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BACKGROUND: Multivariable equations are recommended by primary prevention guidelines to assess absolute risk of cardiovascular disease (CVD). However, current equations have several limitations. Therefore, we developed and validated the American Heart Association Predicting Risk of CVD EVENTs (PREVENT) equations among US adults 30 to 79 years of age without known CVD. METHODS: The derivation sample included individual-level participant data from 25 data sets (N=3281919) between 1992 and 2017. The primary outcome was CVD (atherosclerotic CVD and heart failure). Predictors included traditional risk factors (smoking status, systolic blood pressure, cholesterol, antihypertensive or statin use, and diabetes) and estimated glomerular filtration rate. Models were sex-specific, race-free, developed on the age scale, and adjusted for competing risk of nonCVD death. Analyses were conducted in each data set and meta-analyzed. Discrimination was assessed using the Harrell C-statistic. Calibration was calculated as the slope of the observed versus predicted risk by decile. Additional equations to predict each CVD subtype (atherosclerotic CVD and heart failure) and include optional predictors (urine albumin-tocreatinine ratio and hemoglobin A1c), and social deprivation index were also developed. External validation was performed in 3330085 participants from 21 additional data sets. RESULTS: Among 6612004 adults included, mean±SD age was 53±12 years, and 56% were women. Over a mean±SD follow-up of 4.8±3.1 years, there were 211515 incident total CVD events. The median C-statistics in external validation for CVD were 0.794 (interquartile interval, 0.763–0.809) in female and 0.757 (0.727–0.778) in male participants. The calibration slopes were 1.03 (interquartile interval, 0.81–1.16) and 0.94 (0.81–1.13) among female and male participants, respectively. Similar estimates for discrimination and calibration were observed for atherosclerotic CVD– and heart failure–specific models. The improvement in discrimination was small but statistically significant when urine albumin-to-creatinine ratio, hemoglobin A1c, and social deprivation index were added together to the base model to total CVD (ΔC-statistic [interquartile interval] 0.004 [0.004–0.005] and 0.005 [0.004–0.007] among female and male participants, respectively). Calibration improved significantly when the urine albumin-to-creatinine ratio was added to the base model among those with marked albuminuria (>300 mg/g; 1.05 [0.84–1.20] versus 1.39 [1.14–1.65]; P=0.01). CONCLUSIONS: PREVENT equations accurately and precisely predicted risk for incident CVD and CVD subtypes in a large, diverse, and contemporary sample of US adults by using routinely available clinical variables. [ABSTRACT FROM AUTHOR]

Cardiovascular-kidney-metabolic (CKM) syndrome is a novel construct recently defined by the American Heart Association in response to the high prevalence of metabolic and kidney disease. Epidemiological data demonstrate higher absolute risk of both atherosclerotic cardiovascular disease (CVD) and heart failure as an individual progresses from CKM stage 0 to stage 3, but optimal strategies for risk assessment need to be refined. Absolute risk assessment with the goal to match type and intensity of interventions with predicted risk and expected treatment benefit remains the cornerstone of primary prevention. Given the growing number of therapies in our armamentarium that simultaneously address all 3 CKM axes, novel risk prediction equations are needed that incorporate predictors and outcomes relevant to the CKM context. This should also include social determinants of health, which are key upstream drivers of CVD, to more equitably estimate and address risk. This scientific statement summarizes the background, rationale, and clinical implications for the newly developed sex-specific, race-free risk equations: PREVENT (AHA Predicting Risk of CVD Events). The PREVENT equations enable 10- and 30-year risk estimates for total CVD (composite of atherosclerotic CVD and heart failure), include estimated glomerular filtration rate as a predictor, and adjust for competing risk of non-CVD death among adults 30 to 79 years of age. Additional models accommodate enhanced predictive utility with the addition of CKM factors when clinically indicated for measurement (urine albumin-to-creatinine ratio and hemoglobin A1c) or social determinants of health (social deprivation index) when available. Approaches to implement risk-based prevention using PREVENT across various settings are discussed. [ABSTRACT FROM AUTHOR]

This paper investigates intimal growth in arteries, induced by hemodynamical shear stress, through finite element simulation using the FEniCS computational environment. In our model, the growth of the intima depends on cross-section geometry and shear stress. In this work, the arterial wall is modeled as three distinct layers: the intima, the media and the adventitia, each with different mechanical properties. We assume that the cross-section of the vessel does not change in the axial direction. We further assume that the blood flow is steady, non-turbulent and unidirectional. Blood flow induces shear stress on the endothelium and stimulates the release of platelet derived growth factor (PDGF) which drives the growth. We simulate intimal growth for three distinct arterial cross section geometries. We show that the qualitative nature of intimal thickening varies depending on arterial geometry. For cross section geometries that are annular, the growth of the intima is uniform in the angular direction, and the endothelium stays circular as the intima grows. For non-annular cross section geometries, the intima grows more quickly where it is thicker, and shear stress and intimal thickening are negatively correlated with the distance from the flow center, where the flow velocity is maximal. Over time, the maxima and minima of the curvature increase and decrease, respectively, the PDGF concentration increases and the lumen becomes more polygonal. The model provides a framework for coupling hemodynamics simulations to mathematical descriptions of atherosclerosis, both of which have been modeled separately in great detail., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.)

Vascular stent intervention is a pivotal treatment for coronary atherosclerosis, though in-stent thrombosis remains a significant postoperative complication with an unclear underlying mechanism. This study utilized dissipated particle dynamics analysis to investigate the impact of stent and its injury on platelet behavior. The findings suggest that thrombus formation upstream of the stent is mainly initiated by upstream arterial injury, which leads to increased platelet accumulation and activation in that area. While thrombosis downstream of the stent is more directly influenced by the stent itself. The morphology and size of in-stent thrombosis can vary significantly due to the different contributions of the stent and underlying injuries. Additionally, the volume of in-stent thrombosis is affected by the extent of the injury and the viscosity of platelets, showing a notable increase in volume with the lengthening of the injury area and rise in platelet viscosity. This study provides a novel theoretical framework for optimizing stent placement strategies and structural designs by examining the effects of stent struts and associated injuries on thrombus formation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Computational simulations are widely adopted in cardiovascular biomechanics because of their capability of producing physiological data otherwise impossible to measure with non-invasive modalities. Objective. This study presents openBF, a computational library for simulating the blood dynamics in the cardiovascular system. Approach. openBF adopts a one-dimensional viscoelastic representation of the arterial system, and is coupled with zero-dimensional windkessel models at the outlets. Equations are solved by means of the finite-volume method and the code is written in Julia. We assess its predictions by performing a multiscale validation study on several domains available from the literature. Main results. At all scales, which range from individual arteries to a population of virtual subjects, openBF's solution show excellent agreement with the solutions from existing software. For reported simulations, openBF requires low computational times. Significance. openBF is easy to install, use, and deploy on multiple platforms and architectures, and gives accurate prediction of blood dynamics in short time-frames. It is actively maintained and available open-source on GitHub, which favours contributions from the biomechanical community., (Creative Commons Attribution license.)

Intracranial aneurysms (IA) pose significant health risks and are often challenging to manage. Computational fluid dynamics (CFD) simulation has emerged as a powerful tool for understanding lesion-specific hemodynamics in and around IAs, aiding in the clinical management of patients with an IA. However, the current workflow of CFD simulations is time-consuming, complex, and labor-intensive and, thus, does not fit the clinical environment. To address these challenges, we have developed a semi-automated pipeline integrating multiple open-source software packages to streamline the CFD simulation process. Specifically, the study utilized medical angiography data from 18 patients. An in-house open-source DL image segmentation model (ARU-Net) was employed to generate 3D computer models of the anterior circulation. The segmented intracranial vasculature models, including IAs, were further refined using the Vascular Modeling Toolkit (VMTK), an open-source Python package. This step involved smoothing the surface of the models and extending the inlet and outlet regions to ensure a realistic representation of the vascular geometry. The refined vascular models were then converted into computational meshes using an open-source mesh generator known as TetGen. This process was nearly automated and required minimal user interaction(s). Blood flow simulations of the cerebral vascular models were performed using established SimVascular solvers (an open-source finite element platform for vascular applications) through an application programming interface (API). The CFD simulation process was also conducted using the manual workflow for comparative purposes. The initial assessment compared the geometries derived from manual and DL-based segmentation. The DL-based segmentation demonstrated reliable performance, closely aligning with manually segmented results, evidenced by excellent Pearson correlation coefficient (PCC) values and low relative difference (RD) values ranging from 3% to 10% between the computed geometrical variables derived from both methods. The statistical analysis of the computed hemodynamic variables, including velocity informatics and WSS-related variables, indicated good to excellent reliability for most parameters (e.g., ICC of 0.85-0.95). Given the data investigated, the proposed automated workflow streamlines the process of conducting CFD simulations. It generates results consistent with the current standard manual CFD protocol while minimizing dependence on user input., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

