Feasibility and Influence of Exercise Therapy on Oxygen Uptake and Right Heart Function in CTEPH Patients After PEA

Study Overview
=================
Brief Summary
-----------------
Purpose of this study is to investigate whether and to what extent a cautious respiratory and movement therapy can complement medical treatment and the condition, oxygen uptake, quality of life, the pulmonary vascular pressures, the size of the right heart and the 6-minute walk distance in patients with pulmonary hypertension.

Detailed Description
-----------------
Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of acute pulmonary embolism. According to current knowledge, it is caused by non-resolving fibrothrombotic obstructions of large pulmonary arteries. Some patients show an additional small vessel vasculopathy. Both kinds of obstruction lead to an increase in pulmonary vascular resistance (PVR), increase in mean pulmonary arterial pressure (mPAP), progressive right heart failure, and premature death if left untreated. Current guidelines recommend pulmonary endarterectomy (PEA) as the potentially curative treatment of first choice, which aims to remove fibrotic obstructions from the pulmonary vasculature. The survival of patients undergoing PEA surgery ranges between 76 and 91% after 3 years, which is superior to medical treatment in inoperable CTEPH patients. The majority of operated patients experience almost complete normalisation of haemodynamics and improvements in symptoms. However, 17-51% of operated patients will develop persistent or recurrent pulmonary hypertension (PH). Some patients remain limited in their exercise capacity and prognosis. As patients are monitored on an intensive care unit immediately after PEA, immobilisation after the operation may lead to further peripheral deconditioning. A recent study of 251 CTEPH patients with follow-up until 12 months after PEA showed a persistent exercise limitation in almost 40% of patients despite normalisation of PVR and haemodynamics. This limitation was characterised by a multifactorial aetiology also involving respiratory function abnormalities. Previous studies in patients with inoperable or persistent CTEPH have suggested beneficial effects of exercise training as an add-on to targeted medical therapy, increasing exercise capacity, and quality of life (QoL). However, it is not known, whether early rehabilitation with exercise treatment is safe, feasible, and may further improve exercise capacity after PEA. Prospective studies on exercise training for CTEPH patients shortly after PEA surgery are lacking. Furthermore, to the best of our knowledge, there have been no studies yet describing the early effect within the first weeks after PEA. The aim of this study was therefore to assess the feasibility of supervised exercise training in CTEPH patients shortly after PEA. Furthermore, changes of haemodynamic and clinical parameters including oxygen uptake, QoL, exercise capacity, and right heart function assessed by echocardiography and right heart catheterisation were obtained before and shortly after PEA.

Official Title
-----------------
Feasibility and Influence of Respiratory and Exercise Therapy on Oxygen Uptake, Quality of Life and Right Heart Function in Chronic Thromboembolic Pulmonary Hypertension After Thromboendarterectomy

Conditions
-----------------
CTEPH

Intervention / Treatment
-----------------
* Behavioral: respiratory and exercise therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Consent form men and women> 18 years <80 years CTEPH after pulmonary endarterectomy Exclusion Criteria: Patients with signs of right heart decompensation acute diseases, infections, fever Serious lung disease with FEV1 <50% or TLC <70% of target Other exclusion criteria are the following diseases: active myocarditis, unstable angina pectoris, exercise-induced ventricular arrhythmias, congestive heart failure, significant heart disease, pacemakers, and hypertrophic obstructive cardiomyopathy, or a highly reduced left ventricular function

