Diagnostic Impact of Low-dose Dobutamine Echocardiography in Low-flow Low-gradient Aortic Stenosis (DALLAS)

When aortic valve-area is <1.0cm2 and transvalvular mean-gradient is >40mmHg, the diagnosis of severe aortic stenosis (AS) is straightforward. However, some patients present with an apparently reduced valve-area, despite transvalvular-gradient <40mmHg; Low-flow, low-gradient aortic stenosis (LFLG AS). When a patient with LFLG AS also presents with LVEF <50%, guidelines recommends performing a Low-Dose Dobutamine-echocardiography (LDDE) to confirm true-severe AS. However, nearly 30% of patients with LFLG AS do not show an adequate respond to Dobutamine. More commonly, patients present with the combination of LFLG AS, despite LVEF≥50%. In this group of patients the use of LDDE remains undisclosed.

The purpose of this study is to examine the safety and diagnostic usefulness of LDDE in patients with LFLG AS with LVEF≥50%. Furthermore we will examine factors associated with inadequate response to LDDE.

150 symptomatic and/or asymptomatic patients with LFLG and LVEF≥50% and a control group with LVEF<50% will be enrolled at the Department of Cardiology, OUH. Patients will undergo clinical evaluation including LDDE, blood analyses, CT-scan and cardiac Mri.

Only a limited number of studies examine the possible use of LDDE in patients with LFLG AS and LVEF≥50% and no study has been performed documenting the safety and feasibility.

Study Overview

• Status: Recruiting
• Conditions: Aortic Valve Stenosis; Valvular Heart Disease; Valvular Stenosis
• Intervention / Treatment: Diagnostic test: Dobutamine Stress Echocardiography

• Study Type: Observational
• Enrollment (Anticipated): 150

Contacts and Locations

• Study Contact: Name: Nils Mogensen, MD; Phone Number: +45 61286371; Email: nils.sofus.borg.mogensen@rsyd.dk

Study Locations

• Denmark
  • Fune
    • Odense, Fune, Denmark, 5000
      • Recruiting
      • Odense University Hospital
      • Contact: Nils Mogensen, MD; Phone Number: +45 61283671; Email: nils.sofus.borg.mogensen@rsyd.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with LFLG AS followed at the Department of Cardiology, Odense University Hospital will be offered participation in the study.

Description

Inclusion Criteria:

1. Low-flow (SVi<35 ml/m2) low-gradient (mean gradient <40 mmHg) AS with estimated AVA<1.0 cm2 referred to the Department of Cardiology, Odense University Hospital.
2. Age > 18 years.
3. Signed informed consent.

Exclusion Criteria:

1. Other moderate-severe valvular heart disease.
2. Unwilling to participate in the study.
3. Poor echocardiographic window.
4. Inability to follow-up due to temporary citizenship Registration Number (CPR-Number) or emigration within the study period.
5. Pregnant women.
6. Patients with severe chronic renal failure (eGFR<40 ml/min) will not undergo cardiac MRi or CT angiography.
7. Known contrast allergy.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Classical low-flow low-gradient aortic stenosis; LVEF<50% SVi < 35.0 mL/m2 Aortic mean gradient < 40 mmHg AVA < 1.0 cm2.	Diagnostic test: Dobutamine Stress Echocardiography; Change in echocardiographic 2D and doppler measurements during infusion with Dobutamine 5 µg/kg/min till max dosage of 20 µg/kg/min.
Paradoxical low-flow low-gradient aortic stenosis; LVEF>50% SVi < 35.0 mL/m2 Aortic mean gradient < 40 mmHg AVA < 1.0 cm2.	Diagnostic test: Dobutamine Stress Echocardiography; Change in echocardiographic 2D and doppler measurements during infusion with Dobutamine 5 µg/kg/min till max dosage of 20 µg/kg/min.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse effects during Dobutamine infusion	The occurrence of angina pectoris, severely high systolic blood pressure >200 mmHg or ventricular premature beats Lown Grade >3 or supra-ventricular arrhythmias or tachycardia assessed by ECG.; Occurrence of signs of echocardiographic subvalvular obstruction; (systolic anterior motion of the mitral leaflet (SAM), high velocities (>2 m/sec) in the LV outflow tract and late peaking systolic jet).	Dobutamine infusion, up to 30 minutes
Factors associated with flow-reserve	a) Gender (male/female).	Dobutamine infusion, up to 30 minutes
Factors associated with flow-reserve	b) Aortic valve calcification assessed by cardiac CT (AU).	Dobutamine infusion, up to 30 minutes
Factors associated with flow-reserve	c) Myocardial fibrosis assessed by MRi (%).	Dobutamine infusion, up to 30 minutes
Factors associated with flow-reserve	d) Baseline myocardial systolic and diastolic function estimated by echocardiography (Global Longitudinal Strain (%), Strain Ratesystolic (SRs), deceleration time of mitral E-wave (ms) and end-systolic wall-stress corrected LVEF (dynes).	Dobutamine infusion, up to 30 minutes
Factors associated with flow-reserve	e) The ongoing use of beta-blockers (%, dosis).	Dobutamine infusion, up to 30 minutes
Factors associated with flow-reserve	f) Association with outcomes (rate of AVR, hospitalization for cardiac failure, death).	Dobutamine infusion, up to 30 minutes
The ability of LDDE to predict outcome in patients with paradoxical low-flow, low-gradient aortic stenosis.	Rate of AVR	1 day til 3 years
The ability of LDDE to predict outcome in patients with paradoxical low-flow, low-gradient aortic stenosis.	Hospitalization for cardiac failure	1 day til 3 years
The ability of LDDE to predict outcome in patients with paradoxical low-flow, low-gradient aortic stenosis.	All-cause mortality	1 day til 3 years
The ability of LDDE to predict outcome in patients with paradoxical low-flow, low-gradient aortic stenosis.	Cardiovascular mortality	1 day til 3 years

Collaborators and Investigators

• Sponsor: Odense University Hospital
• Collaborators: University of Southern Denmark; Region of Southern Denmark

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2019
• Primary Completion (Anticipated): September 1, 2021
• Study Completion (Anticipated): August 31, 2022

Study Registration Dates

• First Submitted: July 15, 2021
• First Submitted That Met QC Criteria: August 16, 2021
• First Posted (Actual): August 20, 2021

Study Record Updates

• Last Update Posted (Actual): August 20, 2021
• Last Update Submitted That Met QC Criteria: August 16, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathological Conditions, Anatomical; Aortic Valve Disease; Ventricular Outflow Obstruction; Heart Diseases; Aortic Valve Stenosis; Constriction, Pathologic; Heart Valve Diseases; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Adrenergic Agonists; Cardiotonic Agents; Adrenergic beta-Agonists; Sympathomimetics; Adrenergic beta-1 Receptor Agonists; Dobutamine
• Other Study ID Numbers: S-20190058; 19/34844 (Other Identifier: Danish Data Protection Agency, Sourthern Denmark)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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