Neurodevelopment and Cognition Across the Lifespan in Patients With Single-Ventricle Physiology: Abnormal Brain Maturation and Accumulation of Brain Injuries.

The proportion of adults with single-ventricle physiology (SVP) has significantly increased over time. Improved longevity, however, may be associated with increased risks to brain health in adulthood. Children with SVP are at risk for neurodevelopmental impairment early in life and neurocognitive impairment as they age, and existing epidemiologic evidence suggests that adults with complex congenital heart disease, including SVP, are at increased risk of stroke and dementia, as compared with age-matched controls. Mechanisms that could contribute to increased potential for cognitive impairment in adults with SVP include the following: (i) baseline brain dysmaturation beginning in utero; (ii) subsequent acquired injury occurring in early childhood from staged surgeries; and (iii) pathophysiologic factors related to SVP itself, both in childhood and potentially throughout the lifespan as new arrhythmias, heart failure, and other issues may develop. Associated pathophysiologic mechanisms may include thromboembolism, hypercoagulability, hypoxia, hypoperfusion, and inflammation. Despite increasingly robust pediatric literature with neuroradiologic-neuropsychology correlates in SVP, there is a dearth of similar research in adults, with respect to both complex congenital heart disease overall and SVP specifically. Unanswered questions in adults with SVP include the following: (i) what is the prevalence of baseline brain injury and neurocognitive impairment in adulthood; (ii) what is the incident risk of these issues over time; and (iii) how much may be mediated by incident brain injury across the lifespan in adulthood, as opposed to from underlying susceptibility from dysmaturation and early childhood insults. In this review, we describe what is known regarding the brain health in individuals with SVP across the lifespan, and identify priority areas for future research.