The aim of this study is to test the diagnostic added value of Volume Challenge (VC) to low-dose dobutamine stress echocardiography (LDDSE) in patients with a low-flow, low-gradient aortic stenosis (LFLGAS). This study will assess if LDDSE plus VC allows to increase the proportion of patients in whom a true severe AS can be differentiated from a pseudo severe AS.

The design of the study is a monocentric prospective non-randomized pilot clinical trial. A standard LDDSE will be performed. The stroke volume (SV) will be recorded. The addition of VC with the passive leg raise method at peak dobutamine dose will be performed. A transesophageal echocardiography (TEE) with low dose dobutamine and a bolus of normal saline will be performed as a validation method to measure AVA with the planimetry method. The SV will be recorded. Proportion of patient receiving the diagnosis of true severe AS defined as a combination of AVA <1.0 cm2 and ∆SV ≥ 20% will be compared between standard LDDSE and LDDSE with addition of VC. Calculating sensitivity, specificity, performing ROC curve analysis and calculating the Youden-index, the accuracy of the test method (LDDSE plus passive leg raising) for the detection of truly severe AS in comparison with the reference method (TEE) will be determined.

Inclusion Criteria:

• Age > 18 years
• Written informed consent
• Patients with LFLGAS (mean Gradient: < 40 mmHg, AVA ≤ 1.0 cm2 (by continuity equation using LVOT diameter) SVI ≤ 35 ml/m2), by rest TTE

Exclusion Criteria:

• Hypersensitivity to dobutamine or midazolam
• Lack of safe contraception defined as: Female participants of childbearing potential not using and not willing to continue contraception for study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices.
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc.,
• Enrolment of the investigator, his/her family members, employees and other dependent persons
• Previous enrolment into the current study,

ADDITIONAL SPECIFIC EXCLUSION CRITERIA REGARDING STRESS ECHOCARDIOGRAPHY:

• Systolic left ventricular ejection fraction (LVEF) < 20%
• More than mild aortic regurgitation
• Mitral valve disease, defined by mitral valve area < 2.0 cm2 or more than mild mitral regurgitation
• Unstable angina
• Acute pulmonary oedema
• Signs of relevant left ventricular heart failure defined as crackles more than one fourth of lung field on auscultation
• Signs of relevant right ventricular heart failure defined as central venous pressure (CVP) > 15 mmHg estimated with dilatation and collapsibility of vena cava inferior (VCI)
• Severe pulmonary, renal or hepatic disease

ADDITIONAL SPECIFIC EXCLUSION CRITERIA REGARDING TRANSESOPHAGEAL ECHOCARDIOGRAPHY:

• Oesophageal varices
• History of bariatric surgery