Cardiovascular diseases are the leading cause of death in western countries. In coronary atherosclerosis, local hemodynamics and wall mechanics are key determinants of plaque evolution. Recently, combining computational tools with medical imaging has enabled to profile biomechanical quantities, such as wall shear stress (WSS) and wall stress, with high accuracy. Specifically, patient-specific computational fluid dynamics (CFD) simulations elucidated the role of WSS in coronary atherosclerosis natural history, while finite element analysis (FEA) quantified volumetric wall and plaque stress/strain under patho-physiological loading conditions. However, their clinical applicability is hindered by the assumptions related to the model-based strategy and by the lack of reliable automatic reconstruction methods from clinical imaging.