## 1 Current Role of CCTA in Clinical Practice and Guidelines
### Plaque Morphology  
Although the risk of plaque rupture is proportional to the extent of stenosis, it has been reported that nonobstructive lesions with typical features of plaque composition represent the majority of culprit lesions in ACS. [PERSON] et al. realized a nested case-control study within a cohort of 25,251 patients undergoing CCTA with a follow-up of 3.4 years. ACS and non-event patients without prior CAD were matched for risk factors and CCTA-rated obstructive (\(\geq\)50%) CAD [23]. Thus, separate core laboratories performed a blinded assessment of coronary lesions detected by CCTA, quantifying the percent stenosis diameter (SD), the percent plaque burden (PB), the plaque volume (PV) by composition (calcified, fibrous, fibrofatty, and necrotic core), and identifying high-risk plaques (HRP) (Figures 1 and 2). Notably, HRP was reported in 52% of ACS patients. Moreover, the authors reported higher PB and fibrofatty and necrotic PV in patients with ACS than non-event patients, regardless of stenosis severity [23]. Figure 1: Right coronary artery unstable plaque: (**a**) Coronary computed tomography angiography (CCTA) assessment; (**b**) invasive coronary angiography (ICA) assessment. From a histopathological perspective, a vulnerable plaque is defined by a thin fibrous cap, a large necrotic core, the presence of positive remodeling (PR) (remodeling index > 1.1), perivascular inflammation, and spotty calcifications. Moreover, recent studies have reported a specific attenuation pattern of atherosclerotic plaques on coronary CT images called \"napkin ring sign\" (NRS) [24]. It is described as a plaque core with low CT attenuation surrounded by a rim-like area of higher CT attenuation. The pathophysiology of this finding remains unclear, even if it may be linked to various high-risk characteristics such as contrast enhancement of the vasa vasorum, intraplaque hemorrhage, microcalcifications, or even healed ruptures [19]. Interestingly, [PERSON] et al., in a study involving heart donors, found that the detection of NRS at CCTA had high specificity and positive predictive value for the presence of advanced lesions [25]. Furthermore, [PERSON] et al. evaluated coronary plaque characteristics with both CCTA and optical coherence tomography (OCT) [26]. They showed that PR and the presence of low-attenuation plaques (LAP) detected by CCTA are associated with thin cap fibroatheroma (TCFA) and higher macrophage infiltration evaluated by OCT. Concordantly, [PERSON] et al. described a higher prevalence of remodeling in unstable plaques than in stable plaques [27]. Finally, in a sub-analysis of the NXT (HeartFlowNXT: HeartFlow Analysis of Coronary Blood Flow Using Coronary CT Angiography) study, CCTA, invasive angiography, and fractional flow reserve (FFR) were acquired for 383 lesions in patients with stable coronary syndromes [28]. The study revealed that LAP detected on CCTA significantly correlated with the presence of ischemia identified by FFR. It has also been shown that the evaluation of plaque morphology with the detection of high-risk characteristics by CCTA is a useful method for forecasting future negative outcomes and the advancement of CAD. [PERSON] et al., in a large longitudinal study, reported that both PR and LAP were strong predictors of future ACS events [29]. A sub-analysis of the SCOT-HEART trial revealed that the presence of adverse coronary plaque features confers a 3-fold increased risk of cardiovascular death or nonfatal MI [30]. Therefore, the Coronary Artery Disease Reporting and Data System (CAD-RADS) recommendations advise mentioning the existence of susceptible plaque whenever there are two or more high-risk criteria present (Figure 3) [31]. However, the image quality may be affected by artifacts invalidating the estimation of plaque morphology [32; 33]. The most common are the motion and blooming artifacts, cause of severity overestimation of calcite plaques.