Acute Imposition of Fontan Physiology in The Single Ventricle Patient: Effects on Fibrosis, Function and Drug Intervention
Children's Hospital of Philadelphia
Summary
The purpose of this study is to non-invasively characterize the fibrotic consequences of single ventricle physiology, its possible solution and effect on lymphatics. This project investigates the response to acute imposition of Fontan hemodynamics by examining the interrelationship between liver and cardiac fibrosis/dysfunction and lymphatic congestion along with a pilot trial of the antifibrotic agent, spironolactone, to prevent these consequences and to determine if MRI can discern these differences. The combination of serum biomarkers and MRI form a powerful non-invasive tool in putting together this complicated web of dysfunction.
Description
Fontan patients, unfortunately, suffer multiple complications such as liver fibrosis, cardiac fibrosis and lymphatic congestion. While investigations describing the clinical state are taking place in older children and young adults, the onset of these complications remains unclear. The knowledge gap this proposal seeks to fill is understanding how early liver and cardiac fibrosis develops as well as lymphatic abnormalities by assessing these before as well as early after imposition of the Fontan circulation. Single ventricle case subjects will be between aged 1 and less than or equal to 6 yea…
Eligibility
- Age range
- 1–6 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Single Ventricle (SV) Patients Cohort 1 (Observational Group - no study medication): * Subjects between 1 and ≤ 6 years of age of either gender. * Either single left or single right ventricle. * Subjects who are scheduled to undergo a Fontan operation at CHOP. * Parents signing informed consent. Cohort 1A (formerly part of study drug group who wish continued participation in the observational group): * Subjects who were enrolled in this study in Cohort 2 and are either non-compliant with the medication, no longer want to take the medication, or have an AE that requir…
Interventions
- DrugSpironolactone
Spironolactone is a mild diuretic. Drug dosage will be those used clinically and per the CHOP formulary: 3 mg/kg/day in divided doses every 6-24 hours; the drug will be weight adjusted every \~0.5 kg with a maximum dosage of 200 mg/24 hours. Maximum single dose is 100 mg. Spironolactone, the aldosterone antagonist to be utilized in Specific Aim 2 of this study, is FDA approved, has been on the market for many years and is routinely administered to all types of children with congenital heart disease including SV patients. The choice of which patient this should be administered to is up to the clinician and their patients and therefore, not all SV patients are on this medication.
Location
- Children's Hospital of PhiladelphiaPhiladelphia, Pennsylvania