Microvascular injuries, secondary edema, and inconsistencies in lung vascularization between affected and nonaffected pulmonary segments of non-critically ill hospitalized COVID-19 patients presenting with clinical deterioration.

PURPOSE: We aimed to better understand the pathophysiology of SARS-CoV-2 pneumonia in non-critically ill hospitalized patients secondarily presenting with clinical deterioration and increase in oxygen requirement without any identified worsening factors. METHODS: We consecutively enrolled patients without clinical or biological evidence for superinfection, without left ventricular dysfunction and for whom a pulmonary embolism was discarded by computed tomography (CT) pulmonary angiography. We investigated lung ventilation and perfusion (LVP) by LVP scintigraphy, and, 24 h later, left and right ventricular function by Tc-99m-labeled albumin-gated blood-pool scintigraphy with late (60 mn) tomographic albumin images on the lungs to evaluate lung albumin retention that could indicate microvascular injuries with secondary edema. RESULTS: We included 20 patients with confirmed SARS-CoV-2 pneumonia. All had CT evidence of organizing pneumonia and normal left ventricular ejection fraction. No patient demonstrated preserved ventilation with perfusion defect (mismatch), which may discard a distal lung thrombosis. Patterns of ventilation and perfusion were heterogeneous in seven patients (35%) with healthy lung segments presenting a relative paradoxical hypoperfusion and hypoventilation compared with segments with organizing pneumonia presenting a relative enhancement in perfusion and preserved ventilation. Lung albumin retention in area of organizing pneumonia was observed in 12 patients (60%), indicating microvascular injuries, increase in vessel permeability, and secondary edema. CONCLUSION: In hospitalized non-critically ill patients without evidence of superinfection, pulmonary embolism, or cardiac dysfunction, various types of damage may contribute to clinical deterioration including microvascular injuries and secondary edema, inconsistencies in lung segments vascularization suggesting a dysregulation of the balance in perfusion between segments affected by COVID-19 and others. SUMMARY STATEMENT: Microvascular injuries and dysregulation of the balance in perfusion between segments affected by COVID-19 and others are present in non-critically ill patients without other known aggravating factors. KEY RESULTS: In non-critically ill patients without evidence of superinfection, pulmonary embolism, macroscopic distal thrombosis or cardiac dysfunction, various types of damage may contribute to clinical deterioration including 1/ microvascular injuries and secondary edema, 2/ inconsistencies in lung segments vascularization with hypervascularization of consolidated segments contrasting with hypoperfusion of not affected segments, suggesting a dysregulation of the balance in perfusion between segments affected by COVID-19 and others.

Self-Illusion and Medical Expertise in the Era of COVID-19.

The Dunning-Kruger premise assumes that unqualified people are unaware of their limited skills. We tested this hypothesis in the context of the coronavirus disease 2019 (COVID-19) pandemic. In this cross-sectional study, 2487 participants had to self-estimate their knowledge about COVID-19 in a questionnaire on the topic. Poor performers were more likely to use mass media and social networks as sources of information and had lower levels of education. The mean self-assessment (SD) was 6.88 (2.06) and was not linked to actual level of knowledge. This observation should prompt regulatory agencies and media to apply rules that limit dissemination of "infodemics" during global health crises.

COVID-19 pneumonia: relationship between inflammation assessed by whole-body FDG PET/CT and short-term clinical outcome.

