Metabolic Dysfunction Drives Exercise Intolerance in Fontan Patients

Project Owner

Anita Saraf, MD, PhD

Proposed Innovation

Thanks to advances in congenital heart surgery, most patients born with single-ventricle heart disease now survive into adulthood following the Fontan procedure. But many of these individuals develop progressive heart and liver disease that leads to debilitating exercise intolerance — and eventually may need a heart or combined heart-liver transplantation. While these complications are well recognized, the connection between the heart and liver remains poorly understood.

This project will investigate whether liver dysfunction contributes to declining heart performance and exercise intolerance in Fontan patients.

Improvements in Action

In this study, researchers will combine cardiopulmonary exercise testing with metabolic analysis. Their goal is to evaluate how Fontan patients use energy substrates during exercise. They will measure changes in fatty acids, ketones, glucose, and lactate before, during, and after exercise. The results will be compared with those of healthy individuals.

The project will determine whether impaired liver metabolism contributes to reduced exercise capacity. It is hoped such metabolic changes can serve as early biomarkers of disease progression before doctors can detect cardiac dysfunction using conventional imaging.

Intended Outcomes

This project is expected to demonstrate the metabolic relationship between the heart and liver in Fontan patient, and identify potential targets for earlier diagnosis and treatment. Similar metabolic pathways also are involved in metabolic dysfunction-associated steatotic liver disease (MASLD), so the findings may have broader implications for improving cardiovascular care in millions of affected patients.