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During the Ross procedure, an aortic heart valve is replaced by a patient's own pulmonary valve. The pulmonary autograft subsequently undergoes substantial growth and remodeling (G&R) due to its exposure to increased hemodynamic loads. In this study, we developed a homogenized constrained mixture model to understand the observed adaptation of the autograft leaflets in response to the changed hemodynamic environment. This model was based on the hypothesis that tissue G&R aims to preserve mechanical homeostasis for each tissue constituent. To model the Ross procedure, we simulated the exposure of a pulmonary valve to aortic pressure conditions and the subsequent G&R of the valve. Specifically, we investigated the effects of assuming either stress- or stretch-based mechanical homeostasis, the use of blood pressure control, and the effect of root dilation. With this model, we could explain different observations from published clinical studies, such as the increase in thickness, change in collagen organization, and change in tissue composition. In addition, we found that G&R based on stress-based homeostasis could better capture the observed changes in tissue composition than G&R based on stretch-based homeostasis, and that root dilation or blood pressure control can result in more leaflet elongation. Finally, our model demonstrated that successful adaptation can only occur when the mechanically induced tissue deposition is sufficiently larger than tissue degradation, such that leaflet thickening overrules leaflet dilation. In conclusion, our findings demonstrated that G&R based on mechanical homeostasis can capture the observed heart valve adaptation after the Ross procedure. Finally, this study presents a novel homogenized mixture model that can be used to investigate other cases of heart valve G&R as well., (© 2024. The Author(s).)

Background and Objective: Invasive fractional flow reserve (FFR) measurement is the gold standard method for coronary artery disease (CAD) diagnosis. FFR-CT exploits computational fluid dynamics (CFD) for non-invasive evaluation of FFR, simulating coronary flow in virtual geometries reconstructed from computed tomography (CT), but suffers from cost-intensive computing process and uncertainties in the definition of patient specific boundary conditions (BCs). In this work, we investigated the use of time-averaged steady BCs, compared to pulsatile to reduce the computational time and deployed a self-adjusting method for the tuning of BCs to patient-specific clinical data., Methods: 133 coronary arteries were reconstructed form CT images of patients suffering from CAD. For each vessel, invasive FFR was measured. After segmentation, the geometries were prepared for CFD simulation by clipping the outlets and discretizing into tetrahedral mesh. Steady BCs were defined in two steps: (i) rest BCs were extrapolated from clinical and image-derived data; (ii) hyperemic BCs were computed from resting conditions. Flow rate was iteratively adjusted during the simulation, until patient's aortic pressure was matched. Pulsatile BCs were defined exploiting the convergence values of steady BCs. After CFD simulation, lesion-specific hemodynamic indexes were computed and compared between group of patients for which surgery was indicated and not. The whole pipeline was implemented as a straightforward process, in which each single step is performed automatically., Results: Steady and pulsatile FFR-CT yielded a strong correlation (r = 0.988, p < 0.001) and correlated with invasive FFR (r = 0.797, p < 0.001). The per-point difference between the pressure and FFR-CT field predicted by the two methods was below 1 % and 2 %, respectively. Both approaches exhibited a good diagnostic performance: accuracy was 0.860 and 0.864, the AUC was 0.923 and 0.912, for steady and pulsatile case, respectively. The computational time required by steady BCs CFD was approximatively 30-folds lower than pulsatile case., Conclusions: This work shows the feasibility of using steady BCs CFD for computing the FFR-CT in coronary arteries, as well as its computational and diagnostic performance within a fully automated pipeline., Competing Interests: Declaration of competing interest All authors disclose that they have no conflict of interest, no financial arrangement with products figuring in the submitted manuscript or with a company making a competing product. All those who fulfil the criteria for authorship have been included as authors and each author contributed significantly to the submitted work., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Abstract: Atrial fibrillation (AF) poses a significant therapeutic challenge with drug interventions showing only limited success. Phosphodiesterases (PDE) regulate cardiac electrical stability and may represent an interesting target. Recently, PDE8 inhibition was proposed as an antiarrhythmic intervention by increasing L-type Ca 2+ current (I Ca,L ) and action potential duration (APD). However, the effect size of PDE8 inhibition on I Ca,L and APD seems discrepant and effects on force are unknown. We investigated the impact of PDE8 inhibition on force using PF-04957325 in right atrial appendages, obtained from patients in sinus rhythm (SR) and with persistent AF (peAF) undergoing cardiac surgery. A computational model was used to predict the effects of PDE8 inhibition on APD in SR and peAF. Results showed no increase in force after exposure to increasing concentrations of the PDE8 inhibitor PF-04957325 in either SR or peAF tissues. Furthermore, PDE8 inhibition did not affect the potency or efficacy of norepinephrine-induced inotropic effects in either group. Arrhythmic events triggered by norepinephrine were observed in both SR and peAF, but their frequency remained unaffected by PF-04957325 treatment. Computational modeling predicted that the reported increase in I Ca,L induced by PDE8 inhibition would lead to substantial APD prolongation at all repolarization states, particularly in peAF. Our findings indicate that PDE8 inhibition does not significantly impact force or arrhythmogenicity in human atrial tissue., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The Windkessel (WK) model is a simplified mathematical model used to represent the systemic arterial circulation. While the WK model is useful for studying blood flow dynamics, it suffers from inaccuracies or uncertainties that should be considered when using it to make physiological predictions. This paper aims to develop an efficient and easy-to-implement uncertainty quantification method based on a local gradient-based formulation to quantify the uncertainty of the pressure waveform resulting from aleatory uncertainties of the WK parameters and flow waveform. The proposed methodology, tested against Monte Carlo simulations, demonstrates good agreement in estimating blood pressure uncertainties due to uncertain Windkessel parameters, but less agreement considering uncertain blood-flow waveforms. To illustrate our methodology's applicability, we assessed the aortic pressure uncertainty generated by Windkessel parameters-sets from an available in silico database representing healthy adults. The results from the proposed formulation align qualitatively with those in the database and in vivo data. Furthermore, we investigated how changes in the uncertainty of the Windkessel parameters affect the uncertainty of systolic, diastolic, and pulse pressures. We found that peripheral resistance uncertainty produces the most significant change in the systolic and diastolic blood pressure uncertainties. On the other hand, compliance uncertainty considerably modifies the pulse pressure standard deviation. The presented expansion-based method is a tool for efficiently propagating the Windkessel parameters' uncertainty to the pressure waveform. The Windkessel model's clinical use depends on the reliability of the pressure in the presence of input uncertainties, which can be efficiently investigated with the proposed methodology. For instance, in wearable technology that uses sensor data and the Windkessel model to estimate systolic and diastolic blood pressures, it is important to check the confidence level in these calculations to ensure that the pressures accurately reflect the patient's cardiovascular condition., (© 2024 The Author(s). International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.)

Fibrosis, a pathological increase in extracellular matrix proteins, is a significant health issue that hinders the function of many organs in the body, in some cases fatally. In the heart, fibrosis impacts on electrical propagation in a complex and poorly predictable fashion, potentially serving as a substrate for dangerous arrhythmias. Individual risk depends on the spatial manifestation of fibrotic tissue, and learning the spatial arrangement on the fine scale in order to predict these impacts still relies upon invasive ex vivo procedures. As a result, the effects of spatial variability on the symptomatic impact of cardiac fibrosis remain poorly understood. In this work, we address the issue of availability of such imaging data via a computational methodology for generating new realisations of cardiac fibrosis microstructure. Using the Perlin noise technique from computer graphics, together with an automated calibration process that requires only a single training image, we demonstrate successful capture of collagen texturing in four types of fibrosis microstructure observed in histological sections. We then use this generator to quantitatively analyse the conductive properties of these different types of cardiac fibrosis, as well as produce three-dimensional realisations of histologically-observed patterning. Owing to the generator's flexibility and automated calibration process, we also anticipate that it might be useful in producing additional realisations of other physiological structures., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Blanca Rodriguez reports financial support was provided by Wellcome Trust. Blanca Rodriguez, Alfonso Bueno-Orovio reports financial support was provided by National Centre for the Replacement Refinement and Reduction of Animals in Research. Alfonso Bueno-Orovio reports financial support was provided by British Heart Foundation. Rodrigo Weber dos Santos reports financial support was provided by Minas Gerais State Foundation of Support to the Research., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

