Patients with single ventricle congenital heart disease undergo a series of surgeries in early childhood with the last being the Fontan palliation. This Fontan heart circulation helps patients to survive for many years, but unfortunately, may also cause heart failure and damage to other organs. Heart failure and other organ damage following the Fontan procedure is called Fontan circulatory failure (FCF), a chronic, life-limiting disease. Patients with FCF are often referred for a heart transplant, but their survival after a heart transplant is not as good as others with different types of heart disease. FCF characteristics are not well defined or understood, but are likely the cause of these poorer transplant outcomes. It is also known that each patient responds to the physical and psychological stressors of chronic disease differently. Patients can be physically affected by the overall burden of disease, and this can be measured by assessing frailty. They can also be psychologically affected by disease, and this can be measured by assessing resilience. This study brings together 16 pediatric heart transplant centers to better describe and understand how FCF characteristics affect transplant outcomes and survival after transplant. This information will help us learn the best timing for transplant evaluation in patients with FCF. We will also measure frailty and resilience in patients with FCF undergoing transplant evaluation. This information will help us develop future interventions to reduce transplant risks in patients with FCF. Overall, this study aims to improve physical and psychological outcomes in patients with FCF including those who go on to heart transplant.

In order to improve long-term outcomes for the single ventricle population, it is critical to develop a better understanding of the factors that drive FCF and associated morbidity and mortality. Equally as critical is learning how individual physiologic and psychologic responses to FCF as manifested by frailty and resilience modify FCF risks as these may be ideal targets for intervention to improve FCF and post-HTx survival. Our proposal will leverage a large multicenter collaboration and established, advanced research infrastructure employing modern analytics to clearly identify pre-HTx risk factors in single ventricle patients that affect post-HTx outcomes. To accomplish this, we propose the following aims:

Aim 1: Elucidate the key FCF factors associated with HTx outcomes. We will construct a robust FCF dataset to be analyzed using traditional risk modeling and advanced machine learning methods to elucidate specific patient factors and interactions that influence FCF survival at 1-year post-HTx as well as other markers pre-and-post-HTx morbidity.

Aim 2: Define the impact of frailty and resilience in modifying FCF risk factors and influencing outcomes. Our multicenter collaborative will prospectively collect patient frailty and resilience indices to examine their impact on FCF outcomes. We hypothesize that these factors will mitigate or intensify the impact of FCF risks using the same modeling strategies as in Aim 1.