Determinants of Right Heart Remodeling in Patients With CTEPH or PAH (PRINCEPT)

Determinants of Postoperative Right Heart Remodeling in Patients With Chronic Thrombo-Embolic Pulmonary Hypertension After Endarterectomy, or Pulmonary Arterial Hypertension After Lung Transplantation

Right heart failure is the main cause of morbi-mortality in patients with pulmonary hypertension (PH), including patients of chronic thrombo-embolic pulmonary hypertension (CTEPH) or pulmonary arterial hypertension (PAH) etiologies. Endarterectomy is an effective treatment for patients with CTEPH to lower pulmonary pressure. Evidence of postoperative right heart remodeling are contrasted according to the studies and determinants of right heart failure are still unclear. Similarly, few evidence exists on right ventricular remodeling after bilateral lung transplantation for patients with pulmonary arterial hypertension (PAH). Recent evidence have supported the role of inflammation and immunity in the pathophysiology of PAH . While several cytokines have been shown to predict survival , little is known on the implication of inflammation and immunity in postoperative Right Ventricular failure in patients with PAH.

• The specific translational goal of this current project is to elucidate the role of immune biomarkers in 6 months postoperative right heart adverse remodeling in patients with CTEPH or PAH. We speculate that selected immune biomarkers (such as CXCL9, interleukin -18 or interferon) and growth factors (such as HGF) are correlated with mid-term postoperative right heart failure.

All consecutive adults with either CTEPH referred to our center for endarterectomy, or PAH referred for lung transplantation, will be included, aiming for 150 CTEPH and 50 PAH. After inclusion, patients will undergo assessment of right heart dimensions and function by cardiac magnetic resonance imaging (MRI, including 4-Dimensions blood flow sequences) and 2D and 3D trans-thoracic echocardiography (TTE), as well as immune panel analysis. All patients will undergo as part of routine care right heart catheterization within a week after TTE and MRI imaging. On the day of surgery, pulmonary pressure will be measured by right heart catheterization monitoring (as part of routine care) in order to estimate the drop of pressure and to adjust for the extent of endarterectomy for patients with CTEPH. TTE will also be performed on the day of surgery if possible. At 7 days post-endarterectomy or transplant, clinical outcomes will be collected and peripheral blood will be collected. Patients will be prospectively follow-up for 6 months. Death, need for reintervention, duration of vasopressor after surgery and number, duration and cause of readmission will be recorded. At 6 months after surgery, all survivors will undergo the same biological sampling, as well as an 4D MRI and a 2D and 3D TTE. Data of right heart catheterization at 6 months (as part of routine care) will be collected as well.

Study Overview

• Status: Unknown
• Conditions: Chronic Thrombo-embolic Pulmonary Hypertension and Pulmonary Arterial Hypertension
• Intervention / Treatment: Radiation: magnetic resonance imaging; Procedure: 2D and 3D trans-thoracic echocardiography; Other: Blood samples

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Le Plessis-Robinson, France, 92350
    • Recruiting
    • Hôpital 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:

• adults (age > 18 years old)
• who give their informed consent for the protocol
• with either CTEPH referred to our insitution for pulmonary arterial endarterectomy. CTEPH is defined by invasive mean pulmonary arterial pressure ≥ 25mmHg at rest, secondary to chronic pulmonary embolism confirmed by computed tomographic (CT) angiography and/or ventilation/perfusion scan, according to the lastest guidelines
• Or with PAH referred to our institution for lung transplant. PAH is defined according to the latest guidelines by an invasive mean pulmonary arterial pressure ≥ 25mmHg, secondary to idiopathic, familial, drug or toxin, or connective tissue disease etiology.

Exclusion Criteria:

• pregnant women
• children
• congenital heart diseases
• contraindications for MRI such as metallic foreign bodies or devices, claustrophobia
• contraindication for surgery
• patients requiring preoperative mechanical assistance such as extracorporeal membrane oxygenation
• patients with pulmonary arterial sarcoma

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CTEPH PATIENTS; Patients undergoing pulmonary endarterectomy for the treatment of chronic thromboembolic pulmonary hypertension (CTEPH).	Radiation: magnetic resonance imaging; assessment of right heart dimensions and function by cardiac magnetic resonance Imaging.; Procedure: 2D and 3D trans-thoracic echocardiography; assessment of right heart dimensions and function by 2D and 3D trans-thoracic echocardiography; Other: Blood samples; Blood samples for assays of immune inflammatory biomarkers (InterLeukin-18, CXCL9 or interferon
Experimental: PAH PATIENTS; patients with pulmonary arterial hypertension (PAH) undergoing lung transplantation	Radiation: magnetic resonance imaging; assessment of right heart dimensions and function by cardiac magnetic resonance Imaging.; Procedure: 2D and 3D trans-thoracic echocardiography; assessment of right heart dimensions and function by 2D and 3D trans-thoracic echocardiography; Other: Blood samples; Blood samples for assays of immune inflammatory biomarkers (InterLeukin-18, CXCL9 or interferon

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
right ventricular adverse remodeling	postoperative right ventricular adverse remodeling, defined by increase above 10% in end-systolic right ventricular volume indexed on body surface area assessed by cardiac MRI.	6 months

Collaborators and Investigators

• Sponsor: Centre Chirurgical Marie Lannelongue

Publications and helpful links

General Publications

• Dong ML, Azarine A, Haddad F, Amsallem M, Kim YW, Yang W, Fadel E, Aubrege L, Loecher M, Ennis D, Pavec JL, Vignon-Clementel I, Feinstein JA, Mercier O, Marsden AL. 4D flow cardiovascular magnetic resonance recovery profiles following pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension. J Cardiovasc Magn Reson. 2022 Nov 14;24(1):59. doi: 10.1186/s12968-022-00893-x.

Study record dates

Study Major Dates

• Study Start (Actual): August 9, 2017
• Primary Completion (Anticipated): July 1, 2020
• Study Completion (Anticipated): July 1, 2020

Study Registration Dates

• First Submitted: June 28, 2017
• First Submitted That Met QC Criteria: June 29, 2017
• First Posted (Actual): July 2, 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; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Hypertension, Pulmonary
• Other Study ID Numbers: 2017-A00785-48

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