A left ventricular assist device (LVAD) supports hemodynamics in heart failure patients. To deepen the understanding of hemodynamic changes and the movement of thrombi in the aorta, we examined three distinct LVAD blood flow rates across two implantation sites using the theory of computational fluid dynamics. Our findings revealed the complex dynamics of blood flow during cardiac systole under various scenarios. We also analyzed thrombi residence time and flow probabilities into aortic branches. Simulation results indicate that thrombi distribution in the aorta is significantly influenced by the location of the LVAD outflow graft and the flow rate. When the LVAD outflow graft is implanted into the ascending aorta, higher flow rates may reduce the risk of cerebral thrombosis. However, lower flow rates may reduce the risk of cerebral thrombosis while it is implanted into the descending aorta. The study may offer valuable insights into the LVAD implantation about the risk of cerebrovascular embolism., Competing Interests: Declarations. Ethics Approval and Consent to Participate: The basic images were obtained from a patient who provided informed consent for using the images, and the study was approved by the Ethics Committee of Central South University (approval number: 202308180). All procedures involving human participants were performed in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Consent for Publication: Not applicable. Conflict of Interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Purpose: Valve-sparing root replacement (VSRR) is attractive for aortic root dilation as it preserves the native aortic valve (AoV). Low effective height (eH) after reconstruction is a risk factor for repair failure and reoperation. We developed and validated a quantitative AoV repair strategy to reliably restore normal valve proportions to promote long-term function., Methods: Normal AoV proportions were used to derive geometric relationships for sinotubular junction diameter (D STJ ), free edge length (FEL), free edge angle, and commissure height. These relationships informed two models for predicting eH following VSRR: (1) assuming valve symmetry and (2) accounting for valve asymmetry. Porcine heart (n = 6) ex vivo validation was performed under 4 VSRR scenarios: "Ideal" (tube graft size targeting FEL/D STJ  = 1.28), "Oversized" (one graft size larger than Ideal), "Undersized" (two sizes smaller), and "Undersized + Plicated" (FEL/D STJ  = 1.28 restored with leaflet plication)., Results: Our analytical models predicted eH using preoperative measurements and estimated reconstructed dimensions. The Oversized graft exhibited similar eH to Ideal but higher regurgitation in the ex vivo model, whereas the Undersized graft demonstrated lower eH and regurgitation. Plication in the Undersized graft restored valve function (regurgitation & eH) similar to Ideal in the ex vivo model and above Ideal in the analytical models. Both analytical models predicted ex vivo eH well except in the Oversized and Undersized + Plicated conditions., Conclusion: Utilizing measurements from preoperative imaging and simple mathematical models, patient-specific operative plans for VSRR can be created by estimating valve dimensions necessary to achieve favorable valve features post-repair. Clinical application of this approach promises to improve consistency in achieving optimal long-term dimensions and durability., Competing Interests: Declarations Competing Interests The authors have no relevant financial or non-financial interests to disclose. IRB Approval In vitro studies were performed with exemption by Boston Children’s Hospital IRB. Informed Consent Not applicable., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Purpose: To introduce a computational tool for peri-interventional intracranial aneurysm treatment guidance that maps preoperative planning information from simulation onto real-time X-Ray imaging., Methods: Preoperatively, multiple flow diverter (FD) devices are simulated based on the 3D mesh of the vessel to treat, to choose the optimal size and location. In the peri-operative stage, this 3D information is aligned and mapped to the continuous 2D-X-Ray scan feed from the operating room. The current flow diverter position in the 3D model is estimated by automatically detecting the distal FD marker locations and mapping them to the treated vessel. This allows to visually assess the possible outcome of releasing the device at the current position, and compare it with the one chosen pre-operatively., Results: The full pipeline was validated using retrospectively collected biplane images from four different patients (5 3D-DSA datasets in total). The distal FD marker detector obtained an average F1-score of 0.67 ( ± 0.224 ) in 412 2D-X-Ray scans. After aligning 3D-DSA + 2D-X-Ray datasets, the average difference between simulated and deployed positions was 0.832 mm ( ± 0.521 mm). Finally, we qualitatively show that the proposed approach is able to display the current location of the FD compared to their pre-operatively planned position., Conclusions: The proposed method allows to support the FD deployment procedure by merging and presenting preoperative simulation information to the interventionists, aiding them to make more accurate and less risky decisions., Competing Interests: Declaration. Conflict of interest: HF and LO are employees of Mentice S.L. IL is consultant for Mentice S.L. AD and RU are employees of Acandis. Ethical Approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed Consent: Informed consent was obtained from all individual participants included in the study., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)

OBJECTIVE : The treatment of mitral valve prolapse involves two distinct repair techniques: chordal replacement (Neochordae technique) and leaflet resection (Resection technique). However, there is still a debate in the literature about which is the optimal one. In this context, we performed an image-based computational fluid dynamic study to evaluate blood dynamics in the two surgical techniques. METHODS : We considered a healthy subject (H) and two patients (N and R) who underwent surgery for prolapse of the posterior leaflet and were operated with the Neochordae and Resection technique, respectively. Computational Fluid Dynamics (CFD) was employed with prescribed motion of the entire left heart coming from cine-MRI images, with a Large Eddy Simulation model to describe the transition to turbulence and a resistive method for managing valve dynamics. We created three different virtual scenarios where the operated mitral valves were inserted in the same left heart geometry of the healthy subject to study the differences attributed only to the two techniques. RESULTS : We compared the three scenarios by quantitatively analyzing ventricular velocity patterns and pressures, transition to turbulence, and the ventricle ability to prevent thrombi formation. From these results, we found that the operative techniques affected the ventricular blood dynamics in different ways, with variations attributed to the reduced mobility of the Resection posterior leaflet. Specifically, the Resection technique resulted in turbulent forces, related with the risk of hemolysis formation, up to 640 Pa, while the other two scenarios exhibited a maximum of 240 Pa. Moreover, in correspondence of the ventricular apex, the Resection technique reduced the areas with low velocity to 15%, whereas the healthy case and the Neochordae case maintained these areas at 30 and 48%, respectively. Our findings suggest that the Neochordae technique developed a more physiological flow with respect to the Resection technique. CONCLUSION: Resection technique gives rise to a different direction of the mitral jet during diastole increasing the ability to washout the ventricular apex preventing from thrombi formation, but at the same time it promotes turbulence formation that is associated with ventricular effort and risk of hemolysis., Competing Interests: Declarations Conflict of interest No conflict of interest, financial, or otherwise are declared by the authors. Ethical Approval Ethical review board approval and informed consent were obtained from all patients., (© 2024. The Author(s).)

Percutaneous ventricular assist devices (pVADs) incorporated with admittance electrodes have been validated in animal studies for accurate instantaneous volumetric measurements. Since miniaturization of the pVAD profile is a priority to reduce vascular complications in patients, our study aimed to validate admittance measurements using three electrodes instead of the standard four. Complex admittance was measured between an electrode pair and a pVAD metallic blood-intake tip, both with finite element analysis and on the benchtop. The catheter and electrode arrays were first simulated inside prolate ellipsoid models of the left ventricle (LV) demonstrating current flow throughout all parts of the LV as well as minimal influence of off-center catheter placement in the recorded signal. Admittance measurements were validated in 3D-printed models of healthy and dilated hearts (100-400 mL end-diastolic volumes). Minimal interference between a pVAD motor and the current signal of our admittance system was demonstrated. A modified Wei's equation focused on three electrodes was developed to be compatible with reduced profile pVADs occurring clinically, incorporated with admittance electrodes and wires. The modified equation was compared against Wei's original equation showing improved accuracy of calculated volumes. Reducing electrode footprint can simplify the incorporation of Admittance technology on any pVAD, allowing for instantaneous recognition of native heart recovery and assistance with pVAD weaning., Competing Interests: Declarations Competing interests LADS, ABG, and DN declare no conflicting financial interests. MDF has received funding for research grants from Abiomed and CardioVol Corp. JWV discloses a financial relationship with CardioVol Corp., (© 2024. International Federation for Medical and Biological Engineering.)

