Right Ventricular Metabolism in Pulmonary Arterial Hypertension

Metabolic Intervention in the Right Ventricle in Pulmonary Arterial Hypertension

The purpose of this study is to use non-invasive imaging to determine the metabolic phenotype of the right ventricle in patients with pulmonary arterial hypertension across a spectrum of disease severity.

Study Overview

• Status: Completed
• Conditions: Healthy; Pulmonary Arterial Hypertension

Detailed Description

Current medical therapy for pulmonary arterial hypertension (PAH) is aimed at reducing pulmonary vascular resistance (PVR) but not ameliorating right ventricular (RV) failure, the major cause of death. There are no RV-specific therapies currently available for PAH, in part because the pathophysiology of RV failure is poorly understood.

The investigators hypothesize that the RV in PAH develops a distinct metabolic pattern characterized by increased glycolysis, impaired oxidative metabolism and lipid deposition, which are associated with RV failure.

Specific Aim 1. To test the hypothesis that the RV in human PAH exhibits lipid deposition, increased glycolysis and impaired fatty acid oxidation. The investigators will measure RV oxidative metabolism and glycolysis in PAH patients and controls using positron emission tomography 11C acetate and [18F]fluoro-deoxy-D-glucose imaging and measure myocardial lipid accumulation using magnetic resonance spectroscopy imaging.

Specific Aim 2. To test the hypothesis that an abnormal RV metabolic profile is associated with RV dysfunction and reduced exercise capacity in PAH. PET and MRS findings will be correlated with RV function, patient exercise capacity and a blood metabolic profile.

• Study Type: Observational
• Enrollment (Actual): 34

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Pulmonary Arterial Hypertension (heritable or idiopathic) Healthy Subjects

Description

Inclusion Criteria:

• Heritable or idiopathic PAH
• 18 years or older
• Able to give informed consent

Exclusion Criteria:

• Pregnancy
• Type 1 diabetes mellitus
• Prednisone use
• PAH associated with any condition other than idiopathic or heritable
• Implanted ferromagnetic material incompatible with MRI

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Pulmonary Arterial Hypertension; Patients diagnosed with idiopathic or heritable pulmonary arterial hypertension according to consensus guidelines. RV oxidative metabolism and glycolysis will be measured using PET 11C acetate and [18F]fluoro-deoxy-Dglucose (FDG) imaging and measure myocardial lipid accumulation using MRS imaging.
Subjects without cardiopulmonary disease; Subjects without known cardiopulmonary disease. RV oxidative metabolism and glycolysis will be measured using PET 11C acetate and [18F]fluoro-deoxy-Dglucose (FDG) imaging and measure myocardial lipid accumulation using MRS imaging

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Right ventricular oxygen consumption divided by the rate pressure product	kmono divided by the rate pressure product (heart rate X systolic blood pressure)	At time of C11 acetate PET scan

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Right ventricular oxygen consumption (kmono)		At time of C11 acetate PET scan
Right ventricular glucose uptake (standardized uptake value)		At time of 18-FDG PET scan
Percent myocardial triglyceride content	Percent of myocardial triglyceride measured in the interventricular septum	At time of cardiac magnetic resonance imaging
Correlation of kmono, kmono/RPP, FDG uptake, and myocardial triglyceride content with right ventricular function		Day 1
Correlation of kmono, kmono/RPP, FDG uptake, and myocardial triglyceride content with six minute walk distance		Day 1
Correlation of kmono, kmono/RPP, FDG uptake, and myocardial triglyceride content with plasma metabolic profile		Day 1

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): June 1, 2019
• Study Completion (Actual): June 1, 2019

Study Registration Dates

• First Submitted: April 28, 2016
• First Submitted That Met QC Criteria: May 3, 2016
• First Posted (Estimate): May 5, 2016

Study Record Updates

• Last Update Posted (Actual): May 20, 2020
• Last Update Submitted That Met QC Criteria: May 18, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Healthy Subjects; Pulmonary arterial hypertension; Metabolism; Right ventricle; Right ventricular function; Non-invasive imaging
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension
• Other Study ID Numbers: 131271

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO