechanisms of FANC worked coherently against atherosclerosis.

Impact of protruding and ulcerated aortic atheroma on periprocedural ischemic stroke in patients undergoing transcatheter aortic valve replacement: a comprehensive analysis

Abstract Backgrounds Aortic atherosclerosis has the potential to impact both the strategy and outcomes of transcatheter aortic valve replacement (TAVR). Past research has established a correlation between the thickness and volume of aortic atheroma with periprocedural ischemic stroke and long-term mortality. However, there is limited investigation into the relationship between the morphology of aortic atheroma and outcomes following TAVR. Purpose The study aimed to assess the influence of protruding and ulcerated aortic atheroma on the occurrence of periprocedural ischemic stroke following TAVR. Methods A total of 979 patients who underwent TAVR between February 2012 and May 2019, and had retrospectively available data from contrast-enhanced computed tomography, were included in this analysis. The presence of protruding or ulcerated atheroma was evaluated across four aortic segments: ascending aorta, aortic arch, descending aorta, and abdominal aorta. Protruding aortic atheroma was defined as atheroma with a thickness exceeding 3 mm and protruding components. Ulcerated aortic atheroma was defined as atheroma presenting with ulcer-like disruption of the intima. The primary endpoint assessed was periprocedural ischemic stroke occurring within 48 hours following TAVR. Results The frequencies of protruding and ulcerated aortic atheroma were as follows: 0.2% in the ascending aorta, 6.5% in the aortic arch, 11.1% in the descending aorta, 15.7% in the abdominal aorta, and 24.2% in the entire aorta (Figure 1). Among the 979 patients analyzed, 25 (2.6%) experienced periprocedural ischemic stroke. Patients with protruding or ulcerated aortic atheroma exhibited a significantly higher incidence of periprocedural ischemic stroke compared to those without (5.5% vs. 1.6%, p=0.0010). Multivariate logistic analysis revealed that protruding or ulcerated aortic atheroma, particularly in the aortic arch, independently increased the risk of periprocedural ischemic stroke. (Table 1). Among the subset of patients (309, 34%) undergoing transfemoral TAVR (TF-TAVR) with a self-expandable valve, those with protruding or ulcerated aortic atheroma had a notably higher incidence of periprocedural ischemic stroke compared to those without (9.6% vs. 1.6%, p=0.0083). Conversely, among patients (587, 66%) undergoing TF-TAVR with a balloon-expandable valve, there was no statistically significant difference in the incidence of periprocedural ischemic stroke between those with and without protruding or ulcerated aortic atheroma (4.2% vs. 1.8%, p=0.102). Conclusions Protruding and ulcerated aortic atheroma, particularly in the aortic arch, were linked to a higher risk of periprocedural ischemic stroke post-TAVR. Consequently, careful selection of TAVR strategy, including valve type and procedural approach, is essential for patients with such aortic lesions.Figure 1Table 1

Benefits of prophylactic carotid revascularization in patients with asymptomatic carotid artery stenosis undergoing coronary artery bypass surgery: A narrative review.

Patients undergoing coronary artery bypass grafting (CABG) are at increased risk of perioperative stroke. Carotid atherosclerosis has been identified as an independent risk factor for stroke during and in the early postoperative period of cardiac surgery. However, the pathogenesis of peri-CABG stroke is multifactorial and frequently involves other noncarotid causes, such as cardiac emboli and aortic atheroma. Therefore, routine population-wide screening of carotid stenosis is not recommended, but target screening of patients at high risk of carotid-related perioperative stroke can have benefits. Carotid duplex sonography is recommended as an initial screening tool. Elimination of carotid stenosis before cardiac surgery is indicated in patients in whom carotid atherosclerosis is suspected to be the primary contributor to perioperative stroke. In patients with advanced carotid atherosclerosis, an individualized revascularization approach, including simultaneous or staged procedures, is advocated. The prevailing consensus is that synchronous surgery is safer than staged procedures. Carotid artery stenting represents a less invasive alternative, but its role in high-risk patients requires further investigation. In conclusion, the risk of perioperative stroke in patients undergoing CABG involves different factors, and carotid artery stenosis is involved in its pathogenesis only in some patients. Therefore, individualized approaches and careful consideration of patient risk factors are essential in determining the need for carotid screening and revascularization before CABG.

