Evaluation of Coronary Artery Stenosis by Quantitative Flow Ratio During Invasive Coronary Angiography: The WIFI II Study (Wire-Free Functional Imaging II)

Jelmer Westra, Shengxian Tu, Simon Winther, Louise Nissen, Mai-Britt Vestergaard, Birgitte Krogsgaard Andersen, Emil Nielsen Holck, Camilla Fox Maule, Jane Kirk Johansen, Lene Nyhus Andreasen, Jo Krogsgaard Simonsen, Yimin Zhang, Steen Dalby Kristensen, Michael Maeng, Anne Kaltoft, Christian Juhl Terkelsen, Lars Romer Krusell, Lars Jakobsen, Johan H C Reiber, Jens Flensted Lassen, Morten Bøttcher, Hans Erik Bøtker, Evald Høj Christiansen, Niels Ramsing Holm, Jelmer Westra, Shengxian Tu, Simon Winther, Louise Nissen, Mai-Britt Vestergaard, Birgitte Krogsgaard Andersen, Emil Nielsen Holck, Camilla Fox Maule, Jane Kirk Johansen, Lene Nyhus Andreasen, Jo Krogsgaard Simonsen, Yimin Zhang, Steen Dalby Kristensen, Michael Maeng, Anne Kaltoft, Christian Juhl Terkelsen, Lars Romer Krusell, Lars Jakobsen, Johan H C Reiber, Jens Flensted Lassen, Morten Bøttcher, Hans Erik Bøtker, Evald Høj Christiansen, Niels Ramsing Holm

Abstract

Background: Quantitative flow ratio (QFR) is a novel diagnostic modality for functional testing of coronary artery stenosis without the use of pressure wires and induction of hyperemia. QFR is based on computation of standard invasive coronary angiographic imaging. The purpose of WIFI II (Wire-Free Functional Imaging II) was to evaluate the feasibility and diagnostic performance of QFR in unselected consecutive patients.

Methods and results: WIFI II was a predefined substudy to the Dan-NICAD study (Danish Study of Non-Invasive Diagnostic Testing in Coronary Artery Disease), referring 362 consecutive patients with suspected coronary artery disease on coronary computed tomographic angiography for diagnostic invasive coronary angiography. Fractional flow reserve (FFR) was measured in all segments with 30% to 90% diameter stenosis. Blinded observers calculated QFR (Medis Medical Imaging bv, The Netherlands) for comparison with FFR. FFR was measured in 292 lesions from 191 patients. Ten (5%) and 9 patients (5%) were excluded because of FFR and angiographic core laboratory criteria, respectively. QFR was successfully computed in 240 out of 255 lesions (94%) with a mean diameter stenosis of 50±12%. Mean difference between FFR and QFR was 0.01±0.08. QFR correctly classified 83% of the lesions using FFR with cutoff at 0.80 as reference standard. The area under the receiver operating characteristic curve was 0.86 (95% confidence interval, 0.81-0.91) with a sensitivity, specificity, negative predictive value, and positive predictive value of 77%, 86%, 75%, and 87%, respectively. A QFR-FFR hybrid approach based on the present results enables wire-free and adenosine-free procedures in 68% of cases.

Conclusions: Functional lesion evaluation by QFR assessment showed good agreement and diagnostic accuracy compared with FFR. Studies comparing clinical outcome after QFR- and FFR-based diagnostic strategies are required.

Clinical trial registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02264717.

Keywords: adenosine; angiography; coronary angiography; coronary artery disease; hyperemia.

© 2018 The Authors.

Figures

Figure 1.
Figure 1.
Study enrollment flowchart. Numbers n are study patients. ICA indicates invasive coronary angiography; FFR, fractional flow reserve; LM, left main stem; QFR, quantitative flow ratio; and RCA, right coronary artery.
Figure 2.
Figure 2.
Lesion distribution. Distribution of measurements according to fractional flow reserve (FFR). Median FFR was 0.85 (range 0.39–1.04). Twenty-one percent of the lesions were in the FFR 0.77 to 0.83 interval.
Figure 3.
Figure 3.
Correlation and agreement. Good correlation and agreement of quantitative flow ratio (QFR) and fractional flow reserve (FFR) was observed (r=0.70; mean difference=0.01; A). Bland–Altman plot; dashed line illustrates the mean difference±2 SD (B).
Figure 4.
Figure 4.
Diagnostic performance and clinical application of quantitative flow ratio (QFR). Receiver operating characteristic analysis comparing QFR to 2-dimensional (2D) quantitative coronary angiography (QCA) with fractional flow reserve (FFR) as reference standard (A) and identification of QFR cut points to yield a sensitivity and specificity >90% compared with FFR (B) for use in a hybrid QFR–FFR model (C). AUC indicates area under the receiver operating characteristic curve.

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