This State of the Future Review describes and discusses the potential transformative power of digital twins in cardiac electrophysiology. In this 'big picture' approach, we explore the evolution of mechanistic modelling based digital twins, their current and immediate clinical applications, and envision a future where continuous updates, advanced calibration, and seamless data integration redefine clinical practice of cardiac electrophysiology. Our aim is to inspire researchers and clinicians to embrace the extraordinary possibilities that digital twins offer in the pursuit of precision medicine., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Cardiac ventricular myocyte action potential dynamics are regulated by intricate and nonlinear interactions between the cell transmembrane potential and ionic currents and concentrations. Present technology limits the ability to measure transmembrane potential and multiple ionic currents simultaneously, which narrows the scope of experiments to provide a complete snapshot of the cardiac myocyte state. This limitation presents an obstacle for understanding how perturbations can trigger arrhythmias and more broadly how the myocyte responds to different conditions, such as changes in pacing rate or responses to drug treatment. In this study, we demonstrate that a data-assimilation approach can successfully reconstruct and predict the dynamics of a heterogeneous virtual cardiac ventricular myocyte population in the presence of parameter uncertainty. A population of heterogeneous cardiac ventricular myocytes is generated by varying ionic current conductance parameters, and additional observational uncertainty is mimicked by the addition of Gaussian noise to the transmembrane potential. We demonstrate that the data-assimilation approach accurately reconstructs transmembrane potential, with error less than the magnitude of the noise. Further, the data-assimilation approach successfully estimates the conductances of ionic currents generally with high accuracy and requiring low computational time. As a proof of concept, we apply the data-assimilation approach to reconstruct action potential dynamics from optical mapping experiments in an ex vivo isolated guinea pig heart. Critically, we demonstrate that the ionic conductance parameters estimated from a recording at one pacing frequency can accurately predict action potential dynamics at different rates., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Mixed reality (MR) has the potential to complement numerical simulations for enhanced post-processing and integrate digital models into the daily clinical practice of healthcare professionals. In complex cardiac anatomies, the decision-making process for bioprosthesis implantation involves the challenging analysis of heart valve distribution, positioning, and sealing. This study proposes a framework to visualize computational modeling results in an immersive environment for comprehensive analysis of the geometric implications of implanted devices on human heart function. After computational analysis, the biomechanical behavior of the Living Heart Human Model (LHHM) was used to develop MR content for the immersive visualization of the heart kinematics and the electrical field. Additionally, MR content was developed to assess the spatial implications of left ventricular outflow tract (LVOT) obstruction as observed in transcatheter mitral valve replacement (TMVR). Findings demonstrated that augmented exploration of cardiac biomechanics can be used for a better understanding of the electrical field of the beating heart. In the case of TMVR simulation, MR-related analysis of LVOT obstruction can result in improved visualization and manipulation of 3D anatomies and assessment of device-induced anatomic constraints. We conclude that the synergy between in-silico modeling and MR can potentially enhance physicians' ability to visualize the implications of biomedical device implants in complex cardiac anatomies, benefiting both physicians and simulation experts., 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 IPEM. Published by Elsevier Ltd. All rights reserved.)

In the past two decades there has been rapid development in the field of computational cardiac models. These have included either (i) mechanical models that assumed simultaneous myocardial activation, or (ii) electromechanical models that assumed time-varying myocardial activation. The influence of these modelling assumptions of myocardial activation on clinically relevant metrics, like myocardial strain, commonly used for validation of cardiac models has yet to be systematically examined, leading to uncertainty over their influence on the predictions of these models. This study examined the effects of simultaneous (mechanical), uniform endocardial, 3-patch endocardial (simulating the fascicles of the His-Purkinje system) and 1-patch endocardial (simulating the atrioventricular node) excitation sequences on the mechanical response of a synthetic human left ventricular model. The influence of the duration of the activation and time-to-peak contraction was also investigated. The electromechanical and mechanical models produced different strain distributions in early systole. However, these differences decayed as systole progressed. Using the same activation duration (74 ms) the average peak-systolic circumferential strain difference between the models was 0.65±0.37 %. A slightly prolonged activation duration (134 ms) resulted in no substantial difference increase (0.76±0.47 %). Differences up to 3.5 % were observed for prolonged activation durations (200 ms). Endocardial excitation produced non-physiological cumulative activation time distributions compared to the other models. Septal 1-patch excitation resulted in early systolic strain response that resembled pathological left bundle branch block. Decreased time-to-peak contraction exaggerated the effects of electrophysiology. The study found that excitation sequence minimally affects strain distributions at peak systole for physiological and even slightly pathological activation durations. However, electromechanical models with (patho)physiologically informed activation sequences are important for the accurate prediction of early systolic and pathological late systolic responses., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024. Published by Elsevier Ltd.)

Network represents adjacent relationships, connections, and interactions among constituent elements in complex systems but often loses critical information about spatial configurations. However, structure-function relationships in biological systems, e.g., the human heart, are highly dependent on both connectivity relationships and geometric details. Therefore, this paper presents a new self-organizing approach to derive the geometric structure from a network representation of the heart. We propose to simulate the network as a physical system, where nodes are treated as charged particles and edges as springs and then let these nodes self-organize to reconstruct geometric details. Despite random initiations, this network evolves into a steady topology when its energy is minimized. This study addresses the open question, i.e., "whether a network representation can effectively resemble spatial geometry of a biological system," thereby paving a stepstone to leverage network theory to investigate disease-altered biological functions., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Early afterdepolarizations (EADs) are spontaneous oscillations in membrane potential that occur during the repolarization phase of the action potential. EADs can trigger ventricular arrhythmias, such as Torsades de Pointes, in patients with long QT syndromes. Understanding the theoretical mechanisms behind EAD generation and developing strategies to suppress them are crucial. In this study, we employed bifurcation analysis along with a new fast-slow decomposition method on the O'Hara model of human ventricular myocytes. Our goal was to examine how the calcium ion concentration in the network sarcoplasmic reticulum (NSR) influences the generation of EADs in the context of reduced rapid delayed rectifier K+ current. Our findings identified nine distinct EAD states that coexist and can be controlled by slight adjustments to the NSR calcium ion concentration at a single time point., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

This study introduces an innovative real-time surgical planning platform optimized for the treatment of arterial aneurysms using intrasaccular flow disruption (IFD) devices. This platform incorporates a cutting-edge fast virtual deployment (FVD) algorithm alongside a discrete element method (DEM) for computational fluid dynamics (CFD) analyses. It facilitates the efficient virtual deployment of IFD devices, minimizing computational overhead while allowing for comprehensive postoperative hemodynamic efficacy assessment. The FVD algorithm employs an adaptive wall adherence and curvature control system, validated through both idealized and patient-specific model simulations. Post-treatment hemodynamic shifts are quantified by discretizing device wire filaments into discrete particles, which are then integrated with blood flow simulations for enhanced realism. The FVD algorithm efficiently executes virtual deployment of IFD devices within seconds, producing DEM-CFD computational models that align closely with bench testing, traditional Finite Element Method (FEM) analyses, and angiographic data. DEM-CFD outcomes link occlusion effectiveness to post-implantation hemodynamic characteristics, influenced by the aneurysm's unique anatomical features and clinical intervention strategies. The proposed platform demonstrates substantial improvement in balancing computational efficiency with analytical precision. It provides a viable and innovative framework for real-time surgical planning, presenting significant implications for clinical application in arterial aneurysm management., (© 2024 John Wiley & Sons Ltd.)

Ca 2+ waves are known to trigger delayed after-depolarizations that can cause malignant cardiac arrhythmias. However, modelling Ca 2+ waves using physiologically realistic models has remained a major challenge. Existing models with low Ca 2+ sensitivity of ryanodine receptors (RyRs) necessitate large release currents, leading to an unrealistically large Ca 2+ transient amplitude incompatible with the experimental observations. Consequently, current physiologically detailed models of delayed after-depolarizations resort to unrealistic cell architectures to produce Ca 2+ waves with a normal Ca 2+ transient amplitude. Here, we address these challenges by incorporating RyR cooperativity into a physiologically detailed model with a realistic cell architecture. We represent RyR cooperativity phenomenologically through a Hill coefficient within the sigmoid function of RyR open probability. Simulations in permeabilized myocytes with high Ca 2+ sensitivity reveal that a sufficiently large Hill coefficient is required for Ca 2+ wave propagation via the fire-diffuse-fire mechanism. In intact myocytes, propagating Ca 2+ waves can occur only within an intermediate Hill coefficient range. Within this range, the spark rate is neither too low, enabling Ca 2+ wave propagation, nor too high, allowing for the maintenance of a high sarcoplasmic reticulum load during diastole of the action potential. Moreover, this model successfully replicates other experimentally observed manifestations of Ca 2+ -wave-mediated triggered activity, including phase 2 and phase 3 early after-depolarizations and high-frequency voltage-Ca 2+ oscillations. These oscillations feature an elevated take-off potential with depolarization mediated by the L-type Ca 2+ current. The model also sheds light on the roles of luminal gating of RyRs and the mobile buffer ATP in the genesis of these arrhythmogenic phenomena. KEY POINTS: Existing mathematical models of Ca 2+ waves use an excessively large Ca 2+ -release current or unrealistic diffusive coupling between release units. Our physiologically realistic model, using a Hill coefficient in the ryanodine receptor (RyR) gating function to represent RyR cooperativity, addresses these limitations and generates organized Ca 2+ waves at Hill coefficients ranging from ∼5 to 10, as opposed to the traditional value of 2. This range of Hill coefficients gives a spark rate neither too low, thereby enabling Ca 2+ wave propagation, nor too high, allowing for the maintenance of a high sarcoplasmic reticulum load during the plateau phase of the action potential. Additionally, the model generates Ca 2+ -wave-mediated phase 2 and phase 3 early after-depolarizations, and coupled membrane voltage with Ca 2+ oscillations mediated by the L-type Ca 2+ current. This study suggests that pharmacologically targeting RyR cooperativity could be a promising strategy for treating cardiac arrhythmias linked to Ca 2+ -wave-mediated triggered activity., (© 2024 The Authors. The Journal of Physiology © 2024 The Physiological Society.)

