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Per-lesion versus per-patient analysis of coronary artery disease in predicting the development of obstructive lesions: the Progression of AtheRosclerotic PlAque DetermIned by Computed TmoGraphic Angiography Imaging (PARADIGM) study

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Abstract

To determine whether the assessment of individual plaques is superior in predicting the progression to obstructive coronary artery disease (CAD) on serial coronary computed tomography angiography (CCTA) than per-patient assessment. From a multinational registry of 2252 patients who underwent serial CCTA at a ≥ 2-year inter-scan interval, patients with only non-obstructive lesions at baseline were enrolled. CCTA was quantitatively analyzed at both the per-patient and per-lesion level. Models predicting the development of an obstructive lesion at follow up using either the per-patient or per-lesion level CCTA measures were constructed and compared. From 1297 patients (mean age 60 ± 9 years, 43% men) enrolled, a total of 3218 non-obstructive lesions were identified at baseline. At follow-up (inter-scan interval: 3.8 ± 1.6 years), 76 lesions (2.4%, 60 patients) became obstructive, defined as > 50% diameter stenosis. The C-statistics of Model 1, adjusted only by clinical risk factors, was 0.684. The addition of per-patient level total plaque volume (PV) and the presence of high-risk plaque (HRP) features to Model 1 improved the C-statistics to 0.825 [95% confidence interval (CI) 0.823–0.827]. When per-lesion level PV and the presence of HRP were added to Model 1, the predictive value of the model improved the C-statistics to 0.895 [95% CI 0.893–0.897]. The model utilizing per-lesion level CCTA measures was superior to the model utilizing per-patient level CCTA measures in predicting the development of an obstructive lesion (p < 0.001). Lesion-level analysis of coronary atherosclerotic plaques with CCTA yielded better predictive power for the development of obstructive CAD than the simple quantification of total coronary atherosclerotic burden at a per-patient level.

Clinical Trial Registration: ClinicalTrials.gov NCT0280341

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Data availability

The data that support the findings of this study are available from the corresponding author, upon reasonable request.

Code availability

The relevant SAS and R codes for the statistical analysis are available from the corresponding author, upon reasonable request.

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Funding

This work was supported by the Leading Foreign Research Institute Recruitment Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Science and ICT (MSIT) (Grant No. 2012027176) and Institute for Information & communications Technology Promotion(IITP) grant funded by the Korea government(MSIT) (No.2018-0-00861, Intelligent SW Technology Development for Medical Data Analysis). The study was also funded in part by a generous gift from the Dalio Institute of Cardiovascular Imaging and the Michael Wolk Foundation. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit the manuscript for publication.

Author information

Authors and Affiliations

  1. Division of Cardiology, Department of Internal Medicine, Ewha Womans University Seoul Hospital, Ewha Womans University College of Medicine, Seoul, South Korea

    Sang-Eun Lee

  2. Yonsei-Cedars-Sinai Integrative Cardiovascular Imaging Research Center, Yonsei University College of Medicine, Yonsei University Health System, Seoul, South Korea

    Sang-Eun Lee, Ji Min Sung & Hyuk-Jae Chang

  3. Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Yonsei University Health System, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea

    Ji Min Sung, Sanghoon Shin & Hyuk-Jae Chang

  4. Centro Cardiologico Monzino, IRCCS, Milan, Italy

    Daniele Andreini, Edoardo Conte & Gianluca Pontone

  5. Houston Methodist DeBakey Heart & Vascular Center, Houston Methodist Hospital, Houston, TX, USA

    Mouaz H. Al-Mallah

  6. Department of Medicine, Los Angeles Biomedical Research Institute, Torrance, CA, USA

    Matthew J. Budoff

  7. Cardiovascular Imaging Unit, SDN IRCCS, Naples, Italy

    Filippo Cademartiri

  8. Department of Cardiology, William Beaumont Hospital, Royal Oak, MI, USA

    Kavitha Chinnaiyan

  9. Pusan University Hospital, Busan, South Korea

    Jung Hyun Choi

  10. Seoul National University Bundang Hospital, Seongnam, South Korea

    Eun Ju Chun

  11. Department of Radiology, Casa de Saude São Jose, Rio de Janeiro, Brazil

    Ilan Gottlieb

  12. Department of Radiology and Nuclear Medicine, German Heart Center Munich, Munich, Germany

    Martin Hadamitzky

  13. Department of Internal Medicine, Seoul National University College of Medicine, Cardiovascular Center, Seoul National University Hospital, Seoul, South Korea

    Yong Jin Kim

  14. Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea

    Byoung Kwon Lee

  15. Department of Medicine and Radiology, University of British Columbia, Vancouver, BC, Canada

    Jonathon A. Leipsic

  16. Department of Radiology, Area Vasta 1/ASUR Marche, Urbino, Italy

    Erica Maffei

  17. UNICA, Unit of Cardiovascular Imaging, Hospital da Luz, Lisbon, Portugal

    Hugo Marques & Pedro de Araújo Gonçalves

  18. Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, MA, USA

    Peter H. Stone

  19. Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA

    Habib Samady

  20. Department of Pathology, CVPath Institute, Gaithersburg, MD, USA

    Renu Virmani

  21. Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Jagat Narula

  22. Department of Imaging and Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Daniel S. Berman

  23. Department of Radiology, New York-Presbyterian Hospital and Weill Cornell Medicine, New York, NY, USA

    Leslee J. Shaw, Fay Y. Lin & James K. Min

  24. Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands

    Jeroen J. Bax

Authors
  1. Sang-Eun Lee
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  2. Ji Min Sung
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  3. Daniele Andreini
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  28. Fay Y. Lin
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  29. James K. Min
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  30. Hyuk-Jae Chang
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Contributions

All authors contributed to the data collection. Study conception and design were performed by Dr.Hyuk-Jae Chang, and Dr.Sang-Eun Lee. Material preparation and analysis were performed by Dr.Ji Min Sung and Dr.Sang-Eun Lee. The first draft of the manuscript was written by Dr.Sang-Eun Lee and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Hyuk-Jae Chang.

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Conflict of interest

Dr. Chang receives funding from the Leading Foreign Research Institute Recruitment Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Science and ICT (MSIT) (Grant No. 2012027176). Dr. James K. Min receives funding from the Dalio Foundation, National Institutes of Health, and GE Healthcare. Dr. Min serves on the scientific advisory board of Arineta and GE Healthcare, and has an equity interest in Cleerly. Dr. Habib Samady serves on the scientific advisory board of Philips, has equity interest in Covanos Inc., and has a research grant from Medtronic. The remaining authors have no relevant disclosures.

Ethical approval

The study protocol was approved by the institutional review boards of all participating centers.

Informed consent

The requirement of consent to participate was waived by relevant local Ethics Committees.

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Lee, SE., Sung, J.M., Andreini, D. et al. Per-lesion versus per-patient analysis of coronary artery disease in predicting the development of obstructive lesions: the Progression of AtheRosclerotic PlAque DetermIned by Computed TmoGraphic Angiography Imaging (PARADIGM) study. Int J Cardiovasc Imaging 36, 2357–2364 (2020). https://doi.org/10.1007/s10554-020-01960-z

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