A Comprehensive Guide to Aortic Atheroma: Delving in Its Causes, Detection, and Treatment.

Aortic atheroma, a common disease, is characterized by the formation and accumulation of atheromatous plaques within the aorta. The disease manifestations range from asymptomatic conditions to life-threatening complications like stroke or aortic dissection. The severity of this condition necessitates a detailed look at its pathophysiology, diagnostics, and management options. This guide provides a detailed overview of aortic atheroma, its definition, worldwide occurrence, demographic patterns, and underlying pathophysiology. It also elucidates the symptomatology associated with atheromatous changes in the aorta, diagnostic criteria for identifying the disease, and the latest epidemiological data. This article presents current treatment modalities, focusing on preventive and lifestyle approaches to cease further progression of atheromatous disease. It additionally reviews relevant case studies to give practical insights into the challenges faced and consequences of managing aortic atheroma. The in-depth discussion of aortic atheroma improves the perspective to a broader public health relevance, giving importance to the need for continuous improvement in medical practices, and personalized healthcare strategies to reduce risk and better patient outcomes.

Prognosis of ischemic stroke patients with both aortic atheroma and cardioembolic sources

This study aimed to investigate the relationship between complex aortic plaque (CAP) and short-term as well as long-term outcomes following cardioembolic stroke. CAP is a known risk factor for occurrence and recurrence of ischemic stroke. However, the association of CAP on cardioembolic stroke remains unclear. This was retrospective study using prospective cohort of consecutive patients with cardioembolic stroke who underwent transesophageal echocardiography. The functional outcome was evaluated using the modified Rankin Scale score at 3 months, and long-term outcomes were assessed by recurrence of ischemic stroke and occurrence of major adverse cardiovascular events (MACE). Among 759 patients with cardioembolic stroke, 91 (12.0%) had CAP. Early ischemic stroke recurrence within 3 months was associated with CAP (p = 0.025), whereas CAP was not associated with functional outcome at 3 months (odd ratio 1.01, 95% confidence interval [CI] 0.57–1.84, p = 0.973). During a median follow-up of 3.02 years, CAP was significantly associated with ischemic stroke recurrence (hazard ratio = 2.68, 95% CI 1.48–4.88, p = 0.001) and MACE occurrence (hazard ratio = 1.61, 95% CI 1.03–2.51, p = 0.039). In conclusion, CAP was associated with early ischemic stroke recurrence and poor long-term outcomes in patients with cardioembolic stroke. It might be helpful to consider transesophageal echocardiography for patients with cardioembolic stroke to identify CAP.

Anthrometric dimensions and their impact on cardiovascular risk factors.

Central obesity is an important risk factor for cardiovascular disease. The abdominal subcutaneous adipose tissue thickness (ASATT) can be used to evaluate central obesity. The objective of this study was to compare ASATT with cardiovascular risk factors and other anthropometric parameters to show that ASATT can be a useful tool for the early assessment of heart disease risk. In this observational cross-sectional study, anthropometric measurements of 100 autopsied decedents, including waist circumference, hip circumference, waist/height and waist/hip ratio, aortic outlet and coronary artery atheroma plaque densities, heart weight, ventricular wall thickness, and ASATT, were assessed. The research data were evaluated using the Statistical Package for the Social Sciences for Windows 25.0. The average ASATT of the male group was 40.36 mm (SD: 11.00), and the average of female cases was 46.34 mm (SD: 18.12). There was no statistically significant difference between the sexes and both age groups in terms of the ASATT score (P > .05). There was a positive correlation between ASATT and waist circumference, hip circumference, and waist/height ratio in both sexes (P < .05). While ASATT was not related to atheroma density in the coronary arteries of men (P > .05), it was correlated with atheroma density in all 3 coronary arteries of women (P < .05). In the male group, the aortic inner surface atheroma density was positively correlated with ASATT (P < .05). In both sexes, there was a positive correlation (P < .05) between ASATT and heart weight; however, no such correlation was observed with right and left ventricular wall thickness (P > .05). ASATT is related to other anthropometric measurements, atherosclerosis of critical vessels, and heart weight, and can be used to scan the patient population for heart disease risk assessment with noninvasive methods.

