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

NCT05015829 | Unknown DMC

• 2 other identifiers: S-2019005819/34844
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Aortic Valve Stenosis; Valvular Stenosis; Valvular Heart Disease

Outcome Measures

Primary Outcomes (11)

• Adverse effects during Dobutamine infusion

  1. 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. 2. 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

Study Arms (2)

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

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

Interventions

Dobutamine Stress Echocardiography DIAGNOSTIC_TEST

Change in echocardiographic 2D and doppler measurements during infusion with Dobutamine 5 µg/kg/min till max dosage of 20 µg/kg/min.

Classical low-flow low-gradient aortic stenosis; Paradoxical low-flow low-gradient aortic stenosis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.
• Age \> 18 years.
• Signed informed consent.

You may not qualify if:

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

Sponsors & Collaborators

• Odense University Hospital: lead
• University of Southern Denmark: collaborator
• Region of Southern Denmark: collaborator

Study Sites (1)

Odense University Hospital

Odense, Fune, 5000, Denmark

RECRUITING

MeSH Terms

Conditions

Aortic Valve Stenosis; Heart Valve Diseases

Interventions

Echocardiography, Stress

Condition Hierarchy (Ancestors)

Aortic Valve Disease; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction

Intervention Hierarchy (Ancestors)

Echocardiography; Cardiac Imaging Techniques; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Ultrasonography; Heart Function Tests; Diagnostic Techniques, Cardiovascular

Central Study Contacts

Nils Mogensen, MD

CONTACT

61286371; nils.sofus.borg.mogensen@rsyd.dk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Doctor

Study Record Dates

• First Submitted: July 15, 2021
• First Posted: August 20, 2021
• Study Start: September 1, 2019
• Primary Completion: September 1, 2021
• Study Completion: August 31, 2022
• Last Updated: August 20, 2021

Record last verified: 2021-08

Locations

DK (1)