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Introduction In patients with suspected obstructive coronary artery disease (CAD) on coronary computed tomography (CTA), guidelines endorse second-line selective testing for hemodynamic evaluation of suspected CAD. A variety of non-invasive modalities are available, and myocardial perfusion imaging with Rubidium-82 positron emission tomography (PET) is an established method with high diagnostic performance. Recently, an on-site method estimating computed tomography-derived quantitative flow ratio (CT-QFR) showed promising results for discriminating obstructive CAD. However, no study has compared the diagnostic performances of PET and CT-QFR. Purpose To assess a possible non-inferiority of CT-QFR compared to PET in patients with suspected obstructive CAD at CTA using invasive coronary angiography (ICA) with fractional flow reserve (FFR) as reference. Methods Patients (n=1732, 57% males, age 59±9.5) referred on a clinical indication with symptoms suggestive of obstructive CAD underwent routine CTA. Patients with ≥50% diameter stenosis (DS) on CTA were referred for PET and subsequent ICA with FFR. CT-QFR was analyzed post-hoc blinded to PET and ICA results. Abnormal CT-QFR was defined as CT-QFR ≤0.80 in any vessel with a diameter ≥1.5mm. An independent core-lab evaluated PET scans as abnormal/normal with optional analyst-dependent application of pre-specified criteria; summed stress score of ≥4 in ≥2 contiguous segments, vessel-specific myocardial blood flow (MBF) <2.00 ml/g/min, global myocardial blood flow reserve ≤1.8, and/or transient ischemic dilatation ratio >1.13. Obstructive CAD was defined as ICA with FFR ≤0.80 or high-grade stenosis (≥90% DS). Results In total, 445/1732 patients (25%) had suspected obstructive CAD on CTA of whom 400/445 patients (90%) underwent subsequent PET and ICA. CT-QFR was successfully analysed in 383/400 (96%) patients classifying 174/383 (45%) patients as having disease. In comparison, PET classified 130/383 (34%) patients as having disease. In total, obstructive CAD by ICA with FFR was identified in 162 (42%) patients. There was no significant difference in area under the receiver-operating characteristic curves for CT-QFR compared to the best performing PET metric (lowest vessel-specific MBF); 0.84 (95% CI 0.80–0.89) vs. 0.81 (0.77–0.85), p=0.19)) (Fig. 1). Overall diagnostic accuracy of CT-QFR versus PET was similar (78% (95% CI 74–82) vs. 77% (72–81), p=0.70. Sensitivities for CT-QFR and PET were 78% (71–84) and 63% (55–70), p<0.01, respectively, and specificities 78% (72–84) and 87% (82–91), p=0.01, respectively (Fig. 2). Three-vessel or left main disease on ICA was correctly identified in 30/31 patients by both CT-QFR and PET. Conclusion In patients with suspected obstructive CAD by CTA, second-line CT-QFR was non-inferior to PET for discriminating obstructive CAD by invasive FFR; Although diagnostic accuracy was similar, CT-QFR demonstrated higher sensitivity while PET showed higher specificity Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Aarhus University PhD fellowshipRegion Mid Health Research Foundation

Introduction Guidelines recommend secondary ischemia assessment following a coronary computed tomography angiography (CTA) with suspected obstructive coronary artery disease (CAD). Coronary CTA-derived quantitative flow ratio (CT-QFR) is an on-site technique performed on acquired CTA images that estimates the functional severity of a coronary stenosis. However, CT-QFR measurements are available throughout the coronary vessel with no clear recommendations as to which specific values should be used for identifying obstructive CAD, e.g. most distal or lesion-specific values. Purpose First, to investigate the feasibility of CT-QFR and the correlation and agreement with invasive fractional flow reserve (FFR). Secondly, to compare the diagnostic performance of distal versus lesion-specific CT-QFR for identifying obstructive CAD defined by invasive coronary angiography (ICA) with FFR. Methods A total of 1732 prospectively included patients with symptoms suggestive of CAD referred for CTA were included. All patients with ≥50% diameter stenosis (DS) on CTA were subsequently referred for ICA with conditional FFR in lesions with 30–89%DS. Obstructive CAD was defined by ICA as FFR ≤0.80 or high-grade stenosis by visual assessment (≥90%DS). A blinded analysis of CT-QFR was performed in patients referred to ICA with measurements at the distal end of a vessel (distal CT-QFR) and 1 cm distal to stenotic lesions on CTA (lesion-specific). CT-QFR ≤0.80 was defined as abnormal. For