The prediction of neointimal hyperplasia (NIH) growth, leading to vein graft failure in lower-limb peripheral arterial disease (PAD), is hindered by the multifactorial and multiscale mechanobiological mechanisms underlying the vascular remodelling process. Multiscale in silico models, linking patients' hemodynamics to NIH pathobiological mechanisms, can serve as a clinical support tool to monitor disease progression. Here, we propose a new computational pipeline for simulating NIH growth, carefully balancing model complexity/inclusion of mechanisms and readily available clinical data, and we use it to predict NIH growth for an entire vein graft. To this end, three different fittings to published in vitro data of time-averaged wall shear stress (TAWSS) vs nitric oxide (NO) production were tested for predicting long-term graft response (10-month follow-up) on a single patient. Additionally, the sensitivity of the model's predictions to different inflow boundary conditions (BCs) was assessed. The main findings indicate that: (i) a TAWSS-NO hyperbolic relationship best predicts long-term graft response; (ii) the model is insensitive to the inflow BCs if the waveform shape and the systolic acceleration time are comparable with the one acquired at the same time as the computed-tomography scan. This proof-of-concept study demonstrates the potential of using multiscale, computational techniques to predict NIH growth in lower-limb vein grafts, considering the routine clinical scenario of non-standardised data collection and sparse, incomplete datasets., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Reported in this paper is a cutting-edge computational investigation into the influence of geometric characteristics on abdominal aortic aneurysm (AAA) rupture risk, beyond the traditional measure of maximum aneurysm diameter. A Comprehensive fluid-structure interaction (FSI) analysis was employed to assess risk factors in a range of patient scenarios, with the use of three-dimensional (3D) AAA models reconstructed from patient-specific aortic data and finite element method. Wall shear stress (WSS), and its derivatives such as time-averaged WSS (TAWSS), oscillatory shear index (OSI), relative residence time (RRT) and transverse WSS (transWSS) offer insights into the force dynamics acting on the AAA wall. Emphasis is placed on these WSS-based metrics and seven key geometric indices. By correlating these geometric discrepancies with biomechanical phenomena, this study highlights the novel and profound impact of geometry on risk prediction. This study demonstrates the necessity of a multidimensional assessment approach, future efforts should complement these findings with experimental validations for an applicable approach for clinical use., (© 2024 John Wiley & Sons Ltd.)

Stroke is a leading cause of death and disability worldwide. Atrial myopathy, including fibrosis, is associated with an increased risk of ischaemic stroke, but the mechanisms underlying this association are poorly understood. Fibrosis modifies myocardial structure, impairing electrical propagation and tissue biomechanics, and creating stagnant flow regions where clots could form. Fibrosis can be mapped non-invasively using late gadolinium enhancement magnetic resonance imaging (LGE-MRI). However, fibrosis maps are not currently incorporated into stroke risk calculations or computational electro-mechano-fluidic models. We present multiphysics simulations of left atrial (LA) myocardial motion and haemodynamics using patient-specific anatomies and fibrotic maps from LGE-MRI. We modify tissue stiffness and active tension generation in fibrotic regions and investigate how these changes affect LA flow for different fibrotic burdens. We find that fibrotic regions and, to a lesser extent, non-fibrotic regions experience reduced myocardial strain, resulting in decreased LA emptying fraction consistent with clinical observations. Both fibrotic tissue stiffening and hypocontractility independently reduce LA function, but, together, these two alterations cause more pronounced effects than either one alone. Fibrosis significantly alters flow patterns throughout the atrial chamber, and particularly, the filling and emptying jets of the left atrial appendage (LAA). The effects of fibrosis in LA flow are largely captured by the concomitant changes in LA emptying fraction except inside the LAA, where a multifactorial behaviour is observed. This work illustrates how high-fidelity, multiphysics models can be used to study thrombogenesis mechanisms in patient-specific anatomies, shedding light onto the links between atrial fibrosis and ischaemic stroke. KEY POINTS: Left atrial (LA) fibrosis is associated with arrhythmogenesis and increased risk of ischaemic stroke; its extent and pattern can be quantified on a patient-specific basis using late gadolinium enhancement magnetic resonance imaging. Current stroke risk prediction tools have limited personalization, and their accuracy could be improved by incorporating patient-specific information such as fibrotic maps and haemodynamic patterns. We present the first electro-mechano-fluidic multiphysics computational simulations of LA flow, including fibrosis and anatomies from medical imaging. Mechanical changes in fibrotic tissue impair global LA motion, decreasing LA and left atrial appendage (LAA) emptying fractions, especially in subjects with higher fibrosis burdens. Fibrotic-mediated LA motion impairment alters LA and LAA flow near the endocardium and the whole cavity, ultimately leading to more stagnant blood regions in the LAA., (© 2024 The Authors. The Journal of Physiology © 2024 The Physiological Society.)

This study presents four different impeller designs to compare hydrodynamic forces. Numerical simulation studies are performed via computational fluid dynamics to specify and investigate the hydraulic forces impacting the impeller of the mixed-flow blood pump with a volute. The design point of this pump is that the flow rate is 5 L/min, the rotational speed is 8000 rpm, and the manometric head is 100 mmHg. The designed impellers are placed in the same volute and simulation studies are performed with the same mesh size (17.3 million cells) of the pumps. The simulation studies have been conducted in setting 1050 kg/m 3 blood density, 35 cP fluid viscosity, and SST-kω turbulence model. Additionally, this study examines the changes in hydraulic forces and hydraulic efficiency with fluid viscosity. As a result of experimental simulation studies, the highest hydraulic efficiencies of 40.87% and 39.5% are achieved in the case of the shaftless-grooveless and shafted-grooveless impeller, respectively. The maximum axial forces are obtained from the pump with the shaftless-grooveless impeller. Whereas radial forces, maximum values are calculated in the pump with the shaftless-outer groove impeller for all flow rates. Finally, the wall shear stresses, which are important for blood pump designs, are evaluated and the maximum value of 227 Pa is observed in the pump impeller with a shaftless-grooved., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The mechanisms leading to aneurysm occlusion after treatment with flow-diverting devices are not fully understood. Flow modification induces thrombus formation within the aneurysm cavity, but fibrin can simultaneously accumulate and cover the device scaffold, leading to further flow modification. However, the interplay and relative importance of these processes are not clearly understood. A computational model of fibrin accumulation and flow modification after flow diversion treatment of cerebral aneurysms has been developed under the guidance of in vitro experiments and observations. The model is based on the loose coupling of flow and transport-reaction equations that are solved separately by independent codes. Interaction or reactive terms account for thrombin production from prothrombin stimulated by thrombogenic metallic wires and inhibition by antithrombin as well as fibrin production from fibrinogen stimulated by thrombin and flow shear stress, and fibrin adhesion to device wires and already attached fibrin. The computational model was demonstrated and tested on idealized vessel and aneurysm geometries. The model was able to reproduce the salient features of fibrin accumulation after the deployment of flow-diverting devices in idealized in vitro models of cerebral aneurysms. Namely, fibrin production in regions of high shear stress, initial accumulation at the inflow zone, and progressive occlusion of the device and corresponding flow attenuation. The computational model linking flow dynamics to fibrin production, transport, and adhesion can be used to investigate and better understand the effects that lead to fibrin accumulation and the resulting aneurysm inflow reduction and intra-aneurysmal flow modulation., (© 2024 The Author(s). International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.)

Endovascular coil embolization is the primary therapeutic modality for intracranial aneurysms. Substantial reports have been found regarding the coil packing density and inflow jet. However, the hemodynamic effect of increasing the rate of tamponade in the inflow jet area within the aneurysm remains unclear. In this study, individualized geometries of six intracranial aneurysms were recruited: all six aneurysms were located in the internal carotid artery. Two groups were created by changing the position and orientation of the microcatheter for the release of the third segment of the filling coil. The finite element method was used to simulate coil deployment. Computational fluid dynamics was used to characterize hemodynamics in post-deployment aneurysms. The parameters evaluated included velocity reduction, wall shear stress (WSS), low WSS (LWSS), relative residence time (RRT), flow kinetic energy in the neck region of the aneurysms, and residual flow volume (RFV) in the aneurysms. At the peak time (t = 0.17 s), the targeted deployment group has similar proportion of LWSS area to conventional deployment groups: targeted 78.13% ± 34.59% versus normal 74.20% ± 36.94% (mean ± SD, p = 0.583). The targeted deployment group has a higher RRT area (targeted 16.84% ± 5.58% vs. normal 6.42% ± 5.67% [mean ± SD, p = 0.009]), smaller flow kinetic energy (targeted 9.43 ± 4.33 vs. normal 16.23 ± 5.92 [mean ± SD, p = 0.047]), and a larger RFV in the aneurysms (targeted 35.97 ± 24.35 mm 3 vs. normal 25.80 ± 18.94 mm 3 [mean ± SD, p = 0.44]). Inflow jets play an important role in the treatment of aneurysms, and deploying filling coils in accordance with inflow jets may result in a better hemodynamic environment., (© 2024 John Wiley & Sons Ltd.)