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Respiratory and exercise therapy<br>Early after PEA postoperative three-week inpatient rehabilitation and subsequent continuing of the training at home for 12 weeks. | Behavioral: respiratory and exercise therapy<br>* Conventional therapy with diet, massage, relaxation baths, plus easy strolls specific respiratory and physical therapy plus mental walking training<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Completion rate of exercise rehabilitation program training by CTEPH patients directly after PEA | Assessment of feasibility and tolerance of exercise rehabilitation directly after PEA assessed by the number of patients completing the exercise rehabilitation program | up to 15 weeks after start of rehabilitation with exercise training | 
| Change of peak O2 uptake (VO2peak) during exercise | Change of peak O2 uptake measured by cardiopulmonary exercise test (CPET) | up to 15 weeks after start of rehabilitation with exercise training | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in right atrial pressure (RAP) at rest | Changes in hemodynamics at rest | up to 15 weeks after start of rehabilitation with exercise training | 
| Change in right atrial pressure (RAP) during exercise | Changes in hemodynamics during exercise | up to 15 weeks after start of rehabilitation with exercise training | 
| Change in right ventricular pressure (RVP) at rest | Changes in hemodynamics at rest | up to 15 weeks after start of rehabilitation with exercise training | 
| Change in right ventricular pressure (RVP) during exercise | Changes in hemodynamics during exercise | up to 15 weeks after start of rehabilitation with exercise training | 
| Change in systolic pulmonary arterial pressure (sPAP) at rest | Changes in hemodynamics at rest | up to 15 weeks after start of rehabilitation with exercise training | 
| Change in systolic pulmonary arterial pressure (sPAP) during exercise | Changes in hemodynamics during exercise | up to 15 weeks after start of rehabilitation with exercise training | 
| Change in diastolic pulmonary arterial pressure (dPAP) at rest | Changes in hemodynamics at rest | up to 15 weeks after start of rehabilitation with exercise training | 
| Change in diastolic pulmonary arterial pressure (dPAP) during exercise | Changes in hemodynamics during exercise | up to 15 weeks after start of rehabilitation with exercise training | 
| Change in mean pulmonary arterial pressure (mPAP) at rest | Changes in hemodynamics at rest | up to 15 weeks after start of rehabilitation with exercise training | 
| Change in mean pulmonary arterial pressure (mPAP) during exercise | Changes in hemodynamics during exercise | up to 15 weeks after start of rehabilitation with exercise training | 
| Change in pulmonary arterial wedge pressure (PAWP) at rest | Changes in hemodynamics at rest | up to 15 weeks after start of rehabilitation with exercise training | 
| Change in pulmonary arterial wedge pressure (PAWP) during exercise | Changes in hemodynamics during exercise | up to 15 weeks after start of rehabilitation with exercise training | 
| Change in cardiac output (CO) at rest | Changes in hemodynamics at rest | up to 15 weeks after start of rehabilitation with exercise training | 
| Change in cardiac output (CO) during exercise | Changes in hemodynamics during exercise | up to 15 weeks after start of rehabilitation with exercise training | 
| Change in pulmonary vascular resistance (PVR) at rest | Changes in hemodynamics at rest | up to 15 weeks after start of rehabilitation with exercise training | 
| Change in pulmonary vascular resistance (PVR) during exercise | Changes in hemodynamics during exercise | up to 15 weeks after start of rehabilitation with exercise training | 
| Change in venous oxygen saturation from pulmonary artery (SvO2) during exercise | Changes in hemodynamics during exercise | up to 15 weeks after start of rehabilitation with exercise training | 
| Change in venous oxygen saturation from pulmonary artery (SvO2) at rest | Changes in hemodynamics at rest | up to 15 weeks after start of rehabilitation with exercise training | 
| Change in cardiac index (CI) at rest | Changes in hemodynamics at rest | up to 15 weeks after start of rehabilitation with exercise training | 
| Change in cardiac index (CI) during exercise | Changes in hemodynamics during exercise | up to 15 weeks after start of rehabilitation with exercise training | 
| Change in exercise capacity assessed by six minute walking test | Six Minute Walking distance (6MWD) in meters | up to 15 weeks after start of rehabilitation with exercise training | 
| Change in exercise capacity - workload | recumbent bike (Workload in Watts) during cycle Ergometer test | up to 15 weeks after start of rehabilitation with exercise training | 
| Change in exercise capacity - respiratory economy | EqO2, EqCO2 assessed during cardiopulmonary exercise testing | up to 15 weeks after start of rehabilitation with exercise training | 
| Change of laboratory parameters of right heart function | Measurement of NT-proBNP | up to 15 weeks after start of rehabilitation with exercise training | 
| Change in right atrial area | Change of cm2 of right atrial area measured by 2D echocardiography | up to 15 weeks after start of rehabilitation with exercise training | 
| Change in right ventricular area | Change of cm2 of right ventricular area measured by 2D echocardiography | up to 15 weeks after start of rehabilitation with exercise training | 
| Change in visual right heart pump function | Change of category of right heart pump function (no impairment, slight impairment, moderate impairment, severe impairment) measured by 2D echocardiography | up to 15 weeks after start of rehabilitation with exercise training | 
| Safety of early rehabilitation directly after pulmonary endarterectomy: number of adverse events and serious adverse events | number of adverse events and serious adverse events | up to 15 weeks after start of rehabilitation with exercise training | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
physical training, remaining post-operative pulmonary vascular changes, right ventricular pump function, PEA