Low Wall Shear Stress Research Articles

Sensitivity of coronary hemodynamics to vascular structure variations in health and disease

Local hemodynamics play an essential role in the initiation and progression of coronary artery disease. While vascular geometry alters local hemodynamics, the relationship between vascular structure and hemodynamics is poorly understood. Previous computational fluid dynamics (CFD) studies have explored how anatomy influences plaque-promoting hemodynamics. For example, areas exposed to low wall shear stress (ALWSS) can indicate regions of plaque growth. However, small sample sizes, idealized geometries, and simplified boundary conditions have limited their scope. We generated 230 synthetic models of left coronary arteries and simulated coronary hemodynamics with physiologically realistic boundary conditions. We measured the sensitivity of hemodynamic metrics to changes in bifurcation angles, positions, diameter ratios, tortuosity, and plaque topology. Our results suggest that the diameter ratio between left coronary branches plays a substantial role in generating adverse hemodynamic phenotypes and can amplify the effect of other geometric features such as bifurcation position and angle, and vessel tortuosity. Introducing mild plaque in the models did not change correlations between structure and hemodynamics. However, certain vascular structures can induce ALWSS at the trailing edge of the plaque. Our analysis demonstrates that coronary artery vascular structure can provide key insight into the hemodynamic environments conducive to plaque formation and growth.

Characteristics of transition to turbulence in a healthy thoracic aorta using large eddy simulation

This study employed large eddy simulation (LES) with the wall-adapting local eddy-viscosity (WALE) model to investigate transitional flow characteristics in an idealized model of a healthy thoracic aorta. The OpenFOAM solver pimpleFoam was used to simulate blood flow as an incompressible Newtonian fluid, with the aortic walls treated as rigid boundaries. Simulations were conducted for 30 cardiac cycles and ensemble averaging was employed to ensure statistically reliable results. Main hemodynamic parameters, such as velocity fields, turbulence intensity turbulent kinetic energy (TKE), oscillatory shear index (OSI) and wall shear stress (WSS), were analyzed throughout the circulatory system. Through 3D computational fluid dynamics (CFD) visualization, we explained the transition from laminar to turbulent flow and its development throughout the cardiac cycle. The results demonstrated that turbulence originates in the aortic arch following the peak systole phase and further develops in the aortic arch and descending aorta during the mid-deceleration and end-systole phases, with the maximum turbulence intensity exceeding 25%. WSS reached up to 30 Pa during the peak systole, with an average WSS of 6.5 Pa across the cardiac cycle. Low and oscillatory WSS were observed during diastole which can potentially contribute to the development of vascular diseases including, aortic dissection and atherosclerosis.

Differences in Pulmonary Artery Flow Hemodynamics Between PAH and PH-HFpEF: Insights From 4D-Flow CMR.

Pulmonary artery (PA) flow analysis is crucial for understanding the progression of pulmonary hypertension (PH). We hypothesized that PA flow characteristics vary according to PH etiology. In this study, we used 4D flow cardiovascular magnetic resonance imaging (CMR) to compare PA flow velocity and wall shear stress (WSS) between patients with pulmonary arterial hypertension (PAH) and those with heart failure with preserved ejection fraction and pulmonary hypertension (PH-HFpEF). We enrolled 13 PAH and 15 PH-HFpEF patients. All participants underwent echocardiography, 4D flow CMR, and right heart catheterization. We compared right ventricular outflow tract (RVOT) flow and main pulmonary artery (MPA) hemodynamics, including peak velocity and mean and maximum WSS, between groups. PH-HFpEF patients were older and more likely to have hypertension. PAH patients had higher mean PA pressure (47.8 ± 8.8 vs. 32.9 ± 6.9 mmHg, p < 0.001) and pulmonary vascular resistance (PVR) (8.6 ± 4.6 vs. 2.6 ± 2.2 wood unit, p < 0.001). RVOT systolic notching was more common in PAH patients (8 of 13 vs. 0 of 15), and they had shorter RVOT acceleration time (85.5 ± 20.9 vs. 135.0 ± 21.7 ms, p < 0.001). PAH patients had lower MPA Vmax (0.8 ± 0.2 vs. 1.1 ± 0.4 m/s, p = 0.032), mean WSS (0.29 ± 0.09 vs. 0.36 ± 0.06 Pa, p = 0.035), and maximal WSS (0.99 ± 0.18 vs. 1.21 ± 0.19 Pa, p = 0.011). Anterior MPA analysis confirmed lower WSS in PAH patients. PVR was negatively correlated with MPA mean WSS (r = -0.630, p = 0.002). PAH patients had lower MPA Vmax and lower mean MPA WSS in 4D flow CMR compared to PH-HFpEF patients. These distinct PA flow characteristics suggest that the flow hemodynamics of the PA remodeling process differ depending on the underlying etiology of PH.

