Exercise Hemodynamic, Right Ventricular Coupling and Echocardiography in Pulmonary Hypertension (EXERTION)

This study aims to investigate the exercise profile in pulmonary hypertension patients with either pulmonary arterial hypertension, chronic thromboembolic pulmonary hypertension or pulmonary hypertension due to left heart disease and in disease control.

Study Overview

• Status: Completed
• Conditions: Hypertension, Pulmonary; Hypertension, Pulmonary Arterial
• Intervention / Treatment: Other: Exercise

Detailed Description

This is a dual-center observational prospective study in patients with pulmonary arterial hypertension, chronic thromboembolic pulmonary hypertension, pulmonary hypertension due to left heart disease. Patients undergoing right heart catheterisation due to dyspnoe with invasive exclusion of pulmonary hypertension will be recruited as disease control.

The study comprises a 1-day screening period, followed by a right heart catheterization with exercise challenge.

The study starts with screening, information of the patients and Informed Consent Form signature at day -1. Screening and inclusion of the patient can be performed on the same day. On the day of the planned right heart catheterization based on clinical grounds, exercise right heart catheterisation (RHC) using Swan-Ganz and/or Conductance catheters with simultaneous echocardiography will be performed. End of study is defined as a complete exercise RHC. Adverse events will be assessed until 1 day after the exercise RHC.

After placement of the Swan-ganz or Conductance catheter patients will undergo an exercise challenge using the following protocol in semi-supine position until exhaustion:

• Incremental workload increase of 20Watt every 2-4 min.
• For patients not able to start a 20 Watt, initial workload can be adjusted to a minimum of 5 Watt with 5 Watt increase every 2-4 min until exhaustion
• Maximal exercise duration is 10-12 minutes
• Symptoms of dyspnoea during exercise will be rated by subjects at baseline, after 6 minutes and at maximum according to the Borg perceived dyspnoea (0-10) scale.

Simultaneously, echocardiography and lung ultrasound will be performed before exercise (baseline), after 6 minutes of exercise and at maximum.

After assessment of right ventriclure pressure-volume loops during maximum exercise, guided by echocardiographic the conductance catheter will be placed in the right atrium to obtain right atrium pressure-volume loops during maximum exercise.

Optional, the exercise RHC will be performed without the Conductance catheter and only with the Swan-Ganz catheter. In this case, pressure values and cardiac output will be measured using the thermodilution method, averaging 3-5 measurements at baseline, 6 minutes and maximum. Detailed assessment of right atrial pressure curves (with a and v wave) will be performed at baseline, 6 minutes and maximum exercise.

• Study Type: Observational
• Enrollment (Actual): 120

Contacts and Locations

Study Locations

• Germany
  • Hesse
    • Bad Nauheim, Hesse, Germany
      • Kerckhoff-Klinik
    • Gießen, Hesse, Germany, 35390
      • University of Gießen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Confirmed diagnosis of either pulmonary arterial hypertension; pulmonary hypertension due to left heat disease; chronic thromboembolic pulmonary hypertension; or invasive exclusion of pulmonary hypertension (control group)

Description

Inclusion Criteria:

• Confirmed diagnosis of pulmonary arterial hypertension (World Health Organization group 1)
• Pulmonary hypertension due to left heart disease (World Health Organization group 2)
• Chronic thromboembolic pulmonary hypertension (World Health Organization group 4)
• Invasive exclusion of pulmonary hypertension
• Age ≥ 18 years
• Planned right heart catheterization based on clinical grounds
• Stable specific PAH medications
• Ability to undergo cycle ergometry
• Signed informed consent

Exclusion Criteria:

• Other etiologic groups of pulmonary hypertension (World Health Organization group 3, 5)
• Unstable or severe coronary artery disease
• Uncontrolled arterial hypertension
• Left ventricular ejection fraction < 30%
• Severe congenital or acquired valvular or myocardial disease
• Progressive left heart failure
• History of severe ventricular arrhythmias
• Severe, terminal renal impairment
• Severe obstructive or restrictive lung disease
• Severe lung emphysema or interstitial lung disease

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pulmonary arterial hypertension; Patients with mean pulmonary arterial pressure above 25 mmHg, and a pulmonary capillary wedge pressure below 15 mmHg classified into group 1 of the clinical classification of pulmonary hypertension.	Other: Exercise; After placement of the right heart catheter patients will undergo an exercise challenge in semi-supine position until exhaustion
Pulmonary hypertension due to left heart disease; Patients with mean pulmonary arterial pressure above 25 mmHg, and a pulmonary capillary wedge pressure above 15 mmHg with left heart disease, classified into group 2 of the clinical classification of pulmonary hypertension.	Other: Exercise; After placement of the right heart catheter patients will undergo an exercise challenge in semi-supine position until exhaustion
Chronic thromboembolic pulmonary hypertension; Patients with mean pulmonary arterial pressure above 25 mmHg, and a pulmonary capillary wedge pressure below 15 mmHg with a history of pulmonary embolism, classified into group 4 of the clinical classification of pulmonary hypertension.	Other: Exercise; After placement of the right heart catheter patients will undergo an exercise challenge in semi-supine position until exhaustion
Control; Patients with mean pulmonary arterial pressure below 25 mmHg, and a pulmonary capillary wedge pressure below 15 mmHg with exclusion of pulmonary hypertension.	Other: Exercise; After placement of the right heart catheter patients will undergo an exercise challenge in semi-supine position until exhaustion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
exercise pulmonary arterial pressure	mean pulmonary arterial pressure (mmHg)	1 day
exercise cardiac output	cardiac output (l/min);	1 day
exercise pulmonary wedge pressure	pulmonary arterial wedge pressure (mmHg)	1 day
exercise arterial elastance	arterial elastance (mmHg/mL)	1 day
exercise end-systolic elastance	end-systolic elastance (mmHg/mL)	1 day
exercise mean right atrial pressure	mean right atrial pressure (mmHg)	1 day
exercise right atrial function	right atrial strain (%)	1 day
exercise right volume	right ventricular volume (ml)	1 day
exercise right ventriculare function	right ventricular strain (%)	1 day
exercise right atrial volume-pressure curves	atrial volume to pressure ratio (ml/mmHg)	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
exercise lung congestion	B-Lines	1 day
exercise left atrial function	left atrial strain (%)	1 day
exercise left atrial volume	left atrial volume (ml)	1 day
exercise hepatic backflow	diameter inferior vena cava (mm)	1 day

Collaborators and Investigators

• Sponsor: University of Giessen
• Investigators: Principal Investigator: Richter J Manuel, MD, UKGM Giessen

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2020
• Primary Completion (Actual): November 4, 2022
• Study Completion (Actual): November 4, 2023

Study Registration Dates

• First Submitted: November 5, 2020
• First Submitted That Met QC Criteria: December 4, 2020
• First Posted (Actual): December 10, 2020

Study Record Updates

• Last Update Posted (Actual): May 17, 2024
• Last Update Submitted That Met QC Criteria: May 16, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: exercise; Hypertension, Pulmonary
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Pulmonary Arterial Hypertension; Hypertension, Pulmonary
• Other Study ID Numbers: AZ 11716

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Data will be shared upon request.

Drug and device information, study documents

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