Pathologic cardiac repolarization in pharmacoresistant epilepsy and its potential role in sudden unexpected death in epilepsy: A case–control study

Abstract

SUMMARYPurpose: To determine whether abnormal cardiac repolarization and other electrocardiography (ECG) predictors for cardiac mortality occur in epilepsy patients and whether they are associated with an increased risk for sudden unexpected death in epilepsy (SUDEP). Methods: In a matched-pair case-control study, recordings of adult patients with pharmacoresistant focal epilepsies who died from SUDEP and who had previously had presurgical video-EEG (electroencephalography) telemetry were reviewed. Living controls were matched for age, gender, and date of admission for video-EEG telemetry. Periictal heart rate (HR), corrected QT interval (QTc), postictal HR recovery, HR variability, and cardiac rhythm were assessed. QT dispersion was analyzed with 12-lead ECG. Results: A total of 38 patients (19 per group) had 91 recorded seizures. QTc was prolonged above pathologic upper limits in 9 of 89 seizures and 5 of 38 patients. Nine of 34 patients displayed pathologic QT dispersion. Presence of neither pathologic cardiac repolarization nor other ECG features were specifically associated with SUDEP. SUDEP patients were, however, more likely to lack pathologic cerebral magnetic resonance imaging (MRI) findings, less likely to experience antiepileptic drug reduction during telemetry, and had more secondarily generalized tonic-clonic seizures (SGTCS) per year. Discussion: Our study did not reveal a clear-cut

Enhanced QT shortening and persistent tachycardia after generalized seizures

“…20 Alterations of cardiac repolarization are established predictors of sudden cardiac death, 5,21 and we and others have shown abnormal QTc lengthening with seizures. 4,22 Abnormal QT prolongation was found in 6% of the seizures and 12% of the patients, thus relatively similar to the observed prevalence in our previous study. 4 Prolonged QTc interval is an established risk factor for life-threatening "Torsade de Pointes" tachy- cardia.…”

“…4,22 Abnormal QT prolongation was found in 6% of the seizures and 12% of the patients, thus relatively similar to the observed prevalence in our previous study. 4 Prolonged QTc interval is an established risk factor for life-threatening "Torsade de Pointes" tachy- cardia. 5,21 Thus, peri-ictal QT prolongation could facilitate fatal ventricular tachyarrhythmia.…”

“…4 This is most likely related to the fact that QT shortening seems to occur predominantly immediately or 1 minute after seizure cessation, a time period not usually assessed in other studies.…”

“…18,19,34 Furthermore, chronic epilepsy patients display altered autonomic function with a presumably increased sympathetic tone and enhanced QT dispersion (spatial heterogeneity of cardiac repolarization), which are both independent predictors of cardiac mortality. 4,7,35,36 The latter finding is of particular interest, as enhanced QT dispersion facilitates ventricular tachyarrhythmia with short QT interval. 37 Thus, one plausible explanation for SUDEP would be peri-ictal occurrence of pathologic cardiac repolarization resulting in sudden onset of ventricular tachyarrhythmia.…”

“…Abnormalities in cardiac repolarization, persistent elevations of heart rate (HR) after exercise, and a decreased HR variability (HRV) are established predictors for cardiac mortality and sudden cardiac death in other medical conditions or in healthy populations. [5][6][7] Previous studies have suggested a greater impact of GTCS on cardiac excitability than nongeneralized seizures with higher ictal heart rates in chronic epilepsy and SUDEP patients 4,[8][9][10][11] and possibly more cardiac arrhythmias following GTCS. 8,10 These studies, however, are confounded by the failure to compare the cardiac features in different seizure types within individual patients and they therefore did not take into account individual differences in autonomic nervous system re-…”