Abstract:Coronary artery calcium (CAC) is highly predictive of cardiovascular events. While millions of chest CT scans are performed annually in the United States, CAC is not routinely quantified from scans done for non-cardiac purposes. A deep learning algorithm was developed using 446 expert segmentations to automatically quantify CAC on non-contrast, non-gated CT scans (AI-CAC). Our study differs from prior works as we leverage imaging data across the Veterans Affairs national healthcare system, from 98 medical centers, capturing extensive heterogeneity in imaging protocols, scanners, and patients. AI-CAC performance on non-gated scans was compared against clinical standard ECG-gated CAC scoring. Non-gated AI-CAC differentiated zero vs. non-zero and less than 100 vs. 100 or greater Agatston scores with accuracies of 89.4% (F1 0.93) and 87.3% (F1 0.89), respectively, in 795 patients with paired gated scans within a year of a non-gated CT scan. Non-gated AI-CAC was predictive of 10-year all-cause mortality (CAC 0 vs. >400 group: 25.4% vs. 60.2%, Cox HR 3.49, p < 0.005), and composite first-time stroke, MI, or death (CAC 0 vs. >400 group: 33.5% vs. 63.8%, Cox HR 3.00, p < 0.005). In a screening dataset of 8,052 patients with low-dose lung cancer-screening CTs (LDCT), 3,091/8,052 (38.4%) individuals had AI-CAC >400. Four cardiologists qualitatively reviewed LDCT images from a random sample of >400 AI-CAC patients and verified that 527/531 (99.2%) would benefit from lipid-lowering therapy. To the best of our knowledge, this is the first non-gated CT CAC algorithm developed across a national healthcare system, on multiple imaging protocols, without filtering intra-cardiac hardware, and compared against a strong gated CT reference. We report superior performance relative to previous CAC algorithms evaluated against paired gated scans that included patients with intra-cardiac hardware.