Pressure gradient vs. flow relationships in patients with symptomatic valvular aortic stenosis — PREFLOW

Introduction Management of aortic stenosis, particularly with preserved left ventricular ejection fraction (LVEF) and discordant or borderline echocardiographic findings, remains challenging, both in assessing the true severity of stenosis and in isolating the valvular contribution to symptoms amidst comorbid conditions. This study evaluates the feasibility and physiological insight obtained from invasive pressure measurements across the aortic valve at rest and during exercise in symptomatic patients with aortic stenosis (AS). Methods This prospective cross-sectional study included patients with symptomatic high-gradient severe, low-gradient severe, and moderate aortic stenosis. They underwent invasive pressure gradient measurements across the aortic valve (pressure catheters in the left ventricle and ascending aorta) with concurrent right heart catheterization at rest and during peak supine bicycle exercise. Results Of 28 patients included, invasive measurements during exercise were feasible in 25 patients. Overall, exercise induced increases in aortic valve gradient, flow, and opening area, but there was considerable heterogeneity in individual hemodynamic responses. Notably, of the 14 patients in the low-gradient severe group based on echocardiography, nine demonstrated divergent physiological responses consistent with either moderate or high-gradient severe during exercise. All patients — irrespective of stenosis severity — had differential causes of symptoms during exercise with at least one of the following: chronotropic incompetence, abnormal increase in pulmonary artery or left ventricular end-diastolic pressures, or peripheral impairment of oxygen extraction or utilization. Conclusion These findings demonstrate the safety and feasibility of invasive hemodynamic exercise testing in patients with aortic stenosis and highlight heterogeneity in pressure-flow responses during exercise. Invasive hemodynamic assessment during exercise may help elucidate alternative contributing mechanisms to exertional dyspnea, particularly in patients with aortic stenosis and discordant symptoms and findings.