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Hypertrophic cardiomyopathy (HCM) is one of the most common genetic cardiac disorders and is characterized by different phenotypes of left ventricular hypertrophy with and without obstruction. The effects of left ventricular outflow tract (LVOT) obstruction based on different anatomies may be hemodynamically relevant and influence therapeutic decision making. Cardiovascular magnetic resonance (CMR) provides anatomical information. We aimed to identify different shapes of LVOT-obstruction using Cardiovascular Magnetic Resonance (CMR). The study consisted of two parts: An in-vivo experiment for shape analysis and in-vitro part for the assessment of its hemodynamic consequences. In-vivo a 3D depiction of the LVOT was created using a 3D multi-slice reconstruction from 2D-slices (full coverage cine stack with 7 slices and a thickness of 5-6 mm with no gap) in 125 consecutive HOCM patients (age = 64.17 +/- 12.655; female n = 42). In-vitro an analysis of the LVOT regarding shape and flow behavior was conducted. For this purpose, 2D and 4D measurements were performed on 3D printed phantoms which were based on the anatomical characteristics of the in-vivo study, retrospectively. The in-vivo study identified three main shapes named K- (28.8%), X- (51.2%) and V-shape (10.4%) and a mixed one (9.6%). By analyzing the in-vitro flow measurements every shape showed an individual flow profile in relation to the maximum velocity in cm/s. Here, the V-shape showed the highest value of velocity (max. 138.87 cm/s). The X-shape was characterized by a similar profile but with lower velocity values (max. 125.39 cm/s), whereas the K-shape had an increase of the velocity without decrease (max. 137.11 cm/s). For the first time three different shapes of LVOT-obstruction could be identified. These variants seem to affect the hemodynamics in HOCM., Competing Interests: Declarations Competing interests The authors have no relevant financial or non-financial interests to disclose., (© 2024. The Author(s).)

Donor vessel fractional flow reserve (FFR) usually increases following successful chronic total occlusion (CTO) percutaneous coronary intervention, as documented by pressure wires. In this case, donor vessel physiology changes were assessed using FFR derived from coronary computed tomography angiography (CCTA) and an artificial Intelligence-guided quantitative CCTA ischemia model in combination with pressure wire-based FFR., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Aneurysms are bulges of an artery, which require clinical management solutions. Due to the inherent advantages, endovascular coil filling is emerging as the treatment of choice for intracranial aneurysms (IAs). However, after successful treatment of coil embolization, there is a serious risk of recurrence. It is well known that optimal packing density will enhance treatment outcomes. The main objective of endovascular coil embolization is to achieve flow stasis by enabling significant reduction in intra-aneurysmal flow and facilitate thrombus formation. The present study numerically investigates the effect of framing coil orientation on intra-aneurysmal hemodynamics. For the purpose of analysis, actual shape of the embolic coil is used, instead of simplified ideal coil shape. Typically used details of the framing coil are resolved for the analysis. However, region above the framing coil is assumed to be filled with a porous medium. Present simulations have shown that orientation of the framing coil loop (FCL) greatly influences the intra-aneurysmal hemodynamics. The FCLs which were placed parallel to the outlets of basilar tip aneurysm (Coil A) were found to reduce intra-aneurysmal flow velocity that facilitates thrombus formation. Involving the coil for the region is modeled using a porous medium model with a packing density of 20 % . The simulations indicate that the framing coil loop (FCL) has a significant influence on the overall outcome., (© 2024. International Federation for Medical and Biological Engineering.)

Cardiac catheter ablation requires an adequate contact between myocardium and catheter tip. Our aim was to quantify the relationship between the contact force (CF) and the resulting mechanical deformation induced by the catheter tip using an ex vivo model and computational modeling. The catheter tip was inserted perpendicularly into porcine heart samples. CF values ranged from 10 to 80 g. The computer model was built to simulate the same experimental conditions, and it considered a 3-parameter Mooney-Rivlin model based on hyper-elastic material. We found a strong correlation between the CF and insertion depth (ID) (R 2  = 0.96, P < 0.001), from 0.7 ± 0.3 mm at 10 g to 6.9 ± 0.1 mm at 80 g. Since the surface deformation was asymmetrical, two transversal diameters (minor and major) were identified. Both diameters were strongly correlated with CF (R 2  ≥ 0.95), from 4.0 ± 0.4 mm at 20 g to 10.3 ± 0.0 mm at 80 g (minor), and from 6.4 ± 0.7 mm at 20 g to 16.7 ± 0.1 mm at 80 g (major). An optimal fit between computer and experimental results was achieved, with a prediction error of 0.74 and 0.86 mm for insertion depth and mean surface diameter, respectively., (© 2024. The Author(s).)

Fetal critical aortic stenosis with evolving hypoplastic left heart syndrome (CAS-eHLHS) can progress to a univentricular (UV) birth malformation. Catheter-based fetal aortic valvuloplasty (FAV) can resolve stenosis and reduce the likelihood of malformation progression. However, we have limited understanding of the biomechanical impact of FAV and subsequent LV responses. Therefore, we performed image-based finite element (FE) modeling of 4 CAS-eHLHS fetal hearts, by performing iterative simulations to match image-based characteristics and then back-computing physiological parameters. We used pre-FAV simulations to conduct virtual FAV (vFAV) and compared pre-FAV and post-FAV simulations. vFAV simulations generally enabled partial restoration of several physiological features toward healthy levels, including increased stroke volume and myocardial strains, reduced aortic valve (AV) and mitral valve regurgitation (MVr) velocities, reduced LV and LA pressures, and reduced peak myofiber stress. FAV often leads to aortic valve regurgitation (AVr). Our simulations showed that AVr could compromise LV and LA depressurization but it could also significantly increase stroke volume and myocardial deformational stimuli. Post-FAV scans and simulations showed FAV enabled only partial reduction of the AV dissipative coefficient. Furthermore, LV contractility and peripheral vascular resistance could change in response to FAV, preventing decreases in AV velocity and LV pressure, compared with what would be anticipated from stenosis relief. This suggested that case-specific post-FAV modeling is required to fully capture cardiac functionality. Overall, image-based FE modeling could provide mechanistic details of the effects of FAV, but computational prediction of acute outcomes was difficult due to a patient-dependent physiological response to FAV., (© 2024. The Author(s).)