Calcification and atheroma plaques: is there any impact on the anatomical features of the aortic root and its elements?

ObjectivesMorphometric information of the structures within the borders of the aortic root is a guide for surgical interventions. It is essential to determine the effects of aortic calcification and atheroma plaque findings on the structures of this region. This study aims to establish the normal values of aortic root structures and to investigate the impact of pathologic findings in order to guide diagnosis and treatment in the clinic. MethodsThe aortic root structures were morphometrically analyzed in fresh hearts of 110 patients (89 males, 21 females) brought to the forensic medicine institution. The distances between the bases of the aortic sinuses, their widths and heights, and the lengths of the commissures were measured to differentiate between pathologic and non-pathologic aortic classes. Parameters were compared according to gender, age, body mass index, and body surface area. ResultsThe mean age was 44.71 ± 15.57 years in 21 female patients and 53.66 ± 15.67 years in 89 male patients. The results of the pathologic aorta group with calcification and atheroma plaque findings were higher than the non-pathologic aorta group in all parameters (P < .05). ConclusionsCalcification and the presence of atheroma plaque in the aorta increase the size of the structures at the aortic root. Gender, age, body mass index, and body surface area are among the criteria that will cause changes in the structures of this region. These results will help surgeons to know the normal values of aortic root structures and to consider the effects of pathologic findings in aortic valve repair operations.

Aortogenic calcified cerebral embolism diagnosed with an embolus retrieved by thrombectomy: illustrative case.

Calcified cerebral embolism has been reported as a cause of acute cerebral infarction, but an aortogenic origin has rarely been identified as the embolic source. The authors describe a case of aortogenic calcified cerebral embolism in a patient with other embolic sources. In a patient with cerebral infarction and atrial fibrillation, a white hard embolus was retrieved by mechanical thrombectomy. Pathological analysis of the embolus revealed that it was mostly calcified, with some foam cells and giant cells. The macroscopic and pathological findings allowed the authors to finally diagnose an aortogenic calcified cerebral embolism. Even in patients with cardiogenic embolic sources, it is possible to identify a complex aortic atheroma with calcification as the embolic source, based on the macroscopic and pathological findings of the embolus retrieved by mechanical thrombectomy.

A Rare Case of Multicentric Reticulohistiocytosis in An Elderly Male Patient

Multicentric reticulohistiocytosis (MRH) is a rare systemic proliferative granulomatous disease of non-Langerhans cells. The aim of this study is to report a case of multicentric reticulohistiocytosis that is easily misdiagnosed in clinical practice. A 74-year-old man sought the Rheumatology office in December 2022 with a main complaint of arthralgia for six months, associated with morning stiffness, joint swelling, and upper and lower limb weakness. On physical examination, papules on the dorsal surface of the proximal interphalangeal joints, base of the nose, and lateral surface of the right hallux were observed. Hyperemia was also identified on the back, and edema of the proximal and distal interphalangeal joints, wrists and knees. Laboratory tests revealed ESR and ANA within normal limits. Tests were negative for Anti-Sm, Anti-RO, rheumatoid factor, Anti-CCP, HIV, and HCV. Chest CT-scan showed right axillary lymph node enlargement, measuring 2.7 cm, atheromatous aorta, and streaks with scattered atelectasis in the lower lobe, without other changes. On total abdominal ultrasound, prostate enlargement was detected. Immunohistochemistry of skin biopsy identified atypical acinar proliferation. Histopathology skin biopsy stained with hematoxylin-eosin (January 2023) showed a dense histiocytic infiltrate. Detail of the histiocytic component displayed “ground glass” eosinophilic cytoplasm. Immunohistochemistry was negative for S100 and CD34 and positive for CD68. Final diagnosis was MRH. The patient underwent treatment with drugs. In conclusion, clinical manifestations, including skin and joint changes, with signs and symptoms of rheumatic disorders (e.g. dermatomyositis and rheumatoid arthritis) similar to those of MRH are expected in rheumatology practice. However, knowledge about disease progression in MRH is limited. Therefore, this case report is described due to its rarity Keywords: Non-Langerhans-Cell Histiocytosis, Pathology, Muticentric Reticulohistiocytosis, Rheumatological Diseases,

