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Purpose: The present study investigated the diagnostic accuracy and clinical implications of moderate stenosis (50–69%, CoronaryArtery Disease Reporting and Data System, grade 3) on coronary computed tomography angiography (CCTA), comparedwith invasive coronary angiography (ICA). Materials and Methods: Two hundred and seventy-six patients who underwent ICA due to moderate stenosis alone on CCTAwere selected from our prospective registry cohort. Results: Diagnostic concordance between CCTA and ICA was found in only 50 (18%) patients. Among the 396 vessels and 508segments with moderate stenosis, diagnostic concordance was found in 132 vessels (33%) and 127 segments (25%). Segmentswith calcified plaque had lower diagnostic concordance than those with mixed or non-calcified plaque (22% vs. 28% vs. 27%, respectively,p=0.001). While calcified plaque burden did not have an influence on severe stenosis (≥70%) on ICA, higher burden ofnon-calcified plaque was correlated with a greater incidence of ICA-based severe stenosis, which was more frequent in patientswith ≥3 segments of non-calcified plaque (75%) than those without non-calcified plaque (22%, p<0.001). Typical angina and mixedor non-calcified plaque were correlated with a higher incidence of under-diagnosis, while the use of next-generation computed tomographyscanners reduced the incidence of under-diagnosis. Increased body weight, left circumflex artery involvement, andcalcified plaque were independent factors that increased the risk of over-diagnosis of CCTA. Conclusion: The diagnosis of moderate stenosis by CCTA may be limited in estimating the exact degree of ICA-based anatomicalstenosis. Unlike calcific burden, non-calcific burden was positively correlated with the presence of severe stenosis on ICA.

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