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

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

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.

Study Overview

• Status: Completed
• Conditions: CTEPH
• Intervention / Treatment: Behavioral: respiratory and exercise therapy

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.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Heidelberg, Germany, 69126
    • Center for pulmonary Hypertension, Thoraxclinic Heidelberg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• 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: Respiratory and exercise therapy; Early after PEA postoperative three-week inpatient rehabilitation and subsequent continuing of the training at home for 12 weeks.	Behavioral: respiratory and exercise therapy; Conventional therapy with diet, massage, relaxation baths, plus easy strolls specific respiratory and physical therapy plus mental walking training

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

Collaborators and Investigators

• Sponsor: Heidelberg University
• Investigators: Study Director: Ekkehard Grünig, Professor, Center for pulmonary Hypertension, Thoraxclinic Heidelberg

Publications and helpful links

General Publications

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• Simonneau G, D'Armini AM, Ghofrani HA, Grimminger F, Hoeper MM, Jansa P, Kim NH, Wang C, Wilkins MR, Fritsch A, Davie N, Colorado P, Mayer E. Riociguat for the treatment of chronic thromboembolic pulmonary hypertension: a long-term extension study (CHEST-2). Eur Respir J. 2015 May;45(5):1293-302. doi: 10.1183/09031936.00087114. Epub 2014 Nov 13.
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Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2010
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: June 28, 2011
• First Submitted That Met QC Criteria: July 12, 2011
• First Posted (Estimate): July 13, 2011

Study Record Updates

• Last Update Posted (Actual): May 10, 2021
• Last Update Submitted That Met QC Criteria: May 5, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: physical training; remaining post-operative pulmonary vascular changes; right ventricular pump function; PEA
• Other Study ID Numbers: S-488/2009

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No