Does valproic acid cause cardiac arrhythmias, in particular QT-prolongations, as possible SUDEP risk factor?

Aims: Mortality in epilepsy is increased; in particular relevant is sudden unexpected death in epilepsy (SUDEP). Cardiac arrhythmias caused by anticonvulsive drug treatment are possible etiological risk factors. In adults QT- prolongations by valproic acid (VPA) are discussed.

Methods: This is a prospective study on a total of 50 pediatric patients (mean age 12.2; median 11.25 years) with epilepsy under therapy with VPA for at least 3 months. The protocol included a standardized electrocardiogram (ECG) with determination of the heart positions, ECG-time values and analysis of cardiac hypertrophy and lesions. At the same time VPA-doses and plasma-levels were measured.

Results: 25 female and 25 male patients took VPA for a mean time of 5.8 years (range 3 months up to 32 years), 29 of them took monotherapy; 13 double- and 8 triple-combination. VPA was applied with a mean dose of 26.6mg/kg body weight/d (range 10.5 up to 63.8mg/kg body weight/d), the VPA plasma levels ranged between 19.7 and 147.4µg/ml (mean 88.8µg/ml; median 91µg/ml). The measured ECG-time values were all normal. PR-interval [ms]: range 100–170, median: 124, mean: 126.7; QRS-interval [ms]: range 56–108, median 79, mean 79.94; QT-interval [ms]: range 264–400, median 348, mean 343.34; QTc-interval [ms], normal value <440ms in males and <460ms in females: range 377–433, median 403, mean 402.9. Electrical heart position: 42% indifferent, 46% vertical, 8% left, 2% right type. One patient with tuberous sclerosis showed a total right bundle branch block (TRBBB) due to transection of the electric excitation pathway during rhabdomyoma surgery in the right cardiac ventricle.

Conclusion: In a group of epilepsy patients with therapeutic VPA medication was no evidence of electrocardiographic SUDEP risk factors, especially no QT-prolongations.