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Background: The combination of medical imaging and computational hemodynamics is a promising technology to diagnose/prognose coronary artery disease (CAD). However, the clinical translation of in silico hemodynamic models is still hampered by assumptions/idealizations that must be introduced in model-based strategies and that necessarily imply uncertainty. This study aims to provide a definite answer to the open question of how to properly model blood rheological properties in computational fluid dynamics (CFD) simulations of coronary hemodynamics., Methods: The geometry of the right coronary artery (RCA) of 144 hemodynamically stable patients with different stenosis degree were reconstructed from angiography. On them, unsteady-state CFD simulations were carried out. On each reconstructed RCA two different simulation strategies were applied to account for blood rheological properties, implementing (i) a Newtonian (N) and (ii) a shear-thinning non-Newtonian (non-N) rheological model. Their impact was evaluated in terms of wall shear stress (WSS magnitude, multidirectionality, topological skeleton) and helical flow (strength, topology) profiles. Additionally, luminal surface areas (SAs) exposed to shear disturbances were identified and the co-localization of paired N and non-N SAs was quantified in terms of similarity index (SI)., Results: The comparison between paired N vs. shear-thinning non-N simulations revealed remarkably similar profiles of WSS-based and helicity-based quantities, independent of the adopted blood rheology model and of the degree of stenosis of the vessel. Statistically, for each paired N and non-N hemodynamic quantity emerged negligible bias from Bland-Altman plots, and strong positive linear correlation (r > 0.94 for almost all the WSS-based quantities, r > 0.99 for helicity-based quantities). Moreover, a remarkable co-localization of N vs. non-N luminal SAs exposed to disturbed shear clearly emerged (SI distribution 0.95 [0.93, 0.97]). Helical flow topology resulted to be unaffected by blood rheological properties., Conclusions: This study, performed on 288 angio-based CFD simulations on 144 RCA models presenting with different degrees of stenosis, suggests that the assumptions on blood rheology have negligible impact both on WSS and helical flow profiles associated with CAD, thus definitively answering to the question "is Newtonian assumption for blood rheology adequate in coronary hemodynamics simulations?"., Competing Interests: Declaration of Competing Interest AC reports having consultancy agreements with Medyria, HiD-Imaging and Nanoflex Robotics., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

An interventional robot is a means for vascular diagnosis and treatment, and it can perform dredging, releasing drug and operating. Normal hemodynamic indicators are a prerequisite for the application of interventional robots. The current hemodynamic research is limited to the absence of interventional devices or interventional devices in fixed positions. Considering the coupling effect of blood, vessels and robots, based on the bi-directional fluid-structure interaction, using the computational fluid dynamics and particle image velocimetry methods, combined with the sliding and moving mesh technologies, we theoretically and experimentally study the hemodynamic indicators such as blood flow lines, blood pressure, equivalent stress, deformation and wall shear stress of blood vessels when the robot precesses, rotates or does not intervene in the pulsating blood flow. The results show that the intervention of the robot increase the blood flow rate, blood pressure, equivalent stress and deformation of the vessels by 76.4%, 55.4%, 76.5%, and 346%, respectively. The operating mode of the robot during low-speed operation has little impact on the hemodynamic indicators. Using the methyl silicone oil as the experimental fluid, the elastic silicone pipe as the experimental pipe, and the intervention robot having a bioplastic outer shell, the velocity of the fluid around the robot is measured on the developed experimental device for fluid flow field in a pulsating flow when the robot runs. The experimental results are similar to the numerical results. Our work provides an important reference for the hemodynamic study and optimization of the mobile interventional devices., (© 2023. The Author(s).)

In this work, we performed a computational image-based study of blood dynamics in the whole left heart, both in a healthy subject and in a patient with mitral valve regurgitation. We elaborated multi-series cine-MRI with the aim of reconstructing the geometry and the corresponding motion of left ventricle, left atrium, mitral and aortic valves, and aortic root of the subjects. This allowed us to prescribe such motion to computational blood dynamics simulations where, for the first time, the whole left heart motion of the subject is considered, allowing us to obtain reliable subject-specific information. The final aim is to investigate and compare between the subjects the occurrence of turbulence and the risk of hemolysis and of thrombi formation. In particular, we modeled blood with the Navier-Stokes equations in the arbitrary Lagrangian-Eulerian framework, with a large eddy simulation model to describe the transition to turbulence and a resistive method to manage the valve dynamics, and we used a finite element discretization implemented in an in-house code for the numerical solution., (© 2023. The Author(s).)

A major challenge in the computational fluid dynamics modeling of the heart function is the simulation of isovolumetric phases when the hemodynamics problem is driven by a prescribed boundary displacement. During such phases, both atrioventricular and semilunar valves are closed: consequently, the ventricular pressure may not be uniquely defined, and spurious oscillations may arise in numerical simulations. These oscillations can strongly affect valve dynamics models driven by the blood flow, making unlikely to recovering physiological dynamics. Hence, prescribed opening and closing times are usually employed, or the isovolumetric phases are neglected altogether. In this article, we propose a suitable modification of the Resistive Immersed Implicit Surface (RIIS) method (Fedele et al., Biomech Model Mechanobiol 2017, 16, 1779-1803) by introducing a reaction term to correctly capture the pressure transients during isovolumetric phases. The method, that we call Augmented RIIS (ARIIS) method, extends the previously proposed ARIS method (This et al., Int J Numer Methods Biomed Eng 2020, 36, e3223) to the case of a mesh which is not body-fitted to the valves. We test the proposed method on two different benchmark problems, including a new simplified problem that retains all the characteristics of a heart cycle. We apply the ARIIS method to a fluid dynamics simulation of a realistic left heart geometry, and we show that ARIIS allows to correctly simulate isovolumetric phases, differently from standard RIIS method. Finally, we demonstrate that by the new method the cardiac valves can open and close without prescribing any opening/closing times., (© 2023 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.)

