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Reduced-order models allow for the simulation of blood flow in patient-specific vasculatures. They offer a significant reduction in computational cost and wait time compared to traditional computational fluid dynamics models. Unfortunately, due to the simplifications made in their formulations, reduced-order models can suffer from significantly reduced accuracy. One common simplifying assumption is that of continuity of static or total pressure over vascular bifurcations. In many cases, this assumption has been shown to introduce significant errors in pressure predictions. We propose a model to account for this pressure difference, with the ultimate goal of increasing the accuracy of cardiovascular reduced-order models. Our model successfully uses a structure common in existing reduced-order models in conjunction with machine-learning techniques to predict the pressure difference over a vascular bifurcation. We analyze the performance of our model on steady and transient flows, testing it on three bifurcation cohorts representing three different bifurcation geometric types. We find that our model makes significantly more accurate predictions than other models for approximating bifurcation pressure losses commonly used in the reduced-order cardiovascular modeling community. We also compare the efficacy of different machine-learning techniques and observe that a neural network performs most robustly. Additionally, we consider two different model modalities: one in which the model is fit using both steady and transient flows, and one in which it is optimized for performance in transient flows. We discuss the trade-off between the physical interpretability associated with the first option and the improved accuracy in transient flows associated with the latter option. We also demonstrate the model's ability to generalize by testing it on a combined dataset containing two different bifurcation types. This work marks a step towards improving the accuracy of cardiovascular reduced-order models, thereby increasing their utility for cardiovascular flow modeling., Competing Interests: Declaration of competing interest None Declared., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Equilibrated fluid-solid-growth (FSGe) is a fast, open source, three-dimensional (3D) computational platform for simulating interactions between instantaneous hemodynamics and long-term vessel wall adaptation through mechanobiologically equilibrated growth and remodeling (G&R). Such models can capture evolving geometry, composition, and material properties in health and disease and following clinical interventions. In traditional G&R models, this feedback is modeled through highly simplified fluid solutions, neglecting local variations in blood pressure and wall shear stress (WSS). FSGe overcomes these inherent limitations by strongly coupling the 3D Navier-Stokes equations for blood flow with a 3D equilibrated constrained mixture model (CMMe) for vascular tissue G&R. CMMe allows one to predict long-term evolved mechanobiological equilibria from an original homeostatic state at a computational cost equivalent to that of a standard hyperelastic material model. In illustrative computational examples, we focus on the development of a stable aortic aneurysm in a mouse model to highlight key differences in growth patterns between FSGe and solid-only G&R models. We show that FSGe is especially important in blood vessels with asymmetric stimuli. Simulation results reveal greater local variation in fluid-derived WSS than in intramural stress (IMS). Thus, differences between FSGe and G&R models became more pronounced with the growing influence of WSS relative to pressure. Future applications in highly localized disease processes, such as for lesion formation in atherosclerosis, can now include spatial and temporal variations of WSS., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

In the last decades, many computational models have been developed to predict soft tissue growth and remodeling (G&R). The constrained mixture theory describes fundamental mechanobiological processes in soft tissue G&R and has been widely adopted in cardiovascular models of G&R. However, even after two decades of work, large organ-scale models are rare, mainly due to high computational costs (model evaluation and memory consumption), especially in long-range simulations. We propose two strategies to adaptively integrate history variables in constrained mixture models to enable large organ-scale simulations of G&R. Both strategies exploit that the influence of deposited tissue on the current mixture decreases over time through degradation. One strategy is independent of external loading, allowing the estimation of the computational resources ahead of the simulation. The other adapts the history snapshots based on the local mechanobiological environment so that the additional integration errors can be controlled and kept negligibly small, even in G&R scenarios with severe perturbations. We analyze the adaptively integrated constrained mixture model on a tissue patch for a parameter study and show the performance under different G&R scenarios. To confirm that adaptive strategies enable large organ-scale examples, we show simulations of different hypertension conditions with a real-world example of a biventricular heart discretized with a finite element mesh. In our example, adaptive integrations sped up simulations by a factor of three and reduced memory requirements to one-sixth. The reduction of the computational costs gets even more pronounced for simulations over longer periods. Adaptive integration of the history variables allows studying more finely resolved models and longer G&R periods while computational costs are drastically reduced and largely constant in time., (© 2024 The Author(s). International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.)

