Cardiac Metabolic Remodeling After Pulmonary Vasodilator Therapy in Pulmonary Arterial Hypertension: A Pilot Study

Pulmonary arterial hypertension(PAH) is associated with the development of right heart failure. In the setting of heart failure, the heart shifts to increasing dependence on glucose metabolism. In this study, the investigators will perform cardiac positron emission tomography/magnetic resonance imaging (PET/MRI) scans to measure glucose metabolism in the heart before and after initiation of pulmonary vasodilator therapy for pulmonary arterial hypertension.

Study Overview

• Status: Terminated
• Conditions: Pulmonary Arterial Hypertension; Right-Sided Heart Failure
• Intervention / Treatment: Other: PET/MRI

Detailed Description

Pulmonary arterial hypertension is associated with the development of right heart failure. In the setting of heart failure, the heart shifts to increasing dependence on glucose metabolism. In this study, the investigators will perform cardiac positron emission tomography/magnetic resonance imaging (PET/MRI) scans to measure glucose metabolism in the heart before and after initiation of pulmonary vasodilator therapy for pulmonary arterial hypertension. By utilizing a rest-exercise protocol and continuous PET imaging acquisition, we can capture real-time changes in glucose uptake in the heart in response to acute exercise. By coupling these measures of dynamic glucose utilization with MRI-based cardiac function, we will determine cardiac metabolic efficiency.

• Study Type: Observational
• Enrollment (Actual): 2

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin-Madison

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with IPAH or CTD-PAH

Description

Inclusion Criteria:

• World Health Organization(WHO) group PAH secondary into idiopathic pulmonary arterial hypertension(IPAH) or connective tissue disease associated pulmonary arterial hypertension (CTDPAH)
• New York Heart Association (NYHA) classification I - III heart failure
• Vasodilator therapy naive
• Able to provide informed consent

Exclusion Criteria:

• Metabolic disorders such as uncontrolled diabetes (A1c > 8%) that may interfere with FDG uptake
• Baseline 6-minute walk distance (6MWD) < 400 feet or NYHA class IV heart failure
• Musculoskeletal abnormalities that would prevent exercise
• Contraindications to MRI

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ability to augment glucose uptake ("substrate flexibility"), defined as change in rate of glucose uptake from rest to exercise	Substrate flexibility is defined as the change in myocardial to blood pool glucose uptake rate from rest to exercise.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in substrate flexibility after initiation of pulmonary vasodilator therapy	Substrate flexibility is defined as the change in myocardial to blood pool glucose uptake rate from rest to exercise. Substrate flexibility before and after pulmonary vasodilator therapy will be compared.	6 months

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: United Therapeutics
• Investigators: Principal Investigator: Kara Goss, MD, University of Wisconsin, Madison

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 14, 2019
• Primary Completion (ACTUAL): July 21, 2020
• Study Completion (ACTUAL): July 21, 2020

Study Registration Dates

• First Submitted: September 12, 2019
• First Submitted That Met QC Criteria: September 13, 2019
• First Posted (ACTUAL): September 16, 2019

Study Record Updates

• Last Update Posted (ACTUAL): July 27, 2020
• Last Update Submitted That Met QC Criteria: July 23, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: metabolism; PET/MRI; pulmonary arterial hypertension; right-sided heart failure
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Congenital Abnormalities; Hypertension, Pulmonary; Heart Defects, Congenital; Cardiovascular Abnormalities; Situs Inversus; Heart Failure; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Dextrocardia
• Other Study ID Numbers: 2019-0286; A534285 (Other Identifier: UW Madison); SMPH/MEDICINE/MEDICINE*P (Other Identifier: University of Wisconsin-Madison); Protocol Version 8/2/2019 (OTHER: UW Madison)

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No