Ketonemia, Pulmonary Hypertension
Conditions
Keywords
Right sided heart catheterization, Echocardiography, Hemodynamics
Brief summary
In the present study, patients with idiopathic pulmonary hypertension (IPAH) and chronic thromboembolic pulmonary hypertenion will be investigated in a randomized cross-over design with ketone infusions and placebo. Invasive and non-invasive hemodynamics will be evaluated
Detailed description
Pulmonary hypertension (PH) is a debilitating disease that affects both the pulmonary vasculature and the heart. It is associated with increased mortality and hospitalization and impairs daily life for the affected patients. Despite substantial advances in treatment within the past decade the prognosis remains poor with an 1-year mortality of more than 10%.1 The pathophysiology of PH is multifactorial and can be caused by left sided cardiac disease, pulmonary pathophysiological changes in the pulmonary vessels, respiratory diseases and pulmonary embolism.The treatment is targeted at the underlying cause. Hence, left sided heart disease is treated with anticongestive medications4 and respiratory disease by pulmonary medications. However, pulmonary vascular diseases such as chronic thromboembolic pulmonary hypertension (CTEPH) and idiopathic pulmonary arterial hypertension (IPAH) are treated with pulmonary endarterectomy and vasodilators targeting the pulmonary vasculature, respectively. However, not all patients have an optimal pulmonary hemodynamic response on treatment. If patients are left with persistent pulmonary hypertension the disease may progress further and cause right heart failure which worsens the prognosis. Data from a recent study conducted at the investigator's institution demonstrated 40% increase in cardiac output during infusion of the ketone body 3-hydroxybutyrate (3-OHB). Intriguingly, this was associated with an increase in RV function and a decrease in the pulmonary vascular resistance of approximately 20%. In the present study, 10 patients with IPAH and 10 patients with CETPH will be subjected to placebo and 3-OHB infusion in a randomized cross-over design. Each of the infusions will be given for 2.5 hours and cross-over will be carried out on the same day. Echocardiography and right sided heart catheterization will be applied and blood will be sampled.
Interventions
DIETARY_SUPPLEMENTHyperketonemia - use of ketone (3-OHB) infusion
The effect of intravenous ketone supplement
DIETARY_SUPPLEMENTPlacebo - use of saline infusion
Saline is infused as an comparator
Sponsors
Danish Heart Foundation
University of Aarhus
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
The participant and the endpoint-assessor will be masked to intevention
Intervention model description
Randomized cross-over I.e. Ketone infusion is compared to saline infusion in a randomised cross-ove design. (Ketones are considered dietary supplement as glucose or lipids)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Persistent pulmonary hypertension (defined as PVR \> 3 WU, pulmonary capillary wedge pressure (PCWP) \< 15 mmHG, mean pulmonary arterial pressure (mPAP) ≥25 mmHg) on the most resent right heart catheterization. * Preserved left ventricular ejection fraction (\<50%) on most recent echocardiography * Able to give informed consent
Exclusion criteria
* Other Significant pulmonary, mitral or aortic valve disease * Other disease or treatment making subject unsuitable for study participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cardiac output (L/min | changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion | Measured by Swan-Ganz monitoring |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| systemic blood pressure (mmHg) | changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion | Hemodynamics - non-invasive blood pressure measurement |
| pulmonary capillary pressure (mmHg) | changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion | Hemodynamics - Swan Ganz monitoring |
| Pulmonary pressure (mmHg) | changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion | Hemodynamics - Swan Ganz monitoring |
| TAPSE (mm) | changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion | Echocardiography |
| RV strain (%) | changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion | Echocardiography |
| LV strain (%) | changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion | Echocardiography |
| mixed venous saturation (%) | changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion | Hemodynamics - Swan Ganz monitoring |
| Left ventricular ejection fraction (%) | changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion | Echocardiography |
| Changes in Prostaglandines (pmol/L) | changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion | Blood samples |
| pH | changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion | Blood samples |
| sodium (mM) | changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion | Blood samples |
| potassium (mM) | changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion | Blood samples |
| lactate (mM) | changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion | Blood samples |
| systolic tricuspid plane velocity (cm/sec) | changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion | Echocardiography |
Countries
Denmark
Outcome results
None listed