Background Many cardiocirculatory mechanisms are involved in the adaptation to orthostatic stress. While these mechanisms may be impaired in Fontan patients. However, it is yet unclear how Fontan patients, who exhibit a critical fluid balance, respond to orthostatic stress. Angiotensin converting enzyme inhibitors are often prescribed to Fontan patients, but they may negatively influence orthostatic tolerance. Therefore, we evaluated the response to orthostatic stress in pediatric Fontan patients before and after treatment with enalapril. Methods Thirty-five Fontan patients (aged 14 years) with moderate-good systolic ventricular function without pre-existent enalapril treatment were included. Before and after a three-month enalapril treatment period, the hemodynamic response to head-up tilt test was evaluated by various parameters including cardiac index, blood pressure, cerebral blood flow, aortic stiffness and cardiac autonomous nervous activity. Thirty-four healthy subjects (aged 13 years) served as controls. Results Fontan patients had a decreased cerebral blood flow and increased aortic stiffness in the supine position compared to controls, while all other factors did not differ. Patients and controls showed a comparable response to head-up tilt test for most parameters. Twenty-seven patients completed the enalapril study with a mean dosage of 0.3±0.1mg/kg/day. Most parameters were unaffected by enalapril, only the percent decrease in cardiac index to tilt was higher after treatment, but the cardiac index during tilt was not lower (3.0L/min/m2 pre-enalapril versus 2.8L/min/m2 after treatment; P = 0.15). Conclusion Pediatric Fontan patients adequately respond to orthostasis with maintenance of blood pressure and cerebral blood flow and sufficient autonomic response. Enalapril treatment did not alter the response. Clinical trial information Scientific title: ACE inhibition in Fontan patients: its effect on body fluid regulation (sAFE-study). The Netherlands National Trial Register: Trail NL6415. Registered 2017-07-20. Trial information: https://www.trialregister.nl/trial/6415

Background
Although various determinants of exercise limitation in Fontan patients have been studied, most research has been performed in patients who underwent different surgical procedures with differing haemodynamic characteristics. The aim of the current study was to evaluate non-invasively measured cardiovascular parameters and their influence on exercise performance in paediatric Fontan patients with an extracardiac conduit and moderate-good systolic ventricular function.
Methods
Fontan patients, between 8 and 18 years of age, with moderate to good systolic ventricular function and an extracardiac conduit were included. Exercise performance and cardiovascular assessment, comprising echocardiography, aortic stiffness measurement and ambulatory measurement of cardiac autonomous nervous activity were performed on the same day. Healthy subjects served as controls.
Results
Thirty-six Fontan patients (age 14.0 years) and thirty-five healthy subjects (age 12.8 years) were included. Compared to controls, Fontan patients had reduced diastolic ventricular function and increased arterial stiffness. No differences were found in heart rate (HR) and cardiac parasympathetic nervous activity. In Fontan patients, maximal as well as submaximal exercise capacity was impaired, with the percentage of predicted capacity ranging between 54 and 72%. Chronotropic competence, however, was good with a peak HR of 174 (94% of predicted). Lower maximal and submaximal exercise capacity was correlated with a higher HR at rest, higher pulse wave velocity of the aorta and a lower ratio of early and late diastolic flow velocity.
Conclusion
Contemporary paediatric Fontan patients have an impaired exercise capacity with preserved chronotropic competence. Exercise performance correlates with heart rate at rest, diastolic function and aortic stiffness.

Background:Passive leg raising is used to predict who will benefit from fluid therapy in critically ill patients, including children. Patients with a Fontan circulation may have a different haemodynamic response to a fluid challenge by passive leg raising.Methods:The haemodynamic response of 31 paediatric patients with a Fontan circulation from the outpatient clinic (median age 14.0 years) and 35 healthy controls (median age 12.8 years) to passive leg raising was evaluated non-invasively by echocardiography for the assessment of, e.g., velocity time integral across the (neo)aortic valve, blood pressure measurements, and respiration. Participants were considered responders when the velocity time integral increased ≥ 10.0%.Results:Overall, patients and controls did not differ in the haemodynamic response. Twelve patients (38.7%) and 8 controls (22.9%) were responders, which was not statistically different (P = 0.22). Responders in the patient and control group also had a similar echo-estimated velocity time integral increase of + 18.9% and + 15.2%, respectively (P = 0.91). There was no difference in echo-estimated velocity time integral change between patient and control non-responders with a decrease of −1.4% and −6.4%, respectively (P = 0.70) and no difference in the amount of patients who were negatively affected by passive leg raising, ith a decrease of ≤−10.0% in 7 patients (22.6%) and 9 controls (25.7%)(P = 0.77).Conclusion:The haemodynamic response of ambulatory paediatric patients with a Fontan circulation to passive leg raising is like that of healthy controls. Patients who did not respond were similarly affected as healthy controls. Whether the haemodynamic response is different in critically ill patients warrants further investigation.Trail registration:The Netherlands National Trial Register (NTR), Trial: NL6415; date of registration 20-07-2017; Trial information: https://www.trialregister.nl/trial/6415.