Neuropsychological Performance in Tetralogy of Fallot: A Protocol Integrating Genetics, Cognitive Assessment, and Brain and Cardiac Imaging

Abstract

Introduction: Tetralogy of Fallot (TOF) is the most common form of cyanotic congenital heart disease. Although early surgical repair has increased the survival rates, many clinical and perioperative factors, hypoxemia in particular, seem to be associated with impaired neuropsychological outcomes, such as inattention and dysexecutive function; however, it is unclear whether this outcome is secondary to cerebral damage. A current gap in this field is the correlation between morphofunctional brain changes (including insults occurring from intrauterine to late postoperative development) and cognitive function. 

Objective: To investigate if genetic, clinical factors, brain, and cardiac morphofunctional changes can predict neuropsychological performance. 

Methods: We used a theoretical directed acyclic graph to investigate potential factors impacting neuropsychological performance in TOF patients. Patients and matched controls will undergo neuropsychological testing and behavior questionnaires. In contrast, TOF patients will be evaluated with genetic-molecular exams and advanced cardiac and brain magnetic resonance image examinations to assess structural and functional brain changes. 

Discussion: Through a comprehensive evaluation encompassing brain and cardiac morphofunctional changes, genetic factors, and cognitive performance, we expect to improve our understanding of the neuropsychological profile of patients with TOF. This innovative approach includes the genetic-molecular evaluation, and a control group matched for main environmental factors. This strategy holds the potential to significantly enhance our understanding of the neurodevelopment of patients with TOF, thereby paving the way for improvements in cardiological and pediatric care.