Left ventricular (LV) geometric patterns aid clinicians in the diagnosis and prognostication of various cardiomyopathies. The aim of this study is to assess the accuracy and reproducibility of LV dimensions and wall thickness using deep learning (DL) models. A total of 30,080 unique studies were included; 24,013 studies were used to train a convolutional neural network model to automatically assess, at end-diastole, LV internal diameter (LVID), interventricular septal wall thickness (IVS), posterior wall thickness (PWT), and LV mass. The model was trained to select end-diastolic frames with the largest LVID and to identify four landmarks, marking the dimensions of LVID, IVS, and PWT using manually labeled landmarks as reference. The model was validated with 3,014 echocardiographic cines and the accuracy of the model was evaluated with a test set of 3,053 echocardiographic cines. The model accurately measured LVID, IVS, PWT, and LV mass compared to study report values with a mean relative error of 5.40%, 11.73%, 12.76%, and 13.93%, respectively. The 𝑅 2 of the model for the LVID, IVS, PWT, and the LV mass was 0.88, 0.63, 0.50, and 0.87, respectively. The novel DL model developed in this study was accurate for LV dimension assessment without the need to select end-diastolic frames manually. DL automated measurements of IVS and PWT were less accurate with greater wall thickness. Validation studies in larger and more diverse populations are ongoing., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Coronary artery aneurysms (CAAs) are morphologically classified as saccular and fusiform. There is still a great deal of clinical controversy as to which types of CAA are more likely to cause thrombosis. Therefore, the main objective of this study was to evaluate the trend of thrombus growth in CAAs with different morphologies and to assess the risk of possible long-term complications based on hemodynamic parameters. Utilizing computed tomography angiography (CTA) data from eight healthy coronary arteries, two distinct morphologies of coronary artery aneurysms (CAAs) were reconstructed. Distribution of four wall shear stress (WSS)-based indicators and three helicity indicators was analyzed in this study. Meanwhile, a thrombus growth model was introduced to analyze the thrombus formation in CAAs with different morphologies. The research results showed the distribution of most WSS indicators between saccular and fusiform CAAs was not statistically significant. However, due to the presence of a more pronounced helical flow pattern, irregular helical flow structure and longer time of flow stagnation in saccular CAAs during the cardiac cycle, the mean and maximum relative residence time (RRT) were significantly higher in saccular CAAs than in fusiform CAAs (P < 0.05). This may increase the risk of saccular coronary arteries leading to aneurysmal dilatation or even rupture. Although the two CAAs had similar rates of thrombosis, fusiform CAAs may more early cause obstruction of the main coronary flow channel where the aneurysm is located due to thrombosis growth. Thus, the risk of thrombosis in fusiform coronary aneurysms may warrant greater clinical concern., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Biomechanics-based patient-specific modeling is a promising approach that has proved invaluable for its clinical potential to assess the adversities caused by ischemic heart disease (IHD). In the present study, we propose a framework to find the passive material properties of the myocardium and the unloaded shape of cardiac ventricles simultaneously in patients diagnosed with ischemic cardiomyopathy (ICM). This was achieved by minimizing the difference between the simulated and the target end-diastolic pressure-volume relationships (EDPVRs) using black-box Bayesian optimization, based on the finite element analysis (FEA). End-diastolic (ED) biventricular geometry and the location of the ischemia were determined from cardiac magnetic resonance (CMR) imaging. We employed our pipeline to model the cardiac ventricles of three patients aged between 57 and 66 years, with and without the inclusion of valves. An excellent agreement between the simulated and the target EDPVRs has been reached. Our results revealed that the incorporation of valvular springs typically leads to lower hyperelastic parameters for both healthy and ischemic myocardium, as well as a higher fiber Green strain in the viable regions compared to models without valvular stiffness. Furthermore, the addition of valve-related effects did not result in significant changes in myofiber stress after optimization. We concluded that more accurate results could be obtained when cardiac valves were considered in modeling ventricles. The present novel and practical methodology paves the way for developing digital twins of ischemic cardiac ventricles, providing a non-invasive assessment for designing optimal personalized therapies in precision medicine., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Nowadays, cardiovascular diseases are the most common cause of death worldwide. Besides, atherosclerosis is a cardiovascular disease that occurs with persistent narrowing of arteries, especially medium and large-sized arteries. Atherosclerosis begins with a local elevation in the permeability of the arterial wall as a result of endothelial inflammation. Subsequently, excess LDL permeates into the arterial wall. Then, through several chemical responses and reactions, foam cells are produced. These foam cells serve as a crucial indicator for assessing the development of atherosclerosis within the arteries. In this study, the effect of endothelial layer modeling, heart rate (HR) and hypertension on the foam cell accumulation is numerically investigated in a patient-specific geometry of the human thoracic aorta. Navier-Stokes, Darcy, and mass transfer equations are used to obtain the velocity and concentration field within the domain. Regarding the dependence of endothelial cell properties on time-averaged wall shear stress, it is observed that foam cells are mainly concentrated in the outer curvature of the aortic arch, downstream of the left subclavian artery. However, considering oscillatory-shear-rate as the determinant of endothelial cell properties leads to the accumulation of foam cells in the inner curvature of the descending aorta. Regarding the HR, with the increase of HR, the volume average concentration of the foam cell decreases. However, there is no substantial difference between the cases of different HRs. Moreover, foam cell concentration significantly increases in the hypertension case. This result implies that a slight increase in the blood pressure may induce irreparable problems in the circulatory system., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Neurological complexities resulting from surgery requiring cardiopulmonary bypass (CPB) remain a major concern, encompassing a spectrum of complications including thromboembolic stroke and various cognitive impairments. Surgical manipulation during CPB is considered the primary cause of these neurological complications. This study addresses the overall lack of knowledge concerning CPB hemodynamics within the aorta, employing a combined experimental-computational modeling approach, featuring computational fluid dynamics simulations validated with an in vitro CPB flow loop under steady conditions. Parametric studies were systematically performed, varying parameters associated with CPB techniques (pump flow rate and hemodiluted blood viscosity) and properties related to formed emboli (size and density). This represents the first comprehensive investigation into the individual and combined effects of these factors. Our findings reveal critical insights into the operating conditions of CPB, indicating a positive correlation between pump flow rate and emboli