The production, removal, and remodeling of fibrillar collagen is fundamental to mechanical homeostasis in arteries, including dynamic morphological and microstructural changes that occur in response to sustained changes in blood flow and pressure under physiological conditions. These dynamic processes involve complex, coupled biological, chemical, and mechanical mechanisms that are not completely understood. Nevertheless, recent simulations using constrained mixture models with phenomenologically motivated constitutive relations have proven able to predict salient features of the progression of certain vascular adaptations as well as disease processes. Collagen turnover is modeled, in part, via stress-dependent changes in collagen half-life, typically within the range of 10-70 days. By contrast, in this work we introduce a biochemomechanical approach to model the cellular synthesis of procollagen as well as its transition from an intermediate state of assembled microfibrils to mature cross-linked fibers, with mechano-regulated removal. The resulting model can simulate temporal changes in geometry, composition, and stress during early vascular adaptation (weeks to months) for modest changes in blood flow or pressure. It is shown that these simulations capture salient features from data presented in the literature from different animal models., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The resolution of the inverse problem of electrocardiography represents a major interest in the diagnosis and catheter-based therapy of cardiac arrhythmia. In this context, the ability to simulate several cardiac electrical behaviors was crucial for evaluating and comparing the performance of inversion methods. For this application, existing models are either too complex or do not produce realistic cardiac patterns. In this work, a low-resolution heart-torso model generating realistic whole heart cardiac mappings and electrocardiograms in healthy and pathological cases is designed. This model was built upon a simplified heart-torso geometry and implements the monodomain formalism by using the finite element method. In addition, a model reduction step through a sensitivity analysis was proposed where parameters were identified using an evolutionary optimization approach. Finally, the study illustrates the usefulness of the proposed model by comparing the performance of different variants of Tikhonov-based inversion methods for the determination of the regularization parameter in healthy, ischemic and ventricular tachycardia scenarios. First, results of the sensitivity analysis show that among 58 parameters only 25 are influent. Note also that the level of influence of the parameters depends on the heart region. Besides, the synthesized electrocardiograms globally present the same characteristic shape compared to the reference once with a correlation value that reaches 88%. Regarding inverse problem, results highlight that only Robust Generalized Cross Validation and Discrepancy Principle provide best performance, with a quasi-perfect success rate for both, and a respective relative error, between the generated electrocardiograms to the reference one, of 0.75 and 0.62., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Life-threatening cardiac arrhythmias such as ventricular tachycardia and fibrillation are common precursors to sudden cardiac death. They are associated with the occurrence of abnormal electrical spiral waves in the heart that rotate at a high frequency. In severe cases, arrhythmias are combated with a clinical method called defibrillation, which involves administering a single global high-voltage shock to the heart to reset all its activity and restore sinus rhythm. Despite its high efficiency in controlling arrhythmias, defibrillation is associated with several negative side effects that render the method suboptimal. The best approach to optimize this therapeutic technique is to deepen our understanding of the dynamics of spiral waves. Here, we use computational cardiac optogenetics to study and control the dynamics of a single spiral wave in a two-dimensional, electrophysiologically detailed, light-sensitive model of a mouse ventricle. First, we illuminate the domain globally by applying a sequence of periodic optical pulses with different frequencies in the sub-threshold regime where no excitation wave is induced. In doing so, we obtain epicycloidal, hypocycloidal, and resonant drift trajectories of the spiral wave core. Then, to effectively control the wave dynamics, we use a method called resonant feedback pacing. In this approach, each global optical pulse is applied when the measuring electrode positioned on the domain registers a predefined value of the membrane voltage. This enables us to steer the spiral wave in a desired direction determined by the position of the electrode. Our study thus provides valuable mechanistic insights into the success or failure of global optical stimulation in executing efficient arrhythmia control., (© 2023. The Author(s).)

A novel transverse velocity spectral estimation method is proposed to estimate the velocity component in the direction transverse to the beam axis for ultrafast imaging. The transverse oscillation was introduced by filtering the envelope data after the axial oscillation was removed. The complex transverse oscillated signal was then used to estimate the transverse velocity spectrum and mean velocity. In simulations, both steady flow with a parabolic flow profile and temporally varying flow were simulated to investigate the performance of the proposed method. Next, the proposed approach was used to estimate the flow velocity in a phantom with pulsatile flow, and finally, this method was applied in vivo in a small animal model. Results of the simulation study indicate that the proposed method provided an accurate velocity spectrogram for beam-to-flow angles from 45° to 90°, without significant performance degradation as the angle decreased. For the simulation of temporally varying flow, the proposed method had a reduced bias ( % versus 73.3%) and higher peak-to-background ratio (PBR) (>15.6 versus 10.5 dB) compared to previous methods. Results in a vessel phantom show that the temporally varying flow velocity can be estimated in the transverse direction obtained using the spectrogram produced by the proposed method operating on the envelope data. Finally, the proposed method was used to map the microvascular blood flow velocity in the mouse spinal cord, demonstrating the estimation of pulsatile blood flow in both the axial and transverse directions in vivo over several cardiac cycles.

Ascending aorta simulations provide insight into patient-specific hemodynamic conditions. Numerous studies have assessed fluid biomarkers which show a potential to aid clinicians in the diagnosis process. Unfortunately, there exists a large disparity in the computational methodology used to model turbulence and viscosity. Recognizing this disparity, some authors focused on analysing the influence of either the turbulence or viscosity models on the biomarkers in order to quantify the importance of these model choices. However, no analysis has yet been done on their combined effect. In order to fully understand and quantify the effect of the computational methodology, an assessment of the combined effect of turbulence and viscosity model choice was performed. Our results show that (1) non-Newtonian viscosity has greater impact (2.9-5.0%) on wall shear stress than Large Eddy Simulation turbulence modelling (0.1-1.4%), (2) the contribution of non-Newtonian viscosity is amplified when combined with a subgrid-scale turbulence model, (3) wall shear stress is underestimated when considering Newtonian viscosity by 2.9-5.0% and (4) cycle-to-cycle variability can impact the results as much as the numerical model if insufficient cycles are performed. These results demonstrate that, when assessing the effect of computational methodologies, the resultant combined effect of the different modelling assumptions differs from the aggregated effect of the isolated modifications. Accurate aortic flow modelling requires non-Newtonian viscosity and Large Eddy Simulation turbulence modelling., Competing Interests: Declaration of competing interest 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 © 2023 Elsevier Ltd. All rights reserved.)

Sustained spiral waves, also known as rotors, are pivotal mechanisms in persistent atrial fibrillation (AF). Stochasticity is inevitable in nonlinear biological systems such as the heart; however, it is unclear how noise affects the instability of spiral waves in human AF. This study presents a stochastic two-dimensional mathematical model of human AF and explores how Gaussian white noise affects the instability of spiral waves. In homogeneous tissue models, Gaussian white noise may lead to spiral-wave meandering and wavefront break-up. As the noise intensity increases, the spatial dispersion of phase singularity (PS) points increases. This finding indicates the potential AF-protective effects of cardiac system stochasticity by destabilizing the rotors. By contrast, Gaussian white noise is unlikely to affect the spiral-wave instability in the presence of localized scar or fibrosis regions. The PS points are located at the boundary or inside the scar/fibrosis regions. Localized scar or fibrosis may play a pivotal role in stabilizing spiral waves regardless of the presence of noise. This study suggests that fibrosis and scars are essential for stabilizing the rotors in stochastic mathematical models of AF. Further patient-derived realistic modeling studies are required to confirm the role of scar/fibrosis in AF pathophysiology., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

End-stage Fontan patients with single-ventricle (SV) circulation are often bridged-to-heart transplantation via mechanical circulatory support (MCS). Donor shortage and complexity of the SV physiology demand innovative MCS. In this paper, an out-of-the-box circulation concept, in which the left and right ventricles are switched with each other is introduced as a novel bi-ventricle MCS configuration for the "failing" Fontan patients. In the proposed configuration, the systemic circulation is maintained through a conventional mechanical ventricle assist device (VAD) while the venous circulation is delegated to the native SV. This approach spares the SV and puts it to a new use at the right-side providing the most-needed venous flow pulsatility to the failed Fontan circulation. To analyze its feasibility and performance, eight SV failure modes have been studied via an established multi-compartmental lumped parameter cardiovascular model (LPM). Here the LPM model is experimentally validated against the corresponding pulsatile mock-up flow loop measurements of a representative 15-year-old Fontan patient employing a clinically-approved VAD (Medtronic-HeartWare). The proposed surgical configuration maintained the healthy cardiac index (3-3.5 l/min/m 2 ) and the normal mean systemic arterial pressure levels. For a failed SV with low ejection fraction (EF = 26%), representing a typical systemic Fontan failure, the proposed configuration enabled a ~ 28 mmHg amplitude in the venous/pulmonary waveforms and a 2 mmHg decrease in the central venous pressure (CVP) together with acceptable mean pulmonary artery pressures (17.5 mmHg). The pulmonary vascular resistance (PVR)-SV failure case provided a ~ 5 mmHg drop in the CVP, with venous/pulmonary pulsatility reaching to ~ 22 mmHg. For the high PVR failure case with a healthy SV (EF = 44%) pulmonary hypertension is likely to occur as expected. While this condition is routinely encountered during the heart transplantation and managed through pulmonary vasodilators a need for precise functional assessment of the spared failed-ventricle is recommended if utilized in the PVR failure mode. Comprehensive in vitro and in silico results encourage this novel concept as a low-cost, more physiological alternative to the conventional bi-ventricle MCS pending animal experiments., (© 2023. The Author(s) under exclusive licence to Biomedical Engineering Society.)

