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The human heart is subject to highly variable amounts of strain during day-to-day activities and needs to adapt to a wide range of physiological demands. This adaptation is driven by an autoregulatory loop that includes both electrical and the mechanical components. In particular, mechanical forces are known to feed back into the cardiac electrophysiology system, which can result in pro- and anti-arrhythmic effects. Despite the widespread use of computational modelling and simulation for cardiac electrophysiology research, the majority of in silico experiments ignore this mechano-electric feedback entirely due to the high computational cost associated with solving cardiac mechanics. In this study, we therefore use an electromechanically coupled whole-heart model to investigate the differential and combined effects of electromechanical feedback mechanisms with a focus on their physiological relevance during sinus rhythm. In particular, we consider troponin-bound calcium, the effect of deformation on the tissue diffusion tensor, and stretch-activated channels. We found that activation of the myocardium was only significantly affected when including deformation into the diffusion term of the monodomain equation. Repolarization, on the other hand, was influenced by both troponin-bound calcium and stretch-activated channels and resulted in steeper repolarization gradients in the atria. The latter also caused afterdepolarizations in the atria. Due to its central role for tension development, calcium bound to troponin affected stroke volume and pressure. In conclusion, we found that mechano-electric feedback changes activation and repolarization patterns throughout the heart during sinus rhythm and lead to a markedly more heterogeneous electrophysiological substrate. KEY POINTS: The electrophysiological and mechanical function of the heart are tightly interrelated by excitation-contraction coupling (ECC) in the forward direction and mechano-electric feedback (MEF) in the reverse direction. While ECC is considered in many state-of-the-art computational models of cardiac electromechanics, less is known about the effect of different MEF mechanisms. Accounting for calcium bound to troponin increases stroke volume and delays repolarization. Geometry-mediated MEF leads to more heterogeneous activation and repolarization with steeper gradients. Both effects combine in an additive way. Non-selective stretch-activated channels as an additional MEF mechanism lead to heterogeneous diastolic transmembrane voltage, higher developed tension and delayed repolarization or afterdepolarizations in highly stretched parts of the atria. The differential and combined effects of these three MEF mechanisms during sinus rhythm activation in a human four-chamber heart model may have implications for arrhythmogenesis, both in terms of substrate (repolarization gradients) and triggers (ectopy)., (© 2024 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Previously, we found analytic solutions for single ventricular system based on the lumped parameter model (LPM). In this study, we generalized the method to biventricular system and derived its analytic solutions. LPM is just a set of differential equations, but it is difficult to solve due to time-varying ventricular elastance and high order. Mathematically, there exist no elementary solutions for time-varying equations. It turns out that instead of differential equations, according to volume conservation, a set of algebraic equations can be carried out. The solutions of the set of equations are just physiological states at end of systolic and diastolic phases such as end systolic/diastolic pressure/volume of left ventricle. As a preliminary application, the method is utilized to deduce the hemodynamic effects of VA ECMO. Left ventricular (LV) distension, a serious complication of VA ECMO, is usually attributed to factors such as increased afterload, inadequate LV unloading, reduced myocardial contractility or aortic valve regurgitation (AR), bronchial and Thebesian return in the absence of aortic valve (AoV) opening. Among these, reduced contractility and AR are strongly associated with LV distension. However, in the absence of reduced contractility or AR, it is less clear whether increased afterload or inadequate LV unloading alone can cause LV distension. This leads to the critical question: under what conditions does LV distension occur in the absence of reduced contractility or AR? The analytic formulas derived in this study give conditions for LV distension. Furthermore, the results show that the analytic hemodynamics are coincident with simulated results., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Polin Hsu is the founder and CEO of magAssist, Co., Ltd. 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.

This work introduces the first atrial-specific in-silico human induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) model, based on a set of phenotype-specific I Kur ,I KCa and I K1 membrane currents. This model is built on novel in-vitro experimental data recently published by some of the co-authors to simulate the paced action potential of matured atrial-like hiPSC-CMs. The model consists of a system of stiff ordinary differential equations depending on several parameters, which have been tuned by automatic optimization techniques to closely match selected experimental biomarkers. The new model effectively simulates the electronic in-vitro hiPSC-CMs maturation process, transitioning from an unstable depolarized membrane diastolic potential to a stable hyperpolarized resting potential, and exhibits spontaneous firing activity in unpaced conditions. Moreover, our model accurately reflects the experimental rate dependence data at different cycle length and demonstrates the expected response to a specific current blocker. This atrial-specific in-silico model provides a novel computational tool for electrophysiological studies of cardiac stem cells and their applications to drug evaluation and atrial fibrillation treatment., Competing Interests: Declaration of competing interest There are no conflicts of interest: None Declared., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: Severe congenital aortic valve pathology in the growing patient remains a challenging clinical scenario. Bicuspidization of the diseased aortic valve has proven to be a promising repair technique with acceptable durability. However, most understanding of the procedure is empirical and retrospective. This work seeks to design the optimal gross morphology associated with surgical bicuspidization with simulations based on the hypothesis that modifications to the free edge length cause or relieve stenosis., Methods: Model bicuspid valves were constructed with varying free edge lengths and gross morphology. Fluid-structure interaction simulations were conducted in a single patient-specific model geometry. The models were evaluated for primary targets of stenosis and regurgitation. Secondary targets were assessed and included qualitative hemodynamics, geometric height, effective height, orifice area, and billow., Results: Stenosis decreased with increasing free edge length and was pronounced with free edge length less than or equal to 1.3 times the annular diameter d. With free edge length 1.5d or greater, no stenosis occurred. All models were free of regurgitation. Substantial billow occurred with free edge length 1.7d or greater., Conclusions: Free edge length 1.5d or greater was required to avoid aortic stenosis in simulations. Cases with free edge length 1.7d or greater showed excessive billow and other changes in gross morphology. Cases with free edge length 1.5d to 1.6d have a total free edge length approximately equal to the annular circumference and appeared optimal. These effects should be studied in vitro and in animal studies., Competing Interests: Conflict of Interest Statement The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Flow-diverter stents offer clinicians an effective solution for treating intracranial aneurysms, especially in cases where other devices may be unsuitable. However, strongly deviating success rates among different centres, manufacturers, and aneurysm phenotypes highlight the need for better in-situ studies of these devices. To support research in this area, virtual stenting algorithms have been proposed that, combined with computational fluid dynamics, provide insights into the hemodynamic alterations induced by the device. Yet, many existing algorithms rely on uncertain parameters, such as the forces applied during operation, fail to predict the length of the device after deployment, or lack robust validation steps, raising concerns about their reliability. Therefore, we developed a robust deployment technique that builds upon the geometrical features of the vessel and includes advancements from previous works. The algorithm is detailed and validated against literature examples, in-vitro experiments, and patient data, achieving a mean angular error below 5° in the latter. Furthermore, we describe and demonstrate how the deployed device can be embedded in a computational mesh using open-source tools and anisotropic meshing routines., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: Oscillometric finger pressing is a smartphone-based blood pressure (BP) monitoring method. Finger photoplethysmography (PPG) oscillations and pressure are measured during a steady increase in finger pressure, and an algorithm computes systolic BP (SP) and diastolic BP (DP) from the measurements. The objective was to assess the impact of finger artery viscoelasticity on the BP computation., Methods: Nonlinear viscoelastic models relating transmural pressure (finger BP - applied pressure) to PPG oscillations during finger pressing were developed. The output of each model to a measured transmural pressure input was fitted to measured PPG oscillations from 15 participants. A parametric sensitivity analysis was performed via model simulations to elucidate the viscoelastic effect on the derivative-based BP computation algorithm., Results: A Wiener viscoelastic model comprising a first-order transfer function followed by a static sigmoidal function fitted the measured PPG oscillations better than an elastic model containing only the static function (median (IQR) error of 30.5% (25.6%-34.0%) vs 50.9% (46.7%-53.7%); p<0.01). In Wiener model simulations, the derivative algorithm underestimated SP, especially with high pulse pressure and low transfer function cutoff frequency (i.e., greater viscoelasticity). The mean of the normalized PPG waveform at the maximum oscillation beat was found to correlate with the cutoff frequency (r = -0.8) and could thus possibly be used to compensate for viscoelasticity., Conclusion: Finger artery viscoelasticity negatively impacts oscillometric BP computation algorithms but can potentially be compensated for using available measurements., Significance: These findings may help in converting smartphones into truly cuffless BP monitors for improving hypertension awareness and control.

