Enabling forward uncertainty quantification and sensitivity analysis in cardiac electrophysiology by reduced order modeling and machine learning.

We present a new, computationally efficient framework to perform forward uncertainty quantification (UQ) in cardiac electrophysiology. We consider the monodomain model to describe the electrical activity in the cardiac tissue, coupled with the Aliev-Panfilov model to characterize the ionic activity through the cell membrane. We address a complete forward UQ pipeline, including both: (i) a variance-based global sensitivity analysis for the selection of the most relevant input parameters, and (ii) a way to perform uncertainty propagation to investigate the impact of intra-subject variability on outputs of interest depending on the cardiac potential. Both tasks exploit stochastic sampling techniques, thus implying overwhelming computational costs because of the huge amount of queries to the high-fidelity, full-order computational model obtained by approximating the coupled monodomain/Aliev-Panfilov system through the finite element method. To mitigate this computational burden, we replace the full-order model with computationally inexpensive projection-based reduced-order models (ROMs) aimed at reducing the state-space dimensionality. Resulting approximation errors on the outputs of interest are finally taken into account through artificial neural network (ANN)-based models, enhancing the accuracy of the whole UQ pipeline. Numerical results show that the proposed physics-based ROMs outperform regression-based emulators relying on ANNs built with the same amount of training data, in terms of both numerical accuracy and overall computational efficiency.