PURPOSE: [18F]-2-Fluoro-2-deoxy-D-glucose PET/CT (FDG PET/CT) is a sensitive and quantitative technic for detecting inflammatory process. Glucose uptake is correlated with an increased anaerobic glycolysis seen in activated inflammatory cells such as monocytes, lymphocytes, and granulocytes. The aim of the study was to assess the inflammatory status at the presumed peak of the inflammatory phase in non-critically ill patients requiring admission for COVID-19. METHODS: Patients admitted with COVID-19 were prospectively enrolled. FDG PET/CT was performed from day 6 to day 14 of the onset of symptoms. Depending on FDG PET/CT findings, patients' profiles were classified as "inflammatory" or "low inflammatory." FDG PET/CT data were compared with chest CT evolution and short-term clinical outcome. All inflammatory sites were reported to screen potential extra-pulmonary tropism. RESULTS: Thirteen patients were included. Maximum standardized uptake values ranged from 4.7 to 16.3 in lungs. All patients demonstrated increased mediastinal lymph nodes glucose uptake. Three patients (23%) presented mild nasopharyngeal, two patients (15%) bone marrow, and five patients (38%) splenic mild increase in glucose uptake. No patient had significant digestive focal or segmental glucose uptake. There was no significant physiological myocardial glucose uptake in all patients except one. There was no correlation between PET lung inflammatory status and chest CT evolution or short-term clinical outcome. CONCLUSION: Inflammatory process at the presumed peak of the inflammatory phase in COVID-19 patients is obvious in FDG PET/CT scans. Glucose uptake is heterogeneous and typically focused on lungs. TRIAL REGISTRATION: NCT04441489. Registered 22 June 2020 (retrospectively registered).

Deformable Surface Model for the Evaluation of Abdominal Aortic Aneurysms Treated with an Endovascular Sealing System.

Rupture of abdominal aortic aneurysms (AAA) is responsible for 1-3% of all deaths among the elderly population in developed countries. A novel endograft proposes an endovascular aneurysm sealing (EVAS) system that isolates the aneurysm wall from blood flow using a polymer-filled endobag that surrounds two balloon-expandable stents. The volume of injected polymer is determined by monitoring the endobag pressure but the final AAA expansion remains unknown. We conceived and developed a fully deformable surface model for the comparison of pre-operative sac lumen size and final endobag size (measured using a follow-up scan) with the volume of injected polymer. Computed tomography images were acquired for eight patients. Aneurysms were manually and automatically segmented twice by the same observer. The injected polymer volume resulted 9% higher than the aneurysm pre-operative lumen size (p < 0.05), and 11% lower than the final follow-up endobag volume (p < 0.01). The automated method required minimal user interaction; it was fast and used a single set of parameters for all subjects. Intra-observer and manual vs. automated variability of measured volumes were 0.35 ± 2.11 and 0.07 ± 3.04 mL, respectively. Deformable surface models were used to quantify AAA size and showed that EVAS system devices tended to expand the sac lumen size.

Calcifications of the thoracic aorta on extended non-contrast-enhanced cardiac CT.

BACKGROUND: The presence of calcified atherosclerosis in different vascular beds has been associated with a higher risk of mortality. Thoracic aorta calcium (TAC) can be assessed from computed tomography (CT) scans, originally aimed at coronary artery calcium (CAC) assessment. CAC screening improves cardiovascular risk prediction, beyond standard risk assessment, whereas TAC performance remains controversial. However, the curvilinear portion of the thoracic aorta (TA), that includes the aortic arch, is systematically excluded from TAC analysis. We investigated the prevalence and spatial distribution of TAC all along the TA, to see how those segments that remain invisible in standard TA evaluation were affected. METHODS AND RESULTS: A total of 970 patients (77% men) underwent extended non-contrast cardiac CT scans including the aortic arch. An automated algorithm was designed to extract the vessel centerline and to estimate the vessel diameter in perpendicular planes. Then, calcifications were quantified using the Agatston score and associated with the corresponding thoracic aorta segment. The aortic arch and the proximal descending aorta, "invisible" in routine CAC screening, appeared as two vulnerable sites concentrating 60% of almost 11000 calcifications. The aortic arch was the most affected segment per cm length. Using the extended measurement method, TAC prevalence doubled from 31% to 64%, meaning that 52% of patients would escape detection with a standard scan. In a stratified analysis for CAC and/or TAC assessment, 111 subjects (46% women) were exclusively identified with the enlarged scan. CONCLUSIONS: Calcium screening in the TA revealed that the aortic arch and the proximal descending aorta, hidden in standard TA evaluations, concentrated most of the calcifications. Middle-aged women were more prone to have calcifications in those hidden portions and became candidates for reclassification.