correlation analyses to invasive FFR, CT-QFR was assessed corresponding to the position of the invasive pressure sensor. Results In total, 445/1732 (25%) patients had suspected obstructive CAD at CTA and underwent subsequent ICA. CT-QFR analysis was feasible in 423/445 (95%) patients. CT-QFR correlated (Pearson's rho 0.54, p<0.001) and agreed (mean difference –0.02±0.09) to FFR with CT-QFR overestimating FFR (Fig. 1). Obstructive CAD was identified in 190/423 (44%) patients by ICA. Distal and lesion-specific CT-QFR classified 196 (46%) and 171 (40%) patients as abnormal, respectively. Areas under the receiver-operating characteristic curves for distal versus lesion-specific CT-QFR were similar (0.86 (95% CI: 0.82–0.89) vs. 0.86 (0.82–0.90), p=0.80). Sensitivities for distal and lesion-specific CT-QFR were 78% (95% CI: 71–84) vs. 74% (67–80), p=0.01, respectively, and specificities 79% (95% CI: 74–84) vs. 87% (82–91), p<0.01, respectively. Distal and lesion-specific CT-QFR had similar diagnostic accuracy (79 (95% CI: 75–83), vs. 81 (77–85), p=0.07) (Fig. 2). Conclusion In patients with suspected obstructive CAD on CTA, non-invasive estimation of FFR using CT-QFR is feasible with moderate correlation and good agreement with invasive FFR. Overall diagnostic performance of distal and lesion-specific values for discriminating obstructive CAD by invasive FFR are similar. The use of CT-QFR could therefore potentially reduce the need for referral to invasive angiography after CTA. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Aarhus UniversityRegion Mid Jutland

Background In patients with complex CAD, the presence of left main (LM) disease is an important prognostic factor in assessing the risk balance between PCI and CABG. Functional assessment has become standard of care to evaluate the significance of coronary stenosis and to justify the performance of PCI in the contemporary practice. FFRCT is a well-established method based on 3D reconstruction of coronary artery derived from CCTA. The Murray law-based quantitative flow reserve (μQFR) is a novel computational method of invasive angiography relying on a single angiographic view that takes into account side branches diameters to compute fractal flow division. The aim of the current analysis is to evaluate in patients with complex CAD the feasibility of μQFR in LM bifurcation and its diagnostic concordance with FFRCT. The impact of the optimal viewing angle defined by CCTA on the physiological assessment of the LM bifurcation using a single angiographic view was also evaluated. Methods In 299 consecutive patients with 3-vessel disease with or without LM coronary artery disease, up to 3 analyzable fluoroscopic projections per patient were analysed with μQFR retrospectively. FFRCT and μQFR were measured at 3 fiducial landmark points: i) point of LM bifurcation (POB); ii) proximal LAD 10 mm distal to POB; ii) proximal LCX 10 mm distal to POB. CCTA-based “optimal viewing angle” of LM bifurcation are computed by creating a 3-point closed spline involving the LM, LAD, and LCX at 5mm from the POB and subsequently by reconstructing the “en face” fluoroscopic viewing angle of the spline. The en face viewing angle provides an optimal assessment of the bifurcation geometry [1]. In terms of Rx gantry angulation, the closest angiographic projection to the optimal viewing angle derived from CCTA was defined as the “best fluoroscopic projection” for each patient. Results In 299 patients, 793 projections were analysed with μQFR and compared to FFRCT. Single view μQFR was analyzable in 100%. Correlation and agreement between μQFR and FFRCT for 793 projections in 299 patients are shown in Figure 1A, 2A. The Spearman's correlation coefficient showed moderate correlations at POB (r=0.481, p<0.001) and LCX (r=0.584, p<0.001), and strong correlation at LAD (r=0.642, p<0.001). Correlation and agreement between μQFR and FFRCT for best projections from each patient are shown in Figure 1B, 2B. Correlations were improved in the best projections with the following Spearman's correlation coefficient: at POB (r=0.522, p<0.001), LCX (r=0.622, p<0.001), and LAD (r=0.695, p<0.001). Conclusion Computation of μQFR from a single angiographic view has a high feasibility. Tailored optimal fluoroscopic view is essential for the physiological assessment of the LM bifurcation using a single angiographic view. Evaluation of diagnostic accuracy of μQFR warrants further analysis of the LMCAD after prospective planning of the optimal fluoroscopic view based on the selection of the best CCTA 3D view. Funding Acknowledgement Type of funding sources: None.