Coronary Artery Disease (CAD) is a leading cause of death worldwide, with 315 million cases reported in 2022. CAD onset is characterized by coronary arteries obstruction that reduce blood flow to the heart, increasing the risk of major cardiovascular events. In recent years, the physiological evaluation of CAD has gained momentum both in research and clinical practice, complementing diagnostic imaging techniques. Specifically, pressure gradient-based methods are currently considered a reference standard for assessing obstruction severity, but require invasive procedures with associated risks. A non-invasive alternative is offered by Computational Fluid Dynamics (CFD), but its adoption in the clinical practice is hampered by high computational costs.