Coronary Calcified Nodules: From Pathological Definitions to Intravascular Imaging- and Morphology-Guided PCI

Coronary artery calcification (CAC) is a hallmark of advanced atherosclerosis and a major determinant of procedural complexity during percutaneous coronary intervention (PCI). Once considered a passive consequence of vascular degeneration, CAC is now recognized as an active, highly regulated process driven by inflammation, oxidative stress, extracellular vesicle release, osteogenic differentiation of vascular smooth muscle cells, and biomechanical remodeling. These mechanisms generate a spectrum of calcific phenotypes, ranging from microcalcifications and sheet calcium to nodular calcium and calcified nodules. Calcified nodules represent an advanced fibrocalcific plaque phenotype characterized by fractured calcific plates, luminal calcium protrusion, surface disruption, and variable thrombus formation. They can be characterized using intravascular ultrasound (IVUS), optical coherence tomography (OCT), and hybrid near-infrared spectroscopy-IVUS imaging, and are associated with coronary thrombosis, stent underexpansion, restenosis, target lesion failure, and the need for advanced calcium-modification strategies. A structured literature search of PubMed/MEDLINE, Web of Science Core Collection, and Scopus identified 83 publications published between 2020 and 2026 for inclusion in the narrative synthesis. This narrative review summarizes the biological and biomechaniclam mechanisms of coronary calcification and calcified nodule formation, compares multimodality intravascular imaging criteria, and discusses contemporary imaging-guided PCI strategies, including balloon-based modification, rotational and orbital atherectomy, excimer laser coronary atherectomy, intravascular lithotripsy, and hybrid approaches. By integrating pathobiology, intravascular imaging criteria, and lesion-specific PCI strategies, this review provides a clinically oriented framework for the assessment and management of calcified nodules. Future directions include standardized imaging definitions, prospectively validated morphology-guided treatment algorithms, and computational and artificial intelligence-assisted plaque characterization.