Pulmonary valves do not display a fibrous annulus as do other valves in the heart; thus, pulmonary valves can be implanted at multiple orientations and locations within the right ventricular outflow tract (RVOT). This gives surgeons more freedom when implanting the valve but it also results in uncertainties regarding placement, particularly with respect to valve orientation. We investigate the pulmonary artery hemodynamics and valve leaflet dynamics of pulmonary valve replacements (PVRs) with various orientations via fluid-structure interaction (FSI) models. A canonical model of the branching pulmonary artery is coupled with a dynamic model of a pulmonary valve, and from this we quantify the effect of valve implant orientation on the postvalvular hemodynamics and leaflet dynamics. Metrics such as turbulent kinetic energy (TKE), branch pulmonary artery flow distributions, projected valve opening area (PVOA), and pressure differentials across the valve leaflets are analyzed. Our results indicate that off-axis orientation results in higher pressure forces and flow and energy asymmetry, which potentially have implications for long-term durability of implanted bioprosthetic valves., (Copyright © 2024 by ASME.)

Heart failure with preserved ejection fraction (HFpEF) constitutes approximately 50% of heart failure (HF) cases, and encompasses different phenotypes. Among these, most patients with HFpEF exhibit structural heart changes, often with smaller left ventricular cavities, which pose challenges for utilizing ventricular assist devices (VADs). A left atrial to aortic (LA-Ao) VAD configuration could address these challenges, potentially enhancing patient quality of life by lowering elevated mean left atrial pressure (MLAP). This study assessed the anatomical compatibility and left atrial unloading capacity using a simulated VAD-supported HFpEF patient. A HeartMate3-supported HFpEF patient in an LA-Ao configuration was simulated using a cardiovascular simulator. Hemodynamic parameters were recorded during rest and exercise at seven pump flow rates. Computed tomography scans of 14 HFpEF (NYHA II-III) and six heart failure with reduced ejection fraction patients were analysed for anatomical comparisons. HFpEF models were independently assessed for virtual anatomical fit with the HM3 in the LA-Ao configuration. Baseline MLAP was reduced from 15 to 11 mmHg with the addition of 1 L/min HM3 support in the rest condition. In an exercise simulation, 6 L/min of HM3 support was required to reduce the MLAP from 29 to 16 mmHg. The HM3 successfully accommodated six HFpEF patients without causing interference with other cardiac structures, whereas it caused impingement ranging from 4 to 14 mm in the remaining patients. This study demonstrated that the HM3 in an LA-Ao configuration may be suitable for unloading the left atrium and relieving pulmonary congestion in some HFpEF patients where size-related limitations can be addressed through pre-surgical anatomical fit analysis., Competing Interests: Declarations Conflict of interest The authors have no relevant financial or non-financial interests to disclose., (© 2024. The Author(s).)

Purpose: CoRISMA MCS Systems Inc (Hamden CT) is developing an innovative mechanical circulatory support system (CMCS) as a durable therapeutic option for heart failure (HF) patients. The CMCS system is comprised of an axial flow pump, non-contacting hydrodynamic bearings, and integrated DC motor designed to be fully implantable in a left atrial (LA) to aortic (Ao) configuration; this unloading strategy may be particularly beneficial for HF patients with preserved ejection fraction (HFpEF). The small (5.5 cm 3 ), lightweight (20 g), and low power (5-7 W) device design should allow for a less invasive off-pump implant. We present early-stage engineering development and testing of the prototype CoRISMA pumps., Methods: Computational fluid dynamics (CFD) modeling was performed to evaluate flow and shear in two impeller (3 blades, 0.5 mm thickness, 8.9 mm diameter, 0.15 mm gap, polished titanium) and diffusor (5 blades, polished titanium) candidate designs. Test apparatuses were custom built to expedite development of the impeller/diffuser designs and iteratively refine the CFD models. Two candidate impeller/diffusor designs were fabricated and tested in each of the two test apparatuses (n = 4 impeller/diffuser + test fixture configurations) in static mock flow loops (hydrodynamic H-Q curves, 3.5 cP glycerol solution at 37 °C), and in dynamic mock flow loops (hemodynamics, 3.5 cP glycerol solution at 37 °C) tuned to HF conditions (mean aortic pressure 50 mmHg, central venous pressure 15 mmHg, aortic flow 3.0 L/min, and heart rate 80 bpm)., Results: CFD predicted flows of 4.56 L/min and 4.82 L/min at 100 mmHg for impellers/diffusers 1 and 2, respectively. Impeller 2 required less torque to generate a 6% increase in fluidic flow, and the diffuser had a larger area of high pressure, indicative of lower friction, which likely contributed to the increased efficiency. Experimental testing for all four configurations in the static and dynamic mock loops met performance metrics as evidenced by generating 4.0-4.5 L/min flow against 70-76 mmHg pressure at 25,000 rpm and restoring hemodynamics in the dynamic mock flow loop (MAP = 80 mmHg, CVP = 0 mmHg, total flow = 5.5 L/min) from baseline simulated HF test conditions., Conclusion: These results demonstrate proof-of-concept of the early engineering design and performance of the prototype CoRISMA pumps. Engineering specifications, challenges observed, and proposed solutions for the next design iteration were identified for the continued development of an effective, reliable, and safe LA-to-Ao CMCS system for HF patients. Current design plans are underway for incorporating a wireless energy transfer system for communication and power, eliminating the need for and complications associated with an external driveline, to achieve a fully-implantable system., Competing Interests: Declarations. Competing Interests: James Kelley, Daniel Tamez, Daisy Cross, Mark Kelley, Varun Yetukuri, Michael Theran, Jessica Illg are employees of CoRISMA MCS Systems Inc. Daniel Tamez is a former employee of Artio Medical Inc. Gretel Monreal, Steven Koenig, and Mark Slaughter are investigators on a subcontract with CoRISMA MCS Systems Inc. Gretel Monreal, Steven Koenig, Daniel Tamez and Mark Slaughter are investigators on a NIH grant (R44HL144214) with Inspired Therapeutics unrelated to this project. Gretel Monreal, Steven Koenig, and Mark Slaughter were investigators on now-completed NIH grants all unrelated to this project: R43HL152767 (Bionet Sonar), R43HL149451 (Bionet Sonar), R43HL142385 (MAST), R43HL152894 (MAST), R43HL142337 (Cor Habere), R43HL152774 (RT Cardiac Systems), R43HLI44214 (Inspired Therapeutics). Gretel Monreal and Steven Koenig were investigators on a now-completed NSF EPSCoR grant unrelated to this project. Gretel Monreal and Steven Koenig are investigators on a Kentucky Academy of Science Athey Science Education and Outreach Grant unrelated to this project. Steven Koenig is an investigator on a NIH grant (R01HL150346) unrelated to this project. Steven Koenig was an investigator on a now-completed NIH grant (R43NS115226, Bionet Sonar), unrelated to this project. James Kelley is a principle at EVO3 Medical. Mark Slaughter is a consultant with CoRISMA MCS Systems Inc and Magenta Medical and is on the advisory board of Medtronic. Mark Slaughter is the Editor-in-Chief of ASAIO Journal. Gretel Monreal is supported in part by a gift from Robert M. Prizant to the Legacy Foundation of Kentuckiana. Citation Diversity Statement: The authors support diversity and agree that increasing diversity awareness is important. The authors decline to provide a citation diversity statement, as we are unable/unwilling to attempt to classify people by gender, race, ethnicity, or other features based on their name., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)

In this study, we present a computational framework designed to evaluate virtual scenarios of cardiac resynchronization therapy (CRT) and compare their effectiveness based on relevant clinical biomarkers. Our approach involves electro-mechanical numerical simulations personalized, for patients with left bundle branch block, by means of a calibration obtained using data from Electro-Anatomical Mapping System (EAMS) measures acquired by cardiologists during the CRT procedure, as well as ventricular pressures and volumes, both obtained pre-implantation. We validate the calibration by using EAMS data coming from right pacing conditions. Three patients with fibrosis and three without are considered to explore various conditions. Our virtual scenarios consist of personalized numerical experiments, incorporating different positions of the left electrode along reconstructed epicardial veins; different locations of the right electrode; different ventriculo-ventricular delays. The aim is to offer a comprehensive tool capable of optimizing CRT efficiency for individual patients. We provide preliminary answers on optimal electrode placement and delay, by computing some relevant biomarkers such as d P / d t max , ejection fraction, stroke work. From our numerical experiments, we found that the latest activated segment during sinus rhythm is an effective choice for the non-fibrotic cases for the location of the left electrode. Also, our results showed that the activation of the right electrode before the left one seems to improve the CRT performance for the non-fibrotic cases. Last, we found that the CRT performance seems to improve by positioning the right electrode halfway between the base and the apex. This work is on the line of computational works for the study of CRT and introduces new features in the field, such as the presence of the epicardial veins and the movement of the right electrode. All these studies from the different research groups can in future synergistically flow together in the development of a tool which clinicians could use during the procedure to have quantitative information about the patient's propagation in different scenarios., Competing Interests: Declarations Conflict of interest The authors declare to have no conflict of interest. Ethical approval and consent to participate Ethical review board approval and informed consent were obtained from all patients., (© 2024. The Author(s).)