This work presents a structural computational simulation of a polymeric aortic valve prosthesis, made with a hyperelastic material (Styrene-Ethylene/Propylene-Styrene). The valve has a suture ring, three pillars placed at 120° and three leaflets. The analysis is based on a modification over previous designs consisting in a fillet concave surface to avoid stress concentration at the junctions between leaflets and pillars. Three shapes were simulated. The first one was used to validate the computational method by comparison of the results with a recent paper. The second shape was designed to show that a fillet or "rounding" can be beneficial to the stress leaflet reduction. The third shape was also designed to show that the reduction of leaflet thickness and intercommissural distance between leaflets at the pillar junctions improves the valve opening and closure. The use of fillet with a 0.5 mm radius, reduced 26.5% the maximum Von Mises stresses for the second shape and 33.9% for the third shape. Additionally, for the latter, the opening area was not affected for the high stiffness due to fillet. The results -mainly for the third shape-are promising and give rise to future studies: further shape optimization, analysis for other materials and valve simulation under pathological loads., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The heat transfer mechanism inside the human aorta may be related to the physiological function and lesion formation of the aortic wall. The objective of this study was to acquire the temperature distribution in the three-dimensional idealized aorta. An idealized healthy aortic geometry and three representative diseased aortas: aortic aneurysm, coarctation of the aorta, and aortic dissection were constructed. Advanced fluid-structure interaction (FSI) computational framework was applied to predict the aortic temperature distribution. The movement of the aortic root due to the heartbeat was also considered. The displacement distribution of the aortic vessel wall was consistent with clinical observation. The lesser curvature of the aortic arch, aneurysm body, coarctation region, and false lumen were all exposed to relatively high temperatures (over 310.006 K). We found that the rigid wall assumption slightly underestimated the magnitude of the whole aortic wall-averaged temperature while the changing trend and local temperature were like the results of the FSI method. Besides, the wall-averaged temperature would increase and the temperature inflection point would advance when the aortic vessel wall was loaded with a high heat flux. This pilot study revealed the aortic heat transfer mechanism and temperature distribution, and the findings may help to understand the physiological characteristics of the aortic vessel wall., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This paper presents a mathematical model for arterial dissection based on a novel hypothesis proposed by a surgeon, Axel Haverich, see Haverich (Circulation 135(3):205-207, 2017. https://doi.org/10.1161/circulationaha.116.025407 ). In an attempt and based on clinical observations, he explained how three different arterial diseases, namely atherosclerosis, aneurysm and dissection have the same root in malfunctioning Vasa Vasorums (VVs) which are micro capillaries responsible for artery wall nourishment. The authors already proposed a mathematical framework for the modeling of atherosclerosis which is the thickening of the artery walls due to an inflammatory response to VVs dysfunction. A multiphysics model based on a phase-field approach coupled with mechanical deformation was proposed for this purpose. The kinematics of mechanical deformation was described using finite strain theory. The entire model is three-dimensional and fully based on a macroscopic continuum description. The objective here is to extend that model by incorporating a damage mechanism in order to capture the tearing (rupture) in the artery wall as a result of micro-injuries in VV. Unlike the existing damage-based model of the dissection in the literature, here the damage is driven by the internal bleeding (hematoma) rather than purely mechanical external loading. The numerical implementation is carried out using finite element method (FEM)., (© 2023. The Author(s).)

Objective: To define a reference chart comparing pressure drop vs. flow generated by a set of arterial cannulae currently utilized in cardiopulmonary bypass conditions in pediatric surgery., Methods: Cannulae from two manufacturers were selected considering their design and outer and inner diameters. Cannula performance was evaluated in terms of pressure drop vs. flow during simulated cardiopulmonary bypass conditions. The experimental circuits consisted of a Jostra HL-20 roller pump, a Quadrox-i pediatric oxygenator (Maquet Cardiopulmonary AG, Rastatt, Germany), and a custom pediatric tubing set. The circuit was primed with lactated Ringer's solution only (first condition) and with human packed red blood cells added (second condition) to achieve a hematocrit of 30%. Cannula sizes 8 to 16 Fr were inserted into the cardiopulmonary bypass circuit with a "Y" connector. The flow was adjusted in 100 ml/min increments within typical flow ranges for each cannula. Pre-cannula and post-cannula pressures were measured to calculate the pressure drop., Results: Utilizing a pressure drop limit of 100 mmHg, our results suggest a recommended flow limit of 500, 900, 1400, 2600, and 3100 mL/min for Braile arterial cannulae sizes 8, 10, 12, 14, and 16 Fr, respectively. For Medtronic DLP arterial cannulae sizes 8, 10, 12, 14, and 16 Fr, the recommended flow limit is 600, 1100, 1700, 2700, and 3300 mL/min, respectively., Conclusion: This study reinforces discrepancies in pressure drop between cannulae of the same diameter supplied by different manufacturers and the importance of independent translational research to evaluate components' performance.

Mitral valve function depends on its complex geometry and tissue health, with alterations in shape and tissue response affecting the long-term restorarion of function. Previous computational frameworks for biomechanical assessment are mostly based on patient-specific geometries; however, these are not flexible enough to yield a variety of models and assess mitral closure for individually tuned morphological parameters or material property representations. This study details the finite element approach implemented in our previously developed toolbox to assess mitral valve biomechanics and showcases its flexibility through the generation and biomechanical evaluation of different models. A healthy valve geometry was generated and its computational predictions for biomechanics validated against data in the literature. Moreover, two mitral valve models including geometric alterations associated with disease were generated and analysed. The healthy mitral valve model yielded biomechanical predictions in terms of valve closure dynamics, leaflet stresses and papillary muscle and chordae forces comparable to previous computational and experimental studies. Mitral valve function was compromised in geometries representing disease, expressed by the presence of regurgitating areas, elevated stress on the leaflets and unbalanced subvalvular apparatus forces. This showcases the flexibility of the toolbox concerning the generation of a range of mitral valve models with varying geometric definitions and material properties and the evaluation of their biomechanics., Competing Interests: Declaration of Competing Interest There are no conflicts of interest to declare., (Copyright © 2023 IPEM. Published by Elsevier Ltd. All rights reserved.)