Factors associated with major cardiovascular events in patients with systemic necrotizing vasculitides: results of a longterm followup study.

OBJECTIVE: Systemic necrotizing vasculitides (SNV) are associated with more frequent subclinical atherosclerosis, suggesting that SNV might be associated with a higher risk of major cardiovascular events (MCVE). We aimed to identify factors predictive of MCVE in patients with SNV. METHODS: Patients in remission from SNV were assessed for CV risk factors and subclinical atherosclerosis. MCVE was defined as myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, and/or death from CV causes. MCVE-free survival curves were compared using the log-rank test. RESULTS: Forty-two patients were followed for 7.1±2.6 years. Eight patients (18.9%) had MCVE. The respective 5- and 10-year MCVE rates were 9.5% and 26.8%. National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III)-defined high-risk status [hazard ratio (HR) 5.02 (95% CI: 1.17-27.4), p=0.03], BMI>30 kg/m2 [HR 4.84 (95% CI: 1.46-116), p=0.02], and plaque detection in the abdominal aorta (p=0.01) were significantly associated with MCVE. SNV characteristics, corticosteroid maintenance therapy, and C-reactive protein>5 mg/l were not associated with MCVE. Plaque in the aorta was significantly associated with high-risk status (p<0.001), while BMI and high-risk status were independent variables. Thus, a BMI>30 kg/m2 and/or a high-risk status were strongly associated with MCVE (p=0.004). Carotid intima-media thickness (IMT) identified patients with early MCVE and was correlated with the time to MCVE (r2=0.68, p=0.01). CONCLUSION: These results suggest that factors associated with a higher MCVE risk in patients with SNV are NCEP/ATP III-defined high-risk status and BMI>30 kg/m2. Carotid IMT could help identify patients with SNV at risk of early MCVE.

Identifying the principal modes of variation in human thoracic aorta morphology.

PURPOSE: Diagnosis and management of thoracic aorta (TA) disease demand the assessment of accurate quantitative information of the aortic anatomy. We investigated the principal modes of variation in aortic 3-dimensional geometry paying particular attention to the curvilinear portion. MATERIALS AND METHODS: Images were obtained from extended noncontrast multislice computed tomography scans, originally intended for coronary calcium assessment. The ascending, arch, and descending aortas of 500 asymptomatic patients (57 ± 9 y, 81% male) were segmented using a semiautomated algorithm that sequentially inscribed circles inside the vessel cross-section. Axial planes were used for the descending aorta, whereas oblique reconstructions through a toroid path were required for the arch. Vessel centerline coordinates and the corresponding diameter values were obtained. Twelve size and shape geometric parameters were calculated to perform a principal component analysis. RESULTS: Statistics revealed that the geometric variability of the TA was successfully explained using 3 factors that account for ∼80% of total variability. Averaged aortas were reconstructed varying each factor in 5 intervals. Analyzing the parameter loadings for each principal component, the dominant contributors were interpreted as vessel size (46%), arch unfolding (22%), and arch symmetry (12%). Variables such as age, body size, and risk factors did not substantially modify the correlation coefficients, although some particular differences were observed with sex. CONCLUSIONS: We conclude that vessel size, arch unfolding, and symmetry form the basis for characterizing the variability of TA morphology. The numerical data provided in this study as supplementary material can be exploited to accurately reconstruct the curvilinear shape of normal TAs.

Shear stress regulates endothelial microparticle release.

