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Impaired cardiac function has been described as a frequent complication of COVID-19-related pneumonia. To investigate possible underlying mechanisms, we represented the cardiovascular system by means of a lumped-parameter 0D mathematical model. The model was calibrated using clinical data, recorded in 58 patients hospitalized for COVID-19-related pneumonia, to make it patient-specific and to compute model outputs of clinical interest related to the cardiocirculatory system. We assessed, for each patient with a successful calibration, the statistical reliability of model outputs estimating the uncertainty intervals. Then, we performed a statistical analysis to compare healthy ranges and mean values (over patients) of reliable model outputs to determine which were significantly altered in COVID-19-related pneumonia. Our results showed significant increases in right ventricular systolic pressure, diastolic and mean pulmonary arterial pressure, and capillary wedge pressure. Instead, physical quantities related to the systemic circulation were not significantly altered. Remarkably, statistical analyses made on raw clinical data, without the support of a mathematical model, were unable to detect the effects of COVID-19-related pneumonia in pulmonary circulation, thus suggesting that the use of a calibrated 0D mathematical model to describe the cardiocirculatory system is an effective tool to investigate the impairments of the cardiocirculatory system associated with COVID-19. [ABSTRACT FROM AUTHOR]

The aim of this paper is to introduce a new mathematical model that simulates myocardial blood perfusion that accounts for multiscale and multiphysics features. Our model incorporates cardiac electrophysiology, active and passive mechanics, hemodynamics, valve modeling, and a multicompartment Darcy model of perfusion. We consider a fully coupled electromechanical model of the left heart that provides input for a fully coupled Navier–Stokes–Darcy model for myocardial perfusion. The fluid dynamics problem is modeled in a left heart geometry that includes large epicardial coronaries, while the multicompartment Darcy model is set in a biventricular myocardium. Using a realistic and detailed cardiac geometry, our simulations demonstrate the biophysical fidelity of our model in describing cardiac perfusion. Specifically, we successfully validate the model reliability by comparing in-silico coronary flow rates and average myocardial blood flow with clinically established values ranges reported in relevant literature. Additionally, we investigate the impact of a regurgitant aortic valve on myocardial perfusion, and our results indicate a reduction in myocardial perfusion due to blood flow taken away by the left ventricle during diastole. To the best of our knowledge, our work represents the first instance where electromechanics, hemodynamics, and perfusion are integrated into a single computational framework. [ABSTRACT FROM AUTHOR]

The aim of this paper is to introduce a new mathematical model that simulates myocardial blood perfusion that accounts for multiscale and multiphysics features. Our model incorporates cardiac electrophysiology, active and passive mechanics, hemodynamics, valve modeling, and a multicompartment Darcy model of perfusion. We consider a fully coupled electromechanical model of the left heart that provides input for a fully coupled Navier–Stokes–Darcy Model for myocardial perfusion. The fluid dynamics problem is modeled in a left heart geometry that includes large epicardial coronaries, while the multicompartment Darcy model is set in a biventricular myocardium. Using a realistic and detailed cardiac geometry, our simulations demonstrate the biophysical fidelity of our model in describing cardiac perfusion. Specifically, we successfully validate the model reliability by comparing in-silico coronary flow rates and average myocardial blood flow with clinically established values ranges reported in relevant literature. Additionally, we investigate the impact of a regurgitant aortic valve on myocardial perfusion, and our results indicate a reduction in myocardial perfusion due to blood flow taken away by the left ventricle during diastole. To the best of our knowledge, our work represents the first instance where electromechanics, hemodynamics, and perfusion are integrated into a single computational framework. [ABSTRACT FROM AUTHOR]

