CORA: Generalizable coronary artery disease assessment and risk stratification from coronary CT angiography using pathology-centric representation learning

Coronary artery disease, a leading cause of cardiovascular mortality worldwide, can be assessed non-invasively by coronary computed tomography angiography (CCTA). Although deep learning has advanced automated CCTA analysis, clinical translation remains constrained by the scarcity of expert-annotated data and by the spatial sparsity of coronary pathology, which occupies only a small fraction of each scan. Widely used label-free pretraining strategies, such as masked image modeling and contrastive learning, optimize for global anatomical reconstruction and tend to under-represent these tiny localized pathological features. Here we present CORA, an annotation-efficient model for comprehensive coronary artery disease assessment. Rather than reconstructing background anatomy, CORA learns from volumetric CCTA through a synthesis-driven self-supervised strategy: an anatomy-guided engine inserts diverse synthetic calcified and non-calcified lesions into unlabeled scans, reframing pretraining as an abnormality-detection task that biases representation learning toward clinically relevant disease features. We pretrained CORA on 10,138 unlabeled CCTA volumes and evaluated it across datasets from nine independent hospitals. Across plaque characterization, stenosis detection, and coronary artery segmentation, CORA consistently outperformed strong self-supervised pretraining baselines, with the largest gains on external multi-center data, indicating robust generalization under distributional shift. Coupling the imaging encoder with structured clinical variables further enabled near-term major adverse cardiac event (MACE) risk stratification. Our results show that pathology-centric, synthesis-driven pretraining is an effective and scalable strategy for annotation-efficient coronary artery disease assessment from CCTA.