Background and Objective: Modelling patient-specific aortic biomechanics with advanced computational techniques, such as Fluid-Structure Interaction (FSI), can be crucial to provide effective decision-making indices to enhance current clinical practices. To effectively simulate Ascending Thoracic Aortic Aneurysms (ATAA), the stress-free configuration must be defined. The Zero Pressure Geometry (ZPG) and the Prestress Tensor (PT) are two of the main approaches to tackle this issue. However, their impact on the numerical results is yet to be analysed. Computed Tomography Angiography (CTA) and Magnetic Resonance Imaging (MRI) data were used to develop patient-specific 2-way FSI frameworks., Methods: Three models were developed considering different tissue prestressing approaches to account for the reference configuration and their numerical results were compared. The selected approaches were: (i) ZPG, (ii) PT and (iii) a combination of the PT approach with a regional mapping of material properties (PTCAL)., Results: The pressure fields estimated by all models were equivalent. The estimation of Wall Shear Stress (WSS) based metrics revealed good correspondence between all models except the Relative Residence Time (RRT). Regarding ATAA wall mechanics, the proposed extension to the PT approach presented a closer agreement with the ZPG model than its counterpart. Additionally, the PT and PTCAL approaches required around 60% fewer iterations to achieve cycle-to-cycle convergence than the ZPG algorithm., Conclusion: Using a regional mapping of material properties in combination with the PT method presented a better correspondence with the ZPG approach. The outcomes of this study can pave the way for advancing the accuracy and convergence of ATAA numerical models using the PT methodology., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Xavier, José reports financial support was provided by the Foundation for Science and Technology. Xavier, José reports a relationship with NOVA University Lisbon NOVA School of Science & Technology that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

An ongoing thrombosis on a ruptured atherosclerotic plaque in the carotid may cause stroke. The primary treatment for patients with tandem lesion is stenting. Dual-layer stents have been introduced as an alternative to single-layer stents for elective and emergent carotid artery stenting. While the dual-layer structure shows promise in reducing plaque prolapse through the stent struts and with it the occurrence of post-procedural embolism, there are early signs that this newer generation of stents is more thrombogenic. We investigate a single- and a dual-layer stent design to assess their influence on a set of thrombosis-related flow factors in a novel setup of combined experiments and simulations. The in vitro results reveal that both stents reduce thrombus formation by approximately 50% when human anticoagulated whole blood was perfused through macrofluidic flow chambers coated with either collagen or human atherosclerotic plaque homogenates. Simulations predict that the primary cause is reduced platelet presence in the vicinity of the wall, due to the influence of stents on flow and cellular transport. Both stents significantly alter the near-wall flow conditions, modifying shear rate, shear gradient, cell-free zones, and platelet availability. Additionally, the dual-layer stent has further increased local shear rates on the inner struts. It also displays increased stagnation zones and reduced recirculation between the outer-layer struts. Finally, the dual-layer stent shows further reduced adhesion over an atherosclerotic plaque coating. The novel approach presented here can be used to improve the design optimization process of cardiovascular stents in the future by allowing an in-depth study of the emerging flow characteristics and agonist transport., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Bioprosthetic heart valve (BHV), the most widely and commonly used valves in clinical practice, are susceptible to fatigue damage. Biological valves are always in one or fewer body postures before sampling in pigs and bovines. Nevertheless, human body positions are far more than them. Variations in body position significantly affect the intrinsic environment of blood pressure (BP), heart rate (HR), and peripheral resistance (PR). Such boundary condition changes will inevitably affect the implanted biological valve. In this paper, the immersed boundary method was used to simulate the motion of the aortic valve during the entire cardiac cycle in five postural blood flow environments: upright, sitting, prone, supine and orthostatic hypotension (OH). Several hemodynamic and biomechanical parameters, including the transvalvular pressure gradient and valve displacement, were evaluated. The results showed that the OH group exhibited the worst performance of the valves, accompanied by the greatest regurgitation and high-frequency flutter, predisposing patients to thrombosis and fatigue calcification. For BHVs to serve longer, patients implanted with BHV should avoid OH in their daily routine., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The intricate process of coronary in-stent restenosis (ISR) involves the interplay between different mediators, including platelet-derived growth factor, transforming growth factor-β, extracellular matrix, smooth muscle cells, endothelial cells, and drug elution from the stent. Modeling such complex multiphysics phenomena demands extensive computational resources and time., Methods: This paper proposes a novel non-intrusive data-driven reduced order modeling approach for the underlying multiphysics time-dependent parametrized problem. In the offline phase, a 3D convolutional autoencoder, comprising an encoder and decoder, is trained to achieve dimensionality reduction. The encoder condenses the full-order solution into a lower-dimensional latent space, while the decoder facilitates the reconstruction of the full solution from the latent space. To deal with the 5D input datasets (3D geometry + time series + multiple output channels), two ingredients are explored. The first approach incorporates time as an additional parameter and applies 3D convolution on individual time steps, encoding a distinct latent variable for each parameter instance within each time step. The second approach reshapes the 3D geometry into a 2D plane along a less interactive axis and stacks all time steps in the third direction for each parameter instance. This rearrangement generates a larger and complete dataset for one parameter instance, resulting in a singular latent variable across the entire discrete time-series. In both approaches, the multiple outputs are considered automatically in the convolutions. Moreover, Gaussian process regression is applied to establish correlations between the latent variable and the input parameter., Results: The constitutive model reveals a significant acceleration in neointimal growth between 30-60 days post percutaneous coronary intervention (PCI). The surrogate models applying both approaches exhibit high accuracy in pointwise error, with the first approach showcasing smaller errors across the entire evaluation period for all outputs. The parameter study on drug dosage against ISR rates provides noteworthy insights of neointimal growth, where the nonlinear dependence of ISR rates on the peak drug flux exhibits intriguing periodic patterns. Applying the trained model, the rate of ISR is effectively evaluated, and the optimal parameter range for drug dosage is identified., Conclusion: The demonstrated non-intrusive reduced order surrogate model proves to be a powerful tool for predicting ISR outcomes. Moreover, the proposed method lays the foundation for real-time simulations and optimization of PCI parameters., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Atrial fibrillation (AF) is the most common cardiac arrhythmia with mechanisms of initiation and sustaining that are not fully understood. The clinical procedure for AF contemplates the analysis of the atrial electrograms, whose morphology has been correlated with the underlying structure of the atrial myocardium. This study employs a mathematical model incorporating fractional calculus to simulate cardiac electrical conduction, accounting for tissue structural inhomogeneities using complex-valued orders. Simulations of different wavefront propagation patterns were performed, and virtual electrograms were analyzed using an asymmetry factor. Our results evinced that the shapes of the action potential and the propagating wavefront can be modulated through the fractional order under both healthy and AF conditions. Moreover, the asymmetry factor changes with variations in the fractional order. For a given propagation pattern under AF conditions, variation intervals for the asymmetry factor can be generated by forming sets of simulations with different configurations for the fractional order, representing diverse samples of atrial tissue with varying degrees of structural heterogeneity. This approach successfully reproduces the electrogram negative deflection predominance seen in AF patients, which standard integer-order models cannot predict. Our fractional-order conduction model aligns with the effects of atrial structure on the electrical dynamics observed in clinical AF. Therefore, it offers a valuable tool for studying cardiac electrophysiology, encompassing both electrical and structural interactions of the tissue within a unified model., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Objective: Right ventricular failure increases short-term mortality in the setting of acute myocardial infarction, cardiogenic shock, advanced left-sided heart failure and pulmonary arterial hypertension. Percutaneous and surgically implanted right ventricular assist devices (RVAD) have been investigated in different clinical settings. The use of the ProtekDuo™ is currently a promising approach due to its features such as groin-free approach leading to early mobilisation, easy percutaneous deployment, compatibility with different pumps and oxygenators, and adaptability to different configurations. The aim of this work was to simulate the behaviour of the TandemHeart™ pump applied "in series" and "in parallel" mode and the combination of TandemHeart™ and ProtekDuo™ cannula as RVAD using CARDIOSIM© software simulator platform., Methods: To achieve our aim, two new modules have been implemented in the software. The first module simulated the TandemHeart™ pump in RVAD configuration, both as a right atrial-pulmonary arterial and a right ventricular-pulmonary arterial connection, driven by four different rotational speeds. The second module reproduced the behaviour of the ProtekDuo™ cannula plus TandemHeart™., Results: The effects induced on the main haemodynamic and energetic variables were analysed for both the right atrial-pulmonary arterial and right ventricular-pulmonary arterial configuration with different pump rotational speed and following Milrinone administration. The TandemHeart™ increased right ventricular end systolic volume by 10 %, larger increases were evident for higher speeds (6000 and 7500 rpm) and connections with 21-Fr inflow and 17-Fr outflow cannula, respectively. Both TandemHeart™ and ProtekDuo™ support increased left ventricular preload. When different RVAD settings were used, Milrinone therapy increased the left ventricular pressure-volume area and decreased the right pressure-volume area slightly. A reduction in oxygen consumption (demand) was observed with reduced right stroke work and pressure volume area and increased oxygen supply (coronary blood flow)., Conclusions: The outcome of our simulations confirms the effective haemodynamic assistance provided by the ProtekDuo™ as observed in the acute clinical setting. A simulation approach based on pressure-volume analysis combined with modified time-varying elastance and lumped-parameter modelling remains a suitable tool for clinical applications., Competing Interests: Declaration of competing interest All authors have no conflicts of interest, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Objective: Numerical simulations are valuable tools for studying cardiac arrhythmias. Not only do they complement experimental studies, but there is also an increasing expectation for their use in clinical applications to guide patient-specific procedures. However, numerical studies that solve the reaction-diffusion equations describing cardiac electrical activity remain challenging to set up, are time-consuming, and in many cases, are prohibitively computationally expensive for long studies. The computational cost of cardiac simulations of complex models on anatomically accurate structures necessitates parallel computing. Graphics processing units (GPUs), which have thousands of cores, have been introduced as a viable technology for carrying out fast cardiac simulations, sometimes including real-time interactivity. Our main objective is to increase the performance and accuracy of such GPU implementations while conserving computational resources., Methods: In this work, we present a compression algorithm that can be used to conserve GPU memory and improve efficiency by managing the sparsity that is inherent in using Cartesian grids to represent cardiac structures directly obtained from high-resolution MRI and mCT scans. Furthermore, we present a discretization scheme that includes the cross-diagonal terms in the computational cell to increase numerical accuracy, which is especially important for simulating thin tissue sections without the need for costly mesh refinement., Results: Interactive WebGL simulations of atrial/ventricular structures (on PCs, laptops, tablets, and phones) demonstrate the algorithm's ability to reduce memory demand by an order of magnitude and achieve calculations up to 20x faster. We further showcase its superiority in slender tissues and validate results against experiments performed in live explanted human hearts., Conclusions: In this work, we present a compression algorithm that accelerates electrical activity simulations on realistic anatomies by an order of magnitude (up to 20x), thereby allowing the use of finer grid resolutions while conserving GPU memory. Additionally, improved accuracy is achieved through cross-diagonal terms, which are essential for thin tissues, often found in heart structures such as pectinate muscles and trabeculae, as well as Purkinje fibers. Our method enables interactive simulations with even interactive domain boundary manipulation (unlike finite element/volume methods). Finally, agreement with experiments and ease of mesh import into WebGL paves the way for virtual cohorts and digital twins, aiding arrhythmia analysis and personalized therapies., 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., (Published by Elsevier B.V.)

