CTA-Derived Plaque Characteristics and Risk of Acute Coronary Syndrome in Patients With Coronary Artery Calcium Score of Zero: Insights From the ICONIC Trial

Rebecca A. Jonas, Department of Cardiovascular Disease, Rush University Medical Center, Chicago, IL, USA.
Nick S. Nurmohamed, Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Tami R. Crabtree, Cleerly Inc, Denver, Colorado, USA.
Melissa Aquino, Cleerly Inc, Denver, Colorado, USA.
Robert Jennings, Cleerly Inc, Denver, Colorado, USA.
Andrew D. Choi, Division of Cardiology, The George Washington University School of Medicine, Washington, DC, USA.
Fay Y. Lin, Icahn School of Medicine at Mount Sinai, New York, NY.
Sang-Eun Lee, Division of Cardiology, Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, South Korea.
Daniele Andreini, Centro Cardiologico Monzino, IRCCS, Milan, Italy; Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy.
Jeroen Bax, Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
Fillipo Cademartiri, Fondazione Monasterio/CNR, Pisa, Italy.
Kavitha Chinnaiyan, Beaumont Hospital, Royal Oak, MI.
Benjamin J. Chow, University of Ottawa Heart Institute, Canada, Department of Medicine (Cardiology) & Department of Radiology; University of Ottawa, Canada.
Edoardo Conte, Centro Cardiologico Monzino, IRCCS, Milan, Italy; Division of University Cardiology, IRCCS Ospedale Galeazzi-Sant'Ambrogio, Milan, Italy.
Ricardo Cury, Department of Radiology, Miami Cardiac and Vascular Institute, Miami, FL, USA.
Gudrun Feuchtner, Department of Radiology, Medical University of Innsbruck, Innsbruck, Austria.
Martin Hadamitzky, Department of Radiology and Nuclear Medicine, German Heart Center Munich, Munich, Germany.
Yong-Jin Kim, Department of Internal Medicine, Seoul National University College of Medicine, Cardiovascular Center, Seoul National University Hospital, Seoul, South Korea.
Erica Maffei, IRCCS SYNLAB SDN, Naples, Italy.
Hugo Marques, Faculdade de Medicina da Universidade Católica Portuguesa, Lisboa, Portugal.
Fabian Plank, Department of Radiology, Medical University of Innsbruck, Innsbruck, Austria.
Gianluca Pontone, Department of Perioperative Cardiology and Cardiovascular Imaging, Centro Cardiologico Monzino IRCCS Milan, Italy.
Alexander R. van Rosendael, Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
Todd C. Villines, University of Virginia Health System, Charlottesville, Virginia.
Subhi J. Al'Aref, Department of Medicine, Division of Cardiology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Lohendran Baskaran, Department of Cardiology, National Heart Centre Singapore, Singapore, Singapore.
Iksung Cho, Cardiovascular Division, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, South Korea.
Ibrahim Danad, Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Ran Heo, Yonsei University College of Medicine, Yonsei University Health System, Seoul South Korea.
Ji Hyun Lee, Cardiovascular Division, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, South Korea.
Asim Rizvi, Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, USA.
Wijnand J. Stuijfzand, Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

Document Type

Journal Article

Publication Date

4-30-2025

Journal

AJR. American journal of roentgenology

DOI

10.2214/AJR.24.31476

Abstract

Coronary artery calcium (CAC) scoring is used to stratify acute coronary syndrome (ACS) risk. Nonetheless, patients with CAC score of zero (CAC) remain at risk from noncalcified plaque components. To explore CTA-derived coronary artery plaque characteristics in symptomatic patients with CAC who experience subsequent ACS through comparisons with patients with CAC score greater than zero (CAC) who experience subsequent ACS, and with patients with CAC but without subsequent ACS. This study entailed secondary retrospective analysis of prior prospective registry data. The international multicenter CONFIRM registry collected longitudinal observational data on symptomatic patients who underwent clinically indicated coronary CTA from January, 2004 to May, 2010. ICONIC was a nested cohort study conducted within CONFIRM that identified patients without known coronary artery disease (CAD) at time of CTA who did and did not experience subsequent ACS (i.e., ACS and control groups), propensity matched in a 1:1 ratio based on CAD risk factors and CAD severity on CTA. The present ICONIC substudy selected matched patients in the ACS and control groups who both had documented CAC scores. CTA examinations were analyzed using artificial intelligence software for automated quantitative plaque assessment. In the ACS group, invasive angiography findings were used to identify culprit lesions. The present study included 216 patients (mean age, 55.6 years; 91 female, 125 male), with 108 patients in each of the ACS and control groups. In the ACS group, 23% (n=25) of patients had CAC. In the ACS group, culprit lesions in CAC and CAC subsets showed no significant differences in fibrous, fibrofatty, or necrotic-core plaque volumes (p>.05). In the CAC subset, patients with ACS, compared with control patients, had greater mean fibrous plaque volume (29.4±42.0 vs 5.5±15.2 mm3, p<.001), fibrofatty plaque volume (27.3±52.2 vs 1.3±3.7 mm3, p<.001), and necrotic-core plaque volume (2.8±6.4 vs 1.3±3.7 mm3, p<.001). After propensity-score matching, 23% of patients with ACS had CAC. Patients with CAC in the ACS and control groups showed significant differences in volumes of noncalcified plaque components. Methods that identify and quantify noncalcified plaque forms may help characterize ACS risk in symptomatic patients with CAC.

Department

Medicine

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