The liver circulatory system comprises two blood supply vascular trees (the hepatic artery and portal venous networks), microcirculation through the hepatic capillaries (the sinusoids), and a blood drainage vascular tree (the hepatic vein network). Vasculature changes due to fibrosis -located predominantly at the microcirculation level- lead to a marked increase in resistance to flow causing an increase in portal pressure (portal hypertension). Here, we present a liver fibrosis/cirrhosis model. We build on our 1D model of the healthy hepatic circulation, which considers the elasticity of the vessels walls and the pulsatile character of blood flow and pressure, and recreate the deteriorated liver vasculature due to fibrosis. We emulate altered sinusoids by fibrous tissue (stiffened, compressed and splitting) and propose boundary conditions to investigate the impact of fibrosis on hemodynamic variables within the organ. We obtain that the sinusoids stiffness leads to changes in the amplitude and shape of the blood flow and pressure waveforms but not in their mean value. For the compressed and splitting sinusoids, we observe significant increases in the mean value and amplitude of the pressure waveform in the altered sinusoids and in the portal venous network. In other words, we obtain the portal hypertension clinically observed in fibrotic/cirrhotic patients. We also study the extent of the spreading fibrosis by performing the structural fibrotic changes in an increasingly number of sinusoids. Finally, we calculate the portal pressure gradient (PPG) in the model and obtain values in agreement with those reported in the literature for fibrotic/cirrhotic patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Abdominal aortic aneurysms (AAAs) are a serious condition whose pathophysiology is related to phenomena occurring at different length scales. To gain a better understanding of the disease, this work presents a multi-scale computational study that correlates AAA progression with microstructural and mechanical alterations in the tissue. Macro-scale geometries of a healthy aorta and idealized aneurysms with increasing diameter are developed on the basis of existing experimental data and subjected to physiological boundary conditions. Subsequently, microscopic representative volume elements of the abluminal side of each macro-model are employed to analyse the local kinematics at the cellular scale. The results suggest that the formation of the aneurysm disrupts the micromechanics of healthy tissue, which could trigger collagen growth and remodelling by mechanosensing cells. The resulting changes to the macro-mechanics and microstructure of the tissue seem to establish a new homeostatic state at the cellular scale, at least for the diameter range investigated.

The effect of mechano-electrical feedback on re-entry formation and maintenance was studied using a model of myocardial electromechanics that accounts for two components of myocardial conductivity and delayed strain-dependent changes in membrane capacitance that causes a conduction slowing. Two scenarios were simulated in 2D numerical experiments: (i) propagation of an excitation-contraction wave beyond the edge of a nonconductive nonexcitable obstacle; (ii) circulation of a re-entry wave around a nonconductive nonexcitable obstacle. The simulations demonstrated that the delayed strain-dependent deceleration of the conduction waves promotes the detachment of the excitation-contraction waves from the sharp edge of an elongated obstacle and modulates the re-entry waves rotating around a compact obstacle. The data show that the mechano-electrical feedback, together with an increase in the stimulation frequency and an increase in the excitation threshold, is an arrhythmogenic factor that must be taken into account when analyzing the possibility of the re-entry formation., (© 2022 John Wiley & Sons Ltd.)

Cardiovascular diseases remain the leading cause of death globally. In recent years, vagal nerve stimulation (VNS) has shown promising results in the treatment of a number of cardiovascular diseases. In this approach, mild electrical pulses are sent to the brain via the vagus nerve. This open-loop neurostimulation, however, leads to various side effects due to physiological and inter-patient variability and therefore a closed-loop delivery strategy of electrical pulses that accounts for this variability is desired. In this context, we envision data-driven sparse dynamical model parameterized by patient-specific data as appropriate for use in closed loop controller design. In this work, we build a dynamical model for mean arterial pressure and heart rate using the method sparse identification of nonlinear dynamics (SINDy). As a proxy for real datasets or measurements from a patient, we simulate a mechanistic model from the literature and then discover a data-driven model for predicting mean arterial pressure and heart rate in response to neural stimulus. This discovered model is then used to design a controller to be implemented in closed-loop via model predictive control. We observe that this data-driven model is interpretable, consistent with experiments, provides insights on the sensitivity of different stimulation locations and simplifies the formulation of the optimal control problem. Noting the set-point tracking performance of this closed-loop model-based controller that uses this discovered model, we conclude that the model is adequate in capturing the dynamics of a highly nonlinear cardiovascular system for the purpose of optimal predictive controller design., Competing Interests: Declaration of competing interest The authors do not have any conflict of interest to declare with respect to the results presented in the submitted manuscript., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Distal stent graft-induced new entry tear (dSINE) is an important complication of thoracic endovascular aortic repair (TEVAR) for the treatment of type B aortic dissection (TBAD). This study aims to explore whether the aorta distal to the stent plays an important role in the occurrence of dSINE. Sixty-nine patient-specific geometrical models of twenty-three enrolled patients were reconstructed from preoperative, postoperative, and predSINE computed tomography scans. Computational fluid dynamics (CFD) simulations were performed to calculate the von Mises stress in the CFD group. Meanwhile, morphological measurements were performed in all patients, including measurements of the inverted pyramid index at different follow-up time points and the postoperative true lumen volume change rate. In the CFD study, the time-averaged von Mises stress of the true lumen distal to the stent in dSINE patients was significantly higher than that in the CFD controls (20.42 kPa vs. 15.47 kPa). In the morphological study, a special aortic plane (plane A) with an extremely small area distal to the stent was observed in dSINE patients, which resulted in an inverted pyramid structure in the true lumen distal to the stent. This structure in dSINE patients became increasingly obvious during the follow-up period and finally reached the maximum value before dSINE occurred (mean, 3.91 vs. 1.23). At the same time, enlargement of the true lumen distal to the stent occurs before dSINE, manifesting as a continuous increase in the true lumen volume (mean, 0.70 vs. 013). A new theory of what causes dSINE to occur has been proposed: the inverted pyramid structure of the true lumen distal to the stent caused an increase in the von Mises stress in this region and aortic enlargement, which ultimately led to the occurrence of dSINE., Competing Interests: Declaration of competing interest All authors declare that they have no conflicts of interest., (Copyright © 2023. Published by Elsevier Ltd.)

When modeling complex fluid networks using one-dimensional (1D) approaches, boundary conditions can be imposed using zero-dimensional (0D) models. An application case is the modeling of the entire human circulation using closed-loop models. These models can be considered as a tool to investigate short-term transient and stationary hemodynamic responses to postural changes. The first shortcoming of existing 1D modeling methods in simulating these sudden maneuvers is their inability to deal with rapid variations in flow conditions, as they are limited to the subsonic case. On the other hand, numerical modeling of 0D models representing microvascular beds, venous valves or heart chambers is also currently modeled assuming subsonic flow conditions in 1D connecting vessels, failing when transonic and supersonic flow conditions appear. Therefore, if numerical simulation of sudden maneuvers is a goal in closed-loop models, it is necessary to reformulate the current methodologies used when coupling 0D and 1D models, allowing the correct handling of flow evolution for both subsonic and transonic conditions. This work focuses on the extension of the general methodology for the Junction Riemann Problem (JRP) when coupling 0D and 1D models. As an example of application, the short-term transient response to head-up tilt (HUT) from supine to upright position of a closed-loop model is shown, demonstrating the potential, capability and necessity of the presented numerical models when dealing with sudden maneuvers., (© 2023 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.)

