European Radiology

, Volume 28, Issue 10, pp 4077–4085 | Cite as

Subtraction CT angiography improves evaluation of significant coronary artery disease in patients with severe calcifications or stents—the C-Sub 320 multicenter trial

  • Andreas FuchsEmail author
  • J. Tobias Kühl
  • Marcus Y. Chen
  • David Viladés Medel
  • Xavier Alomar
  • Sujata M. Shanbhag
  • Steffen Helqvist
  • Klaus F. Kofoed



Diagnostic accuracy of conventional coronary CT angiography (CCTAconv) may be compromised by blooming artifacts from calcifications or stents. Blooming artifacts may be reduced by subtraction coronary CT angiography (CCTAsub) in which non-contrast and contrast CT data sets are subtracted digitally. We tested whether CCTAsub in patients with severe coronary calcification or stents reduces the number of false-positive stenosis evaluations compared with CCTAconv.


In this study, 180 symptomatic patients scheduled for invasive coronary angiography (ICA) were prospectively enrolled and CT scanned (2013-2016) at three international centers. CCTAconv, and CCTAsub data sets were reconstructed. Target segments were defined as motion-free coronary segments with a suspected stenosis (> 50% of lumen) potentially due to blooming of either calcium or stents. Target segments were evaluated with respect to misregistration artifacts from the CCTAsub reconstruction process, in which case evaluation was omitted. CCTAsub and CCTAconv were compared with ICA. Primary outcome measure was the frequency of false positives by CCTAconv versus CCTAsub to identify > 50% coronary stenosis by ICA on a per-segment level.


After exclusion of 76 patients, 104 (14% females) with mean age 67 years and median Agatston score 852 were included. There were 136 target segments with misregistration and 121 target segments without. Accuracy calculations in target segments without misregistration showed a reduction of the false positives from 72% [95% confidence interval (CI): 63-80%] in CCTAconv to 33% (CI:25-42%) in CCTAsub, at the expense of 7% (CI:3-14%) false negatives in CCTAsub.


In severely calcified coronary arteries or stents, CCTAsub reduces the false-positive rate in well-aligned, calcified or stent segments suspected of significant stenosis on CCTAconv. Nevertheless, misregistration artifacts are frequent in CCTAsub.

Key Points

• A high calcium-score reduces the diagnostic accuracy in patients scanned with cardiac CT.

• These patients would normally need an invasive angiogram for diagnosis.

• In this prospective, multicenter study, subtraction CT, when evaluable, reduces false-positive stenosis evaluations.

• Subtraction coronary CT angiography may, when evaluable, reduce excessive downstream testing.


Subtraction technique Artifact reduction Computed tomography angiography Coronary artery disease Stents 



Adaptive iterative dose reduction 3D


Coronary artery disease


Coronary computed tomography angiography


Confidence interval


Computed tomography digital subtraction angiography


Invasive coronary angiography



The authors thank project nurses Christina Møller and Bente Andersen for excellent assistance.


The authors state that this work has not received any funding.

Compliance with ethical standards


The scientific guarantor of this publication is tenured senior author: Klaus Fuglsang Kofoed.

Conflict of interest

The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.

Statistics and biometry

Lene Theil Skovgaard, Associate Professor at the Department of Biostatistics, University of Copenhagen, kindly provided statistical advice for this manuscript.

Informed consent

Written informed consent was waived by the Institutional Review Board.

Ethical approval

Institutional Review Board approval was obtained.


• prospective

• diagnostic or prognostic

• multicentre study


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Copyright information

© European Society of Radiology 2018

Authors and Affiliations

  • Andreas Fuchs
    • 1
    Email author
  • J. Tobias Kühl
    • 1
  • Marcus Y. Chen
    • 2
  • David Viladés Medel
    • 3
  • Xavier Alomar
    • 3
  • Sujata M. Shanbhag
    • 2
  • Steffen Helqvist
    • 1
  • Klaus F. Kofoed
    • 1
    • 4
  1. 1.Department of Cardiology, The Heart Center, RigshospitaletUniversity of CopenhagenCopenhagenDenmark
  2. 2.National Heart Lung and Blood InstituteNational Institutes of HealthBethesdaUSA
  3. 3.Clinica Creu BlancaUniversitat Autonoma de BarcelonaBarcelonaSpain
  4. 4.Department of Radiology, The Diagnostic Center, RigshospitaletUniversity of CopenhagenCopenhagenDenmark

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