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This article provides a comprehensive hemodynamic assessment of two endovascular techniques for treating cerebral aneurysms. Through finite volume simulations of pulsatile blood flow in saccular aneurysms, we evaluated hemodynamic factors under two coiling conditions with varying porosities and deformation stages to determine the most effective treatment for each case. Our analysis shows that stent and coiling treatments are more effective for aneurysms with smaller sac volumes. In particular, stent placement is found to be more effective than coiling for managing saccular aneurysms. The results indicate that stent-induced deformation effectively redirects the main blood flow, significantly lowering the risk of aneurysm rupture near the ostium. Obtained results emphasize the role of deformation and porosity in controlling wall shear stress, which is essential for understanding aneurysm progression and potential rupture risk., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

While much about the fundamental mechanisms behind the initiation and progression of Type B aortic dissection (TBAD) is still unknown, predictive models based on patient-specific fluid-structure interaction (FSI) simulations can help in risk stratification and optimal clinical decision-making. Aiming at the development of personalized treatment, FSI models can be leveraged to investigate the interplay between complex aortic flow patterns and anatomical features, while considering the deformation of the arterial wall and the dissection flap. In this study, the hemodynamics of false lumen thrombosis, a large fenestration, and the orbital orientation of the false lumen is studied through image-based FSI simulations on three TBAD patient-specific geometries. A new pipeline is developed leveraging the open-source software SimVascular and ParaView to analyze multiple patients simultaneously and to achieve large-scale parallelization in FSI results based on patients' computed tomography (CT) images. The results of this study suggest that the internal orbital orientation of the false lumen contributes to maintaining a positive luminal pressure difference Δ P T L - F L = P TL - P FL between the true lumen (TL) and the false lumen (FL), despite an impingement area in the false lumen near the entry tear. A positive and high luminal pressure difference is thought to promote TL expansion and FL compression. Moreover, it was also found that FL thrombosis at the entry tear region reduce the magnitude of the negative luminal pressure difference, which in turn may reduce FL expansion and the risk of unstable aortic growth. Finally, this FSI study suggests that the aortic wall and dissection flap stiffness determines the effects of a large fenestration in the descending thoracic aorta on the luminal pressure difference., (© 2024. The Author(s).)

We present the first-ever, fully discrete, stochastic model of triggered cardiac Ca 2+ dynamics. Using anatomically accurate subcellular cardiac myocyte geometries, we simulate the molecular players involved in Ca 2+ handling using high-resolution stochastic and explicit-particle methods at the level of an individual cardiac dyadic junction. Integrating data from multiple experimental sources, the model not only replicates the findings of traditional in silico studies and complements in vitro experimental data but also reveals new insights into the molecular mechanisms driving cardiac dysfunction under stress and disease conditions. We improve upon older, nondiscrete models using the same realistic geometry by incorporating molecular mechanisms for spontaneous, as well as triggered calcium-induced calcium release (CICR). Action potentials are used to activate L-type calcium channels (LTCC), triggering CICR through ryanodine receptors (RyRs) on the surface of the sarcoplasmic reticulum. These improvements allow for the specific focus on the couplon: the structure-function relationship between LTCC and RyR. We investigate the electrophysical effects of normal and diseased action potentials on CICR and interrogate the effects of dyadic junction deformation through detubulation and orphaning of RyR. Our work demonstrates the importance of the electrophysical integrity of the calcium release unit on CICR fidelity, giving insights into the molecular basis of heart disease. Finally, we provide a unique, detailed, molecular view of the CICR process using advanced rendering techniques. This easy-to-use model comes complete with tutorials and the necessary software for use and analysis to maximize usability and reproducibility. Our work focuses on quantifying, qualifying, and visualizing the behavior of the molecular species that underlie the function and dysfunction of subcellular cardiomyocyte systems., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Aims: Short QT syndrome type 1 (SQT1) is a genetic channelopathy caused by gain-of-function variants in human-ether-a-go-go (HERG) underlying the rapid delayed-rectifier K+ current (IKr), leading to QT-shortening, ventricular arrhythmias, and sudden cardiac death. Data on efficient pharmacotherapy for SQT1 are scarce. In patients with primary carnitine-deficiency, acquired-short QT syndrome (SQTS) has been observed and rescued by carnitine supplementation. Here, we assessed whether carnitine exerts direct beneficial (prolonging) effects on cardiac repolarization in genetic SQTS., Methods and Results: Adult wild-type (WT) and transgenic SQT1 rabbits (HERG-N588K, gain of IKr) were used. In vivo electrocardiograms (ECGs), ex vivo monophasic action potentials (APs) in Langendorff-perfused hearts, and cellular ventricular APs and ion currents were assessed at baseline and during L-Carnitine/C16-Carnitine-perfusion. Two-dimensional computer simulations were performed to assess re-entry-based ventricular tachycardia-inducibility. L-Carnitine/C16-Carnitine prolonged QT-intervals in WT and SQT1, leading to QT-normalization in SQT1. Similarly, monophasic and cellular AP duration (APD) was prolonged by L-Carnitine/C16-Carnitine in WT and SQT1. As underlying mechanisms, we identified acute effects on the main repolarizing ion currents: IKr-steady, which is pathologically increased in SQT1, was reduced by L-Carnitine/C16-Carnitine and deactivation kinetics were accelerated. Moreover, L-Carnitine/C16-Carnitine decreased IKs-steady and IK1. In silico modelling identified IKr changes as the main factor for L-Carnitine/C16-Carnitine-induced APD-prolongation. 2D simulations revealed increased sustained re-entry-based arrhythmia formation in SQT1 compared to WT, which was decreased to the WT-level when adding carnitine-induced ion current changes., Conclusion: L-Carnitine/C16-Carnitine prolong/normalize QT and whole-heart/cellular APD in SQT1 rabbits. These beneficial effects are mediated by acute effects on IKr. L-Carnitine may serve as a potential future QT-normalizing, anti-arrhythmic therapy in SQT1., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Purpose: To present a first principle-based, high-fidelity computational model for predicting full three-dimensional (3D) and time-resolved retinal microvascular hemodynamics taking into consideration the flow and deformation of individual blood cells., Methods: The computational model is a 3D fluid-structure interaction model based on combined finite volume/finite element/immersed-boundary methods. Three in silico microvascular networks are built from high-resolution in vivo motion contrast images of the superficial capillary plexus in the parafoveal region of the human retina. The maximum tissue area represented in the model is approximately 500 × 500 µm2, and vessel lumen diameters ranged from 5.5 to 25 µm covering capillaries, arterioles, and venules. Blood is modeled as a suspension of individual blood cells, namely, erythrocytes (RBC), leukocytes (WBC), and platelets in plasma. An accurate and detailed biophysical modeling of each blood cell and their flow-induced deformation is considered. A physiological, pulsatile boundary condition corresponding to an average cardiac cycle of 0.9 second is used., Results: Detailed quantitative data and analysis of 3D retinal microvascular hemodynamics are presented, and their relationship to RBC flow dynamics is illustrated. Blood velocity is shown to have temporal oscillations superimposed on the background pulsatile variation, which arise because of the way RBCs partition at vascular junctions, causing repeated clogging and unclogging of vessels. Temporal variations in RBC velocity and hematocrit are anti-correlated in a given vessel, but their time-averaged distributions are positively correlated across the network. Whole blood velocity is 65% to 85% of RBC velocity, with the discrepancy related to the formation of an RBC-free region, adjacent to the vascular endothelium and typically 0.8 to 1.8 µm thick. The 3D velocity and RBC concentration profiles are shown to be oppositely skewed with respect to each other, because of the way that RBCs "hug" the apex of each bifurcation. RBC deformation is predicted to have biphasic behavior with respect to vessel diameter, with minimal cell length for vessels approximately 7 µm in diameter. The wall shear stress (WSS) exhibits a strongly 3D distribution with local regions of high value and gradient spanning a range of 10 to 80 dyn/cm2. WSS is highest where there is faster flow, greater curvature of the vessel wall, capillary bifurcations, and at locations of RBC crowding and associated thinning of the cell-free layer., Conclusions: This study highlights the usefulness of high-fidelity cell-resolved modeling to obtain accurate and detailed 3D, time-resolved retinal hemodynamic parameters that are not readily available through noninvasive imaging approaches. The results presented are expected to complement and enhance the interpretation of in vivo data, as well as open new avenues to study retinal hemodynamics in health and disease.