Aortic valve (AV) disease is a common valvular lesion in the United States, present in about 5% of the population at age 65 with increasing prevalence with advancing age. While current replacement heart valves have extended life for many, their long-term use remains hampered by limited durability. Non-surgical treatments for AV disease do not yet exist, in large part because our understanding of AV disease etiology remains incomplete. The direct study of human AV disease remains hampered by the fact that clinical data is only available at the time of treatment, where the disease is at or near end stage and any time progression information has been lost. Large animal models, long used to assess replacement AV devices, cannot yet reproduce AV disease processes. As an important alternative mouse animal models are attractive for their ability to perform genetic studies of the AV disease processes and test potential pharmaceutical treatments. While mouse models have been used for cellular and genetic studies of AV disease, their small size and fast heart rates have hindered their use for tissue- and organ-level studies. We have recently developed a novel ex vivo micro-CT-based methodology to 3D reconstruct murine heart valves and estimate the leaflet mechanical behaviors (Feng et al. in Sci Rep 13(1):12852, 2023). In the present study, we extended our approach to 3D reconstruction of the in vivo functional murine AV (mAV) geometry using high-frequency four-dimensional ultrasound (4DUS). From the resulting 4DUS images we digitized the mAV mid-surface coordinates in the fully closed and fully opened states. We then utilized matched high-resolution µCT images of ex vivo mouse mAV to develop mAV NURBS-based geometric model. We then fitted the mAV geometric model to the in vivo data to reconstruct the 3D in vivo mAV geometry in the closed and open states in n = 3 mAV. Results demonstrated high fidelity geometric results. To our knowledge, this is the first time such reconstruction was ever achieved. This robust assessment of in vivo mAV leaflet kinematics in 3D opens up the possibility for longitudinal characterization of murine models that develop aortic valve disease., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)

This study explored the impact of hypertension on atheroma plaque formation through a mechanobiological model. The model incorporates blood flow via the Navier-Stokes equation. Plasma flow through the endothelium is determined by Darcy's law and the Kedem-Katchalsky equations, which consider the three-pore model utilized for substance flow across the endothelium. The behaviour of these substances within the arterial wall is described by convection-diffusion-reaction equations, while the arterial wall itself is modelled as a hyperelastic material using Yeoh's model. To accurately evaluate hypertension's influence, adjustments were made to incorporate wall compression-induced wall compaction by radial compression. This compaction impacts three key variables of the transport phenomena: diffusion, porosity, and permeability. Based on the obtained findings, we can conclude that hypertension significantly augments plaque growth, leading to an over 400% increase in plaque thickness. This effect persists regardless of whether wall mechanics are considered. Tortuosity, arterial wall permeability, and porosity have minimal impact on atheroma plaque growth under normal arterial pressure. However, the atheroma plaque growth changes dramatically in hypertensive cases. In such scenarios, the collective influence of all factors-tortuosity, permeability, and porosity-results in nearly a 20% increase in plaque growth. This emphasizes the importance of considering wall compression due to hypertension in patient studies, where elevated blood pressure and high cholesterol levels commonly coexist., Competing Interests: Declaration of competing interest The 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., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Computational fluid dynamics (CFD) was used to identify factors influencing the accuracy of the hemispherical proximal isovelocity surface area (PISA) method in calculating the effective regurgitant orifice area (EROA) for patients with functional mitral regurgitation (FMR). Ninety-nine CFD models were constructed to investigate the impact of regurgitant orifice shape and leaflet tethering on the EROA calculation using the PISA method. The correction factors for regurgitation orifice shape (CFs) and for leaflet tethering (CFt) were derived by comparing the 2D PISA method and the actual orifice area. The correction formula was then tested in vivo via 2D transthoracic echocardiography with 3D transesophageal echocardiography of the vena contracta area (VCA) as a reference method in 62 patients with FMR. Based on the CFD simulation results, the two major factors for correcting the EROA calculation were vena contracta length (VCL) and coaptation depth (CD). The correction formula for the EROA was corrected effective regurgitant orifice area (CEROA) = EROA*CFs*CFt, where CFs = 0.59 × VCL(cm) + 0.6 × MR Vmax(cm/s)-0.63 × PISA R(cm)-1.51 and CFt = 0.4 × CD (cm) + 0.96. The correction formula was applied to FMR patients, and the bias and LOA between the CEROA and VCA (0.01 ± 0.13 cm 2 ) were much smaller than those between the EROA and VCA (0.26 ± 0.32 cm 2 ). The CFD-based correction formula improves the accuracy of the EROA calculation based on the hemispheric PISA method, possibly leading to more accurate and reliable data for treatment decision-making in FMR patients., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Automated identification of cardiac vortices is a formidable task due to the complex nature of blood flow within the heart chambers. This study proposes a novel approach that algorithmically characterizes the identification criteria of these cardiac vortices based on Lagrangian Averaged Vorticity Deviation (LAVD). For this purpose, the Recurrent All-Pairs Field Transforms (RAFT) is employed to assess the optical flow over the Phase Contrast Magnetic Resonance Imaging (PC-MRI), and to construct a continuous blood flow velocity field and reduce errors that arise from the integral process of LAVD. Additionally, Generalized Hough Transform (GHT) is applied for automated depiction of the structure of cardiac vortices. The effectiveness of this method is demonstrated and validated by the computation of the acquired cardiac flow data. The results of this comprehensive visual and analytical study show that the evolution of cardiac vortices can be effectively described and displayed, and the RAFT framework for optical flow can synthesize the in-between PC-MRIs with high accuracy. This allows cardiologists to acquire a deeper understanding of intracardiac hemodynamics and its impact on cardiac functional performance., 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 © 2024 Elsevier Ltd. All rights reserved.)

To guarantee the safety of medical devices, including embedded systems, it is essential to consider both electronic components and the natural environment during validation and verification. In contrast to prior research, we present a hardware-in-the-loop environment that connects a real medical system to a biological model in real time for validation, including the modeling of the mechanical component of the heart valves in addition to the modeling of the electrical conduction and electrical stimulation of the heart chambers. Our model accounts for the dynamic adaptation of the temporal processes in the heart chambers to the pacing frequency of the individual chambers as a function of the action potential. This study investigates two additional risk factors affecting the heart under different conditions: pacemaker syndrome and electrical stimulation during the vulnerable phase. Both can be life-threatening to the patient if left untreated. In implementing our concept on a physical pacemaker connected to our software-based model of the heart, we discovered that the test pacemaker was unable to generate the required heart rate in three of the scenarios we tested. Additionally, our tests revealed occurrences of pacemaker syndrome and stimulation in the vulnerable phase., Competing Interests: Declaration of competing interest None declared, (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Cerebral arteriovenous malformations (AVMs) present complex neurovascular challenges, characterized by direct arteriovenous connections that disrupt normal brain blood flow dynamics. Traditional lumped parameter models (LPMs) offer a simplified angioarchitectural representation of AVMs, yet often fail to capture the intricate structure within the AVM nidus. This research aims at refining our understanding of AVM hemodynamics through the development of patient-specific LPMs utilizing three-dimensional (3D) medical imaging data for enhanced structural fidelity., Methods: This study commenced with the meticulous delineation of AVM vascular architecture using threshold segmentation and skeletonization techniques. The AVM nidus's core structure was outlined, facilitating the extraction of vessel connections and the formation of a detailed fistulous vascular tree model. Sampling points, spatially distributed and derived from the pixel intensity in imaging data, guided the construction of a complex plexiform tree within the nidus by generating smaller Y-shaped vascular formations. This model was then integrated with an electrical analog model to enable precise numerical simulations of cerebral hemodynamics with AVMs., Results: The study successfully generated two distinct patient-specific AVM networks, mirroring the unique structural and morphological characteristics of the AVMs as captured in medical imaging. The models effectively represented the intricate fistulous and plexiform vessel structures within the nidus. Numerical analysis of these models revealed that AVMs induce a blood shunt effect, thereby diminishing blood perfusion to adjacent brain tissues., Conclusion: This investigation enhances the theoretical framework for AVM research by constructing patient-specific LPMs that accurately reflect the true vascular structures of AVMs. These models offer profound insights into the hemodynamic behaviors of AVMs, including their impact on cerebral circulation and the blood steal phenomenon. Further incorporation of clinical data into these models holds the promise of deepening the theoretical comprehension of AVMs and fostering advancements in the diagnosis and treatment of AVMs., Competing Interests: Declaration of competing interest The authors would like to declare on behalf of the co-authors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part. No conflict of interest exists in the submission of this manuscript, and the manuscript is approved by all authors for publication., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Flowmotion analysis of the microcirculatory blood flow is a method to extract information about the vessel regulatory function. It has previously shown promise when applied to measurements during a post-occlusive reactive hyperemia. However, the reperfusion peak and the following monotonic decline introduces false low frequencies that should not be interpreted as rhythmic vasomotion effect., Aim: To develop and validate a robust method for flowmotion analysis of post-occlusive reactive hyperemia signals., Method: The occlusion-induced reperfusion response contains a typical rapid increase followed by a monotonic decline to baseline. A mathematical model is proposed to detrend this transient part of the signal to enable further flowmotion analysis. The model is validated in 96 measurements on healthy volunteers., Results: Applying the proposed model corrects the flowmotion signal without adding any substantial new false flowmotion components., Conclusion: Future studies should use the proposed method or equivalent when analyzing flowmotion during post-occlusive reactive hyperemia to ensure valid results., 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 © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Major challenges for clinical applications of in silico medicine are limitations in time and computational resources. Computational approaches should therefore be tailored to specific applications with relatively low complexity and must be verified and validated against clinical gold standards., Methods: This study performed computational fluid dynamics simulations of left ventricular hemodynamics of different complexity based on shape reconstruction from steady state gradient echo magnetic resonance imaging (MRI) data. Computed flow results of a rigid wall model (RWM) and a prescribed motion fluid-structure interaction (PM-FSI) model were compared against phase-contrast MRI measurements for three healthy subjects., Results: Extracted boundary conditions from the steady state MRI sequences as well as computed metrics, such as flow rate, valve velocities, and kinetic energy show good agreement with in vivo flow measurements. Regional flow analysis reveals larger differences., Conclusion: Basic flow structures are well captured with RWM and PM-FSI. For the computation of further biomarkers like washout or flow efficiency, usage of PM-FSI is required. Regarding boundary-near flow, more accurate anatomical models are inevitable., Significance: These results delineate areas of application of both methods and lay a foundation for larger validation studies and sensitivity analysis for healthy and diseased cases, being an essential step upon clinical translations.

