Atrial Septal Defect - Exercise Capacity and Pulmonary Hypertension
Atrial Septal Defect - Exercise Capacity and Pulmonary Hypertension
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.
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.
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.