Background: The Fontan operation, a palliative procedure for single ventricle patients, has evolved to improve outcomes and reduce complications. While extracardiac conduit (ECC) is favored for its simplicity and potential hemodynamic benefits, concerns arise about conduit size adequacy over time. Undersized ECC conduits may cause hemodynamic inefficiencies and long-term complications, while oversizing can lead to flow disturbances, stagnation, and thrombosis, necessitating surgical revision or upsizing to optimize hemodynamics., Objectives: The study aimed to predict the impact of upsizing by developing a patient-specific workflow using cardiac magnetic resonance-based imaging and computational fluid dynamics to assess Fontan hemodynamic changes and determine the most optimal conduit size., Methods: We simulated upsizing in patient-specific models, computing reduction in power loss (PL), and analyzed pressure gradients, wall shear stress (WSS), and other local flow dynamic parameters such as vorticity and viscous dissipation that influence PL in a Fontan. Additionally, we quantified the impact of upsizing on hepatic flow distribution (HFD)., Results: Across the patient cohort, upsizing resulted in a PL reduction of 16 %-63 %, with the greatest reduction observed in patients with the smallest pre-existing conduit sizes (14 mm). The optimal conduit size for minimizing PL was highly patient-specific. For instance, a 20 mm conduit reduced PL by 63 % in one patient, while another patient showed 16 % reduction with upsizing. Pressure gradients decreased by 15 %-35 %, correlating with the reduction in PL, while WSS decreased consistently with upsizing. Vorticity and viscous dissipation exhibited more variability but followed the overall trend of reduced PL. HFD changes were modest with a maximum variation of 30 %., Conclusions: Our findings underscore the importance of individualized approaches in Fontan conduit upsizing. CFD-based quantitative evaluations of PL, pressure gradients, HFD, and WSS can guide optimal conduit sizing, improving long-term outcomes for patients., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:VG reports research funding from the AHA (19TPA34860013), the NHLBI/NIH (R01HL161507) and in-kind research support from NSF (high-performance computing resources from TACC). AS, EE, DH, PEH, and RR report research funding from the NHLBI/NIH (R01HL161507)., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Most of the modeling of the Left Ventricular Assist Devices (LVADs) coupled with the cardiovascular system is based on the assumption of constant rotational speed. Compared with the traditional inertial model, the validated hysteresis model can take into account the unsteady characteristics of LVADs, but it fails to work under the condition of variable speed modulation., Method: This study takes into consideration the impact of speed variations on the unsteady hysteresis effects. The time constant in the hysteresis model is treated as a time-varying parameter, thereby developing a new model applicable to variable speed modulation. Under sinusoidal speed modulation at various phases, a comparative analysis was undertaken among the steady-state model, inertial model, and the new model. Transient Computational Fluid Dynamics (CFD) simulations and existing experimental results are used for validation., Results: The new model provides a more accurate method for the predicting the characteristics of LVAD in the coupled model under varying pump speeds, and exhibits higher linearity in the work done by the left ventricle and the blood pump, and R 2 = 0 . 9998 , which is aligning closely with the experimental results. This enhancement renders it applicable for proactive control predictions and passive control validations., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Detection of clinically relevant stenosis within coronary arteries as well as planning of treatment (stent implantation) are important topics in clinical cardiology. In this study a thorough methodology for virtual stenting assistance is proposed, that includes the 3D reconstruction of a patient-specific coronary artery from X-ray angiography images, hemodynamic simulations of blood flow, computation of a fractional flow reserve (FFR) equivalent, virtual stenting procedure and an optimization of the virtual stenting, by considering not only the value of computed FFR, but also the low and high WSS regions and the state of arterial wall after stenting. The evaluation of the proposed methodology is performed in two ways: the calculated values of FFR are compared with clinically measured values; and the results obtained for automated optimized virtual stenting are compared with virtual stenting performed manually by an expert clinician for the whole considered dataset. The agreement of the results in almost all cases demonstrates the accuracy of the proposed approach, and the small discrepancies only show the capabilities and benefits this approach can offer. The automated optimized virtual stenting technique can provide information about the most optimal stent position that ensures the maximum achievable FFR, while also considering the distribution of WSS and the state of arterial wall. The proposed methodology and developed software can therefore be used as a noninvasive method for planning of optimal patient-specific treatment strategies before invasive procedures and thus help to improve the clinical outcome of interventions and provide better treatment planning adapted to the particular patient., Competing Interests: Declaration of competing interest None Declared., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background and Objective: Prosthetic heart valve interventions such as TAVR have surged over the past decade, but the associated complication of long-term, life-threatening thrombotic events continues to undermine patient outcomes. Thus, improving thrombogenic risk analysis of TAVR devices is crucial. In vitro studies for thrombogenicity are typically difficult to perform. However, revised ISO testing standards include computational testing for thrombogenic risk assessment of cardiovascular implants. We present a fluid-structure interaction (FSI) approach for assessing thrombogenic risk of transcatheter aortic valves., Methods: An FSI framework was implemented via the incompressible computational fluid dynamics multi-physics solver of the ANSYS LS-DYNA software. The numerical modeling approach for flow analysis was validated by comparing the derived flow rate of the 29 mm CoreValve device from benchtop testing and orifice areas of commercial TAVR valves in the literature to in silico results. Thrombogenic risk was analyzed by computing stress accumulation (SA) on virtual platelets seeded in the flow fields via ANSYS EnSight. The integrated FSI-thrombogenicity methodology was subsequently employed to examine hemodynamics and thrombogenic risk of TAVR devices with two approaches: 1) engineering optimization and 2) clinical assessment., Results: Simulated effective orifice areas for commercial valves were in reported ranges. In silico cardiac output and flow rate during the positive pressure differential period matched experimental results by approximately 93 %. The approach was used to analyze the effect of various TAVR leaflet designs on hemodynamics, where platelets experienced instantaneous stresses reaching around 10 Pa. Post-TAVR deployment hemodynamics in patient-specific bicuspid aortic valve anatomies revealed varying degrees of thrombogenic risk with the highest median SA around 70 dyn·s/cm 2 - nearly double the activation threshold - despite those being clinically classified as "mild" paravalvular leaks., Conclusions: Our methodology can be used to improve the thromboresistance of prosthetic valves from the initial design stage to the clinic. It allows for unparalleled optimization of devices, uncovering key TAVR leaflet design parameters that can be used to mitigate thrombogenic risk, in addition to patient-specific modeling to evaluate device performance. This work demonstrates the utility of advanced in silico analysis of TAVR devices that can be utilized for thrombogenic risk assessment of other blood recirculating devices., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Danny Bluestein reports financial support was provided by National Institutes of Health. Author Kyle Baylous is a consultant for PolyNova Cardiovascular Inc. Authors Danny Bluestein and Marvin Slepian have an equity interest in PolyNova Cardiovascular Inc. Authors Rodrigo Paz and Marc Horner are employees of ANSYS, Inc., which develops the software for computational modeling and simulation used in the study., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Crystalline methamphetamine hydrochloride is an illegal drug with a high addictive potential, better known by its colloquial name "ice" or "crystal meth". The abuse of this drug has led to significant health problems worldwide. Like other amphetamine-type stimulants, chronic consumption of methamphetamine leads to direct toxic effects on the central nervous system, causing cognitive impairment, depressive behavior, and other severe neurological or psychiatric symptoms. Besides its neurotoxicity, the drug exhibits numerous deleterious effects on the cardiovascular system, including hypertension, accelerated atherosclerosis, vasospasm-induced acute coronary syndromes, sudden cardiac death, and dilated cardiomyopathy with congestive heart failure and left ventricular dysfunction. The excessive release of catecholamines upon methamphetamine exposure causes vasoconstriction and vasospasm, which ultimately lead to hypertension, tachycardia, endothelial dysfunction, and cardiotoxicity. While numerous studies have focused on transcription factors expressed in the brain that cause the neurotoxic effects of the drug, much less is known about transcription factors involved in the development of methamphetamine-induced heart failure. In this article, we provide an overview of the Janus kinase-signal transducer and activator of transcription 3 (JAK-STAT3) pathway involved in ischemia/reperfusion injury in the myocardium, which may be activated by the vasospasm-inducing action of the drug. However, much more work is needed to decipher the precise role of STAT protein family members, including the potentially cardioprotective STAT3, in the pathogenesis of methamphetamine-induced cardiotoxicity., Competing Interests: Declarations. Conflict of interest: K. Annawald, K. Streckfuss-Bömeke and T. Meyer declare that they have no competing interests. For this article no studies with human participants or animals were performed by any of the authors. All studies mentioned were in accordance with the ethical standards indicated in each case., (© 2024. The Author(s).)

