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TAVR has emerged as a standard approach for treating severe aortic stenosis patients. However, it is associated with several clinical complications, including subclinical leaflet thrombosis characterized by Hypoattenuated Leaflet Thickening (HALT). A rigorous analysis of TAVR device thrombogenicity considering anatomical variations is essential for estimating this risk. Clinicians use the Sinotubular Junction (STJ) diameter for TAVR sizing, but there is a paucity of research on its influence on TAVR devices thrombogenicity. A Medtronic Evolut® TAVR device was deployed in three patient models with varying STJ diameters (26, 30, and 34 mm) to evaluate its impact on post-deployment hemodynamics and thrombogenicity, employing a novel computational framework combining prosthesis deployment and fluid-structure interaction analysis. The 30 mm STJ patient case exhibited the best hemodynamic performance: 5.94 mmHg mean transvalvular pressure gradient (TPG), 2.64 cm 2 mean geometric orifice area (GOA), and the lowest mean residence time (T R )-indicating a reduced thrombogenic risk; 26 mm STJ exhibited a 10 % reduction in GOA and a 35% increase in mean TPG compared to the 30 mm STJ; 34 mm STJ depicted hemodynamics comparable to the 30 mm STJ, but with a 6% increase in T R and elevated platelet stress accumulation. A smaller STJ size impairs adequate expansion of the TAVR stent, which may lead to suboptimal hemodynamic performance. Conversely, a larger STJ size marginally enhances the hemodynamic performance but increases the risk of TAVR leaflet thrombosis. Such analysis can aid pre-procedural planning and minimize the risk of TAVR leaflet thrombosis., (© 2023. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Background and Objectives: Coronary obstruction is a complication that may affect patients receiving Transcatheter Aortic Valve Replacement (TAVR), with catastrophic consequences and long-term negative effects. To enable healthy coronary perfusion, it is fundamental to appropriately position the device with respect to the coronary ostia. Nonetheless, most TAVR delivery systems do not control commissural alignment to do so. Moreover, no in silico study has directly assessed the effect of commissural alignment on coronary perfusion. This work aims to evaluate the effect of TAVR commissural alignment on coronary perfusion and device performance., Methods: A two-way computational fluid-structure interaction model is used to predict coronary perfusion at different commissural alignments. Moreover, in each scenario, hemodynamic biomarkers are evaluated to assess device performance., Results: Commissural misalignment is shown to reduce the total coronary perfusion by -3.2% and the flow rate to a single coronary branch by -6.8%. It is also observed to impair valvular function by reducing the systolic geometric orifice area by -2.5% and increasing the systolic transvalvular pressure gradients by +5.3% and the diastolic leaflet stresses by +16.0%., Conclusions: The present TAVR patient model indicates that coronary perfusion, hemodynamic and structural performance are minimized when the prosthesis commissures are fully misaligned with the native ones. These results support the importance of enabling axial control in new TAVR delivery catheter systems and defining recommended values of commissural alignment in upcoming clinical treatment guidelines., Competing Interests: Declaration of Competing Interest Mariano Vázquez is the CTO and CSO of ELEM Biotech, and David Oks is a business development engineer at ELEM Biotech. The rest of the authors declare no potential conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Stroke is the second leading cause of death worldwide. Nearly two-thirds of strokes are produced by cardioembolisms, and half of cardioembolic strokes are triggered by Atrial Fibrillation (AF), the most common type of arrhythmia. A more recent cause of cardioembolisms is Transcatheter Aortic Valve Replacements (TAVRs), which may onset post-procedural adverse events such as stroke and Silent Brain Infarcts (SBIs), for which no definitive treatment exists, and which will only get worse as TAVRs are implanted in younger and lower risk patients. It is well known that some specific characteristics of elderly patients may lower the safety and efficacy of anticoagulation therapy, making it a real urgency to find alternative therapies. We propose a device consisting of a strut structure placed at the base of the treated artery to model the potential risk of cerebral embolisms caused by dislodged debris of varying sizes. This work analyzes a design based on a patented medical device, intended to block cardioembolisms from entering the cerebrovascular system, with a particular focus on AF, and potentially TAVR patients. The study has been carried out in two stages. Both of them based on computational fluid dynamics (CFD) coupled with Lagrangian particle tracking method. The first stage of the work evaluates a variety of strut thicknesses and inter-strut spacings, contrasting with the device-free baseline geometry. The analysis is carried out by imposing flowrate waveforms characteristic of both healthy and AF patients. Boundary conditions are calibrated to reproduce physiological flowrates and pressures in a patient's aortic arch. In the second stage, the optimal geometric design from the first stage was employed, with the addition of lateral struts to prevent the filtration of particles and electronegatively charged strut surfaces, studying the effect of electrical forces on the clots if they are considered charged. Flowrate boundary conditions were used to emulate both healthy and AF conditions. Results from numerical simulations coming form the first stage indicate that the device blocks particles of sizes larger than the inter-strut spacing. It was found that lateral strut space had the highest impact on efficacy. Based on the results of the second stage, deploying the electronegatively charged device in all three aortic arch arteries, the number of particles entering these arteries was reduced on average by 62.6% and 51.2%, for the healthy and diseased models respectively, matching or surpassing current oral anticoagulant efficacy. In conclusion, the device demonstrated a two-fold mechanism for filtering emboli: while the smallest particles are deflected by electrostatic repulsion, avoiding microembolisms, which could lead to cognitive impairment, the largest ones are mechanically filtered since they cannot fit in between the struts, effectively blocking the full range of particle sizes analyzed in this study. The device presented in this manuscript offers an anticoagulant-free method to prevent stroke and SBIs, imperative given the growing population of AF and elderly patients., Competing Interests: DO, MF, ACM and MV are employed by ELEM Biotech. MV is an investor of ELEM Biotech. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Eguzkitza, Oks, Navia, Houzeaux, Butakoff, Fisa, Campoy Millán and Vázquez.)

