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

Background: Coronary artery calcium (CAC) scoring is used to stratify acute coronary syndrome (ACS) risk. Nonetheless, patients with CAC score of zero (CAC0) remain at risk from noncalcified plaque components. Objective: To explore CTA-derived coronary artery plaque characteristics in symptomatic patients with CAC0 who experience subsequent ACS through comparisons with patients with CAC score greater than zero (CAC>0) who experience subsequent ACS, and with patients with CAC0 but without subsequent ACS. Methods: 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. Results: 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 CAC0. In the ACS group, culprit lesions in CAC0 and CAC>0 subsets showed no significant differences in fibrous, fibrofatty, or necrotic-core plaque volumes (p>.05). In the CAC0 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). Conclusion: After propensity-score matching, 23% of patients with ACS had CAC0. Patients with CAC0 in the ACS and control groups showed significant differences in volumes of noncalcified plaque components. Clinical Impact: Methods that identify and quantify noncalcified plaque forms may help characterize ACS risk in symptomatic patients with CAC0.