Aortic valve calcification is an important cardiovascular disorder that deteriorates the accurate functioning of the valve leaflets. The increasing stiffness due to the calcification prevents the complete closure of the valve and therefore leads to significant hemodynamic alterations. Computational fluid dynamics (CFD) modeling enables the investigation of the entire flow domain by processing medical images from aortic valve patients. In this study, we computationally modeled and simulated a 3D aortic valve using patient-specific dimensions of the aortic root and aortic sinus. Leaflet stiffness is deteriorated in aortic valve disease due to calcification. In order to investigate the influence of leaflet calcification on flow dynamics, three different leaflet-stiffness values were considered for healthy, mildly calcified, and severely calcified leaflets. Time-dependent CFD results were used for applying the Lagrangian coherent structures (LCS) technique by performing finite-time Lyapunov exponent (FTLE) computations along with Lagrangian particle residence time (PRT) analysis to identify unique vortex structures at the front and backside of the leaflets. Obtained results indicated that the peak flow velocity at the valve orifice increased with the calcification rate. For the healthy aortic valve, a low-pressure field was observed at the leaflet tips. This low-pressure field gradually expanded through the entire aortic sinus as the calcification level increased. FTLE field plots of the healthy and calcified valves showed a variety of differences in terms of flow structures. When the number of fluid particles in the healthy valve model was taken as reference, 1.59 and 1.74 times more particles accumulated in the mildly and severely calcified valves, respectively, indicating that the calcified valves were not sufficiently opened to allow normal mass flow rates.

Hemodynamics significantly impact the biology of endothelial cells (ECs) lining the blood vessels. ECs are exposed to various hemodynamic forces, particularly frictional shear stress from flowing blood. While physiological flows are critical for the normal functioning of ECs, abnormal flow dynamics, known as disturbed flows, may trigger endothelial dysfunction leading to atherosclerosis and other vascular conditions. Such flows can occur due to sudden geometrical variations and vascular abnormalities in the cardiovascular system. In the current study, a microfluidic system was used to investigate the impact of different flow conditions (i.e, normal vs. disturbed) on ECs in vitro. We particularly explored the relationship between specific flow patterns and cellular pathways linked to oxidative stress and inflammation related to atherosclerosis. Here, we utilized a 2D cell culture perfusion system featuring an immortalized human vascular endothelial cell line (EA.hy926) connected to a modified peristaltic pump system to generate either steady laminar flows, representing healthy conditions, or disturbed oscillatory flows, representing diseased conditions. EA.hy926 were exposed to an oscillatory flow shear stress of 0.5 dynes/cm² or a laminar flow shear stress of 2 dynes/cm² up to 24 h. Following flow exposure, cells were harvested from the perfusion chamber for quantitative PCR analysis of gene expression. Reactive oxygen species (ROS) generation under various shear stress conditions was also measured using DCFDA/H2DCFDA fluorescent assays. Under oscillatory shear stress flow conditions (0.5 dynes/cm²), EA.hy926 ECs showed a 3.5-fold increase in the transcription factor nuclear factor (NFκ-B) and a remarkable 28.6-fold increase in cyclooxygenase-2 (COX-2) mRNA expression, which are both proinflammatory markers, compared to static culture. Transforming growth factor-beta (TGFβ) mRNA expression was downregulated in oscillatory and laminar flow conditions compared to the static culture. Apoptosis marker transcription factor Jun (C-Jun) mRNA expression increased in both flow conditions. Apoptosis marker C/EBP homologous protein (CHOP) mRNA levels increased significantly in oscillatory flow, with no difference in laminar flow. Endothelial nitric oxide synthase (eNOS) mRNA expression was significantly decreased in cells exposed to oscillatory flow, whereas there was no change in laminar flow. Endothelin-1 (ET-1) mRNA expression levels dropped significantly by 0.5- and 0.8-fold in cells exposed to oscillatory and laminar flow, respectively. ECs subjected to oscillatory flow exhibited a significant increase in ROS at both 4 and 24 h compared to the control and laminar flow. Laminar flow-treated cells exhibited a ROS generation pattern similar to that of static culture, but at a significantly lower level. Overall, by exposing ECs to disturbed and normal flows with varying shear stresses, significant changes in gene expression related to inflammation, endothelial function, and oxidative stress were observed. In this study, we present a practical, optimized system as an in vitro model that can be employed to investigate flow-associated diseases, such as atherosclerosis and aortic aneurysm, thereby supporting the understanding of the underlying molecular mechanisms.

Background/Objectives: For transcatheter aortic valve implantation (TAVI) therapy, a catheter-guided crimped valve is deployed into the aortic root. Valve types such as Edwards balloon-expandable valves and Medtronic self-expandable valves come in different sizes and are chosen based on patient-specific aortic anatomy, including aortic root diameter measurement. Complications may arise due to variations in anatomical characteristics and the implantation procedure, making pre-implantation assessment important for predicting complications. Methods: Computational modeling, particularly finite element analysis (FEA), has become popular for assessing wall stresses and deformations in TAVI. In this study, a finite element model including the aorta, native leaflets, and TAVI device was used to simulate procedures and assess patient-specific wall stresses and deformations. Results: Using the Medtronic Evolut R valve, we simulated TAVI for 14 patients to analyze the effects of geometrical variations on structural stresses. Virtual TAVIs with different valve sizes were also simulated to study the influence of TAV size on stresses. Our results show that variations in aortic wall geometries and TAV sizes significantly influence wall stresses and deformations. Conclusions: Our study is one of the first comprehensive FEA investigations of aortic geometrical variations and valve sizes on post-TAVI stresses, demonstrating the non-linear relationship between aortic dimensions, TAV sizes, and wall stresses.

The anatomy and mechanical strength of aortic valve leaflets are critical determinants of their biomechanical behavior and long-term structural integrity. The embryonic developmental period, when valves are forming, is critical to establish baseline leaflet properties. However, fetal stages of valve development, when valve leaflets are still forming and remodeling, are not well understood. The goal of this study is to investigate the biomechanical stress and deformation modes of developing valve leaflets during systole, and how leaflet biomechanics are affected by anatomy and material properties. To this end, the study employs a parametric approach to model the leaflet anatomy of an HH40 chick embryo, used here as a model of fetal cardiac development. To perform biomechanical analysis, a pressure profile derived from in ovo Doppler ultrasound measurements was applied, and an Ogden hyperelastic material model was employed following a sensitivity analysis. To determine the effect of valve anatomy on leaflet tissue deformation and stresses, we changed the leaflet midline curve (belly curve) from its native curvature to a linear profile and quantified biomechanical responses. Our analysis revealed a strong decrease in average leaflet effective stress as the belly curvature was shifted towards a linear profile. However, this reduction in average stress was at the expense of a biomechanical trade-off. The shift induced a progressive localization of stress concentration at the leaflet tips and commissures, and a distinct bending deformation mode at the tip under peak load. Our findings demonstrate that while the belly curve of the leaflet modulates tissue stress during valve opening, a low-stress anatomy does not align with hemodynamic performance. This work characterizes competing leaflet biomechanical responses (stress reduction versus failure modes) that shape valve leaflet formation, providing fundamental insights into developmental valve biomechanics.