Machine Learning-Based CCTA-Guided Intensive Atheroprotective Strategy in a Middle-Aged INOCA Patient With Challenging Arterial Features

Background: Management of ischemia with nonobstructive coronary arteries (INOCA) remains insufficiently defined in current guidelines, particularly when complicated by symptomatic myocardial bridging, evolving nonobstructive atherosclerosis, and systemic inflammation. Such overlapping mechanisms create complex diagnostic and therapeutic challenges that require individualized care. Case Summary: A 39-year-old man with recurrent chest discomfort, left anterior descending myocardial bridging, and suspected microvascular dysfunction was found to have progressive high-risk atherosclerosis and elevated systemic inflammatory burden, despite the absence of obstructive coronary disease. Multimodal imaging—including coronary computed tomography angiography with machine learning (ML)–based ischemia risk scoring and pericoronary adipose tissue analysis—enabled precise characterization of both functional and structural risk. A tailored, intensive regimen targeting lipid lowering, myocardial unloading, and inflammation control led to regression of high-risk plaque features, reduction in pericoronary adipose tissue attenuation, normalization of inflammatory markers, and complete resolution of symptoms over 15 months. Why Beyond the Guidelines: No established guideline recommendations address INOCA with concurrent symptomatic myocardial bridging, subclinical plaque progression, and residual inflammatory risk. A multimodal, off-label pharmacologic strategy was required to stabilize disease activity and restore functional status. Discussion: This case underscores the utility of phenotype-specific, imaging-guided therapy in complex INOCA presentations. Integration of ML-enhanced coronary computed tomography angiography and individualized prevention enabled both anatomic regression and physiologic recovery in a high-risk but nonobstructive phenotype. Take-Home Messages: INOCA with symptomatic myocardial bridging and inflammation may require off-label, intensive therapy. ML-enhanced multimodal imaging facilitates dynamic risk stratification and tailored treatment adjustments.