Mechanical circulatory support is a potential treatment for failing Fontan patients. In this study, we performed a theoretical analysis using a computational model to clarify the effects of systemic ventricular assist device (VAD) in failing Fontan patients. Cardiac chambers and vascular systems were described using the time-varying elastance model and modified Windkessel model, respectively. A VAD was simulated as a nonlinear function. In systolic and diastolic ventricular dysfunction and atrioventricular valve regurgitation models, systemic VAD increased the cardiac index and decreased the central venous pressure (CVP). However, in the high pulmonary vascular resistance model, CVP became extremely high above 15 mmHg to maintain the cardiac index when the pulmonary vascular resistance index (PVRI) was above 5 Wood units m 2 . In Fontan patients with ventricular dysfunction or atrioventricular valve regurgitation, systemic VAD efficiently improves the hemodynamics. In Fontan patients with PVRI of > 5 Wood units m 2 , systemic VAD seems ineffective., (© 2024. The Author(s).)

The waveform of ventricular action potential (AP) is a key determinant of the cardiac cycle, a marker of beating pathophysiology, and a target for anti-arrhythmic drug design. The information contained in the waveform, though, is limited to the actual dynamics of the AP under consideration. By measuring quasi-instantaneous current-voltage relationships during repolarization, I propose a three-dimensional representation of the ventricular AP which includes potential dynamic responses that the beat can show when electrically perturbed. This representation is described in the case of a numerically reconstructed ventricular AP, but it can be, at least partially, derived in real cardiomyocytes. Simulation allows to disclose the potentialities and the limitations of the approach, that can be extended to any non-cardiac AP. By reporting, at any AP time, the ion current available within the physiological membrane potential range at that time, the representation makes all together available: (1) refractory period, (2) thresholds for eliciting full or calcium-driven APs, (3) threshold for all-or-none repolarization, (4) membrane resistance during repolarization, (5) the safety of membrane repolarization. It provides further evidence of a negative membrane resistance during the late phase of ventricular AP and a quantitative estimate of repolarization reserve (RR), key determinants of repolarization dynamics., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

The co-ordinated electrical activity of ∼2 billion cardiac cells ensures stability of the heartbeat. Indeed, the remarkably low incidence (<1%) of ventricular arrhythmias in the healthy heart is only possible when the electrical event across this syncytium is closely controlled. In contrast, the diseased myocardium is associated with increased electrophysiological heterogeneity, unstable rhythm, and increased incidence of lethal arrhythmias. But what is the link between cellular and tissue level heterogeneity? Recent research has shown the existence of considerable cellular heterogeneity even in the healthy heart, suggesting that cell-to-cell variability in electrical (e.g. action potential duration) and mechanical performance (e.g. twitch amplitude) is a normal property. This observation has been previously unappreciated because the aggregated function in the form of QT-interval and cardiac output varies <1% on a beat-to-beat basis. This article describes the underlying cellular variability that is tolerated-and perhaps needed-by different regions of the heart for normal function and indicates why this variability is not apparent in function at the chamber and organ level. Thus, in contrast to the current dominant view, this article postulates that heterogeneity is normal and potentially endows various functional benefits. This new view of how the component parts of the heart come together to function also suggests novel mechanisms for cardiac pathologies, namely that dysfunction may emerge from changes in the extent and/or nature of heterogeneity. Once understood, restoring normal forms of heterogeneity could be a novel approach to treatment., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Physics-based computer models based on numerical solutions of the governing equations generally cannot make rapid predictions, which in turn limits their applications in the clinic. To address this issue, we developed a physics-informed neural network (PINN) model that encodes the physics of a closed-loop blood circulation system embedding a left ventricle (LV). The PINN model is trained to satisfy a system of ordinary differential equations (ODEs) associated with a lumped parameter description of the circulatory system. The model predictions have a maximum error of less than 5% when compared to those obtained by solving the ODEs numerically. An inverse modeling approach using the PINN model is also developed to rapidly estimate model parameters (in ∼ 3 min) from single-beat LV pressure and volume waveforms. Using synthetic LV pressure and volume waveforms generated by the PINN model with different model parameter values, we show that the inverse modeling approach can recover the corresponding ground truth values for LV contractility indexed by the end-systolic elastance E es with a 1% error, which suggests that this parameter is unique. The estimated E es is about 58% to 284% higher for the data associated with dobutamine compared to those without, which implies that this approach can be used to estimate LV contractility using single-beat measurements. The PINN inverse modeling can potentially be used in the clinic to simultaneously estimate LV contractility and other physiological parameters from single-beat measurements., 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 B.V. All rights reserved.)

The organization of myofibers and extra cellular matrix within the myocardium plays a significant role in defining cardiac function. When pathological events occur, such as myocardial infarction (MI), this organization can become disrupted, leading to degraded pumping performance. The current study proposes a multiscale finite element (FE) framework to determine realistic fiber distributions in the left ventricle (LV). This is achieved by implementing a stress-based fiber reorientation law, which seeks to align the fibers with local traction vectors, such that contractile force and load bearing capabilities are maximized. By utilizing the total stress (passive and active), both myofibers and collagen fibers are reoriented. Simulations are conducted to predict the baseline fiber configuration in a normal LV as well as the adverse fiber reorientation that occurs due to different size MIs. The baseline model successfully captures the transmural variation of helical fiber angles within the LV wall, as well as the transverse fiber angle variation from base to apex. In the models of MI, the patterns of fiber reorientation in the infarct, border zone, and remote regions closely align with previous experimental findings, with a significant increase in fibers oriented in a left-handed helical configuration and increased dispersion in the infarct region. Furthermore, the severity of fiber reorientation and impairment of pumping performance both showed a correlation with the size of the infarct. The proposed multiscale modeling framework allows for the effective prediction of adverse remodeling and offers the potential for assessing the effectiveness of therapeutic interventions in the future. STATEMENT OF SIGNIFICANCE: The organization of muscle and collagen fibers within the heart plays a significant role in defining cardiac function. This organization can become disrupted after a heart attack, leading to degraded pumping performance. In the current study, we implemented a stress-based fiber reorientation law into a computer model of the heart, which seeks to realign the fibers such that contractile force and load bearing capabilities are maximized. The primary goal was to evaluate the effects of different sized heart attacks. We observed substantial fiber remodeling in the heart, which matched experimental observations. The proposed computational framework allows for the effective prediction of adverse remodeling and offers the potential for assessing the effectiveness of therapeutic interventions in the future., Competing Interests: Declaration of competing interests 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 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The control of left ventricular assist devices (LVADs) requires sensors and/or estimators to account for the physiological state of the patient and apply advanced controllers. Sensor characteristics are a challenge when using implantable pressure sensors because they influence the quality of physiological control and the robustness of the controlled system. The objective of this work is to investigate the performance and robustness of LVAD controllers that operate based on LVAD integrated pressure sensors. Four pressure-based LVAD controllers are tested with a HeartMate 3 that has an integrated pressure sensor. Controller sensitivity as well as robustness to sensor drift and noise are evaluated based on controller response to large changes in preload and afterload. A fail-safe strategy for sensor failure used also to investigate the reliable operation of the LVAD in realistic conditions. All tested controllers are sensitive to drifting pressure signals, which can lead to unstable behavior. The results show that two controllers are robust to noise. The other two controllers show high deviation and oscillation in cardiac output even for small noise. Additionally, a noticeable difference of the controller's response between simulated and measured pressure input was observed, indicating the need for a robust controller design. Reliable operation even in the event of a sensor failure was achieved on the basis of a fail-safe control system.