Endothelial cell (EC)-specific CTGF/CCN2 Expression Increases EC Reprogramming and Atherosclerosis.

Arterial endothelial cells (ECs) reside in a complex biomechanical environment. ECs sense and respond to wall shear stress. Low and oscillatory wall shear stress is characteristic of disturbed flow and commonly found at arterial bifurcations and around atherosclerotic plaques. Disturbed flow is pro-inflammatory to ECs. Arteries also stiffen with aging and/or the onset of vascular disease. ECs sense and respond to stiffening in a pro-fibrotic manner. Thus, flow and stiffening disturbances elicit EC responses that promote pathologic arterial remodeling. However, the pathways elicited by ECs under pathologic stiffening and disturbed flow are not well understood. The objective of this work was to discover and test the modifiability of key pathways in ECs. To do this we used the partial carotid ligation model to impose disturbed flow onto the precociously stiffened fibulin-5 knockout (Fbln5-/-) mouse carotid arteries. Biomechanical testing demonstrated that Fbln5-/- arteries under disturbed flow approximate the stiffness ratio of diseased human arteries, and the ECs in these Fbln5-/- arteries underwent rapid reprogramming via endothelial to mesenchymal transition (EndMT). Under atherogenic conditions, disturbed flow Fbln5-/- arteries developed more vulnerable plaques than the wild type (WT) mouse arteries. Connective tissue growth factor/cellular communication network factor 2 (Ctgf/Ccn2) was upregulated in vivo in ECs with aging, with stiffening in the Fbln5-/- arteries, and increased again by disturbed flow under stiffened conditions, supporting CTGF as a key biomarker for flow and stiffening. This was validated by immunohistochemistry, which demonstrated increased CTGF deposition in areas of disturbed flow in patient carotid endarterectomy and peripheral artery disease (PAD) specimens. Finally, to test the role of CTGF in regulating and combining these processes, we created an EC-specific Ctgf knockout (Ctgfecko). We identified that carotid arteries under disturbed flow and atherogenic conditions in male Ctgfecko, but not female, mice had decreased plaque area compared to WT control mice. We then tested the Ctgf expression in the carotid endothelium exposed to disturbed or stable flow in WT and Fbln5-/- mice. Here we found that under disturbed flow male mice had greater Ctgf expression than female mice. This work demonstrates that stiffened + disturbed flow conditions drive EC reprogramming, that CTGF is increased by these conditions, and that this increase is more prominent in male carotid arteries. Future exploration of sex-based differences in these fibrotic pathways are warranted to develop targeted therapeutics to limit pathologic arterial remodeling under pathologically stiffened + disturbed flow environments.

Rupture prediction of medium to large-sized abdominal aortic aneurysm combining wall shear stress-related parameters and anatomical characteristics: A computational, experimental, and statistical analysis

A diameter of 50 or 55 mm is the primary clinical criterion for assessing abdominal aortic aneurysm (AAA) rupture risk. However, although larger diameters may induce higher rupture risk, not all AAAs exceeding intervention threshold will rupture, highlighting the need for indicators besides diameter to help rupture prediction and treatment of AAA ≥ 50 mm. The study aims to combine computation, experiment, and statistics to establish rupture prediction models for AAAs ≥ 50 mm and explore the optimal predictors of AAA rupture with different diameters by anatomical and hemodynamic characteristics. Through numerical simulation and in vitro experiment, morphological and hemodynamic parameters were obtained from 82 AAAs (41 ruptured) ≥ 50 mm. The results of significance test and logistic regression indicate that low time-averaged wall shear stress (TAWSS) of AAA and maximum diameter of common iliac artery, and high oscillatory shear index (OSI) of AAA, TAWSS of iliac artery and tortuosity of abdominal aorta increase rupture risk of AAA ≥ 50 mm. The prediction model combining these variables was established with high accuracy (area under curve = 0.978). Furthermore, univariable analyses for AAAs of different diameters imply the OSI is a risk factor for AAA rupture of 50–65 mm, while higher TAWSS decreases the risk of AAA rupture of 65–80 and ≥ 80 mm. The findings may contribute to accurate rupture prediction and personalized management of AAAs ≥ 50 mm and with different diameters, and further demonstrate potential value and application prospects of combining morphology and hemodynamics in clinical practice.