Mechano-electric regulations (MER) play an important role in the maintenance of cardiac performance. Mechano-calcium and mechano-electric feedback (MCF and MEF) pathways adjust the cardiomyocyte contractile force according to mechanical perturbations and affects electro-mechanical coupling. MER integrates all these regulations in one unit resulting in a complex phenomenon. Computational modelling is a useful tool to accelerate the mechanistic understanding of complex experimental phenomena. We have developed a novel model that integrates the MER loop for human atrial cardiomyocytes with proper consideration of feedforward and feedback pathways. The model couples a modified version of the action potential (AP) Koivumäki model with the contraction model by Quarteroni group. The model simulates iso-sarcometric and isometric twitches and the feedback effects on AP and Ca 2+ -handling. The model showed a biphasic response of Ca 2+ transient (CaT) peak to increasing pacing rates and highlights the possible mechanisms involved. The model has shown a shift of the threshold for AP and CaT alternans from 4.6 to 4 Hz under post-operative atrial fibrillation, induced by depressed SERCA activity. The alternans incidence was dependent on a chain of mechanisms including RyRs availability time, MCF coupling, CaMKII phosphorylation, and the stretch levels. As a result, the model predicted a 10% slowdown of conduction velocity for a 20% stretch, suggesting a role of stretch in creation of substrate formation for atrial fibrillation. Overall, we conclude that the developed model provides a physiological CaT followed by a physiological twitch. This model can open pathways for the future studies of human atrial electromechanics. KEY POINTS: With the availability of human atrial cellular data, interest in atrial-specific model integration has been enhanced. We have developed a detailed mathematical model of human atrial cardiomyocytes including the mechano-electric regulatory loop. The model has gone through calibration and evaluation phases against a wide collection of available human in-vitro data. The usefulness of the model for analysing clinical problems has been preliminaryly tested by simulating the increased incidence of Ca 2+ transient and action potential alternans at high rates in post-operative atrial fibrillation condition. The model determines the possible role of mechano-electric feedback in alternans incidence, which can increase vulnerability to atrial arrhythmias by varying stretch levels. We found that our physiologically accurate description of Ca 2+ handling can reproduce many experimental phenomena and can help to gain insights into the underlying pathophysiological mechanisms., (© 2023 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

The hemodynamics in Fontan patients with single ventricles rely on favorable flow and energetics, especially in the absence of a subpulmonary ventricle. Age-related changes in energetics for extracardiac and lateral tunnel Fontan procedures are not well understood. Vorticity (VOR) and viscous dissipation rate (VDR) are two descriptors that can provide insights into flow dynamics and dissipative areas in Fontan pathways, potentially contributing to power loss. This study examined power loss and its correlation with spatio-temporal flow descriptors (vorticity and VDR). Data from 414 Fontan patients were used to establish a relationship between the superior vena cava (SVC) to inferior vena cava (IVC) flow ratio and age. Computational flow modeling was conducted for both extracardiac conduits (ECC, n = 16) and lateral tunnels (LT, n = 25) at different caval inflow ratios of 2, 1, and 0.5 that corresponded with ages 3, 8, and 15+. In both cohorts, vorticity and VDR correlated well with PL, but ECC cohort exhibited a slightly stronger correlation for PL-VOR (>0.83) and PL-VDR (>0.89) than that for LT cohort (>0.76 and > 0.77, respectively) at all ages. Our data also suggested that absolute and indexed PL increase (p < 0.02) non-linearly as caval inflow changes with age and are highly patient-specific. Comparison of indexed power loss between our ECC and LT cohort showed that while ECC had a slightly higher median PL for all 3 caval inflow ratio examined (3.3, 8.3, 15.3) as opposed to (2.7, 7.6, 14.8), these differences were statistically non-significant. Lastly, there was a consistent rise in pressure gradient across the TCPC with age-related increase in IVC flows for both ECC and LT Fontan patient cohort. Our study provided hemodynamic insights into Fontan energetics and how they are impacted by age-dependent change in caval inflow. This workflow may help assess the long-term sustainability of the Fontan circulation and inform the design of more efficient Fontan conduits., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Ventricular ventricular interaction (VVI) affects blood volume and pressure in the right and left ventricles of the heart due to the location and balance of forces on the septal wall separating the ventricles. In healthy patients, the pressure of the left ventricle is considerably higher than the right, resulting in a septal wall that bows into the right ventricle. However, in patients with pulmonary hypertension, the pressure in the right ventricle increases significantly to a point where the pressure is similar to or surpasses that of the left ventricle during portions of the cardiac cycle. For these patients, the septal wall deviates towards the left ventricle, impacting its function. It is possible to study this effect using mathematical modeling, but existing models are nonlinear, leading to a system of algebraic differential equations that can be challenging to solve in patient-specific optimizations of clinical data. This study demonstrates that a simplified linearized model is sufficient to account for the effect of VVI and that, as expected, the impact is significantly more pronounced in patients with pulmonary hypertension., Competing Interests: Declaration of competing interest All authors of this study do not have any financial and personal relationships with other people or organizations that could inappropriately influence (bias) this work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Contrary to most vessels, the ascending thoracic aorta (ATA) not only distends but also elongates in the axial direction. The purpose of this study is to investigate the biomechanical behavior of the ascending thoracic aorta (ATA) in response to dynamic axial stretching during the cardiac cycle. In addition, the implications of neglecting this dynamic axial stretching when estimating the constitutive model parameters of the ATA are investigated. The investigations were performed through in silico simulations by assuming a Gasser-Ogden-Holzapfel (GOH) constitutive model representative of ATA tissue material. The GOH model parameters were obtained from biaxial tests performed on four human ATA tissues in a previous study. Pressure-diameter curves were simulated as synthetic data to assess the effect of neglecting dynamic axial stretching on estimating constitutive model parameters. Our findings reveal a significant increase in axial stress (~ 16%) and stored strain energy (~ 18%) in the vessel when dynamic axial stretching is considered, as opposed to assuming a fixed axial stretch. All but one artery showed increased volume compliance while considering a dynamic axial stretching condition. Furthermore, we observe a notable difference in the estimated constitutive model parameters when dynamic axial stretching of the ATA is neglected, compared to the ground truth model parameters. These results underscore the critical importance of accounting for axial deformations when conducting in vivo biomechanical characterization of the ascending thoracic aorta., (© 2024. The Author(s).)

Transcatheter aortic heart valve thrombosis (THVT) affects long-term valve durability, transvalvular pressure gradient and leaflet mobility. In this study, we conduct high-fidelity fluid-structure interaction simulations to perform Lagrangian particle tracing in a generic model with larger aortic diameters (THVT model) with and without neo-sinus which is compared to a model of unaffected TAVI patients (control model). Platelet activation indices are computed for each particle to assess the risk of thrombus formation induced by high shear stresses followed by flow stagnation. Particle tracing indicates that fewer particles contribute to sinus washout of the THVT model with and without neo-sinus compared to the control model (-34.9%/-34.1%). Stagnating particles in the native sinus of the THVT model show higher platelet activation indices than for the control model (+39.6% without neo-sinus, +45.3% with neo-sinus). Highest activation indices are present for particles stagnating in the neo-sinus of the larger aorta representing THVT patients (+80.2% compared to control). This fluid-structure interaction (FSI) study suggests that larger aortas lead to less efficient sinus washout in combination with higher risk of platelet activation among stagnating particles, especially within the neo-sinus. This could explain (a) a higher occurrence of thrombus formation in transcatheter valves compared to surgical valves without neo-sinus and (b) the neo-sinus as the prevalent region for thrombi in TAV. Pre-procedural identification of larger aortic roots could contribute to better risk assessment of patients and improved selection of a patient-specific anti-coagulation therapy., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: Through their contractile and synthetic capacity, vascular smooth muscle cells (VSMCs) can regulate the stiffness and resistance of the circulation. To model the contraction of blood vessels, an active stress component can be added to the (passive) Cauchy stress tensor. Different constitutive formulations have been proposed to describe this active stress component. Notably, however, measuring biomechanical behaviour of contracted blood vessels ex vivo presents several experimental challenges, which complicate the acquisition of comprehensive datasets to inform complex active stress models. In this work, we examine formulations for use with limited experimental contraction data as well as those developed to capture more comprehensive datasets., Methods: First, we prove analytically that a subset of constitutive active stress formulations exhibits unstable behaviours (i.e., a non-unique diameter solution for a given pressure) in certain parameter ranges, particularly for large contractile deformations. Second, using experimental literature data, we present two case studies where these formulations are used to capture the contractile response of VSMCs in the presence of (1) limited and (2) extensive contraction data., Results: We show how limited contraction data complicates selecting an appropriate active stress model for vascular applications, potentially resulting in unrealistic modelled behaviours., Conclusion: Our data provide a useful reference for selecting an active stress model which balances the trade-off between accuracy and available biomechanical information. Whilst complex physiologically motivated models' superior accuracy is recommended whenever active biomechanics can be extensively characterised experimentally, a constant 2nd Piola-Kirchhoff active stress model balances well accuracy and applicability with sparse contractile data., (© 2024. The Author(s).)

