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

Lennert Minten; Keir McCutcheon; Maarten Vanhaverbeke; Laurine Wouters; Stéphanie Bézy; Pierluigi Lesizza; Sander Jentjens; Pascal Frederiks; Tijs Bringmans; Jens-Uwe Voigt; Tom Adriaenssens; Walter Desmet; Peter Sinnaeve; Steven Jacobs; Peter Verbrugghe; Bart Meuris; Stefan Janssens; William F Fearon; Johan Bennett; Christophe Dubois

doi:10.1016/j.jcin.2024.10.024

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

JACC Cardiovasc Interv. 2024 Oct 18:S1936-8798(24)01421-3. doi: 10.1016/j.jcin.2024.10.024. Online ahead of print.

Authors

Lennert Minten¹, Keir McCutcheon², Maarten Vanhaverbeke³, Laurine Wouters², Stéphanie Bézy², Pierluigi Lesizza⁴, Sander Jentjens⁵, Pascal Frederiks⁴, Tijs Bringmans⁶, Jens-Uwe Voigt⁷, Tom Adriaenssens⁷, Walter Desmet⁷, Peter Sinnaeve⁷, Steven Jacobs⁸, Peter Verbrugghe⁸, Bart Meuris⁸, Stefan Janssens⁷, William F Fearon⁹, Johan Bennett⁷, Christophe Dubois⁷

Affiliations

¹ Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium; Department of Cardiovascular Medicine, University Hospitals Leuven (UZ Leuven), Leuven Belgium. Electronic address: Lennert.minten@gmail.com.
² Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium.
³ Department of Cardiology, AZ Delta, Roeselare, Belgium.
⁴ Department of Cardiovascular Medicine, University Hospitals Leuven (UZ Leuven), Leuven Belgium.
⁵ Department of Nuclear Medicine, University Hospitals Leuven (UZ Leuven), Leuven Belgium.
⁶ Department of Cardiology, University hospital Antwerp (UZA), Antwerp, Belgium.
⁷ Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium; Department of Cardiovascular Medicine, University Hospitals Leuven (UZ Leuven), Leuven Belgium.
⁸ Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium; Department of cardiac, University Hospitals Leuven (UZ Leuven), Leuven, Belgium.
⁹ Division of Cardiovascular medicine, Stanford University, Stanford, CA, USA; The VA Palo Alto Health Care System, Palo Alto, CA, USA.

PMID: 39474985
DOI: 10.1016/j.jcin.2024.10.024

Abstract

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.

Keywords: AVR; CFR; FFR; IMR; MRR; NHPR; RFR; SPECT; TAVR; aortic valve replacement; aortic valve stenosis; coronary artery disease; coronary physiology; microvascular function.