This project has the purpose of using HPC to enable advanced numerical simulations that can deepen the scientific understanding of the intricate electrical activities in the heart. Specifically, we aim to facilitate resource-efficient use of supercomputers, such as the current Wisteria/BDEC-01 system and the upcoming OFP-II system, for running huge-scale simulations of cutting-edge mathematical models of cardiac electrophysiology. Moreover, this project will consolidate the existing expertise of the project partners on, respectively, hue-scale simulations involving unstructured meshes, optimized parallel programming and use of non-x86 architecture (A64FX processors) & hardware accelerator (Nvidia GPUs). The cutting-edge mathematical models to be targeted by this project include the EMI model [1] as well as the newly derived KNM (Kirchhoff network model [2]) and SKNM (simplified KNM [3]) strategies. (A brief description of these advanced, cell-resolved models will be given below.) These new models overcome the limitations of the standard bidomain and monodomain models which for simplicity “merge” the intracellular and extracellular spaces together with the cell membranes, thereby missing the per-cell details. However, due to either the extreme amount of computation required for EMI or the recent arrival of KNM and SKNM, they have till now only be simulated with moderate scales, thus demanding more performant and scalable simulators. By combining efficient numerical algorithms with hardware-compatible software implementations, we want to enable novel, huge-scale “in-silico” experiments that can resolve the individual cardiac cells. These new simulators are expected to provide an unprecedented platform where new hypotheses of electrophysiology can be tested.