Lymphatic Function in Patients With a Fontan-Kreutzer Circulation

Study Overview
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Brief Summary
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The lymphatics regulate the interstitial fluid by removing excessive fluid. It represents an extremely important step in the prevention of edema. The Fontan-Kreutzer procedure has revolutionized the treatment of univentricular hearts. However, it is associated with severe complications such as protein-losing enteropathy (PLE) and peripheral edema that may involve the lymphatic circulation. Our hypothesis is that patients with a univentricular circulation have a reduced functionality of the lymphatic vasculature, which predisposes them to developing complications such as edema and PLE. The functional state of lymphatics is investigated using near infrared fluorescence imaging, NIRF. The anatomy is described using non-contrast MRI and the capillary filtration rate is measured using plethysmography.

Detailed Description
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Background: The lymphatics regulate the interstitial fluid by removing excessive fluid. It represents an extremely important step in the prevention of edema. The Fontan-Kreutzer procedure has revolutionized the treatment of univentricular hearts. However, it is associated with severe complications such as protein-losing enteropathy (PLE) and peripheral edema that may involve the lymphatic circulation. Hypothesis: Patients with a univentricular circulation have a reduced functionality of the lymphatic vasculature, which predisposes them to developing complications such as edema and PLE. Material and Methods: The functional state of lymphatics is investigated using near infrared fluorescence imaging, NIRF. The anatomy is described using non-contrast MRI and the capillary filtration rate is measured using plethysmography. The study population is patients with Fontan-Kreutzer circulation operated at Aarhus University hospital. Exclusion criteria is BMI>30 and age (years) < 18. The Fontan-Kreutzer group will be compared with an age, gender and weight matched control group of healthy volunteers.

Official Title
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The Lymphatic Morphology and Function of Fontan-Kreutzer Operated Patients

Conditions
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Lymphatic Abnormalities, Lymphatic Edema, Univentricular Heart

Intervention / Treatment
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* Diagnostic Test: Near Infrared Fluorescence Imaging
* Diagnostic Test: Non-contrast MRI
* Diagnostic Test: Strain Gauge Plethysmography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Fontan-Kreutzer circulation Exclusion Criteria: BMI>30, Age<18 Mental illness

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Fontan-Kreutzer operated patients<br>Patients with a Fontan-Kreutzer circulation. No interventions are done. (The intervention is the operation done 15-20 years ago) | Diagnostic Test: Near Infrared Fluorescence Imaging<br>* The functional state of lymphatics is investigated using near infrared fluorescence imaging, NIRF.<br>* Other names: Strain-Gauge Plethysmography;Diagnostic Test: Non-contrast MRI<br>* The anatomy is described using non-contrast MRI.<br>Diagnostic Test: Strain Gauge Plethysmography<br>* The capillary filtration rate is measured using plethysmography<br>|
| Healthy Control subjects<br>Age, gender and weight matched control subjects | Diagnostic Test: Near Infrared Fluorescence Imaging<br>* The functional state of lymphatics is investigated using near infrared fluorescence imaging, NIRF.<br>* Other names: Strain-Gauge Plethysmography;Diagnostic Test: Non-contrast MRI<br>* The anatomy is described using non-contrast MRI.<br>Diagnostic Test: Strain Gauge Plethysmography<br>* The capillary filtration rate is measured using plethysmography<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pumping pressure | Occlusion of lymphatic flow by inflating a cuff (Hokanson E20 Rapid cuff inflator, Hokanson AG101 air source) to 70mmHg and then reducing the pressure with 5mmHg each 5th minute. The highest pressure under which the fluorescent dye is able to cross the inflatable cuff is labelled Ppump. | 1 hour | 
| Contraction Frequency | Contraction frequency in vessels in the main drainage pathway of the legs (ventromedial bundle) as well as vessels draining the area behind the medial malleolus. | 6 min | 
| Refill time | The time it takes for a 10 cm long vessel to refill after emptying the vessel with massage | 20 min | 
| Velocity | The velocity measured in cm/s for a packet of lymph moving from one region of interest (ROI) to another through atlas a 5 cm straight vessel | 6 min | 
| Capillary Filtration Rate | A 5-step 20-min venous congestion protocol will be used to measure capillary filtration. The capillary filtration rate (µl·100 ml-1 ·min-1 ) is measured as the slope of the time-volume change (%) curve at steady state at the end of each pressure phase. | 25 min |