Coronary Physiological Indexes to Evaluate Myocardial Ischemia in Patients With Aortic Stenosis Undergoing Valve Replacement

Background: The 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 the 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 were: 1) to describe the relationship between hyperemic and resting indexes; 2) to investigate the acute and long-term effects of aortic valve replacement (AVR) on epicardial indexes and microvascular function; 3) to assess the impact of these changes on clinical decision making; and 4) to determine FFR/RFR ischemia cutoff points in AS.

Methods: In this prospective multicentric study, we performed serial measurements of FFR and RFR and evaluated MVD by means of coronary flow reserve, the index of microvascular resistance, and microvascular resistance reserve in patients with severe AS and intermediate to severe CAD before and 6 months after AVR. Patients underwent myocardial perfusion single-photon emission computed tomography before AVR.

Results: In total, 146 coronary lesions in 116 patients were included. Before AVR, we observed high FFR/RFR discordance according to standard cutoff 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), whereas RFR remained stable (0.0140 ± 0.0673; P = 0.3089). Six months after AVR, FFR decreased (-0.0279 ± 0.0368), whereas 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 cutoff lines, respectively. Left ventricular mass decreased significantly (153.68 ± 44.22 g before vs 134.66 ± 37.26 g after; P < 0.0001). MVD was frequently observed at baseline (32.1% abnormal index of microvascular resistance and 68.6% abnormal microvascular resistance reserve) with all microvascular parameters improving after AVR. The most accurate cutoffs 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, whereas RFR increases significantly with a simultaneous decrease of left ventricular mass and an improvement of microvascular function.