Real-time estimation of patient cardiovascular states, including cardiac output and systemic vascular resistance, is necessary for personalized hemodynamic monitoring and management. Highly invasive measurements enable reliable estimation of these states but increase patient risk. Prior methods using minimally invasive measurements reduce patient risk but have produced unreliable estimates limited due to trade-offs in accuracy and time resolution. Our objective was to develop an approach to estimate cardiac output and systemic vascular resistance with both a high time resolution and high accuracy from minimally invasive measurements. Using the two-element Windkessel model, we formulated a state-space method to estimate a dynamic time constant - the product of systemic vascular resistance and compliance - from arterial blood pressure measurements. From this time constant, we derived proportional estimates of systemic vascular resistance and cardiac output. We then validated our method with a swine cardiovascular dataset. Our estimates produced using arterial blood pressure measurements not only closely align with those using highly invasive measurements, but also closely align when derived from three separate locations on the arterial tree. Moreover, our estimates predictably change in response to standard cardiovascular drugs. Overall, our approach produces reliable, real-time estimates of cardiovascular states crucial for monitoring and control of the cardiovascular system.

Background: Despite the frequency of persistent new-onset conduction disturbances after transcatheter aortic valve replacement (TAVR), few preoperative methods of prediction exist., Methods: Patients who underwent TAVR in the Department of Cardiology of the Second Affiliated Hospital of the Army Medical University from December 2020 to September 2021 and postoperative aortic root modeling via the FEOPS finite element analysis were included in this single-center case-control study, divided into persistent conduction disturbances (PCD) and non-PCD groups according to their pre- and postoperative electrocardiograms in the first month. Risk factors affecting PCD were identified by comparing the baseline data of these two groups, including echocardiograms, computed tomography angiography of the aortic root, surgical decision-making, and FEOPS data. Independent risk factors were screened using logistic regression modeling, and the receiver operating characteristic (ROC) curve was used to test the predictive ability., Results: A total of 56 patients were included in this study, 37 with bicuspid aortic valve (BAV) and 19 with trileaflet aortic valve (TAV), with 17 cases of PCD. The contact pressure index (CPI) of FEOPS, valve oversize ratio, differences between membranous interventricular septum length and implantation depth (ΔMSID) and valve implantation depth were statistically different (P < 0.05). CPI could be used as an independent risk factor for PCD (P < 0.05), and the ROC curve comparison showed that the CPI was more predictive (AUC = 0.806, 95% CI: 0.684-0.928, P = 0.001)., Conclusions: The CPI of FEOPS has better predictive value for new-onset conduction disturbance after TAVR compared to other known predictors., (© 2024. The Author(s).)

The hemodynamic parameters in arteries are difficult to measure non-invasively, and the analysis and prediction of hemodynamic parameters based on computational fluid dynamics (CFD) has become one of the important research hotspots in biomechanics. This article establishes 15 idealized left coronary artery bifurcation models with concomitant stenosis and aneurysm lesions, and uses CFD method to numerically simulate them, exploring the effects of left anterior descending branch (LAD) stenosis rate and curvature radius on the hemodynamics inside the aneurysm. This study compared models with different stenosis rates and curvature radii and found that as the stenosis rate increased, the oscillatory shear index (OSI) and relative residence time (RRT) showed a trend of increase; In addition, the decrease in curvature radius led to an increase in the degree of vascular curvature and an increased risk of vascular aneurysm rupture. Among them, when the stenosis rate was less than 60%, the impact of stenosis rate on aneurysm rupture was greater, and when the stenosis rate was greater than 60%, the impact of curvature radius was more significant. Based on the research results of this article, it can be concluded that by comprehensively considering the effects of stenosis rate and curvature radius on hemodynamic parameters, the risk of aneurysm rupture can be analyzed and predicted. This article uses CFD methods to deeply explore the effects of stenosis rate and curvature radius on the hemodynamics of aneurysms, providing new theoretical basis and prediction methods for the assessment of aneurysm rupture risk, which has important academic value and practical guidance significance.

Positive end-expiratory pressure results in a sustained positive intrathoracic pressure, which exerts pressure on intrathoracic vessels, resulting in cardiopulmonary interactions. This sustained positive intrathoracic pressure is known to decrease cardiac preload, and thus, decrease venous return, ultimately reducing both the stroke volume and stressed blood volume of the cardiovascular system. Currently, cardiovascular and pulmonary care are provided independently of one another. That positive end-expiratory pressure alters both stroke volume and stressed blood volume suggests both the pulmonary and cardiovascular state should be conjointly optimised. Optimising these systems in isolation may benefit one system, but have highly detrimental effects on the other. A combined cardiopulmonary model has the potential to provide a better understanding of patient specific pulmonary and cardiovascular state, as well as resulting cardiopulmonary interactions. This would enable simultaneous optimisation of all cardiovascular and pulmonary parameters. Cardiopulmonary interactions are highly patient specific and unpredictable, making accurate modelling of these interactions challenging. A previously validated cardiopulmonary model was found to have increasing errors at high positive end-expiratory pressures. A new iteration, the alpha model, was introduced to resolve this issue. This paper aims to review the alpha model against its predecessors, the previous cardiopulmonary model, and the original three chamber cardiovascular system model. All models are used to identify cardiovascular system parameters from measurements of 4 pigs during a preload reduction manoeuvre. Outputs and parameter estimations from models are compared to assess the relative performance of the alpha model against its predecessors. The novel alpha model was able to reduce model errors under high positive end-expiratory pressure, resulting in more accurate model outputs. At high positive end-expiratory pressures (20cmH2O), the alpha model had an average error of 11.24%, while the original cardiopulmonary model had a much higher error of 52.21%. Furthermore, identified outputs of the alpha model more closely matched those of the 3 chamber model than the previous cardiopulmonary model. On average, at high positive end-expiratory levels, identified model parameters from the alpha model showed a 6.21% difference to those of the 3 chamber model, while the cardiopulmonary model displayed a 39.43% difference. The alpha model proved to be more stable than the original cardiopulmonary model, making it a good candidate for model based care. However, it produced similar parameter outputs to the simpler three chamber cardiovascular model, bringing into question whether the additional complexity is justified, especially considering the low availability of clinical data in the ICU. There is a critical need for model based care to guide important procedures in ICU, such as fluid therapy. Candidate models should be continuously reviewed in order to guarantee the best possible care., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Cushway 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.)

