Invasive Coronary Physiology in Contemporary Practice: From Lesion Selection to Comprehensive PCI Guidance and Functional Phenotyping

Background/Objectives: Invasive coronary physiology has evolved from a tool for assessing intermediate stenoses to a comprehensive framework for guiding diagnosis and treatment across the spectrum of coronary artery disease (CAD). This review aims to provide an updated, catheterization laboratory-centered overview of contemporary invasive coronary physiology, emphasizing its role in optimizing percutaneous coronary intervention (PCI) and in evaluating patients with angina and non-obstructive coronary arteries (ANOCA/INOCA). Methods: A narrative review of contemporary evidence, including randomized trials, consensus documents, and guideline recommendations, was conducted. Key physiological indices—fractional flow reserve (FFR), non-hyperemic pressure ratios (NHPRs), coronary flow reserve (CFR), and index of microcirculatory resistance (IMR)—were examined alongside emerging tools such as longitudinal vessel analysis and the pullback pressure gradient (PPG). Applications in pre- and post-PCI assessment, physiology–imaging integration, and comprehensive functional testing in ANOCA/INOCA were evaluated. Results: Physiology-guided PCI improves clinical outcomes and resource utilization compared with angiography-guided strategies. Longitudinal vessel assessment and PPG enable characterization of focal versus diffuse CAD, improving procedural planning and prediction of post-PCI physiological results. Post-PCI physiological assessment identifies residual ischemia and guides optimization strategies. In patients without obstructive CAD, combined assessment of microvascular function and vasomotor reactivity allows identification of distinct pathophysiological endotypes, supporting mechanism-based, individualized therapy. Integration with intracoronary imaging further enhances procedural precision. Conclusions: Contemporary invasive coronary physiology provides a multidimensional approach integrating epicardial, microvascular, and vasomotor domains. This framework supports personalized decision-making, optimizes revascularization, and reduces unnecessary interventions, representing a cornerstone of modern coronary care.