Subtraction Improves the Accuracy of Coronary CT Angiography in Patients with Severe Calcifications in Identifying Moderate and Severe Stenosis: A Multicenter Study

Published:December 29, 2022DOI:

      Rationale and Objectives

      To investigate the diagnostic accuracy of subtraction coronary computed tomographic angiography (CCTAsub) in identifying ≥ 50% and ≥ 70% coronary stenosis in patients with different degrees of calcification.

      Materials and Methods

      In this study, 180 patients with coronary calcified plaques who underwent both coronary CT angiography and invasive coronary angiography (ICA) were prospectively enrolled at five centers. Patients were divided into three groups according to the Agatston score: group A (low to moderate, < 400), group B (high, 400-999), and group C (very high, ≥ 1000). Diagnostic accuracies estimated by area under the receiver operating characteristic curve (AUC) were compared between conventional CCTA (CCTAcon) and CCTAsub, with ICA as a reference standard.


      There were 86 patients in group A, 44 in group B, and 50 in group C. In identifying ≥ 70% coronary stenosis, subtraction improved the diagnostic accuracies on a per-segment basis in group B (AUC: 0.80 vs 0.92, p = 0.001) and group C (AUC: 0.75 vs 0.84, p = 0.001) after subtraction. When identifying ≥ 50% coronary stenosis, the per-segment AUC of CCTAsub in group B and C were significantly higher than that in CCTAcon (group B: 0.81 vs 0.92, p < 0.001; group C: 0.77 vs 0.88, p < 0.001). However, no improvement was observed in group A.


      Subtraction achieved better diagnostic accuracy in patients with Agatston score ≥ 400, both in identifying ≥ 50% and ≥ 70% coronary stenosis, which was instructive for the application of subtraction in clinical practice.