RATIONALE: Endothelial activation and apoptosis release membrane-shed microparticles (EMP) that emerge as important biological effectors. OBJECTIVE: Because laminar shear stress (SS) is a major physiological regulator of endothelial survival, we tested the hypothesis that SS regulates EMP release. METHODS AND RESULTS: EMP levels were quantified by flow cytometry in medium of endothelial cells subjected to low or high SS (2 and 20 dyne/cm(2)). EMP levels augmented with time in low SS conditions compared with high SS conditions. This effect was sensitive to extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and Rho kinases inhibitors but unaffected by caspase inhibitors. Low SS-stimulated EMP release was associated with increased endothelial Rho kinases and ERK1/2 activities and cytoskeletal reorganization. Overexpression of constitutively active RhoA stimulated EMP release under high SS. We also examined the effect of nitric oxide (NO) in mediating SS effects. L-NG-nitroarginine methyl ester (L-NAME), but not D-NG-nitroarginine methyl ester, increased high SS-induced EMP levels by 3-fold, whereas the NO donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP) decreased it. L-NAME and SNAP did not affect Rho kinases and ERK1/2 activities. Then, we investigated NO effect on membrane remodeling because microparticle release is abolished in ABCA1-deficient cells. ABCA1 expression, which was greater under low SS than under high SS, was augmented by L-NAME under high SS and decreased by SNAP under low SS conditions. CONCLUSIONS: Altogether, these results demonstrate that sustained atheroprone low SS stimulates EMP release through activation of Rho kinases and ERK1/2 pathways, whereas atheroprotective high SS limits EMP release in a NO-dependent regulation of ABCA1 expression and of cytoskeletal reorganization. These findings, therefore, identify endothelial SS as a physiological regulator of microparticle release.

Carotid circumferential wall stress homeostasis in early remodeling: theoretical approach and clinical application.

PURPOSE: To assess the influence of cardiovascular risk factors on arterial wall growth and the remodeling process. METHODS: In a theoretical part, we used a well-established relationship linking the rate of thickening of the arterial wall to the circumferential wall stress (CWS) increase. In a clinical part, we measured the intima-media thickness (IMT) in 166 subjects with increased cardiovascular risk score but no treatment for hypertension or hypercholesterolemia, no diabetes, and no cardiovascular disease. Far wall IMT and lumen diameter were measured along the right carotid artery by high-resolution ultrasonography and computerized image analysis. RESULTS: A decreasing linear relationship between IMT and CWS was deduced from the theoretical model, implying that an increase in CWS would result in an IMT increase, and that the higher the IMT-CWS slope, the higher the thickening response. Subjects with advanced age, renal insufficiency, high 10-year Framingham risk, carotid atherosclerosis, and advanced atherosclerosis at other sites had sharper IMT-CWS slope (p < 0.05), in agreement with the homeostasis of CWS hypothesis. CONCLUSIONS: The IMT increase responding to a CWS increase was greater in high-risk patients.

[Cardiovascular risk as assessed by traditional risk factors]. / Diagnostic du risque cardiovasculaire par les facteurs de risque traditionnels.

Although traditional cardiovascular risk factors play a proven aetiologic role in atherosclerosis-related cardiovascular disease, they fail to predict the occurrence of future clinical events, and, taken separately, they provide useful therapeutic target rather than diagnostic tools. Apart from the situation of severe monorisk, more frequent is the presentation of one individual with numerous moderate risk factors, the resulting global risk of whom being estimated by risk scores, such as the Framingham risk score or its derivatives. These models suffer various limitations, including the lack of applicability depending on geographic zones, and the lack of discrimination in the intermediate risk category, as compared to a better predictive value in the low risk and high risk categories. This lack is partially overcome by models that include complementary risk factors, requiring the need for other tools of reclassification, including the detection of subclinical atherosclerosis.

[New biomarkers for cardiovascular risk evaluation]. / Nouveaux biomarqueurs d'évaluation du risque cardiovasculaire.

