Atrial Septal Defect - Exercise Capacity and Pulmonary Hypertension

NCT ID: NCT03565471

Last Updated: 2021-05-06

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 57 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-08-01
• Study Completion Date: 2019-11-01

Brief 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.

Detailed 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.

Conditions

Atrial Septal Defect; Pulmonary Hypertension

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

ASD patients with surgical closure

Patients diagnosed with an ASD who have had a surgical closure of the defect more than 3 years ago.

Echocardiography, right side catheterization, exercise testing and Holter monitoring are performed on all participants.

Echocardiography

Intervention Type: DIAGNOSTIC_TEST

Standard echocardiography.

Right side catheterization

Intervention Type: DIAGNOSTIC_TEST

Right side catheterization with the purpose of measuring pulmonary vascular pressures and blood saturation.

Exercise test

Intervention Type: DIAGNOSTIC_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

Intervention Type: DIAGNOSTIC_TEST

Holter monitor worn for 2 whole days registering heart rate.

ASD patients with transcatheter closure

Patients diagnosed with an ASD who have had a transcatheter closure of the defect more than 3 years ago.

Echocardiography, right side catheterization, exercise testing and Holter monitoring are performed on all participants.

Echocardiography

Intervention Type: DIAGNOSTIC_TEST

Standard echocardiography.

Right side catheterization

Intervention Type: DIAGNOSTIC_TEST

Right side catheterization with the purpose of measuring pulmonary vascular pressures and blood saturation.

Exercise test

Intervention Type: DIAGNOSTIC_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

Intervention Type: DIAGNOSTIC_TEST

Holter monitor worn for 2 whole days registering heart rate.

Controls

Controls who do not have any cardiac or pulmonary diagnoses nor use prescription drugs that may affect the cardiopulmonary function.

Echocardiography, right side catheterization, exercise testing and Holter monitoring are performed on all participants.

Echocardiography

Intervention Type: DIAGNOSTIC_TEST

Standard echocardiography.

Right side catheterization

Intervention Type: DIAGNOSTIC_TEST

Right side catheterization with the purpose of measuring pulmonary vascular pressures and blood saturation.

Exercise test

Intervention Type: DIAGNOSTIC_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

Intervention Type: DIAGNOSTIC_TEST

Holter monitor worn for 2 whole days registering heart rate.

Interventions

Echocardiography

Standard echocardiography.

Intervention Type: DIAGNOSTIC_TEST

Right side catheterization

Right side catheterization with the purpose of measuring pulmonary vascular pressures and blood saturation.

Intervention Type: DIAGNOSTIC_TEST

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.

Intervention Type: DIAGNOSTIC_TEST

Holter monitor

Holter monitor worn for 2 whole days registering heart rate.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Aarhus University Hospital

OTHER

Sponsor Role: collaborator

University of Aarhus

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Zarmiga Karunanithi, MD

Role: PRINCIPAL_INVESTIGATOR

University of Aarhus

Locations

Dept. of Cardiothoracic & Vascular Surgery, Aarhus University Hospital

Aarhus, , Denmark

Countries

Denmark

References

Karunanithi Z, Andersen MJ, Mellemkjaer S, Alstrup M, Waziri F, Skibsted Clemmensen T, Elisabeth Hjortdal V, Hvitfeldt Poulsen S. Elevated Left and Right Atrial Pressures Long-Term After Atrial Septal Defect Correction: An Invasive Exercise Hemodynamic Study. J Am Heart Assoc. 2021 Jul 20;10(14):e020692. doi: 10.1161/JAHA.120.020692. Epub 2021 Jul 14.

Reference Type: DERIVED

PMID: 34259012 (View on PubMed)

Alstrup M, Karunanithi Z, Maagaard MO, Poulsen SH, Hjortdal VE. Sympathovagal imbalance decades after atrial septal defect repair: a long-term follow-up study. Eur J Cardiothorac Surg. 2021 Dec 27;61(1):83-89. doi: 10.1093/ejcts/ezab235.

Reference Type: DERIVED

PMID: 34015096 (View on PubMed)

Other Identifiers

2018-21

Identifier Type: -

Identifier Source: org_study_id