Using CARDIac simulations to run in-silicO clinical TRIALS

Objetivo

Clinical trials are a key tool for advancing medical knowledge, but they consist of a long and costly process entailing the recruitment of a representative cohort of participants to properly account for the population statistical variability. Computational engineering is a promising approach to gain more insight into patients' cardiac pathologies and to test innovative medical devices before running conclusive in-vivo experiments on animals or medical trials on humans. This technological breakthrough, however, is limited by some technical and epistemic challenges: (i) the reliability of cardiovascular computational models depends on the accurate solution of the hemodynamics coupled with the deforming biologic tissues; (ii) the resulting multi-physics solver requires an immense computational power and long time-to-results; (iii) a great variability among individuals exists, thus calling for a statistical approach. For the first time I will accomplish and employ a computational platform for determining the outcome of pathologies or devices implantation by combining my GPU-accelerated multi-physics solver for the accurate solution of cardiac dynamics with an uncertainty quantification analysis to account for the individuals variability. The input parameters of the computational model will be treated as aleatory variables, whose probability distribution function will be obtained using three-dimensional datasets of cardiac configurations available to the PI's group and acquired in-vivo by the clinical members involved in the project. Simulation campaigns (rather than a single simulation) will be then run in order to sweep the uncertain input distributions and obtain the synthetic population response in the case of selected pathologies like myocardial infarction and the optimal stimulation pattern for cardiac resynchronization therapy. My approach removes the main barrier that keeps up from a systematic use of computational engineering to run in-silico clinical trials.