transport into the aortic branches, potentially increasing the risk of stroke. It was also found that larger emboli were more often transported into the aortic branches at higher pump flow rates, while smaller emboli preferred lower flow rates. Further, as blood is commonly diluted during CPB to decrease its viscosity, more emboli were found to enter the aortic branches with greater hemodilution. The combined effects of these parameters are captured using the non-dimensional Stokes number, which was found to positively correlate with emboli transport into the aortic branches. These findings contribute to our understanding of embolic stroke risk factors during CPB and shed light on the complex interplay between CPB parameters., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Red blood cells (RBCs) carry oxygen and make up 40-45% of blood by volume in large vessels down to 10% or less in smaller capillaries. Because of their finite size and large volume fraction, they are heterogeneously distributed throughout the body. This is partially because RBCs are distributed or partitioned nonuniformly at diverging vessel bifurcations where blood flows from one vessel into two. Despite its increased recognition as an important player in the microvasculature, few studies have explored how the endothelial surface layer (ESL; a vessel wall coating) may affect partitioning and RBC dynamics at diverging vessel bifurcations. Here, we use a mathematical and computational model to consider how altering ESL properties, as can occur in pathological scenarios, change RBC partitioning, deformation, and penetration of the ESL. The two-dimensional finite element model considers pairs of cells, represented by interconnected viscoelastic elements, passing through an ESL-lined diverging vessel bifurcation. The properties of the ESL include the hydraulic resistivity and an osmotic pressure difference modeling how easily fluid flows through the ESL and how easily the ESL is structurally compressed, respectively. We find that cell-cell interaction leads to more uniform partitioning and greatly enhances the effects of ESL properties, especially for deformation and penetration. This includes the trend that increased hydraulic resistivity leads to more uniform partitioning, increased deformation, and decreased penetration. It also includes the trend that decreased osmotic pressure increases penetration., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Pulmonary artery stenosis (PAS) often presents in children with congenital heart disease, altering blood flow and pressure during critical periods of growth and development. Variability in stenosis onset, duration, and severity result in variable growth and remodeling of the pulmonary vasculature. Computational fluid dynamics (CFD) models enable investigation into the hemodynamic impact and altered mechanics associated with PAS. In this study, a one-dimensional (1D) fluid dynamics model was used to simulate hemodynamics throughout the pulmonary arteries of individual animals. The geometry of the large pulmonary arteries was prescribed by animal-specific imaging, whereas the distal vasculature was simulated by a three-element Windkessel model at each terminal vessel outlet. Remodeling of the pulmonary vasculature, which cannot be measured in vivo, was estimated via model-fitted parameters. The large artery stiffness was significantly higher on the left side of the vasculature in the left pulmonary artery (LPA) stenosis group, but neither side differed from the sham group. The sham group exhibited a balanced distribution of total distal vascular resistance, whereas the left side was generally larger in the LPA stenosis group, with no significant differences between groups. In contrast, the peripheral compliance on the right side of the LPA stenosis group was significantly greater than the corresponding side of the sham group. Further analysis indicated the underperfused distal vasculature likely moderately decreased in radius with little change in stiffness given the increase in thickness observed with histology. Ultimately, our model enables greater understanding of pulmonary arterial adaptation due to LPA stenosis and has potential for use as a tool to noninvasively estimate remodeling of the pulmonary vasculature., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The mechanism behind hemodialysis arteriovenous fistula (AVF) failure remains poorly understood, despite previous efforts to correlate altered hemodynamics with vascular remodeling. We have recently demonstrated that transitional flow induces high-frequency vibrations in the AVF wall, albeit with a simplified model. This study addresses the key limitations of our original fluid-structure interaction (FSI) approach, aiming to evaluate the vibration response using a more realistic model. A 3D AVF geometry was generated from contrast-free MRI and high-fidelity FSI simulations were performed. Patient-specific inflow and pressure were incorporated, and a three-term Mooney-Rivlin model was fitted using experimental data. The viscoelastic effect of perivascular tissue was modeled with Robin boundary conditions. Prescribing pulsatile inflow and pressure resulted in a substantial increase in vein displacement ( + 400 %) and strain ( + 317 %), with a higher maximum spectral frequency becoming visible above -42 dB (from 200 to 500 Hz). Transitioning from Saint Venant-Kirchhoff to Mooney-Rivlin model led to displacement amplitudes exceeding 10 micrometers and had a substantial impact on strain ( + 116 %). Robin boundary conditions significantly damped high-frequency displacement ( - 60 %). Incorporating venous tissue properties increased vibrations by 91%, extending up to 700 Hz, with a maximum strain of 0.158. Notably, our results show localized, high levels of vibration at the inner curvature of the vein, a site known for experiencing pronounced remodeling. Our findings, consistent with experimental and clinical reports of bruits and thrills, underscore the significance of incorporating physiologically plausible modeling approaches to investigate the role of wall vibrations in AVF remodeling and failure., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Coronary computed angiography (CCTA) with non-invasive fractional flow reserve (FFR) calculates lesion-specific ischemia when compared with invasive FFR and can be considered for patients with stable chest pain and intermediate-grade stenoses according to recent guidelines. The objective of this study was to compare a new CCTA-based artificial-intelligence deep-learning model for FFR prediction (FFR AI ) to computational fluid dynamics CT-derived FFR (FFR CT ) in patients with intermediate-grade coronary stenoses with FFR as reference standard. The FFR AI model was trained with curved multiplanar-reconstruction CCTA images of 500 stenotic vessels in 413 patients, using FFR measurements as the ground truth. We included 37 patients with 39 intermediate-grade stenoses on CCTA and invasive coronary angiography, and with FFR CT and FFR measurements in this retrospective proof of concept study. FFR AI was compared with FFR CT regarding the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy for predicting FFR ≤ 0.80. Sensitivity, specificity, PPV, NPV, and diagnostic accuracy of FFR AI in predicting FFR ≤ 0.80 were 91% (10/11), 82% (23/28), 67% (10/15), 96% (23/24), and 85% (33/39), respectively. Corresponding values for FFR CT were 82% (9/11), 75% (21/28), 56% (9/16), 91% (21/23), and 77% (30/39), respectively. Diagnostic accuracy did not differ significantly between FFR AI and FFR CT (p = 0.12). FFR AI performed similarly to FFR CT for predicting intermediate-grade coronary stenoses with FFR ≤ 0.80. These findings suggest FFR AI as a potential non-invasive imaging tool for guiding therapeutic management in these stenoses., (© 2024. The Author(s).)