The Role of Transcranial Doppler in Patients with Cryptogenic Stroke

Identifying the stroke mechanism is crucial for secondary prevention of ischemic stroke. However, approximately 20% to 30% of patients with ischemic stroke do not display a discernible cause after standard diagnostic evaluation and are classified as having cryptogenic stroke. Most cryptogenic strokes are believed to be of embolic origin, referred to as embolic stroke of undetermined source. Several potential causes, including occult atrial fibrillation, aortic arch atheroma, non-stenotic atherosclerosis, coagulopathy, and patent foramen ovale (PFO), are significant contributors to cryptogenic stroke. Among these, PFO-associated strokes often manifest as small cortical lesions in the posterior circulation and are associated with fewer traditional risk factors. Ischemic stroke is considered a high risk if there is a large PFO with significant shunting or the presence of an atrial septal aneurysm. Although transesophageal echocardiography is regarded as the gold standard for diagnosing PFO, its invasiveness, high cost, and challenges in certain stroke patients necessitate alternative approaches. Recently, transcranial Doppler (TCD) has emerged as a valuable screening tool for detecting high-risk PFOs, as supported by recent research. Accurate determination of the culprit PFO responsible for ischemic stroke remains crucial for guiding appropriate treatment decisions. This article provides a comprehensive review of the different modalities used to diagnose PFO, strategies for assessing the risk of PFO causing paradoxical embolism, and the role of TCD in patients with cryptogenic stroke caused by other etiologies.

Aortic arch atheroma and stroke recurrence in mild stroke patients: ADS post-hoc analysis

BackgroundAortic arch atheroma is one of the embolic sources in patients with ischemic stroke. Although transesophageal echocardiogram (TEE) is the golden standard to evaluate the aortic arch atheroma, it is invasive and may be limited to patients with suspected embolism. Present post-hoc analysis evaluated the acute dual study data on mild stroke patients who had aortic arch atheroma proven by TEE and evaluate whether combined cilostazol and aspirin therapy might reduce the rate of stroke recurrence comparing aspirin therapy. MethodsAortic arch atheroma was defined as aortic arch plaque with a maximal intima-medial thickness of ≥4.0 mm. Stroke recurrence included new diffusion-weighted image (DWI) lesions within 14 days. ResultAmong 316 (227 [72%] men; median, 66 [interquartile, 60–76] years old) patients, TEE found that 93 patients (29%) had the aortic arch atheroma, and 223 (71%) did not had it. The aortic arch atheroma group was older (P = 0.001) and accompanied with diabetes mellitus (P = 0.003), dyslipidemia (P = 0.046), smoking (P = 0.034), and had previous ischemic stroke history (P = 0.042) and multiple infarcts (P = 0.024) on admission. During hospitalization, new DWI lesion was frequently observed in the aortic arch atheroma group compared to the group without it (14.1% vs. 6.8%, P = 0.049). The rates of new DWI lesion were not different between dual antiplatelet therapy group and aspirin group (14.9% vs. 13.3%, P = 1.000). ConclusionAortic arch atheroma was the representative of systematic arteriosclerosis associated with new DWI lesion in short-term. Combined antiplatelet therapy using cilostazol did not prevent new DWI appearance comparing aspirin therapy in this cohort.

Aortopathy: Effects of Lipid-Lowering Therapy.

Aortopathies can be congenital or acquired. Aortic atherosclerosis, abdominal aortic aneurysm, and degenerative aortic stenosis are some of the major manifestations of acquired aortopathy. Dyslipidemia, an imbalance of plasma lipid levels, is strongly associated with common aortopathies. A relationship between abdominal aortic aneurysm, degenerative aortic stenosis, and dyslipidemia has been identified in the literature but finding effective preventive strategies has been challenging. Nevertheless, lipid-lowering therapy remains a mainstay of both treatment and prevention. In patients with aortic atheroma, statins were found to be protective through the review of this study. There is currently no place for statins in the treatment or prevention of disease progression in patients with calcific aortic stenosis. Their low cost, widespread availability, and strong safety profile tip the risk-to-benefit ratio toward statins for abdominal aortic aneurysms but more research is needed. A review of proprotein convertase subtilisin/kexin type 9 inhibitors may yield similar benefits for all aortopathy patients; however, those results are not yet available.