Biomarkers aim at refining risk prediction and at better identifying individuals at high cardiovascular risk. To be recommended in clinical practice, a novel biomarker should be simple to measure, non-invasive, cost-effective, reproducible, and should provide a predictive and discriminative value independently of, and beyond existing risk scores. In addition, it should offer a favourable impact on morbidity, mortality and disability of the disease. Among the hundreds of candidate circulating biomarkers, certain have shown solid statistical associations with the incidence of future events, as is the case for high-sensitivity C-reactive protein. However, contrary to subclinical atherosclerosis assessment, they offer only a modest increase in the predictive value of current scores. To date, the main interest of cardiovascular biomarkers in primary prevention is to better understand pathophysiological mechanisms of atherosclerosis in the research setting.

Aging impact on thoracic aorta 3D morphometry in intermediate-risk subjects: looking beyond coronary arteries with non-contrast cardiac CT.

An increasing number of intermediate risk asymptomatic subjects benefit from measures of atherosclerosis burden like coronary artery calcification studies with non-contrast heart computed tomography (CT). However, additional information can be derived from these studies, looking beyond the coronary arteries and without exposing the patients to further radiation. We report a semi-automatic method that objectively assesses ascending, arch and descending aorta dimension and shape from non-contrast CT datasets to investigate the effect of aging on thoracic aorta geometry. First, the segmentation process identifies the vessel centerline coordinates following a toroidal path for the curvilinear portion and axial planes for descending aorta. Then, reconstructing oblique planes orthogonal to the centerline direction, it iteratively fits circles inside the vessel cross-section. Finally, regional thoracic aorta dimensions (diameter, volume and length) and shape (vessel curvature and tortuosity) are calculated. A population of 200 normotensive men was recruited. Length, mean diameter and volume differed by 1.2 cm, 0.13 cm and 21 cm(3) per decade of life, respectively. Aortic shape uncoiled with aging, reducing its tortuosity and increasing its radius of curvature. The arch was the most affected segment. In conclusion, non-contrast cardiac CT imaging can be successfully employed to assess thoracic aorta 3D morphometry.

Effects of aging on thoracic aorta size and shape: a non-contrast CT study.

Measures of atherosclerosis burden like coronary artery calcification are performed using non-contrast heart CT. However, additional information can be derived from these studies, looking beyond the coronary arteries without exposing the patients to further radiation. We present a semi-automated method to assess ascending, arch and descending aorta geometry from non-contrast CT datasets in 250 normotensive patients. We investigated the effect of aging on thoracic aorta morphometry. The algorithm identifies the aortic centerline coordinates following a toroidal path for the curvilinear portion and axial planes for descending aorta. Then it reconstructs oblique planes orthogonal to the centerline direction and a circle fitting process estimates the vessel cross-section. Finally, global thoracic aorta dimensions (diameter, volume and length) and shape (vessel curvature and tortuosity, aortic arch width and height) are calculated. From a multivariate analysis, adjusted for gender and body-size area, aortic volume and arch width were the descriptors that better represented the aortic size and shape alterations with aging. The thoracic aorta suffers an expanding and unfolding process with aging that deserves further attention to prevent aortic aneurisms.

Microparticles, vascular function, and atherothrombosis.

Membrane-shed submicron microparticles (MPs) are released after cell activation or apoptosis. High levels of MPs circulate in the blood of patients with atherothrombotic diseases, where they could serve as a useful biomarker of vascular injury and a potential predictor of cardiovascular mortality and major adverse cardiovascular events. Atherosclerotic lesions also accumulate large numbers of MPs of leukocyte, smooth muscle cell, endothelial, and erythrocyte origin. A large body of evidence supports the role of MPs at different steps of atherosclerosis development, progression, and complications. Circulating MPs impair the atheroprotective function of the vascular endothelium, at least partly, by decreased nitric oxide synthesis. Plaque MPs favor local inflammation by augmenting the expression of adhesion molecule, such as intercellular adhesion molecule -1 at the surface of endothelial cell, and monocyte recruitment within the lesion. In addition, plaque MPs stimulate angiogenesis, a key event in the transition from stable to unstable lesions. MPs also may promote local cell apoptosis, leading to the release and accumulation of new MPs, and thus creating a vicious circle. Furthermore, highly thrombogenic plaque MPs could increase thrombus formation at the time of rupture, together with circulating MPs released in this context by activated platelets and leukocytes. Finally, MPs also could participate in repairing the consequences of arterial occlusion and tissue ischemia by promoting postischemic neovascularization.