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

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

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).)

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.)

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).)

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).)

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.)

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).)

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

The blood protein Von Willebrand factor (VWF) is critical in facilitating arterial thrombosis. At pathologically high shear rates, the protein unfolds and binds to the arterial wall, enabling the rapid deposition of platelets from the blood. We present a novel continuum model for VWF dynamics in flow based on a modified viscoelastic fluid model that incorporates a single constitutive relation to describe the propensity of VWF to unfold as a function of the scalar shear rate. Using experimental data of VWF unfolding in pure shear flow, we fix the parameters for VWF's unfolding propensity and the maximum VWF length, so that the protein is half unfolded at a shear rate of approximately 5000 s - 1 . We then use the theoretical model to predict VWF's behaviour in two complex flows where experimental data are challenging to obtain: pure elongational flow and stenotic arterial flow. In pure elongational flow, our model predicts that VWF is 50% unfolded at approximately 2000 s - 1 , matching the established hypothesis that VWF unfolds at lower shear rates in elongational flow than in shear flow. We demonstrate the sensitivity of this elongational flow prediction to the value of maximum VWF length used in the model, which varies significantly across experimental studies, predicting that VWF can unfold between 2000 and 3200 s - 1 depending on the selected value. Finally, we examine VWF dynamics in a range of idealised arterial stenoses, predicting the relative extension of VWF in elongational flow structures in the centre of the artery compared to high shear regions near the arterial walls., (© 2024. The Author(s).)

Endovascular treatment has become the standard therapy for cerebral aneurysms, while the effective treatment for middle cerebral artery (MCA) bifurcation aneurysms remains a challenge. Current flow-diverting techniques with endovascular coils cover the aneurysm orifice as well as adjacent vessel branches, which may lead to branch occlusion. Novel endovascular flow disruptors, such as the Contour device (Cerus Endovascular), are of great potential to eliminate the risk of branch occlusion. However, there is a lack of valid comparison between novel flow disruptors and conventional (intraluminal) flow-diverters. In this study, two in silico MCA bifurcation aneurysm models were treated by specific Contour devices and flow-diverters using fast-deployment algorithms. Computational fluid dynamic simulations were used to examine the performance and efficiency of deployed devices. Hemodynamic parameters, including aneurysm inflow and wall shear stress, were compared among each Contour device, conventional flow-diverter, and untreated condition. Our results show that the placement of devices can effectively reduce the risk of aneurysm rupture, while the deployment of a Contour device causes more flow reduction than using flow-diverters (e.g. Silk Vista Baby). Besides, the Contour device presents the flow diversion capability of targeting the aneurysm neck without occluding the daughter vessel. In summary, the in silico aneurysm models presented in this study can serve as a powerful pre-planning tool for testing new treatment techniques, optimising device deployment, and predicting the performance in patient-specific aneurysm cases. Contour device is proved to be an effective treatment of MCA bifurcation aneurysms with less daughter vessel occlusion., (© 2024. The Author(s).)

Purpose: Patient-specific simulations of transcatheter aortic valve (TAV) using computational fluid dynamics (CFD) often rely on assumptions regarding proximal and distal anatomy due to the limited availability of high-resolution imaging away from the TAV site and the primary research focus being near the TAV. However, the influence of these anatomical assumptions on computational efficiency and resulting flow characteristics remains uncertain. This study aimed to investigate the impact of different distal aortic arch anatomies-some of them commonly used in literature-on flow and hemodynamics in the vicinity of the TAV using large eddy simulations (LES)., Methods: Three aortic root anatomical configurations with four representative distal aortic arch types were considered in this study. The arch types included a 90-degree bend, an idealized distal aortic arch anatomy, a clipped version of the idealized distal aortic arch, and an anatomy extruded along the normal of segmented anatomical boundary. Hemodynamic parameters both instantaneous and time-averaged such as Wall Shear Stress (WSS), and Oscillatory Shear Index (OSI) were derived and compared from high-fidelity CFD data., Results: While there were minor differences in flow and hemodynamics across the configurations examined, they were generally not significant within our region of interest i.e., the aortic root. The choice of extension type had a modest impact on TAV hemodynamics, especially in the vicinity of the TAV with variations observed in local flow patterns and parameters near the TAV. However, these differences were not substantial enough to cause significant deviations in the overall flow and hemodynamic characteristics., Conclusions: The results suggest that under the given configuration and boundary conditions, the type of outflow extension had a modest impact on hemodynamics proximal to the TAV. The findings contribute to a better understanding of flow dynamics in TAV configurations, providing insights for future studies in TAV-related experiments as well as numerical simulations. Additionally, they help mitigate the uncertainties associated with patient-specific geometries, offering increased flexibility in computational modeling., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Computer simulations of coronary fractional flow reserve (FFR) based on coronary imaging have emerged as an attractive alternative to invasive measurements. However, most methods are proprietary and employ non-physiological assumptions. Our aims were to develop and validate a physiologically realistic open-source simulation model for coronary flow, and to use this model to predict FFR based on intracoronary optical coherence tomography (OCT) data in individual patients. We included patients undergoing elective coronary angiography with angiographic borderline coronary stenosis. Invasive measurements of coronary hyperemic pressure and absolute flow and OCT imaging were performed. A computer model of coronary flow incorporating pulsatile flow and the effect of left ventricular contraction was developed and calibrated, and patient-specific flow simulation was performed. Forty-eight coronary arteries from 41 patients were included in the analysis. Average FFR was 0.79 ± 0.14, and 50% had FFR ≤ 0.80. Correlation between simulated and measured FFR was high (r = 0.83, p < 0.001). Average difference between simulated FFR and observed FFR in individual patients was - 0.009 ± 0.076. Overall diagnostic accuracy for simulated FFR ≤ 0.80 in predicting observed FFR ≤ 0.80 was 0.88 (0.75-0.95) with sensitivity 0.79 (0.58-0.93) and specificity 0.96 (0.79-1.00). The positive predictive value was 0.95 (0.75-1.00) and the negative predictive value was 0.82 (0.63-0.94). In conclusion, realistic simulations of whole-cycle coronary flow can be produced based on intracoronary OCT data with a new, computationally simple simulation model. Simulated FFR had moderate numerical agreement with observed FFR and a good diagnostic accuracy for predicting hemodynamic significance of coronary stenoses., (© 2024. The Author(s).)

