Abstracts

Rationale: Seizures and epilepsy are reported in inherited cardiac ion channel diseases, such as Long QT (LQT) and Brugada (BrS) Syndrome. Mutated genes in LQT1-3 are also expressed in the brain. The prevalence of seizures in LQT remains not entirely understood. We hypothesized LQT mutations and QT prolongation on the ECG are positive risk factors for seizures; LQT with seizures is associated with an increased risk of cardiac arrhythmias and aborted cardiac arrest. Methods: Using the Rochester LQT Registry the prevalence of seizures was assessed in 3885 consented registrants, with individual/parent follow-up. LQT analysis was limited to LQT1-3 (n=965, comprising 86% of all LQT) and LQT genotype negative (n=936) registrants. People were assigned to the seizure group if during recruitment/follow-up they answered yes to seizures/epilepsy, or reported an anti-seizure medication (those medications also used as antiarrhythmics, antipsychotics, anti-anxiety, or sedatives were not defined as anti-seizure medication.) Outcomes included frequency of registrants with seizures, cardiac arrhythmias, and aborted cardiac arrest. Results: Overall prevalence of seizures was 8.75%, with 78.6% of genotyped seizure registrants positive for a LQT mutation. There were 5% of the LQT genotype negative registrants in the seizure group, yet 14% of LQT positive were in the seizure group (p<0.0001.) There was a positive correlation of QT interval to number of registrants in the seizure group. While 5% with normal QT intervals (<430ms male, <450ms female) were in the seizure group, 9% of borderline LQT (430-449ms male, 450-469ms female), 15% of LQT (≥450ms male, ≥470ms female), and 21% of severe LQT (≥500ms) registrants were in the seizure group (all p<0.0001 vs. normal QT interval). Subdividing the registrants by LQT genotype and QT interval, the frequency of LQT positive registrants with prolonged QT in the seizure group was 3 times greater than LQT positive registrants with normal QT, and 6 times greater than LQT negative registrants with normal QT (Figure 1). The frequency of LQT negative registrants with prolonged QT in the seizure group was 2 times larger than those with normal QT intervals. The number of people with syncope was 2 times greater in both the LQT genotype positive and negative groups with seizures compared to without seizures (p<0.006). The presence of ventricular couplet beats, (non-sustained) ventricular tachycardia, torsades-de-pointes, ventricular fibrillation, and aborted cardiac arrest were virtually absent in LQT negative registrants with and without seizures. Yet, these events were 4-9 times greater in the LQT positive seizure as compared with LQT no-seizure group (p<0.01). Conclusions: People with LQT mutations or QT prolongation are more likely to experience seizures. LQT registrants with seizures have higher risk of syncope, cardiac arrhythmias, and aborted cardiac arrest. It is critical to take a multi-system approach to studying and treating inherited ion channel diseases. The complex network of factors all coalesce to establish conditions for electrical disturbances in both the brain and the heart.