Abstract
OBJECTIVES: Whether a stenosis can cause hemodynamic lesion-specific ischemia is critical for the treatment decision in patients with coronary artery disease (CAD). Based on coronary computed tomography angiography (CCTA), CT fractional flow reserve (FFR(CT)) can be used to assess lesion-specific ischemia. The selection of an appropriate site along the coronary artery tree is vital for measuring FFR(CT). However the optimal site to measure FFR(CT) for a target stenosis remains to be adequately determined. The purpose of this study was to determine the optimal site to measure FFR(CT) for a target lesion in detecting lesion-specific ischemia in CAD patients by evaluating the performance of FFR(CT) measured at different sites distal to the target lesion in detecting lesion-specific ischemia with FFR measured with invasive coronary angiography (ICA) as reference standard. METHODS: In this single-center retrospective cohort study, a total of 401 patients suspected of having CAD underwent invasive ICA and FFR between March 2017 and December 2021 were identified. 52 patients having both CCTA and invasive FFR within 90 days were enrolled. Patients with vessels 30%-90% diameter stenosis as determined by ICA were referred to invasive FFR evaluation, which was performed 2-3 cm distal to the stenosis under the condition of hyperemia. For each vessel with 30%-90% diameter stenosis, if only one stenosis was present, this stenosis was selected as the target lesion; if serial stenoses were present, the stenosis most distal to the vessel end was chosen as the target lesion. FFR(CT) was measured at four sites: 1 cm, 2 cm, and 3 cm distal to the lower border of the target lesion (FFR(CT)-1 cm, FFR(CT)-2 cm, FFR(CT)-3 cm), and the lowest FFR(CT) at the distal vessel tip (FFR(CT)-lowest). The normality of quantitative data was assessed using the Shapiro-Wilk test. Pearson's correlation analysis and Bland-Altman plots were used for assessing the correlation and difference between invasive FFR and FFR(CT). Correlation coefficients derived from Chi-suqare test were used to assess the correlation between invasive FFR and the cominbaiton of FFR(CT) measred at four sites. The performances of significant obstruction stenosis (diameter stenosis ≥ 50%) at CCTA and FFR(CT) measured at the four sites and their combinations in diagnosing lesion-specific ischemia were evaluated by receiver-operating characteristic (ROC) curves using invasive FFR as the reference standard. The areas under ROC curves (AUCs) of CCTA and FFR(CT) were compared by the DeLong test. RESULTS: A total of 72 coronary arteries in 52 patients were included for analysis. Twenty-five vessels (34.7%) had lesion-specific ischemia detected by invasive FFR and 47 vesseles (65.3%) had no lesion-spefifice ischemia. Good correlation was found between invasive FFR and FFR(CT)-2 cm and FFR(CT)-3 cm (r = 0.80, 95% CI, 0.70 to 0.87, p < 0.001; r = 0.82, 95% CI, 0.72 to 0.88, p < 0.001). Moderate correlation was found between invasive FFR and FFR(CT)-1 cm and FFR(CT)-lowest (r = 0.77, 95% CI, 0.65 to 0.85, p < 0.001; r = 0.78, 95% CI, 0.67 to 0.86, p < 0.001). FFR(CT)-1 cm + FFR(CT)-2 cm, FFR(CT)-2 cm + FFR(CT)-3 cm, FFR(CT)-3 cm + FFR(CT)-lowest, FFR(CT)-1 cm + FFR(CT)-2 cm + FFR(CT)-3 cm, and FFR(CT)-2 cm + FFR(CT)-3 cm + FFR(CT)-lowest were correatled with invasive FFR (r = 0.722; 0.722; 0.701; 0.722; and 0.722, respectively; p < 0.001 for all). Bland-Altman plots revealed a mild difference between invasive FFR and the four FFR(CT) (invasive FFR vs. FFR(CT)-1 cm, mean difference -0.0158, 95% limits of agreement: -0.1475 to 0.1159; invasive FFR vs. FFR(CT)-2 cm, mean difference 0.0001, 95% limits of agreement: -0.1222 to 0.1220; invasive FFR vs. FFR(CT)-3 cm, mean difference 0.0117, 95% limits of agreement: -0.1085 to 0.1318; and invasive FFR vs. FFR(CT)-lowest, mean difference 0.0343, 95% limits of agreement: -0.1033 to 0.1720). AUCs of CCTA, FFR(CT)-1 cm, FFR(CT)-2 cm, FFR(CT)-3 cm, and FFR(CT)-lowest in detecting lesion-specific ischemia were 0.578, 0.768, 0.857, 0.856 and 0.770, respectively. All FFR(CT) had a higher AUC than CCTA (all p < 0.05), FFR(CT)-2 cm achieved the highest AUC at 0.857. The AUCs of FFR(CT)-2 cm and FFR(CT)-3 cm were comparable (p > 0.05). The AUCs were similar between FFR(CT)-1 cm + FFR(CT)-2 cm, FFR(CT)-3 cm + FFR(CT)-lowest and FFR(CT)-2 cm alone (AUC = 0.857, 0.857, 0.857, respectively; p > 0.05 for all). The AUCs of FFR(CT)-2 cm + FFR(CT)-3 cm, FFR(CT)-1 cm + FFR(CT)-2 cm + FFR(CT)-3 cm, FFR(CT)-and 2 cm + FFR(CT)-3 cm + FFR(CT)-lowest (0.871, 0.871, 0.872, respectively) were slightly higher than that of FFR(CT)-2 cm alone (0.857), but without significnacne differences (p > 0.05 for all). CONCLUSIONS: FFR(CT) measured at 2 cm distal to the lower border of the target lesion is the optimal measurement site for identifying lesion-specific ischemia in patients with CAD.