Traditional medical imaging and biomechanical studies have challenges in analyzing the long-term evolution process of abdominal aortic aneurysm (AAA). The homogenized constrained mixture theory (HCMT) allows for quantitative analysis of the changes in the multidimensional morphology and composition of AAA. However, the accuracy of HCMT still requires further clinical verification. This study aims to establish a patient-specific AAA growth model based on HCMT, simulate the long-term growth and remodeling (G&R) process of AAA, and validate the feasibility and accuracy of the method using two additional AAA cases with five follow-up datasets. The media and adventitia layers of AAA were modeled as mixtures composed of elastin, collagen fibers, and smooth muscle cells (SMCs). The strain energy function was used to describe the continuous deposition and degradation effect of the mixture during the AAA evolution. Multiple sets of growth parameters were applied to finite element simulations, and the simulation results were compared with the follow-up data for gradually selecting the optimal growth parameters. Two additional AAA patients with different growth rates were used for validating this method, the optimal growth parameters were obtained using the first two follow-up imaging data, and the growth model was applied to simulate the subsequent four time points. The differences between the simulated diameters and the follow-up diameters of AAA were compared to validate the accuracy of the mechanistic model. The growth parameters, especially the stress-mediated substance deposition gain factor, are highly related to the AAA G&R process. When setting the optimal growth parameters to simulate AAA growth, the proportion of simulation results within the distance of less than 0.5 mm from the baseline models is above 80%. For the validating cases, the mean difference rates between the simulated diameter and the real-world diameter are within 2.5%, which basically meets the clinical demand for quantitatively predicting the AAA growth in maximum diameters. This study simulated the growth process of AAA, and validated the accuracy of this mechanistic model. This method was proved to be used to predict the G&R process of AAA caused by dynamic changes in the mixtures of the AAA vessel wall during long-term, assisting accurately and quantitatively predicting the multidimensional morphological development and mixtures evolution process of AAA in the clinic., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A data-driven reduced order model (ROM) based on a proper orthogonal decomposition-radial basis function (POD-RBF) approach is adopted in this paper for the analysis of blood flow dynamics in a patient-specific case of atrial fibrillation (AF). The full order model (FOM) is represented by incompressible Navier-Stokes equations, discretized with a finite volume (FV) approach. Both the Newtonian and the Casson's constitutive laws are employed. The aim is to build a computational tool able to efficiently and accurately reconstruct the patterns of relevant hemodynamics indices related to the stasis of the blood in a physical parametrization framework including the cardiac output in the Newtonian case and also the plasma viscosity and the hematocrit in the non-Newtonian one. Many FOM-ROM comparisons are shown to analyze the performance of our approach as regards errors and computational speed-up., (© 2024. The Author(s).)

Finite Element simulations are a robust way of investigating cardiac biomechanics. To date, it has only been performed with the left ventricle (LV) alone for fetal hearts, even though results are likely different with biventricular (BiV) simulations. In this research, we conduct BiV simulations of the fetal heart based on 4D echocardiography images to show that it can capture the biomechanics of the normal healthy fetal heart, as well as those of fetal aortic stenosis better than the LV alone simulations. We found that performing LV alone simulations resulted in overestimation of LV stresses and pressures, compared to BiV simulations. Interestingly, inserting a compliance between the LV and right ventricle (RV) in the lumped parameter model of the LV only simulation effectively resolved these overestimations, demonstrating that the septum could be considered to play a LV-RV pressure communication role. However, stresses and strains spatial patterns remained altered from BiV simulations after the addition of the compliance. The BiV simulations corroborated previous studies in showing disease effects on the LV, where fetal aortic stenosis (AS) drastically elevated LV pressures and reduced strains and stroke volumes, which were moderated down with the addition of mitral regurgitation (MR). However, BiV simulations enabled an evaluation of the RV as well, where we observed that effects of the AS and MR on pressures and stroke volumes were generally much smaller and less consistent. The BiV simulations also enabled investigations of septal dynamics, which showed a rightward shift with AS, and partial restoration with MR. Interestingly, AS tended to enhance RV stroke volume, but MR moderated that down., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: In-vitro modelling can be used to investigate haemodynamics of arterial geometry and stent implants. However, in-vitro model fidelity relies on precise matching of in-vivo conditions. In pulsatile flow, velocity distribution and wall shear stress depend on compliance, and the Reynolds and Womersley numbers. However, matching such values may lead to unachievable tolerances in phantom fabrication., Methods: Published Reynolds and Womersley numbers for 14 major arteries in the human body were determined via a literature search. Preference was given to in-vivo publications but in-vitro and in-silico values were presented when in-vivo values were not found. Subsequently ascending aorta and carotid artery case studies were presented to highlight the limitations dynamic matching would apply to phantom fabrication., Results: Seven studies reported the in-vivo Reynolds and Womersley numbers for the aorta and two for the carotid artery. However, only one study each reported in-vivo numbers for the remaining ten arteries. No in-vivo data could be found for the femoral, superior mesenteric and renal arteries. Thus, information derived in-vitro and in-silico were provided instead. The ascending aorta and carotid artery models required scaling to 1.5× and 3× life-scale, respectively, to achieve dimensional tolerance restrictions. Modelling the ascending aorta with the comparatively high viscosity water/glycerine solution will lead to high pump power demands. However, all the working fluids considered could be dynamically matched with low pump demand for the carotid model., Conclusion: This paper compiles available human haemodynamic information, and highlights the paucity of information for some arteries. It also provides a method for optimal in-vitro experimental configuration., (© 2024. The Author(s).)

The vast majority of heart attacks occur when vulnerable plaques rupture, releasing their lipid content into the blood stream leading to thrombus formation and blockage of a coronary artery. Detection of these unstable plaques before they rupture remains a challenge. Hemodynamic features including wall shear stress (WSS) and wall shear stress gradient (WSSG) near the vulnerable plaque and local inflammation are known to affect plaque instability. In this work, a computational workflow has been developed to enable a comprehensive parametric study detailing the effects of 3D plaque shape on local hemodynamics and their implications for plaque instability. Parameterized geometric 3D plaque models are created within a patient-specific coronary artery tree using a NURBS (non-uniform rational B-splines)-based vascular modeling pipeline. Realistic blood flow features are simulated by using a Navier-Stokes solver within an isogeometric finite-element analysis framework. Near wall hemodynamic quantities such as WSS and WSSG are quantified, and vascular distribution of an inflammatory marker (VCAM-1) is estimated. Results show that proximally skewed eccentric plaques have the most vulnerable combination of high WSS and high positive spatial WSSG, and the presence of multiple lesions increases risk of rupture. The computational tool developed in this work, in conjunction with clinical data, -could help identify surrogate markers of plaque instability, potentially leading to a noninvasive clinical procedure for the detection of vulnerable plaques before rupture., (© 2024. The Author(s).)

