Christoph M Augustin

Medical University of Graz · Institute of Biophysics

High-resolution and anatomically realistic computer models of biological soft tissues play a significant role in the understanding of the function of cardiovascular components in health and disease. However, the computational effort to handle fine grids to resolve the geometries as well as sophisticated tissue models is very challenging. One possib...

Electromechanical (EM) models of the heart have been used successfully to study fundamental mechanisms underlying a heart beat in health and disease. However, in all modeling studies reported so far numerous simplifications were made in terms of representing biophysical details of cellular function and its heterogeneity, gross anatomy and tissue mi...

Aims Models of blood flow in the left ventricle (LV) and aorta are an important tool for analysing the interplay between LV deformation and flow patterns. Typically, image-based kinematic models describing endocardial motion are used as an input to blood flow simulations. While such models are suitable for analysing the hemodynamic status quo, they...

Computer models of cardiac electro-mechanics (EM) show promise as an effective means for the quantitative analysis of clinical data and, potentially, for predicting therapeutic responses. To realize such advanced applications methodological key challenges must be addressed. Enhanced computational efficiency and robustness is crucial to facilitate,...

Fiber-reinforced soft biological tissues are typically modeled as hyperelastic, anisotropic, and nearly incompressible materials. To enforce incompressibility a multiplicative split of the deformation gradient into a volumetric and an isochoric part is a very common approach. However, the finite element analysis of such problems often suffers from...

Computer models of the human ventricular cardiomyocyte action potential (AP) have reached a level of detail and maturity that has led to an increasing number of applications in the pharmaceutical sector. However, interfacing the models with experimental data can become a significant computational burden. To mitigate the computational burden, the pr...

Cardiac pump function arises from a series of highly orchestrated events across multiple scales. Computational electromechanics can encode these events in physics-constrained models. However, the large number of parameters in these models has made the systematic study of the link between cellular, tissue, and organ scale parameters to whole heart p...

Pericardiectomy is recommended therapy for pericarditis, an inflammation of the pericardial layers that surround the heart and play a central role in maintaining cardiac performance. In some cases, the pericardium can be repaired or patched. However, the impact of changes in the pericardium on cardiac function is not clear. The objective of this st...

Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Union's Horizon 2020 research and innovation program under the ERA-NET co-fund action No. 680969 with ANR (ERA-CVD SICVALVES) and Agence Nationale de la Recherche Background Extracellular volume (ECV) determined by magnetic resonance im...

Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This research has also received funding from the European Union’s Horizon 2020 research and innovation programme under the ERA-NET co-fund action No. 680969 (ERA-CVD SICVALVES) funded by the Austrian Science Fund (FWF), Grant I 4652-B to CMA. Thi...

Mechanoelectric feedback (MEF) in the heart operates through several mechanisms which serve to regulate cardiac function. Stretch activated channels (SACs) in the myocyte membrane open in response to cell lengthening, while tension generation depends on stretch, shortening velocity, and calcium concentration. How all of these mechanisms interact an...

Previous patient-specific model calibration techniques have treated each patient independently, making the methods expensive for large-scale clinical adoption. In this work, we show how we can reuse simulations to accelerate the patient-specific model calibration pipeline. To represent anatomy, we used a Statistical Shape Model and to represent fun...

Background The role of sex-specific electrophysiology in the development of lethal ventricular arrhythmia is poorly understood. Since female ventricles have a longer action potential duration (APD) than male ventricles, we hypothesized that female hearts are more vulnerable to sustained ventricular arrhythmia in the presence of known arrhythmogenic...

Computer models capable of representing the intrinsic personal electrophysiology (EP) of the heart in silico are termed virtual heart technologies. When anatomy and EP are tailored to individual patients within the model, such technologies are promising clinical and industrial tools. Regardless of their vast potential, few virtual technologies simu...

A key factor governing the mechanical performance of the heart is the bidirectional coupling with the vascular system, where alterations in vascular properties modulate the pulsatile load imposed on the heart. Current models of cardiac electromechanics (EM) use simplified 0D representations of the vascular system when coupling to anatomically accur...

