The Right Ventricle in Chronic Pressure Overload: Identifying Novel Molecular Targets for Functional Imaging (MVD)

Chronically elevated pulmonary pressures do not immediately result in right ventricular failure. During the initial period of exposure, the RV adapts to the increased afterload by altering its metabolism and morphology so as to meet the increased work requirement. Several, interconnected adaptive mechanisms have been proposed, including myocyte hypertrophy, a switch in the primary fuel used for ATP generation, increased angiogenesis, and decreased production of mitochondrial reactive oxygen species. While adaptation is initially successful in many cases, it is temporary, and after an uncertain period of time, the ventricle begins to fail. This transition from a compensated to decompensated state is difficult to predict clinically, and patients with different etiologies of CPOS progress to overt RV failure over significantly different time periods. This variability hinders the implementation of treatments that are tailored to a specific disease stage.

Study Overview

• Status: Completed
• Conditions: Chronic Thromboembolic Pulmonary Hypertension
• Intervention / Treatment: Procedure: Right ventricular biopsies

Detailed Description

Chronically elevated pulmonary pressures do not immediately result in right ventricular failure. During the initial period of exposure, the RV adapts to the increased afterload by altering its metabolism and morphology so as to meet the increased work requirement. Several, interconnected adaptive mechanisms have been proposed, including myocyte hypertrophy, a switch in the primary fuel used for ATP generation, increased angiogenesis, and decreased production of mitochondrial reactive oxygen species. While adaptation is initially successful in many cases, it is temporary, and after an uncertain period of time, the ventricle begins to fail. This transition from a compensated to decompensated state is difficult to predict clinically, and patients with different etiologies of CPOS progress to overt RV failure over significantly different time periods. This variability hinders the implementation of treatments that are tailored to a specific disease stage. As right heart failure is the primary outcome determinant in patients with pulmonary hypertension, understanding the major mediators of RV compensation, failure and recovery is essential to improving patient survival. Recently, there have been significant advances in the ability to assess RV function in vivo using functional imaging techniques, including positron emission tomography (PET) and cardiac MRI (CMR). CMR is an established and validated method of precisely defining cardiac structure and function, and new PET protocols have been developed that measure glucose utilization, oxygen consumption, apoptosis and angiogenesis. Importantly, the in vivo nature of PET and CMR allow for the non-invasive collection of detailed structural, metabolic and physiologic data on the performance of the RV5. When taken in combination with established echocardiographic evaluation, these new platforms allow in-depth analysis of cardiac structure and function without the need for invasive procedures. In order to maximize the potential of these techniques, however, a molecular imaging target needs to be identified so as to allow physicians to detect the transition from a compensated to decompensated state. Such a marker has not yet been reported

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Le Plessis-Robinson, France, 92350
    • Centre Chirurgical Marie Lannelongue

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:

Chronic thromboembolic pulmonary hypertension group:

• Patients undergoing pulmonary endarterectomy at Marie Lannelongue Surgical Center for the treatment of chronic thromboembolic pulmonary hypertension.

Control group:

• Patients undergoing adult cardiac surgery without evidence of pulmonary hypertension on preoperative assessment
• Exclusion Criteria:

Chronic thromboembolic pulmonary hypertension group:

• Insufficient biopsy material,
• pre-operative therapy with bosentan or sildenafil

Control group:

• Insufficient biopsy sample,
• ischemic cardiomyopathy,
• miral or tricuspid valve disease,
• pre-operative pulmonary hypertension.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CTEPH; Patients undergoing pulmonary endarterectomy for the treatment of chronic thromboembolic pulmonary hypertension (CTEPH).	Procedure: Right ventricular biopsies; a right ventricular biopsy will be taken intraoperatively during either pulmonary endarterectomy (experimental group) or open cardiac surgery (control group).
Other: Control group; Patients undergoing adult cardiac surgery without evidence of pulmonary hypertension.	Procedure: Right ventricular biopsies; a right ventricular biopsy will be taken intraoperatively during either pulmonary endarterectomy (experimental group) or open cardiac surgery (control group).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
relationship between the metabolic, morphologic and functional alterations in the right ventricle	to investigate the relationship between the metabolic, morphologic and functional alterations in the right ventricle before surgery,one and six months after surgery.

Secondary Outcome Measures

Outcome Measure	Time Frame
validation in human subjects of metabolic signaling pathway alterations found in animal model	analyse gene and protein expression during surgery

Collaborators and Investigators

• Sponsor: Centre Chirurgical Marie Lannelongue
• Investigators: Principal Investigator: Olaf Mercier, MD, PhD, Marie Lannelongue Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2017
• Primary Completion (Actual): November 20, 2017
• Study Completion (Actual): October 20, 2018

Study Registration Dates

• First Submitted: March 22, 2017
• First Submitted That Met QC Criteria: June 23, 2017
• First Posted (Actual): June 26, 2017

Study Record Updates

• Last Update Posted (Actual): January 23, 2020
• Last Update Submitted That Met QC Criteria: January 21, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary
• Other Study ID Numbers: 2015-A00149-40

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