Diagnostic performance of coronary computed tomography (CT) angiography derived fractional flow reserve (CTFFR) in patients with coronary artery calcification: insights from multi-center experiments in China

Abstract

Background: Coronary computed tomography angiography (CCTA) is affected by calcification artifacts, which reduces its diagnostic efficacy. CT-derived fractional flow reserve (CTFFR) based on CCTA has been proven to be accurate in the diagnosis of non-calcified patients, but its clinical use in patients with calcified coronary artery disease remains to be investigated. The purpose of this study was to determine the effect of coronary artery calcification on CTFFR.

Methods: CCTA, coronary angiography, and FFR were performed on 128 patients in three clinical medical centers. Local investigators performed an assessment of stenosis for CCTA and the core laboratory performed the CTFFR calculations. CTFFR ≤0.8 and diameter stenosis ≥50% for CCTA was identified as lesion-specific ischemia. The diagnostic performance of CTFFR in identifying the diagnostic sensitivity, specificity, and accuracy was analyzed using an invasive FFR ≤0.8 as the gold standard. We compared the diagnostic performances between CTFFR and CCTA according to the level of calcification. We divided patients into four groups based on the coronary artery calcification score [coronary artery calcification score (CACS) =0, >0 to <100, ≥100 to <400, and ≥400].

Results: The Youden index indicated an optimal threshold of 0.80 for CTFFR to identify functionally ischemic lesions. The sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and area under receiver operating characteristic curve (AUC) for CTFFR on a per-patient basis were 90% (80-96%), 98% (92-99%), 94% (89-97%), 98% (91-99%), 92% (83-97%), and 96.9% (94.2-99.6%), respectively. Compared to CCTA, CTFFR had a higher specificity, accuracy, PPV, NPV, and AUC in both the low to intermediate calcification group and the high calcification group. The diagnostic efficacy of CTFFR was higher than that of CCTA without the influence of calcification.

Conclusions: This Chinese multi-center study showed that CTFFR based on novel computational fluid dynamics (CFD) modeling demonstrated very high diagnostic efficacy compared to the invasive measurement of FFR in all lesions suspected coronary artery disease (CAD). Of particular note are the high specificity, sensitivity, and accuracy of CTFFR, even in patients with calcification, which were significantly better than previous CCTA assessments.

Keywords: CT-derived fractional flow reserve (CTFFR); computed tomography angiography (CTA); coronary artery calcification.

Figure 1

Flow chart of this study. CCTA, coronary computed tomography angiography; CTA, computed tomography angiography; CTFFR, fractional flow reserve derived from coronary computed tomography angiography; FFR, fractional flow reserve; CACS, coronary artery calcification score.

Figure 2

Receiver operating characteristic curve of the diagnostic performances of CTFFR and CCTA fractional flow reserve. AUC of the detection of ischemia with CTFFR (≤0.80) and CCTA (≥50% stenosis) using FFR as the reference standard. (A) Patients with all lesions; (B) patients with low calcification; (C) patients with high calcification. CTFFR, fractional flow reserve derived from coronary computed tomography angiography; AUC, area under the receiver operating characteristic curve; CCTA, coronary computed tomography angiography; FFR, fractional flow reserve; 95% CI, 95% confidence interval.

Figure 3

Bland-Altman and Scatter plots of the association between CTFFR and FFR. Bland-Altman plots (a-c) and correlation (A-C) of invasive FFR versus CTFFR. For all patients (n=128) (A,a); for patients with low calcification (B,b); for patients with high calcification (C,c). CTFFR, fractional flow reserve derived from coronary computed tomography angiography; FFR, fractional flow reserve; SD, standard deviation; 95% CI, 95% confidence interval.