RECRUITINGPhase 1 / Phase 2INTERVENTIONAL

Haemodynamic Effects of Dobutamine in Patients With Wild-type Transthyretin Amyloid Cardiomyopathy (ATTRwt)

About This Trial

The goal of this clinical trial is to test the effects of the inotropic drug named dobutamine, in patients with wild-type Transthyretin Amyoid Cardiomyopathy (ATTRwt). The main questions it aims to answer are: * What are the effects of increasing dosages of dobutamine infusion on cardiac output and filling pressures in patients with symptomatic ATTRwt. * Safety of dobutamine infusion in this patient population. Participants will be given increasing dosages of dobutamine infusion, and its effect on cardiac output and filling pressures will be assessed non-invasively by echocardiography, and invasively by right heart catheterization, simultaneously.

Who May Be Eligible (Plain English)

Who May Qualify: 1. ATTRwt, diagnosis confirmed by genetic testing, 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scintigraphy and/or endomyocardial biopsy. 2. Treated with loop diuretics. 3. New York Heart Association class II-IV. 4. Age ≥ 65 years. 5. Left ventricular ejection fraction (LVEF) \< 50 % and/or SVI assessed by echocardiography \< 35 ml/m2. 6. Thorough oral and written willing to sign a consent form to participate in the study. Who Should NOT Join This Trial: 1. Moderate to severe aortic stenosis (participants with aortic sclerosis will not be excluded). 2. Other significant valvular diseases. 3. Known severe coronary artery diseases: left main stem stenosis or 3-vessel disease, or recent acute myocardial infarction (\< 4 weeks). 4. Contraindications to the use of dobutamine: Known allergy to dobutamine or sulfite, phaeochromocytoma or ventricular tachycardia (VT). 5. End stage renal disease (eGFR of less than 15 mL/min/1,73 m2). Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: 1. ATTRwt, diagnosis confirmed by genetic testing, 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scintigraphy and/or endomyocardial biopsy. 2. Treated with loop diuretics. 3. New York Heart Association class II-IV. 4. Age ≥ 65 years. 5. Left ventricular ejection fraction (LVEF) \< 50 % and/or SVI assessed by echocardiography \< 35 ml/m2. 6. Thorough oral and written informed consent to participate in the study. Exclusion Criteria: 1. Moderate to severe aortic stenosis (participants with aortic sclerosis will not be excluded). 2. Other significant valvular diseases. 3. Known severe coronary artery diseases: left main stem stenosis or 3-vessel disease, or recent acute myocardial infarction (\< 4 weeks). 4. Contraindications to the use of dobutamine: Known allergy to dobutamine or sulfite, phaeochromocytoma or ventricular tachycardia (VT). 5. End stage renal disease (eGFR of less than 15 mL/min/1,73 m2).

Treatments Being Tested

DRUG

Dobutrex

Dobutamine (Dobutrex®) infusion. will be performed with a stepwise dobutamine dosage increase every 5 minutes (2,3,5,10,20 ug/kg/min). Dobutamine dosage will only be increased to 40 ug/kg/min in participants with ongoing beta-blocker treatment to ensure an appropriate dobutamine response. As dobutamine and its metabolites are excreted renally, the dose will be reduced to max 10 ug/kg/min in participants with eGFR below 30 mL/min/1,73 m2. Echocardiography, blood pressure, heart rate, and invasive pressure and flow measurements will be obtained before the infusion starts, at each infusion stage, and during the recovery period after the infusion is stopped.

Locations (1)

Department of Cardiology, Aarhus University Hospital

Aarhus, Denmark