Targeted nasal drug delivery can provide improved efficacy for drug formulations to be delivered at high efficacy rates. Some parameters that influence drug delivery have a dependency on the patient's technique of administration and the spray device itself. When the different parameters, each having a specific range of values are combined, the combinatory permutations for studying its effects on particle deposition become large. In this study, we combine six input spray parameters (the spray half-cone angle, the mean spray exit velocity, the breakup length from the nozzle exit, the diameter of the nozzle spray device, the particle size, and the sagittal angle of the spray) with a range of values to produce 384 combinations of spray characteristics. This was repeated for three inhalation flow rates of 20, 40, and 60 L/min. To reduce the computational costs of a full transient Large Eddy Simulation flow field, we create a time-averaged frozen field and perform the time integration of particle trajectories through the flow field to determine the particle deposition in four anatomical regions of the nasal cavity (anterior, middle, olfactory and posterior) for each of the 384 spray field. A sensitivity analysis determined the significance of each input variable on the deposition. It was found the particle size distribution significantly affected deposition in the olfactory and posterior regions, while the spray device insertion angle was significant for deposition in the anterior and middle regions. Five machine learning models were evaluated based on 384 cases and it was found that despite the small sample dataset the simulation data was sufficient to provide accurate machine-learning predictions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

This work intends to study the effect of aortic annulus eccentricity and leaflet rigidity on the performance, thrombogenic risk and calcification risk in bioprosthetic aortic valve replacements (BAVRs). To address these questions, a two-way immersed fluid-structure interaction (FSI) computational model was implemented in a high-performance computing (HPC) multi-physics simulation software, and validated against a well-known FSI benchmark. The aortic valve bioprosthesis model is qualitatively contrasted against experimental data, showing good agreement in closed and open states. Regarding the performance of BAVRs, the model predicts that increasing eccentricities yield lower geometric orifice areas (GOAs) and higher normalized transvalvular pressure gradients (TPGs) for healthy cardiac outputs during systole, agreeing with in vitro experiments. Regions with peak values of residence time are observed to grow with eccentricity in the sinus of Valsalva, indicating an elevated risk of thrombus formation for eccentric configurations. In addition, the computational model is used to analyze the effect of varying leaflet rigidity on both performance, thrombogenic and calcification risks with applications to tissue-engineered prostheses. For more rigid leaflets it predicts an increase in systolic and diastolic TPGs, and decrease in systolic GOA, which translates to decreased valve performance. The peak shear rate and residence time regions increase with leaflet rigidity, but their volume-averaged values were not significantly affected. Peak solid stresses are also analyzed, and observed to increase with rigidity, elevating risk of valve calcification and structural failure. To the authors' knowledge this is the first computational FSI model to study the effect of eccentricity or leaflet rigidity on thrombogenic biomarkers, providing a novel tool to aid device manufacturers and clinical practitioners., (© 2022 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.)

Validating numerical models against experimental models of nasal spray deposition is challenging since many aspects must be considered. That being said, it is a critical step in the product development process of nasal spray devices. This work presents the validation process of a nasal deposition model, which demonstrates a high degree of consistency of the numerical model with experimental data when the nasal cavity is segmented into two regions but not into three. Furthermore, by modelling the flow as stationary, the computational cost is drastically reduced while maintaining quality of particle deposition results. Thanks to this reduction, a sensitivity analysis of the numerical model could be performed, consisting of 96 simulations. The objective was to quantify the impact of four inputs: the spray half cone angle, mean spray exit velocity, breakup length from the nozzle exit and the diameter of the nozzle spray device, on the three quantities of interest: the percentage of the accumulated number of particles deposited on the anterior, middle and posterior sections of the nasal cavity. The results of the sensitivity analysis demonstrated that the deposition on anterior and middle sections are sensitive to injection angle and breakup length, and the deposition on posterior section is only, but highly, sensitive to the injection velocity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)