Acute myocardial infarction (MI) leads to a loss of cardiac function which, following adverse ventricular remodeling (AVR), can ultimately result in heart failure. Tissue-engineered contractile patches placed over the infarct offer potential for restoring cardiac function and reducing AVR. In this computational study, we investigate how improvement of pump function depends on the orientation of the cardiac patch and the fibers therein relative to the left ventricle (LV). Additionally, we examine how model outcome depends on the choice of material properties for healthy and infarct tissue. In a finite element model of LV mechanics, an infarction was induced by eliminating active stress generation and increasing passive tissue stiffness in a region comprising 15% of the LV wall volume. The cardiac patch was modeled as a rectangular piece of healthy myocardium with a volume of 25% of the infarcted tissue. The orientation of the patch was varied from 0 to 150 ∘ relative to the circumferential plane. The infarct reduced stroke work by 34% compared to the healthy heart. Optimal patch support was achieved when the patch was oriented parallel to the subepicardial fiber direction, restoring 9% of lost functionality. Typically, about one-third of the total recovery was attributed to the patch, while the remainder resulted from restored functionality in native myocardium adjacent to the infarct. The patch contributes to cardiac function through two mechanisms. A contribution of tissue in the patch and an increased contribution of native tissue, due to favorable changes in mechanical boundary conditions., Competing Interests: Declarations Conflict of interest The authors declare no Conflict of interest, (© 2024. The Author(s).)

An aneurysm is a disease condition, which is due to the pathological weakening of an arterial wall. These aneurysms are often found in various branch points and bifurcations of an artery in the cerebral circulation. Most aneurysms come to medical attention, either due to brain hemorrhages caused by rupture or found unruptured. To consider surgically invasive treatment modalities, clinicians need scientific methods such as, hemodynamic analysis to assess rupture risk. The arterial wall loses its structural integrity when wall shear stress (WSS) and other hemodynamic parameters exceed a certain threshold. In the present study, numerical simulations are carried out for unruptured middle cerebral artery (MCA) aneurysms. Three distinct representative sizes are chosen from a larger patient pool of 26 MCA aneurysms. Logically, these aneurysms represent three growth stages of any patient with similar anatomical structure. Simulations are performed to compare the three growth phases (with different aspect ratios) of an aneurysm and correlate their hemodynamic parameters. Simulations with patient specific boundary conditions reveal that, aneurysms with a higher aspect ratio (AR) correspond to an attendant decrease in both time-averaged wall shear stress (TAWSS) and spatial wall shear stress gradients (WSSG). Smaller MCAs were observed to have higher positive wall shear stress divergence (WSSD), exemplifying the tensile nature of arterial wall stretching. Present study identifies positive wall shear stress divergence (PWSSD) to be a potential biomarker for evaluating the growth of an aneurysm.

The mortality rates due to cardiovascular diseases are on a rise globally. One of the major cardiovascular diseases is stroke which occurs due to atherosclerotic plaques build-up in the carotid artery. The common carotid artery (CCA) bifurcates into the internal carotid artery (ICA) and external carotid artery (ECA). Sinus present at ICA is an ellipsoidal-shaped dilated region acting as a pressure receptor and blood flow regulator. Dimensions of the sinus vary from person to person, affecting the hemodynamics of the carotid artery. The current numerical study manifests a 3D flow analysis by varying the sinus length to investigate its local and global effects on the hemodynamics of the carotid artery using various biomechanical risk analysis parameters of atherosclerosis. User-defined function (UDF) dictates the pulsatile flow velocity profile imposed at the inlet. Near the outer wall (OW) of the sinus, the blood flow velocities are lower and recirculation zones are more. Though the recirculation zones for shorter sinus will be close to the inner wall (IW), interestingly, with an increase in the sinus length, the recirculation zones shift toward the OW with higher strength. These significantly decrease the x-wall shear stress (x-WSS) and time-averaged wall shear stress (TAWSS) values on the OW of the longer sinus. The other risk analysis parameters, like oscillatory shear index (OSI) and relative residence time (RRT), support the described consequences. These results reveal that sinus of increased length is more prone to developing atherosclerotic plaque.

Accurate modeling of blood dynamics in the coronary microcirculation is a crucial step toward the clinical application of in silico methods for the diagnosis of coronary artery disease. In this work, we present a new mathematical model of microcirculatory hemodynamics accounting for microvasculature compliance and cardiac contraction; we also present its application to a full simulation of hyperemic coronary blood flow and 3D myocardial perfusion in real clinical cases. Microvasculature hemodynamics is modeled with a compliant multi-compartment Darcy formulation, with the new compliance terms depending on the local intramyocardial pressure generated by cardiac contraction. Nonlinear analytical relationships for vessels distensibility are included based on experimental data, and all the parameters of the model are reformulated based on histologically relevant quantities, allowing a deeper model personalization. Phasic flow patterns of high arterial inflow in diastole and venous outflow in systole are obtained, with flow waveforms morphology and pressure distribution along the microcirculation reproduced in accordance with experimental and in vivo measures. Phasic diameter change for arterioles and capillaries is also obtained with relevant differences depending on the depth location. Coronary blood dynamics exhibits a disturbed flow at the systolic onset, while the obtained 3D perfusion maps reproduce the systolic impediment effect and show relevant regional and transmural heterogeneities in myocardial blood flow (MBF). The proposed model successfully reproduces microvasculature hemodynamics over the whole heartbeat and along the entire intramural vessels. Quantification of phasic flow patterns, diameter changes, regional and transmural heterogeneities in MBF represent key steps ahead in the direction of the predictive simulation of cardiac perfusion., (© 2024. The Author(s).)

Aortic dissection is a life-threatening disease that consists in the development of a tear in the wall of the aorta. The initial tear propagates as a discontinuity leading to separation within the aortic wall, which can result in the creation of a so-called false lumen. A fatal threat occurs if the rupture extends through the whole thickness of the aortic wall, as blood may then leak. It is generally accepted that the dissection, which can sometime extend along the entire length of the aorta, propagates via a delamination mechanism. The aim of the present paper is to provide experimentally validated parameters of a mathematical model for the description of the wall's cohesion. A model of the peeling experiment was built in Abaqus. The delamination interface was described by a piecewise linear traction-separation law. The bulk behavior of the aorta was assumed to be nonlinearly elastic, anisotropic, and incompressible. Our simulations resulted in estimates of the material parameters for the traction-separation law of the human descending thoracic aorta, which were obtained by minimizing the differences between the FEM predictions and the delamination force given by the regression of the peeling experiments. The results show that the stress at damage initiation, T c , should be understood as an age-dependent quantity, and under the assumptions of our model this dependence can be expressed by linear regression as Tc =  - 13.03·10 -4 ·Age + 0.2485 if the crack front advances in the axial direction, and Tc =  - 7.58·10 -4 ·Age + 0.1897 if the crack front advances in the direction of the aortic circumference (T c [MPa], Age [years]). Other model parameters were the stiffness K and the separation at failure, δ f -δ c (K = 0.5 MPa/mm, δ f -δ c  = 0.1 mm). The material parameters provided by our study can be used in numerical simulations of the biomechanics of dissection propagation through the aorta especially when age-associated phenomena are studied., Competing Interests: Declarations Conflict of interest There are no competing interests., (© 2024. The Author(s).)

