Atrial Septal Defect - Exercise Capacity and Pulmonary Hypertension

Pulmonary Hypertension Clinical Trial

Official title:

Atrial Septal Defect - Exercise Capacity and Pulmonary Hypertension

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03565471
• Other study ID #: 2018-21
• Status: Completed
• Start date: August 1, 2018
• Est. completion date: November 1, 2019

Study information

• Verified date: June 2019
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of the study is to compare exercise capacity, cardiac contractility, pulmonary vascular pressures and heart rate variability between patients with an atrial septal defect and healthy controls.

Description:

1. Background Patients born with atrial septal defect (ASD) in the heart, have long been assumed healthy after closure of their defect. However, recent studies show, that despite closure of the ASD the risks of arrhythmia, stroke and pneumonia are increased. It is also shown that ASD patients die earlier than the background population and the cause of death is most often cardiac. The reason for this higher mortality and morbidity is unknown and the scope of this thesis.

2. Aim To determine if closed (both surgical and transcatheter) ASD patients have reduced exercise capacity, impaired right and left ventricular function, increased pressure in the pulmonary system, and reduced heart rate variability when compared with healthy controls. The investigators will also examine if method of closure is of importance.

3. Hypothesis

Primary endpoint:

The shunting effect alters the hemodynamic in the ASD heart resulting in lower cardiopulmonary exercise capacity when compared with healthy controls.

Secondary endpoints:

The shunting effect alters the hemodynamic in the ASD heart when compared with healthy controls resulting in

• Impaired force frequency relationship with a reduction in contractility at optimal heart rate.

• Increased pulmonary arterial pressure.

• Twice as many ASD patients with decreased heart rate variability.

Surgical closure is thought to have a higher impact on the ventricular function than catheter closure resulting in

• Lower contractility in the surgically closed patients as compared to the catheter closure as evaluated by force frequency.

• Twice as many surgically closed patients with decreased heart rate variability compared to catheter closed patients.

4. Materials and methods

4.1) Power calculation The number of participants needed in the project is calculated based on the exercise capacity test, which is the primary endpoint.

The normal exercise test result is 48 ml O2/kg/min with a standard deviation of 7 ml O2/kg/min. With an expected difference between groups and healthy controls of 15% and a power of 85%, the number of patients needed in each group is 18. Possible drop-outs are taken into account and therefore 20 participants will be included in each ASD group, they will each be matched one to one with controls, resulting in a total of 80 project participants.

The secondary endpoints are of a more explorative character, why 20 ASD patients in each group is assumed to be sufficient.

4.2) Exercise capacity, force frequency relationship and pulmonary hypertension 4.2.1) The exercise capacity test is conducted on a semi-supine bicycle, while the patients wears a mask measuring the ventilation, oxygen uptake, carbon dioxide release and respiratory exchange rate. Patients pedal until maximal exhaustion, which should be obtained after 8-12 minutes.

4.2.2) During exercise testing, the force frequency relationship is examined using echocardiography.

4.2.3) A Swan-Ganz catheter is used to measure right-sided hemodynamic pressures and blood saturation.

4.3) Heart rate variability Electrocardiographic (ECG) activity and heart rate variability will be monitored using a 2-channel Holter monitor. The data will be analyzed with the Pathfinder analysis software.

5. Statistical analysis Results for each group will be expressed as means standard deviation or median range or 95% confidence intervals. One way analysis of variance (ANOVA), paired t-tests and regression analyses will be performed. Analyses will be adjusted for age and sex. The issue of multiple testing/multiple comparisons may arise and only relevant comparisons and analyses will be performed.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: November 1, 2019
• Est. primary completion date: November 1, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 18 years and above.

• Informed consent to participate.

• Patients: Diagnosed with an atrial septal defect. More than 3 years have passed since closure of the atrial septal defect.

• Controls: No history of heart or lung disease.

Exclusion Criteria:

• Lung disease.

• Ischemic heart disease.

• Diabetes.

• Hypertension.

• Valve pathology.

• Patients: Concomitant heart disease

• Controls: Usage of prescription drugs interfering with the cardiopulmonary function.

Related Conditions & MeSH terms

• Atrial Septal Defect
• Heart Septal Defects
• Heart Septal Defects, Atrial
• Hypertension
• Hypertension, Pulmonary
• Pulmonary Hypertension

Intervention

Diagnostic Test:
• Echocardiography
Standard echocardiography.
• Right side catheterization
Right side catheterization with the purpose of measuring pulmonary vascular pressures and blood saturation.
• Exercise test
Exercise test on a supine bicycle with gradual increase in work load while wearing a mask that measures ventilation, oxygen uptake, carbon dioxide release and respiratory exchange rate.
• Holter monitor
Holter monitor worn for 2 whole days registering heart rate.

Locations

Country	Name	City	State
Denmark	Dept. of Cardiothoracic & Vascular Surgery, Aarhus University Hospital	Aarhus

Sponsors (2)

Lead Sponsor	Collaborator
University of Aarhus	Aarhus University Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Peak oxygen uptake (ml O2/kg/min)	using exercise testing	8-12 minutes
Primary	Peak exercise minute ventilation (ml/min)	using exercise testing	8-12 minutes
Primary	Peak heart rate (beats/min)	using exercise testing	8-12 minutes
Primary	Maximal workload (W/kg)	using exercise testing	8-12 minutes
Secondary	Tricuspid annular peak systolic velocity (mm)	using echocardiography	8-12 minutes
Secondary	Return gradient at the tricuspid valve (mmHg)	using echocardiography	8-12 minutes
Secondary	Cardiac output (L/min)	using right sided catheterization	8-12 minutes
Secondary	Cardiac index (L/min)	using right sided catheterization, derived measure adjusted for body surface area	8-12 minutes
Secondary	Central venous pressure (mmHg)	using right sided catheterization	8-12 minutes
Secondary	Pulmonary artery wedge pressure (mmHg)	using right sided catheterization	8-12 minutes
Secondary	Pulmonary artery pressure (mmHg)	using right sided catheterization	8-12 minutes
Secondary	Mixed venous oxygen saturation (%)	using right sided catheterization	8-12 minutes
Secondary	Heart rate variability	using Holter monitoring	48 hours
Secondary	Heart rate, minimum, maximum and mean (beats/min)	using Holter monitoring	48 hours