To investigate the effects of Dobutamine on RV contractility and oxygen consumption in patients with pulmonary arterial hypertension (PAH).
ID
Source
Brief title
Condition
- Heart failures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main study parameters will be:
• Myocardial oxygen consumption (kmono [C11]-acetate)
• Contractility measured as end-systolic elastance (Ees). Which is calculated
using the single beat method
Secondary outcome
Secondary study parameters are:
• Serum dihydroxyphenylacetic acid (DOPAC), dihydroxyphenylglycol (DHPG),
norepinephrine (NE), normetanephrine (NMN), methoxyhydroxyphenylglycol (MHPG)
which are metabolites of catecholamine degradation by monoamine oxidase (MAO).
• Heart rate
Background summary
In the pulmonary hypertension (PH) guidelines inotropic support with dobutamine
is the recommended treatment in patients with decompensated right heart failure
due to PH. However recent research has shown that during exercise RV
contractile reserve is diminished in PH patients. In addition, Dobutamine is
known to increase myocardial oxygen consumption. Hence, the efficacy of
Dobutamine administration in patients with severe right heart failure could be
questioned. Therefore we aim to study the effects of Dobutamine on RV
contractility and oxygen consumption.
Study objective
To investigate the effects of Dobutamine on RV contractility and oxygen
consumption in patients with pulmonary arterial hypertension (PAH).
Study design
This is a prospective non-blinded, non-randomized interventional study. We will
prospectively include 16 PAH or CTEPH patients in New York Health Association
(NYHA) functional class III or IV.
To be able to correct for the impact of perfusion on the uptake patterns of the
[11C]-acetate
tracer, a [15]-H2O scan will be performed first at both days. Subsequently, the
[11C]-acetate scan will be performed. Low-dose CT-scans will be performed for
attenuation correction. During the PET-procedures, venous samples will be
collected at different time points.
On day 1 a CMRI and PET-scan will be performed in resting conditions. On day 2,
patients will undergo a right heart catheterization. During RHC blood samples
are withdrawn for catecholamine levels before and after initiation of
dobutamine infusion. Dobutamine infusion is started after baseline
measurements. After 10 minutes of infusion peak plasma concentrations and peak
effects occur. Dobutamine infusion is discontinued when the second PET-scan and
CMR are obtained.
Abbreviations: CMRI = cardiac magnetic resonance imaging, CT = computed
tomography, RHC = right heart catheterization.
Intervention
Not applicable
Study burden and risks
Extensive study protocol where patients are scanned (PET + CMR) on two
consecutive days and will undergo a right heart catheterization. The tracers
are given through one intravenous (iv) line in a peripheral vein. Blood samples
are withdrawn from the same iv-line. The total amount of blood is 120 ml during
the entire protocol. The radiation dose of 7.0 mSv remains below the allowed
maximum radiation dose of 10 mSv. The right hearth catheterization and one CMR
in the protocol are standard follow up procedures. Dobutamine dosage is low; 10
µg.kg-1.min-1, which was well tolerated by PAH patients in earlier studies.
De Boelelaan 1117
Amsterdam 1081 HZ
NL
De Boelelaan 1117
Amsterdam 1081 HZ
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible to participate in this study, a subject must meet all
of the following criteria:
• Age >18 years
• Patients have to be diagnosed with idiopathic -, hereditary -, or drug- and
toxins induced PAH or chronic thrombo-embolic pulmonary hypertension (CTEPH)
conform ESC/ERS guidelines. PAH is diagnosed when the following criteria are
met:
o Mean Pulmonary Artery Pressure (mPAP) >= 25 mmHg
o Pulmonary Arterial Wedge Pressure (PAWP) > 15 mmHg
o Other possible causes of PAH are excluded
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded
from participation in this study:
• <1 year since last participation in research that included nuclear imaging
• Congenital heart disease
• Left sided heart disease
• Pulmonary Hypertension other than idiopathic -, hereditary -, or drug- and
toxins induced PAH or CTEPH
• Known coronary artery disease
• Pregnancy
• Malignancies
• Kidney failure
• Anemia (Hb < 8.0)
• Atrial fibrillation
• Use of β-blockers or α-blockers
• Use of ACE-inhibitors
• Age > 70 years
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-004844-40-NL |
| CCMO | NL64257.029.18 |