Congenital heart disease (CHD) is one of the most common congenital disorders in newborns. Even mild forms of CHD can lead to long-term damage to central nervous system damage, significantly increasing the risk of various neurological conditions such as migraine, neurodevelopmental disorders, epilepsy, and cryptogenic stroke.
Epilepsy is a chronic neurological disorder that affects over 7 million people worldwide. Epidemiological studies suggest that patent foramen ovale (PFO), patent ductus arteriosus (PDA), atrial septal defect (ASD), and ventricular septal defect (VSD) are the commonest simple congenital heart defects associated with abnormal cardiac shunting. This prospective cohort study published in CNS Neuroscience & Therapeutics demonstrated the relationship between epilepsy risk and simple CHD types.
In this study, the patients with simple CHD (N = 10,914; 39.33% male, 60.67% female, median age = 35 years [interquartile range, IQR:14–54]) including PFO (n = 2135), PDA (n = 1432), ASD (n = 4985) and VSD (n = 2362) were recruited from West China Hospital of Sichuan University. Patients with two or more CHD types, history of seizures, and misdiagnosis of CHD were excluded. The follow-up telephonic survey was conducted from January 2008 once a year from diagnosis of simple CHD to epilepsy and loss to follow-up or conclusion of the study in June 2022. The risk ratio (RR) and 95% confidence interval (CI) were determined by using Poisson regression analysis.
The average follow-up period for the study was 2.19 years, ranging from 3 days to 13.25 years. A total of 108 patients (ASD = 30, PDA = 11, VSD = 21, PFO = 46) were diagnosed with epilepsy during this period. Patients with PFO had a higher prevalence of diabetes, stroke, congenital anomalies, and hypertension compared to other types of simple CHD. Moreover, the prevalence of birth hypoxia and febrile convulsions were similar among different types of simple CHD.
The incidence of epilepsy was 8.58, 2.63, 3.98, and 4.85/1000 person-years in patients with PFO, ASD, PDA, and VSD, respectively. The greatest statistical difference was observed in the incidence rate (IR) of PFO group compared to reference group (ASD) with IR difference (IRD) of 5.95 (95% CI: 3.30–9.60) whereas a non-significant difference was observed in PDA (IRD = 1.34, 95% CI: −1.19–3.88) and VSD (IRD = 2.22, 95% CI: −0.06–4.50) groups. The risk of epilepsy was higher in PFO type (RR = 3.28, 95% CI: 2.00–5.43), PDA (RR = 1.46, 95% CI: 0.70–2.82), and VSD type (RR = 1.47, 95% CI: 0.79–2.68) compared to ASD type.
In sub-group analysis, it was found that patients who underwent CHD surgery had a lower risk of epilepsy compared to those who did not. Additionally, it was demonstrated that the RR value was not significant in the PFO group that underwent surgery (RR = 1.92, 95% CI: 0.58–5.26) compared to those who did not (RR = 2.55, 95% CI: 1.27–5.68). This study’s limitations include low epilepsy incidence affecting statistical analysis and lack of behavior and lifestyle data, depending on hospital records.
In conclusion, this study suggests that PFO was associated with a 3.28 times higher risk of epilepsy compared to ASD, while PFO surgery was linked to a reduced risk of epilepsy. These findings are crucial for the implementation of future evidence studies on PFO pathogenesis and CNS diseases, as well as the prevention and management of epilepsy in PFO patients.
Reference: Chen L, Yang Z, Ji S, et al. Comparing the Risk of Epilepsy in Patients With Simple Congenital Heart Diseases: A Prospective Cohort Study. CNS Neurosci Ther. 2025;31(2):e70230. doi:10.1111/cns.70230
