Wall shear stress alterations at left atrium and left atrial appendage employing abnormal blood velocity profiles

Grigoriadis, Grigoris; Sakellarios, Antonis I.; Kosmidou, Ioanna; Naka, Katerina K.; Ellis, Christopher R.; Michalis, Lampros K.; Fotiadis, Dimitrios I.

doi:10.1109/embc44109.2020.9175235

Cited by 10 publications

(13 citation statements)

References 10 publications

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“…We consider PV flow splits in the ranges (left/right) 40-50%/50-60% to compare differences in LA hemodynamics between the even split [7, 17, 24, 37, 66, 67] and equal velocity inflow conditions [19, 21, 34, 68, 69] often used in simulation studies, and the more physiological uneven splits caused by the right lung being larger than the left lung. However, multiple factors can alter the PV flow split outside of the range we studied, including common ones like changes in body position [41] and less common ones like abnormalities in the pulmonary artery or veins [70, 71], or lung resection surgeries [72].…”

Section: Discussionmentioning

confidence: 99%

Pulmonary vein flow split effects in patient-specific simulations of left atrial flow

Durán

García-Villalba

Martínez‐Legazpi

et al. 2023

Preprint

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Disruptions to left atrial (LA) blood flow, such as those caused by atrial fibrillation (AF), can lead to thrombosis in the left atrial appendage (LAA) and an increased risk of systemic embolism. LA hemodynamics are influenced by various factors, including LA anatomy and function, and pulmonary vein (PV) inflow conditions. In particular, the PV flow split can vary significantly among and within patients depending on multiple factors. In this study, we investigated how changes in PV flow split affect LA flow transport, focusing on blood stasis in the LAA, using a high-fidelity patient-specific computational fluid dynamics (CFD) model. We analyzed LA anatomies from eight patients with varying atrial function, including three with AF and either a LAA thrombus or a history of TIAs. Using four different flow splits (60/40\% and 55/45\% through right and left PVs, even flow rate, and same velocity through each PV), we found that flow patterns are sensitive to PV flow split variations, particularly in planes parallel to the mitral valve. Changes in PV flow split also had a significant impact on blood stasis and could contribute to increased risk for thrombosis inside the LAA, particularly in patients with AF and previous LAA thrombus or a history of TIAs. Our study highlights the importance of considering patient-specific PV flow split variations when assessing LA hemodynamics and identifying patients at increased risk for thrombosis and stroke.

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Section: Discussionmentioning

confidence: 99%

Pulmonary vein flow split effects in patient-specific simulations of left atrial flow

Durán

García-Villalba

Martínez‐Legazpi

et al. 2023

Preprint

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“…Irregular contraction and LA wall rigidity in AF prevented effective blood flow to the ventricles, resulting in blood stasis and decreased shear strain rate in the LAA. Studies have identified the exact shear stress in the LA of patients with AF, a mean of 2−3 dyn/cm 2 42,43 . Therefore, we simulated shear stress to incubate EECs and detect the increased expression of ADAMTS1 and decreased activity of TFPI and TFPI2.…”

Section: Discussionmentioning

confidence: 99%

Single‐cell RNA sequencing reveals a mechanism underlying the susceptibility of the left atrial appendage to intracardiac thrombogenesis during atrial fibrillation

Yang

Sun

et al. 2023

Clinical & Translational Med

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Background Atrial fibrillation (AF) is associated with an increased risk of thrombosis of the left atrial appendage (LAA). However, the molecular mechanisms underlying this site‐specificity remain poorly understood. Here, we present a comparative single‐cell transcriptional profile of paired atrial appendages from patients with AF and illustrate the chamber‐specific properties of the main cell types. Methods Single‐cell RNA sequencing analysis of matched atrial appendage samples from three patients with persistent AF was evaluated by 10× genomics. The AF mice model was created using Tbx5 knockout mice. Validation experiments were performed by glutathione S‐transferase pull‐down assays, coimmunoprecipitation (Co‐IP), cleavage assays and shear stress experiments in vitro. Results In LAA, phenotype switching from endothelial cells to fibroblasts and inflammation associated with proinflammatory macrophage infiltration were observed. Importantly, the coagulation cascade is highly enriched in LAA endocardial endothelial cells (EECs), accompanying the up‐regulation of a disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1) and the down‐regulation of the tissue factor pathway inhibitor (TFPI) and TFPI2. Similar alterations were verified in an AF mouse model (Tbx5+/−) and EECs treated with simulated AF shear stress in vitro. Furthermore, we revealed that the cleavage of both TFPI and TFPI2 based on their interaction with ADAMTS1 would lead to loss of anticoagulant activities of EECs. Conclusions This study highlights the decrease in the anticoagulant status of EECs in LAA as a potential mechanism underlying the propensity for thrombosis, which may aid the development of anticoagulation therapeutic approaches targeting functionally distinct cell subsets or molecules during AF.

