Dobutamine Stress Echocardiography in LF/LG Aortic Stenosis and Wild-type Transthyretin Amyloid Cardiomyopathy

NCT06372301 | Recruiting

• 1 other identifier: 1-10-72-179-23
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this prospective clinical study is improve the diagnosis of Low-flow low-gradient aortic stenosis (LF/LG AS), in patients with co-existing wild-type transthyretin cardiac amyloidosis (ATTRwt). The main question it aims to answer is whether the classic dobutamine-stress echocardiography can be used to determine AS severity in patients with ATTRwt and LF/LG AS This question will be tried to answer by comparing dobutamine stress echocardiography, with the invasively measured aortic valve area (which is considered as the gold standard). In addition we aim to assess the degree of myocardial fibrosis and amyloid infiltration, assessed by light microscopy and cardiac magnetic resonance (CMRI) and evaluation of myocyte mitochondrial function by high resolution respirometry and their relation to AS severity and hemodynamic response to dobutamine.

Conditions

Transthyretin Amyloid Cardiomyopathy; Aortic Stenosis

Keywords

ATTR-CM; wild-type cardiac amyloidosis; aortic stenosis; low-flow low-gradient aortic stenosis; Dobutamine

Outcome Measures

Primary Outcomes (1)

• The correlation between echocardiography derived projected aortic valve area (AVAproj) and invasively assessed AVAproj under dobutamine infusion.

  Evaluated at the end of dobutamine infusion.

Secondary Outcomes (6)

• Correlation between echocardiography derived AVA and invasively assessed AVA at rest and at different dobutamine infusion levels.

  Evaluated at rest, at every dobutamine dose-level, and at the end of infusion.

• Increase of SVI, LV ejection fraction and LV-global longitudinal strain of 10 % during maximal dobutamine stimulation.

  Evaluated at the end of dobutamine infusion.

• Correlation between echo- and invasive measured SVI.

  Evaluated at the end of dobutamine infusion.

• Degree of myocardial fibrosis, amyloid infiltration and mitochondrial dysfunction and its relation to AS severity and hemodynamic response to dobutamine

  CMRI would be performed within a max of 2 months from the trial day.

• Reduction of mean pulmonary artery wedge pressure and/or mean pulmonary artery pressure by 10 %.

  Evaluated at the end of dobutamine infusion.

Study Arms (1)

Co-existing AS and ATTRwt

EXPERIMENTAL

Symptomatic patients with co-existing wild-type transthyretin amyloid cardiomyopathy and low-flow low gradient AS.

Diagnostic Test: Dobutamine stress echocardiography

Interventions

Dobutamine stress echocardiography DIAGNOSTIC_TEST

Patients will be investigated with dobutamine stress echocardiography (increasing doses of dobutamine infusion and simulatneous echocardiogarphic evaluation) to assess aortic valve area and projected aortic valve area.

Co-existing AS and ATTRwt

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• ATTRwt, diagnosis confirmed by 99mtc-3,3-Diphosphono-1,2-Propanodicarboxylic Acid (DPD) scintigraphy, genetic testing, and/or endomyocardial biopsy.
• Symptomatic patients (New York Heart Association \> class I) treated with loop diuretics.
• LF/LG AS: Defined as, aortic valve area ≤ 1 cm2 and mean gradient \< 40 mmHg, and SVI ≤35 ml/m2.
• Age ≥ 65 years.
• Oral and written informed consent.

You may not qualify if:

• Other significant valvular disease.
• Known severe coronary artery diseases: left main stem stenosis or 3-vessel disease, or recent acute myocardial infarction (\< 4 weeks).
• Contraindications to the use of dobutamine: Known allergy to dobutamine or sulfite, phaeochromocytoma or ventricular tachycardia (VT).

Sponsors & Collaborators

• Steen Hvitfeldt Poulsen: lead

Study Sites (1)

Department of Cardiology, Aarhus University Hospital

Aarhus, 8200, Denmark

RECRUITING

MeSH Terms

Conditions

Aortic Valve Stenosis

Interventions

Echocardiography, Stress

Condition Hierarchy (Ancestors)

Aortic Valve Disease; Heart Valve Diseases; 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

Ali Hussein Jaber Mejren

CONTACT

+4591651848; alimej@clin.au.dk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, DMSc.

Study Record Dates

• First Submitted: April 15, 2024
• First Posted: April 18, 2024
• Study Start: April 2, 2024
• Primary Completion: November 1, 2025
• Study Completion: April 1, 2026
• Last Updated: April 18, 2024

Record last verified: 2024-04

Locations

DK (1)