Instantaneous Wave-Free Ratio for the Assessment of Intermediate Left Main Coronary Artery Stenosis: Correlations With Fractional Flow Reserve/Intravascular Ultrasound and Prognostic Implications: The iLITRO-EPIC07 Study

Oriol Rodriguez-Leor, José María de la Torre Hernández, Tamara García-Camarero, Bruno García Del Blanco, Ramón López-Palop, Eduard Fernández-Nofrerías, Carlos Cuellas Ramón, Marcelo Jiménez-Kockar, Jesús Jiménez-Mazuecos, Francisco Fernández Salinas, Josep Gómez-Lara, Salvatore Brugaletta, Fernando Alfonso, Ricardo Palma, Antonio E Gómez-Menchero, Raúl Millán, David Tejada Ponce, José Antonio Linares Vicente, Soledad Ojeda, Eduardo Pinar, Estefanía Fernández-Pelegrina, Francisco J Morales-Ponce, Ana Belén Cid-Álvarez, Juan Carlos Rama-Merchan, Eduardo Molina Navarro, Javier Escaned, Armando Pérez de Prado, Oriol Rodriguez-Leor, José María de la Torre Hernández, Tamara García-Camarero, Bruno García Del Blanco, Ramón López-Palop, Eduard Fernández-Nofrerías, Carlos Cuellas Ramón, Marcelo Jiménez-Kockar, Jesús Jiménez-Mazuecos, Francisco Fernández Salinas, Josep Gómez-Lara, Salvatore Brugaletta, Fernando Alfonso, Ricardo Palma, Antonio E Gómez-Menchero, Raúl Millán, David Tejada Ponce, José Antonio Linares Vicente, Soledad Ojeda, Eduardo Pinar, Estefanía Fernández-Pelegrina, Francisco J Morales-Ponce, Ana Belén Cid-Álvarez, Juan Carlos Rama-Merchan, Eduardo Molina Navarro, Javier Escaned, Armando Pérez de Prado

Abstract

Background: There is little information available on agreement between fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) in left main coronary artery (LMCA) intermediate stenosis. Besides, several meta-analyses support the use of FFR to guide LMCA revascularization, but limited information is available on iFR in this setting. Our aims were to establish the concordance between FFR and iFR in intermediate LMCA lesions, to evaluate with intravascular ultrasound (IVUS) in cases of FFR/iFR discordance, and to prospectively validate the safety of deferring revascularization based on a hybrid decision-making strategy combining iFR and IVUS.

Methods: Prospective, observational, multicenter registry with 300 consecutive patients with intermediate LMCA stenosis who underwent FFR and iFR and, in case of discordance, IVUS and minimal lumen area measurements. Primary clinical end point was a composite of cardiovascular death, LMCA lesion-related nonfatal myocardial infarction, or unplanned LMCA revascularization.

Results: FFR and iFR had an agreement of 80% (both positive in 67 and both negative in 167 patients); in case of disagreement (31 FFR+/iFR- and 29 FFR-/iFR+) minimal lumen area was ≥6 mm2 in 8.7% of patients with FFR+ and 14.6% with iFR+. Among the 300 patients, 105 (35%) underwent revascularization and 181 (60%) were deferred according to iFR and IVUS. At a median follow-up of 20 months, major adverse cardiac events incidence was 8.3% in the defer group and 13.3% in the revascularization group (hazard ratio, 0.71 [95% CI 0.30-1.72]; P=0.45).

Conclusions: In patients with intermediate LMCA stenosis, a physiology-guided treatment decision is feasible either with FFR or iFR with moderate concordance between both indices. In case of disagreement, the use of IVUS may be useful to indicate revascularization. Deferral of revascularization based on iFR appears to be safe in terms of major adverse cardiac events.

Registration: URL: https://www.

Clinicaltrials: gov; Unique identifier: NCT03767621.

Keywords: coronary artery disease; left main coronary artery disease; ultrasound imaging.

Figures

Figure 1.
Figure 1.
Patient classification according to the concordance between fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) as well as intravascular ultrasound (IVUS) significance. FFR and iFR were measured from left anterior descending coronary artery (LAD) in 291 patients and from left circumflex coronary artery (LCX) in 257 patients. There were 3 patients with measurements from LCX but not from the LAD, and 6 patients only with iFR measurement. LMCA indicates left main coronary artery; and MLA, minimal lumen area.
Figure 2.
Figure 2.
Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) correlation, receiver operating curve and values distribution when measured from left anterior descending coronary artery (LAD) and left circumflex coronary artery (LCX). A, Measurements from LAD; (B) measurements from LCX. LMCA indicates left main coronary artery.
Figure 3.
Figure 3.
Concordance between fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) according to a minimal lumen area (MLA) cutoff of 6 mm2 in patients with intravascular ultrasound (IVUS) evaluation. This analysis was performed in 188 patients with MLA, FFR, and iFR measurements (in 6 patients with IVUS study only iFR was measured). LMCA indicates left main coronary artery.
Figure 4.
Figure 4.
Treatment decision according to instantaneous wave-free ratio (iFR), fractional flow reserve (FFR), and minimal lumen area (MLA) values. In patients with discordant FFR and iFR, protocol recommended to perform intravascular ultrasound (IVUS) and decide revascularization if MLA2, but local heart team had the final decision. LMCA indicates left main coronary artery.
Figure 5.
Figure 5.
Major adverse cardiac events (MACE) in follow-up. Kaplan-Meier event-free curves showing major cardiac events in the 2 groups. There was no difference between the deferred according to protocol recommendation and revascularized groups. HR indicates hazard ratio; and LMCA, left main coronary artery.

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