Modelling the Effects of Conductive Polymers and Stem Cells Derived Myocytes on Scarred Heart Tissue

Damiano Fassina1, Caroline Mendonca Costa1, Sian Harding2, steven niederer1
1King's College London, 2Imperial College London


Introduction: Scarring subsequent to myocardial infarction is irreversible and impairs cardiac function. Engineered heart tissue (EHT) offers an innovative treatment to augment and recover function in scarred regions. However, electrical heterogeneity between ETC and native tissue can be pro-arrhythmic. Combining EHT with conductive polymers (CP) may mitigate these effects. Aims: Identify EHT and CP conductivity and thickness that minimize the electrical impact for different scar properties. Methods: We created a 2D model of a slab of rabbit myocardial tissue with scar in the presence of EHT and CP. The CP patch was modelled as ohmic with variable conductivity. The EHT and viable myocardium were modelled using the mono-domain equations with a stem cells-derived cardiomyocyte and rabbit myocyte cell model, respectively. A set of 10 design variables (tissue, bath, EHT, CP thickness and conductivity, scar radius, depth and conductivity, thickness of EHT-slab tissue contact area) were defined, with ranges from the literature. 1000 parameter combinations were simulated using a Latin hypercube design. Activation times were computed at assigned points in the slab and the wave path was identified. A Gaussian process emulator was fitted to our model, enabling a Global Sensitivity Analysis (GSA) to identify which parameters had the largest impact on propagation. Results: From the GSA the total effect (TE) indexes indicate each parameter’s contribution to the output variance. When scar properties are varied, scar conductivity and depth explained 48.3% and 38.3% respectively of the variability. When scar properties are fixed, EHT conductivity (TE=36.4%) and the thickness of the EHT-slab tissue contact area (TE=49.6%) are important parameters. Conclusion: We predict that the scar properties are crucial in determining the activation across a scar. However, in case of transmural scar, the model indicated the EHT conductivity and the EHT-slab tissue contact area to have an active role in influencing stimulus propagation.