This study aimed to develop a force analysis model correlating fluoroscopic images of self-expandable valves with stress distribution. For this purpose, a nonmetallic measuring device designed to apply diverse forces at specific positions on a valve stent while simultaneously measuring force magnitude was manufactured, obtaining 465 sets of fluorescent films under different force conditions, resulting in 5580 images and their corresponding force tables. Using the XrayGLM, a mechanical analysis model based on valve fluorescence images was trained. The accuracy of the image force analysis using this model was approximately 70% (50-88.3%), with a relative accuracy of 93.3% (75-100%). This confirms that fluoroscopic images of transcatheter aortic valve replacement (TAVR) valve stents contain a wealth of mechanical information, and machine learning can be used to train models to recognize the relationship between stent images and force distribution, enhancing the understanding of TAVR complications., Competing Interests: Declarations. Ethics Approval: Not applicable. Consent to Participate: Not applicable. Conflict of Interest: The authors declare that they have no conflict of interest., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Right ventricular assist devices (RVADs) have been extensively used to provide hemodynamic support for patients with end-stage right heart (RV) failure. However, conventional in-parallel RVADs can lead to an elevation of pulmonary artery (PA) pressure, consequently increasing the right ventricular (RV) afterload, which is unfavorable for the relaxation of cardiac muscles and reduction of valve complications. The aim of this study is to investigate the hemodynamic effects of the pulsatile frequency of the RVAD on pulmonary artery. Firstly, a mathematical model incorporating heart, systemic circulation, pulmonary circulation, and RVAD is developed to simulate the cardiovascular system. Subsequently, the frequency characteristics of the pulmonary circulation system are analyzed, and the calculated results demonstrate that the pulsatile frequency of the RVAD has a substantive impact on the pulmonary artery pressure. Finally, to verify the analysis results, the hemodynamic effects of the pulsatile frequency of the RVAD on pulmonary artery are compared under diffident support modes. It is found that the pulmonary artery pressure decreases by approximately 6% when the pulsatile frequency changes from 1 to 3 Hz. The increased pulsatile frequency of RA-PA support mode may facilitate the opening of the pulmonary valve, while the RV-PA support mode can more effectively reduce the load of RV. This work provides a useful method to decrease the pulmonary artery pressure during the RVAD supports and may be beneficial for improving myocardial function in patients with end-stage right heart failure, especially those with pulmonary hypertension., Competing Interests: Declarations Conflict of interest The authors declare no competing interests., (© 2024. International Federation for Medical and Biological Engineering.)

Comprehensive optimization of rotodynamic blood pumps (RBPs) requires the consideration of three partially conflicting objectives: size, hemocompatibility, and motor efficiency. Optimizing these individual objectives independently, the potential of multiobjective optimizations often remains untapped. This study aimed at the multiobjective optimization of an RBP for cavopulmonary support accounting for all three objectives simultaneously. Hydraulic and electromagnetic design spaces were characterized using computational fluid dynamics and computational electromagnetics, respectively. Design variables included secondary flow gap widths, impeller diameters, and stator heights. The size objective encompassed the RBP widths and heights, the hemocompatibility objective was a weighted composite measure of well-established metrics, and the motor objective was determined by motor losses. Multiobjective optimization was performed through Pareto analysis. 81 designs were considered, and 21 Pareto-optimal designs were identified. The Pareto analysis indicated that hemocompatibility performance could be improved by 72.4% with a concomitant 1.5% reduction in the baseline pump volume. This, however, entailed an increase in motor losses by 0.2 W, while still meeting design requirements, with maximum local temperature rises remaining below 0.4 K. The multiobjective optimization led to a Pareto front, demonstrating the feasibility to improve hemocompatibility at reduced pump volume, however, at the cost of a diminished yet still acceptable motor performance., Competing Interests: Disclosure: M.G. received personal fees and grants from BerlinHeart GmbH. The other authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

Aortic valves with bicuspids have two rather than three leaflets, which is a congenital heart condition. About 0.5-2% of people have a bicuspid aortic valve. Blood flow through the aorta is commonly believed to be laminar, although aortic valve disorders can cause turbulent transitions. Understanding the impact of turbulence is crucial for foreseeing how the disease will progress. The study's objective was use large eddy simulation to provide a thorough analysis of the turbulence in bicuspid aortic valve dysfunction. Using a large eddy simulation, the blood flow patterns of the bicuspid and tricuspid aortic valves were compared, and significant discrepancies were found. The velocity field in flow in bicuspid configurations was asymmetrically distributed toward the ascending aorta. In tricuspid aortic valve (TAV) the flow, on the other hand, was symmetrical within the same aortic segment. Moreover, we looked into standard deviation, Q-criterion, viscosity ratio and wall shear stresses for each cases to understand transition to turbulence. Our findings indicate that in the bicuspid aortic valve (BAV) case, the fluid-dynamic abnormalities increase. The global turbulent kinetic energy and time-averaged wall shear stress for the TAV and BAV scenarios were also examined. We discovered that the global turbulent kinetic energy was higher in the BAV case compared to TAV, in addition to the increased wall shear stress induced by the BAV in the ascending aorta.

Pulmonary hypertension (PH) is a debilitating disease that alters the structure and function of both the proximal and distal pulmonary vasculature. This alters pressure-flow relationships in the pulmonary arterial and venous trees, though there is a critical knowledge gap in the relationships between proximal and distal hemodynamics in disease. Multiscale computational models enable simulations in both the proximal and distal vasculature. However, model inputs and measured data are inherently uncertain, requiring a full analysis of the sensitivity and uncertainty of the model. Thus, this study quantifies model sensitivity and output uncertainty in a spatially multiscale, pulse-wave propagation model of pulmonary hemodynamics. The model includes fifteen proximal arteries and twelve proximal veins, connected by a two-sided, structured tree model of the distal vasculature. We use polynomial chaos expansions to expedite sensitivity and uncertainty quantification analyses and provide results for both the proximal and distal vasculature. We quantify uncertainty in blood pressure, blood flow rate, wave intensity, wall shear stress, and cyclic stretch. The latter two are important stimuli for endothelial cell mechanotransduction. We conclude that, while nearly all the parameters in our system have some influence on model predictions, the parameters describing the density of the microvascular beds have the largest effects on all simulated quantities in both the proximal and distal arterial and venous circulations., Competing Interests: Declarations Conflict of 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. Citation diversity statement In agreement with the editorial from the Biomedical Engineering Society (BMES) (Rowson et al. 2021) on biases in citation practices, we have performed an analysis of the gender and race of our bibliography. This was done manually, though automatic probabilistic tools exist. We recognize existing race and gender biases in citation practices and promote the use of diversity statements like this for encouraging fair gender and racial author inclusion and identifying gaps in scientific representation.Our references contain 16% woman(first)/woman(last), 12% man/woman, 16% woman/man, and 56% man/man. This binary gender categorization is limited in that it cannot account for intersex, nonbinary, or transgender people. In addition, our references contain 0% author of color (first)/author of color(last), 5% white author/author of color, 16% author of color/white author, and 79% white author/white author. Our approach to gender and race categorization is limited in that gender and race are assigned by us based on publicly available information and online media. We look forward to future databases that would allow all authors to self-identify race and gender in appropriately anonymized and searchable fashion and new research that enables and supports equitable practices in science., (© 2024. The Author(s).)

