Predictors of fractional flow reserve/instantaneous wave-free ratio discordance: impact of tailored diagnostic cut-offs on clinical outcomes of deferred lesions

BACKGROUND: Patient-related and lesion-related factors may influence instantaneous wave-free ratio (iFR)/fractional flow reserve (FFR) concordance, potentially affecting the safety of revascularization deferral. METHODS: Consecutive patients with at least an intermediate coronary stenosis evaluated by both iFR and FFR were retrospectively enrolled. The agreement between iFR and FFR at their diagnostic cut-offs (FFR 0.80, iFR 0.89) was assessed. Predictors of discordance were assessed using multivariate analyses. Tailored iFR cut-offs according to predictors of discordance best matching an FFR of 0.80 were identified. The impact of reclassification according to tailored iFR cut-offs on major cardiovascular events (MACE: cardiovascular death, myocardial infarction or target-lesion revascularization) among deferred lesions was investigated. RESULTS: Two hundred and ninety-nine intermediate coronary stenosis [FFR 0.84 (0.78-0.89), iFR 0.91 (0.87-0.95), 202 left main/left anterior descending (LM/LAD) vessels, 67.6%] of 260 patients were studied. Discordance rate was 23.4% (n = 70, 10.7% iFR-negative discordant, 12.7% iFR-positive discordant). Predictors of discordance were LM/LAD disease, multivessel disease, non-ST-elevation myocardial infarction, smoking, reduced eGFR and hypertension. Lesion reclassification with tailored iFR cut-offs based on patient-level predictors carried no prognostic value among deferred lesions. Reclassification according to lesion location, which was entirely driven by LM/LAD lesions (iFR cut-offs: 0.93 for LM/LAD, 0.89 for non-LM/LAD), identified increased MACE among lesions deferred based on a negative FFR, between patients with a positive as compared with a negative iFR (19.4 vs. 6.1%, P = 0.044), whereas the same association was not observed with the conventional 0.89 iFR cut-off (15 vs. 8.6%, P = 0.303). CONCLUSION: Tailored vessel-based iFR cut-offs carry prognostic value among FFR-negative lesions, suggesting that a one-size-fit-all iFR cut-off might be clinically unsatisfactory.