Quantitative coronary calcification analysis for prediction of myocardial ischemia using non-contrast CT calcium scoring
Authors: Juhwan Lee, Sadeer Al-Kindi, Ammar Hoori, Tao Hu, Hao Wu, Justin N. Kim, Robert Gilkeson, Sanjay Rajagopalan, +1 more
Organizations: Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA, 23284, USA · Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, 44106, USA · DeBakey Heart and Vascular Institute, Houston Methodist Hospital, Houston, TX, 77030 · Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, 44106, USA · Department of Radiology, Case Western Reserve University, Cleveland, OH, 44106, USA
Abstract
Non-contrast computed tomography calcium scoring (CTCS) is widely recognized as an effective tool for cardiovascular risk stratification. This study aimed to develop a novel machine learning framework for predicting myocardial ischemia from routine non-contrast CTCS scans using quantitative coronary calcium assessment. This study analyzed 1,375 patients who underwent both non-contrast CTCS and regadenoson stress cardiac positron emission tomography myocardial perfusion imaging within one year at University Hospitals Cleveland Medical Center. A total of 74 variables, including clinical variables, Agatston score, and calcium-omics features, were evaluated. Relevant features were identified using XGBoost with Shapley Additive exPlanations (SHAP). Predictive models were trained and evaluated using 5-fold cross-validation. Among 987 patients, 89 (9%) were positive for myocardial ischemia. The final model incorporated the Agatston score, eight calcium-omics features, and age. The proposed model achieved a precision of 98.9+/-3.0%, sensitivity of 79.2+/-8.4, and F1 score of 87.7+/-5.3%. The addition of calcium-omics features significantly improved predictive performance compared with models using clinical variables alone or clinical variables with the Agatston score (p<0.05). Interestingly, the number of calcified arteries, despite being the lowest-ranked feature based on SHAP analysis, showed the strongest association with myocardial ischemia in logistic regression analysis (odds ratio: 3.63, 95% confidence interval: 2.80-4.77, p<0.00001). We developed a machine learning approach for predicting myocardial ischemia using routinely acquired non-contrast CTCS scans. Calcium-omics features provided incremental predictive value beyond conventional risk factors and Agatston scoring and may support more accessible cardiovascular risk stratification.
Non-contrast computed tomography calcium scoring (CTCS) is a cost-effective imaging modality widely used to detect coronary artery calcifications. This study aimed to develop an advanced machine learning framework that utilizes quantitative analyses of coronary calcium and epicardial fat from CTCS images to predict obstructive coronary artery disease (CAD). The study population consisted of 1,324 patients from the SCOT-HEART clinical trial who underwent both CTCS and coronary CT angiography. We extracted and analyzed a broad range of features, including 24 clinical variables, 189 calcium-omics, and 211 epicardial fat-omics features from the CTCS images. Feature selection was conducted using the CatBoost algorithm combined with SHapley Additive exPlanation (SHAP) values. Predictive modeling utilized the CatBoost gradient boosting method, focusing on the most informative features. From an initial set of 424 candidate features, 14 were identified as most predictive through the CatBoost-SHAP method. The top two predictive features originated from fat-omics, with the remaining 12 features derived from calcium-omics. The optimized model achieved robust predictive capabilities, demonstrating a sensitivity of 83.1+/-4.6%, specificity of 93.8+/-1.7%, accuracy of 85.3+/-2.0%, and an F1 score of 73.9+/-3.3%. Inclusion of calcium-omics and fat-omics data significantly improved predictive performance. Notably, the model also showed reliable predictive accuracy in patients with diverse coronary calcium scores, including cases with obstructive CAD despite a zero-calcium score. This innovative approach holds promise for improving clinical decision-making and potentially reducing dependence on contrast-enhanced or invasive diagnostic procedures, particularly within low-to intermediate-risk patient groups.
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.
Coronary artery stenosis is a common cardiovascular disease, with severe, untreated cases posing significant risks of heart attack. Although coronary (X-ray) angiograms remain the standard for stenosis diagnosis, they are invasive, time- and resource-intensive, and therefore only performed on patients with a high probability of disease based on symptoms and prior clinical tests. However, a subset of patients, especially those without symptoms, may remain undiagnosed. Detecting indications of stenosis from ECGs, which are fast, cheap, non-invasive, and thus routinely acquired even in asymptomatic patients, would support early diagnosis. However, as no reliable stenosis-specific signal has been identified in ECGs, they can not currently be used for stenosis risk stratification. To address this, we introduce StenCE, a pretraining framework, allowing stratification of patients based on features derived directly from ECGs. Evaluations across varying stenosis severity thresholds and additional ECG disease classification tasks demonstrate consistent performance improvements across different ECG encoders, outperforming previous work. The obtained models successfully detect signals for stenosis diagnosis in ECGs and are the first to achieve high performance in severe stenosis classification. The source code is available at https://github.com/NikolaCenic/ecg-stenosis-cls.