Systolic function of the single ventricle and exercise capacity, endothelial function, muscle mass and strength in paediatric Fontan patients
Authors: Nunez Gallegos F , Bernstein D , Punn R , Long J , Leonard M , Stauffer K J , Thorson K , Desai M , Chen S , Davila T , Lui M , Olson I , Myers J , Palaniappan L , Tierney S 
Published: June 2023

Abstract

Funding Acknowledgements
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): NHLBI.

Background
By age 40, 50% of Fontan patients will have died or undergone heart transplantation. Poor exercise capacity, diminished muscle mass and strength, and endothelial dysfunction all impact disease progression.

Purpose
Here, we present the baseline systolic function data of the single ventricle (SV) in paediatric Fontan patients prior to entering an exercise intervention (RE-ENERGIZE FONTAN) and assess its relationship to exercise capacity, endothelial function, muscle mass, and strength.

Methods
This randomised controlled trial in Fontan patients utilizes live-video conferencing to deliver a supervised exercise intervention. The patients are randomised to intervention or usual care at baseline. Inclusion criteria include: (1) Age 8–19 years; (2) Exercise clearance by primary cardiologist; (3) English-speaking patient. Exclusion criteria include: (1) NYHA Class IV, (2) Acute illness within the past three months; (3) Active protein losing enteropathy (albumin &lt;2.5 mg/dL); 4) Pacemaker; and/or 5) Cognitive delay impeding participation in the intervention. At baseline, patients underwent a 2D and 3D echocardiogram to measure SV systolic function, a cardiopulmonary exercise test to obtain peak oxygen consumption (peak VO2), endothelial pulse amplitude testing (EndoPAT) to assess endothelial function, Dual Energy X-ray Absorptiometry (DEXA) to assess muscle mass and isokinetic dynamometry to assess handgrip and leg strength. Tom-Tec derived 3D ejection fraction (EF) was calculated. Reactive hyperaemia index (RHI) and the natural log of RHI (lnRHI) were obtained using EndoPAT as measures of endothelial function. Leg lean mass was expressed as sex and age-specific z-score adjusted for leg length.

Results
We have enrolled 73 Fontan patients. The median age at baseline visit was 13.2 years [IQR, 10.8–15.6]. The median time from Fontan operation was 9.2 years [IQR, 7.1–12.0]. 43 (60%) had a single right ventricle. 3D EF was 49.9±7.2%. Peak VO2 was 1366±520 ml/min and indexed peak VO2 was 27.7±6.5 ml/min/kg. RHI and lnRHI were 1.41±0.51 and 0.31±0.31, respectively. Leg lean mass z-score was −0.84±1.41. Handgrip strength was 18.6±8.01 kg, while leg strength extension and flexion were 58.0±32.9 and 27.2±15.11 ft bls, respectively. 3D EF correlated positively with RHI and lnRHI (Figure 1, p-values: 0.04 and 0.02, respectively).

Conclusions
In this cohort of paediatric Fontan patients, SV systolic function was diminished and there was a direct correlation between SV systolic function and endothelial function. However, there was no correlation between SV systolic function and exercise capacity, leg lean mass, or muscle strength. Our exercise intervention is designed to demonstrate the impact of aerobic and strength training on cardiac function, exercise capacity, endothelial function, and muscle mass and strength with the ultimate goal of instituting an "exercise prescription" in Fontan patients to decrease long-term morbidity and mortality.