Subjects with amputation of the lower limbs are at increased risk of cardiovascular mortality and morbidity. We hypothesize that amputation-induced alterations in the arterial tree negatively impact arterial biomechanics, blood pressure and flow behavior. These changes may interact with other biological factors, potentially increasing cardiovascular risk. To evaluate this hypothesis regarding the purely mechanical impact of amputation on the arterial tree, we used a simulation computer model including a detailed one-dimensional (1D) arterial network model (143 arterial segments) coupled with a zero-dimensional (0D) model of the left ventricle. Our simulations included five settings of the arterial network: (1) 4-limbs control, (2) unilateral amputee (right lower limb), (3) bilateral amputee (both lower limbs), (4) trilateral amputee (lower-limbs and right upper-limb), and (5) quadrilateral amputee (lower and upper limbs). Analysis of regional stiffness, as calculated by pulse wave velocity (PWV) for large-, medium- and small-sized arteries, showed that, while aortic stiffness did not change with increasing degree of amputation, stiffness of medium and smaller-sized arteries increased with greater amputation severity. Despite a staged decrease in cardiac output, the systolic and diastolic blood pressure values increased, resulting in an increase in both central and peripheral pulse pressures but with an attenuation of pulse pressure amplification. The most significant increase in peak systolic pressure and decrease in peak systolic blood flow was observed at the site of the abdominal aorta. Wave separation analysis indicated no changes in the shape of the forward and backward wave components. However, the results from wave intensity analysis showed that with extended amputation, there was an increase in peak forward wave intensity and a rise in the inverse peak of the backward wave intensity, suggesting potential alterations in cardiac hemodynamic load. In conclusion, this simulation study showed that biomechanical and hemodynamic changes in the arterial network geometry could interact with additional risk factors to increase the cardiovascular risk in patients with amputations., (© 2024. The Author(s).)

Background/Objectives: Arteriovenous (AV) graft is a procedure for hemodialysis performed in the arm. Optimizing AV graft design is vital to enhance haemodialytic efficiency in patients with kidney disease. Despite being a standard procedure, making it work optimally is still difficult due to various graft diameters and anastomosis configurations, which have limited studies. This research aims to find the ideal AV graft tube diameter on blood flow and pressure gradients and the ideal body site for AV graft implantation and to study their angles for dialysate flow. Methods: Nine models were designed in Autodesk Fusion 360 with 40°, 50°, and 60° angles each having 2 mm, 5.1 mm, and 14.5 mm diameters, all following specific equations on continuity, momentum (Navier-Stokes Equation)), and the Reynolds Stress Model (RSM). The CFD simulation of these models was performed in ANSYS Fluent with an established parameter of 0.3 m/s inlet velocity and stiff/no-slip graft and artery wall boundary condition. Results: As a result, the design with a diameter of 14.5 mm and a 40° angle was overall the most ideal in terms of minimal wall shear stress and turbulence. Conclusions: Thus the brachiocephalic area or the forearm is calculated to be the most optimal implantation site. Additionally, varying angles do affect dialysate flow, as smaller values cause less stress.

A computational model enables the extraction of two critical myocardial tissue properties: activation time (AT) and contractility (Con) from recorded cardiac strains. However, interference between these parameters reduces the precision and accuracy of the extraction process. This study investigates whether leveraging features in the parameter space can enhance parameter extraction. We utilized a computational model to simulate sarcomere mechanics, creating a parameter space grid of 41 × 41 AT and Con pairs. Each pair generated a simulated strain pattern, and by scanning the grid, we identified cohorts of similar strain patterns for each simulation. These cohorts were represented as binary images-synthetic fingerprints-where the position and shape of each blob indicated extraction uniqueness. We also generated a measurement fingerprint for a strain pattern from a patient with left bundle branch block and compared it to the synthetic fingerprints to calculate a proximity map based on their similarity. This approach allowed us to extract AT and Con using both the measurement fingerprint and the proximity map, corresponding to simple optimization and enhanced parameter extraction methods, respectively. Each synthetic fingerprint consisted of a single connected blob whose size and shape varied characteristically within the parameter space. The AT values extracted from the measurement fingerprint and the proximity map ranged from -59 to 19 ms and from -16 to 14 ms, respectively, while Con values ranged from 48% to 110% and from 85% to 110%, respectively. This study demonstrates that similarity in simulations leads to an asymmetric distribution of parameter values in the parameter space. By using a proximity map, this distortion is considered, significantly improving the accuracy of parameter extraction., Competing Interests: The author declares no conflicts of interest., (Copyright © 2024 Borut Kirn.)

In patients with dyssynchronous heart failure (DHF), cardiac conduction abnormalities cause the regional distribution of myocardial work to be non-homogeneous. Cardiac resynchronization therapy (CRT) using an implantable, programmed biventricular pacemaker/defibrillator, can improve the synchrony of contraction between the right and left ventricles in DHF, resulting in reduced morbidity and mortality and increased quality of life. Since regional work depends on wall stress, which cannot be measured in patients, we used computational methods to investigate regional work distributions and their changes after CRT. We used three-dimensional multi-scale patient-specific computational models parameterized by anatomic, functional, hemodynamic, and electrophysiological measurements in eight patients with heart failure and left bundle branch block (LBBB) who received CRT. To increase clinical translatability, we also explored whether streamlined computational methods provide accurate estimates of regional myocardial work. We found that CRT increased global myocardial work efficiency with significant improvements in non-responders. Reverse ventricular remodeling after CRT was greatest in patients with the highest heterogeneity of regional work at baseline, however the efficacy of CRT was not related to the decrease in overall work heterogeneity or to the reduction in late-activated regions of high myocardial work. Rather, decreases in early-activated regions of myocardium performing negative myocardial work following CRT best explained patient variations in reverse remodeling. These findings were also observed when regional myocardial work was estimated using ventricular pressure as a surrogate for myocardial stress and changes in endocardial surface area as a surrogate for strain. These new findings suggest that CRT promotes reverse ventricular remodeling in human dyssynchronous heart failure by increasing regional myocardial work in early-activated regions of the ventricles, where dyssynchrony is specifically associated with hypoperfusion, late systolic stretch, and altered metabolic activity and that measurement of these changes can be performed using streamlined approaches., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Patent applications related to the technology described here have been submitted in the United States (“Compositions and methods for patient-specific modeling to predict outcomes of cardiac resynchronization therapy,” serial no. P00015-268P01; “Patient-specific modeling of ventricular activation pattern using surface ECG-derived vectorcardiogram in bundle branch block,” serial no. PCT/US15/36788). A.D.M and J.H.O are co-founders and equity-holders in Insilicomed, Inc., a licensee of UC San Diego software used in this research. A.D.M, C.T.V, and D.E.K. are co-founders and equity holders of Vektor Medical Inc., which was not involved in this research. Vektor Medical and Insilicomed, Inc. had no involvement at all in design, performance, analysis or funding of the present study. Vektor Medical and Insilicomed are licensees of intellectual property arising from or used in this research. This relationship has been disclosed to, reviewed, and approved by the University of California San Diego in accordance with its conflict of interest policies., (Copyright: © 2024 Craine 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.)