Purposr: This study created 3D CFD models of the Norwood procedure for hypoplastic left heart syndrome (HLHS) using standard angiography and echocardiogram data to investigate the impact of shunt characteristics on pulmonary artery (PA) hemodynamics. Leveraging routine clinical data offers advantages such as availability and cost-effectiveness without subjecting patients to additional invasive procedures., Methods: Patient-specific geometries of the intrathoracic arteries of two Norwood patients were generated from biplane cineangiograms. "Virtual surgery" was then performed to simulate the hemodynamics of alternative PA shunt configurations, including shunt type (modified Blalock-Thomas-Taussig shunt (mBTTS) vs. right ventricle-to-pulmonary artery shunt (RVPAS)), shunt diameter, and pulmonary artery anastomosis angle. Left-right pulmonary flow differential, Q p /Q s , time-averaged wall shear stress (TAWSS), and oscillatory shear index (OSI) were evaluated., Results: There was strong agreement between clinically measured data and CFD model output throughout the patient-specific models. Geometries with a RVPAS tended toward more balanced left-right pulmonary flow, lower Q p /Q s , and greater TAWSS and OSI than models with a mBTTS. For both shunt types, larger shunts resulted in a higher Q p /Q s and higher TAWSS, with minimal effect on OSI. Low TAWSS areas correlated with regions of low flow and changing the PA-shunt anastomosis angle to face toward low TAWSS regions increased TAWSS., Conclusion: Excellent correlation between clinically measured and CFD model data shows that 3D CFD models of HLHS Norwood can be developed using standard angiography and echocardiographic data. The CFD analysis also revealed consistent changes in PA TAWSS, flow differential, and OSI as a function of shunt characteristics., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Vascular tone regulation is a crucial aspect of cardiovascular physiology, with significant implications for overall cardiovascular health. However, the precise physiological mechanisms governing smooth muscle cell contraction and relaxation remain uncertain. The complexity of vascular tone regulation stems from its multiscale and multifactorial nature, involving global hemodynamics, local flow conditions, tissue mechanics, and biochemical pathways. Bridging this knowledge gap and translating it into clinical practice presents a challenge. In this paper, a computational model is presented to integrate chemo-mechano-biological pathways with cardiovascular biomechanics, aiming to unravel the intricacies of vascular tone regulation. The computational framework combines an algebraic description of global hemodynamics with detailed finite element analyses at the scale of vascular segments for describing their passive and active mechanical response, as well as the molecular transport problem linked with chemo-biological pathways triggered by wall shear stresses. Their coupling is accounted for by considering a two-way interaction. Specifically, the focus is on the role of nitric oxide-related molecular pathways, which play a critical role in modulating smooth muscle contraction and relaxation to maintain vascular tone. The computational framework is employed to examine the interplay between localized alterations in the biomechanical response of a specific vessel segment-such as those induced by calcifications or endothelial dysfunction-and the broader global hemodynamic conditions-both under basal and altered states. The proposed approach aims to advance our understanding of vascular tone regulation and its impact on cardiovascular health. By incorporating chemo-mechano-biological mechanisms into in silico models, this study allows us to investigate cardiovascular responses to multifactorial stimuli and incorporate the role of adaptive homeostasis in computational biomechanics frameworks., (© 2024. The Author(s).)

Aortic dissection, a critical cardiovascular condition with life-threatening implications, is distinguished by the development of a tear and its propagation within the aortic wall. A thorough understanding of the initiation and progression of these tears, or cracks, is essential for accurate diagnosis and effective treatment. This paper undertakes a fracture mechanics approach to delve into the mechanics of tear propagation in aortic dissection. Our objective is to elucidate the impact of geometric and material parameters, providing valuable insights into the determinants of this pivotal cardiovascular event. Through our investigation, we have gained an understanding of how various parameters influence the energy release rate for tear propagation in both longitudinal and circumferential directions, aligning our findings with clinical data., (© 2024. The Author(s).)

Atherosclerotic plaques are fatty deposits that form in the walls of major arteries and are one of the major causes of heart attacks and strokes. Macrophages are the main immune cells in plaques and macrophage dynamics influence whether plaques grow or regress. Macrophage proliferation is a key process in atherosclerosis, particularly in the development of mid-stage plaques, but very few mathematical models include proliferation. In this paper we reframe the lipid-structured model of Ford et al. (J Theor Biol 479:48-63, 2019. https://doi.org/10.1016/j.jtbi.2019.07.003 ) to account for macrophage proliferation. Proliferation is modelled as a non-local decrease in the lipid structural variable. Steady state analysis indicates that proliferation assists in reducing eventual necrotic core lipid content and spreads the lipid load of the macrophage population amongst the cells. The contribution of plaque macrophages from proliferation relative to recruitment from the bloodstream is also examined. The model suggests that a more proliferative plaque differs from an equivalent (defined as having the same lipid content and cell numbers) recruitment-dominant plaque in the way lipid is distributed amongst the macrophages. The macrophage lipid distribution of an equivalent proliferation-dominant plaque is less skewed and exhibits a local maximum near the endogenous lipid content., (© 2024. The Author(s).)

Coronary artery calcification is a significant predictor of cardiovascular disease, with current detection methods like Agatston scoring having limitations in sensitivity. This study aimed to evaluate the effectiveness of a novel CAC quantification method using dual-energy material decomposition, particularly its ability to detect low-density calcium and microcalcifications. A simulation study was conducted comparing the dual-energy material decomposition technique against the established Agatston scoring method and the newer volume fraction calcium mass technique. Detection accuracy and calcium mass measurement were the primary evaluation metrics. The dual-energy material decomposition technique demonstrated fewer false negatives than both Agatston scoring and volume fraction calcium mass, indicating higher sensitivity. In low-density phantom measurements, material decomposition resulted in only 7.41% false-negative (CAC = 0) measurements compared to 83.95% for Agatston scoring. For high-density phantoms, false negatives were removed (0.0%) compared to 20.99% in Agatston scoring. The dual-energy material decomposition technique presents a more sensitive and reliable method for CAC quantification., (© 2024. The Author(s).)