Background: Aortic dissection and atherosclerosis are two common pathological conditions affecting the aorta. Aortic biomechanics are believed to be closely associated with the pathological development of these diseases. However, the biomechanical environment that predisposes the aortic wall to these pathological conditions remains unclear., Methods: Sixteen ascending aortic specimens were harvested from 16 human subjects and further categorized into three groups according to their disease states: aortic dissection group, aortic dissection with accompanied atherosclerosis group and healthy group. Experimental stress-strain data from biaxial tensile testing were used to fit the anisotropic Mooney-Rivlin model to determine material parameters. Computed tomography images or transesophageal echocardiography images were collected to construct computational models to simulate the stress/strain distributions in aortas at the pre-dissection state. Statistical analyses were performed to identify the biomechanical factors to distinguish three groups of aortic tissues., Results: Material parameters of anisotropic Mooney-Rivlin model were fitted with average R 2 value 0.9749. The aortic diameter showed no significant difference among three groups. Changes of maximum and average stress values from minimum pressure to maximum pressure (△MaxStress and △AveStress) had significantly difference between dissection group and dissection with accompanied atherosclerosis group (p = 0.0201 and 0.0102). Changes of maximum and average strain values from minimum pressure to maximum pressure (△MaxStrain and △AveStrain) from dissection group were significant different from healthy group (p = 0.0171 and 0.0281)., Conclusion: Changes of stress and strain values during the cardiac cycle are good biomechanical factors for predicting potential aortic dissection and aortic dissection accompanied with atherosclerosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Head-flow HQ curves for a Fontan cavopulmonary assist device (CPAD) were measured using a blood surrogate in a mock circulatory loop and simulated with various computational fluid dynamics (CFD) models. The tests benchmarked the CFD tools for further enhancement of the CPAD design. Recommended Reynolds-Averaged Navier-Stokes (RANS) CFD approaches for the development of conventional ventricular assist devices (VAD) were found to have shortcomings when applied to the Fontan CPAD, which is designed to neutralize off-condition obstruction risks that could contribute to a major adverse event. The no-obstruction condition is achieved with a von Karman pump, utilizing large clearances and small blade heights, which challenge conventional VAD RANS-based CFD hemodynamic simulations. High-fidelity large eddy simulation (LES) is always recommended; however, this may be cost-inhibitive for optimization studies in commercial settings, thus the reliance on RANS models. This study compares head and power predictions of various RANS turbulence models, employing experimental measurements and LES results as a basis for comparison. The models include standard k-ϵ, re-normalization group k-ϵ, realizable k-ϵ, shear stress transport (SST) k-ω, SST with transitional turbulence, and Generalized k-ω. For the pressure head predictions, it was observed that the standard k-ϵ model provided far better agreement with experiment. For the rotor torque, k-ϵ predictions were 30% lower than LES, while the SST and LES torque values were near identical. For the Fontan CPAD, the findings support using LES for the final design simulations, k-ϵ model for head and general flow simulation, and SST for power, shear stress, hemolysis, and thrombogenicity predictions., (Copyright © 2023 by ASME.)

Testing the mechanical properties of veins is important for diagnosing some cardiovascular diseases such as deep venous thrombosis. Additionally, it plays a crucial role in designing body protective products such as head protective gear, where simulations are necessary to predict the mechanical responses of bridging veins during head impacts. The data on venous mechanical properties reported in the literature have mainly been obtained from ex vivo experiments, and inferring the material parameters of veins in vivo is challenging. Here, we address this issue by proposing a guided wave elastography method in which guided waves are generated in the jugular veins with focused acoustic radiation force and tracked by an ultrafast ultrasound imaging system. Then, a mechanical model considering the effects of the perivascular soft tissues and prestresses in the veins was applied to analyze the wave motions in the jugular veins. Our model enables the development of an inverse method to infer the elastic properties of the veins from measured guided waves. Phantom experiments were performed to validate the theory, and in vivo experiments were carried out to demonstrate the usefulness of the inverse method in practice., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Blood flow within the left ventricle provides important information regarding cardiac function in health and disease. The mitral valve strongly influences the formation of flow structures and there exist various approaches for the representation of the valve in numerical models of left ventricular blood flow. However, a systematic comparison of the various mitral valve models is missing, making a priori decisions considering the overall model's context of use impossible. Within this study, a benchmark setup to compare the influence of mitral valve modeling strategies on intraventricular flow features was developed. Then, five mitral valve models of increasing complexity: no modeling, static wall, 2D and 3D porous medium with time-dependent porosity, and one-way fluid-structure interaction (FSI) were compared with each other. The flow features velocity, kinetic energy, transmitral pressure drop, vortex formation, flow asymmetry as well as computational cost and ease-of-implementation were evaluated. The one-way FSI approach provides the highest level of flow detail, which is accompanied by the highest numerical costs and challenges with the implementation. As an alternative, the porous medium approach with the expansion including time-dependent porosity provides good results with up to 10% deviations in the flow features (except the transmitral pressure drop) in comparison to the FSI model and only a fraction (11%) of numerical costs. However, jet propagation speed is highly underestimated by all alternative approaches to the FSI model. Taken together, our benchmark setup allows a quantitative comparison of various mitral valve modeling approaches and is provided to the scientific community for further testing and expansion., (© 2023 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.)

A stent implantation is a standard medical procedure for treating coronary artery diseases. Over the years, various different designs have been explored for the stents which come with a range of limitations, including late in-stent restenosis (due to low radial strength), foreshortening, radial recoil, etc. Contrary, stents with auxetic design, characterized by a negative Poisson's ratio, display unique deformation characteristics that result in enhanced mechanical properties in terms of its radial strength, radial recoil, foreshortening, and more. In this study, we have analysed a novel double arrowhead (DA) auxetic stent that aims to overcome the limitations associated with traditional stents, specifically in terms of radial strength, foreshortening, and radial recoil. The parametric analysis was done initially on the DA's unit ring structure to optimize the design by evaluating the effect of three design parameters (angle, amplitude, and width) on the mechanical characteristics (radial strength and radial recoil) using finite element analysis. The width of the strut was found to be the primary determinant of the stent structure's properties. Consequently, the angle and width were found to have the least effect on altering the stent's mechanical properties. After performing the parametric analysis, optimal design factors were selected to design the full-length DA auxetic stent. The mechanical characteristics of the DA auxetic stent were assessed and compared in a case study with the Cypher™ commercial stent. The radial strength of DA auxetic stent was found to be 7.26 N/mm, which is more than double the Cypher™ commercial stent's radial strength. Additionally, the proposed stent possesses reduced radial recoil property and completely eliminates the stent foreshortening issue, which shows the superior mechanical properties of the proposed auxetic stent and its potential as a promising candidate for future stent designs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Additive Manufacturing is noted for ease of product customization and short production run cost-effectiveness. As our global population approaches 8 billion, additive manufacturing has a future in maintaining and improving average human life expectancy for the same reasons that it has advantaged general manufacturing. In recent years, additive manufacturing has been applied to tissue engineering, regenerative medicine, and drug delivery. Additive Manufacturing combined with tissue engineering and biocompatibility studies offers future opportunities for various complex cardiovascular implants and surgeries. This paper is a comprehensive overview of current technological advancements in additive manufacturing with potential for cardiovascular application. The current limitations and prospects of the technology for cardiovascular applications are explored and evaluated., (© 2023. The Author(s).)