Nearly 1% of babies are born with congenital heart disease-many of whom will require heart surgery within the first few years of life. A detailed understanding of cardiac maturation can help to expand our knowledge on cardiac diseases that develop during gestation, identify age-appropriate drug therapies, and inform clinical care decisions related to surgical repair and postoperative management. Yet, to date, our knowledge of the temporal changes that cardiomyocytes undergo during postnatal development is limited. In this study, we collected right atrial tissue samples from pediatric patients ( n = 117) undergoing heart surgery. Patients were stratified into five age groups. We measured age-dependent adaptations in cardiac gene expression and used computational modeling to simulate action potential and calcium transients. Enrichment of differentially expressed genes revealed age-dependent changes in several key biological processes (e.g., cell cycle, structural organization), cardiac ion channels, and calcium handling genes. Gene-associated changes in ionic currents exhibited age-dependent trends, with changes in calcium handling ( I NCX ) and repolarization ( I K1 ) most strongly associated with an age-dependent decrease in the action potential plateau potential and increase in triangulation, respectively. We observed a shift in repolarization reserve, with lower I Kr expression in younger patients, a finding potentially tied to an increased amplitude of I Ks that could be triggered by elevated sympathetic activation in pediatric patients. Collectively, this study provides valuable insights into age-dependent changes in human cardiac gene expression and electrophysiology, shedding light on molecular mechanisms underlying cardiac maturation and function throughout development. NEW & NOTEWORTHY To date, our knowledge of the temporal changes that cardiomyocytes undergo during postnatal development is limited. In this study, we demonstrate age-dependent adaptations in the gene expression profile of >100 atrial tissue samples collected from congenital heart disease patients. We coupled transcriptomics datasets with computational modeling to simulate action potentials and calcium transients for different pediatric age groups.

Reentry, the most common cause of severe arrhythmias, is initiated by slow conduction and conduction block. Hence, evaluating conduction velocity and conduction block is of primary importance. However, the assessment of cardiac conduction safety in experimental and clinical settings remains elusive. To identify markers of conduction instability that can be determined experimentally, we developed an approach based on new pacing paradigms. Conduction across a cardiac tissue expansion was assessed in computer simulations and in experiments using cultures of neonatal murine cardiomyocytes on microelectrode arrays. Simulated and in vitro tissues were paced at a progressively increasing rate, with stochastic or alternating variations of cycle length, until conduction block occurred. Increasing pacing rate led to conduction block near the expansion. When stochastic or alternating variations were introduced into the pacing protocol, the standard deviation and the amplitude of alternating variations of local conduction times emerged as markers of unstable conduction prone to block. In both simulations and experiments, conduction delays were prolonged at the expansion but increased only slightly during the pacing protocol. In contrast, these markers of instability increased several-fold, early before block occurrence. The first and second moments of these two metrics provided an estimation of the site of block and the accuracy of this estimation. Therefore, when beat-to-beat variations of pacing cycle length are introduced into a pacing protocol, the local variability of conduction permits to predict sites of block. Our pacing paradigms may have translational applications in clinical cardiac electrophysiology, particularly in identifying ablation targets during mapping procedures., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Ltd.)

Background and Objective: It is an indisputable physiological phenomenon that the arterial axial pre-stretch ratio (AAPSR) decreases with age, but little attention has been paid to the effect of this reduction on chronic diseases during aging., Methods: Here we reported an experimental method to simulate arteries aging, developed a fluid-structure interaction model with the effect of AAPSR changes, and compared it with the anatomy data and structural parameters of the human thoracic aorta., Results: We showed that with the process of aging, the decrease of AAPSR leads to a decline of arterial elasticity, a decrease of arterial elastic strain energy, which weakens the ability to promote blood circulation, the corresponding decrease in cardiac output (CO) and cerebral blood flow (CBF) causes distal organ and body tissue ischemia, which is one of the main causes of increased blood pressure and decreased cerebral perfusion in the elderly., Conclusions: Thus, reduced AAPSR is the one of main manifestation of arteries aging and has an important impact on hypertension and hypoperfusion of the brain in the process of human aging. The research contributes to a better understanding of the physiological and pathological mechanisms of aging-related diseases., Competing Interests: Declaration of competing interest All the authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Doppler ultrasound is a commonly used method to assess hemodynamics of the fetal cardiovascular system and to monitor the well-being of the fetus. Indices based on the velocity profile are often used for diagnosis. However, precisely linking these indices to specific underlying physiology factors is challenging. Several influences, including wave reflections, fetal growth, vessel stiffness, and resistance distal to the vessel, contribute to these indices. Understanding these data is essential for making informed clinical decisions. Mathematical models can be used to investigate the relation between velocity profiles and physiological properties. This study presents a mathematical model designed to simulate velocity wave propagation throughout the fetal cardiovascular system, facilitating the assessment of factors influencing velocity-based indices. The model combines a one-fiber model of the heart with a 1D wave propagation model describing the larger vessels of the circulatory system and a lumped parameter model for the microcirculation. Fetal growth from 20 to 40 weeks of gestational age is incorporated by adjusting cardiac and circulatory parameter settings according to scaling laws. The model's results, including cardiac function, cardiac output distribution, and volume distribution, show a good agreement with literature studies for a growing healthy fetus from 20 to 40 weeks. In addition, Doppler indices are simulated in various vessels and agree with literature as well. In conclusion, this study introduces a novel closed-loop 0D-1D mathematical model that has been verified against literature studies. This model offers a valuable platform for analyzing factors influencing velocity-based indices in the fetal cardiovascular system., (© 2024 The Author(s). International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.)

Pulmonary valve dysfunction is common in congenital heart disease, often leading to interventions like right ventricular outflow tract reconstruction. Transcatheter pulmonary valve replacement (TPVR) has emerged as a successful alternative to surgery, showcasing promising outcomes for managing postoperative RVOT complications. The study aimed to compare two bioprosthetic valves-Carpentier Edwards Perimount Magna Ease surgical valve and Edwards SAPIEN 3 transcatheter valve-originally designed for aortic use but adapted for pulmonary applications. The hemodynamic characteristics of a 26-mm SAPIEN 3 and a 25-mm Magna Ease were assessed in a pulse duplicator under both pulmonary and aortic conditions. Furthermore, detailed structural analyses of the leaflets were conducted using computational simulations under these conditions. The results highlighted significant differences in the hydrodynamic and structural characteristics of these two bioprosthetic valves when exposed to pulmonary versus aortic conditions. The study enhances our understanding of the biomechanics involved in surgical and transcatheter pulmonary valve replacement., Competing Interests: Declarations. Human Subjects: No human studies were carried out by the authors for this article. Animal Studies: No animal studies were carried out by the authors for this article. Competing Interests: The authors have no conflict of interest to declare., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: The inverse problem of electrocardiography describes non-invasively the electrical activity of the heart using potential recordings from tens to hundreds of torso electrodes. Regrettably, the use of numerous electrodes poses a challenge to its integration into routine clinical practice., Methods: Optimal electrode placements, ranging from 8 to 112 electrodes, were derived from the singular values of the transfer matrices computed for all feasible positions of a single dipole cardiac source across 12 patients with unique geometrical characteristics from the Bratislava dataset. The transfer matrices were computed using the boundary element method. Subsequently, these optimal electrode placements were used to compute the inverse solution for localizing the origin of premature ventricular contraction (PVC) with a single dipole cardiac source. The localization error (LE) was computed as the Euclidean distance between the true PVC origin, obtained through an invasive radiofrequency ablation, and the inverse solution. This enabled a direct comparison of LE computed for each optimal electrode placement with that from the full 128-electrode set., Results: Results showed that subsets of electrodes, particularly 32 to 112, provided comparable localization accuracy (LE of 30.5 ± 15.0 mm and 26.8 ± 12.6 mm) to the full 128-electrode set (LE of 27.2 ± 11.5 mm). High errors were observed with 8 and 16-electrode placements (LE of 48.6 ± 21.3 mm and 41.0 ± 18.3 mm)., Conclusion: Precise PVC localization can be achieved using strategically positioned subsets of electrodes, offering advantages in reduced preparation time, enhanced patient comfort, and improved cost-effectiveness of body surface potential mapping., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Objective: Incorporating tissue support in fluid-structure interaction analysis of cardiovascular flows is crucial for accurately representing physiological constraints, achieving realistic vessel wall motion, and minimizing artificial oscillations. The generalized Robin boundary condition, which models tissue support with a spring-damper-type force, uses elastic and damping parameters to represent the viscoelastic behavior of perivascular tissues. Using spatially distributed parameters for tissue support, rather than uniform ones, is more realistic and aligns with the varying properties of vessel walls. However, considering the spatial distribution of both can increase the complexity of preprocessing and numerical implementation. In this work, we develop an effective property method for efficient modeling of non-uniform tissue support and quantifying the contribution of tissue support to the mechanical behaviors of vessel walls., Methods: Based on the theory of linear viscoelasticity, we derive the mathematical formulas for the effective property method, integrating the parameters of generalized Robin boundary condition into vessel wall properties. The pulse wave velocity incorporating the influence of tissue support is also analyzed. Furthermore, we modify the coupled momentum method, originally formulated for elastic problems, to account for the viscoelastic properties of the vessel wall., Results: The method is verified with three-dimensional fluid-structure interaction simulations, achieving a maximum relative error of less than 2.2% for flow rate and less than 0.7% for pressure. This method shows that tissue support parameters can be integrated into vessel wall properties, resulting in increased apparent wall stiffness and viscosity, and further changing pressure, flow rate, and wave propagation., Conclusion: In this study, we develop an effective property method for quantitatively assessing the impact of tissue support and for efficiently modeling non-uniform tissue support. Moreover, this method offers further insights into clinically measured pulse wave velocity, demonstrating that it reflects the combined influence of both vessel wall properties and tissue support., 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.)