Cardiac rhythms are related to heart electrical activity, being the essential aspect of the cardiovascular physiology. Usually, these rhythms are represented by electrocardiograms (ECGs) that are useful to detect cardiac pathologies. Essentially, the heart activity starts in the sinoatrial node (SA) node, the natural pacemaker, propagating to the atrioventricular node (AV), and finally reaching the His-Purkinje complex (HP). This paper investigates the control of cardiac rhythms in order to induce normal rhythms from pathological responses. A mathematical model that presents close agreement with experimental measurements is employed to represent the heart functioning. The adopted model comprises a network of three nonlinear oscillators that represent each one of the cardiac nodes, connected by delayed couplings. The pathological behavior is induced by an external stimulus in the SA node. An adaptive controller is proposed acting in the SA node considering an strategy based on the signal obtained by the natural pacemaker and its regularization. The incorporation of adaptive compensation in a Lyapunov-based control scheme allows the compensation for the unknown dynamics. The controller ability to deal with interpatient variability is evaluated by assuming that the heart model is not available to the controller design, being used only in the simulator to assess the control performance. Results show that the adaptive term can reduce the control effort by around 3% while reducing the tracking error by 20%, when compared to the conventional feedback approach. Additionally, the controller can avoid abnormal rhythms, turning the ECG closer to the expected normal behavior and preventing critical cardiac responses. Therefore, this work demonstrates that an adaptive controller can be used to regulate the ECG signal without prior information about the system and disregarding inter- and intrapatient variability., (© 2024. The Author(s).)

This study investigates the influence of body physiology on the rupture risk of cerebral saccular aneurysms. Comprehensive hemodynamic analyses were conducted using computational fluid dynamics to assess the potential for aneurysm rupture under three physiological conditions: rest, normal activity, and exercise. Contours of wall shear stress, oscillatory shear index, and pressure were analyzed and compared to identify regions at high risk of rupture. Additionally, statistical analysis was performed to evaluate the rupture risk of aneurysms. Blood flow dynamics during the peak systolic phase were also examined under these conditions. Our findings indicate that the dome area, where blood pressure is highest and the incoming blood flow first contacts the aneurysm sac, is the critical region with a heightened risk of rupture., (© 2024. The Author(s).)

Computational models can be at the basis of new powerful technologies for studying and classifying disorders like pre-eclampsia, where it is difficult to distinguish pre-eclamptic patients from non-pre-eclamptic based on pressure when patients have a track record of hypertension. Computational models now enable a detailed analysis of how pregnancy affects the cardiovascular system. Therefore, new non-invasive biomarkers were developed that can aid the classification of pre-eclampsia through the integration of six different measured non-invasive cardiovascular signals. Datasets of 21 pregnant women (no early onset pre-eclampsia, n = 12; early onset pre-eclampsia, n = 9) were used to create personalised cardiovascular models through computational modelling resulting in predictions of blood pressure and flow waveforms in all major and minor vessels of the utero-ovarian system. The analysis performed revealed that the new predictors PPI (pressure pulsatility index) and RI (resistance index) calculated in arcuate and radial/spiral arteries are able to differentiate between the 2 groups of women (t-test scores of p < .001) better than PI (pulsatility index) and RI (Doppler calculated in the uterine artery) for both supervised and unsupervised classification. In conclusion, two novel high-performing biomarkers for the classification of pre-eclampsia have been identified based on blood velocity and pressure predictions in the smaller placental vasculatures where non-invasive measurements are not feasible., (© 2024. The Author(s).)

Aims: Pathophysiology of atrial fibrillation (AF) remains unclear. Interactions between scar and conduction velocity (CV) and their impact on wavefront propagation in sinus rhythm (SR) and rotational activity burden in AF were evaluated., Methods and Results: Local activation times (LATs) and voltage data were obtained from patients undergoing ablation for persistent AF. Omnipolar voltage (OV) and bipolar voltage (BV) data were obtained during AF and SR at pacing intervals of 600 and 250 ms. Local activation times were used to determine CV dynamics and their relationship to the underlying voltage and pivot points in SR. Computational modelling studies were performed to evaluate the impact of CVs and fibrosis on rotational activity burden in AF. Data from 60 patients with a total of 2 768 400 LAT and voltage points were analysed (46 140 ± 5689 points/patient). Voltage determined CV dynamics. Enhanced CV heterogeneity sites were predominantly mapped to low-voltage zones (LVZs) (0.2-0.49 mV) (128/168, 76.2%) rather than LVZs (<0.2 mV) and frequently co-located to pivot points (151/168, 89.9%). Atrial fibrillation OV maps correlated better with SR BV 250 ms than 600 ms maps, thereby representing fixed and functional remodelling. Sinus rhythm maps at 250 ms compared with 600 ms harboured a greater number of pivot points. Increased CV slowing and functional remodelling on computational models resulted in a greater rotational activity burden., Conclusion: Conduction velocity dynamics are impacted by the degree of scar. Conduction velocity heterogeneity and functional remodelling impacts wavefront propagation in SR and rotational activity burden in AF. This study provides insight into the pathophysiology of AF and identifies potential novel ablation targets., Competing Interests: Conflict of interest: R.J.H. has received research grants, educational grants, and speaker’s fees from Biosense Webster, Medtronic, and Abbott. P.D.L. receives speaker fees and research grants from Medtronic, Abbott, and Boston Scientific. S.H. has received speaker’s fee from Abbott. S.H. and R.J.H. are inventors of the STAR mapping system and are shareholders in Rhythm AI Ltd. S.H. is a British Heart Foundation Clinical Intermediate Fellow and receives a grant from the British Heart Foundation. The remaining authors have nothing to disclose., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: The effective refractory period (ERP) is one of the main electrophysiological properties governing arrhythmia, yet ERP personalization is rarely performed when creating patient-specific computer models of the atria to inform clinical decision-making. This study evaluates the impact of integrating clinical ERP measurements into personalized in silico models on arrhythmia vulnerability., Methods and Results: Clinical ERP measurements were obtained in seven patients from multiple locations in the atria. Atrial geometries from the electroanatomical mapping system were used to generate personalized anatomical atrial models. The Courtemanche M. et al. cellular model was adjusted to reproduce patient-specific ERP. Four modeling approaches were compared: homogeneous (A), heterogeneous (B), regional (C), and continuous (D) ERP distributions. Non-personalized approaches (A and B) were based on literature data, while personalized approaches (C and D) were based on patient measurements. Modeling effects were assessed on arrhythmia vulnerability and tachycardia cycle length, with sensitivity analysis on ERP measurement uncertainty. Mean vulnerability was 3.4 ± 4.0%, 7.7 ± 3.4%, 9.0 ± 5.1%, and 7.0 ± 3.6% for scenarios A-D, respectively. Mean tachycardia cycle length was 167.1 ± 12.6 ms, 158.4 ± 27.5 ms, 265.2 ± 39.9 ms, and 285.9 ± 77.3 ms for scenarios A-D, respectively. Incorporating perturbations to the measured ERP in the range of 2, 5, 10, 20, and 50 ms changed the vulnerability of the model to 5.8 ± 2.7%, 6.1 ± 3.5%, 6.9 ± 3.7%, 5.2 ± 3.5%, and 9.7 ± 10.0%, respectively., Conclusion: Increased ERP dispersion had a greater effect on re-entry dynamics than on vulnerability. Inducibility was higher in personalized scenarios compared with scenarios with uniformly reduced ERP; however, this effect was reversed when incorporating fibrosis informed by low-voltage areas. Effective refractory period measurement uncertainty up to 20 ms slightly influenced vulnerability. Electrophysiological personalization of atrial in silico models appears essential and requires confirmation in larger cohorts., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Endovascular procedures rely on navigating guidewires, catheters and other devices through tortuous vasculature to treat disease. A critical challenge in these procedures is catheter herniation, in which the device deviates from its intended path, often irrecoverably. To elucidate the mechanics of herniation, we developed a physical flow model of the aortic arch that enables direct measurement of device curvature during experimentally simulated neuroendovascular procedures conducted from an upper arterial access. Combined with measurements of initial, unstressed device shapes and flexural rigidities, the method enables the experimental estimation of the device bending energies during these simulated procedures. Characteristic energy profiles revealed distinct stages in both herniation and successful navigation, governed by the interplay between device properties and vascular anatomy. A deterministic progression from successful navigation to herniation was identified, with catheter systems following paths determined by measurable energy barriers. Increasing guidewire stiffness or decreasing catheter stiffness reduced the energy barrier for successful navigation while increasing that for herniation. This framework enables the prediction of endovascular herniation risk and offers unique insight into improved device design and clinical decision-making.