Defining the Role of Anaortic Coronary Artery Bypass Grafting.

As the population ages and co-morbidities become more prevalent, the complexity of patients presenting for coronary artery bypass surgery is increasing. Cardiopulmonary bypass and aortic cross-clamping in these patients carry increased risk and, indeed, in some patients, with ascending aortic disease, the risks are prohibitive. Total-arterial anaortic coronary artery surgery is a technique that provides complete surgical coronary artery revascularization without cardiopulmonary bypass and without manipulating the ascending aorta. The technique essentially eliminates the risk of cerebral embolization of aortic atheroma and aortic injury. Anaortic techniques are an essential skillset for coronary artery surgery centers treating higher-risk patients.

#6030 CARDIAC ULTRASOUND ASSESSMENT AND THE NOVEL INFLAMMATION, FIBROSIS AND CALCIFICATION BIOMARKERS IN ESKD PATIENTS ON HD THERAPY: A PILOT STUDY

Abstract Background and Aims Novel biomarkers for inflammation, fibrosis, and vascular calcification have been recently used for further assessment of cardiovascular risk. The aim of our prospective study is to assess the relation between the novel cardiovascular biomarkers and biomarkers for vascular calcification with cardiac ultrasound function/morphology alteration in high cardiovascular risk patients with end stage kidney disease (ESKD) on haemodialysis (HD) therapy. Baseline findings are discussed in this pilot paper Method The study included 58 ESKD patients [55% men, mean age of 60.3 ± 11.7 years, and median hemodialysis therapy duration of 6.2 years (1.2 -25.7)], treated with HD (3 sessions of 4 hours /week with high flux dialyzers). Personal and laboratory data have been retrieved from the patients HD files. Cardiac ultrasound assessment was performed during the second HD session of the week, after 2 hours of HD therapy. Blood samples have been taken before the same HD session in order to determine FGF 23, BMP 2, IL 1 beta, Galectin 3 and soluble ST 2 levels. All patients signed an informed consent for the study participation and the use of personal and laboratory data for scientific purposes. The study was approved by the medical ethics committee of the “Victor Babes” University of medicine and pharmacy and of the ethics committee of the HD center. Results On cardiac ultrasound assessment the patients presented aorta atheroma in 74.1%, aorta valve fibrosis in 74.1%, mitral valve fibrosis in 74.1% of the cases. Calcifications have been evidenced at aorta valve level in 58.6%, mitral valve level in 75.8% and endomyocardial level in 67.2% of the cases. Increased left ventricular mass was present in 82.7%, enlarged interventricular septum in 74.1% of the cases. Decreased left ventricle diastolic filing (Appleton pattern - E/A) was evidenced in 55,1% of the cases and decreased left ventricular ejection fraction in 37.9%. Right ventricle enlargement was detected in 24.1% of the patients. At baseline, FGF 23 was inversely corelated with HD therapy duration (p = 0.01), ESA dose (p = 0.016), and directly with galectin 3 levels (p &amp;lt; 0.05) but not with the ultrasound findings. BMP 2 levels corelated directly with serum albumin levels and inversely with left ventricle diastolic filing (E/A) (p &amp;lt; 0.05). IL1 levels were inversely corelated with iPTH (p = 0.046), calcium (p = 0.046 and phosphate (p = 0.030) levels but not ultrasound findings, Galectin 3 inversely corelated with cu Hb (p = 0.002), Urea (p = 0.036) and K levels (p = 0.001) and directly with bicarbonate (p = 0.035), FGF 23 (p &amp;lt; 0.05) and CRP levels (p&amp;lt;0.0001), ST2 inversely corelated with ESA dose (p = 0.009) and decreased left ventricle diastolic filing (E/A) (p &amp;lt; 0.05). At one year follow-up 12% of the patients died and mortality was significantly influenced by inter ventricle sept and right ventricle enlargement. Conclusion At baseline, though the investigated ESKD patients on HD therapy presented extensive cardiac valve fibrosis and heart valve and endomyocardial calcifications the investigated biomarker changes were not significantly supporting the ultrasound findings. One- and two-years follow-up results may reveal the utility of biomarker assessment for cardiovascular outcomes in HD treated ESKD patients.