Background and Objective: Atrial fibrillation (AF) is the most common cardiac arrhythmia, inducing accelerated and irregular beating. Beside well-known disabling symptoms - such as palpitations, reduced exercise tolerance, and chest discomfort - there is growing evidence that an alteration of deep cerebral hemodynamics due to AF increases the risk of vascular dementia and cognitive impairment, even in the absence of clinical strokes. The alteration of deep cerebral circulation in AF represents one of the least investigated among the possible mechanisms. Lenticulostriate arteries (LSAs) are small perforating arteries mainly departing from the middle cerebral artery (MCA) and susceptible to small vessel disease, which is one of the mechanisms of subcortical vascular dementia development. The purpose of this study is to investigate the impact of different LSAs morphologies on the cerebral hemodynamics during AF., Methods: By combining a computational fluid dynamics (CFD) analysis of LSAs with 7T high-resolution magnetic resonance imaging (MRI), we performed different CFD-based multivariate regression analyses to detect which geometrical and morphological vessel features mostly affect AF hemodynamics in terms of wall shear stress. We exploited 17 cerebral 7T-MRI derived LSA vascular geometries extracted from 10 subjects and internal carotid artery data from validated 0D cardiovascular-cerebral modeling as inflow conditions., Results: Our results revealed that few geometrical variables - namely the size of the MCA and the bifurcation angles between MCA and LSA - are able to satisfactorily predict the AF impact. In particular, the present study indicates that LSA morphologies exhibiting markedly obtuse LSA-MCA inlet angles and small MCA size downstream of the LSA-MCA bifurcation may be more prone to vascular damage induced by AF., Conclusions: The present MRI-based computational study has been able for the first time to: (i) investigate the net impact of LSAs vascular morphologies on cerebral hemodynamics during AF events; (ii) detect which combination of morphological features worsens the hemodynamic response in the presence of AF. Awaiting necessary clinical confirmation, our analysis suggests that the local hemodynamics of LSAs is affected by their geometrical features and some LSA morphologies undergo greater hemodynamic alterations in the presence of AF., 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 © 2024. Published by Elsevier B.V.)

Pulmonary valve replacement (PVR) consists of substituting a patient's original valve with a prosthetic one, primarily addressing pulmonary valve insufficiency, which is crucially relevant in Tetralogy of Fallot repairment. While extensive clinical and computational literature on aortic and mitral valve replacements is available, PVR's post-procedural haemodynamics in the pulmonary artery and the impact of prosthetic valve dynamics remain significantly understudied. Addressing this gap, we introduce a reduced Fluid-Structure Interaction (rFSI) model, applied for the first time to the pulmonary valve. This model couples a three-dimensional computational representation of pulmonary artery haemodynamics with a one-degree-of-freedom model to account for valve structural mechanics. Through this approach, we analyse patient-specific haemodynamics pre and post PVR. Patient-specific geometries, reconstructed from CT scans, are virtually equipped with a template valve geometry. Boundary conditions for the model are established using a lumped-parameter model, fine-tuned based on clinical patient data. Our model accurately reproduces patient-specific haemodynamic changes across different scenarios: pre-PVR, six months post-PVR, and a follow-up condition after a decade. It effectively demonstrates the impact of valve implantation on sustaining the diastolic pressure gradient across the valve. The numerical results indicate that our valve model is able to reproduce overall physiological and/or pathological conditions, as preliminary assessed on two different patients. This promising approach provides insights into post-PVR haemodynamics and prosthetic valve effects, shedding light on potential implications for patient-specific outcomes., (© 2024 The Author(s). International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.)

Myocardial stretch physiologically activates NADPH oxidase 2 (NOX2) to increase reactive oxygen species (ROS) production. Although physiological low-level ROS are known to be important as signalling molecules, the role of stretch-induced ROS in the intact myocardium remains unclear. To address this, we investigated the effects of stretch-induced ROS on myocardial cellular contractility and calcium transients in C57BL/6J and NOX2 -/- mice. Axial stretch was applied to the isolated cardiomyocytes using a pair of carbon fibres attached to both cell ends to evaluate stretch-induced modulation in the time course of the contraction curve and calcium transient, as well as to evaluate maximum cellular elastance, an index of cellular contractility, which is obtained from the end-systolic force-length relationship. In NOX2 -/- mice, the peak calcium transient was not altered by stretch, as that in wild-type mice, but the lack of stretch-induced ROS delayed the rise of calcium transients and reduced contractility. Our mathematical modelling studies suggest that the augmented activation of ryanodine receptors by stretch-induced ROS causes a rapid and large increase in the calcium release flux, resulting in a faster rise in the calcium transient. The slight increase in the magnitude of calcium transients is offset by a decrease in sarcoplasmic reticulum calcium content as a result of ROS-induced calcium leakage, but the faster rise in calcium transients still maintains higher contractility. In conclusion, a physiological role of stretch-induced ROS is to increase contractility to counteract a given preload, that is, it contributes to the Frank-Starling law of the heart. KEY POINTS: Myocardial stretch increases the production of reactive oxygen species by NADPH oxidase 2. We used NADPH oxidase 2 knockout mice to elucidate the physiological role of stretch-induced reactive oxygen species in the heart. We showed that stretch-induced reactive oxygen species modulate the rising phase of calcium transients and increase myocardial contractility. A mathematical model simulation study demonstrated that rapid activation of ryanodine receptors by reactive oxygen species is important for increased contractility. This response is advantageous for the myocardium, which must contract against a given preload., (© 2023 The Authors. The Journal of Physiology © 2023 The Physiological Society.)

