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 a CAC score of zero (CAC₀) remain at risk from noncalcified plaque components. OBJECTIVE. The purpose of this study was to explore CTA-derived coronary artery plaque characteristics in symptomatic patients with CAC₀ who subsequently have ACS through comparisons with patients with a CAC score greater than 0 (CAC_{> 0}) who subsequently have ACS as well as with patients with CAC₀ who do not subsequently have ACS. METHODS. This study entailed a secondary retrospective analysis of prior prospective registry data. The international multicenter CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) registry collected longitudinal observational data on symptomatic patients who underwent clinically indicated coronary CTA from January 2004 to May 2010. ICONIC (Incident Coronary Syndromes Identified by CT) was a nested cohort study conducted within CONFIRM that identified patients without known coronary artery disease (CAD) at the time of CTA who did and did not subsequently have ACS (i.e., the ACS and control groups, respectively) and who were propensity matched in a 1:1 ratio on the basis of 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 women and 125 men), 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 the subsets of patients with CAC₀ and CAC_{> 0} 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 (± SD) 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 0.0 ± 0.1 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.