This work dealt with the assessment of a computational tool to estimate the electrical activation in the left ventricle focusing on the latest electrically activated segment (LEAS) in patients with left bundle branch block and possible myocardial fibrosis. We considered the Eikonal-diffusion equation and to recover the electrical activation maps in the myocardium. The model was calibrated by using activation times acquired in the coronary sinus (CS) branches or in the CS solely with an electroanatomic mapping system (EAMS) during cardiac resynchronization therapy (CRT). We applied our computational tool to ten patients founding an excellent accordance with EAMS measures; in particular, the error for LEAS location was less than 4 mm. We also calibrated our model using only information in the CS, still obtaining an excellent agreement with the measured LEAS. The proposed tool was able to accurately reproduce the electrical activation maps and in particular LEAS location in the CS branches, with an almost real-time computational effort, regardless of the presence of myocardial fibrosis, even when information only at CS was used to calibrate the model. This could be useful in the clinical practice since LEAS is often used as a target site for the left lead placement during CRT. Overall picture of the computational pipeline for the estimation of LEAS. [ABSTRACT FROM AUTHOR]

Purpose: Quantification of myocardial blood flow (MBF) and functional assessment of coronary artery disease (CAD) can be achieved through stress myocardial computed tomography perfusion (stress-CTP). This requires an additional scan after the resting coronary computed tomography angiography (cCTA) and administration of an intravenous stressor. This complex protocol has limited reproducibility and non-negligible side effects for the patient. We aim to mitigate these drawbacks by proposing a computational model able to reproduce MBF maps. Methods: A computational perfusion model was used to reproduce MBF maps. The model parameters were estimated by using information from cCTA and MBF measured from stress-CTP (MBFCTP) maps. The relative error between the computational MBF under stress conditions (MBFCOMP) and MBFCTP was evaluated to assess the accuracy of the proposed computational model. Results: Applying our method to 9 patients (4 control subjects without ischemia vs 5 patients with myocardial ischemia), we found an excellent agreement between the values of MBFCOMP and MBFCTP. In all patients, the relative error was below 8% over all the myocardium, with an average-in-space value below 4%. Conclusion: The results of this pilot work demonstrate the accuracy and reliability of the proposed computational model in reproducing MBF under stress conditions. This consistency test is a preliminary step in the framework of a more ambitious project which is currently under investigation, i.e., the construction of a computational tool able to predict MBF avoiding the stress protocol and potential side effects while reducing radiation exposure. [ABSTRACT FROM AUTHOR]

In the current work, we present a descriptive fluid-structure interaction computational study of the end-to-side radio-cephalic arteriovenous fistula. This allows us to account for the different thicknesses and elastic properties of the radial artery and cephalic vein. The core of the work consists in simulating different arteriovenous fistula configurations obtained by virtually varying the anastomosis angle, i.e. the angle between the end of the cephalic vein and the side of the radial artery. Since the aim of the work is to understand the blood dynamics in the very first days after the surgical intervention, the radial artery is considered stiffer and thicker than the cephalic vein. Our results demonstrate that both the diameter of the cephalic vein and the anastomosis angle play a crucial role to obtain a blood dynamics without re-circulation regions that could prevent fistula failure. When an anastomosis angle close to the perpendicular direction with respect to the radial artery is combined with a large diameter of the cephalic vein, the recirculation regions and the low Wall Shear Stress (WSS) zones are reduced. Conversely, from a structural point of view, a low anastomosis angle with a large diameter of the cephalic vein reduces the mechanical stress acting on the vessel walls. • Fluid-structure interaction analysis for different configurations of the arteriovenous fistula. • Mismatch of the arterial and venous Young's moduli and different vessel thicknesses. • Real reconstruction of the shape of the anastomosis region. • The diameter of the cephalic vein drastically influences the hemodynamics. [ABSTRACT FROM AUTHOR]

We present a new model of human cardiac electromechanics for the left ventricle where electrophysiology is described by a Reaction–Eikonal model and which enables an off-line resolution of the reaction model, thus entailing a big saving of computational time. Subcellular dynamics is coupled with a model of tissue mechanics, which is in turn coupled with a Windkessel model for blood circulation. Our numerical results show that the proposed model is able to provide a physiological response to changes in certain variables (end-diastolic volume, total peripheral resistance, contractility). We also show that our model is able to reproduce with high accuracy and with a considerably lower computational time the results that we would obtain if the monodomain model should be used in place of the Eikonal model. [ABSTRACT FROM AUTHOR]

