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

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Surges R, Adjei P, Kallis C, Erhuero J, Scott CA, Bell GS, Sander JW, and Walker MC (2010) Pathologic cardiac repolarization in pharmacoresistant epilepsy and its potential role in sudden unexpected death in epilepsy: a case-control study. Epilepsia 51:2 233–42.

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Abstract: PURPOSE: 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 ECG predictor for SUDEP. Pathologic cardiac repolarization is not uncommon in adult patients with pharmacoresistant focal epilepsy and could favor occurrence of fatal tachyarrhythmia as one plausible cause for SUDEP. SGTCS are a risk factor for SUDEP, have, as compared to complex-partial seizures, a greater, unfavorable impact on heart activity, and may thereby additionally compromise cardiac function.

Keywords: Long QT, Heart rate variability,Heart rate recovery, Sudden cardiac death,QT dispersion

Context

  • Retrospective case-control study comparing EEG and simultaneous EKG in patients who died of SUDEP. Controls were matched living patients with similarly severe epilepsy who underwent monitoring for surgical consideration at the same EMU. Among the 19 patients in each group, 13 patients were reviewed. While corrected QT interval and QT dispersion were elevated in some decedents, there was no difference between groups in these or other EKG parameters. Note: Most assessments of significance accept a risk of false postivity of 1 in 20. When many possible associations are evaluated, then, some spurious correlations will inevitably achieve statistical significance. This could explain some of the findings such as the greater likelihood among SUDEP patients of normal MRI findings and the lower likelihood of adverese drug reactions during telemetry. While other correlations present in this study such as the greater number of GTCS per year among SUDEP victims are more intuitively plausible, they too are subject to the same potential for false determination of significance. A Bonferroni correction for multiple comparisons should be considered to address this possibility.

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