Biomechanical modeling and simulation is expected to play a significant role in the development of the next generation tools in many fields of medicine. However, full-order finite element models of complex organs such as the heart can be computationally very expensive, thus limiting their practical usability. Therefore, reduced models are much valuable to be used, for example, for pre-calibration of full-order models, fast predictions, real-time applications, and so forth. In this work, focused on the left ventricle, we develop a reduced model by defining reduced geometry & kinematics while keeping general motion and behavior laws, allowing to derive a reduced model where all variables & parameters have a strong physical meaning. More specifically, we propose a reduced ventricular model based on cylindrical geometry & kinematics, which allows to describe the myofiber orientation through the ventricular wall and to represent contraction patterns such as ventricular twist, two important features of ventricular mechanics. Our model is based on the original cylindrical model of Guccione, McCulloch, & Waldman (1991); Guccione, Waldman, & McCulloch (1993), albeit with multiple differences: we propose a fully dynamical formulation, integrated into an open-loop lumped circulation model, and based on a material behavior that incorporates a fine description of contraction mechanisms; moreover, the issue of the cylinder closure has been completely reformulated; our numerical approach is novel aswell, with consistent spatial (finite element) and time discretizations. Finally, we analyze the sensitivity of the model response to various numerical and physical parameters, and study its physiological response., (© 2023 John Wiley & Sons Ltd.)

Retinal hemodynamics and biomechanics play a significant role in understanding the pathophysiology of several ocular diseases. However, these parameters are significantly affected due to changed blood vessel morphology ascribed to pathological conditions, particularly diabetes. In this study, an image-based computational fluid dynamics (CFD) model is applied to examine the effects of changed vascular morphology due to diabetes on blood flow velocity, vorticity, wall shear stress (WSS), and oxygen distribution and compare it with healthy. The 3D patient-specific vascular architecture of diabetic and healthy retina is extracted from Optical Coherence Tomography Angiography (OCTA) images and fundus to extract the capillary level information. Further, Fluid-structure interaction (FSI) simulations have been performed to compare the induced tissue stresses in diabetic and healthy conditions. Results illustrate that most arterioles possess higher velocity, vorticity, WSS, and lesser oxygen concentration than arteries for healthy and diabetic cases. However, an opposite trend is observed for venules and veins. Comparisons show that, on average, the blood flow velocity in the healthy case decreases by 42 % in arteries and 21 % in veins, respectively, compared to diabetic. In addition, the WSS and von Mises stress (VMS) in healthy case decrease by 49 % and 72 % in arteries and by 6 % and 28 % in veins, respectively, when compared with diabetic, making diabetic blood vessels more susceptible to wall rupture and tissue damage. The in-silico results may help predict the possible abnormalities region early, helping the ophthalmologists use these estimates as prognostic tools and tailor patient-specific treatment plans., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Abdominal aortic aneurysm can exhibit transitional flow characteristics in laminar flow regimes. To report transitional flow characteristics, we examined the convergence of phase-averaged solutions by executing blood flow simulations of a patient-specific abdominal aortic aneurysmal model for 257 cardiac cycles with periodic, pulsatile boundary conditions. The phase-averaged solutions were computed by averaging the solutions over various numbers of cardiac cycles and compared against the ones averaged over 124 cycles. The phase-averaged solutions reported small differences when they were averaged over a large number of cardiac cycles. The instantaneous solutions, however, failed to exhibit fluctuations reported in the phase-averaged solutions. To study transitional blood flows in the aneurysmal region, we need to report phase-averaged solutions as they exhibit nonperiodic, disturbed flow characteristics. Additionally, when reporting phase-averaged solutions, it is preferred to compute an average over a large number of cardiac cycles to be able to represent flow structures of the converged phase-averaged solutions., (Copyright © 2023 by ASME.)

Cerebral perfusion modelling is a promising tool to predict the impact of acute ischaemic stroke treatments on the spatial distribution of cerebral blood flow (CBF) in the human brain. To estimate treatment efficacy based on CBF, perfusion simulations need to become suitable for group-level investigations and thus account for physiological variability between individuals. However, computational perfusion modelling to date has been restricted to a few patient-specific cases. This study set out to establish automated parameter inference for perfusion modelling based on neuroimaging data and thus enable CBF simulations of groups. Magnetic resonance imaging (MRI) data from 75 healthy senior adults were utilised. Brain geometries were computed from healthy reference subjects' T1-weighted MRI. Haemodynamic model parameters were determined from spatial CBF maps measured by arterial spin labelling (ASL) perfusion MRI. Thereafter, perfusion simulations were conducted in 75 healthy cases followed by 150 acute ischaemic stroke cases representing an occlusion and CBF cessation in the left and right middle cerebral arteries. The anatomical fitness of the brain geometries was evaluated by comparing the simulated grey (GM) and white matter (WM) volumes to measurements in healthy reference subjects. Strong positive correlations were found in both tissue types (GM: Pearson's r 0.74, P<0.001; WM: Pearson's r 0.84, P<0.001). Haemodynamic parameter tuning was verified by comparing the total volumetric blood flow rate to the brain in healthy reference subjects and simulations (Pearson's r 0.89, P<0.001). In acute ischaemic stroke cases, the simulated infarct volume using a perfusion-based estimate was 197±25 ml. Computational predictions were in agreement with anatomical and haemodynamic values from the literature concerning T1-weighted, T2-weighted, and phase-contrast MRI measurements in healthy scenarios and acute ischaemic stroke cases. The acute stroke simulations did not capture small infarcts (left tail of the distribution), which could be explained by neglected compensatory mechanisms, e.g. collaterals. The proposed parameter inference method provides a foundation for group-level CBF simulations and for in silico clinical stroke trials which could assist in medical device and drug development., Competing Interests: Declaration of competing interest The authors declare that they do not have conflicting interests., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Biaxial mechanical characterizations are the accepted approach to determine the mechanical response of many biological soft tissues. Although several computational and experimental studies have examined how experimental factors (e.g., clamped vs. suture mounting) affect the acquired tissue mechanical behavior, little is known about the role of specimen dimensions in data acquisition and the subsequent modeling. In this study, we combined our established mechanical characterization framework with an iterative size-reduction protocol to test the hypothesis that specimen dimensions affect the observed mechanical behavior of biaxial characterizations. Our findings indicated that there were non-significant differences in the peak equibiaxial stretches of tricuspid valve leaflets across four specimen dimensions ranging from 4.5×4.5mm to 9 × 9mm. Further analyses revealed that there were significant differences in the low-tensile modulus of the circumferential tissue direction. These differences resulted in significantly different constitutive model parameters for the Tong-Fung model between different specimen dimensions of the posterior and septal leaflets. Overall, our findings demonstrate that specimen dimensions play an important role in experimental characterizations, but not necessarily in constitutive modeling of soft tissue mechanical behavior during biaxial testing with the commercial CellScale BioTester., Competing Interests: Declaration of competing interest We hold no financial or personal relationships with other people or organizations that could inappropriately influence or bias our work. We hereby also declare that all authors were fully involved in the study and preparation of the manuscript and the material within has not been and will not be submitted for publication elsewhere., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Aims: Atrial fibrillation (AF), the most prevalent clinical arrhythmia, is associated with atrial remodelling manifesting as acute and chronic alterations in expression, function, and regulation of atrial electrophysiological and Ca2+-handling processes. These AF-induced modifications crosstalk and propagate across spatial scales creating a complex pathophysiological network, which renders AF resistant to existing pharmacotherapies that predominantly target transmembrane ion channels. Developing innovative therapeutic strategies requires a systems approach to disentangle quantitatively the pro-arrhythmic contributions of individual AF-induced alterations., Methods and Results: Here, we built a novel computational framework for simulating electrophysiology and Ca2+-handling in human atrial cardiomyocytes and tissues, and their regulation by key upstream signalling pathways [i.e. protein kinase A (PKA), and Ca2+/calmodulin-dependent protein kinase II (CaMKII)] involved in AF-pathogenesis. Populations of atrial cardiomyocyte models were constructed to determine the influence of subcellular ionic processes, signalling components, and regulatory networks on atrial arrhythmogenesis. Our results reveal a novel synergistic crosstalk between PKA and CaMKII that promotes atrial cardiomyocyte electrical instability and arrhythmogenic triggered activity. Simulations of heterogeneous tissue demonstrate that this cellular triggered activity is further amplified by CaMKII- and PKA-dependent alterations of tissue properties, further exacerbating atrial arrhythmogenesis., Conclusions: Our analysis reveals potential mechanisms by which the stress-associated adaptive changes turn into maladaptive pro-arrhythmic triggers at the cellular and tissue levels and identifies potential anti-AF targets. Collectively, our integrative approach is powerful and instrumental to assemble and reconcile existing knowledge into a systems network for identifying novel anti-AF targets and innovative approaches moving beyond the traditional ion channel-based strategy., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Translating the proposed European Health Data Space (EHDS) regulations and requirements into reality is a challenging task. In this work, we provide a roadmap for aligning the EHDS requirement into the cardiovascular (CV) digital health domain in Austria. To achieve that, we first examined the current eHealth infrastructure and initiatives in Austria. Then, we created a CV-connected health model and addressed the challenges facing cardiac telerehabilitation in Austria. Finally, we mapped the European CV strategies to the Austrian context for EHDS implementation. Accordingly, we were able to provide an Enterprise Architecture (EA) framework for aligning CV digital health with the Austrian EHDS context. The created EA model can be also used as a guiding framework for aligning other medical domains in Austria with EHDS.