Purpose: Aortic dissection is associated with a high mortality rate. Although computational approaches have shed light on many aspects of the disease, a sensitivity analysis is required to determine the significance of different factors. Because of its complex geometry and high computational expense, the three-dimensional (3D) fluid-structure interaction (FSI) simulation is not a suitable approach for sensitivity analysis., Methods: We performed a Monte Carlo simulation (MCS) to investigate the sensitivity of hemodynamic quantities to the lumped parameters of our zero-dimensional (0D) model with numerically calculated lumped parameters. We performed local and global analyses on the effect of the model parameters on important hemodynamic quantities., Results: The MCS showed that a larger lumped resistance value for the false lumen and the tears result in a higher retrograde flow rate in the false lumen (the coefficient of variation, c v , i = 0.0183 , the sensitivity S X i σ = 0.54 , Spearman's coefficient, ρ s = 0.464 ). For the intraluminal pressure, our results show a significant role in the resistance and inertance of the true lumen (the coefficient of variation, c v , i = 0.0640 , the sensitivity S X i σ = 0.85 , and Spearman's coefficient, ρ s = 0.855 for the inertance of the true lumen)., Conclusion: This study highlights the necessity of comparing the results of the local and global sensitivity analyses to understand the significance of multiple lumped parameters. Because of the efficiency of the method, our approach is potentially useful to investigate and analyze medical planning., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)

In vitro modeling of the left heart relies on accurately replicating the physiological conditions of the native heart. The targeted physiological conditions include the complex fluid dynamics coming along with the opening and closing of the aortic and mitral valves. As the mitral valve possess a highly sophisticated apparatus, thence, accurately modeling it remained a missing piece in the perfect heart duplicator puzzle. In this study, we explore using a hydrogel-based mitral valve that offers a full representation of the mitral valve apparatus. The valve is tested using a custom-made mock circulatory loop to replicate the left heart. The flow analysis includes performing particle image velocimetry measurements in both left atrium and ventricle. The results showed the ability of the new mitral valve to replicate the real interventricular and atrial flow patterns during the whole cardiac cycle. Moreover, the investigated valve has a ventricular vortex formation time of 5.2, while the peak e- and a-wave ventricular velocities was 0.9 m/s and 0.4 m/s respectively., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)

The common carotid artery (CCA) is an accessible and informative site for assessing cardiovascular function which makes it a prime candidate for clinically relevant computational modelling. The interpretation of supplemental information possible through modelling is encumbered by measurement uncertainty and population variability in model parameters. The distribution of model parameters likely depends on the specific sub-population of interest and delineation based on sex, age or health status may correspond to distinct ranges of typical parameter values. To assess this impact in a 1D-CCA-model, we delineated specific sub-populations based on age, sex and health status and carried out uncertainty quantification and sensitivity analysis for each sub-population. We performed a structured literature review to characterize sub-population-specific variabilities for eight model parameters without consideration of health status; variations for a healthy sub-populations were based on previously established references values. The variabilities of diameter and distensibility found in the literature review differed from those previously established in a healthy population. Model diameter change and pulse pressure were most sensitive to variations in distensibility, while pressure was most sensitive to resistance in the Windkessel model for all groups. Uncertainties were lower when variabilities were based on a healthy sub-population; however, the qualitative distribution of sensitivity indices was largely similar between the healthy and general population. Average sensitivity of the pressure waveform showed a moderate dependence on age with decreasing sensitivity to distal resistance and increasing sensitivity to distensibility and diameter. The female population was less sensitive to variations in diameter but more sensitive to distensibility coefficient than the male population. Overall, as hypothesized input variabilities differed between sub-populations and resulted in distinct uncertainties and sensitivities of the 1D-CCA-model outputs, particularly over age for the pressure waveform and between males and females for pulse pressure., (© 2024. The Author(s).)

In silico simulations can be used to evaluate and optimize the safety, quality, efficacy and applicability of medical devices. Furthermore, in silico modeling is a powerful tool in therapy planning to optimally tailor treatment for each patient. For this purpose, a workflow to perform fast preoperative risk assessment of paravalvular leakage (PVL) after transcatheter aortic valve replacement (TAVR) is presented in this paper. To this end, a novel, efficient method is introduced to calculate the regurgitant volume in a simplified, but sufficiently accurate manner. A proof of concept of the method is obtained by comparison of the calculated results with results obtained from in vitro experiments. Furthermore, computational fluid dynamics (CFD) simulations are used to validate more complex stenosis scenarios. Comparing the simplified leakage model to CFD simulations reveals its potential for procedure planning and qualitative preoperative risk assessment of PVL. Finally, a 3D device deployment model and the efficient leakage model are combined to showcase the application of the presented leakage model, by studying the effect of stent size and the degree of stenosis on the regurgitant volume. The presented leakage model is also used to visualize the leakage path. To generalize the leakage model to a wide range of clinical applications, further validation on a large cohort of patients is needed to validate the accuracy of the model's prediction under various patient-specific conditions., (© 2024. The Author(s).)

Introduction: Compliance mismatch between the aortic wall and Dacron Grafts is a clinical problem concerning aortic haemodynamics and morphological degeneration. The aortic stiffness introduced by grafts can lead to an increased left ventricular (LV) afterload. This study quantifies the impact of compliance mismatch by virtually testing different Type-B aortic dissection (TBAD) surgical grafting strategies in patient-specific, compliant computational fluid dynamics (CFD) simulations., Materials and Methods: A post-operative case of TBAD was segmented from computed tomography angiography data. Three virtual surgeries were generated using different grafts; two additional cases with compliant grafts were assessed. Compliant CFD simulations were performed using a patient-specific inlet flow rate and three-element Windkessel outlet boundary conditions informed by 2D-Flow MRI data. The wall compliance was calibrated using Cine-MRI images. Pressure, wall shear stress (WSS) indices and energy loss (EL) were computed., Results: Increased aortic stiffness and longer grafts increased aortic pressure and EL. Implementing a compliant graft matching the aortic compliance of the patient reduced the pulse pressure by 11% and EL by 4%. The endothelial cell activation potential (ECAP) differed the most within the aneurysm, where the maximum percentage difference between the reference case and the mid (MDA) and complete (CDA) descending aorta replacements increased by 16% and 20%, respectively., Conclusion: This study suggests that by minimising graft length and matching its compliance to the native aorta whilst aligning with surgical requirements, the risk of LV hypertrophy may be reduced. This provides evidence that compliance-matching grafts may enhance patient outcomes., (© 2024. The Author(s).)

Introduction: Fractional Flow Reserve (FFR) is used to characterize the functional significance of coronary artery stenoses. FFR is assessed under hyperemic conditions by invasive measurements of trans-stenotic pressure thanks to the insertion of a pressure guidewire across the coronary stenosis during catheterization. In order to overcome the potential risk related to the invasive procedure and to reduce the associated high costs, three-dimensional blood flow simulations that incorporate clinical imaging and patient-specific characteristics have been proposed., Purpose: Most CCTA-derived FFR models neglect the potential influence of the guidewire on computed flow and pressure. Here we aim to quantify the impact of taking into account the presence of the guidewire in model-based FFR prediction., Methods: We adopt a CCTA-derived FFR model and perform simulations with and without the guidewire for 18 patients with suspected stable CAD., Results: Presented results show that the presence of the guidewire leads to a tendency to predict a lower FFR value. The FFR reduction is prominent in cases of severe stenoses, while the influence of the guidewire is less pronounced in cases of moderate stenoses., Conclusion: From a clinical decision-making point of view, including of the pressure guidewire is potentially relevant only for intermediate stenosis cases., (© 2024. The Author(s).)

Central to the clinical adoption of patient-specific modeling strategies is demonstrating that simulation results are reliable and safe. Indeed, simulation frameworks must be robust to uncertainty in model input(s), and levels of confidence should accompany results. In this study, we applied a coupled uncertainty quantification-finite element (FE) framework to understand the impact of uncertainty in vascular material properties on variability in predicted stresses. Univariate probability distributions were fit to material parameters derived from layer-specific mechanical behavior testing of human coronary tissue. Parameters were assumed to be probabilistically independent, allowing for efficient parameter ensemble sampling. In an idealized coronary artery geometry, a forward FE model for each parameter ensemble was created to predict tissue stresses under physiologic loading. An emulator was constructed within the UncertainSCI software using polynomial chaos techniques, and statistics and sensitivities were directly computed. Results demonstrated that material parameter uncertainty propagates to variability in predicted stresses across the vessel wall, with the largest dispersions in stress within the adventitial layer. Variability in stress was most sensitive to uncertainties in the anisotropic component of the strain energy function. Moreover, unary and binary interactions within the adventitial layer were the main contributors to stress variance, and the leading factor in stress variability was uncertainty in the stress-like material parameter that describes the contribution of the embedded fibers to the overall artery stiffness. Results from a patient-specific coronary model confirmed many of these findings. Collectively, these data highlight the impact of material property variation on uncertainty in predicted artery stresses and present a pipeline to explore and characterize forward model uncertainty in computational biomechanics., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: This study introduces an algorithm specifically designed for processing unprocessed 12-lead electrocardiogram (ECG) data, with the primary aim of detecting cardiac abnormalities., Methods: The proposed model integrates Diagonal State Space Sequence (S4D) model into its architecture, leveraging its effectiveness in capturing dynamics within time-series data. The S4D model is designed with stacked S4D layers for processing raw input data and a simplified decoder using a dense layer for predicting abnormality types. Experimental optimization determines the optimal number of S4D layers, striking a balance between computational efficiency and predictive performance. This comprehensive approach ensures the model's suitability for real-time processing on hardware devices with limited capabilities, offering a streamlined yet effective solution for heart monitoring., Results: Among the notable features of this algorithm is its strong resilience to noise, enabling the algorithm to achieve an average F1-score of 81.2% and an AUROC of 95.5% in generalization. The model underwent testing specifically on the lead II ECG signal, exhibiting consistent performance with an F1-score of 79.5% and an AUROC of 95.7%., Conclusion: It is characterized by the elimination of pre-processing features and the availability of a low-complexity architecture that makes it suitable for implementation on numerous computing devices because it is easily implementable. Consequently, this algorithm exhibits considerable potential for practical applications in analyzing real-world ECG data. This model can be placed on the cloud for diagnosis. The model was also tested on lead II of the ECG alone and has demonstrated promising results, supporting its potential for on-device application., (© 2024. The Author(s).)

Conduction system pacing (CSP) has the potential to achieve physiological-paced activation by pacing the ventricular conduction system. Before CSP is adopted in standard clinical practice, large, randomised, and multi-centre trials are required to investigate CSP safety and efficacy compared to standard biventricular pacing (BVP). Furthermore, there are unanswered questions about pacing thresholds required to achieve optimal pacing delivery while preventing device battery draining, and about which patient groups are more likely to benefit from CSP rather than BVP. In silico studies have been increasingly used to investigate mechanisms underlying changes in cardiac function in response to pathologies and treatment. In the context of CSP, they have been used to improve our understanding of conduction system capture to optimise CSP delivery and battery life, and noninvasively compare different pacing methods on different patient groups. In this review, we discuss the in silico studies published to date investigating different aspects of CSP delivery., (© 2023. The Author(s).)

Background: Nutcracker syndrome is a disease characterized by complex symptoms, making its diagnosis challenging and often delayed, often resulting in a painful experience for the patients., Objective: This study aimed to investigate the pathogenesis of nutcracker syndrome through the perspective of hemodynamics by simulating blood flow with varying compression degrees of the left renal vein., Methods: 3D patient-specific vascular models of the abdominal aorta, superior mesenteric artery and left renal vein were constructed based on CT images of patients suspected of having nutcracker syndrome. A hemodynamic simulation was then conducted using computational fluid dynamics to identify the correlation between alterations in hemodynamic parameters and varying degrees of compression., Results: The study indicated the presence of an evident gradient in velocity distribution over the left renal vein with relatively high degrees of stenosis (α ≤ 50°), with maximum velocity in the central region of the stenosis. Additionally, when the compression degree of the left renal vein increases, the pressure distribution of the left renal vein presents an increasing number of gradient layers. Furthermore, the wall shear stress shows a correlation with the variation of blood flow velocity, i.e., the increase of wall shear stress correlates with the acceleration of the blood flow velocity., Conclusions: Using computational fluid dynamics as a non-invasive instrument to obtain the hemodynamic characteristics of nutcracker syndrome is feasible and could provide insights into the pathological mechanisms of the nutcracker syndrome supporting clinicians in diagnosis., (© 2024. The Author(s) under exclusive licence to Italian Society of Nephrology.)