Coronary artery blood flow is influenced by various factors including vessel geometry, hemodynamic conditions, timing in the cardiac cycle, and rheological conditions. Multiple patterns of disturbed coronary flow may occur when blood flow separates from the laminar plane, associated with inefficient blood transit, and pathological processes modulated by the vascular endothelium in response to abnormal wall shear stress. Current simulation techniques, including computational fluid dynamics and fluid-structure interaction, can provide substantial detail on disturbed coronary flow and have advanced the contemporary understanding of the natural history of coronary disease. However, the clinical application of these techniques has been limited to hemodynamic assessment of coronary disease severity, with the potential to refine the assessment and management of coronary disease. Improved computational efficiency and large clinical trials are required to provide an incremental clinical benefit of these techniques beyond existing tools. This contemporary review is a clinically relevant overview of the disturbed coronary flow and its associated pathological consequences. The contemporary methods to assess disturbed flow are reviewed, including clinical applications of these techniques. Current limitations and future opportunities in the field are also discussed.

Objective: Non-invasive computation of the index of microcirculatory resistance from coronary computed tomography angiography (CTA), referred to as IMR[Formula: see text], is a promising approach for quantitative assessment of coronary microvascular dysfunction (CMD). However, the computation of IMR[Formula: see text] remains an important unresolved problem due to its high requirement for the accuracy of coronary blood flow. Existing CTA-based methods for estimating coronary blood flow rely on physiological assumption models to indirectly identify, which leads to inadequate personalization of total and vessel-specific flow., Methods: To overcome this challenge, we propose a vascular deformation-based flow estimation (VDFE) model to directly estimate coronary blood flow for reliable IMR[Formula: see text] computation. Specifically, we extract the vascular deformation of each vascular segment from multi-phase CTA. The concept of inverse problem solving is applied to implicitly derive coronary blood flow based on the physical constraint relationship between blood flow and vascular deformation. The vascular deformation constraints imposed on each segment within the vascular structure ensure sufficient individualization of coronary blood flow., Results: Experimental studies on 106 vessels collected from 89 subjects demonstrate the validity of our VDFE, achieving an IMR[Formula: see text] accuracy of 82.08 %. The coronary blood flow estimated by VDFE has better reliability than the other four existing methods., Conclusion: Our proposed VDFE is an effective approach to non-invasively compute IMR[Formula: see text] with excellent diagnostic performance., Significance: The VDFE has the potential to serve as a safe, effective, and cost-effective clinical tool for guiding CMD clinical treatment and assessing prognosis.

We present a case of a 45-year-old male with symptomatic supraventricular tachycardia. Electrophysiology study and 3-dimensional (3D) electroanatomic mapping showed a focal atrial tachycardia originating from a large left atrial diverticulum. Due to the unusual anatomy, 3D printing models were used to aid successful catheter ablation of the atrial tachycardia., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

Wall Shear Stress (WSS) is one of the most important parameters used in cardiovascular fluid mechanics, and it provides a lot of information like the risk level caused by any vascular occlusion. Since WSS cannot be measured directly and other available relevant methods have issues like low resolution, uncertainty and high cost, this study proposes a novel method by combining computational fluid dynamics (CFD), fluid-structure interaction (FSI), conditional generative adversarial network (cGAN) and convolutional neural network (CNN) to predict coronary artery occlusion risk using only noninvasive images accurately and rapidly. First, a cGAN model called WSSGAN was developed to predict the WSS contours on the vessel wall by training and testing the model based on the calculated WSS contours using coupling CFD-FSI simulations. Then, an 11-layer CNN was used to classify the WSS contours into three grades of occlusions, i.e. low risk, medium risk and high risk. To verify the proposed method for predicting the coronary artery occlusion risk in a real case, the patient's Magnetic Resonance Imaging (MRI) images were converted into a 3D geometry for use in the WASSGAN model. Then, the predicted WSS contours by the WSSGAN were entered into the CNN model to classify the occlusion grade., (© 2024. The Author(s).)

The present research extensively investigates the significance of the sac centerline length of the anterior cerebral artery (ACA) on aneurysm rupture risk. Hemodynamic factors influencing aneurysm rupture are assessed to identify critical regions prone to rupture. Wall shear stress is analyzed by modeling blood flow in three real saccular ACA cases with varying sac centerline lengths. A one-way fluid-solid interaction (FSI) model is employed to examine the interaction between blood flow and vessel deformation. The computational study reveals that wall shear stress on the ACA saccular aneurysm wall is significantly higher when the sac centerline length is shorter. Conversely, the mean oscillatory index changes with different sac centerline lengths, showing that an increase in sac centerline length leads to higher blood oscillation within the sac area in ACA cases., (© 2024. The Author(s).)

Left atrial appendage occlusion devices (LAAO) are a feasible alternative for non-valvular atrial fibrillation (AF) patients at high risk of thromboembolic stroke and contraindication to antithrombotic therapies. However, optimal LAAO device configurations (i.e., size, type, location) remain unstandardized due to the large anatomical variability of the left atrial appendage (LAA) morphology, leading to a 4-6% incidence of device-related thrombus (DRT). In-silico simulations have the potential to assess DRT risk and identify the key factors, such as suboptimal device positioning. This work presents fluid simulation results computed on 20 patient-specific left atrial geometries, analysing different commercially available LAAO occluders, including plug-type and pacifier-type devices. In addition, we explored two distinct device positions: 1) the real post-LAAO intervention configuration derived from follow-up imaging; and 2) one covering the pulmonary ridge if it was not achieved during the implantation (13 out of 20). In total, 33 different configurations were analysed. In-silico indices indicating high risk of DRT (e.g., low blood flow velocities and flow complexity around the device) were combined with particle deposition analysis based on a discrete phase model. The obtained results revealed that covering the pulmonary ridge with the LAAO device may be one of the key factors to prevent DRT, resulting in higher velocities and reduced flow recirculations (e.g., mean velocities of 0.183 ± 0.12 m/s and 0.236 ± 0.16 m/s for uncovered versus covered positions in DRT patients). Moreover, disk-based devices exhibited enhanced adaptability to various LAA morphologies and, generally, demonstrated a lower risk of abnormal events after LAAO implantation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Albors 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.)