Introduction: Various catheter designs are appearing for Pulsed Field Ablation (PFA). It is unclear if they differ in terms of safety and efficiency. PFA studies have reported hemolysis, kidney injury, high troponin, among other side effects., Methods: Using a CT-derived computer model, we compared catheter designs using two metrics: (1) efficiency: power delivered to an atrial wall target, expressed as a percent of total generator power; and (2) safety: electric current to achieve 90% transmurality (since more energy causes more collateral effects), as well as the corresponding electrode current density (ECD), a heat and bubble metric. The following catheter designs were compared: penta-spline basket, Nitinol spheres (focal 9 mm and large 1-shot), circular, balloon, and flex-circuit. Target was a 6 × 47 mm circumferential segment of atrial wall at LPV antrum. Transmurality was defined as percent of target having >600 volts per centimeter (V/cm) electric field needed for electroporation., Results: Efficiency was 0.9, 1.4, 2.7, 5.9, 10, and 12% for the large 1-shot and 9 mm Nitinol spheres, penta-spline, circular, flex spline, and balloon catheters, respectively. Regarding safety, currents for 90% transmurality were 70, 39,36,12.5, 5.3, and 4 Amps for the same respective catheters, with less being safer. ECD was 124, 25, 74, 83, 41, and 31 A/cm 2 , respectively., Conclusion: Computer models demonstrated a remarkable range in efficiency among catheters studied. Those having less atrial blood exposure had the highest efficiencies, with factors of up to 13X more efficiency compared to exposed ones. Higher efficiency designs have less collateral current and are safer. Confirmatory in-vivo studies are required., (© 2024 The Author(s). Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

Background and Objectives: The higher clinical significance of central aortic blood pressure (CABP) compared to peripheral blood pressures has been extensively demonstrated. Accordingly, many methods for noninvasively estimating CABP have been proposed. However, there still lacks a systematic comparison of existing methods, especially in terms of how they differ in the ability to tolerate individual differences or measurement errors. The present study was designed to address this gap., Methods: A large-scale 'virtual subject' dataset (n = 600) was created using a computational model of the cardiovascular system, and applied to examine several classical CABP estimation methods, including the direct method, generalized transfer function (GTF) method, n-point moving average (NPMA) method, second systolic pressure of periphery (SBP2) method, physical model-based wave analysis (MBWA) method, and suprasystolic cuff-based waveform reconstruction (SCWR) method. The errors of CABP estimation were analyzed and compared among methods with respect to the magnitude/distribution, correlations with physiological/hemodynamic factors, and sensitivities to noninvasive measurement errors., Results: The errors of CABP estimation exhibited evident inter-method differences in terms of the mean and standard deviation (SD). Relatively, the estimation errors of the methods adopting pre-trained algorithms (i.e., the GTF and SCWR methods) were overall smaller and less sensitive to variations in physiological/hemodynamic conditions and random errors in noninvasive measurement of brachial arterial blood pressure (used for calibrating peripheral pulse wave). The performances of all the methods worsened following the introduction of random errors to peripheral pulse wave (used for deriving CABP), as characterized by the enlarged SD and/or increased mean of the estimation errors. Notably, the GTF and SCWR methods did not exhibit a better capability of tolerating pulse wave errors in comparison with other methods., Conclusions: Classical noninvasive methods for estimating CABP were found to differ considerably in both the accuracy and error source, which provided theoretical evidence for understanding the specific advantages and disadvantages of each method. Knowledge about the method-specific error source and sensitivities of errors to different physiological/hemodynamic factors may contribute as theoretical references for interpreting clinical observations and exploring factors underlying large estimation errors, or provide guidance for optimizing existing methods or developing new methods., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Objective: This study aimed to investigate the impact of different stenotic degrees on platelet deposition in the left anterior descending branch of the coronary artery., Methods: The idealized model of coronary artery stenosis of 30 %, 40 %, 50 %, 60 %, 70 % and four patient-specific models of 22.17 %, 34.88 %, 51.23 % and 62.96 % were established. A discrete phase model was used to calculate the deposition of platelet particles in blood., Results: (1) As the stenotic degree increased from 30 % to 70 %, the maximum deposition rates were 4.23e - 2 kg/(m 2 ·s), 3.47e - 2 kg/(m 2 ·s), 0.14 kg/(m 2 ·s), 0.15 kg/(m 2 ·s), and 0.38 kg/(m 2 ·s), respectively. (2) The greater the stenotic degree, the more points of platelet deposition. (3) Platelets were mainly deposited at the proximal segment of mild stenosis. When the stenotic degree exceeded 50 %, the deposition position moved to the distal segment of the stenosis. (4) The results in the real coronary artery models were similar to those in the idealized model., Conclusion: The study suggests that the location and number of platelet deposition are related to the degree of stenosis. Moderate to severe stenosis is more likely to spread downstream., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Angioplasty with stent placement is a widely used treatment strategy for patients with stenotic blood vessels. However, it is often challenging to predict the outcomes of this procedure for individual patients. Image-based computational fluid dynamics (CFD) is a powerful technique for making these predictions. To perform CFD analysis of a stented vessel, a virtual model of the vessel must first be created. This model is typically made by manipulating two-dimensional contours of the vessel in its pre-stent state to reflect its post-stent shape. However, improper contour-editing can cause invalid geometric artifacts in the resulting mesh that then distort the subsequent CFD predictions. To address this limitation, we have developed a novel shape-editing method that deforms surface meshes of stenosed vessels to create stented models., Methods: Our method uses physics-based simulations via Extended Position Based Dynamics to guide these deformations. We embed an inflating stent inside a vessel and apply collision-generated forces to deform the vessel and expand its cross-section., Results: We demonstrate that this technique is feasible and applicable for a wide range of vascular anatomies, while yielding clinically compatible results. We also illustrate the ability to parametrically vary the stented shape and create models allowing CFD analyses., Conclusion: Our stenting method will help clinicians predict the hemodynamic results of stenting interventions and adapt treatments to achieve target outcomes for patients. It will also enable generation of synthetic data for data-intensive applications, such as machine learning, to support cardiovascular research endeavors., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflict of interest., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Background: Cardioembolic strokes are commonly occurred in non-valvular atrial fibrillation (AF) patients, with over 90% of cases originating from clot in left atrial appendage (LAA), which is believed to be greatly related with hemodynamic characters. Numerical simulation is widely accepted in the hemodynamic analysis, and patient-specific boundaries are required for realistic numerical simulations., Method: This paper firstly proposed a method that maps personalized pulmonary venous flow (PVF) by utilizing the volume changes of the left atrium (LA) over the cardiac cycle. Then we used data from patients with AF to investigate the correlation between PVF patterns and hemodynamics within the LAA. Meanwhile, we conducted a fluid-structure interaction analysis to assess the impact of velocity- and time-related PVF parameters on LAA hemodynamic characters., Results: The analysis reveal that the ratio of systolic to diastolic peak velocity (V S /V D ), and systolic velocity-time integral (VTI) showed a significant influence on LAA velocity in patients with atrial fibrillation, and the increases of velocity- and time-related parameters were found to be positively correlated with the blood update in the LAA., Conclusions: This study established a method for mapping patient-specific PVF based on LA volume change, and evaluated the relationship between PVF parameters and thrombosis risk. The present work provides an insight from PVF characters to evaluate the risk of thrombus formation within LAA in patients with AF., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled “Patient-specific pulmonary venous flow characterization and its impact on left atrial appendage thrombosis in patients with atrial fibrillation”., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The intricate lung structure is crucial for gas exchange within the alveolar region. Despite extensive research, questions remain about the connection between capillaries and the vascular tree. We propose a computational approach combining three-dimensional (3-D) morphological modeling with computational fluid dynamics simulations to explore alveolar capillary network connectivity based on blood flow dynamics. We developed three-dimensional sheet-flow models to accurately represent alveolar capillary morphology and conducted simulations to predict flow velocities and pressure distributions. Our approach leverages functional features to identify plausible system architectures. Given capillary flow velocities and arteriole-to-venule pressure drops, we deduced arteriole connectivity details. Preliminary analyses for nonhuman species indicate a single alveolus connects to at least two 20-µm arterioles or one 30-µm arteriole. Hence, our approach narrows down potential connectivity scenarios, but a unique solution may not always be expected. Integrating our blood flow model results into our previously published gas exchange application, Alvin, we linked these scenarios to gas exchange efficiency. We found that increased blood flow velocity correlates with higher gas exchange efficiency. Our study provides insights into pulmonary microvasculature structure by evaluating blood flow dynamics, offering a new strategy to explore the morphology-physiology relationship that is applicable to other tissues and organs. Future availability of experimental data will be crucial in validating and refining our computational models and hypotheses. NEW & NOTEWORTHY The alveolus is pivotal for gas exchange. Its complex, dynamic nature makes structural experimental studies challenging. Computational modeling offers an alternative. We developed a data-based three-dimensional (3-D) model of the alveolar capillary network and performed blood flow simulations within it. Choosing a novel perspective, we inferred structure from function. We systematically varied the properties of vessels connected to our capillary network and analyzed simulation results for blood flow and gas exchange to obtain plausible vessel configurations.