Purpose: To summarize experience with and the efficacy of fenestrated/branched thoracic endovascular repair (F/B-TEVAR) using physician-modified stent-grafts (PMSGs) under 3D printing guidance in triple aortic arch branch reconstruction., Materials and Methods: From February 2018 to April 2022, 14 cases of aortic arch aneurysms and 30 cases of aortic arch dissection (22 acute aortic arch dissection and 8 long-term aortic arch dissection)were treated by F/B-TEVAR in our department, including 34 males and 10 females, with an average age of 59.84 ± 11.72 years. Three aortic arch branches were affected in all patients. A 3D-printed model was made according to computed tomography angiography images and used to guide the fabrication of PMSGs. All patients were followed up., Results: A total of 132 branches were successfully reconstructed with no case of conversion to open surgery. The average operation time was 4.97 ± 1.40 hours, including a mean 44.05 ± 7.72 minutes for stent-graft customization, the mean postoperative hospitalization duration was 9.91 ± 4.47 days, the average intraoperative blood loss was 480.91 mL (100-2810 mL), and the mean postoperative intensive care unit monitoring duration was 1.02 days (0-5 days). No deaths occurred within 30 days of surgery. Postoperative neurological complications occurred in 1 case (2.3%), and retrograde type A dissection occurred in 1 case (2.3%)., Conclusion: Compared with conventional surgery, triple aortic arch branch reconstruction under the guidance of 3D printing is a minimally invasive treatment method with the advantages of accurate positioning, rapid postoperative recovery, few complications, and reliable short- to mid-term effects., Clinical Impact: At present the PMSG usually depend on imaging data and software calculation. With the guidance of 3D printing technology, image data could be transformed into 3D model, which has improved the accuracy of the positioning of the fenestrations. The diameter reduction technique and the internal mini cuff technique have made a complement to the slimed-down fenestration selection process and the low rate of endoleak. As reproducible study, our results may provide reference for TEVAR in different cases., 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.

Purpose: To investigate the effect of changing systolic and diastolic blood pressures (SBP and DBP, respectively) on sinus flow and valvular and epicardial coronary flow dynamics after TAVR and SAVR., Methods: SAPIEN 3 and Magna valves were deployed in an idealized aortic root model as part of a pulse duplicating left heart flow loop simulator. Different combinations of SBP and DBP were applied to the test setup and the resulting change in total coronary flow from baseline (120/60 mmHg), effective orifice area (EOA), and left ventricular (LV) workload, with each combination, was assessed. In addition, particle image velocimetry was used to assess the Laplacian of pressure ( ∇ 2 P ) in the sinus, coronary and main flow velocities, the energy dissipation rate (EDR) in the sinus and the LV workload., Results: This study shows that under an elevated SBP, there is an increase in the total coronary flow, EOA, LV workload, peak velocities downstream of the valve, ∇ 2 P , and EDR. With an elevated DBP, there was an increase in the total coronary flow and ∇ 2 P . However, EOA and LV workload decreased with an increase in DBP, and EDR increased with a decrease in DBP., Conclusions: Blood pressure alters the hemodynamics in the sinus and downstream flow following aortic valve replacement, potentially influencing outcomes in some patients., Competing Interests: Declarations Competing Interests The authors do not report any relevant conflict of interest. Dr. Lindman has consulted for and received investigator-initiated research grant funding from Edwards Lifesciences and consulted for AstraZeneca., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Purpose: Flow diverting stents (FDS) are used to treat cerebral aneurysms, by promoting thrombosis and occlusion of the aneurysm sac. However, retreatment is required in some cases, and the biologic basis behind treatment outcome is not known. The goal of this study was to understand how changes in hemodynamic flow after FDS placement affect aneurysmal endothelial cell (EC) activity., Methods: Three-dimensional models of patient-specific aneurysms were created to quantify the EC response to FDS placement. Computational fluid dynamic simulations were used to determine the hemodynamic impact of FDS. Two identical models were created for each patient; into one a FDS was inserted. Each model was then populated with human carotid ECs and subjected to patient-specific pulsatile flow for 24 h. ECs were isolated from aneurysm dome from each model and bulk RNA sequencing was performed., Results: Paired untreated and treated models were created for four patients. Aneurysm dome EC analysis revealed 366 (2.6%) significant gene changes between the untreated and FDS conditions, out of 13909 total expressed genes. Gene set enrichment analysis of the untreated models demonstrated enriched gene ontology terms related to cell adhesion, growth/tensile activity, cytoskeletal organization, and calcium ion binding. In the FDS models, enriched terms were related to cellular proliferation, ribosomal activity, RNA splicing, and protein folding., Conclusion: Treatment of cerebral aneurysms with FDS induces significant EC gene transcription changes related to aneurysm hemodynamics in patient-specific in vitro 3D-printed models subjected to pulsatile flow. Further investigation is needed into the relationship between transcriptional change and treatment outcome., Competing Interests: Declarations Conflict of interest Dr. Levitt is the recipient of educational grants from Stryker and Medtronic. He reports equity interest in Synchron, Stroke Diagnostics, Proprio, Hyperion Surgical, Fluid Biomed, and Apertur. He is an advisor for Metis Innovative, and is a consultant for Medtronic, Aeaean Advisors and Stereotaxis. He is on the editorial board of Journal of NeuroInterventional Surgery and the Data Safety Monitoring Board of Arsenal Medical., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Purpose: The purpose is to demonstrate the difference in closing volume fraction between the single opening&closing valve tester (SOCVT) and continuous pulsatile flow valve tester (CPFVT)., Methods: A comparative study was conducted in four hemodynamic conditions selected from the ISO 5840 on the four mitral valve states: normal annulus, 40% annulus dilation, 60% annulus dilation, and repaired valve with a clip device in both the SOCVT and CPFVT. The closing volume fractions were compared and errors calculated in the 16 cases., Results: In the CPFVT, the flowrate waveform depends more on hemodynamic conditions rather than the valve morphology. For closing volume fractions in the two testers, twelve cases had errors between 10% and 20% and 3 cases had errors between 2.2% and 5.5%. There was no statistic difference in the closing volume fraction between the CPFVT and SOCVT for the normal annulus, 40% valve annulus dilation, 60% valve annulus dilation and repaired valves (P values = 0.44, 0.44, 0.33, and 0.08, respectively, n = 4)., Conclusion: There is certain error in closing volume measurements, even if no statistic difference in closing volume measured by the SOCVT and CPFVT. The typical flow waveforms of the mitral valve may be available to standardize testing of the SOCVT to evaluate valve hemodynamics. The SOCVT may be an alternative to the valve testing., Competing Interests: Declarations. Ethical Approval: Not applicable. Consent to Participate: Not applicable. Consent for Publication: Not applicable. Competing of Interests: Hao Wang is the inventor of the single opening&closing tester. The other authors do not have competing interest., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Purpose: The Wall Shear Stress (WSS) is the component tangential to the boundary of the normal stress tensor in an incompressible fluid, and it has been recognized as a quantity of primary importance in predicting possible adverse events in cardiovascular diseases, in general, and in coronary diseases, in particular. The quantification of the WSS in patient-specific settings can be achieved by performing a Computational Fluid Dynamics (CFD) analysis based on patient geometry, or it can be retrieved by a numerical approximation based on blood flow velocity data, e.g., ultrasound (US) Doppler measurements. This paper presents a novel method for WSS quantification from 2D vector Doppler measurements., Methods: Images were obtained through unfocused plane waves and transverse oscillation to acquire both in-plane velocity components. These velocity components were processed using pseudo-spectral differentiation techniques based on Fourier approximations of the derivatives to compute the WSS., Results: Our Pseudo-Spectral Method (PSM) is tested in two vessel phantoms, straight and stenotic, where a steady flow of 15 mL/min is applied. The method is successfully validated against CFD simulations and compared against current techniques based on the assumption of a parabolic velocity profile. The PSM accurately detected Wall Shear Stress (WSS) variations in geometries differing from straight cylinders, and is less sensitive to measurement noise. In particular, when using synthetic data (noise free, e.g., generated by CFD) on cylindrical geometries, the Poiseuille-based methods and PSM have comparable accuracy; on the contrary, when using the data retrieved from US measures, the average error of the WSS obtained with the PSM turned out to be 3 to 9 times smaller than that obtained by state-of-the-art methods., Conclusion: The pseudo-spectral approach allows controlling the approximation errors in the presence of noisy data. This gives a more accurate alternative to the present standard and a less computationally expensive choice compared to CFD, which also requires high-quality data to reconstruct the vessel geometry., Competing Interests: Declarations. Conflict of interest: The authors have no financial or proprietary interests in any material discussed in this article., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Thrombotic and bleeding events are the most common hematologic complications in patients with mechanically assisted circulation and are closely related to device-induced platelet dysfunction. In this study, we sought to link computational fluid dynamics (CFD) modeling of blood pumps with device-induced platelet defects. Fresh human blood was circulated in circulatory loops with four pumps (CentriMag, HVAD, HeartMate II, and CH-VAD) operated under a total of six clinically representative conditions. Blood samples were collected and analyzed for glycoprotein (GP) IIb/IIIa activation and receptor shedding of GPIbα and GPVI. In parallel, CFD modeling was performed to characterize the blood flow in these pumps. Numerical indices of platelet defects were derived from CFD modeling incorporating previously derived power-law models under constant shear conditions. Numerical results were correlated with experimental results by regression analysis. The results suggested that a scalar shear stress of less than 75 Pa may have limited contribution to platelet damage. The platelet defect indices predicted by the CFD power-law models after excluding shear stress <75 Pa correlated excellently with experimentally measured indices. Although numerical prediction based on the power-law model cannot directly reproduce the experimental data. The power-law model has proven its effectiveness, especially for quantitative comparisons., Competing Interests: Disclosure: Z.J.W. and B.P.G. disclose financial interest in Abiomed-Breethe, Inc. and intellectual property for ECMO systems, blood pumps blood pumps, and relevant enabling technologies. Z.J.W. serves as a consultant to Daiichi Sankyo, Inc. and CH Biomedical USA, Inc. J.Z. discloses financial interest in intellectual property for ECMO systems and blood pumps. The other authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

