Positive Bias in the Prolonged QT Interval in Epilepsy is Related to the Calculation Method Rather Than Specific Anti-seizure Medications

Variable effects of epilepsy or its therapeutic agents showed variable effects on the heart.Epileptic patients, particularly those using carbamazepine and sodium valproate, were at risk of developing cardiac arrhythmias. 1 Evidence of ventricular repolarization, as shown by the prolongation of the QT period in the electrocardiogram (ECG) record, was observed during the interictal period in epilepsy patients. 2QT interval, which is corrected QT (QTc) by using Bazett's formula, has been reported to be prolonged with carbamazepine, sodium valproate, and levetiracetam in epileptic patients. 3Lamotrigine in different doses produced a non-significant decrease in the QTc interval estimated by using the Framingham equation. 4In healthy subjects, gabapentin enalapril at higher doses did not produce a significant effect on the QTc interval estimated by using Fridericia's equation, 5 as did topiramate, carbamazepine, or sodium valproate as monotherapy, which did not produce effects on the QTc interval calculated by Fridericia's equation in epileptic children. 6The variability in the effects of anti-seizure medicines (ASMs) may be related to the different methods of calculating the QTc interval.Several methods are used to calculate the QTc interval, including Bazett's, Fridericia's, Hodges', Framingham's, and other equations.In addition, the accuracy of the QT-nomogram is varied with each formula, as it has been found that the application of Rautaharju's formula [which used a cutoff value of 477 milliseconds (ms)] is superior to Bazett's or Fridericia's formulas. 7,8Another study proposed a new formula derived from Bazett's, Hodges's, Fridericia's, and Framingham's formulas for calculating the QTc interval at a heart rate between 40 and 140 beats per minute, which showed agreement with Hodges's but not with other formulas by using Bland-Altman analysis. 9Therefore, it is necessary to include the specifications of each formula in the assessment of the cardiac effects of ASMs, as the estimation of QTc by one method could be within normal limits, while using the other method will be significantly prolonged.This study aimed to detect the negative or positive bias by applying Bland-Altman analysis in calculating the QTc interval in epileptic patients treated with sodium valproate or levetiracetam compared with non-treated patients by applying different methods of calculation.