Aortic dissection leads to late complications due to chronic degeneration and dilatation of the false lumen. However, the interaction between hemodynamics and microstructural remodeling driving long-term changes is not fully understood. This study examines the progression of a patient's aortic dissection, tracked from pre-dissection to the chronic phase using computed tomography angiography. Fluid-structure interaction models that account for tissue prestress, external support, and anisotropic properties were used to analyze hemodynamic markers. Each aortic wall layer had distinct thicknesses and material properties. The boundary conditions were guided by in vitro 4D-flow MRI and the patient's blood pressure. Quantitative measurements during routine clinical care showed that aortic dilatation was most significant distal to the left subclavian artery, reaching 6cm in the chronic phase. Simulations resulted in a flow jet velocity through the entry tear that peaked at 185cm/s in the subacute phase and decreased to 123 to 133 cm/s in the chronic phase, corresponding to an increased entry tear size. Flow jet impingement on the false lumen resulted in a localized pressure increase of 11 and 2mmHg in the subacute and chronic phases, with the wall shear stress reaching 4,Pa. These hemodynamic changes appear to be the main drivers of aortic growth and morphological changes. Despite moderate overall flap movement, in-plane displacement increased from 0.6 to 1.8mm as disease progressed, which was associated with an overall increase in aortic diameter. Additional simulations with a significant reduction in flap stiffness during the subacute phase resulted in increased flap motion up to 9.5mm. Although these results are based on a single patient, they suggest a strong relationship between hemodynamics and aortic growth.

In the last decades, many computational models have been developed to predict soft tissue growth and remodeling (G&R). The constrained mixture theory describes fundamental mechanobiological processes in soft tissue G&R and has been widely adopted in cardiovascular models of G&R. However, even after two decades of work, large organ-scale models are rare, mainly due to high computational costs (model evaluation and memory consumption), especially in long-range simulations. We propose two strategies to adaptively integrate history variables in constrained mixture models to enable large organ-scale simulations of G&R. Both strategies exploit that the influence of deposited tissue on the current mixture decreases over time through degradation. One strategy is independent of external loading, allowing the estimation of the computational resources ahead of the simulation. The other adapts the history snapshots based on the local mechanobiological environment so that the additional integration errors can be controlled and kept negligibly small, even in G&R scenarios with severe perturbations. We analyze the adaptively integrated constrained mixture model on a tissue patch for a parameter study and show the performance under different G&R scenarios. To confirm that adaptive strategies enable large organ-scale examples, we show simulations of different hypertension conditions with a real-world example of a biventricular heart discretized with a finite element mesh. In our example, adaptive integrations sped up simulations by a factor of three and reduced memory requirements to one-sixth. The reduction of the computational costs gets even more pronounced for simulations over longer periods. Adaptive integration of the history variables allows studying more finely resolved models and longer G&R periods while computational costs are drastically reduced and largely constant in time.

The substantial computational cost of high-fidelity models in numerical hemodynamics has, so far, relegated their use mainly to offline treatment planning. New breakthroughs in data-driven architectures and optimization techniques for fast surrogate modeling provide an exciting opportunity to overcome these limitations, enabling the use of such technology for time-critical decisions. We discuss an application to the repair of multiple stenosis in peripheral pulmonary artery disease through either transcatheter pulmonary artery rehabilitation or surgery, where it is of interest to achieve desired pressures and flows at specific locations in the pulmonary artery tree, while minimizing the risk for the patient. Since different degrees of success can be achieved in practice during treatment, we formulate the problem in probability, and solve it through a sample-based approach. We propose a new offline-online pipeline for probabilistic real-time treatment planning which combines offline assimilation of boundary conditions, model reduction, and training dataset generation with online estimation of marginal probabilities, possibly conditioned on the degree of augmentation observed in already repaired lesions. Moreover, we propose a new approach for the parametrization of arbitrarily shaped vascular repairs through iterative corrections of a zero-dimensional approximant. We demonstrate this pipeline for a diseased model of the pulmonary artery tree available through the Vascular Model Repository., (© 2024 John Wiley & Sons Ltd.)

