Fractional Flow Reserve/InstantaneousWave-Free Ratio Discordance in Angiographically Intermediate CoronaryStenoses

Fro Fo Am Ca De Re OBJECTIVES The study sought to determine the coronary flow characteristics of angiographically intermediate stenoses classified as discordant by fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR). BACKGROUND Discordance between FFR and iFR occurs in up to 20% of cases. No comparisons have been reported between the coronary flow characteristics of FFR/iFR discordant and angiographically unobstructed vessels. METHODS Baseline and hyperemic coronary flow velocity and coronary flow reserve (CFR) were compared across 5 vessel groups: FFRþ/iFRþ (108 vessels, n 1⁄4 91), FFR–/iFRþ (28 vessels, n 1⁄4 24), FFRþ/iFR– (22 vessels, n 1⁄4 22), FFR–/iFR– (208 vessels, n 1⁄4 154), and an unobstructed vessel group (201 vessels, n 1⁄4 153), in a post hoc analysis of the largest combined pressure and Doppler flow velocity registry (IDEAL [Iberian-Dutch-English] collaborators study). RESULTS FFR disagreedwith iFR in 14% (50of 366). Baselineflow velocitywas similar across all 5 vessel groups, including the unobstructedvesselgroup(p1⁄40.34forvariance). InFFRþ/iFR–discordants,hyperemicflowvelocityandCFRweresimilar toboth FFR–/iFR– and unobstructed groups; 37.6 (interquartile range [IQR]: 26.1 to 50.4) cm/s vs. 40.0 [IQR: 29.7 to 52.3] cm/s and 42.2 [IQR: 33.8 to 53.2] cm/s and CFR 2.36 [IQR: 1.93 to 2.81] vs. 2.41 [IQR: 1.84 to 2.94] and 2.50 [IQR: 2.11 to 3.17], respectively (p> 0.05 for all). In FFR–/iFRþ discordants, hyperemic flow velocity, and CFR were similar to the FFRþ/iFRþ group; 28.2 (IQR: 20.5 to 39.7) cm/s versus 23.5 (IQR: 16.4 to 34.9) cm/s and CFR 1.44 (IQR: 1.29 to 1.85) versus 1.39 (IQR: 1.06 to 1.88), respectively (p> 0.05 for all). CONCLUSIONS FFR/iFR disagreement was explained by differences in hyperemic coronary flow velocity. Furthermore, coronary stenoses classified as FFRþ/iFR– demonstrated similar coronary flow characteristics to angiographically unobstructed vessels. (J Am Coll Cardiol Intv 2017;10:2514–24) © 2017 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). m the Imperial College London, London, United Kingdom; St. Francis Hospital, Roslyn, New York; Cardiovascular Research undation, New York, New York; VU University Medical Centre, Amsterdam, the Netherlands; Academic Medical Centre, sterdam, the Netherlands; Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Mexico City; East rolina Heart Institute at East Carolina University, Greenville, North Carolina; Amphia Hospital, Breda, the Netherlands; partment of Medicine, Columbia University Medical Center, New York, New York; Seoul National University Hospital, Seoul, public of Korea; and the Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain. This study was funded in part by J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S V O L . 1 0 , N O . 2 4 , 2 0 1 7 Cook et al. D E C E M B E R 2 6 , 2 0 1 7 : 2 5 1 4 – 2 4 Mechanisms of FFR/iFR Discordance 2515 AB BR E V I A T I O N S

I n determining the physiological significance of an angiographically intermediate coronary stenosis, the fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) both quantify the trans-stenotic pressure ratio as a surrogate measure of coronary flow. FFR is measured under conditions of maximal pharmacological hyperemia (1) whereas iFR is measured in the resting state (2).
In up to 20% of cases, FFR and iFR disagree on the functional significance of a stenosis (3). The recently  (7). The IDEAL study is the largest international, multicenter, nonrandomized, prospective analysis in patients with coronary artery disease undergoing physiological lesion assessment by combined pressure (FFR and iFR) and Doppler flow velocity measurements. All patients recruited were scheduled for elective coronary angiography with physiological stenosis assessment by FFR and gave written informed consent for acquisition of additional physiological data for study purposes. Stenosed vessels were defined as vessels that had an angiographically visible stenosis between 40% to 70% severity, as determined visually by the operating physician at the time of coronary angiography.
Unobstructed vessels were defined as vessels with a complete absence of any angiographically visible stenosis. As part of the original IDEAL study protocol, all angiogram cines were reviewed and adjudicated by 2 independent assessors to ensure compliance with the aforementioned definitions (7).     Table 1. Values are n, mean AE SD, n (%), or n/N (%).
RELATIONSHIPS BETWEEN FFR AND iFR. Figure 2 shows the scatter plot between FFR and iFR pressure-only indices of stenosis severity.  Values are n, mean AE SD, or median (interquartile range).
Abbreviations as in Table 1.

DISCUSSION
The main findings of the study were as follows.  STUDY LIMITATIONS. In this study, discordance was identified by differences in functional classification determined according to a single binary cut point value. Although myocardial ischemia must surely be a continuum, the use of binary cutpoints to distinguish hemodynamic significance from nonsignificance is ubiquitous in the literature, clinical outcome trials (4,5,9,23), and revascularization and appropriate use criteria guidelines (24)(25)(26). This largely reflects the  The coronary angiogram image displays a proximal circumflex stenosis. Quantitative coronary angiography derived percentage diameter stenosis, area stenosis, and minimal lumen diameter were 62%, 85%, and 1.20 mm, respectively. Invasive pressure-based coronary physiology assessment revealed discordant iFR (negative) and FFR (positive) results. Upon measuring combined coronary pressure-and-flow data, the FFRþ/iFR-discordant result can be attributed to high CFR. Abbreviations as in Figure 1.  Table 4).
Last, in keeping with a previous large-scale study of discordance between hyperemic and resting pressure indices (16), the statistical unit of our analysis was vessels rather than patients. Accordingly, there is a potential for both statistical and biological interaction for different vessels analyzed within the same patient. However, across both the FFR-/iFRþ and FFRþ/iFR-discordant groups, all but 4 vessels were from individual patients, and no patient contributed more than 1 vessel to both discordant groups. Indeed, repeat analysis after removal of discordant vessels from within the same patient did not alter the overall study findings (Online Figures 5 and 6). To permit a per-patient analysis, patients with more than 1 stenosis would need to be excluded, or alternatively,