# RE-ENERGIZE FONTAN - RandomizEd Exercise INtERvention desiGned to MaximIZE Fitness in Pediatric FONTAN patients

> **NIH NIH R33** · STANFORD UNIVERSITY · 2021 · $734,288

## Abstract

PROJECT SUMMARY
Survival of children with single ventricles (“half a heart”) beyond the neonatal period has increased dramatically
with the staged Fontan palliation. Yet, long-term morbidity remains high. By the age of 40, 50% of Fontan patients
will have died or undergone heart transplantation. With >1,000 Fontan palliations performed in the US annually,
there is a burgeoning population of Fontan patients at risk for progressive heart failure and death. Factors that
contribute to onset and progression of heart failure in Fontan patients remain incompletely understood. However,
it is established that Fontan patients have poor exercise capacity, associated with a greater risk of morbidity and
mortality, in addition to decreased muscle mass, abnormal muscle function, and endothelial dysfunction
contributing to disease progression. In adult patients with two ventricles and heart failure, reduced exercise
capacity, muscle mass, and muscle strength are powerful predictors of poor outcomes, and exercise
interventions can not only improve exercise capacity and muscle mass, but also reverse endothelial dysfunction.
Limited exercise interventions in children with congenital heart disease have demonstrated that exercise is safe
and effective; however, these studies have been conducted in small, heterogeneous groups, and most had few
Fontan patients. Furthermore, none of these interventions have studied the impact of exercise on muscle mass
or mitochondrial function, or endothelial function. We propose a milestone-driven, randomized controlled
trial in pediatric Fontan patients to test the hypothesis that a live-video-supervised exercise (aerobic +
resistance) intervention will improve cardiac and physical capacity; muscle mass, strength and function;
and endothelial function. Adherence is a major limitation in pediatric exercise interventions delivered on-site,
with adherence rates as low as 10%, due to distance from site, transportation difficulties, and missed school or
work days. To overcome these challenges, we will utilize live-video conferencing to deliver the supervised
exercise sessions. In our pilot exercise interventions, this approach resulted in excellent adherence (>85%)
and improved exercise capacity and endothelial function. This proposal is designed to determine if the
intervention improves: (Aim 1) cardiac and physical capacity (primary outcome: VO2 max), (Aim 2) muscle mass
strength and function; and (Aim 3) endothelial function in pediatric Fontan patients. Our multidisciplinary team of
experts will assess the effectiveness of a live-video-supervised exercise intervention, rigorously designed to
maximize adherence and improve key and novel measures of health in pediatric Fontan patients associated with
poor long-term outcomes. The use of exercise as a non-pharmacologic treatment modality in pediatric Fontan
patients represents a paradigm shift, where standard therapies have failed. Our ultimate goal is the translation
of this model to cl...

## Key facts

- **NIH application ID:** 10274780
- **Project number:** 4R33HL146775-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Daniel Bernstein
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $734,288
- **Award type:** 4N
- **Project period:** 2020-03-10 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10274780

## Citation

> US National Institutes of Health, RePORTER application 10274780, RE-ENERGIZE FONTAN - RandomizEd Exercise INtERvention desiGned to MaximIZE Fitness in Pediatric FONTAN patients (4R33HL146775-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10274780. Licensed CC0.

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