The Circle of Willis (CoW) is a ring-like network of blood vessels that perfuses the brain. Flow in the collateral pathways that connect major arterial inputs in the CoW change dynamically in response to vessel narrowing or occlusion. Vasospasm is an involuntary constriction of blood vessels following subarachnoid hemorrhage (SAH), which can lead to stroke. This study investigated interactions between localization of vasospasm in the CoW, vasospasm severity, anatomical variations, and changes in collateral flow directions. Patient-specific computational fluid dynamics (CFD) simulations were created for 25 vasospasm patients. Computed tomographic angiography scans were segmented capturing the anatomical variation and stenosis due to vasospasm. Transcranial Doppler ultrasound measurements of velocity were used to define boundary conditions. Digital subtraction angiography was analyzed to determine the directions and magnitudes of collateral flows as well as vasospasm severity in each vessel. Percent changes in resistance and viscous dissipation were analyzed to quantify vasospasm severity and localization of vasospasm in a specific region of the CoW. Angiographic severity correlated well with percent changes in resistance and viscous dissipation across all cerebral vessels. Changes in flow direction were observed in collateral pathways of some patients with localized vasospasm, while no significant changes in flow direction were observed in others. CFD simulations can be leveraged to quantify the localization and severity of vasospasm in SAH patients. These factors as well as anatomical variation may lead to changes in collateral flow directions. Future work could relate localization and vasospasm severity to clinical outcomes like the development of infarct., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Recent clinical studies have reported that heart failure with preserved ejection fraction (HFpEF) can be divided into two phenotypes based on the range of ejection fraction (EF), namely HFpEF with higher EF and HFpEF with lower EF. These phenotypes exhibit distinct left ventricle (LV) remodelling patterns and dynamics. However, the influence of LV remodelling on various LV functional indices and the underlying mechanics for these two phenotypes are not well understood. To address these issues, this study employs a coupled finite element analysis (FEA) framework to analyse the impact of various ventricular remodelling patterns, specifically concentric remodelling (CR), concentric hypertrophy (CH), and eccentric hypertrophy (EH), with and without LV wall thickening on LV functional indices. Further, the geometries with a moderate level of remodelling from each pattern are subjected to fibre stiffening and contractile impairment to examine their effect in replicating the different features of HFpEF. The results show that with severe CR, LV could exhibit the characteristics of HFpEF with higher EF, as observed in recent clinical studies. Controlled fibre stiffening can simultaneously increase the end-diastolic pressure (EDP) and reduce the peak longitudinal strain (e ll ) without significant reduction in EF, facilitating the moderate CR geometries to fit into this phenotype. Similarly, fibre stiffening can assist the CH and 'EH with wall thickening' cases to replicate HFpEF with lower EF. These findings suggest that potential treatment for these two phenotypes should target the bio-origins of their distinct ventricular remodelling patterns and the extent of myocardial stiffening., 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 © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In this study, a physics-based model is developed to describe the entire flow mediated dilation (FMD) response. A parameter quantifying the arterial wall's tendency to recover arises from the model, thereby providing a more elaborate description of the artery's physical state, in concert with other parameters characterizing mechanotransduction and structural aspects of the arterial wall. The arterial diameter's behavior throughout the full response is successfully reproduced by the model. Experimental FMD response data were obtained from healthy volunteers. The model's parameters are then adjusted to yield the closest match to the observed experimental response, hence delivering the parameter values pertaining to each subject. This study establishes a foundation based on which future potential clinical applications can be introduced, where endothelial function and general cardiovascular health are inexpensively and noninvasively quantified., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background and Objective: The implantation of ventricular assist devices (VADs) has become an important treatment option for patients with heart failure. Aortic valve insufficiency is a common complication caused by VADs implantation. Currently, there is very little quantitative research on the effects of transcatheter micro VADs or the intervention pumps on the aortic valves., Methods: In this study, the multi-component arbitrary Lagrange-Eulerian method is used to perform fluid-structure interaction simulations of the aortic valve model with and without intervention pumps. The effects of intervention pumps implantation on the opening area of the aortic valves, the stress distribution, and the flow characteristics are quantitatively analyzed. Statistical results are consistent with clinical guidelines and experiments., Results: The implantation of intervention pumps leads to the valve insufficiency and causes weak valve regurgitation. In the short-term treatment, the valve regurgitation is within a controllable range. The distribution and variation of stress on the leaflets are also affected by intervention pumps. The whirling flow in the flow direction affects the closing speed of the aortic valves and optimizes the stress distribution of the valves. In the models with whirling flow, the effects of intervention pumps implantation on valve motion and stress distribution differ from those without whirling flow. However, the valve insufficiency and valve regurgitation caused by intervention pumps still exist in the models with whirling flow. Conventional artificial bioprosthetic valves have limited effectiveness in treating the valve diseases caused by intervention pumps implantation., Conclusions: This study quantitatively investigates the impact of intervention pumps on the aortic valves, and investigates the effect of blood rotation on the valve behavior, which is a gap in previous research. We suggest that in the short-term treatment, the implantation of intervention pumps has limited impact on aortic valves, caution should be exercised against valve regurgitation issues caused by intervention pumps., Competing Interests: Declaration of competing interest The 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., (Copyright © 2024. Published by Elsevier B.V.)

In this work we present a novel methodology for the numerical simulation of patient-specific aortic dissections. Our proposal, which targets the seamless virtual prototyping of customized scenarios, combines an innovative two-step segmentation procedure with a CutFEM technique capable of dealing with thin-walled bodies such as the intimal flap. First, we generate the fluid mesh from the outer aortic wall disregarding the intimal flap, similarly to what would be done in a healthy aorta. Second, we create a surface mesh from the approximate midline of the intimal flap. This approach allows us to decouple the segmentation of the fluid volume from that of the intimal flap, thereby bypassing the need to create a volumetric mesh around a thin-walled body, an operation widely known to be complex and error-prone. Once the two meshes are obtained, the original configuration of the dissection into true and false lumen is recovered by embedding the surface mesh into the volumetric one and calculating a level set function that implicitly represents the intimal flap in terms of the volumetric mesh entities. We then leverage the capabilities of unfitted mesh methods, specifically relying on a CutFEM technique tailored for thin-walled bodies, to impose the wall boundary conditions over the embedded intimal flap. We tested the method by simulating the flow in four patient-specific aortic dissections, all involving intricate geometrical patterns. In all cases, the preprocess is greatly simplified with no impact on the computational times. Additionally, the obtained results are consistent with clinical evidence and previous research., 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 © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: The characterization and selection of heart failure (HF) patients for cardiac resynchronization therapy (CRT) remain challenging, with around 30% non-responder rate despite following current guidelines. This study aims to propose a novel hybrid approach, integrating machine-learning and personalized models, to identify explainable phenogroups of HF patients and predict their CRT response., Methods: The paper proposes the creation of a complete personalized model population based on preoperative CRT patient strain curves. Based on the parameters and features extracted from these personalized models, phenotypes of patients are identified thanks to a clustering algorithm and a random forest classification is provided., Results: A close match was observed between the 162 experimental and simulated myocardial strain curves, with a mean RMSE of 4.48% (±1.08) for the 162 patients. Five phenogroups of personalized models were identified from the clustering, with response rates ranging from 52% to 94%. The classification results show a mean area under the curves (AUC) of 0.86 ± 0.06 and provided a feature importance analysis with 22 features selected. Results show both regional myocardial contractility (from 22.5% to 33.0%), tissue viability and electrical activation delays importance on CRT response for each HF patient (from 55.8 ms to 88.4 ms)., Discussion: The patient-specific model parameters' analysis provides an explainable interpretation of HF patient phenogroups in relation to physiological mechanisms that seem predictive of the CRT response. These novel combined approaches appear as promising tools to improve understanding of LV mechanical dyssynchrony for HF patient characterization and CRT selection., Competing Interests: Declaration of competing interest No conflict of interest exists. We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background and Objective: In this work, the analysis of the importance of hemodynamic updates on a mechanobiological model of atheroma plaque formation is proposed., Methods: For that, we use an idealized and axisymmetric model of carotid artery. In addition, the behavior of endothelial cells depending on hemodynamical changes is analyzed too. A total of three computational simulations are carried out and their results are compared: an uncoupled model and two models that consider the opposite behavior of endothelial cells caused by hemodynamic changes. The model considers transient blood flow using the Navier-Stokes equation. Plasma flow across the endothelium is determined with Darcy's law and the Kedem-Katchalsky equations, considering the three-pore model, which is also employed for the flow of substances across the endothelium. The behavior of the considered substances in the arterial wall is modeled with convection-diffusion-reaction equations, and the arterial wall is modeled as a hyperelastic Yeoh's material., Results: Significant variations are noted in both the morphology and stenosis ratio of the plaques when comparing the uncoupled model to the two models incorporating updates for geometry and hemodynamic stimuli. Besides, the phenomenon of double-stenosis is naturally reproduced in the models that consider both geometric and hemodynamical changes due to plaque growth, whereas it cannot be predicted in the uncoupled model., Conclusions: The findings indicate that integrating the plaque growth model with geometric and hemodynamic settings is essential in determining the ultimate shape and dimensions of the carotid plaque., 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 © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: The high efficacy of flow diverters (FD) in the case of wide-neck aneurysms is well demonstrated, yet new challenges have arisen because of reported posttreatment failures and the growing number of new generation of devices. Our aim is to present a measurement-supported in silico workflow that automates the virtual deployment and subsequent hemodynamic analysis of FDs. In this work, the objective is to analyze the effects of FD deployment variability of two manufacturers on posttreatment flow reduction., Methods: The virtual deployment procedure is based on detailed mechanical calibration of the flow diverters, while the flow representation is based on hydrodynamic resistance (HR) measurements. Computational fluid dynamic simulations resulted in 5 untreated and 80 virtually treated scenarios, including 2 FD designs in nominal and oversized deployment states. The simulated aneurysmal velocity reduction (AMVR) is correlated with the HR values and deployment scenarios., Results: The linear HR coefficient and AMVR revealed a power-law relationship considering all 80 deployments. In nominal deployment scenarios, a significantly larger average AMVR was obtained (60.3%) for the 64-wire FDs than for 48-wire FDs (51.9%). In oversized deployments, the average AMVR was almost the same for 64-wire and 48-wire device types, 27.5% and 25.7%, respectively., Conclusion: The applicability of our numerical workflow was demonstrated, also in large-scale hemodynamic investigations. The study revealed a robust power-law relationship between a HR coefficient and AMVR. Furthermore, the 64 wire configurations in nominal sizing produced a significantly higher posttreatment flow reduction, replicating the results of other in vitro studies., (© 2024. The Author(s).)

