Fibrosis and the Fontan

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.

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 years of age of either gender, whether single left or right ventricle, who are scheduled to undergo a Fontan operation at the Children's Hospital of Philadelphia (CHOP) and control subjects will be aged between 1 and less than or equal to 6 years of age with normal ventricular function and normal livers who present to CHOP for a clinically indicated MRI. Review of medical records, demographic/social history, physical examination (performed for clinical purposes), administer study drug (spironolactone), blood tests (serum biomarkers), MRI/CMR (including a non-FDA approved MRI sequence), liver assessment, administration of contrast and general anesthesia for case subjects (in some instances, an extension of clinically indicated anesthesia for control and some case subjects approximately 15-20 minutes) as applicable. The difference between enrollment and 1 year after Fontan surgery for a) liver fibrosis measured by Magnetic Resonance Elastography (MRE) and T1 mapping, b) cardiac fibrosis measured by T1 mapping using global extracellular volume (ECV) and c) percentage of myocardial mass which demonstrates delayed enhancement (DE). This is for both non-drug and spironolactone administered groups