Timothy syndrome type 1 (TS1), a malignant variant of Long QT Syndrome, is caused by L-type Ca2+ Channel (LTCC) inactivation defects secondary to the p.Gly406Arg mutation in the CACNA1C gene. Leveraging on the experimental in vitro data from our TS1 knock-in swine model and their wild-type (WT) littermates, we first developed a mathematical model of WT large white swine ventricular cardiomyocyte electrophysiology that reproduces a wide range of experimental data, including ionic current properties, action potential (AP) dynamics, and Ca 2 + handling. A sensitivity analysis tested robustness and facilitated comparison with the parent ORd human model. Introducing 22% of TS1-mutated LTCCs, the model faithfully reproduced key disease features, including marked AP prolongation, steeper rate-dependent adaptation of AP duration, Ca 2 + overload, and CaMKII-mediated decreased upstroke velocity. Translational relevance of the TS1 model was investigated by: dissecting the roles of primary and secondary contributors to TS1 phenotype; demonstrating the arrhythmogenic potential of TS1 vs. WT cells; and evaluating the model's capability to identify novel pharmacological targets which could modulate the cellular phenotype. In conclusion, we developed a mathematical large white swine ventricular myocyte model, demonstrating its utility in exploring arrhythmogenic mechanisms and therapeutic interventions in cardiac diseases, such as TS1., Competing Interests: Declarations. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Self-organizing spiral electrical waves are produced in the heart during fatal cardiac arrhythmias. Controlling these waves is therefore an essential step in managing the disease. Here we present an effective method for controlling cardiac spiral waves using optogenetics. The method involves using photons to actively scan the surface of the heart for phase singularities. Once detected, these phase singularities are redirected to an inexcitable wall to be eliminated. Thus, spiral waves can be controlled in a double-blind fashion. We present two theoretical mechanisms with ex vivo validation.

Background: Transmural propagation and endoepicardial delays in activation observed in patients with atrial fibrillation are hypothesized to be associated with structural remodeling and endoepicardial dissociation. We aim to explore in a computational model how the distribution of delays and the rate of endo- and epicardial breakthrough activation patterns are affected by fibrosis and heterogeneous layer dissociation., Methods: A bilayer interconnected cable model of the left atrium was used to simulate a total of 4,800 episodes of atrial fibrillation on 960 different arrhythmogenic substrates with up to 30% epicardium-only diffuse fibrosis. Endoepicardial connections were heterogeneously distributed following random spatial patterns (characteristic length scale from 1.6 to 11.4 mm). Intermediate nodes were introduced in the transmural connections to enable the simulation of weaker coupling. This heterogeneous interlayer dissociation divided the atrial bilayer into connected and disconnected regions (from 27 to 48,000 connected regions). Activation time series were extracted in both layers to compute endoepicardial delays and detect breakthrough patterns., Results: Because of epicardial fibrosis, fibrillatory waves were driven by the endocardium, which generated endoepicardial delays. The delays in the connected regions (up to 10 ms, but generally < 5 ms) were prolonged by higher fibrosis density and weaker coupling. Disconnected regions allowed longer delays (> 15 ms) and promoted the occurrence of breakthroughs. These breakthroughs had short lifespan (< 10-20 ms) and were more prevalent with higher fibrosis density and heterogeneous dissociation (larger disconnected regions). Severe remodeling (< 500 connected regions) was needed to produce clinically reported rates (> 0.1 breakthrough/cycle/cm2)., Conclusion: Heterogeneous endoepicardial dissociation aggravates activation delays and increases the prevalence of epicardial breakthroughs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zakeri Zafarghandi, Jacquemet. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Many extended chemical and biological systems self-organise into complex patterns that drive the medium behaviour in a non-linear fashion. An important class of such systems are excitable media, including neural and cardiac tissues. In extended excitable media, wave breaks can form rotating patterns and turbulence. However, the onset, sustaining and elimination of such complex patterns is currently incompletely understood. The classical theory of phase singularities in excitable media was recently challenged, as extended lines of conduction block were identified as phase discontinuities. Here, we provide a theoretical framework that captures the rich dynamics in excitable systems in terms of three quasiparticles: heads, tails, and pivots. We propose to call these quasiparticles 'cardions'. In simulations and experiments, we show that these basic building blocks combine into at least four different bound states. By representing their interactions similarly to Feynman diagrams in physics, the creation and annihilation of vortex pairs are shown to be sequences of dynamical creation, annihilation, and recombination of the identified quasiparticles. We draw such diagrams for numerical simulations, as well as optical voltage mapping experiments performed on cultured human atrial myocytes (hiAMs). Our results provide a new, unified language for a more detailed theory, analysis, and mechanistic insights of dynamical transitions in excitation patterns., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

We propose a deep learning method to model and generate synthetic aortic shapes based on representing shapes as the zero-level set of a neural signed distance field, conditioned by a family of trainable embedding vectors with encode the geometric features of each shape. The network is trained on a dataset of aortic root meshes reconstructed from CT images by making the neural field vanish on sampled surface points and enforcing its spatial gradient to have unit norm. Empirical results show that our model can represent aortic shapes with high fidelity. Moreover, by sampling from the learned embedding vectors, we can generate novel shapes that resemble real patient anatomies, which can be used for in-silico trials.

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

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

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

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

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

Objectives: Distal stent graft-induced new entry (dSINE), a new intimal tear at the distal edge of the frozen elephant trunk (FET), is a complication of FET. Preventive measures for dSINE have not yet been established. This study aimed to clarify the mechanisms underlying the development of dSINE by simulating the mechanical environment at the distal edge of the FET., Methods: The stress field in the aortic wall after FET deployment was calculated using finite element analysis. Blood flow in the intraluminal space of the aorta and FET models was simulated using computational fluid dynamics. The simulations were conducted with various oversizing rates of FET ranging from 0 to 30% under the condition of FET with elastic recoil., Results: The elastic recoil of the FET, which caused its distal edge to push against the greater curvature of the aorta, induced a concentration of circumferential stress and increased wall shear stress (WSS) at the aorta. Elastic recoil also created a discontinuous notch on the lesser curvature of the aorta, causing flow stagnation. An increase in the oversizing rate of the FET widened the large circumferential stress area on the greater curvature and increases the maximum stress. Conversely, a decrease in the oversizing rate of the FET increased the WSS and widened the area with high WSS., Conclusions: Circumferential stress concentration due to an oversized FET and high WSS due to an undersized FET can cause a dSINE. The selection of smaller-sized FET alone might not prevent dSINE., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

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

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

Background: Macroreentry stands as the predominant mechanism of typical and atypical flutter. Despite advances in mapping, many aspects of macroreentrant atrial tachycardia remain unsolved. In this translational study, we applied principles of topology to understand the activation patterns, entrainment characteristics, and ablation responses in a large clinical macroreentrant atrial tachycardia database., Methods: Because the atrium can be topologically seen as a closed sphere with holes, we used a computational fixed spherical mesh model with a finite number of holes to induce and analyze macroreentrant atrial tachycardia. The ensuing insights were used to interpret high-density activation maps, postpacing interval-tachycardia cycle length values (difference between postpacing interval and tachycardia cycle length), and ablation response in 131 cases of typical and atypical flutter (n=106 left atrium, n=25 right atrium)., Results: Modeling of macroreentrant atrial tachycardia revealed that reentry on closed surfaces consistently manifests itself as paired rotation and that an odd number of critical boundaries is mathematically impossible. Together with mathematical confirmation by the index theorem, this led to a unifying construct that could explain the number of loops, difference between postpacing interval and tachycardia cycle length values, and ablation outcomes (termination, no change, or prolongation in tachycardia cycle length) in all 131 cases., Conclusions: Combining topology with the index theorem offers a novel and cohesive framework for understanding and managing typical and atypical flutter., Competing Interests: Dr Vandersickel, R. Van den Abeele, and S. Hendrickx have submitted a patent for description of the algorithm to find the critical boundaries automatically. The other authors report no conflicts.