Blood pressure gradient ( Δ P ) across an aortic coarctation (CoA) is an important measurement to diagnose CoA severity and gauge treatment efficacy. Invasive cardiac catheterization is currently the gold-standard method for measuring blood pressure. The objective of this study was to evaluate the accuracy of Δ P estimates derived non-invasively using patient-specific 0D and 3D deformable wall simulations. Medical imaging and routine clinical measurements were used to create patient-specific models of patients with CoA (N = 17). 0D simulations were performed first and used to tune boundary conditions and initialize 3D simulations. Δ P across the CoA estimated using both 0D and 3D simulations were compared to invasive catheter-based pressure measurements for validation. The 0D simulations were extremely efficient ( ∼ 15 s computation time) compared to 3D simulations ( ∼ 30 h computation time on a cluster). However, the 0D Δ P estimates, unsurprisingly, had larger mean errors when compared to catheterization than 3D estimates (12.1 ± 9.9 mmHg vs 5.3 ± 5.4 mmHg). In particular, the 0D model performance degraded in cases where the CoA was adjacent to a bifurcation. The 0D model classified patients with severe CoA requiring intervention (defined as Δ P ≥ 20 mmHg) with 76% accuracy and 3D simulations improved this to 88%. Overall, a combined approach, using 0D models to efficiently tune and launch 3D models, offers the best combination of speed and accuracy for non-invasive classification of CoA severity., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)

In numerical simulations of cardiac mechanics, coupling the heart to a model of the circulatory system is essential for capturing physiological cardiac behavior. A popular and efficient technique is to use an electrical circuit analogy, known as a lumped parameter network or zero-dimensional (0D) fluid model, to represent blood flow throughout the cardiovascular system. Due to the strong physical interaction between the heart and the blood circulation, developing accurate and efficient numerical coupling methods remains an active area of research. In this work, we present a modular framework for implicitly coupling three-dimensional (3D) finite element simulations of cardiac mechanics to 0D models of blood circulation. The framework is modular in that the circulation model can be modified independently of the 3D finite element solver, and vice versa. The numerical scheme builds upon a previous work that combines 3D blood flow models with 0D circulation models (3D fluid - 0D fluid). Here, we extend it to couple 3D cardiac tissue mechanics models with 0D circulation models (3D structure - 0D fluid), showing that both mathematical problems can be solved within a unified coupling scheme. The effectiveness, temporal convergence, and computational cost of the algorithm are assessed through multiple examples relevant to the cardiovascular modeling community. Importantly, in an idealized left ventricle example, we show that the coupled model yields physiological pressure-volume loops and naturally recapitulates the isovolumic contraction and relaxation phases of the cardiac cycle without any additional numerical techniques. Furthermore, we provide a new derivation of the scheme inspired by the Approximate Newton Method of Chan (1985), explaining how the proposed numerical scheme combines the stability of monolithic approaches with the modularity and flexibility of partitioned approaches., Competing Interests: Declaration of Interests The authors declare that they have no known competng fnancial interests or personal relatonships that could have appeared to infuence the work reported in this paper.

Reduced-order models based on physics are a popular choice in cardiovascular modeling due to their efficiency, but they may experience loss in accuracy when working with anatomies that contain numerous junctions or pathological conditions. We develop one-dimensional reduced-order models that simulate blood flow dynamics using a graph neural network trained on three-dimensional hemodynamic simulation data. Given the initial condition of the system, the network iteratively predicts the pressure and flow rate at the vessel centerline nodes. Our numerical results demonstrate the accuracy and generalizability of our method in physiological geometries comprising a variety of anatomies and boundary conditions. Our findings demonstrate that our approach can achieve errors below 3% for pressure and flow rate, provided there is adequate training data. As a result, our method exhibits superior performance compared to physics-based one-dimensional models while maintaining high efficiency at inference time., Competing Interests: Declaration of competing interest None declared., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

We implement full, three-dimensional constrained mixture theory for vascular growth and remodeling into a finite element fluid-structure interaction (FSI) solver. The resulting "fluid-solid-growth" (FSG) solver allows long term, patient-specific predictions of changing hemodynamics, vessel wall morphology, tissue composition, and material properties. This extension from short term (FSI) to long term (FSG) simulations increases clinical relevance by enabling mechanobioloigcally-dependent studies of disease progression in complex domains., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Cardiac growth and remodeling (G&R) patterns change ventricular size, shape, and function both globally and locally. Biomechanical, neurohormonal, and genetic stimuli drive these patterns through changes in myocyte dimension and fibrosis. We propose a novel microstructure-motivated model that predicts organ-scale G&R in the heart based on the homogenized constrained mixture theory. Previous models, based on the kinematic growth theory, reproduced consequences of G&R in bulk myocardial tissue by prescribing the direction and extent of growth but neglected underlying cellular mechanisms. In our model, the direction and extent of G&R emerge naturally from intra- and extracellular turnover processes in myocardial tissue constituents and their preferred homeostatic stretch state. We additionally propose a method to obtain a mechanobiologically equilibrated reference configuration. We test our model on an idealized 3D left ventricular geometry and demonstrate that our model aims to maintain tensional homeostasis in hypertension conditions. In a stability map, we identify regions of stable and unstable G&R from an identical parameter set with varying systolic pressures and growth factors. Furthermore, we show the extent of G&R reversal after returning the systolic pressure to baseline following stage 1 and 2 hypertension. A realistic model of organ-scale cardiac G&R has the potential to identify patients at risk of heart failure, enable personalized cardiac therapies, and facilitate the optimal design of medical devices., (© 2023. The Author(s).)