Heterozygosity for ADP-ribosylation factor 6 suppresses the burden and severity of atherosclerosis.

Atherosclerosis is the root cause of major cardiovascular diseases (CVD) such as myocardial infarction and stroke. ADP-ribosylation factor 6 (Arf6) is a ubiquitously expressed GTPase known to be involved in inflammation, vascular permeability and is sensitive to changes in shear stress. Here, using atheroprone, ApoE-/- mice, with a single allele deletion of Arf6 (HET) or wildtype Arf6 (WT), we demonstrate that reduction in Arf6 attenuates atherosclerotic plaque burden and severity. We found that plaque burden in the descending aorta was lower in HET compared to WT mice (p˂0.001) after the consumption of an atherogenic Paigen diet for 5 weeks. Likewise, luminal occlusion, necrotic core size, plaque grade, elastic lamina breaks, and matrix deposition were lower in the aortic root atheromas of HET compared to WT mice (all p≤0.05). We also induced advanced human-like complex atherosclerotic plaque in the left carotid artery using partial carotid ligation surgery and found that atheroma area, plaque grade, intimal necrosis, intraplaque hemorrhage, thrombosis, and calcification were lower in HET compared to WT mice (all p≤0.04). Our findings suggest that the atheroprotection afforded by Arf6 heterozygosity may result from reduced immune cell migration (all p≤0.005) as well as endothelial and vascular smooth muscle cell proliferation (both p≤0.001) but independent of changes in circulating lipids (all p≥0.40). These findings demonstrate a critical role for Arf6 in the development and severity of atherosclerosis and suggest that Arf6 inhibition can be explored as a novel therapeutic strategy for the treatment of atherosclerotic CVD.

Advancing age increases the size and severity of spontaneous atheromas in mouse models of atherosclerosis

Using multiple mouse models, we explored the impact of aging on the size and severity of atherosclerotic lesions. In young, middle-aged and old apolipoprotein E knockout mice (ApoE−/−) fed an atherogenic diet (AD) for 3–8 weeks, plaque/atheroma formation in the descending aorta and aortic root, and atheroma development in the carotid in response to partial carotid ligation (PCL) were assessed. Total and LDL cholesterol, and triglycerides were higher in old compared to both other age groups, regardless of AD duration. Aortic plaque burden increased with AD duration in all ages. The size and plaque morphology grade of aortic root atheromas was higher with age; however, there was no effect of age on the size or severity of carotid atheromas after PCL. We additionally induced hyperlipidemia in young and old C57BL/6 mice by adeno-associated virus mediated upregulation of LDL receptor regulator, Pcsk9, and 5 weeks of AD. Despite lower cholesterol in old compared to young Pcsk9 mice, there was a greater size and severity of aortic root atheromas in old mice. However, like the ApoE−/− mice, there was no effect of age on size or severity of PCL-induced carotid artery atheromas in Pcsk9 mice. Together, these results suggest that aging increases the size and severity of spontaneous aortic atheromas.

Redo mitral surgery after coronary artery bypass grafts under hyperkalemic hypothermia using thoracotomy and axillary artery cannulation in a patient with functioning bilateral internal thoracic arteries and atheromatous aorta

BackgroundRedo mitral valve surgery using resternotomy after coronary artery bypass grafting (CABG) is challenging as previous CABG with patent internal thoracic artery (ITA) poses a risk of injury due to dense adhesion. It is paramount to have alternative method to minimize this risk.Case presentation: We report a case of redo mitral and tricuspid valve repair via right thoracotomy under hypothermia and systemic potassium administration with axillary artery cannulation in a patient after CABG with patent bilateral ITA grafts crossing over the sternum. Herein, critical dissection around the aorta and functioning ITA grafts was avoided by performing the procedure under systemic hypothermia via thoracotomy. Furthermore, considering the presence of atheroma in the aorta, the axillary artery was used as a perfusion route to prevent stroke events. Postoperative course was uneventful and echocardiography demonstrated preserved cardiac function.ConclusionPerforming axillary artery cannulation and right thoracotomy under hypothermic cardiac arrest with systemic hyperkalemia without clamping the patent bilateral ITAs and aorta allowed us to perform redo mitral valve surgery after CABG without major postoperative cardiac or cerebral complications.

