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In this thesis we investigated: a) the prognostic role of FFR in functional evaluation of epicardial stenosis in different anatomical and clinical settings of patients with stable CAD, heart valve disease and LVD; b) the role of IMR, CFR and absolute coronary flow and microvascular resistances assessment with a new dedicated thermodilution catheter; c) the diagnostic performance of two new angiography-derived FFR technologies for a quantitative and functional assessment of CAD; d) the impact of antiplatelet agents and BVS Absorb™ implantantion on procedure-related microvascular impairment, platelet activation and the related myonecrosis; e) the safety and feasibility of new 2-stent bifurcation techniques and the clinical outcome of known bifurcations techniques. We believe that many answers have been provided by our extensive translational research. FFR remains the milestone in functional assessment of the ischemic burden related to coronary stenoses. Our findings corroborate the strong clinical outcome background of FFR, supporting FFR-guided revascularization strategies above angio-based decision making, and therefore strongly discouraging any purely anatomy guided revascularization attempts in different clinical and anatomical settings. Absolute coronary blood flow (Q) and microvascular resistance (R) can be safely and reproducibly measured with continuous thermodilution, opening new opportunities for the study of the coronary microcirculation. FFRangio and QFR provide both a comprehensive physiological assessment of the entire coronary tree within few minutes, enabling online FFR measurement during the angiographic procedure. This, in turn, may facilitate the adoption of FFR-based clinical decision making regarding coronary revascularization. Both prasugrel and BVS Abosrb™ have proven a beneficial acute effect on peri-procedural coronary microvascular function and platelet activation. Although BVS Absorb™ did not live up to its promise because of the higher events in the mid-term due to greater scaffold thrombosis, our findings are at least reassuring on the acute impact of these devices on the microcirculation. Lastly in PCI of bifurcation lesions, our feasibility results of in vitro tests, offer new solutions for both complex anatomy requiring 2-stent-technique and bailout technique in case of failure of the most consolidated provisional T-stenting.