Hemodynamic Effects of BPA at Rest and During Exercise in CTEPH

Study Overview
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Brief Summary
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Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by obstruction of the pulmonary vasculature by residual organized thrombi, leading to increased pulmonary vascular resistance (PVR), progressive pulmonary hypertension, and right heart failure. Medical therapy and balloon angioplasty (BPA) are effective treatment alternatives in lowering pulmonary pressures and increasing pulmonary flow. The aim of this study is to assess the hemodynamic effects of BPA or medical therapy on the pressure-flow relationship in the pulmonary vasculature and the pulmonary vascular compliance.

Detailed Description
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Chronic thromboembolic pulmonary hypertension [CTEPH] is a rare condition with a significant risk of morbidity and mortality. The primary cause of CTEPH is thrombotic lesions, which did not resolve after acute pulmonary embolism. This causes increased pulmonary vascular resistance [PVR], leading to secondary remodeling of pulmonary arteries causing pulmonary hypertension and ultimately progressive right heart failure. The treatment of choice is surgical pulmonary endarterectomy [PEA], however up to 40% cases are not treated surgically, due to operability, anatomic location of the lesions, patient choice and comorbidities significantly increasing procedural risk. A new alternative procedure, balloon pulmonary angioplasty [BPA] has been proposed for patients with inoperable CTEPH or persistent pulmonary hypertension after pulmonary endarterectomy (PEA) and is currently characterized with good outcome in functional capacity, hemodynamic parameters, biomarkers, and health-related quality of life. Exercise stress tests of the pulmonary circulation are used in workup and diagnosis of pulmonary hypertension as a hemodynamic abnormality. The approach has allowed identification of patients with normal or marginally increased mPAP at rest but with symptomatic increases in mPAP at exercise, related to either increased resistance or increased left atrial pressure. Although this differential diagnosis is of obvious therapeutic relevance, guidelines about exercise stress studies of the pulmonary circulation have not been developed until now for lack of robust evidence allowing for a consensus on clearly defined cutoff values. Neither the pathophysiology of the exercise limitation nor the underlying mechanisms of the BPA - induced improvement were studied before. Therefore the aim of this study is to assess the hemodynamic effects of BPA treatment on the pressure-flow relationship in the pulmonary vasculature and the pulmonary vascular compliance. Furthermore, the investigators will explore possible differences in treatment effect across centers. Especially explore the timing of medical therapy vs balloon angioplasty. .

Official Title
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An International Multicenter Observational Study to Assess the Hemodynamic Effects of Balloon Pulmonary Angioplasty (BPA) at Rest and During Exercise in Chronic Thromboembolic Pulmonary Hypertension (CTEPH) or Chronic Thromboembolic Pulmonary Disease (CTED) Patients (EXPERT-BPA)

Conditions
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Chronic Thromboembolic Pulmonary Hypertension

Intervention / Treatment
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* Diagnostic Test: Invasive exercise testing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: -Patients with CTEPH or CTED eligible for balloon pulmonary angioplasty. Exclusion Criteria: -Patients unable to perform ergometer exercise

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: Exercise is added to the resting right heart catheterization.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: All patients<br>Exercise is added to resting right heart catheterization | Diagnostic Test: Invasive exercise testing<br>* Invasive hemodynamic exercise testing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Slope of mPA/CO after BPA | Change from Baseline in Slope of mean pulmonary artery pressure/cardiac output after BPA at 6 months | 6 months after last BPA session | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in resting PVR after BPA | Change from Baseline in pulmonary vascular resistance (PVR) after BPA at 6 months | 6 months after last BPA session | 
| Change in 6 MWT after BPA | Change from Baseline in 6 minute walk test (MWT) after BPA at 6 months | 6 months after last BPA session | 
| Change in NT-proBNP after BPA | Change from Baseline in NT-proBNP after BPA at 6 months | 6 months after last BPA session |