[This corrects the article DOI: 10.1371/journal.pcbi.1008851.].

Cardiac fiber direction is an important factor determining the propagation of electrical activity, as well as the development of mechanical force. In this article, we imaged the ventricles of several species with special attention to the intraventricular septum to determine the functional consequences of septal fiber organization. First, we identif...

Personalised computer models of cardiac function, referred to as cardiac digital twins, are envisioned to play an important role in clinical precision therapies of cardiovascular diseases. A major obstacle hampering clinical translation involves the significant computational costs involved in the personalisation of biophysically detailed mechanisti...

The impact of increased stiffness and pulsatile load on the circulation and their influence on heart performance have been documented not only for cardiovascular events but also for ventricular dysfunctions. For this reason, computer models of cardiac electromechanics (EM) have to integrate effects of the circulatory system on heart function to be...

Fiber-reinforced soft biological tissues are typically modeled as hyperelastic, anisotropic, and nearly incompressible materials. To enforce incompressibility a multiplicative split of the deformation gradient into a volumetric and an isochoric part is a very common approach. However, due to the high stiffness of anisotropic materials in the prefer...

Cardiac digital twins (Cardiac Digital Twin (CDT)s) of human electrophysiology (Electrophysiology (EP)) are digital replicas of patient hearts derived from clinical data that match like-for-like all available clinical observations. Due to their inherent predictive potential, CDTs show high promise as a complementary modality aiding in clinical deci...

Cardiac output is dependent on the tight coupling between atrial and ventricular function. The study of such interaction mechanisms is hindered by their complexity, and therefore requires a systematic approach. We have developed a four-chamber closed-loop cardiac electromechanics model which, through the coupling of the chambers with a closed-loop...

Background and objective: Cardiac electrophysiology is a medical specialty with a long and rich tradition of computational modeling. Nevertheless, no community standard for cardiac electrophysiology simulation software has evolved yet. Here, we present the openCARP simulation environment as one solution that could foster the needs of large parts o...

Cardiac anatomy plays a crucial role in determining cardiac function. However, there is a poor understanding of how specific and localised anatomical changes affect different cardiac functional outputs. In this work, we test the hypothesis that in a statistical shape model (SSM), the modes that are most relevant for describing anatomy are also most...

Background and Objective Cardiac electrophysiology is a medical specialty with a long and rich tradition of computational modeling. Nevertheless, no community standard for cardiac electrophysiology simulation software has evolved yet. Here, we present the openCARP simulation environment as one solution that could foster the needs of large parts of...

Image-based computational models of the heart represent a powerful tool to shed new light on the mechanisms underlying physiological and pathological conditions in cardiac function and to improve diagnosis and therapy planning. However, in order to enable the clinical translation of such models, it is crucial to develop personalized models that are...

Computational modeling of cardiovascular biomechanics should generally start from a homeostatic state. This is particularly relevant for image-based modeling, where the reference configuration is the loaded in vivo state obtained from imaging. This state includes residual stress of the vascular constituents, as well as anisotropy from the spatially...

Computer models of cardiac electro-mechanics (EM) have the potential to enhance our understanding of underlying mechanisms in the analysis of normal and dysfunctional hearts and show promise as a guidance in designing and developing new treatment. Here, pre- and afterload conditions play a critical role in governing and regulating heart function un...

Computational models of the heart are increasingly being used in the development of devices, patient diagnosis and therapy guidance. While software techniques have been developed for simulating single hearts, there remain significant challenges in simulating cohorts of virtual hearts from multiple patients. To facilitate the development of new simu...

The left atrium (LA) has a complex anatomy with heterogeneous wall thickness and curvature. The anatomy plays an important role in determining local wall stress; however, the relative contribution of wall thickness and curvature in determining wall stress in the LA is unknown. We have developed electromechanical finite element (FE) models of the LA...