Pulmonary valve replacement (PVR) consists of substituting a patient's original valve with a prosthetic one, primarily addressing pulmonary valve insufficiency, which is crucially relevant in Tetralogy of Fallot repairment. While extensive clinical and computational literature on aortic and mitral valve replacements is available, PVR's post‐procedural haemodynamics in the pulmonary artery and the impact of prosthetic valve dynamics remain significantly understudied. Addressing this gap, we introduce a reduced Fluid–Structure Interaction (rFSI) model, applied for the first time to the pulmonary valve. This model couples a three‐dimensional computational representation of pulmonary artery haemodynamics with a one‐degree‐of‐freedom model to account for valve structural mechanics. Through this approach, we analyse patient‐specific haemodynamics pre and post PVR. Patient‐specific geometries, reconstructed from CT scans, are virtually equipped with a template valve geometry. Boundary conditions for the model are established using a lumped‐parameter model, fine‐tuned based on clinical patient data. Our model accurately reproduces patient‐specific haemodynamic changes across different scenarios: pre‐PVR, six months post‐PVR, and a follow‐up condition after a decade. It effectively demonstrates the impact of valve implantation on sustaining the diastolic pressure gradient across the valve. The numerical results indicate that our valve model is able to reproduce overall physiological and/or pathological conditions, as preliminary assessed on two different patients. This promising approach provides insights into post‐PVR haemodynamics and prosthetic valve effects, shedding light on potential implications for patient‐specific outcomes. [ABSTRACT FROM AUTHOR]

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

Transcatheter aortic valve implantation (TAVI) is a minimally invasive intervention for the treatment of severe aortic valve stenosis. The main cause of failure is the structural deterioration of the implanted prosthetic leaflets, possibly inducing a valvular re‐stenosis 5–10 years after the implantation. Based solely on pre‐implantation data, the aim of this work is to identify fluid‐dynamics and structural indices that may predict the possible valvular deterioration, in order to assist the clinicians in the decision‐making phase and in the intervention design. Patient‐specific, pre‐implantation geometries of the aortic root, the ascending aorta, and the native valvular calcifications were reconstructed from computed tomography images. The stent of the prosthesis was modeled as a hollow cylinder and virtually implanted in the reconstructed domain. The fluid‐structure interaction between the blood flow, the stent, and the residual native tissue surrounding the prosthesis was simulated by a computational solver with suitable boundary conditions. Hemodynamical and structural indicators were analyzed for five different patients that underwent TAVI – three with prosthetic valve degeneration and two without degeneration – and the comparison of the results showed a correlation between the leaflets' structural degeneration and the wall shear stress distribution on the proximal aortic wall. This investigation represents a first step towards computational predictive analysis of TAVI degeneration, based on pre‐implantation data and without requiring additional peri‐operative or follow‐up information. Indeed, being able to identify patients more likely to experience degeneration after TAVI may help to schedule a patient‐specific timing of follow‐up. [ABSTRACT FROM AUTHOR]

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 dP/dtmax\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$dP/dt_{max}$$\end{document}, 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. [ABSTRACT FROM AUTHOR]

