An Integrated Workflow for Building Digital Twins of Cardiac Electromechanics-A Multi-Fidelity Approach for Personalising Active Mechanics.

Personalised computer models of cardiac function, referred to as cardiac digital twins, are envisioned to play an important role in clinical precision therapies of cardiovascular diseases. A major obstacle hampering clinical translation involves the significant computational costs involved in the personalisation of biophysically detailed mechanistic models that require the identification of high-dimensional parameter vectors. An important aspect to identify in electromechanics (EM) models are active mechanics parameters that govern cardiac contraction and relaxation. In this study, we present a novel, fully automated, and efficient approach for personalising biophysically detailed active mechanics models using a two-step multi-fidelity solution. In the first step, active mechanical behaviour in a given 3D EM model is represented by a purely phenomenological, low-fidelity model, which is personalised at the organ scale by calibration to clinical cavity pressure data. Then, in the second step, median traces of nodal cellular active stress, intracellular calcium concentration, and fibre stretch are generated and utilised to personalise the desired high-fidelity model at the cellular scale using a 0D model of cardiac EM. Our novel approach was tested on a cohort of seven human left ventricular (LV) EM models, created from patients treated for aortic coarctation (CoA). Goodness of fit, computational cost, and robustness of the algorithm against uncertainty in the clinical data and variations of initial guesses were evaluated. We demonstrate that our multi-fidelity approach facilitates the personalisation of a biophysically detailed active stress model within only a few (2 to 4) expensive 3D organ-scale simulations-a computational effort compatible with clinical model applications.