This paper presents a patient-sensitive simulation strategy capable of using the most efficient way the high-performance computational resources. The proposed strategy directly involves three different players: Computational Mechanics Scientists (CMS), Image Processing Scientists and Cardiologists, each one mastering its own expertise area within the project. This paper describes the general integrative scheme but focusing on the CMS side presents a massively parallel implementation of computational electrophysiology applied to cardiac tissue simulation. The paper covers different angles of the computational problem: equations, numerical issues, the algorithm and parallel implementation. The proposed methodology is illustrated with numerical simulations testing all the different possibilities, ranging from small domains up to very large ones. A key issue is the almost ideal scalability not only for large and complex problems but also for medium-size meshes. The explicit formulation is particularly well suited for solving this highly transient problems, with very short time-scale. Copyright © 2011 John Wiley & Sons, Ltd.