Coronary Physiological Indices to Evaluate Myocardial Ischemia in Patients with Aortic Stenosis Undergoing Valve Replacement.

Background: Evaluation of myocardial ischemia in patients with aortic valve stenosis (AS) with concomitant coronary artery disease (CAD) and possible microvascular dysfunction (MVD) is challenging because fractional flow reserve (FFR) and resting full-cycle ratio (RFR) have not been validated in this clinical setting.

Objectives: The objectives of this study in patients with AS and CAD are: 1. to describe the relationship between hyperemic and resting indices. 2. to investigate the acute and long-term effects of aortic valve replacement (AVR) on epicardial indices and microvascular function. 3. To assess the impact of these changes on clinical decision making. 4. To determine FFR/RFR ischemia cut-off points in AS.

Methods: In this prospective multicentric study, we performed serial measurements of FFR, RFR, and evaluated MVD by means of coronary flow reserve (CFR), the index of microvascular resistance (IMR) and microvascular resistance reserve (MRR) in patients with severe AS and intermediate-to-severe CAD, before and six months after AVR. Patients underwent myocardial perfusion single-photon emission computed tomography (SPECT) before AVR.

Results: In total, 146 coronary lesions in 116 patients were included. Before AVR, we observed high FFR/RFR discordance according to standard cut-off values: FFR-negative (>0.80)/RFR-positive (≤0.89) in 42.3% (68/137) of these lesions. Acutely after AVR, FFR decreased significantly (-0.0120 ± 0.0192, p=0.0045) while RFR remained stable (0.0140 ± 0.0673, p=0.3089). Six months after AVR, FFR decreased (-0.0279±0.0368) while RFR increased significantly (+0.0410±0.0487) (p<0.0001 for both), resulting in 21.5% (21/98) and 39.8% (39/98) of lesions crossing traditional FFR and RFR cut-off lines, respectively. LV-mass decreased significantly (153.68g ± 44.22 before vs 134.66g ± 37.26 after, p<0.0001). MVD was frequently observed at baseline (32.1% abnormal IMR; 68.6% abnormal MRR) with all microvascular parameters improving after AVR. Most accurate cut-offs to predict ischemia were FFR ≤0.83 and RFR ≤0.85 with comparable accuracy (75-80%).

Conclusions: In patients with severe AS and CAD, FFR ≤0.83 and RFR ≤0.85 appear to predict myocardial ischemia more accurately. Six months after AVR, FFR decreases while RFR increases significantly, with simultaneous decrease of LV mass and improvement of microvascular function.