Spatial patterns of elevated wall shear stress and pressure due to blood flow past aortic stenosis (AS) are studied using GPU-accelerated patient-specific computational fluid dynamics. Three cases of moderate to severe AS, one with a dilated ascending aorta and two within the normal range (root diameter less than 4cm) are simulated for physiological waveforms obtained from echocardiography. The computational framework is built based on sharp-interface Immersed Boundary Method, where aortic geometries segmented from CT angiograms are integrated into a high-order incompressible Navier-Stokes solver. The key question addressed here is, given the presence of turbulence due to AS which increases wall shear stress (WSS) levels, why some AS patients undergo much less aortic dilation. Recent case studies of AS have linked the existence of an elevated WSS hotspot (due to impingement of AS on the aortic wall) to the dilation process. Herein we further investigate the WSS distribution for cases with and without dilation to understand the possible hemodynamics which may impact the dilation process. We show that the spatial distribution of elevated WSS is significantly more focused for the case with dilation than those without dilation. We further show that this focal area accommodates a persistent pocket of high pressure, which may have contributed to the dilation process through an increased wall-normal forcing. The cases without dilation, on the contrary, showed a rather oscillatory pressure behaviour, with no persistent pressure "buildup" effect. We further argue that a more proximal branching of the aortic arch could explain the lack of a focal area of elevated WSS and pressure, because it interferes with the impingement process due to fluid suction effects. These phenomena are further illustrated using an idealized aortic geometry. We finally show that a restored inflow eliminates the focal area of elevated WSS and pressure zone from the ascending aorta., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Zolfaghari et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Importance: The Million Hearts Model paid health care organizations to assess and reduce cardiovascular disease (CVD) risk. Model effects on long-term outcomes are unknown., Objective: To estimate model effects on first-time myocardial infarctions (MIs) and strokes and Medicare spending over a period up to 5 years., Design, Setting, and Participants: This pragmatic cluster-randomized trial ran from 2017 to 2021, with organizations assigned to a model intervention group or standard care control group. Randomized organizations included 516 US-based primary care and specialty practices, health centers, and hospital-based outpatient clinics participating voluntarily. Of these organizations, 342 entered patients into the study population, which included Medicare fee-for-service beneficiaries aged 40 to 79 years with no previous MI or stroke and with high or medium CVD risk (a 10-year predicted probability of MI or stroke [ie, CVD risk score] ≥15%) in 2017-2018., Intervention: Organizations agreed to perform guideline-concordant care, including routine CVD risk assessment and cardiovascular care management for high-risk patients. The Centers for Medicare & Medicaid Services paid organizations to calculate CVD risk scores for Medicare fee-for-service beneficiaries. CMS further rewarded organizations for reducing risk among high-risk beneficiaries (CVD risk score ≥30%)., Main Outcomes and Measures: Outcomes included first-time CVD events (MIs, strokes, and transient ischemic attacks) identified in Medicare claims, combined first-time CVD events from claims and CVD deaths (coronary heart disease or cerebrovascular disease deaths) identified using the National Death Index, and Medicare Parts A and B spending for CVD events and overall. Outcomes were measured through 2021., Results: High- and medium-risk model intervention beneficiaries (n = 130 578) and standard care control beneficiaries (n = 88 286) were similar in age (median age, 72-73 y), sex (58%-59% men), race (7%-8% Black), and baseline CVD risk score (median, 24%). The probability of a first-time CVD event within 5 years was 0.3 percentage points lower for intervention beneficiaries than control beneficiaries (3.3% relative effect; adjusted hazard ratio [HR], 0.97 [90% CI, 0.93-1.00]; P = .09). The 5-year probability of combined first-time CVD events and CVD deaths was 0.4 percentage points lower in the intervention group (4.2% relative effect; HR, 0.96 [90% CI, 0.93-0.99]; P = .02). Medicare spending for CVD events was similar between the groups (effect estimate, -$1.83 per beneficiary per month [90% CI, -$3.97 to -$0.30]; P = .16), as was overall Medicare spending including model payments (effect estimate, $2.11 per beneficiary per month [90% CI, -$16.66 to $20.89]; P = .85)., Conclusions and Relevance: The Million Hearts Model, which encouraged and paid for CVD risk assessment and reduction, reduced first-time MIs and strokes. Results support guidelines to use risk scores for CVD primary prevention., Trial Registration: ClinicalTrials.gov Identifier: NCT04047147.