Impact of Vein Wall Hyperelasticity and Blood Flow Turbulence on Hemodynamic Parameters in the Inferior Vena Cava with a Filter.

Inferior vena cava (IVC) filters are vital in preventing pulmonary embolism (PE) by trapping large blood clots, especially in patients unsuitable for anticoagulation. In this study, the accuracy of two common simplifying assumptions in numerical studies of IVC filters-the rigid wall assumption and the laminar flow model-is examined, contrasting them with more realistic hyperelastic wall and turbulent flow models. Using fluid-structure interaction (FSI) and computational fluid dynamics (CFD) techniques, the investigation focuses on three hemodynamic parameters: time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), and relative residence time (RRT). Simulations are conducted with varying sizes of clots captured in the filter. The findings show that, in regions of high wall shear stress, the rigid wall model predicted higher TAWSS values, suggesting an increased disease risk compared to the hyperelastic model. However, the laminar and turbulent flow models did not show significant differences in TAWSS predictions. Conversely, in areas of low wall shear stress, the rigid wall model indicated lower OSI and RRT, hinting at a reduced risk compared to the hyperelastic model, with this discrepancy being more evident with larger clots. While the predictions for OSI and TAWSS were closely aligned for both laminar and turbulent flows, divergences in RRT predictions became apparent, especially in scenarios with very large clots.

Near-Wall Slow Flow Contributes to Wall Enhancement of Middle Cerebral Artery Bifurcation Aneurysms on Vessel Wall MRI.

Background: The mechanism of aneurysm wall enhancement (AWE) in middle cerebral artery (MCA) bifurcation aneurysms on vessel wall magnetic resonance imaging (VW-MRI) remains unclear. We aimed to explore the morphologically related hemodynamic mechanism for the AWE of MCA bifurcation aneurysms. Methods: Patients with unruptured MCA bifurcation aneurysms undergoing VW-MRI were enrolled. Logistic regression analyses were performed to determine the risk factors for AWE. Based on the results of retrospective analyses, bifurcation aneurysm silicone models with a specific aspect ratio (AR) were designed and underwent VW-MRI with different inlet velocities. Computational fluid dynamics (CFD) analyses were conducted on both silicone models and patients' aneurysms. Results: A total of 104 aneurysms in 95 patients (mean age 60; 34 males) were included for baseline analysis and morphological analysis. Logistic regression analysis indicated AR (OR, 5.92; 95% CI, 2.00-17.55; p = 0.001) was associated with AWE. In the high-AR group of 45 aneurysms with AWE, the aneurysm sac exhibited lower blood flow velocity, lower wall shear stress, a larger proportion of low-flow regions and higher wall enhancement values. In total, 15 silicone models were analyzed, divided into three subgroups based on neck width (4 mm, 6 mm, and 8 mm). Each subgroup contained aneurysms with five different ARs: 1.0, 1.25, 1.5, 1.75, and 2.0. In silicone models, contrast enhancement (CE) was mainly located beneath the dome of the aneurysm wall. With the same inlet velocity, CE gradually increased as the AR increased. Similarly, at the same AR, CE increased as the inlet velocity decreased. CFD demonstrated a moderate positive correlation between the near-wall enhancement index and the ratio of the low-velocity area (r = 0.6672, p < 0.001). Conclusions: The AR is associated with the AWE of MCA bifurcation aneurysms. A high AR may promote wall enhancement by causing near-wall slow flow.

Zebrafish model for functional screening of flow-responsive genes controlling endothelial cell proliferation

Local haemodynamics control arterial homeostasis and dysfunction by generating wall shear stress (WSS) which regulates endothelial cell (EC) physiology. Here we use a zebrafish model to identify genes that regulate EC proliferation in response to flow. Suppression of blood flow in zebrafish embryos (by targeting cardiac troponin) reduced EC proliferation in the intersegmental vessels (ISVs) compared to controls exposed to flow. The expression of candidate regulators of proliferation was analysed in EC isolated from zebrafish embryos by qRT-PCR. Genes shown to be expressed in EC were analysed for the ability to regulate proliferation in zebrafish vasculature exposed to flow or no-flow conditions using a knockdown approach. wnk1 negatively regulated proliferation in no-flow conditions, whereas fzd5, gsk3β, trpm7 and bmp2a promoted proliferation in EC exposed to flow. Immunofluorescent staining of mammalian arteries revealed that WNK1 is expressed at sites of low WSS in the murine aorta, and in EC overlying human atherosclerotic plaques. We conclude that WNK1 is expressed in EC at sites of low WSS and in diseased arteries and may influence vascular homeostasis by reducing EC proliferation.

