Pathology of calcified nodules in coronary arteries

Calcified nodule (CN) is a unique calcified plaque morphology that is pathologically characterized by fibrous-cap disruption and luminal thrombus associated with eruptive, dense calcific nodules. Although CNs account for a small proportion of acute coronary syndrome, they remain challenging substrates for percutaneous coronary intervention (PCI) due to high risks of underexpansion and in-stent restenosis. To understand their unpredictable mechanical behavior, it is crucial to recognize their origin: CNs typically arise from the fragmentation of mechanically vulnerable necrotic core calcification under mechanical stress, often exacerbated by adjacent rigid sheet calcium. Crucially, while intravascular imaging typically classifies CNs into "eruptive" or "non-eruptive" forms, this binary classification alone is sometimes insufficient to predict lesion compliance or "softness." A deeper understanding of the underlying pathological evolution-from fresh, thrombus-covered nodules to mature, ossified masses-is essential to distinguish deformable lesions from rigid ones. This review bridges this gap by proposing a pathology-imaging continuum that links histological maturity to mechanical behavior, enabling more precise phenotyping beyond surface appearance. We finally discuss how this integrated approach informs contemporary PCI strategies, including atherectomy, intravascular lithotripsy, and lifetime management, to optimize clinical outcomes.