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Aortic stenosis (AS) is frequently associated with coronary artery disease (CAD). However, the best tool to functionally assess CAD in AS remains undetermined. Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) have never been validated in AS.FFR, iFR and stress single photon emission computed tomography (SPECT) were performed in a consecutive series of 28 patients with severe AS and 41 borderline coronary lesions during the work-up for valve replacement.Both FFR and iFR were correlated with an abnormal SPECT. At ROC analysis, FFR yielded an AUC = 0.91 with negative predictive value (NPV) = 95% in detecting ischemia according to SPECT. iFR showed significant worse agreement with myocardial perfusion imaging compared to FFR (59% vs 85%, p = 0.014). Specifically, a significant larger proportion of false positive measurements (negative SPECT and iFR 0.89) was observed using iFR vs FFR: 39% vs 12%, p = 0.011. Using a pre-specified 0.82 cut-off, the iFR agreement with SPECT increased to 73%.FFR yielded a good correlation with SPECT and a high NPV in detecting ischemia-provoking lesions. iFR diagnostic metrics were inferior compared with FFR and improved adopting a lower ischemic threshold.

BACKGROUND The complexity of coronary physiology in presence of severe aortic stenosis (AS) raises concerns about the reliability of pressure-derived indexes in this clinical setting. Furthermore, neither fractional flow reserve (FFR) nor instantaneous wave-free period (iFR) has been validated in AS. Combining iFR and FFR in a tailored decision-making strategy may help to increase simplicity, accuracy and safety of physiology-guided revascularization in AS. METHODS In this prospective observational study iFR and FFR were measured before and after TAVI during the same procedure in patients with severe AS and concomitant coronary artery disease (CAD). All decisions about revascularization were based on post-TAVI FFR assessment. The best iFR "defer" and "treatment" values were identified according to their baseline negative (NPV) and positive predictive values (PPV) respectively. A post-hoc analysis was then performed to compare the hybrid iFR-FFR approach with the FFR-only strategy. RESULTS Sixty-two patients underwent pre- and post-TAVI pressure-wire assessment and were included in the analysis. A "defer iFR value" >0.93 yielded a NPV of 98.4% (91.7%-99.9%) to exclude FFR non-significant stenosis (>0.80), and a "treatment iFR value"