Physics-based computational models of the cardiovascular system are increasingly used to simulate hemodynamics, tissue mechanics, and physiology in evolving healthy and diseased states. While predictive models using computational fluid dynamics (CFD) originated primarily for use in surgical planning, their application now extends well beyond this purpose. In this review, we describe an increasingly wide range of modeling applications aimed at uncovering fundamental mechanisms of disease progression and development, performing model-guided design, and generating testable hypotheses to drive targeted experiments. Increasingly, models are incorporating multiple physical processes spanning a wide range of time and length scales in the heart and vasculature. With these expanded capabilities, clinical adoption of patient-specific modeling in congenital and acquired cardiovascular disease is also increasing, impacting clinical care and treatment decisions in complex congenital heart disease, coronary artery disease, vascular surgery, pulmonary artery disease, and medical device design. In support of these efforts, we discuss recent advances in modeling methodology, which are most impactful when driven by clinical needs. We describe pivotal recent developments in image processing, fluid-structure interaction, modeling under uncertainty, and reduced order modeling to enable simulations in clinically relevant timeframes. In all these areas, we argue that traditional CFD alone is insufficient to tackle increasingly complex clinical and biological problems across scales and systems. Rather, CFD should be coupled with appropriate multiscale biological, physical, and physiological models needed to produce comprehensive, impactful models of mechanobiological systems and complex clinical scenarios. With this perspective, we finally outline open problems and future challenges in the field., (© 2023 Author(s).)

We propose svMorph, a framework for interactive virtual sculpting of patient-specific vascular anatomic models. Our framework includes three tools for the creation of tortuosity, aneurysms, and stenoses in tubular vascular geometries. These shape edits are performed via geometric operations on the surface mesh and vessel centerline curves of the input model. The tortuosity tool also uses the physics-based Oriented Particles method, coupled with linear blend skinning, to achieve smooth, elastic-like deformations. Our tools can be applied separately or in combination to produce simulation-suitable morphed models. They are also compatible with popular vascular modeling software, such as simvascular. To illustrate our tools, we morph several image-based, patient-specific models to create a range of shape changes and simulate the resulting hemodynamics via three-dimensional, computational fluid dynamics. We also demonstrate the ability to quickly estimate the hemodynamic effects of the shape changes via the automated generation of associated zero-dimensional lumped-parameter models., (Copyright © 2023 by ASME.)

Three-dimensional (3D) cardiovascular fluid dynamics simulations typically require hours to days of computing time on a high-performance computing cluster. One-dimensional (1D) and lumped-parameter zero-dimensional (0D) models show great promise for accurately predicting blood bulk flow and pressure waveforms with only a fraction of the cost. They can also accelerate uncertainty quantification, optimization, and design parameterization studies. Despite several prior studies generating 1D and 0D models and comparing them to 3D solutions, these were typically limited to either 1D or 0D and a singular category of vascular anatomies. This work proposes a fully automated and openly available framework to generate and simulate 1D and 0D models from 3D patient-specific geometries, automatically detecting vessel junctions and stenosis segments. Our only input is the 3D geometry; we do not use any prior knowledge from 3D simulations. All computational tools presented in this work are implemented in the open-source software platform SimVascular. We demonstrate the reduced-order approximation quality against rigid-wall 3D solutions in a comprehensive comparison with N = 72 publicly available models from various anatomies, vessel types, and disease conditions. Relative average approximation errors of flows and pressures typically ranged from 1% to 10% for both 1D and 0D models, measured at the outlets of terminal vessel branches. In general, 0D model errors were only slightly higher than 1D model errors despite requiring only a third of the 1D runtime. Automatically generated ROMs can significantly speed up model development and shift the computational load from high-performance machines to personal computers., (© 2022 John Wiley & Sons Ltd.)