      Key Words


      CCTA (Coronary computed tomographic angiography), CAD (coronary artery disease), CAC (coronary artery calcium), CCTAsub (subtraction coronary computed tomographic angiography), CACS (coronary artery calcium score), CCTAcon (conventional coronary computed tomographic angiography), ICA (invasive coronary angiography), RCA (right coronary artery), LAD (left anterior descending), LCx (left circumflex artery), IQR (interquartile ranges), AUC (area under the curve), ROC (receiver operating characteristic curve), FFR (fractional flow reserve)
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        • Fuchs A
        • Kühl JT
        • Chen MY
        • et al.
        Feasibility of coronary calcium and stent image subtraction using 320-detector row CT angiography.
        J Cardiovasc Comput Tomogr. 2015; 9: 393-398
        • Kwan AC
        • Gransar H
        • Tzolos E
        • et al.
        The accuracy of coronary CT angiography in patients with coronary calcium score above 1000 Agatston Units: comparison with quantitative coronary angiography.
        J Cardiovasc Comput Tomogr. 2021; 15: 412-418
        • Fuchs A
        • Kühl JT
        • Chen MY
        • et al.
        Subtraction CT angiography improves evaluation of significant coronary artery disease in patients with severe calcifications or stents-the C-Sub 320 multicenter trial.
        Eur Radiol. 2018; 28: 4077-4085
        • Yoshioka K
        • Tanaka R
        • Muranaka K
        • et al.
        Subtraction coronary CT angiography using second-generation 320-detector row CT.
        Int J Cardiovasc Imaging. 2015; 31: 51-58
        • Guo W
        • Tripathi P
        • Yang S
        • et al.
        Modified Subtraction Coronary CT Angiography with a Two-Breathhold Technique: image quality and diagnostic accuracy in patients with Coronary Calcifications.
        Korean J Radiol. 2019; 20: 1146-1155
        • Chen CC
        • Wu PW
        • Tsay PK
        • et al.
        Subtracted Computed Tomography Angiography in the Evaluation of Coronary Arteries with Severe Calcification or Stents using a 320-Row Computed Tomography Scanner.
        J Thorac Imaging. 2020; 35: 317-325
        • Tanaka R
        • Yoshioka K
        • Muranaka K
        • et al.
        Improved evaluation of calcified segments on coronary CT angiography: a feasibility study of coronary calcium subtraction.
        Int J Cardiovasc Imaging. 2013; 29: 75-81
        • Viladés Medel D
        • Leta R
        • Alomar Serralach X
        • et al.
        Reliability of a new method for coronary artery calcium or metal subtraction by 320-row cardiac CT.
        Eur Radiol. 2016; 26: 3208-3214
        • Cury RC
        • Leipsic J
        • Abbara S
        • et al.
        CAD-RADS 2.0 - 2022 Coronary Artery Disease-Reporting and Data System: an Expert Consensus Document of the Society of Cardiovascular Computed Tomography (SCCT), the American College of Cardiology (ACC), the American College of Radiology (ACR), and the North America Society of Cardiovascular Imaging (NASCI) [published online ahead of print, 2022 Sep 9].
        JACC Cardiovasc Imaging. 2022; (S1936-878X(22)00401-6)
        • Yoshioka K
        • Tanaka R
        • Muranaka K.
        Subtraction coronary CT angiography for calcified lesions.
        Cardiol Clin. 2012; 30: 93-102
        • Cury RC
        • Abbara S
        • Achenbach S
        • et al.
        CAD-RADS(TM) Coronary Artery Disease - Reporting and Data System. An expert consensus document of the Society of Cardiovascular Computed Tomography (SCCT), the American College of Radiology (ACR) and the North American Society for Cardiovascular Imaging (NASCI). Endorsed by the American College of Cardiology.
        J Cardiovasc Comput Tomogr. 2016; 10: 269-281
        • Huang C
        • Wan WJ
        • Yao YH
        • et al.
        Feasibility of Subtraction Coronary Computed Tomographic Angiography and influencing factor analysis: a Retrospective Study.
        Curr Med Sci. 2021; 41: 821-826
        • Xu L
        • Li F
        • Wu K
        • et al.
        Subtraction improves the accuracy of coronary CT angiography for detecting obstructive disease in severely calcified segments.
        Eur Radiol. 2021; 31: 6211-6219
        • Agatston AS
        • Janowitz WR
        • Hildner FJ
        • et al.
        Quantification of coronary artery calcium using ultrafast computed tomography.
        J Am Coll Cardiol. 1990; 15: 827-832
        • Osborne-Grinter M
        • Kwiecinski J
        • Doris M
        • et al.
        Association of coronary artery calcium score with qualitatively and quantitatively assessed adverse plaque on coronary CT angiography in the SCOT-HEART trial.
        Eur Heart J Cardiovasc Imaging. 2022; 23: 1210-1221
        • Yuoness SA
        • Goha AM
        • Romsa JG
        • et al.
        Very high coronary artery calcium score with normal myocardial perfusion SPECT imaging is associated with a moderate incidence of severe coronary artery disease.
        Eur J Nucl Med Mol Imaging. 2015; 42: 1542-1550
        • Leipsic J
        • Abbara S
        • Achenbach S
        • et al.
        SCCT guidelines for the interpretation and reporting of coronary CT angiography: a report of the Society of Cardiovascular Computed Tomography Guidelines Committee.
        J Cardiovasc Comput Tomogr. 2014; 8: 342-358
        • Yi Y
        • Xu C
        • Guo N
        • et al.
        Performance of an Artificial Intelligence-based Application for the Detection of Plaque-based Stenosis on Monoenergetic Coronary CT Angiography: validation by Invasive Coronary Angiography.
        Acad Radiol. 2022; 29: S49-S58
        • Maurovich-Horvat P
        • Bosserdt M
        • et al.
        • DISCHARGE Trial Group
        CT or Invasive Coronary Angiography in Stable Chest Pain.
        N Engl J Med. 2022; 386: 1591-1602
        • Ciusdel C
        • Turcea A
        • Puiu A
        • et al.
        Deep neural networks for ECG-free cardiac phase and end-diastolic frame detection on coronary angiographies.
        Comput Med Imaging Graph. 2020; 84101749
        • Amanuma M
        • Kondo T
        • Sano T
        • et al.
        Subtraction coronary Computed Tomography in patients with severe calcification.
        Int J Cardiovasc Imaging. 2015; 31: 1635-1642
        • Takahashi M
        • Takaoka H
        • Ota J
        • et al.
        An increased diagnostic accuracy of significant Coronary Artery Stenosis using 320-slice Computed Tomography with Model-based Iterative reconstruction in cases with severely calcified Coronary Arteries.
        Intern Med. 2022;
        • Budoff MJ
        • Li D
        • Kazerooni EA
        • et al.
        Diagnostic accuracy of noninvasive 64-row Computed Tomographic Coronary Angiography (CCTA) compared with Myocardial Perfusion Imaging (MPI): the PICTURE Study, A Prospective Multicenter Trial.
        Acad Radiol. 2017; 24: 22-29
        • Opolski MP
        • Kim WK
        • Liebetrau C
        • et al.
        Diagnostic accuracy of Computed Tomography angiography for the detection of coronary artery disease in patients referred for transcatheter aortic valve implantation.
        Clin Res Cardiol. 2015; 104: 471-480
        • Gatti M
        • Gallone G
        • Poggi V
        • et al.
        Diagnostic accuracy of coronary computed tomography angiography for the evaluation of obstructive coronary artery disease in patients referred for transcatheter aortic valve implantation: a systematic review and meta-analysis.
        Eur Radiol. 2022; 32: 5189-5200
        • Budoff MJ
        • Dowe D
        • Jollis JG
        • et al.
        Diagnostic performance of 64-multidetector row coronary Computed Tomographic angiography for evaluation of coronary artery stenosis in individuals without known coronary artery disease: results from the prospective multicenter ACCURACY (Assessment by Coronary Computed Tomographic Angiography of individuals undergoing invasive coronary angiography) trial.
        J Am Coll Cardiol. 2008; 52: 1724-1732
        • Cheng V
        • Gutstein A
        • Wolak A
        • et al.
        Moving beyond binary grading of coronary arterial stenoses on coronary computed tomographic angiography: insights for the imager and referring clinician.
        JACC Cardiovasc Imaging. 2008; 1: 460-471
        • Abdulla J
        • Pedersen KS
        • Budoff M
        • et al.
        Influence of coronary calcification on the diagnostic accuracy of 64-slice Computed Tomography coronary angiography: a systematic review and meta-analysis.
        Int J Cardiovasc Imaging. 2012; 28: 943-953
        • Li F
        • He Q
        • Xu L
        • et al.
        Diagnostic accuracy of Subtraction Coronary CT Angiography in severely calcified segments: comparison between readers with different levels of experience.
        Front Cardiovasc Med. 2022; 9828751
        • Kamo Y
        • Fujimoto S
        • Nozaki YO
        • et al.
        Incremental diagnostic value of CT Fractional Flow Reserve using subtraction method in patients with severe Calcification: aPilot Study.
        J Clin Med. 2021; 10: 4398
        • Kalisz K
        • Buethe J
        • Saboo SS
        • et al.
        Artifacts at Cardiac CT: physics and solutions.
        Radiographics. 2016; 36: 2064-2083
        • De Santis D
        • Jin KN
        • Schoepf UJ
        • et al.
        Heavily calcified Coronary Arteries: advanced Calcium Subtraction improves Luminal Visualization and Diagnostic Confidence in Dual-Energy Coronary Computed Tomography Angiography.
        Invest Radiol. 2018; 53: 103-109