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Personalized MultiSystems Simulations for Honing Cardiac Resynchronization Therapy

Abstract: Heart failure is a major cause of death in industrialized countries. It is often associated with disturbances to the cardiac electrical conduction system, leading to abnormal cardiac activation and compromised hemodynamic response. Cardiac Resynchronization therapy (CRT) is a proven treatment to retard progress of the disease. This necessitates implantation of a pacing device with multiple leads, but optimal lead position remains an open question. While it is recognized that activation time should be reduced, minimizing it alone does not improve mechanical response better than placing leads elsewhere. A significant fraction (30-50%) of patients does not respond at all to this expensive therapy, with large inter-patient variability leading to the poor results. The heart is an electrically activated mechanical fluid pump. Confounding its understanding is the feedback between physical components: Electrical events trigger mechanical contraction. Contraction causes blood flow, which is mediated by the vascular resistance. Deformation in turn affects electrical function through stretch activated ionic channels and mechanics through prestretch. This project will bring together electrical, mechanical and hemodynamic function in the most detailed multiphysics, multiscale representation of the heart to date. Tightly coupled electromechanical behavior will interface to a circulatory model providing the appropriate boundary conditions to the mechanical model and form a closed circuit. Personalized models will be constructed based on imaging, noninvasive electrical measurements and hemodynamic performance. We hypothesize specific differences in wall activation that should be minimized. A complete multi-system model is needed to understand lead placement in CRT due to non-electrical factors, which have too long been ignored. Validating on detailed animal studies, retrospective and prospective studies will help us develop a predictive tool to determine optimal CRT lead placement.

Keywords: Elektrokardiogramm; Herzmechanik; Kardiale Elektrophysiologie; Kardiale Resynchronisationstherapie; Kardiales Reizleitungssystem

Local Subprojectlead:: Plank Gernot

Duration:: 01.01.2016-31.12.2019

Programme:: FWF andere

Subprogramme: ERA-Net

Type of Research: basic research

Staff: Plank, Gernot, Project Leader; Prassl, Anton, Co-worker; Gsell, Matthias, Co-worker

MUG Research Units: Division of Medical Physics and Biophysics

Project partners: Maastricht University, Department of Physiology, Cardiovascular Research Institute Maastricht, Netherlands
Contact person: joost.lumens@maastrichtuniversity.nl;; Maastricht University, Department of Physiology, Cardiovascular Research Institute Maastricht, Netherlands; University of Bordeaux, Institute LYRIC, France

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

Project results published: > Determining anatomical and electrophysiological de... Comput Biol Med. 2022; 141:105061; > Automated Framework for the Inclusion of a His-Pur... Ann Biomed Eng. 2021; 49(12):3143-3153; > Non-invasive simulated electrical and measured mec... Comput Biol Med. 2021; 138: 104872; > His-bundle and left bundle pacing with optimized a... Heart Rhythm. 2020; 17(11):1922-1929; > A publicly available virtual cohort of four-chambe... PLoS One. 2020; 15(6):e0235145; > Automating image-based mesh generation and manipul... SoftwareX. 2020; 11: 100454-100454.; > An Inverse Eikonal Method for Identifying Ventricu... J Comput Phys. 2020; 419:; > Towards a Computational Framework for Modeling the... Front Physiol. 2018; 9(12):538-538; > Universal ventricular coordinates: A generic frame... Med Image Anal. 2018; 45:83-93; > Electro-biomechanical Modeling... CARS 2018 Computer Assisted Radiology and Surgery; JUN 20-23, 2018; Berlin, GERMANY. 2018.; > Personalizing models of total heart function... Multi-scale hard and soft tissue modelling workshop; JUN 18-20, 2018; Sheffield. 2018.