BACKGROUND: Discrepancies between stenosis severity assessed at coronary computed tomography angiography (CCTA) and ischemia might depend on vessel type. Coronary plaque features are associated with ischemia. Thus, we evaluated the vessel-specific correlation of CCTA-derived diameter stenosis (DS) and invasive fractional flow reserve (FFR) and explored whether integrating morphological plaque features stratified by vessel might increase the predictive yield in identifying vessel-specific ischemia. METHODS: Observational cohort study including patients undergoing CCTA for suspected coronary artery disease, with at least one vessel with DS ≥ 50 % at CCTA, undergoing invasive coronary angiography and FFR. Plaque analysis was performed using validated semi-automated software. Coronary vessels were stratified in left anterior descending (LAD), left circumflex (LCX), and right coronary artery (RCA). Per vessel independent predictors of ischemia among CCTA-derived anatomical and morphologic plaque features were tested at univariable and multivariable logistic regression analysis. The best cut-off to predict ischemia was determined by Youden's index. Ischemia was defined by FFR≤0.80. RESULTS: The study population consisted of 192 patients, of whom 224 vessels (61 % LAD, 19 % LCX, 20 % RCA) had lesions with DS ≥ 50 % interrogated by FFR. Despite similar DS, the rate of FFR≤0.80 was higher in the LAD compared to LCX and RCA (67.2 % vs 43.2 % and 44.2 %, respectively, p = 0.018). A significant correlation between DS and FFR was observed only in LAD (p = 0.003). At multivariable analysis stratified by vessel, the vessel-specific independent predictors of positive FFR were percent atheroma volume (threshold>
17 %) for LAD, non-calcified plaque volume (threshold >
130 mm CONCLUSIONS: Integrating DS and vessel-specific morphological plaque features significantly increased the predictive yield for vessel-specific ischemia compared to DS alone, potentially improving patients' referral to the catheterization laboratory.