Ithildin is an open-source library and framework for efficient parallelized simulations of excitable media, written in the C++ programming language. It uses parallelization on multiple CPU processors via the message passing interface (MPI). We demonstrate the library's versatility through a series of simulations in the context of the monodomain description of cardiac electrophysiology, including the S1S2 protocol, spiral break-up, and spiral waves in ventricular geometry. Our work demonstrates the power of Ithildin as a tool for studying complex wave patterns in cardiac tissue and its potential to inform future experimental and theoretical studies. We publish our full code with this paper in the name of open science., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kabus 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.)

Competing Interests: Declaration of interests The author declares no relevant financial relationships that could be construed as potential conflicts of interest.

The length-dependent activation (LDA) of maximum force and calcium sensitivity are established features of cardiac muscle contraction but the dominant underlying mechanisms remain to be fully clarified. Alongside the well-documented regulation of contraction via the thin filaments, experiments have identified an additional force-dependent thick-filament activation, whereby myosin heads parked in a so-called off state become available to generate force. This process produces a feedback effect that may potentially drive LDA. Using biomechanical modeling of a human left-ventricular myocyte, this study investigates the extent to which the off-state dynamics could, by itself, plausibly account for LDA, depending on the specific mathematical formulation of the feedback. We hypothesized four different models of the off-state regulatory feedback based on (A) total force, (B) active force, (C) sarcomere strain, and (D) passive force. We tested if these models could reproduce the isometric steady-state and dynamic LDA features predicted by an earlier published model of a human left-ventricle myocyte featuring purely phenomenological length dependences. The results suggest that only total-force feedback (A) is capable of reproducing the expected behaviors, but that passive tension could provide a length-dependent signal on which to initiate the feedback. Furthermore, by attributing LDA to off-state dynamics, our proposed model also qualitatively reproduces experimentally observed effects of the off-state-stabilizing drug mavacamten. Taken together, these results support off-state dynamics as a plausible primary mechanism underlying LDA., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Human-based modelling and simulation offer an ideal testbed for novel medical therapies to guide experimental and clinical studies. Myocardial infarction (MI) is a common cause of heart failure and mortality, for which novel therapies are urgently needed. Although cell therapy offers promise, electrophysiological heterogeneity raises pro-arrhythmic safety concerns, where underlying complex spatio-temporal dynamics cannot be investigated experimentally. Here, after demonstrating credibility of the modelling and simulation framework, we investigate cell therapy in acute versus chronic MI and the role of cell heterogeneity, scar size and the Purkinje system. Simulations agreed with experimental and clinical recordings from ionic to ECG dynamics in acute and chronic infarction. Following cell delivery, spontaneous beats were facilitated by heterogeneity in cell populations, chronic MI due to tissue depolarisation and slow sinus rhythm. Subsequent re-entrant arrhythmias occurred, in some instances with Purkinje involvement and their susceptibility was enhanced by impaired Purkinje-myocardium coupling, large scars and acute infarction. We conclude that homogeneity in injected ventricular-like cell populations minimises their spontaneous beating, which is enhanced by chronic MI, whereas a healthy Purkinje-myocardium coupling is key to prevent subsequent re-entrant arrhythmias, particularly for large scars., (© 2024. The Author(s).)

Unruptured giant intracranial aneurysms (GIA) are those with diameters of 25 mm or greater. As aneurysm size is correlated with rupture risk, GIA natural history is poor. Parent artery occlusion or trapping plus bypass revascularization should be considered to encourage intra-aneurysmal thrombosis when other treatment options are contraindicated. The mechanistic background of these methods is poorly studied. Thus, we assessed the potential of computational fluid dynamics (CFD) and fluid-structure interaction (FSI) analyses for clinical use in the preoperative stage. A CFD investigation in three patient-specific flexible models of whole arterial brain circulation was performed. A C6 ICA segment GIA model was created based on CT angiography. Two models were then constructed that simulated a virtual bypass in combination with proximal GIA occlusion, but with differing middle cerebral artery (MCA) recipient vessels for the anastomosis. FSI and CFD investigations were performed in three models to assess changes in flow pattern and haemodynamic parameters alternations (wall shear stress (WSS), oscillatory shear index (OSI), maximal time averaged WSS (TAWSS), and pressure). General flow splitting across the entire domain was affected by virtual bypass procedures, and any deficiency was partially compensated by a specific configuration of the circle of Willis. Following the implementation of bypass procedures, a reduction in haemodynamic parameters was observed within the aneurysm in both cases under analysis. In the case of the temporal MCA branch bypass, the decreases in the studied parameters were slightly greater than in the frontal MCA branch bypass. The reduction in the magnitude of the chosen area-averaged parameters (averaged over the aneurysm wall surface) was as follows: WSS 35.7%, OSI 19.0%, TAWSS 94.7%, and pressure 24.2%. FSI CFD investigation based on patient-specific anatomy models with subsequent stimulation of virtual proximal aneurysm occlusion in conjunction with bypass showed that this method creates a pro-thrombotic favourable environment whilst reducing intra-aneurysmal pressure leading to shrinking. MCA branch recipient selection for optimum haemodynamic conditions should be evaluated individually in the preoperative stage., (© 2024. The Author(s).)

Atherosclerosis involves an inflammatory response due to plaque formation within the arteries, which can lead to ischemic stroke and heart disease. It is one of the leading causes of death worldwide, with various contributing factors such as hyperlipidemia, hypertension, obesity, diabetes, and smoking. Wall shear stress (WSS) is also known as a contributing factor of the formation of atherosclerotic plaques. Since the causes of atherosclerosis cannot be attributed to a single factor, clearly understanding the mechanisms and causes of its occurrence is crucial for preventing the disease and developing effective treatment strategies. To better understand atherosclerosis and define the correlation between various contributing factors, computational fluid dynamics (CFD) analysis is primarily used. CFD simulates WSS, the frictional force caused by blood flow on the vessel wall with various hemodynamic changes. Using apolipoprotein E knockout (ApoE-KO) mice subjected to partial ligation and a high-fat diet at 1-week, 2-week, and 4-week intervals as an atherosclerosis model, CFD analysis was conducted along with the reconstruction of carotid artery blood flow via magnetic resonance imaging (MRI) and compared to the inflammatory factors and pathological staining. In this experiment, a comparative analysis of the effects of high WSS and low WSS was conducted by comparing the standard deviation of time-averaged wall shear stress (TAWSS) at each point within the vessel wall. As a novel approach, the standard deviation of TAWSS within the vessel was analyzed with the staining results and pathological features. Since the onset of atherosclerosis cannot be explained by a single factor, the aim was to find the correlation between the thickness of atherosclerotic plaques and inflammatory factors through standard deviation analysis. As a result, the gap between low WSS and high WSS widened as the interval between weeks in the atherosclerosis mouse model increased. This finding not only linked the occurrence of atherosclerosis to WSS differences but also provided a connection to the causes of vulnerable plaques., Competing Interests: The authors declare no conflicts of interest.

Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have gained traction as a powerful model in cardiac disease and therapeutics research, since iPSCs are self-renewing and can be derived from healthy and diseased patients without invasive surgery. However, current iPSC-CM differentiation methods produce cardiomyocytes with immature, fetal-like electrophysiological phenotypes, and the variety of maturation protocols in the literature results in phenotypic differences between labs. Heterogeneity of iPSC donor genetic backgrounds contributes to additional phenotypic variability. Several mathematical models of iPSC-CM electrophysiology have been developed to help to predict cell responses, but these models individually do not capture the phenotypic variability observed in iPSC-CMs. Here, we tackle these limitations by developing a computational pipeline to calibrate cell preparation-specific iPSC-CM electrophysiological parameters. We used the genetic algorithm (GA), a heuristic parameter calibration method, to tune ion channel parameters in a mathematical model of iPSC-CM physiology. To systematically optimize an experimental protocol that generates sufficient data for parameter calibration, we created in silico datasets by simulating various protocols applied to a population of models with known conductance variations, and then fitted parameters to those datasets. We found that calibrating to voltage and calcium transient data under 3 varied experimental conditions, including electrical pacing combined with ion channel blockade and changing buffer ion concentrations, improved model parameter estimates and model predictions of unseen channel block responses. This observation also held when the fitted data were normalized, suggesting that normalized fluorescence recordings, which are more accessible and higher throughput than patch clamp recordings, could sufficiently inform conductance parameters. Therefore, this computational pipeline can be applied to different iPSC-CM preparations to determine cell line-specific ion channel properties and understand the mechanisms behind variability in perturbation responses., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: "Tetsuro Wakatsuki and Neil Daily are employees with an ownership stake in Invivo Sciences. This company received an NIH SBIR grant that partially funded the research described in the study.", (Copyright: © 2024 Yang 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.)

Self-organizing spiral waves of excitation occur in many complex excitable systems. In the heart, for example, they are associated with the occurrence of fatal cardiac arrhythmias such as tachycardia and fibrillation, which can lead to sudden cardiac death. The control of these waves is therefore necessary for the treatment of the disease. In this letter, I present an innovative approach to control cardiac arrhythmias using low (nonfreezing) temperatures. This approach differs from all previous established techniques in that it involves no drugs, no genetic modification, no injection of foreign bodies, no application of voltage shocks (high or low, single or pulsed), and no curative damage to the heart. It relies on regional cooling of cardiac tissue to create a transient inhomogeneity in the electrophysiological properties. This inhomogeneity can then be manipulated to control the dynamics of the reentrant waves. This approach is, to my knowledge, the most sustainable theoretical proposal for the treatment of cardiac arrhythmias in the clinic., Competing Interests: Declaration of interests The author declares no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. 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.

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.

This study aimed to systematically review the use of clinical prediction models (CPMs) in personalised lifestyle interventions for the prevention of cardiovascular disease. We searched PubMed and PsycInfo for articles describing relevant studies published up to August 1, 2021. These were supplemented with items retrieved via screening references of citations and cited by references. In total, 32 studies were included. Nineteen different CPMs were used to guide the intervention. Most frequently, a version of the Framingham risk score was used. The CPM was used to inform the intensity of the intervention in five studies (16 %), and the intervention’s type in 31 studies (97 %). The CPM was supplemented with relative risk estimates for additional risk factors in three studies (9 %), and relative risk estimates for intervention effects in four (13 %). In addition to the estimated risk, the personalisation was determined using criteria based on univariable risk factors in 18 studies (56 %), a lifestyle score in three (9 %), and a physical examination index in one (3 %). We noted insufficient detail in reporting regarding the CPM’s use in 20 studies (63 %). In 15 studies (47 %), the primary outcome was a CPM estimate. A statistically significant effect favouring the intervention to the comparator arm was reported in four out of eight analyses (50 %), and a statistically significant improvement compared to baseline in five out of seven analyses (71 %). Due to the design of the included studies, the effect of the use of CPMs is still unclear. Therefore, we see a need for future research.

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.

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).)

Blood flow reconstruction in the vasculature is important for many clinical applications. However, in clinical settings, the available data are often quite limited. For instance, transcranial Doppler ultrasound is a non-invasive clinical tool that is commonly used in clinical settings to measure blood velocity waveforms at several locations. This amount of data is grossly insufficient for training machine learning surrogate models, such as deep neural networks or Gaussian process regression. In this work, we propose a Gaussian process regression approach based on empirical kernels constructed by data generated from physics-based simulations-enabling near-real-time reconstruction of blood flow in data-poor regimes. We introduce a novel methodology to reconstruct the kernel within the vascular network. The proposed kernel encodes both spatiotemporal and vessel-to-vessel correlations, thus enabling blood flow reconstruction in vessels that lack direct measurements. We demonstrate that any prediction made with the proposed kernel satisfies the conservation of mass principle. The kernel is constructed by running stochastic one-dimensional blood flow simulations, where the stochasticity captures the epistemic uncertainties, such as lack of knowledge about boundary conditions and uncertainties in vasculature geometries. We demonstrate the performance of the model on three test cases, namely, a simple Y-shaped bifurcation, abdominal aorta and the circle of Willis in the brain.

Background Pulse wave velocity (PWV) is a marker of arterial stiffness and local measurements could facilitate its widescale clinical use. However, confluence of incident and early reflected waves leads to biased spatiotemporal PWV estimates. Objective We introduce the Double Gaussian Propagation Model (DGPM) to measure local PWV in consideration of wave confluence (PWV[Formula: see text]) and compare it against conventional spatiotemporal PWV (PWV[Formula: see text]), with Bramwell-Hill PWV (PWV[Formula: see text]) and blood pressure (BP) as reference measures. Methods Ten subjects ranging from normotension to hypertension were repeatedly measured at rest and with induced PWV changes. Carotid distension waveforms over a 19 mm wide segment were acquired from ultrasonography, simultaneously with noninvasive continuous BP. Per cardiac cycle, the 8-parameter DGPM (amplitude, centroid, width, and velocity, respectively of forward and backward propagating wave) was fitted to the distension waveforms' systolic foot and dicrotic notch complexes. Corresponding PWV[Formula: see text] was computed from linear fittings of respective feature timings and distances. Regression analyses were conducted with PWV[Formula: see text] and PWV[Formula: see text] as predictors, and various PWV and BP measures as response variables. Results Whereas PWV[Formula: see text] correlations were insignificant, PWV[Formula: see text] estimated the reference PWV[Formula: see text] with a significant reduction in errors (P < 0.001), explained up to 65% PWV[Formula: see text] variability at rest, demonstrated higher intra-method consistency and correlated significantly with all BP measures (P < 0.001). Conclusion The proposed DGPM measures local carotid PWV in consideration of wave confluence, showing significant correlations with Bramwell-Hill PWV and BP at two distinct waveform complexes. Thereby PWV[Formula: see text] outperforms the conventional PWV[Formula: see text] in all investigated respects, potentially enabling PWV assessment in routine clinical practice.