Collateral arteries bridge opposing artery branches, forming a natural bypass that can deliver blood flow downstream of an occlusion. Inducing coronary collateral arteries could treat cardiac ischemia, but more knowledge on their developmental mechanisms and functional capabilities is required. Here we used whole-organ imaging and three-dimensional computational fluid dynamics modeling to define spatial architecture and predict blood flow through collaterals in neonate and adult mouse hearts. Neonate collaterals were more numerous, larger in diameter and more effective at restoring blood flow. Decreased blood flow restoration in adults arose because during postnatal growth coronary arteries expanded by adding branches rather than increasing diameters, altering pressure distributions. In humans, adult hearts with total coronary occlusions averaged 2 large collaterals, with predicted moderate function, while normal fetal hearts showed over 40 collaterals, likely too small to be functionally relevant. Thus, we quantify the functional impact of collateral arteries during heart regeneration and repair-a critical step toward realizing their therapeutic potential., Competing Interests: Competing Interests Statement The authors declare no competing interests.

Three-dimensional cardiovascular fluid dynamics simulations typically require computation of several cardiac cycles before they reach a periodic solution, rendering them computationally expensive. Furthermore, there is currently no standardized method to determine whether a simulation has yet reached that periodic state. In this work, we propose the use of an asymptotic error measurement to quantify the difference between simulation results and their ideal periodic state using open-loop lumped-parameter modeling. We further show that initial conditions are crucial in reducing computational time and develop an automated framework to generate appropriate initial conditions from a one-dimensional model of blood flow. We demonstrate the performance of our initialization method using six patient-specific models from the Vascular Model Repository. In our examples, our initialization protocol achieves periodic convergence within one or two cardiac cycles, leading to a significant reduction in computational cost compared to standard methods. All computational tools used in this work are implemented in the open-source software platform SimVascular. Automatically generated initial conditions have the potential to significantly reduce computation time in cardiovascular fluid dynamics simulations., (© 2021. Biomedical Engineering Society.)

We are interested in a reduced order method for the efficient simulation of blood flow in arteries. The blood dynamics is modeled by means of the incompressible Navier-Stokes equations. Our algorithm is based on an approximated domain-decomposition of the target geometry into a number of subdomains obtained from the parametrized deformation of geometrical building blocks (e.g., straight tubes and model bifurcations). On each of these building blocks, we build a set of spectral functions by Proper Orthogonal Decomposition of a large number of snapshots of finite element solutions (offline phase). The global solution of the Navier-Stokes equations on a target geometry is then found by coupling linear combinations of these local basis functions by means of spectral Lagrange multipliers (online phase). Being that the number of reduced degrees of freedom is considerably smaller than their finite element counterpart, this approach allows us to significantly decrease the size of the linear system to be solved in each iteration of the Newton-Raphson algorithm. We achieve large speedups with respect to the full order simulation (in our numerical experiments, the gain is at least of one order of magnitude and grows inversely with respect to the reduced basis size), whilst still retaining satisfactory accuracy for most cardiovascular simulations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Predictive high-fidelity finite element simulations of human cardiac mechanics commonly require a large number of structural degrees of freedom. Additionally, these models are often coupled with lumped-parameter models of hemodynamics. High computational demands, however, slow down model calibration and therefore limit the use of cardiac simulations in clinical practice. As cardiac models rely on several patient-specific parameters, just one solution corresponding to one specific parameter set does not at all meet clinical demands. Moreover, while solving the nonlinear problem, 90% of the computation time is spent solving linear systems of equations. We propose to reduce the structural dimension of a monolithically coupled structure-Windkessel system by projection onto a lower-dimensional subspace. We obtain a good approximation of the displacement field as well as of key scalar cardiac outputs even with very few reduced degrees of freedom, while achieving considerable speedups. For subspace generation, we use proper orthogonal decomposition of displacement snapshots. Following a brief comparison of subspace interpolation methods, we demonstrate how projection-based model order reduction can be easily integrated into a gradient-based optimization. We demonstrate the performance of our method in a real-world multivariate inverse analysis scenario. Using the presented projection-based model order reduction approach can significantly speed up model personalization and could be used for many-query tasks in a clinical setting., (© 2020 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.)

Knowledge of appropriate local fiber architecture is necessary to simulate patient-specific electromechanics in the human heart. However, it is not yet possible to reliably measure in vivo fiber directions especially in human atria. Thus, we present a method that defines the fiber architecture in arbitrarily shaped atria using image registration and reorientation methods based on atlas atria with fibers predefined from detailed histological observations. Thereby, it is possible to generate detailed fiber families in every new patient-specific geometry in an automated, time-efficient process. We demonstrate the good performance of the image registration and fiber definition on 10 differently shaped human atria. Additionally, we show that characteristics of the electrophysiological activation pattern that appear in the atlas atria also appear in the patients' atria. We arrive to analogous conclusions for coupled electro-mechano-hemodynamical computations., (© 2019 The Authors International Journal for Numerical Methods in Biomedical Engineering Published by John Wiley & Sons Ltd.)