Hemodynamic relationship with angioarchitecture of cerebral arteriovenous malformation and changes after embolization: a pilot study by 4D flow MR.

The hemodynamics of cerebral arteriovenous malformation (cAVM) is difficult to evaluate with conventional imaging or clinical grading. The aim of this study is to: (I) investigate the association between the angioarchitecture and hemodynamic parameters in cAVM based on 4-dimentional flow magnetic resonance (4D flow MR); (II) quantify flow changes during follow-up after embolization and explore the potential of flow-guided staged embolization. Twenty-one patients with digital subtraction angiography (DSA)-diagnosed cAVM were prospectively enrolled in a tertiary hospital consecutively from April 2022 to January 2024 for a cohort study. Lesion angioarchitecture at baseline was assessed by DSA. 4D flow MR was performed to assess hemodynamics. Flow-derived parameters included velocity, flow, time averaged wall shear stress (WSS) of the main feeding artery, and inflow-to-outflow ratio. Hemodynamic metrics were compared between groups with different angioarchitecture and rupture status. Seven patients had a post embolization follow-up 4D flow MR scan with a median interval of 8.9 months. Among multiple angioarchitectural features, supply by a single feeding artery (6/7 in the ruptured group and 0/14 in the unruptured group, P<0.001) and intra nidal aneurysm (7/7 in the ruptured group and 5/14 in the unruptured group, P=0.007) were significantly associated with lesion rupture. The ruptured cAVM showed lower total flow of feeding arteries (2.09±3.15 vs. 6.05±3.76 mL/s, P=0.029), lower WSS (0.99±0.73 vs. 2.10±0.45 Pa, P=0.023) and higher inflow-to-outflow ratio (2.46±0.79 vs. 1.46±0.55, P=0.041). During follow-up, the total flow of the lesions decreased by 10-100% after the embolization. The nidus volume decreased significantly (reduction rate: 59.6-100%, P=0.009). The flow of the minor feeding artery increased in 2 cases out of 5, indicating flow remodeling. Three patients had a second embolization guided by the follow-up imaging. cAVM lesions tend to have heterogeneous hemodynamics even with similar angioarchitecture. This could be captured and quantified on an individual basis using 4D flow MR. Flow analysis by MR offers the potential to guide a second embolization.

Comparison of stable carotid plaques in patients with mild-to-moderate carotid stenosis with vulnerable plaques in patients with significant carotid stenosis.

To compare the characteristics of stable and vulnerable carotid plaques, and investigate the diagnostic performance of wall shear stress (WSS) based on magnetic resonance plaque imaging in carotid plaques. Retrospectively analyzed and divided 64 atherosclerotic plaques into stable carotid plaque groups with mild-to-moderate stenosis and vulnerable carotid plaque groups with significant stenosis. Computational fluid dynamics simulations were performed to calculate WSS parameters by using three-dimensional wall geometry based on high-resolution magnetic resonance plaque imaging of carotid bifurcation and patient specific boundary conditions obtained through color Doppler ultrasound. WSS parameters including upstream (WSSup), downstream (WSSdown), and core (WSScore) of plaque. The WSS parameters values were compared between the stable and vulnerable carotid plaque groups. Receiver operating characteristic curves and area under the curve (ROC-AUC) and Python were used to evaluate discriminative efficacy of WSS. WSSdown exhibited significant decrease in the vulnerable carotid plaque group (2.88 ± 0.41 Pa) compared to the stable carotid plaque group (4.47 ± 0.84 Pa) (P = .003). The difference of WSSup (3.28 ± 0.85 Pa vs 4.02 ± 0.74 Pa) and WSScore (1.12 ± 0.18 Pa vs 1.38 ± 0.38 Pa) between the two groups were also pronounced (P = .02, 0.01, respectively). The ROC-AUC values for WSSup, WSSdown, WSScore were 0.75 (95% CI, 0.58-0.93), 0.96 (95% CI, 0.79-1.14), 0.69 (95% CI, 0.56-0.83) respectively. When the value of WSSdown was 3.5 Pa, the sensitivity was 93.7% (95% CI, 76.1-111), specificity and accuracy was 87.5% (95% CI, 70.0-105), 88.4% (95% CI, 70.6-105) respectively. Notably, among these parameters, WSSdown demonstrated the highest discriminative efficiency with a F1 Score of 0.90, Diagnostic Odds Ratio of 105.0 and Matthews Correlation Coefficient of 0.81. Vulnerable carotid plaques with significant stenosis have lower WSS compared to stable plaques with mild-to-moderate stenosis, and downstream WSS showing the highest diagnostic efficacy.

