Dysregulation of Lipid Metabolism and Right Ventricular Function in PAH

Right ventricular (RV) failure is the predominant cause of death in pulmonary arterial hypertension (PAH). No RV-specific therapies are available, in part because the underlying mechanisms of RV dysfunction are poorly understood. Given the heart's preference for fatty acids (FA) as an energy source, a deeper understanding of FA metabolism may shed light on RV adaptation to elevated afterload in PAH. The purpose of this study is to test the hypothesis that defects in fatty acid metabolism are common in PAH and contribute to RV failure. The investigators will measure peripheral and transcardiac lipid and glucose metabolites in PAH patients in comparison with patients with pulmonary venous hypertension and no evidence of pulmonary hypertension. The investigators will also correlate metabolites with concurrent measurement of right ventricular function.

Study Overview

• Status: Completed
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Other: Cardiac MRI; Procedure: Blood Sampling

• Study Type: Observational
• Enrollment (Actual): 15

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Vanderbilt Univeristy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

PAH

Description

Inclusion Criteria:

• ≥ 18 years old
• Scheduled to undergo cardiac catheterization (right ± left heart catheterization) and/or electrophysiology study in the VHVI cardiac catheterization laboratory (CCL)/electrophysiology laboratory (EP lab)
• Hemoglobin value ≥ 10 g/dL or hematocrit of ≥ 30% (measured on clinically-indicated blood draw within 30 days or a point-of-care measurement in CCL/EP Laboratory if clinically-indicated value is not available)

Exclusion Criteria:

• Any individual that is anemic and has a hemoglobin value < 10 g/dL and hematocrit of < 30% will be excluded from the study.
• If a physician performing the procedure believes that performing the extra steps and /or acquiring the additional blood samples will delay or otherwise compromise participants' care, he/she can abandon acquisition of those data at his/her discretion.

• Contraindication to cardiac MRI (applies only to patients undergoing CMR as part of this protocol).

  • Implanted ferromagnetic material
  • Glomerular filtration rate < 60mL/min (measured on clinically-indicated blood draw within 30 days of CMR or a point-of-care measurement in the CMR Laboratory if clinically-indicated GFR is not available)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pulmonary Arterial Hypertension; Clinical diagnosis of pulmonary arterial hypertension	Other: Cardiac MRI; Procedure: Blood Sampling
Healthy subjects and patients with other causes of PH; Patients referred for right heart catheterization who do not have PAH	Procedure: Blood Sampling

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peripheral blood oleoylcarnitine in PAH versus control		At time of clinic visit, within 24 hrs prior to right heart catheritization
Percent change across the cardiac circulation of oleate and the glucose/lactate ratio.	The combination of these findings will indicate if there is a decreased reliance on FAO and and increased glycolysis	At time of right heart catheterization

Secondary Outcome Measures

Outcome Measure	Time Frame
Correlation of oleoylcarnitine, other acylcarnitines and free fatty acids with the homeostatic index of insulin resistance, tricuspid annular plane systolic excursion, and six minute walk distance	At time of clinic visit, within 24hrs prior to right heart catheritization
Correlation of the trans-cardiac gradient of oleate and lactate/glucose with right ventricular ejection fraction on cardiac MRI and six minute walk distance.	At time of right heart catheterization
Measurement of trans-cardiac acylcarnitines	At time of right heart catheterization
Measurement of trans-cardiac and trans-pulmonary glucose metabolites	At time of right heart catheterization
Measurement of trans-cardiac and trans-pulmonary lipid metabolites	At time of right heart catheterization
Measurement of trans-cardiac and trans-pulmonary amino acid metabolites	At time of right heart catheterization

Collaborators and Investigators

• Sponsor: Vanderbilt University
• Investigators: Principal Investigator: Evan Brittain, MD, MSCI, Vanderbilt Univerisy

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Actual): June 1, 2019
• Study Completion (Actual): June 1, 2019

Study Registration Dates

• First Submitted: December 12, 2014
• First Submitted That Met QC Criteria: December 11, 2015
• First Posted (Estimate): December 16, 2015

Study Record Updates

• Last Update Posted (Actual): July 16, 2019
• Last Update Submitted That Met QC Criteria: July 15, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension
• Other Study ID Numbers: 140983