Personalized, image-based computational heart modelling is a powerful technology that can be used to improve patient-specific arrhythmia risk stratification and ventricular tachycardia (VT) ablation targeting. However, most state-of-the-art methods still require manual interactions by expert users. The goal of this study is to evaluate the feasibility of an automated, deep learning-based workflow for reconstructing personalized computational electrophysiological heart models to guide patient-specific treatment of VT. Contrast-enhanced computed tomography (CE-CT) images with expert ventricular myocardium segmentations were acquired from 111 patients across five cohorts from three different institutions. A deep convolutional neural network (CNN) for segmenting left ventricular myocardium from CE-CT was developed, trained and evaluated. From both CNN-based and expert segmentations in a subset of patients, personalized electrophysiological heart models were reconstructed and rapid pacing was used to induce VTs. CNN-based and expert segmentations were more concordant in the middle myocardium than in the heart's base or apex. Wavefront propagation during pacing was similar between CNN-based and original heart models. Between most sets of heart models, VT inducibility was the same, the number of induced VTs was strongly correlated, and VT circuits co-localized. Our results demonstrate that personalized computational heart models reconstructed from deep learning-based segmentations even with a small training set size can predict similar VT inducibility and circuit locations as those from expertly-derived heart models. Hence, a user-independent, automated framework for simulating arrhythmias in personalized heart models could feasibly be used in clinical settings to aid VT risk stratification and guide VT ablation therapy. KEY POINTS: Personalized electrophysiological heart modelling can aid in patient-specific ventricular tachycardia (VT) risk stratification and VT ablation targeting. Current state-of-the-art, image-based heart models for VT prediction require expert-dependent, manual interactions that may not be accessible across clinical settings. In this study, we develop an automated, deep learning-based workflow for reconstructing personalized heart models capable of simulating arrhythmias and compare its predictions with that of expert-generated heart models. The number and location of VTs was similar between heart models generated from the deep learning-based workflow and expert-generated heart models. These results demonstrate the feasibility of using an automated computational heart modelling workflow to aid in VT therapeutics and has implications for generalizing personalized computational heart technology to a broad range of clinical centres., (© 2023 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Cardiac electrophysiology and mechanics are strongly interconnected. Their interaction is, among others, mediated by mechano-electric feedback through stretch-activated ion channels (SACs). The electrophysiological changes induced by SACs may contribute to arrhythmogenesis, but the precise SAC-induced electrophysiological changes remain incompletely understood. Here, we provide a systematic characterization of stretch effects through three distinguished SACs on cardiac electrophysiology using computational modelling. We implemented potassium-selective, calcium-selective and non-selective SACs in the Tomek-Rodriguez-O'Hara-Rudy model of human ventricular electrophysiology. The model was calibrated to experimental data from isolated cardiomyocytes undergoing stretch, considering inter-species differences, and disease-related remodelling of SACs. SAC-mediated effects on the action potential (AP) were analysed by varying stretch amplitude, application timing and/or duration. Afterdepolarizations of different amplitudes were observed with transient 10-ms stretch stimuli of 15-18% applied during phase 4, while stretch ≥18% during phase 4 elicited triggered APs. Longer stimuli shifted the threshold of AP trigger during phase 4 to lower amplitudes, while shorter stimuli increased it. Continuous stretch provoked electrophysiological remodelling. Furthermore, stretch shortened duration or changed morphology of a subsequent electrically evoked AP, and, if applied during a vulnerable time window with sufficient amplitude, prevented its occurrence because of stretch-induced modulation of sodium and L-type calcium channel gating. These effects were more pronounced with disease-related SAC remodelling due to increased stretch sensitivity of diseased hearts. We showed that SACs may induce afterdepolarizations and triggered activities, and prevent subsequent AP generation or change its morphology. These effects depend on cardiomyocyte stretch characteristics and disease-related SACs remodelling and may contribute to cardiac arrhythmogenesis. KEY POINTS: The interplay between cardiac electrophysiology and mechanics is mediated by mechano-electric feedback through stretch-activated ion channels (SACs). These channels may be pro-arrhythmic, but their precise effect on electrophysiology remains unclear. Here we present a systematic in silico characterization of stretch effects through three SACs by implementing inter-species differences as well as disease-related remodelling of SACs in a novel computational model of human ventricular cardiomyocyte electrophysiology. Our simulations showed that, at the cellular level, SACs may provoke electrophysiological remodelling, afterdepolarizations, triggered activities, change the morphology or shorten subsequent electrically evoked action potentials. The model further suggests that a vulnerable window exists in which stretch prevents the following electrically triggered beat occurrence. The pro-arrhythmic effects of stretch strongly depend on disease-related SAC remodelling as well as on stretch characteristics, such as amplitude, time of application and duration. Our study helps in understanding the role of stretch in cardiac arrhythmogenesis and revealing the underlying cellular mechanisms., (© 2023 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Mathematical models can be used to generate high-fidelity simulations of the cardiopulmonary system. Such models, when applied to real patients, can provide valuable insights into underlying physiological processes that are hard for clinicians to observe directly. In this work, we propose a novel modelling strategy capable of generating scenario-specific cardiopulmonary simulations to replicate the vital physiological signals clinicians use to determine the state of a patient. This model is composed of a tree-like pulmonary system that features a novel, non-linear alveoli opening strategy, based on the dynamics of balloon inflation, that interacts with the cardiovascular system via the thorax. A baseline simulation of the model is performed to measure the response of the system during spontaneous breathing which is subsequently compared to the same system under mechanical ventilation. To test the new lung opening mechanics and systematic recruitment of alveolar units, a positive end-expiratory pressure (PEEP) test is performed and its results are then compared to simulations of a deep spontaneous breath. The system displays a marked decrease in tidal volume as PEEP increases, replicating a sigmoidal curve relationship between volume and pressure. At high PEEP, cardiovascular function is shown to be visibly impaired, in contrast to the deep breath test where normal function is maintained., 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 © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Platelet aggregation is a dynamic process that can obstruct blood flow, leading to cardiovascular diseases. While many studies have demonstrated clear connections between shear rate and platelet aggregation, the impact of flow-derived mechanical signals on this process is not fully understood. The objective of this work is to investigate the role of flow conditions on platelet aggregation dynamics, including effects on growth, shape, density composition, and their potential correlation with binding processes that are characterised by longer (e.g., via αIIbβ3 integrin) and shorter (e.g., via VWF) initial binding times. In vitro blood perfusion experiments were conducted at wall shear rates of 800, 1600 and 4000 s -1 . Detailed analysis of two modalities of experimental images was performed to offer insights into the morphology of platelet aggregates. A consistent structural pattern was observed across all samples: a high-density core enveloped by a low-density outer shell. An image-based 3D computational blood flow model was subsequently employed to study the local flow conditions, including binding availability time and flow-derived mechanical signals via shear rate and rate of elongation. The results show substantial dependence of the aggregation dynamics on these flow parameters. We found that the different binding mechanisms that prefer different flow regimes do not have a monotonic cross-over in efficiency as the flow increases. There is a significant dip in the cumulative aggregation potential in-between the preferred regimes. The results suggest that treatments targeting the biomechanical pathways could benefit from creating conditions that exploit these low-efficiency zones of aggregation., 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 © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Extracting phenotype-representative flow patterns and their associated numerical metrics is a bottleneck in the clinical translation of advanced cardiac flow imaging modalities. We hypothesized that reduced-order models (ROMs) are a suitable strategy for deriving simple and interpretable clinical metrics of intraventricular flow suitable for further assessments. Combined with machine learning (ML) flow-based ROMs could provide new insight to help diagnose and risk-stratify patients., Methods: We analyzed 2D color-Doppler echocardiograms of 81 non-ischemic dilated cardiomyopathy (DCM) patients, 51 hypertrophic cardiomyopathy (HCM) patients, and 77 normal volunteers (Control). We applied proper orthogonal decomposition (POD) to build patient-specific and cohort-specific ROMs of LV flow. Each ROM aggregates a low number of components representing a spatially dependent velocity map modulated along the cardiac cycle by a time-dependent coefficient. We tested three classifiers using deliberately simple ML analyses of these ROMs with varying supervision levels. In supervised models, hyperparameter grid search was used to derive the ROMs that maximize classification power. The classifiers were blinded to LV chamber geometry and function. We ran vector flow mapping on the color-Doppler sequences to help visualize flow patterns and interpret the ML results., Results: POD-based ROMs stably represented each cohort through 10-fold cross-validation. The principal POD mode captured >80 % of the flow kinetic energy (KE) in all cohorts and represented the LV filling/emptying jets. Mode 2 represented the diastolic vortex and its KE contribution ranged from <1 % (HCM) to 13 % (DCM). Semi-unsupervised classification using patient-specific ROMs revealed that the KE ratio of these two principal modes, the vortex-to-jet (V2J) energy ratio, is a simple, interpretable metric that discriminates DCM, HCM, and Control patients. Receiver operating characteristic curves using V2J as classifier had areas under the curve of 0.81, 0.91, and 0.95 for distinguishing HCM vs. Control, DCM vs. Control, and DCM vs. HCM, respectively., Conclusions: Modal decomposition of cardiac flow can be used to create ROMs of normal and pathological flow patterns, uncovering simple interpretable flow metrics with power to discriminate disease states, and particularly suitable for further processing using ML., 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 © 2024. Published by Elsevier Ltd.)

Vascular diseases are greatly influenced by the hemodynamic parameters and the accuracy of determining these parameters depends on the use of correct boundary conditions. The present work carries out a two-way fluid-structure interaction (FSI) simulation to investigate the effects of outlet pressure boundary conditions on the hemodynamics through the left coronary artery bifurcation with moderate stenosis (50%) in the left anterior descending (LAD) branch. The Carreau viscosity model is employed to characterise the shear-thinning behaviour of blood. The results of the study reveal that the employment of zero pressure at the outlet boundaries significantly overestimates the values of hemodynamic variables like wall shear stress (WSS), and time-averaged wall shear stress (TAWSS) compared with human healthy and pulsatile pressure outlet conditions. However, the difference between these variables is marginally low for human healthy and pulsatile pressure outlets. The oscillatory shear index (OSI) remains the same across all scenarios, indicating independence from the outlet boundary condition. Furthermore, the magnitude of negative axial velocity and pressure drop across the plaque are found to be higher at the zero pressure outlet boundary condition., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

2'-deoxy-ATP (dATP) improves cardiac function by increasing the rate of crossbridge cycling and Ca[Formula: see text] transient decay. However, the mechanisms of these effects and how therapeutic responses to dATP are achieved when dATP is only a small fraction of the total ATP pool remain poorly understood. Here, we used a multiscale computational modeling approach to analyze the mechanisms by which dATP improves ventricular function. We integrated atomistic simulations of prepowerstroke myosin and actomyosin association, filament-scale Markov state modeling of sarcomere mechanics, cell-scale analysis of myocyte Ca[Formula: see text] dynamics and contraction, organ-scale modeling of biventricular mechanoenergetics, and systems level modeling of circulatory dynamics. Molecular and Brownian dynamics simulations showed that dATP increases the actomyosin association rate by 1.9 fold. Markov state models predicted that dATP increases the pool of myosin heads available for crossbridge cycling, increasing steady-state force development at low dATP fractions by 1.3 fold due to mechanosensing and nearest-neighbor cooperativity. This was found to be the dominant mechanism by which small amounts of dATP can improve contractile function at myofilament to organ scales. Together with faster myocyte Ca[Formula: see text] handling, this led to improved ventricular contractility, especially in a failing heart model in which dATP increased ejection fraction by 16% and the energy efficiency of cardiac contraction by 1%. This work represents a complete multiscale model analysis of a small molecule myosin modulator from single molecule to organ system biophysics and elucidates how the molecular mechanisms of dATP may improve cardiovascular function in heart failure with reduced ejection fraction., Competing Interests: Competing interests statement:A.D.M. is a cofounder of and has equity interests in Insilicomed Inc. and Vektor Medical, Inc. He serves as scientific advisor to both companies. Some of A.D.M.’s research grants have been identified for conflict of interest management based on the overall scope of the project and its potential benefit to Insilicomed Inc. and Vektor Medical, Inc. The author is required to disclose this relationship in publications acknowledging the grant support; however, the research subject and findings reported in this study did not involve the companies in any way and have no relationship with the business activities or scientific interests of either company. The terms of this arrangement have been reviewed and approved by the University of California San Diego in accordance with its conflict of interest policies.

To investigate the biomechanical effects of direct ventricular assistance and explore the optimal loading mode, this study established a left ventricular model of heart failure patients based on the finite element method. It proposed a loading mode that maintains peak pressure compression, and compared it with the traditional sinusoidal loading mode from both hemodynamic and biomechanical perspectives. The results showed that both modes significantly improved hemodynamic parameters, with ejection fraction increased from a baseline of 29.33% to 37.32% and 37.77%, respectively, while peak pressure, stroke volume, and stroke work parameters also increased. Additionally, both modes showed improvements in stress concentration and excessive fiber strain. Moreover, considering the phase error of the assist device's working cycle, the proposed assist mode in this study was less affected. Therefore, this research may provide theoretical support for the design and optimization of direct ventricular assist devices.

One of the many unresolved obstacles in the field of cardiovascular research is an uncompromising in vitro cardiac model. While primary cell sources from animal models offer both advantages and disadvantages, efforts over the past half-century have aimed to reduce their use. Additionally, obtaining a sufficient quantity of human primary cardiomyocytes faces ethical and legal challenges. As the practically unlimited source of human cardiomyocytes from induced pluripotent stem cells (hiPSC-CM) is now mostly resolved, there are great efforts to improve their quality and applicability by overcoming their intrinsic limitations. The greatest bottleneck in the field is the in vitro ageing of hiPSC-CMs to reach a maturity status that closely resembles that of the adult heart, thereby allowing for more appropriate drug developmental procedures as there is a clear correlation between ageing and developing cardiovascular diseases. Here, we review the current state-of-the-art techniques in the most realistic heart models used in disease modelling and toxicity evaluations from hiPSC-CM maturation through heart-on-a-chip platforms and in silico models to the in vitro models of certain cardiovascular diseases.

Flow fluctuations have emerged as a promising hemodynamic metric for understanding of hemodynamics in intracranial aneurysms. Several investigations have reported flow instabilities using numerical tools. In this study, the occurrence of flow fluctuations is investigated using either Newtonian or non-Newtonian fluid models in five patient-specific intracranial aneurysms using high-resolution lattice Boltzmann simulation methods. Flow instabilities are quantified by computing power spectral density, proper orthogonal decomposition, and fluctuating kinetic energy of velocity fluctuations. Our simulations reveal substantial flow instabilities in two of the ruptured aneurysms, where the pulsatile inflow through the neck leads to hydrodynamic instability, particularly around the rupture position, throughout the entire cardiac cycle. In other monitoring points, the flow instability is primarily observed during the deceleration phase; typically, the fluctuations begin just after peak systole, gradually decay, and the flow returns to its original, laminar pulsatile state during diastole. Additionally, we assess the rheological impact on flow dynamics. The disparity between Newtonian and non-Newtonian outcomes remains minimal in unruptured aneurysms, with less than a 5% difference in key metrics. However, in ruptured cases, adopting a non-Newtonian model yields a substantial increase in the fluctuations within the aneurysm sac, with up to a 30% higher fluctuating kinetic energy compared to the Newtonian model. The study highlights the importance of using appropriate high-resolution simulations and non-Newtonian models to capture flow fluctuation characteristics that may be critical for assessing aneurysm rupture risk., (© 2024. The Author(s).)

Heart rate variability (HRV) is an important metric in cardiovascular health monitoring. Spectral analysis of HRV provides essential insights into the functioning of the cardiac autonomic nervous system. However, data artefacts could degrade signal quality, potentially leading to unreliable assessments of cardiac activities. In this study, we introduced a novel approach for estimating uncertainties in HRV spectrum based on matrix completion. The proposed method utilises the low-rank characteristic of HRV spectrum matrix to efficiently estimate data uncertainties. In addition, we developed a refined matrix completion technique to enhance the estimation accuracy and computational cost. Benchmarking on five public datasets, our model shows effectiveness and reliability in estimating uncertainties in HRV spectrum, and has superior performance against five deep learning models. The results underscore the potential of our developed matrix completion-based statistical machine learning model in providing reliable HRV spectrum uncertainty estimation.

Macrophages in atherosclerotic lesions exhibit a spectrum of behaviours or phenotypes. The phenotypic distribution of monocyte-derived macrophages (MDMs), its correlation with MDM lipid content, and relation to blood lipoprotein densities are not well understood. Of particular interest is the balance between low density lipoproteins (LDL) and high density lipoproteins (HDL), which carry bad and good cholesterol respectively. To address these issues, we have developed a mathematical model for early atherosclerosis in which the MDM population is structured by phenotype and lipid content. The model admits a simpler, closed subsystem whose analysis shows how lesion composition becomes more pathological as the blood density of LDL increases relative to the HDL capacity. We use asymptotic analysis to derive a power-law relationship between MDM phenotype and lipid content at steady-state. This relationship enables us to understand why, for example, lipid-laden MDMs have a more inflammatory phenotype than lipid-poor MDMs when blood LDL lipid density greatly exceeds HDL capacity. We show further that the MDM phenotype distribution always attains a local maximum, while the lipid content distribution may be unimodal, adopt a quasi-uniform profile or decrease monotonically. Pathological lesions exhibit a local maximum in both the phenotype and lipid content MDM distributions, with the maximum at an inflammatory phenotype and near the lipid content capacity respectively. These results illustrate how macrophage heterogeneity arises in early atherosclerosis and provide a framework for future model validation through comparison with single-cell RNA sequencing data., (© 2024. The Author(s).)