Computational hemodynamic pathophysiology of internal carotid artery blister aneurysms

ObjectiveBlister aneurysms of the internal carotid artery (ICA) are rare and are primarily documented in the literature through small series and case reports. The intraoperative observation of a hemorrhage in the artery wall proximal to the aneurysmal bulge led to the hypothesis that some of these aneurysms might develop in a retrograde manner.MethodsWe developed software to reconstruct the ICA with and without Type I and II blister aneurysms using patients’ imagery as input to simulate hemodynamic conditions before and after their formation. Kinematic blood flow data before and after aneurysm formation were obtained using a finite volume solver. We compared the wall shear stress (WSS) distribution of the arterial wall prior to aneurysm formation.ResultsIn two out of four cases, WSS was significantly elevated on the dorsal wall of the supraclinoid segment of the ICA at the distal part of the future site of the aneurysm sac, suggesting that the aneurysm sac may ultimately develop in a retrograde fashion. Once the structural changes have been initiated, WSS gradient (WSSG) was significantly elevated at the proximal and distal boundaries of the bulging aneurysmal pouch. Low WSS and high WSSG at the proximal part of the aneurysm sac seem to contribute to the extension of the proximal intramural hematoma observed during blister aneurysm surgery.ConclusionsBy enabling assessment of the impact of elevated WSS and its gradient, our computational pipeline supports the hypothesis that the development of blister aneurysms may occur either in a retrograde or anterograde fashion.

In-silico Analysis of In-stent Restenosis Prediction of Stented Renal Artery

In-stent restenosis (ISR) is a common complication after renal artery stenting, and stent design may influence the formation of ISR. This study aims to predict the effect of stent design on the risk of ISR formation after renal artery stenting. Using computer-aided design, a simplified renal artery model was modelled and later assembled with stents similar to commercial stents. Computational Fluid Mechanics (CFD) analysis was employed to simulate the blood flow in these stented models. Stent 1 exhibited superior hemodynamic performance with minimal low Wall Shear Stress (WSS) exposure in the stented region. Additionally, the study found that the thinnest Stent 1 was the most effective in reducing the risk of ISR formation. Thus, stent strut configuration with largespacing may reduce ISR risk, with the thinnest Stent 1 design showed promising performance in mitigating ISR. Hence, it is worth further investigation.

Insights from Computational Fluid Dynamics and In Vitro Studies for Stent Protrusion in Iliac Vein: How Far Shall We Go?

These findings provide significant implications for the enhancement of iliac vein stent implantation strategies and stent design. The prevalent use of stents for treating Iliac Vein Compression Syndrome (IVCS) has shown efficacy, yet the associated clinical adverse events, including stent restenosis and postoperative thrombosis, are significant concerns. Up to now, the mechanism how the stent implantation induces the restenosis and DVT is still unclear. Our study hypothesizes that these adverse outcomes arise from altered blood flow dynamics following stent implantation. Employing computational modeling and medical imaging, we simulated IVCS after various stenting procedures to assess their impact on venous blood flow characteristics, including wall shear stress (WSS), residence time (RRT), and oscillatory shear index (OSI). Our findings reveal that a stent protruding into the vena cava impedes blood circulation, with increased protrusion exacerbating this obstruction. This is particularly evident at the vein bifurcation, where low WSS and elevated OSI and RRT are observed. Moreover, a higher stent strut density further obstructs blood flow, deteriorating the hemodynamic environment. Consequently, stent protrusion into the vena cava can enhance the likelihood of adverse post-surgical events. These insights have profound implications for optimizing iliac vein stent implantation techniques and stent design.

Therapeutic Effect of Targeted Deployment Filling Coils in the Treatment of Intracranial Aneurysms.