Due to the anatomical complexity of the aortic arch for the development of stent-grafts for total repair, this region remains without a validated and routinely used endovascular option. In this work, a modular stent-graft for aneurysms that covers all aortic arch zones, proposed by us and previously structurally evaluated, was evaluated from the point of view of haemodynamics using fluid-structural numerical simulations. Blood was assumed to be non-Newtonian shear-thinning using the Carreau model, and the arterial wall was assumed to be anisotropic hyperelastic using the Holzapfel model. Nitinol and expanded polytetrafluoroethylene (PTFE-e) were used as materials for the stents and the graft, respectively. Nitinol was modelled as a superelastic material with shape memory by the Auricchio model, and PTFE-e was modelled as an isotropic linear elastic material. To validate the numerical model, a silicone model representative of the aneurysmal aorta was subjected to tests on an experimental bench representative of the circulatory system. The numerical results showed that the stent-graft restored flow behaviour, making it less oscillatory, but increasing the strain rate, turbulence kinetic energy, and viscosity compared to the pathological case. Taking the mean of the entire cycle, the increase in turbulence kinetic energy was 198.82% in the brachiocephalic trunk, 144.63% in the left common carotid artery and 284.03% in the left subclavian artery after stent-graft implantation. Based on wall shear stress parameters, it was possible to identify that the internal branches of the stent-graft and the stent-graft fixation sites in the artery were the most favourable regions for the deposition and accumulation of thrombus. In these regions, the oscillating shear index reached the maximum value of 0.5 and the time-averaged wall shear stress was close to zero, which led the relative residence time to reach values above 15 Pa -1 . The stent-graft was able to preserve flow in the supra-aortic branches., Competing Interests: Declarations Conflict of interest The authors declare that they have no conflict of interest. Ethical approval Computed tomography (CT) reconstruction of a patient’s aorta was approved by the Comitê de Ética em Pesquisa da Universidade Federal de Minas Gerais (CEP-UFMG), Certificado de Apresentação de Apreciação Ética (CAAE) number 02405712.5.1001.5149, opinion number 4523374., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The hemodynamic performance of different prosthetic heart valves is difficult to compare among studies due to a variety of test conditions and experimental techniques. Existing studies are typically limited to one family of valves (biological or mechanical) and testing conditions of 5l/min and often lack sufficient spatial resolution. To address these limitations, a pulse duplicator with a multi-view imaging system (Tomo-PIV) was employed to investigate the three-dimensional flow field in the aortic root of three different valves: a tri-leaflet mechanical heart valve (TRIFLO, Novostia), a bi-leaflet mechanical heart valve (On-X, Artivion), and a biological heart valve (Perimount, Edwards Lifesciences). The valves were tested at low (3 l/min), normal (5 l/min), and elevated (7 l/min) cardiac output ( C O ) under hypotensive (40/60mmHg), normotensive (80/120mmHg), and moderate hypertensive (105/170mmHg) pressure conditions, respectively. Compared to the Perimount, peak mean velocity was - 33%, - 24%, - 18% for the TRIFLO and - 32%, - 20%, - 11% for the On-X at low, moderate, and elevated CO , respectively. Corresponding peak TKE values decreased by - 66%, - 57%, - 44% (TRIFLO) and - 60%, - 50%, - 36% (On-X). At low CO , EOA was lower for Perimount (1.07cm 2 ) than for TRIFLO (1.47cm 2 ) and On-X (1.52cm 2 ), while it increased for elevated CO to 2.75cm 2 (TRIFLO) and 2.16cm 2 (Perimount and On-X). For all valves, increasing CO led to increased flow velocities, higher E O A , and higher levels of turbulence, and the spatial influence of the valve on the flow field in the ascending aorta was extended. TKE peaked closer to the STJ than for TRIFLO and Perimount., Competing Interests: Declarations Competing interests The authors have received financial support and valve specimen from Novostia SA (Epalinges, Switzerland). DO has served on an advisory board for Novostia SA (Epanlinges, Switzerland)., (© 2024. The Author(s).)

Background: The improvement of controllers of left ventricular assist device (LVAD) technology supporting heart failure (HF) patients has enormous impact, given the high prevalence and mortality of HF in the population. The use of reinforcement learning for control applications in LVAD remains minimally explored. This work introduces a preload-based deep reinforcement learning control for LVAD based on the proximal policy optimization algorithm., Methods: The deep reinforcement learning control is built upon data derived from a deterministic high-fidelity cardiorespiratory simulator exposed to variations of total blood volume, heart rate, systemic vascular resistance, pulmonary vascular resistance, right ventricular end-systolic elastance, and left ventricular end-systolic elastance, to replicate realistic inter- and intra-patient variability of patients with a severe HF supported by LVAD. The deep reinforcement learning control obtained in this work is trained to avoid ventricular suction and allow aortic valve opening by using left ventricular pressure signals: end-diastolic pressure, maximum pressure in the left ventricle (LV), and maximum pressure in the aorta., Results: The results show controller obtained in this work, compared to the constant speed LVAD alternative, assures a more stable end-diastolic volume (EDV), with a standard deviation of 5 mL and 9 mL, respectively, and a higher degree of aortic flow, with an average flow of 1.1 L/min and 0.9 L/min, respectively., Conclusion: This work implements a deep reinforcement learning controller in a high-fidelity cardiorespiratory simulator, resulting in increases of flow through the aortic valve and increases of EDV stability, when compared to a constant speed LVAD strategy., (© 2024 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Purpose: The development of new endovascular technologies for transarterial embolization has relied on animal studies to validate efficacy before clinical trials are undertaken. Because embolizations in animals and patients are primarily conducted with fluoroscopy alone, local hemodynamic changes are not assessed during testing. However, such hemodynamic metrics could be important indicators of procedure efficacy that could support improved patient outcomes, such as via the determination of procedural endpoints. The purpose of this study is to create a high-fidelity benchtop system for multiparametric (i.e., hemodynamic and imaging) assessment of transarterial embolization procedures., Methods: The benchtop system consists of a 3D printed, anatomically accurate vascular phantom; a flow loop with a cardiac output simulator; a high-speed video camera; and pressure transducers and flow meters. This system enabled us to vary the heart rate and blood pressure and to simulate clinically relevant hemodynamic states, such as healthy adult, aortic regurgitation, and hypovolemic shock., Results: With our radiation-free angiography-mimetic imaging system, we could simultaneously assess gauge pressure and flow values during transarterial embolization. We demonstrated the feasibility of recapitulating the digital subtraction angiography workflow. Finally, we highlighted the utility of this system by characterizing the relationship between an imaging-based metric of procedural endpoint and intravascular flow. We also characterized hemodynamic changes associated with particle embolization within a branch of the hepatic artery and found them to be within reported patient data., Conclusion: Our benchtop vascular system was low-cost and reproduced transarterial embolization-related hemodynamic phenomena with high fidelity. We believe that this novel platform enables the characterization of patient physiology, novel catheterization devices, and techniques., Competing Interests: Declarations. Conflict of interest: CRW receives grant support from Medtronic, Guerbet, Siemens Healthcare, and Boston Scientific and consultancy fees from Medtronic, Guerbet, Boston Scientific, and Siemens Healthcare. APP is currently receiving grants (5R01CA237597-03 and 5R01DE027957-04) from the National Institutes of Health. The remaining authors declare no conflicts of interest., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Purpose: Neo-sinus flow stasis has ben correlated with transcatheter heart valve (THV) thrombosis severity and occurrence. Standard benchtop flow field quantification techniques require optical access or modified prosthesis models that may not reflect the true nature of the original valve. En face and fluoroscopic videodensitometry enable visualization of washout in regions otherwise unviewable., Methods: This study compares two in vitro methods of assessing flow stasis in scenarios with insufficient optical access for traditional techniques such as particle image velocimetry (PIV). A series of seven paired experiments were conducted using a previously described laser-enhanced video densitometry (LEVD) and fluoroscopic video densitometry (FVD). Both sets of experiments were analyzed to calculate washout time as a measure of flow stasis. A novel flow stasis measure termed contrast attenuation ratio (CAR) is proposed as a viable single measure of flow stasis obtainable from only a small number of cardiac cycles of in vitro or in vivo fluoroscopic data. Retrospective fluoroscopic datasets (n = 72) were analyzed to assess the feasibility of obtaining this metric from routine clinical practice and its ability to stratify results., Results: Neo-sinus flow stasis calculated from in vitro fluoroscopy was well correlated with LEVD (r 2  = 0.77, p = 0.009). The newly proposed CAR metric showed good agreement with the commonly used "washout time" measure of flow stasis (r 2  = 0.91, p < 0.001) while allowing for assessment with incomplete or truncated data. As a proof of concept, CAR was measured in 72 consecutive retrospective fluoroscopic datasets. CAR averaged 10.6 ± 4.6% with a range of 1.5-20.3% in these patients., Conclusions: This study demonstrates two in vitro methods that can be used to assess relative flow stasis in otherwise optically inaccessible regions surrounding cardiac or vascular implants. In addition, the fluoroscopic benchtop technique was used to validate a metric that allows for extension to routine clinical fluoroscopy. This contrast attenuation ratio (CAR) metric was found to be both accurate and clinically obtainable, and potentially offers a new method for valve thrombosis risk stratification., Competing Interests: Declarations. Competing interests: Vahid Sadri PhD Ajit Yoganathan, PhD is a consultant or researcher for Abbott, Boston Scientific, and Edwards Lifesciences. Vasilis Babaliaros, MD is a consultant or researcher for Edwards Lifesciences, Medtronic, and Abbott. Rahul Sharma, MD is a consultant or researcher for Edwards Lifesciences, Boston Scientific, Keystone Heart, and Abbott. Prem Midha, PhD, Vahid Sadri, PhD, and Phillip Trusty, PhD are now employees of Abbott Laboratories; however, this work was performed at Georgia Institute of Technology. The other authors have nothing to disclose., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)