A human-based biventricular strongly coupled electromechanics model for post myocardial infarction

Zhinuo Jenny Wang1, Lei Wang1, Xin Zhou1, Francesca Margara1, Alfonso Santiago2, Francesc Levrero-Florencio3, Mariano Vazquez4, Blanca Rodriguez1
1University of Oxford, 2Barcelona Supercomputing Centre, 3University of Oxford, OnScale Ltd, 4Barcelona Supercomputing Center, ELEM Biotech


Abstract

Myocardial infarction (MI) is a major cause of mortality worldwide, due to increased arrhythmic risk and reduced mechanical function. Risk stratification of post-MI patients is still challenging, and novel mechanistic insights into mechanical dysfunction and pro-arrhythmic risk in post-MI are needed. Our goal is to develop a computer modelling and simulation framework to investigate the electromechanical alterations caused by post-MI in the human heart.

A human ventricular baseline model with anatomy extracted from magnetic resonance datasets and realistic fibre orientation was adapted to introduce the electromechanical consequences of post-MI scar and borderzone. Simulations were conducted using Alya, the Barcelona Supercomputing Center in-house tool for simulation. The biventricular electromechanical model includes state-of-the-art human-based membrane kinetics, excitation-contraction and active tension models, with orthotropic biomechanics and mechano-electric feedback. Endocardial stimulation was imposed to model Purkinje-like activation, as in experimental recordings. In healthy conditions, this yielded simulated standard ECG placements with physiological R-wave progression, T-wave polarity, and QRS duration in line with clinical recordings. A set of biventricular pressure boundary conditions were developed with bi-phasic diastole, which has an active relaxation phase and a passive filling phase, to produce physiological pressure-volume loops.

Electromechanical alterations caused by post-MI scar with borderzones were then added into the model. The scar region included no electrical conductivity or active tension with a ten-fold increase in stiffness oriented along the circumferential direction. The borderzone was modelled with ionic remodelling and reduced conductivity and had an increasing contractility radiating from the scar to the surrounding normal region. A fully transmural LAD infarction was simulated and showed abnormal ECG and mechanical biomarkers.

We present the development and evaluation of a baseline biventricular model with strongly coupled electromechanics and demonstrated its ability to simulate dysfunction in post-MI electromechanics. This paves the way for future hypothesis testing for post-MI disease mechanisms.