Endovascular coil embolization is the primary therapeutic modality for intracranial aneurysms. Substantial reports have been found regarding the coil packing density and inflow jet. However, the hemodynamic effect of increasing the rate of tamponade in the inflow jet area within the aneurysm remains unclear. In this study, individualized geometries of six intracranial aneurysms were recruited: all six aneurysms were located in the internal carotid artery. Two groups were created by changing the position and orientation of the microcatheter for the release of the third segment of the filling coil. The finite element method was used to simulate coil deployment. Computational fluid dynamics was used to characterize hemodynamics in post-deployment aneurysms. The parameters evaluated included velocity reduction, wall shear stress (WSS), low WSS (LWSS), relative residence time (RRT), flow kinetic energy in the neck region of the aneurysms, and residual flow volume (RFV) in the aneurysms. At the peak time (t = 0.17 s), the targeted deployment group has similar proportion of LWSS area to conventional deployment groups: targeted 78.13% ± 34.59% versus normal 74.20% ± 36.94% (mean ± SD, p = 0.583). The targeted deployment group has a higher RRT area (targeted 16.84% ± 5.58% vs. normal 6.42% ± 5.67% [mean ± SD, p = 0.009]), smaller flow kinetic energy (targeted 9.43 ± 4.33 vs. normal 16.23 ± 5.92 [mean ± SD, p = 0.047]), and a larger RFV in the aneurysms (targeted 35.97 ± 24.35 mm3 vs. normal 25.80 ± 18.94 mm3 [mean ± SD, p = 0.44]). Inflow jets play an important role in the treatment of aneurysms, and deploying filling coils in accordance with inflow jets may result in a better hemodynamic environment.

Prognostic significance of pre-procedure wall shear stress in the ascending aorta in patients with aortic stenosis undergoing transcatheter aortic valve replacement

Abstract Background Accurate prognostication before the procedure is challenging in patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). Recently, blood flow dynamics assessed by four-dimensional flow cardiovascular magnetic resonance imaging (4D-flow CMR) showed a significant reduction in average wall shear stress (WSS) in the ascending aorta (AAo) after TAVR. However, the prognostic value of pre-procedure average WSS in the AAo is controversial. Purpose We aimed to investigate whether pre-procedure average WSS was associated with clinical outcomes in patients with AS undergoing TAVR. Methods We prospectively examined 159 consecutive AS patients who underwent TAVR (57 males, mean age 83.6 ± 4.7 years, median left ventricular ejection fraction 63.4%) between May 2018 and May 2022. We assessed average WSS in the AAo before TAVR using 4D-flow CMR. We divided the patients into high WSS (≥6.60 Pa, n = 79) and low WSS (&amp;lt;6.60 Pa, n = 80) groups according to the median value of pre-TAVR WSS. The primary outcome of interest was a composite of all-cause death and hospitalization for worsening heart failure. Results Patients with high WSS had lower age compared to those with low WSS. There were no significant differences on sex, body mass index, systolic blood pressure, hemoglobin, serum albumin, N-terminal pro b-type natriuretic peptide, left ventricular ejection fraction, mean transaortic valvular gradient, annulus area in aortic valve and AAo diameter between the groups. During a median follow-up period of 19.8 months (interquartile range 6.0-37.1), the primary outcome more frequently occurred in patients with low WSS than in those with high WSS (28% vs 5%, P &amp;lt;0.001) (Figure 1). A multivariable Cox regression showed that lower WSS independently associated with increased risk of the primary outcome (hazard ratio 0.69, 95% confidence interval [CI] 0.53-0.91, P &amp;lt;0.001), even after adjustment for significant prognostic covariates including age, sex, serum albumin, history of chronic obstructive pulmonary disease, peripheral artery disease and malignancy, and estimated glomerular filtration rate. Predictive performance for the primary outcome was improved when adding the value of WSS in the AAo to representative prognostic factors (c-index 0.81 95%CI 0.72-0.90 vs. 0.77 95%CI 0.67-0.88) (Figure 2). Conclusions In patients with AS who underwent TAVR, lower average WSS in the AAo before procedure was associated with higher risk of worse clinical outcomes, suggesting that pre-TAVR average WSS in the AAo would be a surrogate marker and useful for the risk stratification.Survival analysis for primary outcomePredictive performance

Relative size matters: Spawning substrate roughness size and spacing affect egg dislodgement and retention in the benthos