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“…In the majority of CFD studies of atrial flows, the authors have sought correlations between hemodynamics and disease. 7,11,17 It is generally difficult to contextualize the results of our study, as much of the analyses have been qualitative, and there is generally a lack of quantitative data in the literature. However, if we set aside all modeling variabilities, there are some points of reference that we can compare our results against.…”

Section: Relevancementioning

confidence: 99%

“…Mesh convergence studies have previously only reported differences below 5%, and in contrast to us, concluded that normal spatial resolution is sufficient. 17,21,41,52 Although we cannot pinpoint the precise cause, there are distinct methodological approaches. The previous range of the mesh sizes seem narrow compared with ours, typically only spanning a few 100,000 elements, and not orders of magnitude as we have done.…”

Section: Relation To Othersmentioning

confidence: 99%

“…The most commonly computed hemodynamic indices in the left atrial fluid modeling literature are time-averaged wall shear stress (WSS), [7][8][9][10] oscillatory shear index (OSI), [7][8][9][10][11] relative residence time (RRT), [7][8][9][10][11] and endothelial cell activation potential (ECAP). 8,[10][11][12][13][14] Some have focused on correlating hemodynamics and different LAA morphologies, 8,[15][16][17][18][19] whereas other studies 8,[16][17][18] investigated the influence of pulmonary vein configuration in LAA flow stasis. The effect of atrial wall functionality has also been studied to investigate how it could contribute to thrombus formation.…”

Section: Introductionmentioning

confidence: 99%

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On the importance of fundamental computational fluid dynamics toward a robust and reliable model of left atrial flows

Khalili,

Daversin‐Catty,

Olivares

et al. 2024

Numer Methods Biomed Eng

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Computational fluid dynamics (CFD) studies of left atrial flows have reached a sophisticated level, for example, revealing plausible relationships between hemodynamics and stresses with atrial fibrillation. However, little focus has been on fundamental fluid modeling of LA flows. The purpose of this study was to investigate the spatiotemporal convergence, along with the differences between high‐ (HR) versus normal‐resolution/accuracy (NR) solution strategies, respectively. Rigid wall CFD simulations were conducted on 12 patient‐specific left atrial geometries obtained from computed tomography scans, utilizing a second‐order accurate and space/time‐centered solver. The convergence studies showed an average variability of around 30% and 55% for time averaged wall shear stress (WSS), oscillatory shear index (OSI), relative residence time (RRT), and endothelial cell activation potential (ECAP), even between intermediate spatial and temporal resolutions, in the left atrium (LA) and left atrial appendage (LAA), respectively. The comparison between HR and NR simulations showed good correlation in the LA for WSS, RRT, and ECAP (), but not for OSI (). However, there were poor correlations in the LAA especially for OSI, RRT, and ECAP ( .55, .63, and .61, respectively), except for WSS (). The errors are comparable to differences previously reported with disease correlations. To robustly predict atrial hemodynamics and stresses, numerical resolutions of 10 M elements (i.e., .5 mm) and 10 k time‐steps per cycle seem necessary (i.e., one order of magnitude higher than normally used in both space and time). In conclusion, attention to fundamental numerical aspects is essential toward establishing a plausible, robust, and reliable model of LA flows.

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Wall shear stress alterations at left atrium and left atrial appendage employing abnormal blood velocity profiles

Cited by 10 publications

References 10 publications

Pulmonary vein flow split effects in patient-specific simulations of left atrial flow

Pulmonary vein flow split effects in patient-specific simulations of left atrial flow

Single‐cell RNA sequencing reveals a mechanism underlying the susceptibility of the left atrial appendage to intracardiac thrombogenesis during atrial fibrillation

On the importance of fundamental computational fluid dynamics toward a robust and reliable model of left atrial flows

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