Cardiac autonomic function in patients with single ventricle physiology after Fontan palliation: A literature review

Background: The Fontan operation has significantly improved survival in patients with single ventricle physiology. This comes at a price of highly prevalent long-term complications. Autonomic dysfunction has been documented in patients after Fontan palliation. Although autonomic dysfunction is associated with a range of adverse outcomes, the exact clinical implications in patients with a Fontan circulation remain unclear. Aims: The aims of this review are to address (1) the extent and characteristics of autonomic dysfunction in Fontan patients; (2) its association with clinical short- and long-term outcomes, and (3) identify key gaps in the literature. Methods: A literature search was performed in PubMed using a dedicated query for single ventricle disease and cardiac autonomic (dys)function. Results: Data from the literature consistently indicated overt autonomic dysfunction in patients after Fontan operation versus controls, marked by reduced heart rate variability and impaired parasympathetic tone. However, autonomic dysfunction showed different associations with clinical outcomes in Fontan patients. Several studies reported an association with diminished exercise capacity, arrhythmias, organ function markers, while other studies found no clear predictive value. Gaps in literature include data on adult patients, the influence of anatomical substrate, sex and lifestyle, as well as specific "driving" factors for the development of cardiac autonomic dysfunction. Conclusion: Autonomic dysfunction in Fontan patients is a persistent and potentially progressive condition, characterized by reduced heart rate variability and reduced parasympathetic tone. Long-term studies are needed to clarify its clinical significance and address gaps in literature relating to contributing factors like sex, anatomy, and underlying mechanisms.