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

Physics-based computer models based on numerical solutions of the governing equations generally cannot make rapid predictions, which in turn limits their applications in the clinic. To address this issue, we developed a physics-informed neural network (PINN) model that encodes the physics of a closed-loop blood circulation system embedding a left ventricle (LV). The PINN model is trained to satisfy a system of ordinary differential equations (ODEs) associated with a lumped parameter description of the circulatory system. The model predictions have a maximum error of less than 5% when compared to those obtained by solving the ODEs numerically. An inverse modeling approach using the PINN model is also developed to rapidly estimate model parameters (in ∼ 3 min) from single-beat LV pressure and volume waveforms. Using synthetic LV pressure and volume waveforms generated by the PINN model with different model parameter values, we show that the inverse modeling approach can recover the corresponding ground truth values for LV contractility indexed by the end-systolic elastance E es with a 1% error, which suggests that this parameter is unique. The estimated E es is about 58% to 284% higher for the data associated with dobutamine compared to those without, which implies that this approach can be used to estimate LV contractility using single-beat measurements. The PINN inverse modeling can potentially be used in the clinic to simultaneously estimate LV contractility and other physiological parameters from single-beat measurements., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Stent underexpansion is a significant challenge in percutaneous coronary intervention, critically impacting patient outcomes. While excimer laser coronary angioplasty (ELCA) and intravascular lithotripsy (IVL) are increasingly used to address this issue, their full impact on the integrity of drug-eluting stents remains unclear, raising concerns about their safety and efficacy., Methods: This in vitro study assessed the effects of ELCA and IVL on the structural integrity of drug-eluting stents using scanning electron microscopy. Nine stents, 5 Onyx Frontier (with durable circumferential polymer coating) and 4 Cre8 (polymer-free), were implanted in a 3-dimensional coronary artery simulator following standardized protocols. After implantation, treatments with saline-ELCA, contrast-ELCA, IVL, and high-pressure balloon dilatation were applied. A comprehensive evaluation of the stent surface was performed at 60-fold magnification., Results: Scanning electron microscopy analysis revealed significant differences in polymer damage between the techniques. High-pressure balloon dilatation and contrast-ELCA exhibited substantial polymer fragmentation and detachment compared with IVL, saline-ELCA, and conventional dilatation. High-pressure balloon dilatation demonstrated the highest incidence of polymer shaving and overcoating. No significant alterations were observed in polymer-free stents, regardless of the technique used., Conclusions: IVL and saline-ELCA applied immediately after stent implantation produce minimal polymer damage, whereas high-pressure balloon dilatation and contrast-ELCA cause significant damage to the polymer coating. The integrity of polymer-free drug-eluting stent appears stable regardless of the technique used. Further research is needed to validate these findings and explore their clinical implications., Competing Interests: Dr Rivero-Santana is a Rio Hortega Researcher at the Carlos III Health Institute (CM23/00121). Dr Jurado-Roman received speaker fees from Shockwave, Philips, Abbott, Boston Scientific, and Biotronik. In addition, Dr Jurado-Roman has served as a proctor for Philips, Abbott, Boston Scientific, and World Medica. The other authors report no conflicts.

Atherosclerosis is one of the important diseases of the circulatory system because atherosclerotic plaques cause significant disruption of blood flow. Therefore, it is very important to properly understand these processes and skillfully simulate blood flow. In our work, we consider blood flow through an abdominal aorta with iliac arteries, assuming that the right iliac artery is narrowed by an atherosclerotic lesion. Blood flow is simulated using the laminar, standard k - ω and standard k - ϵ models. The obtained results show that despite the use of identical initial conditions, the distribution of velocity flow and wall shear stress depends on the choice of flow simulation model. For the k - ϵ model, we obtain higher values of speed and wall shear stress on atherosclerotic plaque than in the other two models. The laminar and k - ω models predict larger areas where reverse blood flow occurs in the area behind the atherosclerotic lesion. This effect is associated with negative wall shear stress. These two models give very similar results. The results obtained by us, and those reported in the literature, indicate that k - ω model is the most suitable for blood flow analysis., (© 2024. The Author(s).)

This study evaluates the efficacy of annuloplasty repair as a standalone procedure for treating bileaflet mitral valve prolapse with mitral regurgitation (MR). Various flexible ring bands for MR of different severities were compared to assess their biomechanical impact and treatment outcomes. Computational beating heart models, based on the Living Heart Human Model, were utilized to simulate annuloplasty repairs. Repairs using bands of varying lengths were modeled on moderate and severe MR cases, considering bileaflet mitral valve prolapse. Key parameters, including regurgitant orifice area (ROA), prolapse severity, coaptation length, leaflet position, and deformation, were computed to compare conditions before and after implantation. Annuloplasty repairs effectively reduced the ROA in both moderate and severe MR cases, achieving complete sealing in selective instances. Additionally, annuloplasty repair corrected bileaflet prolapse, with prolapse severity decreasing as the annular size increased. Successful coaptation was indicated by the expansion of each leaflet's contact area distribution and percentage in contact with the opposing leaflet. The risk of systolic anterior motion, that may obstruct the left ventricular outflow tract, was minimized, as the anterior leaflet was directed towards the posterior position. In conclusion, annuloplasty repair alone can effectively treat MR when an appropriate band length is selected. It facilitates a significant reduction in ROA, correction of bileaflet prolapse, and improvement in leaflet coaptation. These findings have important clinical implications, potentially offering a less complex surgical treatment avenue and reducing complications in the management of MR., 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.)

Understanding cardiovascular control mediated by the autonomic system remains challenging due to its inherent complexity. Consequently, syndromes such as orthostatic intolerance continue to evoke debates regarding the underlying pathophysiological mechanisms. This study develops a comprehensive mathematical model simulating the control of the sympathetic branch of the cardiovascular system in individuals with normal and abnormal responses to the head-up-tilt test. We recruited four young women: one control, one with vasovagal syncope, one with orthostatic hypertension, and one with orthostatic hypotension, exposing them to an orthostatic head-up tilt test (HUTT) employing non-invasive methods to measure electrocardiography and continuous blood pressure. Our work encompasses a compartmental model formulated using a system of ordinary differential equations. Using heart rate as input, we predict blood pressure, flow, and volume in compartments representing the veins, arteries, heart, and the sympathetic branch of the baroreflex control system. The latter is modulated by high- and low-pressure baroreceptor afferents activated by changes in blood pressure induced by the HUTT. Sensitivity analysis, parameter subset selection, and optimization are employed to estimate patient-specific parameters associated with autonomic performance. The model has seven sensitive and identifiable parameters with significant physiological relevance that can serve as biomarkers for patient classification. Results show that the model can reproduce a spectrum of blood pressure responses successfully, fitting the trajectory displayed by the experimental data. The controller exhibits behavior that emulates the operation of the sympathetic system. These encouraging findings underscore the potential of computational methods in evaluating pathologies associated with autonomic nervous system control, warranting further exploration and novel approaches., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Maria Rodriguez-Fernandez reports financial support was provided by National Agency for Research and Innovation. 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 Elsevier Inc. All rights reserved.)