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Multiscale Modeling of Valvular Heart Diseases - Understanding the Mechanisms of Adverse Remodeling to Improve Precision Medicine.

Abstract: SICVALVES – Multiscale modeling of Valvular Heart Diseases
Understanding the mechanisms of adverse remodeling to improve precision medicine

Background: Valvular Heart Diseases (VHD) are a detrimental health burden to the aging population where aortic valve stenosis alone has reached an incidence of more than 12% of patients >70y. It is a chronic-progressive disease that varies with gender and age. If left untreated, VHDs can cause malignant arrhythmias and severe heart failure. However, existing guidelines for treatment planning are using only rough function parameters that fail to account for inter-individual variability and are far away from the demands of precision medicine. In the age of digital medicine, computational modeling has the potential to unveil important pathophysiological mechanisms and to contribution towards personalized precision medicine.
Objectives: To use advanced models of the cell, tissue, and organ level in VHD to gain mechanistic insights about triggers of ventricular arrhythmias, diastolic, and systolic dysfunction and myocardial metabolic alterations and how these processes reinforce each other. Gender differences will be systematically taken into account. Ultimately, models shall contribute to improve diagnostics, risk assessment, and treatment planning of VHDs.
Methods: Based on our previous work, we will technologically advance, test, and validate existing computational models of biomechanics, electrophysiology, and hemodynamics. For model parameterization we use existing multidimensional clinical data (imaging, sensors, omics) from own previous research in patients with VHD (obtained before and after valve replacement). Validation of the model's accuracy to predict mechanistic changes will be done with data obtained before and after aortic valve replacement.
Innovation: Advanced computational models will be leveraged to build personalized models and use these for quantitative assessment of hypertrophic remodeling and propensity for arrhythmias. Novel methodologies will be developed to understand important mechanisms of adverse remodeling in VHDs, as well as to improve patient care by optimizing patient selection and precision treatment planning in valve disease.

Keywords: Aortenstenose; Herzklappenerkrankungen; Herzklappenersatz; Kardiales Remodeling; Präzisionsmedizin

Project Leader:: Augustin Christoph

Duration:: 01.05.2020-31.08.2024

Programme:: ERA-Net Beteiligungen

Type of Research: applied research

Staff: Augustin, Christoph, Project Leader; Kariman, Mohammadreza, Co-worker; Zappon, Elena, Co-worker; Jung, Alexander, Co-worker

MUG Research Units: Division of Medical Physics and Biophysics

Funded by: FWF, Fonds zur Förderung der Wissenschaftlichen Forschung, Wien, Austria

Project results published: > Multiphysics simulations reveal haemodynamic impac... J Physiol. 2024; 602(24):6789-6812; > Mechanoelectric effects in healthy cardiac functio... Comput Biol Med. 2023; 156:106696; > An accurate, robust, and efficient finite element ... Comput Methods Appl Mech Eng. 2022; 394: 114887; > An accurate and efficient finite element framework... Austrian Numerical Analysis Day; MAY 4-6, 2022; Linz, Austria. 2022.; > Multiscale modelling of Valvular Heart Diseases. U... ERA-Net Symposium on Cardiovascular Diseases; SEP 19-20, 2022; Riga, LATVIA. 2022.; > Physiologically valid 3D-0D models of the heart an... 9th World Congress of Biomechanics; JUL 10-14; Taipei, TAIWAN. 2022.; > Physiologically valid 3D-0D models of cardiac elec... Abstracts of the 2022 Joint Annual Conference of the Austrian (ÖGBMT), German (VDE DGBMT) and Swiss (SSBE) Societies for Biomedical Engineering, including the 14th Vienna International Workshop on Functional Electrical Stimulation. 2022; -Joint Annual Conference of the Austrian (ÖGBMT), German (VDE DGBMT) and Swiss (SSBE) Societies for Biomedical Engineering; SEP 28-30, 2022; Innsbruck, AUSTRIA;.; > The interplay of sex-specific electrophysiology an... EUR HEART J. 2022; 43: 2518-2518.; > Digital Twin Models of Cardiac Function for Clinic... Meeting Research Field "Metabolism and Circulation"; JUN 24, 2021; Graz, Austria. 2021.; > A physiologically valid 3D-0D closed loop model of... CompBioMed Conference 2021; SEP 15-17; London, UK. 2021.; > Physiologically valid 3D-0D models of the heart an... Cardiac Electro-Mechanics Research Group Seminar; SEP 27; London, UK. 2021.