Liver Disease, Myocardial Fibrosis and Collaterals in the Adult Fontan Patient a Metabolomics and Proteomics Approach

Study Overview
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Brief Summary
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Out objective is to identify the mechanisms that promote hepatic and myocardial fibrosis, and collateral vessel formation in patients with complex congenital heart disease and Fontan circulation.

Detailed Description
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In their prior works the investigators could show that there is evidence of a proinflammatory condition in a certain subgroup of patients with complex congenital heart disease and a so called Fontan circulation. Those patients are also prone to develop hepatic and myocardial fibrosis as well as to reveal collateral vessel formation. The investigators' hypothesis is that this pro-inflammatory condition is not only reflecting pre-stages of one or more of those 3 issues, but that this is also a main driving mechanism to develop and hepatic or myocardial fibrosis and collateral vessels. The objective of the here proposed study thus is to identify the mechanisms that promote hepatic and myocardial fibrosis, and collateral vessel formation, and thus provide insight into the determination of those Fontan patients that tend to develop those conditions. The investigators attempt to link the issues of hepatic and myocardial fibrosis and collateral vessel formation by directing our focus on the phospholipid, amino acid and bile acid metabolism and on cell surface markers, cytokines, and chemokines as surrogates for proinflammatory, profibrotic and proangiogenic conditions. This study would thereby allow for a deeper insight into Fontan pathophysiology and sequelae and might provide first steps towards the identification of possible diagnostic or eventually therapeutic targets.

Official Title
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Liver Disease, Myocardial Fibrosis and Collaterals in the Adult Fontan Patient - a Metabolomics and Proteomics Approach

Conditions
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Patient Participation, Heart Defects, Congenital, Liver Diseases, Collateral Circulation, Any Site, Myocardial Fibrosis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: written informed consent of participants age at testing of ≥18 years 8 h fasting before blood sampling Fontan circulation (patients) biventricular heart without structural or functional abnormality (controls) Exclusion Criteria: Protein losing enteropathy (PLE) (patients are defined as PLE positive if there is/are serum protein <5g/dL and serum albumin <3g/dL (duration for more than 3 months and exclusion of other causes for hypoproteinemia) and documented enteric protein loss: faecal alpha-1-antitrypsin ≥400 µg/g medication directly affecting metabolic state, such as cholesterol-lowering agents, or haemodynamic state, such as beta-blockers or sildenafil, with the exception of angiotensin converting enzyme inhibitors, diuretics, and anticoagulants atrial or ventricular arrhythmia coronary artery disease (history of myocardial infarction, myocardial revascularisation, percutaneous coronary intervention, or coronary artery bypass surgery) any metabolic disease, such as diabetes mellitus malignancy obesity (body mass index (BMI) >25 kg/m2) underweight (BMI < 18 kg/m2) renal disease inflammatory disease such as acute or chronic infection myeloproliferative disorder pregnancy or lactation malnourishment mental handicap not allowing valid consent to participation in the study or CMR need of sedation or general anesthesia for CMR typical contraindications for performing CMR such as metal-containing mechanical or electronic implants claustrophobia

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 |
| --- | --- |
| Patients<br>Patients with Fontan circulation. No intervention planned (observational study) | |
| Controls<br>Healthy, biventricular controls. No intervention planned (observational study) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants | When aspired number of participants is reached | July 2021-December 2023 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fontan, congenital heart disease, inflammation, Fontan-associated liver disease, Myocardial fibrosis, Collateral vessel