Dysregulation of Lipid Metabolism and Right Ventricular Function in PAH

Completed

• Conditions: Pulmonary Arterial Hypertension
• Interventions: Procedure: Blood Sampling; Other: Cardiac MRI

• Registration Number: NCT02631421
• Lead Sponsor: Vanderbilt University

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-12-12
• Study Start: 2015-01
• Study First Submitted QC: 2015-12-11
• Study First Posted: 2015-12-16
• Primary Completion: 2019-06
• Study Completion: 2019-06
• Status Verified: 2019-07
• Last Update Submitted: 2019-07-15
• Last Update Posted: 2019-07-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

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

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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 and trans-pulmonary lipid metabolites	At time of right heart catheterization
Measurement of trans-cardiac and trans-pulmonary glucose metabolites	At time of right heart catheterization
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
Measurement of trans-cardiac acylcarnitines	At time of right heart catheterization
Measurement of trans-cardiac and trans-pulmonary amino acid metabolites	At time of right heart catheterization

Trial Locations

Locations (1)

Vanderbilt Univeristy; 🇺🇸 Nashville, Tennessee, United States