The importance of myocardial perfusion at the outset of cardiac disease remains largely understudied. To address this topic we present a mathematical model that considers the systemic circulation, the coronary vessels, the myocardium, and the interactions among these components. The core of the whole model is the description of the myocardium as a multicompartment poromechanics system. A novel decomposition of the poroelastic Helmholtz potential involved in the poromechanics model allows for a quasi-incompressible model that adequately describes the physical interaction among all components in the porous medium. We further provide a rigorous mathematical analysis that gives guidelines for the choice of the Helmholtz potential. To reduce the computational cost of our integrated model we propose decoupling the deformation of the tissue and systemic circulation from the porous flow in the myocardium and coronary vessels, which allows us to apply the model also in combination with precomputed cardiac displacements, obtained form other models or medical imaging data. We test the methodology through the simulation of a heartbeat in healthy conditions that replicates the systolic impediment phenomenon, which is particularly challenging to capture as it arises from the interaction of several parts of the model. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: We designed a retrospective computational study to evaluate the effects of hemodynamics on portal confluence remodeling in real models of patients with malignancies of the pancreatic head. Methods: Patient-specific models were created according to computed tomography data. Fluid dynamics was simulated by using finite-element methods. Computational results were compared to morphological findings. Results: Five patients underwent total pancreatectomy, one had duodenopancreatectomy. Vein resection was performed en-bloc with the specimen. Histopathological findings showed that in patients without a vein stenosis and a normal hemodynamics, the three-layered wall of the vein was preserved. In patients with a stenosis > 70% of vein diameter and modified hemodynamics, the three-layered structure of the resected vein was replaced by a dense inflammatory infiltrate in absence of tumor infiltration. Conclusions: The portal confluence involved by malignancies of the pancreatic head undergoes a remodeling that is not mainly due to a wall infiltration by the tumor but instead to a persistent pathological hemodynamics that disrupts the balance between eutrophic remodeling and degradative process of the vein wall that can lead to the complete upheaval of the three-layered vein wall. This finding can have useful surgical application in planning resection of the vein involved by tumor growth. [ABSTRACT FROM AUTHOR]

We present a loosely coupled scheme for the numerical simulation of the cardiac electro-fluid-structure interaction problem, whose solution is typically computationally intensive due to the need to suitably treat the coupling of the different submodels. Our scheme relies on a segregated treatment of the subproblems, in particular on an explicit Robin-Neumann algorithm for the fluid-structure interaction, aiming at reducing the computational burden of numerical simulations. The results, both in an ideal and a realistic cardiac setting, show that the proposed scheme is stable at the regimes typical of cardiac simulations. From a comparison with a scheme with implicit fluid-structure interaction, it emerges that, while conservation properties are not fully preserved, computational times significantly benefit from the explicit scheme. Overall, the explicit discretization represents a good trade-off between accuracy and cost, and is a valuable alternative to implicit schemes for fast large-scale simulations. • We present an explicit scheme for the simulation of cardiac electro-fluid-structure interaction. • The scheme uses Robin-Neumann fluid-structure interface conditions. • We analyze the stability, accuracy and efficiency of the explicit scheme. • The explicit scheme provides a compromise between accuracy and computational cost. [ABSTRACT FROM AUTHOR]

In this special issue, we collect some recent works in this field. In the recent years, there have been remarkable developments in the field of numerical simulations of the cardiovascular system. In particular, the works presented here cover both methodological and applicative issues in two fields of great interest, such as cardiac electrophysiology and hemodynamics. [Extracted from the article]

Two crucial factors for accurate numerical simulations of cardiac electromechanics, which are also essential to reproduce the synchronous activity of the heart, are: (i) accounting for the interaction between the heart and the circulatory system that determines pressures and volumes loads in the heart chambers; (ii) reconstructing the muscular fiber architecture that drives the electrophysiology signal and the myocardium contraction. In this work, we present a 3D biventricular electromechanical model coupled with a 0D closed-loop model of the whole cardiovascular system that addresses the two former crucial factors. With this aim, we introduce a boundary condition for the mechanical problem that accounts for the neglected part of the domain located on top of the biventricular basal plane and that is consistent with the principles of momentum and energy conservation. We also discuss in detail the coupling conditions behind the 3D and the 0D models. We perform electromechanical simulations in physiological conditions using the 3D–0D model and we show that our results match the experimental data of relevant mechanical biomarkers available in the literature. Furthermore, we investigate different arrangements in cross-fibers active contraction. We prove that an active tension along the sheet direction counteracts the myofiber contraction, while the one along the sheet-normal direction enhances the cardiac work. Finally, several myofiber architectures are analyzed. We show that a different fiber field in the septal area and in the transmural wall affects the pumping functionality of the left ventricle. • 3D electromechanical biventricular model coupled with a 0D hemodynamic closed-loop model. • A novel effective mechanical boundary condition for the biventricular basal plane. • Numerical results on a realistic biventricular model matching the experimental data. • Study of different configurations in cross-fibers active contraction. • Evaluation of the impact of different myofibers architectures on biventricular electromechanics. [ABSTRACT FROM AUTHOR]