Diagnostic Performance of In-Procedure Angiography-Derived Quantitative Flow Reserve Compared to Pressure-Derived Fractional Flow Reserve: The FAVOR II Europe-Japan Study

Jelmer Westra, Birgitte Krogsgaard Andersen, Gianluca Campo, Hitoshi Matsuo, Lukasz Koltowski, Ashkan Eftekhari, Tommy Liu, Luigi Di Serafino, Domenico Di Girolamo, Javier Escaned, Holger Nef, Christoph Naber, Marco Barbierato, Shengxian Tu, Omeed Neghabat, Morten Madsen, Matteo Tebaldi, Toru Tanigaki, Janusz Kochman, Samer Somi, Giovanni Esposito, Giuseppe Mercone, Hernan Mejia-Renteria, Federico Ronco, Hans Erik Bøtker, William Wijns, Evald Høj Christiansen, Niels Ramsing Holm, Jelmer Westra, Birgitte Krogsgaard Andersen, Gianluca Campo, Hitoshi Matsuo, Lukasz Koltowski, Ashkan Eftekhari, Tommy Liu, Luigi Di Serafino, Domenico Di Girolamo, Javier Escaned, Holger Nef, Christoph Naber, Marco Barbierato, Shengxian Tu, Omeed Neghabat, Morten Madsen, Matteo Tebaldi, Toru Tanigaki, Janusz Kochman, Samer Somi, Giovanni Esposito, Giuseppe Mercone, Hernan Mejia-Renteria, Federico Ronco, Hans Erik Bøtker, William Wijns, Evald Høj Christiansen, Niels Ramsing Holm

Abstract

Background: Quantitative flow ratio (QFR) is a novel modality for physiological lesion assessment based on 3-dimensional vessel reconstructions and contrast flow velocity estimates. We evaluated the value of online QFR during routine invasive coronary angiography for procedural feasibility, diagnostic performance, and agreement with pressure-wire-derived fractional flow reserve (FFR) as a gold standard in an international multicenter study.

Methods and results: FAVOR II E-J (Functional Assessment by Various Flow Reconstructions II Europe-Japan) was a prospective, observational, investigator-initiated study. Patients with stable angina pectoris were enrolled in 11 international centers. FFR and online QFR computation were performed in all eligible lesions. An independent core lab performed 2-dimensional quantitative coronary angiography (2D-QCA) analysis of all lesions assessed with QFR and FFR. The primary comparison was sensitivity and specificity of QFR compared with 2D-QCA using FFR as a reference standard. A total of 329 patients were enrolled. Paired assessment of FFR, QFR, and 2D-QCA was available for 317 lesions. Mean FFR, QFR, and percent diameter stenosis were 0.83±0.09, 0.82±10, and 45±10%, respectively. FFR was ≤0.80 in 104 (33%) lesions. Sensitivity and specificity by QFR was significantly higher than by 2D-QCA (sensitivity, 86.5% (78.4-92.4) versus 44.2% (34.5-54.3); P<0.001; specificity, 86.9% (81.6-91.1) versus 76.5% (70.3-82.0); P=0.002). Area under the receiver curve was significantly higher for QFR compared with 2D-QCA (area under the receiver curve, 0.92 [0.89-0.96] versus 0.64 [0.57-0.70]; P<0.001). Median time to QFR was significantly lower than median time to FFR (time to QFR, 5.0 minutes [interquartile range, -6.1] versus time to FFR, 7.0 minutes [interquartile range, 5.0-10.0]; P<0.001).

Conclusions: Online computation of QFR in the catheterization laboratory is clinically feasible and is superior to angiographic assessment for evaluation of intermediary coronary artery stenosis using FFR as a reference standard.

Clinical trial registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02959814.

Keywords: fractional flow reserve; quantitative coronary angiography.

© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Figures

Figure 1
Figure 1
Study enrollment flow chart. FFR indicates fractional flow reserve; N, number of patients; QCA, quantitative coronary angiography; QFR, quantitative flow ratio; RCA, right coronary artery.
Figure 2
Figure 2
Sensitivity and specificity for QFR and 2D‐QCA with FFR as reference. QFR was superior to 2D‐QCA on sensitivity and specificity with FFR as reference standard. Diagnostic cutoffs: ≤0.80 for FFR and QFR; ≥50% DS for 2D‐QCA. 2D‐QCA indicates 2‐dimensional coronary angiography; QFR, quantitative flow ratio.
Figure 3
Figure 3
Per‐vessel level diagnostic performance. FFR≤0.80 was used as reference. 2D‐QCA indicates 2‐dimensional coronary angiography; AUC, area under the receiver operating curve; QFR, quantitative flow ratio.
Figure 4
Figure 4
Agreement between QFR and FFR. A good correlation (A) and agreement (B) of QFR and FFR was observed. Dashed lines in Bland–Altman plot illustrate mean difference ±2 SD. FFR indicates fractional flow reserve; QFR, quantitative flow ratio.
Figure 5
Figure 5
Comparison of time to FFR and time to QFR. FFR indicates fractional flow reserve; IQR, inter quartile range; m, minutes; QFR, quantitative flow ratio.

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