Fractional Flow Reserve Versus Instantaneous Wave-Free Ratio in Assessment of Lesion Hemodynamic Significance and Explanation of their Discrepancies. International, Multicenter and Prospective Trial: The FiGARO Study

Tomas Kovarnik, Matsuo Hitoshi, Ales Kral, Stepan Jerabek, David Zemanek, Yoshiaki Kawase, Hiroyuki Omori, Toru Tanigaki, Jan Pudil, Alexandra Vodzinska, Marian Branny, Roman Stipal, Petr Kala, Jan Mrozek, Martin Porzer, Tomas Grezl, Kamil Novobilsky, Oscar Mendiz, Karel Kopriva, Martin Mates, Martin Chval, Zhi Chen, Pavel Martasek, Ales Linhart, FiGARO trial investigators, Tomas Kovarnik, Ales Kral, Stepan Jerabek, David Zemanek, Jan Pudil, Jiri Humhal, Karel Gorican, Michael Padour, Stanislav Šimek, Jan Belohlavek, Daniel Rob, Michaela Hronova, Ales Kral, Matsuo Hitoshi, Yoshiaki Kawase, Hiroyuki Omori, Toru Tanigaki, Alexandra Vodzinska, Jindrich Cerny, Jan Indrak, Miroslav Hudec, Marian Branny, Jan Mrozek, Martin Porzer, Tomas Grezl, Roman Stipal, Petr Kala, Jan Kanovsky, Otakar Bocek, Martin Poloczek, Petr Jerabek, Kamil Novobilsky, Tomas Kolomaznik, Oscar Mendiz, Karel Kopriva, Martin Mates, Frantisek Holy, Martin Chval, Zhi Chen, Pavel Martasek, Lubomir Kralik, Tomas Kovarnik, Matsuo Hitoshi, Ales Kral, Stepan Jerabek, David Zemanek, Yoshiaki Kawase, Hiroyuki Omori, Toru Tanigaki, Jan Pudil, Alexandra Vodzinska, Marian Branny, Roman Stipal, Petr Kala, Jan Mrozek, Martin Porzer, Tomas Grezl, Kamil Novobilsky, Oscar Mendiz, Karel Kopriva, Martin Mates, Martin Chval, Zhi Chen, Pavel Martasek, Ales Linhart, FiGARO trial investigators, Tomas Kovarnik, Ales Kral, Stepan Jerabek, David Zemanek, Jan Pudil, Jiri Humhal, Karel Gorican, Michael Padour, Stanislav Šimek, Jan Belohlavek, Daniel Rob, Michaela Hronova, Ales Kral, Matsuo Hitoshi, Yoshiaki Kawase, Hiroyuki Omori, Toru Tanigaki, Alexandra Vodzinska, Jindrich Cerny, Jan Indrak, Miroslav Hudec, Marian Branny, Jan Mrozek, Martin Porzer, Tomas Grezl, Roman Stipal, Petr Kala, Jan Kanovsky, Otakar Bocek, Martin Poloczek, Petr Jerabek, Kamil Novobilsky, Tomas Kolomaznik, Oscar Mendiz, Karel Kopriva, Martin Mates, Frantisek Holy, Martin Chval, Zhi Chen, Pavel Martasek, Lubomir Kralik

Abstract

Background The FiGARO (FFR versus iFR in Assessment of Hemodynamic Lesion Significance, and an Explanation of Their Discrepancies) trial is a prospective registry searching for predictors of fractional flow reserve/instantaneous wave-free ratio (FFR/iFR) discrepancy. Methods and Results FFR/iFR were analyzed using a Verrata wire, and coronary flow reserve was analyzed using a Combomap machine (both Philips-Volcano). The risk polymorphisms for endothelial nitric oxide synthase and for heme oxygenase-1 were analyzed. In total, 1884 FFR/iFR measurements from 1564 patients were included. The FFR/iFR discrepancy occurred in 393 measurements (20.9%): FFRp (positive)/iFRn (negative) type (264 lesions, 14.0%) and FFRn/iFRp (129 lesions, 6.8%) type. Coronary flow reserve was measured in 343 lesions, correlating better with iFR (R=0.56, P<0.0001) than FFR (R=0.36, P<0.0001). The coronary flow reserve value in FFRp/iFRn lesions (2.24±0.7) was significantly higher compared with both FFRp/iFRp (1.39±0.36), and FFRn/iFRn lesions (1.8±0.64, P<0.0001). Multivariable logistic regression analysis confirmed (1) sex, age, and lesion location in the right coronary artery as predictors for FFRp/iFRn discrepancy; and (2) hemoglobin level, smoking, and renal insufficiency as predictors for FFRn/iFRp discrepancy. The FFRn/iFRp type of discrepancy was significantly more frequent in patients with both risk types of polymorphisms (endothelial nitric oxide synthaser+heme oxygenase-1r): 8 patients (24.2%) compared with FFRp/iFRn type of discrepancy: 2 patients (5.9%), P=0.03. Conclusions Predictors for FFRp/iFRn discrepancy were sex, age, and location in the right coronary artery. Predictors for FFRn/iFRp were hemoglobin level, smoking, and renal insufficiency. The risk type of polymorphism in endothelial nitric oxide synthase and heme oxygenase-1 genes was more frequently found in patients with FFRn/iFRp type of discrepancy. Registration URL: https://ichgcp.net/clinical-trials-registry/NCT03033810" title="See in ClinicalTrials.gov">NCT03033810.

Keywords: coronary flow reserve; fractional flow reserve; instantaneous wave‐free ratio.

Figures

Figure 1. A 3‐dimensional image of the…
Figure 1. A 3‐dimensional image of the ENOS heme domains.
Left panel: the homodimeric structure, alongside heme (pink) and the structural zinc atom (grey). Right panel: the Glu298 (blue) and Asp298 (yellow) represent amino acid residues corresponding to the polymorphic change. ENOS indicates endothelial nitric oxide synthase.
Figure 2. Correlation between FFR and iFR…
Figure 2. Correlation between FFR and iFR values and histograms for FFR and iFR values.
FFR indicates fractional flow reserve; and iFR, instantaneous wave‐free ratio.
Figure 3. Bland‐Altman plot of difference between…
Figure 3. Bland‐Altman plot of difference between FFR and iFR.
FFR indicates fractional flow reserve; and iFR, instantaneous wave‐free ratio.
Figure 4. Correlation between CFR and FFR,…
Figure 4. Correlation between CFR and FFR, and between CFR and iFR.
CFR indicates coronary flow reserve; FFR, fractional flow reserve; and iFR, instantaneous wave‐free ratio.

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