Volume Challenge Added to DSE in the Diagnosis of Severe LFLGAS (FLOW-AS)

Volume Challenge Added to Dobutamine Stress Echocardiography in the Diagnosis of Severe Low-Flow, Low-Gradient Aortic Stenosis

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.

Study Overview

• Status: Completed
• Conditions: Aortic Valve Stenosis
• Intervention / Treatment: Diagnostic test: Volume Challenge

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Bern, Switzerland, 3010
    • Bern University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Arm Volume Challenge; 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 TEE with low dose dobutamine and a bolus of normal saline will be performed as a validation method.	Diagnostic test: Volume Challenge; Addition volume challenge with passive leg raising method in LDDSE as well as administration of normal saline and dobutamine during TEE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnosis of true severe AS	Proportion of patients 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	Measures taken during echocardiograph a few minutes after administration of VC

Collaborators and Investigators

• Sponsor: University Hospital Inselspital, Berne
• Investigators: Principal Investigator: Christian Seiler, MD, University Clinic for Cardiology, Inselspital, Bern; Study Chair: Stefano de Marchi, MD, University Clinic for Cardiology, Inselspital, Bern

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2018
• Primary Completion (Actual): December 31, 2020
• Study Completion (Actual): December 31, 2020

Study Registration Dates

• First Submitted: July 31, 2018
• First Submitted That Met QC Criteria: July 31, 2018
• First Posted (Actual): August 6, 2018

Study Record Updates

• Last Update Posted (Actual): May 17, 2022
• Last Update Submitted That Met QC Criteria: May 16, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Echocardiography; Low - flow; Low - gradient; Low - dose dobutamine; Volume challenge
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis; Constriction, Pathologic
• Other Study ID Numbers: 3635

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No