Vascular compliance is considered both a cause and a consequence of cardiovascular disease and a significant factor in the mid- and long-term patency of vascular grafts. However, the biomechanical effects of localised changes in compliance cannot be satisfactorily studied with the available medical imaging technologies or surgical simulation materials. To address this unmet need, we developed a coupled silico-vitro platform which allows for the validation of numerical fluid-structure interaction results as a numerical model and physical prototype. This numerical one-way and two-way fluid-structure interaction study is based on a three-dimensional computer model of an idealised femoral artery which is validated against patient measurements derived from the literature. The numerical results are then compared with experimental values collected from compliant arterial phantoms via direct pressurisation and ring tensile testing. Phantoms within a compliance range of 1.4-68.0%/100 mmHg were fabricated via additive manufacturing and silicone casting, then mechanically characterised via ring tensile testing and optical analysis under direct pressurisation with moderately statistically significant differences in measured compliance ranging between 10 and 20% for the two methods. One-way fluid-structure interaction coupling underestimated arterial wall compliance by up to 14.7% compared with two-way coupled models. Overall, Solaris™ (Smooth-On) matched the compliance range of the numerical and in vivo patient models most closely out of the tested silicone materials. Our approach is promising for vascular applications where mechanical compliance is especially important, such as the study of diseases which commonly affect arterial wall stiffness, such as atherosclerosis, and the model-based design, surgical training, and optimisation of vascular prostheses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: In object-oriented or acausal modelling, components of the model can be connected topologically, following the inherent structure of the physical system, and system equations can be formulated automatically. This technique allows individuals without a mathematics background to develop knowledge-based models and facilitates collaboration in multidisciplinary fields like biomedical engineering. This study conducts a preclinical evaluation of a ventricular assist device (VAD) in assisting advanced-stage heart failure patients in an acausal modelling environment., Methods: A comprehensive object-oriented model of the cardiovascular system with a VAD is developed in MATLAB/SIMSCAPE, and its hemodynamic behaviour is studied. An analytically derived pump model is calibrated for the experimental prototype of the Istanbul Heart VAD. Hemodynamics are produced under healthy, diseased, and assisted conditions. The study features a comprehensive collection of advanced-stage heart failure patients' data from the literature to identify parameters for disease modelling and to validate the resulting hemodynamics., Results: Regurgitation, suction, and optimal speeds are identified, and trends in different hemodynamic parameters are observed for the simulated pathophysiological conditions. Using pertinent parameters in disease modelling allows for more accurate results compared to the traditional approach of arbitrary reduction in left ventricular contractility to model dilated cardiomyopathy., Conclusion: The current research provides a comprehensive and validated framework for the preclinical evaluation of cardiac assist devices. Due to its object-oriented nature, the featured model is readily modifiable for other cardiovascular diseases for studying the effect of pump operating conditions on hemodynamics and vice versa in silico and hybrid mock circulatory loops. The work also provides a potential teaching tool for understanding the pathophysiology of heart failure, diagnosis rationale, and degree of assist requirements., (© 2023. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Non-invasive stenosis detection has always been difficult. A new concept of applying external pressure over the artery was compared with stenosis growth in this computational study. When stenosis develops, the artery constricts, obstructing blood flow in that area. Under external pressure, the constricted artery behaves similarly. The current fluid-structure interaction study compares the hemodynamic parameters of a stenosed artery and an artery subjected to external pressure. Significant similarities were discovered when the velocity profile and arterial displacement for both scenarios were compared. This study can be used to characterise stenosis experimentally while remaining non-invasive.

Coronary arteries are uniformly exposed to traditional cardiovascular risk factors. However, atherosclerotic lesions occur in preferential regions of the coronary tree, especially in areas with disturbed local blood flow, such as coronary bifurcations. Over the latest years, secondary flows have been linked to the inception and progression of atherosclerosis. Most of these novel findings have been obtained in the field of computational fluid dynamic (CFD) analysis and biomechanics but remain poorly understood by cardiovascular interventionalists, despite the important impact that they may have in clinical practice. We aimed to summarize the current available data regarding the pathophysiological role of secondary flows in coronary artery bifurcation, providing an interpretation of these findings from an interventional perspective., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Image-based blood flow simulations are increasingly used to investigate the hemodynamics in intracranial aneurysms (IAs). However, a strong variability in segmentation approaches as well as the absence of individualized boundary conditions (BCs) influence the quality of these simulation results leading to imprecision and decreased reliability. This study aims to analyze these influences on relevant hemodynamic parameters within IAs., Methods: As a follow-up study of an international multiple aneurysms challenge, the segmentation results of five IAs differing in size and location were investigated. Specifically, five possible outlet BCs were considered in each of the IAs. These are comprised of the zero-pressure condition (BC1), a flow distribution based on Murray's law with the exponents n = 2 (BC2) and n = 3 (BC3) as well as two advanced flow-splitting models considering the real vessels by including circular cross sections (BC4) or anatomical cross sections (BC5), respectively. In total, 120 time-dependent blood flow simulations were analyzed qualitatively and quantitatively, focusing on five representative intra-aneurysmal flow and five shear parameters such as vorticity and wall shear stress., Results: The outlet BC variation revealed substantial differences. Higher shear stresses (up to Δ9.69 Pa), intrasaccular velocities (up to Δ0.15 m/s) and vorticities (up to Δ629.22 1/s) were detected when advanced flow-splitting was applied compared to the widely used zero-pressure BC. The tendency of outlets BCs to over- or underestimate hemodynamic parameters is consistent across different segmentations of a single aneurysm model. Segmentation-induced variability reaches Δ19.58 Pa, Δ0.42 m/s and Δ957.27 1/s, respectively. Excluding low fidelity segmentations, however, (a) reduces the deviation drastically (>43%) and (b) leads to a lower impact of the outlet BC on hemodynamic predictions., Conclusion: With a more realistic lumen segmentation, the influence of the BC on the resulting hemodynamics is decreased. A realistic lumen segmentation can be ensured, e.g., by using high-resolved 2D images. Furthermore, the selection of an advanced outflow-splitting model is advised and the use of a zero-pressure BC and BC based on Murray's law with exponent n = 3 should be avoided., (© 2023. The Author(s).)

Prosthetic polymeric heart valves (PHVs) have the potential to overcome the inherent material and design limitations of traditional valves in the treatment of valvular heart disease; however, their durability remains limited. Optimal design of the valve structure is necessary to improve their durability. This study aimed to enhance the fatigue resistance of PHVs by improving the stress distribution. Iterative subregional thickening of the leaflets was used, and the mechanical stress distribution and hemodynamics of these polymeric tri-leaflet valves were characterized using a fluid-structure interaction approach. Subregional thickening led to a reduction in stress concentration on the leaflet, with the effective orifice area still meeting ISO 5840-3 and the regurgitant volume achieving a similar value to those in previous studies. The maximum stress in the final iteration was reduced by 28% compared with that of the prototype. The proposed method shows potential for analyzing the stress distribution and hemodynamic performance of subregional thickened valves and can further improve the durability of PHVs., (© 2023 John Wiley & Sons Ltd.)

Statistical shape modeling (SSM) is an emerging tool for risk assessment of thoracic aortic aneurysm. However, the head branches of the aortic arch are often excluded in SSM. We introduced an SSM strategy based on principal component analysis that accounts for aortic branches and applied it to a set of patient scans. Computational fluid dynamics were performed on the reconstructed geometries to identify the extent to which branch model accuracy affects the calculated wall shear stress (WSS) and pressure. Surface-averaged and location-specific values of pressure did not change significantly, but local WSS error was high near branches when inaccurately modeled.

The immersed boundary (IB) method is a mathematical framework for fluid-structure interaction problems (FSI) that was originally developed to simulate flows around heart valves. Direct comparison of FSI simulations around heart valves against experimental data is challenging, however, due to the difficulty of performing robust and effective simulations, the complications of modeling a specific physical experiment, and the need to acquire experimental data that is directly comparable to simulation data. Such comparators are a necessary precursor for further formal validation studies of FSI simulations involving heart valves. In this work, we performed physical experiments of flow through a pulmonary valve in an in vitro pulse duplicator, and measured the corresponding velocity field using 4D flow MRI (4-dimensional flow magnetic resonance imaging). We constructed a computer model of this pulmonary artery setup, including modeling valve geometry and material properties via a technique called design-based elasticity, and simulated flow through it with the IB method. The simulated flow fields showed excellent qualitative agreement with experiments, excellent agreement on integral metrics, and reasonable relative error in the entire flow domain and on slices of interest. These results illustrate how to construct a computational model of a physical experiment for use as a comparator., (© 2023. The Author(s) under exclusive licence to Biomedical Engineering Society.)