Impact of coronary artery calcium on cardiovascular risk categorization and lipid-lowering drug eligibility in asymptomatic hypercholesterolemic men.

BACKGROUND: Application of coronary artery calcium (CAC) for stratifying coronary heart disease (CHD) risk may change the proportion of subjects eligible for risk reduction treatment and decrease cost-effectiveness of primary prevention. We therefore aimed to analyze the impact of CAC on CHD risk categorization. METHODS: We measured CAC with electron beam computed tomography in 500 asymptomatic untreated hypercholesterolemic men and re-calibrated 10-year Framingham CHD risk by adding CAC score information (post CAC test risk) via an algorithm integrating relative risk and expected distribution of CAC in the population tested. Proportions of low (<10%), intermediate (10-20%) and high (>20%) risk categories, and of eligibility for lipid-lowering treatment, were compared between Framingham risk and post CAC test risk. RESULTS: In the overall population, post CAC test risk calculation changed risk categorization defined by Framingham assessment alone, with 10% more low risk and 10% less intermediate risk (p<0.01). Risk reclassifications were bidirectional since 30% of high and 30% of intermediate Framingham risk were downgraded to intermediate and low risk categories respectively, while 11% of low and 14% of intermediate Framingham risk were upgraded to intermediate and high-risk categories respectively. Post CAC test risk did not change the proportion of Framingham-based lipid-lowering treatment eligibility in the overall population but decreased it by 8% in intermediate Framingham risk subgroup (p<0.05). CONCLUSIONS: Addition of CAC to risk prediction resulted rather in downgrading than in upgrading risk and did not change treatment eligibility, except in intermediate risk subjects, less frequently eligible for treatment.

Early thoracic aorta enlargement in asymptomatic individuals at risk for cardiovascular disease: determinant factors and clinical implication.

OBJECTIVES: We analyzed, in above-average risk asymptomatic individuals, the factors determining early thoracic aorta enlargement. METHODS: Ascending aortic diameter (AAD) was measured with noncontrast multidetector computed tomography in 345 participants (mean age 56 years; 78% men) without cardiovascular disease. We analyzed the associations of AAD with risk factors and Framingham risk score (FRS), multidetector computed tomography-assessed coronary artery calcium (CAC), and ultrasound interrogation of plaque presence at five sites (right and left carotid arteries, right and left femoral arteries, and abdominal aorta), the number of diseased sites with presence of plaque being counted from 0 to 5. RESULTS: AAD was positively associated with age (P < 0.001), male sex (P < 0.01), body surface area (BSA; P < 0.001), hypertension (P < 0.001), systolic and diastolic blood pressures in individuals without antihypertensive medication (P < 0.05, P < 0.01), and FRS (P < 0.001). AAD was positively associated with CAC score after adjusting for age, sex, and BSA (P < 0001) or for FRS and BSA (P < 0.001). AAD was higher in the presence of three, four, or five than in the presence of no, one, or two diseased sites with plaque, after adjusting for age, sex, and BSA (P < 0.05) or for FRS and BSA (P < 0.001). When participants were divided into subsets by AAD tertiles and by number of sites with plaque, FRS and CAC score were greatest in individuals with AAD top tertile and 3-5 sites with plaque and lowest in those with AAD bottom tertile and 0-2 sites with plaque (P < 0.001). CONCLUSION: These findings suggest that thoracic ascending aorta dilatation is related to hypertension and represents a part of a generalized atherosclerotic process of the entire vasculature.