BackgroundDobutamine stress echocardiography (DSE) is recommended by guidelines to distinguish between true-severe and pseudo-severe aortic stenosis (AS) in patients with low-gradients and left ventricular ejection fraction (LVEF) 50%.MethodsPatients with aortic mean gradient 2, and stroke volume index ≤35 mL/m2undergoing DSE and Cardiac Computer Tomography (C-CT) were identified from three prospectively collected patient cohorts, and stratified according to LVEF; LVEF 50%. Severe AS was defined as AVC score ≥2000 AU among men, and ≥1200 AU for women on C-CT.ResultsTwo hundred twenty-one patients were included in the study. Seventy-eight (35%) presented with LVEF 50%. DSE was performed without adverse symptoms or significant arrhythmias in 215 (96%) patients and stroke volume increased uniformly with no significant differences between groups (p=0.28).Mean gradient and Vmaxduring DSE showed significantly diagnostic heterogeneity between LVEF groups, being most precise when LVEF ConclusionWhile DSE is safe and leads to a uniform increase in stroke volume in patients with low gradient AS regardless of baseline LVEF, the association between DSE gradients and AS severity assessed by C-CT demonstrates important heterogeneity depending on LVEF, with highest accuracy in patients with LVEF Clinical perspectiveWhat is new?Dobutamine stress echocardiography (DSE) is safe in patients with low-gradient AS with LVEF >50%, and leads to similar increase in stroke volume as in patients with LVEF The diagnostic accuracy of DSE, compared to AVC as the reference for severe AS, depends on LVEF with highest accuracy in patients with LVEF Suggested reference thresholds for DSE may not be the most accurate for AS severity, when compared to AVC.What are the clinical implications?Based on our study, we suggest that DSE should primarily be used for determining AS severity in patients with LVEF