How to interpret coronary physiology in patients with severe aortic stenosis and coronary artery disease before and after valve replacement ?

Abstract Background Coronary artery disease (CAD) is a very frequent and clinically important issue in patients undergoing transcatheter aortic valve implantation for severe aortic stenosis (AS). CAD is related to worse outcomes and physiology-guided treatment has been shown to reduce future coronary events. Purpose Factors that influence coronary physiological indices in AS are understudied. Truly understanding the effect of aortic valve replacement (AVR) on coronary pressure indices is essential. Methods In this prospective multicentric study, we performed serial measurements of RFR, FFR, CFR, IMR and MRR in 146 coronary lesions using a pressure wire X to assess hemodynamic importance and microvascular function in patients with severe AS, before and 6 months after AVR. Results Six-months after AVR FFR decreased and RFR increased significantly, while all microvascular parameters improved significantly. The difference between absolute values of RFR and FFR (RF -FFR) decreased six months after AVR. We observed a weak positive correlation between the RFR-FFR difference and the CFR (Pearson r = 0.350, p 0.001)(Fig.1A) but not with baseline IMR (Pearson r = 0.125, p = 0.165)(Fig.1B). This suggests that an increased basal flow drives the smaller difference between hyperaemic and resting indices in AS. Coronary lesions severity does not significantly influence the six-month change in FFR (Fig.1C-D). In contrast, coronary lesion severity influences the change in RFR, with more severe lesions being associated with a larger increase in RFR values (Pearson r = 0.663, p 0.001)(Fig.1E-F). Both the baseline MRR and the change in MRR are significantly correlated with the magnitude of change six months after valvular replacement. A lower baseline MRR predicts a larger decrease in FFR (Pearson r = 0.232, p 0.037)(Fig.2A) and larger increase in RFR (Pearson r = -0.223, p 0.047)(Fig.2B). Moreover, a larger increase in MRR was associated with a larger decrease in FFR (Pearson r = -0.231, p 0.041)(Fig.2C) and a larger increase in RFR (Pearson r = 0.233, p 0.042)(Fig.2D). CFR (baseline and delta) had a comparable relation to changes in FFR/RFR as MRR. In contrast, baseline and delta IMR did not have a significant relationship with the observed changed in FFR/RFR. Both left ventricular end-diastolic pressure (LVEDP) and peak-to-peak trans aortic valve (AV) gradients had no impact on changes in RFR (Fig.2F and 2H). In contrast, baseline LVEDPs (Pearson r = -0.367, p 0.030)(Fig.2E) and AV-gradients (Pearson r = -0.393, p 0.020)(Fig.2G) were both significantly correlated with delta FFR and higher values predicted larger changes. Conclusion Severe AS has an significant influence on coronary indices and microvascular function and hyperaemic and resting indices are influenced completely different. Understanding the factors that predict these changes can improve and personalize the treatment of coronary artery disease in patients undergoing valve replacement.Figure 1 Figure 2