Inferior vena cava filter (IVCF) implantation is a common method of thrombus capture. By implanting a filter in the inferior vena cava (IVC), microemboli can be effectively blocked from entering the pulmonary circulation, thereby avoiding acute pulmonary embolism (PE). Inspired by the helical flow effect in the human arterial system, we propose a helical retrievable IVCF, which, due to the presence of a helical structure inducing a helical flow pattern of blood in the region near the IVCF, can effectively avoid the deposition of microemboli in the vicinity of the IVCF while promoting the cleavage of the captured thrombus clot. It also reduces the risk of IVCF dislodging and slipping in the vessel because its shape expands in the radial direction, allowing its distal end to fit closely to the IVC wall, and because its contact structure with the inner IVC wall is curved, increasing the contact area and reducing the risk of the vessel wall being punctured by the IVCF support structure. We used ANSYS 2023 software to conduct unidirectional fluid-structure coupling simulation of four different forms of IVCF, combined with microthrombus capture experiments in vitro, to explore the impact of these four forms of IVCF on blood flow patterns and to evaluate the risk of IVCF perforation and IVCF dislocation. It can be seen from the numerical simulation results that the helical structure does have the function of inducing blood flow to undergo helical flow dynamics, and the increase in wall shear stress (WSS) brought about by this function can improve the situation of thrombosis accumulation to a certain extent. Meanwhile, the placement of IVCF will change the flow state of blood flow and lead to the deformation of blood vessels. In in vitro experiments, we found that the density of the helical support rod is a key factor affecting the thrombus trapping efficiency, and in addition, the contact area between the IVCF and the vessel wall has a major influence on the risk of IVCF displacement., (© 2024. The Author(s).)

The assessment and reduction of haemolysis within mechanical circulatory support (MCS) remains a concern with regard to device safety and regulatory approval. Numerical methods for predicting haemolysis have typically been applied to rotary MCS devices and the extent to which these methods apply to positive-displacement MCS is unclear. The aim of this study was to evaluate the suitability of these methods for assessing haemolysis in positive-displacement blood pumps. Eulerian scalar-transport and Lagrangian particle-tracking approaches derived from the shear-based power-law relationship were used to calculate haemolysis in a computational fluid dynamics model of the Realheart total artificial heart. A range of power-law constants and their effect on simulated haemolysis were also investigated. Both Eulerian and Lagrangian methods identified the same key mechanism of haemolysis: leakage flow through the bileaflet valves. Whilst the magnitude of haemolysis varied with different power-law constants, the method of haemolysis generation remained consistent. The Eulerian method was more robust and reliable at identifying sites of haemolysis generation, as it was able to capture the persistent leakage flow throughout the entire pumping cycle. This study paves the way for different positive-displacement MCS devices to be compared across different operating conditions, enabling the optimisation of these pumps for improved patient outcomes., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: S.F.Z, A.N., T.F. and I.L.P. are employees of or consultants to and/or shareholders of Scandinavian Real Heart AB. J.B., A.N.C. and K.H.F. declare no potential conflicts of interest.

Spiral waves in cardiac tissue have been identified as a significant factor leading to life-threatening arrhythmias and ventricular fibrillation. Consequently, understanding the mechanisms underlying the dynamics of such waves and exploring strategies for their elimination have garnered substantial interest and emerged as crucial research objectives. Spiral waves often become pinned (trapped) at anatomical obstacles in cardiac tissue, resulting in increased stability and posing challenges for their elimination. The unpinning of spiral waves can be achieved through the application of an external electric field and has been the subject of previous research. Recently, optogenetics has emerged as an alternative method to modulate electrical activity by illumination of cardiac tissue. In this paper, we employ mathematical modeling to investigate the potential of utilizing local illumination to unpin and eliminate spiral waves in cardiac tissue. We also extend this methodology to explore the effects of more complex turbulent excitation patterns. We conduct simulations using low-dimensional (Barkley) and ionic (Fenton-Karma) models of cardiac tissue, incorporating optogenetical channels. Our findings demonstrate that local suprathreshold illumination can successfully unpin spiral waves in 100% of cases. Notably, unlike unpinning by electrical field stimulation, this approach does not necessitate precise timing of stimulus application during a specific phase of rotation. Additionally, we demonstrate that periodic optogenetical stimulation can effectively eliminate both unpinned spiral waves and turbulence by moving them toward the boundary via an antitachycardia pacing mechanism.

Medical advancements, particularly in ventricular assist devices (VADs), have notably advanced heart failure (HF) treatment, improving patient outcomes. However, challenges such as adverse events (strokes, bleeding and thrombosis) persist. Computational fluid dynamics (CFD) simulations are instrumental in understanding VAD flow dynamics and the associated flow-induced adverse events resulting from non-physiological flow conditions in the VAD.This study aims to validate critical CFD simulation parameters for accurate VAD simulations interacting with the cardiovascular system, building upon the groundwork laid by Hahne et al. A bidirectional coupling technique was used to model dynamic (pulsatile) flow conditions of the VAD CFD interacting with the cardiovascular system. Mesh size, time steps and simulation method (URANS, LES) were systematically varied to evaluate their impact on the dynamic pump performance (dynamic H - Q curve) of the HeartMate 3, aiming to find the optimal simulation configuration for accurately reproduce the dynamic H - Q curve. The new Overlapping Ratio (OR) method was developed and applied to quantify dynamic H - Q curves.In particular, mesh and time step sizes were found to have the greatest influence on the calculated pump performance. Therefore, small time steps and large mesh sizes are recommended to obtain accurate dynamic H - Q curves. On the other hand, the influence of the simulation method was not significant in this study. This study contributes to advancing VAD simulations, ultimately enhancing clinical efficacy and patient outcomes., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Intimal tears caused by aortic dissection can weaken the arterial wall and lead to aortic aneurysms. However, the effect of different tear states on the blood flow behaviour remains complex. This study uses a novel approach that combines numerical haemodynamic simulation with in vitro experiments to elucidate the effect of arterial dissection rupture on the complex blood flow state within the abdominal aneurysm and the endogenous causes of end-organ malperfusion., Materials and Methods: Based on the CT imaging data and clinical physiological parameters, the overall arterial models including aortic dissection and aneurysm with single tear and double tear were established, and the turbulence behaviours and haemodynamic characteristics of arterial dissection and aneurysm under different blood pressures were simulated by using non-Newtonian flow fluids with the pulsatile blood flow rate of the clinical patients as a cycle, and the results of the numerical simulation were verified by in vitro simulation experiments., Results: Hemodynamic simulations revealed that the aneurysm and single-tear false lumen generated a maximum pressure of 320.591 mmHg, 267 % over the 120 mmHg criterion. The pressure differential generates reflux, leading to a WSS of 2247.9 Pa at the TL inlet and blood flow velocities of up to 6.41 m/s inducing extend of the inlet. DTD Medium FL instantaneous WP above 120 mmHg Standard 151 % Additionally, there was 82.5 % higher flow in the right iliac aorta than in the left iliac aorta, which triggered malperfusion. Thrombus was accumulated distal to the tear and turbulence. These results are consistent with the findings of the in vitro experiments., Conclusions: This study reveals the haemodynamic mechanisms by which aortic dissection induces aortic aneurysms to produce different risk states. This will contribute to in vitro simulation studies as a new fulcrum in the process of moving from numerical simulation to clinical trials., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 IPEM. Published by Elsevier Ltd. All rights reserved.)

Background and Objective: Imaging methodologies such as, computed tomography (CT) aid in three-dimensional (3D) reconstruction of patient-specific aneurysms. The radiological data is useful in understanding their location, shape, size, and disease progression. However, there are serious impediments in discerning the blood vessel wall thickness due to limitations in the current imaging modalities. This further restricts the ability to perform high-fidelity fluid structure interaction (FSI) studies for an accurate assessment of rupture risk. FSI studies would require the arterial wall mesh to be generated to determine realistic maximum allowable wall stresses by performing coupled calculations for the hemodynamic forces with the arterial walls., Methods: In the present study, a novel methodology is developed to geometrically model variable vessel wall thickness for the lumen isosurface extracted from CT scan slices of patient-specific aneurysms based on clinical and histopathological inputs. FSI simulations are carried out with the reconstructed models to assess the importance of near realistic wall thickness model on rupture risk predictions., Results: During surgery, clinicians often observe translucent vessel walls, indicating the presence of thin regions. The need to generate variable vessel wall thickness model, that embodies the wall thickness gradation, is closer to such clinical observations. Hence, corresponding FSI simulations performed can improve clinical outcomes. Considerable differences in the magnitude of instantaneous wall shear stresses and von Mises stresses in the walls of the aneurysm was observed between a uniform wall thickness and a variable wall thickness model., Conclusion: In the present study, a variable vessel wall thickness generation algorithm is implemented. It was shown that, a realistic wall thickness modeling is necessary for an accurate prediction of the shear stresses on the wall as well as von Mises stresses in the wall. FSI simulations are performed to demonstrate the utility of variable wall thickness modeling., Competing Interests: Declaration of Competing Interest The authors declare no potential conflict of interest., (Copyright © 2024 IPEM. Published by Elsevier Ltd. All rights reserved.)