The human heart is enclosed in the pericardial cavity. The pericardium consists of a layered thin sac and is separated from the myocardium by a thin film of fluid. It provides a fixture in space and frictionless sliding of the myocardium. The influence of the pericardium is essential for predictive mechanical simulations of the heart. However, there is no consensus on physiologically correct and computationally tractable pericardial boundary conditions. Here, we propose to model the pericardial influence as a parallel spring and dashpot acting in normal direction to the epicardium. Using a four-chamber geometry, we compare a model with pericardial boundary conditions to a model with fixated apex. The influence of pericardial stiffness is demonstrated in a parametric study. Comparing simulation results to measurements from cine magnetic resonance imaging reveals that adding pericardial boundary conditions yields a better approximation with respect to atrioventricular plane displacement, atrial filling, and overall spatial approximation error. We demonstrate that this simple model of pericardial-myocardial interaction can correctly predict the pumping mechanisms of the heart as previously assessed in clinical studies. Utilizing a pericardial model not only can provide much more realistic cardiac mechanics simulations but also allows new insights into pericardial-myocardial interaction which cannot be assessed in clinical measurements yet.

Cardiac electrophysiology simulations are numerically challenging because of the propagation of a steep electrochemical wave front and thus require discretizations with small mesh sizes to obtain accurate results. In this work, we present an approach based on the hybridizable discontinuous Galerkin method (HDG), which allows an efficient implementation of high-order discretizations into a computational framework. In particular, using the advantage of the discontinuous function space, we present an efficient p-adaptive strategy for accurately tracking the wave front. The HDG allows to reduce the overall degrees of freedom in the final linear system to those only on the element interfaces. Additionally, we propose a rule for a suitable integration accuracy for the ionic current term depending on the polynomial order and the cell model to handle high-order polynomials. Our results show that for the same number of degrees of freedom, coarse high-order elements provide more accurate results than fine low-order elements. Introducing p-adaptivity further reduces computational costs while maintaining accuracy by restricting the use of high-order elements to resolve the wave front. For a patient-specific simulation of a cardiac cycle, p-adaptivity reduces the average number of degrees of freedom by 95% compared to the nonadaptive model. In addition to reducing computational costs, using coarse meshes with our p-adaptive high-order HDG method also simplifies practical aspects of mesh generation and postprocessing., (Copyright © 2018 John Wiley & Sons, Ltd.)

The aim of this study was to develop a computational framework to compare the impact of standard ablation concepts on the mechanical performance of the atria, since different line combinations cannot be applied in practice to the same patient. For this purpuse, we coupled electro-mechano-hemodynamic mathematical models based on biophysical principles and simulate the contractile performance of the atria. We computed systolic pressures and volumes in two patient-specific atrial geometries (one of normal size and one hypertrophied) with various ablation concepts. We found that our computational model is able to detect the differences in the left atrial contractility and ejection fraction for various electrical activation sequences resulting from different ablation line combinations. We show that multiphysics modeling has the potential to quantify the hemodynamic performance of left atria for different ablation lines, which could be used as additional pre-operative clinical information for the choice of the ablation concept in the future.

Progressive airflow obstruction is a classical hallmark of chronic lung disease, affecting more than one fourth of the adult population. As the disease progresses, the inner layer of the airway wall grows, folds inwards, and narrows the lumen. The critical failure conditions for airway folding have been studied intensely for idealized circular cross-sections. However, the role of airway branching during this process is unknown. Here, we show that the geometry of the bronchial tree plays a crucial role in chronic airway obstruction and that critical failure conditions vary significantly along a branching airway segment. We perform systematic parametric studies for varying airway cross-sections using a computational model for mucosal thickening based on the theory of finite growth. Our simulations indicate that smaller airways are at a higher risk of narrowing than larger airways and that regions away from a branch narrow more drastically than regions close to a branch. These results agree with clinical observations and could help explain the underlying mechanisms of progressive airway obstruction. Understanding growth-induced instabilities in constrained geometries has immediate biomedical applications beyond asthma and chronic bronchitis in the diagnostics and treatment of chronic gastritis, obstructive sleep apnea and breast cancer.