CLEAR-AS: CT-FFR-Guided Revascularization in Patients With Severe Aortic Stenosis

Patients with severe aortic stenosis (AS) frequently have concomitant coronary artery disease (CAD), which complicates pre-operative evaluation and clinical decision-making for transcatheter (TAVR) or surgical aortic valve replacement (SAVR). Although coronary computed tomography angiography (CCTA) provides excellent anatomical evaluation and has become a standard pre-AVR workflow, it is insufficient for determining the functional and hemodynamic significance of coronary lesions. CT-derived fractional flow reserve (CT-FFR) offers a novel, non-invasive method to evaluate the ischemic burden.

The objective of this prospective, single-center, randomized, parallel-controlled trial is to determine whether a "functional + anatomical" assessment strategy using CT-FFR provides incremental value over an "anatomical-only" strategy.

A total of 300 eligible patients with severe AS planned for AVR will be randomized in a 1:1 ratio into two groups:

• Experimental Group (CCTA + CT-FFR): The Heart Team will formulate the revascularization strategy (e.g., concomitant or staged PCI/CABG) based on both CCTA anatomical stenosis and CT-FFR physiological data (using a threshold of CT-FFR ≤0.80 to define hemodynamically significant ischemia).
• Active Comparator Group (CCTA alone): The Heart Team will formulate the revascularization strategy based solely on CCTA anatomical grading according to the CAD-RADS classification.

All participants will be followed for 365 days post-AVR. The primary endpoint is a patient-oriented composite of major adverse cardiovascular events (MACE, including nonfatal myocardial infarction, unstable angina, cardiac death, or heart failure admission), disabling stroke, clinically-driven target vessel revascularization, valve re-intervention, and life-threatening or disabling bleeding. The study hypothesizes that incorporating CT-FFR into routine pre-AVR evaluation will optimize concomitant revascularization decisions, avoid unnecessary invasive procedures, and ultimately reduce the risk of post-operative adverse events.

Inclusion criteria

• Age >18 years.
• Severe aortic stenosis confirmed by echocardiography, defined as peak aortic jet velocity (Vmax) ≥4.0 m/s, mean transvalvular gradient ≥40 mmHg, or aortic valve area (AVA) ≤1.0 cm² [or indexed aortic valve area (AVAi) ≤0.6 cm²/m²].
• New York Heart Association (NYHA) functional class II or higher.
• Eligible for both transfemoral transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR).
• Undergoing preoperative coronary computed tomography angiography (CCTA).
• Willing to participate in the study and able to provide written informed consent.

Exclusion criteria

• Allergy to prosthetic valve materials or iodinated contrast agents.
• Contraindication or allergic reaction to anticoagulants or antiplatelet agents, or inability to tolerate required anticoagulant or antiplatelet therapy.
• Active infective endocarditis or any other active infection.
• Severe vascular disease precluding safe implantation of a prosthetic valve.
• Ascending aortic diameter ≥50 mm.
• Prior prosthetic valve implantation in any cardiac position or prior coronary artery bypass grafting (CABG).
• Preoperative imaging confirming aortic root anatomy unsuitable for transcatheter aortic valve implantation.
• Intracardiac mass, left ventricular or left atrial thrombus, or vegetation confirmed by preoperative echocardiography.
• Acute myocardial infarction within 30 days before surgery.
• Clinically diagnosed stroke or transient ischemic attack within 3 months before surgery.
• Bleeding or coagulation disorders within 3 months before surgery that required hospitalization or blood transfusion or were otherwise clinically significant and would preclude the antiplatelet therapy required in this study.