Computer models of left ventricular (LV) electro-mechanics (EM) show promise as a tool for assessing the impact of increased afterload upon LV performance. However, the identification of unique afterload model parameters and the personalization of EM LV models remains challenging due to significant clinical input uncertainties. Here, we personalize...

Cardiac growth and remodeling (G&R) refers to structural changes in myocardial tissue in response to chronic alterations in loading conditions. One such condition is pressure overload where elevated wall stresses stimulate the growth in cardiomyocyte thickness, associated with a phenotype of concentric hypertrophy at the organ scale, and promote fi...

The pericardium affects cardiac motion by limiting epicardial displacement normal to the surface. In computational studies, it is important for the model to replicate realistic motion, as this affects the physiological fidelity of the model. Previous computational studies showed that accounting for the effect of the pericardium allows for a more re...

Computational formulations for large strain, polyconvex, nearly incompressible elasticity have been extensively studied, but research on enhancing solution schemes that offer better tradeoffs between accuracy, robustness, and computational efficiency remains to be highly relevant. In this paper, we present two methods to overcome locking phenomena,...

Cardiovascular diseases (CVDs) are the leading causes of mortality worldwide. The contraction and relaxation of left ventricle (LV) is the main driving force of blood circulation. Altered LV hemodynamics is believed to be associated with the initiation and progression of many CVDs. Thus, understanding and evaluating the flow pattern inside a patien...

FEniCS Mechanics is a Python package to facilitate computational mechanics simulations. The Python library dolfin, from the FEniCS Project, is used to formulate and numerically solve the problem in variational form. The general balance laws from continuum mechanics are used to enable rapid prototyping of different material laws. In addition to its...

Saccharomyces cerevisiae target of rapamycin (TOR) complex 2 (TORC2) is an essential regulator of plasma membrane lipid and protein homeostasis. How TORC2 activity is modulated in response to changes in the status of the cell envelope is unclear. Here we document that TORC2 subunit Avo2 is a direct target of Slt2, the mitogen-activated protein kina...

To observe internalization of the yeast pheromone receptor Ste2 by fluorescence microscopy in live cells in real time, we visualized only those molecules present at the cell surface at the time of agonist engagement (rather than the total cellular pool) by tagging this receptor at its N-terminus with an exocellular fluorogen-activating protein (FAP...

Introduction: Stenotic aortic valve disease (AS) causes pressure overload of the left ventricle (LV) that may trigger adverse remodeling and precipitate progression towards heart failure (HF). As myocardial energetics can be impaired during AS, LV wall stresses and biomechanical power provide a complementary view of LV performance that may aide in...

Computational fluid dynamics (CFD) models of blood flow in the left ventricle (LV) and aorta are important tools for analyzing the mechanistic links between myocardial deformation and flow patterns. Typically, the use of image-based kinematic CFD models prevails in applications such as predicting the acute response to interventions which alter LV a...

Models of cardiac mechanics are increasingly used to investigate cardiac physiology. These models are characterized by a high level of complexity, including the particular anisotropic material properties of biological tissue and the actively contracting material. A large number of independent simulation codes have been developed, but a consistent w...

Computational models of cardiac electromechanics (EM) are increasingly being applied to clinical problems, with patient-specific models being generated from high fidelity imaging and used to simulate patient physiology, pathophysiology and response to treatment. Current structured meshes are limited in their ability to fully represent the detailed...

Biological materials such as the myocardium or the artery are characterized by anisotropic and nonlinear material properties. The high complexity of the underlying nonlinear equations as well as fine geometrical structures of the cardiovascular components demand fast solving algorithms. In this work a domain decomposition algorithm, more precisely...

Computational modeling of ventricular electromechanics is considered to be among the most promising approaches to gain novel insight into cardiac function in health and disease. Such models allow to integrate the wealth of available experimental data into a mechanistic framework which allows to study complex cause-effect relationships across severa...

In this paper we describe the application of finite element tearing and interconnecting methods for the simulation of biological tissues, as a particular application we consider the myocardium. As most other tissues, this material is characterized by anisotropic and nonlinear behavior.