A Pilot Study Evaluating Heart and Lung Metabolism in Pulmonary Hypertension Associated With Left Heart Disease

Evaluation of Cardiopulmonary Metabolism and Pulmonary Vascular Remodeling in Pulmonary Hypertension Associated With Left Heart Disease

Right ventricular (RV) failure is the leading cause of death in pulmonary arterial hypertension. (PAH) Right ventricular ejection fraction is one of the most important predictors of prognosis in heart failure patients regardless of cause. It is estimated that 30-50% of patients with heart failure and preserved ejection fraction (HFpEF) have right ventricular dysfunction and up to 70% of these patients will have significant pulmonary hypertension (PH), both of which are related to much worse prognosis. Right ventricular failure is becoming an increasingly prevalent and significant cause of morbidity in patients with left heart disease. Despite the significance of RV function to survival, there are no therapies available that directly or selectively improve RV function.

The overall theme of this research project is to evaluate the mechanisms that contribute to the cause of right heart failure. This small study is designed to look at the role of heart and lung metabolism and pulmonary hypertension as they relate to the development of right heart failure in cardiovascular disease.(PH-LHD)

Study Overview

• Status: Terminated
• Conditions: Pulmonary Hypertension
• Intervention / Treatment: Radiation: FDG PET scan

Detailed Description

The hemodynamic definition of PH-LHD involves a mean pulmonary artery pressure (mPAP) >25mm Hg at rest and pulmonary capillary wedge pressure (PCWP) of ≥15.The coexistence of mitral insufficiency is also a characteristic of PH-LHD. HFpEF is a condition caused by impaired relaxation of a stiffened myocardium as a consequence of an increased load to the left ventricle due to elevated systemic pressures.

Pulmonary hemodynamics can be used to classify PH LHD as either passive or reactive, irrespective of LV function. It has been suggested that diastolic pressure gradient (DPG) may offer added prognostic value as a more accurate indicator of pulmonary vascular remodeling.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1Y4W7
      • University of OttawaHeart Institute

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients must be able to provide their written informed consent to participate in the study after having received adequate previous information and prior to any study specific procedures.
• At least 18 years of age at the time of screening.
• Patients with PH secondary to left heart disease (known as group II PH) defined as a mean PAP>25 mmHg and a PCWP of ≥15 mmHg.

Exclusion Criteria:

• All other types of pulmonary hypertension including Dana Point Classification Group 1, 3, 5.
• Type II Diabetes mellitus requiring medical therapy
• Previous myocardial infarction within the 3 months prior to screening.
• Renal insufficiency (glomerular filtration rate < 30 ml/min.
• ALT or AST > 3times ULN and/or severe hepatic insufficiency.
• Contraindication to MRI imaging.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: FDG PET scan; A PET scan using F-18 FDG, N-13 Ammonia will be performed

Radiation: FDG PET scan; Following an overnight fast, subjects will be positioned in the Discovery 660 PET/VCT scanner. Following a scout scan to confirm patient positioning, low dose xray CT scan is performed for photon attenuation. A 20 minute dynamic PET scan is started simultaneously with 3 MBq/kg of N-13 ammonia to measure myocardial perfusion. Following N-13 decay,a 60 minute dynamic PET scan with 3 MBq/kg F-18- FDG to measure myocardial glucose uptake. Blood sampling for glucose and insulin will occur at pre specified time points throughout the scan.; Other Names: F-18-FDG; N-13 ammonia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiac and pulmonary metabolism role in development of right heart failure in pulmonary hypertension in left heart disease.	Relationship between lung fludeoxyglucose (FDG)uptake and hemodynamic type pulmonary hypertension using PET scanning	Baseline

Collaborators and Investigators

• Sponsor: Ottawa Heart Institute Research Corporation

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2014
• Primary Completion (Actual): August 1, 2018
• Study Completion (Actual): August 1, 2018

Study Registration Dates

• First Submitted: August 29, 2014
• First Submitted That Met QC Criteria: September 8, 2014
• First Posted (Estimate): September 11, 2014

Study Record Updates

• Last Update Posted (Actual): August 31, 2018
• Last Update Submitted That Met QC Criteria: August 28, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: FDG lung and RV uptake
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Heart Diseases; Hypertension; Hypertension, Pulmonary
• Other Study ID Numbers: 20140602

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Only 2 participants were enrolled in this study. One of the main reasons was no clinical indication to repeat a right heart catherization in this population.