AbstractThe consequences of hydrodynamic effects on survival of embryonic benthic organisms remain unknown. This is because the interaction of hydrodynamics and substrate roughness is complex, but it can be conceptualized in two dimensions by roughness flow regimes (isolated, wake interference, and skimming flow) or roughness types (k‐ and d‐type). We examined the effect of different roughness flow regimes/roughness types and roughness heights (k) on the dislodgement of walleye (Sander vitreus) eggs (2 mm diameter, ⌀) using a wall jet apparatus. We expected that lower wall shear stress (τw) would be required for dislodgement in more‐exposed/less‐sheltered roughness type/flow regimes (i.e., k‐type/isolated roughness flow) and when k ≤ ⌀. Surprisingly, the opposite was found, indicating that other mechanism(s) are also responsible for egg dislodgement on these rough surfaces. Hydrodynamic sheltering occurred when flow was directed over exposed eggs (k ≤ ⌀) adjacent to roughness elements effectively increasing their width, and thus requiring higher τw for rolling and then ejection. When k &gt; ⌀, eggs dislodgement likely occurred via the lower pressure in the eddies recirculating in the groove width between roughness elements, rather than due to τw. These results indicate the relevance of heterogeneous sorting and sizing of substrate elements to provide suitable spawning habitats in benthic environments.

Low shear-induced fibrillar fibronectin: comparative analyses of morphologies and cellular effects on bovine aortic endothelial cell adhesion and proliferation

Wall shear stress (WSS) is a critical factor in vascular biology, and both high and low WSS are implicated in atherosclerosis. Fibronectin (FN) is a key extracellular matrix protein that plays an important role in cell activities. Under high shear stress, plasma FN undergoes fibrillogenesis; however, its behavior under low shear stress remains unclear. This study aimed to investigate the formation ofin vitrocell-free fibrillar FN (FFN) under low shear rate conditions and its effect on bovine aortic endothelial cell behavior. FN (500µg ml-1) was perfused through slide chambers at three flow rates (0.16 ml h-1, 0.25 ml h-1, and 0.48 ml h-1), corresponding to low shear rates of 0.35 s-1, 0.55 s-1, and 1.05 s-1, respectively, for 4 h at room temperature. The formed FN matrices were observed using fluorescence microscopy and scanning electron microscopy. Under low shear rates, distinct FN matrix structures were observed. FFN0.48 formed immense fibrils with smooth surfaces, FFN0.25 formed a matrix with a rough surface, and FFN16 exhibited nodular structures. FFN0.25 supported cell activities to a greater extent than native FN and other FFN surfaces. Our study suggests that abnormally low shear conditions impact FN structure and function and enhance the understanding of FN fibrillogenesis in vascular biology, particularly in atherosclerosis.

Exploring the hemodynamic behavior of residual aneurysms after coiling and clipping: A computational flow dynamic analysis.

Residual intracranial aneurysms post-clipping or coiling pose a poorly established risk of rupture. Computational fluid dynamic (CFD) offers insights into hemodynamic changes following such interventions. This study aims to assess hemodynamic parameters in residual aneurysms pre- and post-treatment with surgical clips or coils using CFD. A retrospective analysis of consecutive patients between January 2015 and January 2024 was conducted. Digital subtraction angiography images were reconstructed using 3D modeling techniques, and hemodynamic parameters were analyzed with ANSYS® software. Six aneurysms were analyzed: Five unruptured and one ruptured. The aneurysms were located at the basilar apex (2), middle cerebral artery bifurcation (2), and origin of the posterior communicating artery (2). Post-treatment, there was a significant reduction in both aneurysm area (median reduction of 33.73%) and volume (median reduction of 25.3%). Five of the six cases demonstrated fewer low wall shear stress (WSS) areas, which could indicate a reduction in regions prone to thrombus formation and diminished risk of rupture. In the unruptured aneurysms, there was a median increase of 137.6% in average WSS. Notably, the only case with increased low WSS area also had the highest increase in average WSS. One basilar artery aneurysm showed increased WSS across all parameters, suggesting a higher rupture risk. The increase in average and high WSS area, along with a decrease in low WSS area, reflects a complex balance between factors of stability and rupture risk. However, a simultaneous increase in all WSS parameters may represent the highest rupture risk due to increased mechanical stress on the aneurysm wall, necessitating closer monitoring.

Silent brain ischemia within the TAXINOMISIS framework: association with clinical and advanced ultrasound metrics.

IntroductionThe relationship between carotid artery stenosis (CAS) and ipsilateral silent brain ischemia (SBI) remains unclear, with uncertain therapeutic implications. The present study, part of the TAXINOMISIS project (nr. 755,320), aimed to investigate SBIs in patients with asymptomatic CAS, correlating them with clinical, carotid ultrasonographic data, and CFD analyses.MethodsThe TAXINOMISIS clinical trial study (nr. NCT03495830) involved six vascular surgery centers across Europe, enrolling patients with asymptomatic and symptomatic CAS ranging from 50 to 99%. Patients underwent carotid ultrasound and magnetic resonance imaging (MRI), including brain diffusion-weighted, T2-weighted/FLAIR, and T1-weighted sequences. Brain MRI scans were analyzed for the presence of SBI according to established definitions. Ultrasound assessments included Doppler and CFD analysis. Only asymptomatic patients were included in this substudy.ResultsAmong 195 asymptomatic patients, the mean stenosis (NASCET) was 64.1%. Of these, a total of 33 patients (16.9%) had at least one SBI detected on a brain MRI scan. Specifically, 19 out of 33 patients (57.6%) had cortical infarcts, 4 out of 33 patients (12.1%) had ipsilateral lacunar infarcts, 6 out of 33 patients had (18.2%) subcortical infarcts, 1 out of 33 patients (3.0%) had both cortical and lacunar infarcts, and 3 out of 33 patients (9.1%) both cortical and subcortical infarcts. Patients with SBIs exhibited significantly higher risk factors, including a higher body mass index (28.52 ± 9.38 vs. 26.39 ± 3.35, p = 0.02), diastolic blood pressure (80.87 ± 15.73 mmHg vs. 80.06 ± 8.49 mmHg, p = 0.02), creatinine levels (93.66 ± 34.61 μmol/L vs. 84.69 ± 23.67 μmol/L, p = 0.02), and blood triglycerides (1.8 ± 1.06 mmol/L vs. 1.48 ± 0.78 mmol/L, p = 0.03). They also had a higher prevalence of cardiovascular interventions (29.6% vs. 13.8%, p = 0.04), greater usage of third/fourth-line antihypertensive treatment (50%vs16%, p = 0.03), and anticoagulant medications (60% vs. 16%, p = 0.01). Additionally, the number of contralateral cerebral infarcts was higher in patients with SBIs (35.5% vs. 13.4%, p &amp;lt; 0.01). Moreover, carotid ultrasound revealed higher Saint Mary’s ratios (15.33 ± 12.45 vs. 12.96 ± 7.99, p = 0.02), and CFD analysis demonstrated larger areas of low wall shear stress (WSS) (0.0004 ± 0.0004 m2 vs. 0.0002 ± 0.0002 m2, p &amp;lt; 0.01).ConclusionThe TAXINOMISIS clinical trial provides valuable insights into the prevalence and risk factors associated with SBIs in patients with moderate asymptomatic carotid stenosis. The findings suggest that specific hemodynamic and arterial wall characteristics may contribute to the development of silent brain infarcts.

Relative Residence Time Can Account for Half of the Anatomical Variation in Fatty Streak Prevalence Within the Right Coronary Artery.

The patchy anatomical distribution of atherosclerosis has been attributed to variation in haemodynamic wall shear stress (WSS). The consensus is that low WSS and a high Oscillatory Shear Index (OSI) trigger the disease. We found that atherosclerosis at aortic branch sites correlates threefold better with transverse WSS (transWSS), a metric which quantifies multidirectional near-wall flow. Coronary artery disease has greater clinical significance than aortic disease but computation of WSS metrics is complicated by the substantial vessel motion occurring during each cardiac cycle. Here we present the first comparison of the distribution of atherosclerosis with WSS metrics computed for moving coronary arteries. Maps of WSS metrics were computed using dynamic geometries reconstructed from angiograms of ten non-stenosed human right coronary arteries (RCAs). They were compared with maps of fatty streak prevalence derived from a previous study of 1852 RCAs. Time average WSS (TAWSS), OSI, transWSS and the cross-flow index (CFI), a non-dimensional form of the transWSS, gave non-significant or significant but low spatial correlations with lesion prevalence. The highest correlation coefficient (0.71) was for the relative residence time (RRT), a metric that decreases with TAWSS and increases with OSI. The coefficient was not changed if RRT was calculated using CFI, which captures multidirectional WSS only, rather than OSI, which encompasses both multidirectional and oscillatory WSS. Contrary to our earlier findings in the aorta, low WSS in combination with highly multidirectional flow correlates best with lesion location in the RCA, explaining approximately half of its anatomical variation.