# Acute Imposition of Fontan Physiology in The Single Ventricle Patient: Effects on Fibrosis, Function and Drug Intervention

> **NIH NIH R01** · CHILDREN'S HOSP OF PHILADELPHIA · 2020 · $856,639

## Abstract

Project Summary/Abstract
 Congenital heart disease (CHD) complicates 0.8–1% of live births and is one of leading causes of death in
children. Those born with only one pumping chamber, a single ventricle (SV), are most prone to morbidity and
mortality, consuming a significant and disproportionate amount of medical resources. These infants survive to
adulthood following a series of palliative heart operations culminating in the Fontan operation. Nearly 85% of
those undergoing the Fontan operation are alive up to 30 years after surgery with an estimated 60,000 such
patients living today. Unfortunately, they suffer multiple complications such as liver fibrosis, lymphatic
congestion and protein loosing enteropathy to name a few. In addition, the unique pathophysiology of the
Fontan circulation may itself cause cardiac fibrosis and failure for many reasons (eg one pumping chamber
performing the work of two). While studies 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 the starting point of liver and cardiac fibrosis as well as lymphatic abnormalities along with the
interplay between them by assessing these before as well as relatively early after imposition of the Fontan
circulation. In addition, a pilot trial of the antifibrotic agent spironolactone will be undertaken to determine if
this approach could decrease fibrosis and if magnetic resonance imaging (MRI) can discern this difference.
 The purpose of this study is to characterize by non-invasive means the fibrotic consequences of the acute
imposition of Fontan hemodynamics, and to investigate the interrelationship between liver and cardiac fibrosis,
abnormal hemodynamics and lymphatic congestion. The pilot trial of spironolactone will determine
mechanistically whether it can mitigate fibrosis in SV patients and if MRI can discern this difference. The
combination of serum biomarkers and MRI form a powerful non-invasive tool in putting together the
complicated web of organ dysfunction. Prior to, one, two and possibly three years after Fontan operation,
children will undergo MRI to assess liver and cardiac fibrosis, ventricular function and flows and lymphatic
assessment. The interrelationship between all these metrics will be explored.
 Now that Fontan mortality has markedly decreased over the past 20 years, it’s imperative to
investigate fibrotic insults in order to improve lifelong well-being. This study is significant because it
aims to understand how to alleviate morbidity as these children enter their adult years by appreciating
how the imposition of Fontan hemodynamics plays a role in its earliest stage and the effects of
spironolactone administration on this physiology, determining if MRI can discern this difference.

## Key facts

- **NIH application ID:** 10050652
- **Project number:** 1R01HL149139-01A1
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** Mark A Fogel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $856,639
- **Award type:** 1
- **Project period:** 2020-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10050652

## Citation

> US National Institutes of Health, RePORTER application 10050652, Acute Imposition of Fontan Physiology in The Single Ventricle Patient: Effects on Fibrosis, Function and Drug Intervention (1R01HL149139-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10050652. Licensed CC0.

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