Autonomic Cardiovascular Regulation in Children with Hypoplastic Left Heart Syndrome and the Fontan Circulation

Abstract

Background: Hypoplastic left heart syndrome (HLHS) is a congenital heart disease phenotype where the left side of the heart is severely underdeveloped and cannot support systemic circulation. Children with HLHS undergo the Fontan operation, where the caval veins are attached to the pulmonary artery, and the right ventricle pumps blood through the aorta. Children with HLHS with Fontan circulation (HLHS-FC) have a reduced exercise tolerance and suffer from autonomic dysfunction. Understanding the role of autonomic dysfunction by studying the exercise pressor reflex through the stimulation of mechano- and metaboreceptors could provide further insight on potential mechanisms contributing to exercise intolerance. We hypothesized than children with HLHS-FC would have an augmented exercise pressor response resulting in increased sympathetic stimulation through mechno- and metaboreflex (handgrip) and metaboreflex only (post-exercise circulatory occlusion, PECO) as defined by change in mean arterial pressure (MAP) versus healthy controls (CTL). Methods and Results: Nine HLHS-FC (f=3, m=6; 134 y) and 9 CTL (f=3, m=6; 133 y) rested supine for 10 minutes to assess heart rate variability (HRV) and resting physiologic parameters, then performed 2 minutes of 40% maximal voluntary contraction isometric handgrip exercise, followed by 3 minutes of PECO on the exercised arm. Continuous blood pressure, heart rate (HR), ventilation, and forearm blood flow (FBF) of the contralateral limb were measured throughout the protocol. Children with HLHS-FC had lower resting heart rate variability (HRV) values of standard deviation of normal R-R intervals (31.932.4 vs. 70.424.0; P = 0.011), root mean square of successive R-R interval differences (31.932.3 vs. 70.324.0; P = 0.011), percentage of consecutive normal R-R intervals that differ by more than 50ms (19.828.2 vs. 44.718.8; P = 0.043), low frequency power percentage (21.85.4 vs. 35.710.4; P = 0.003), high frequency power percentage (31.515.4 vs. 46.89.7; P < 0.023) than CTL. Mean arterial pressure (MAP) increased significantly less during handgrip (55mmHg vs 1610mmHg; P < 0.001) and PECO (45mmHg vs 149mmHg P = 0.002) in HLHS-FC than CTL. There was a blunted exercise HR response in HLHS-FC compared to CTL (67 bpm vs. 248 bpm; P <0.001). Ventilation was lower in HLHS-FC than CTL during handgrip (0.321.15 L/min vs 3.363.94 L/min; P = 0.003). In HLHS-FC FBF increased substantially during PECO when compared to rest (0 mL/min/m2 vs 19.832.6 mL/min/m2; P = 0.012) and handgrip (2.916.7 mL/min/m2 vs 19.832.6 mL/min/m2; P = 0.036). Conclusion: Children with HLHS-FC suffer from autonomic dysfunction, with a sympathovagal balance favouring the sympathetic nervous system, and contrary to our hypothesis, have a blunted exercise pressor reflex response to increased sympathetic stimulation. The exercise pressor reflex may play a key role in the exercise intolerance encountered by children with HLHS-FC.