From anatomy to vulnerability: A comprehensive appraisal of coronary physiology and plaque characterization.

A substantial proportion of acute coronary syndromes arise from non-obstructive plaques with high-risk biological, morphological, and biomechanical features. This review summarizes contemporary concepts of plaque vulnerability, including plaque rupture, plaque erosion, and calcified nodules, and examines the role of invasive imaging and computational techniques in identifying lesions at increased risk of future events. Intravascular ultrasound, near-infrared spectroscopy, and optical coherence tomography provide complementary information on plaque burden, lipid content, fibrous cap thickness, macrophage infiltration, calcification, and thrombotic substrates. However, their routine use may be limited by cost, procedural complexity, contrast requirements, and operator dependency. Emerging angiography-derived approaches, particularly radial wall strain, offer a simplified method to assess plaque deformability and biomechanical instability from standard coronary angiography. Elevated radial wall strain has shown correlation with optical coherence tomography-defined vulnerable plaque features and independent prognostic value for adverse cardiovascular outcomes, including in non-flow-limiting lesions. Integration of coronary physiology, plaque morphology, and biomechanical indices may therefore refine lesion-level risk stratification and support a more personalized approach to coronary artery disease management. Further prospective studies are needed to determine whether vulnerability-guided diagnostic and therapeutic strategies can improve clinical outcomes beyond current anatomy- and ischaemia-based paradigms.