Supra-renal aortic atheroma extent and composition predict acute kidney injury after transcatheter aortic valve replacement: A three-dimensional computed tomography study

ObjectiveAcute kidney injury (AKI) may complicate transcatheter aortic valve replacement (TAVR) and could be linked to atheroembolization associated with catheter manipulation in the supra-renal (SR) aorta.We sought to determine the impact of SR aortic atheroma burden (SR-AAB) and composition, as well as of the aortic valve calcium score (AV-CS), measured at pre-operative multislice computed tomography (PO-MSCT), on AKI-TAVR. MethodsAll TAVR-patients 3 January-2018 to December-2020 were included. A three-dimensional analysis of PO-MSCT was performed, calculating percentage SR-AAB (%SR-AAB) as [(absolute SR-AAB volume)*100/vessel volume]. Types of plaque were defined according to Hounsfield unit (HU) intensity ranges. Calcified plaque was subcategorized into 3 strata: low- (351–700 HU), mid- (701–1000 HU), and high‑calcium (>1000 HU, termed 1 K-plaque). ResultsThe study population included 222 patients [mean age 83.3 ± 5.7 years, 95 (42.8%) males], AKI-TAVR occurred in 67/222 (30.2%). Absolute SR-AAB (41.3 ± 16.4 cm3 vs. 32.5 ± 10.7 cm3,p < 0.001) and %SR-AAB (17.6 ± 5.1% vs. 13.9 ± 4.3%,p < 0.001) were significantly higher in patients developing AKI-TAVR.Patients who developed AKI-TAVR had higher mid‑calcium (6.9 ± 3.8% vs. 4.2 ± 3.5%,p < 0.001) and 1 K-plaque (5.4 ± 3.7% vs. 2.4 ± 2.4%,p < 0.001) with no difference in AV-CS (p = 0.691).Adjusted multivariable logistic regression analysis showed that %SR-AAB [OR (x%increase): 1.12, 95%CI: 1.04–1.22,p = 0.006] and %SR-calcified plaque [OR (x%increase): 5.60, 95%CI: 2.50–13.36,p < 0.001] were associated with AKI-TAVR. Finally, 3-knots spline analyses identified %SR-AAB >15.0% and %SR-calcified plaque >7.0% as optimal thresholds to predict an increased risk of AKI-TAVR. ConclusionsSuprarenal aortic atheroma, when highly calcified, is associated with AKI-TAVR. Perioperative-MSCT assessment of aortic atherosclerosis may help in identification of patients at high-risk for AKI-TAVR, who could benefit from higher peri-operative surveillance.

Postoperative stroke assessment inconsistencies in cardiac surgery: Contributors to higher stroke-related mortality?

ObjectivesIn-hospital stroke mortality is surprisingly much worse than for strokes occurring outside of the hospital. Cardiac surgery patients are amongst the highest risk groups for in-hospital stroke and experience high stroke-related mortality. Variability in institutional practices appears to play an important role in the diagnosis, management, and outcome of postoperative stroke. We therefore tested the hypothesis that variability in postoperative stroke management of cardiac surgical patients exists across institutions. Materials and methodsA 13 item survey was employed to determine postoperative stroke practice patterns for cardiac surgical patients across 45 academic institutions. ResultsLess than half (44%) reported any formal clinical effort to preoperatively identify patients at high risk for postoperative stroke. Epiaortic ultrasonography for the detection of aortic atheroma, a proven preventative measure, was routinely practiced in only 16% of institutions. Forty-four percent (44%) reported not knowing whether a validated stroke assessment tool was utilized for the detection of postoperative stroke, and 20% reported that validated tools were not routinely used. All responders, however, confirmed the availability of stroke intervention teams. ConclusionsAdoption of a best practices approach to the management of postoperative stroke is highly variable and may improve outcomes in postoperative stroke after cardiac surgery.