OBJECTIVE: Cardiac abnormalities resulting from chronic epilepsy (\"the epileptic heart\") constitute a well-recognized comorbidity. However, the association of cardiac alterations with epilepsy duration remains understudied. We sought to evaluate this association using electrocardiogram (ECG).
METHODS: We prospectively enrolled children between 1 months and 18 years of age without known cardiac conditions or ion channelopathies during routine clinic visits. ECGs were categorized as abnormal if there were alterations in rhythm; PR, QRS, or corrected QT interval; QRS axis or morphology; ST segment or T wave. An independent association between ECG abnormalities and epilepsy duration was evaluated using multivariable logistic regression modeling.
RESULTS: 213 children were enrolled. 100 ECGs (47%) exhibited at least one alteration; most commonly in the ST segment (37, 17%) and T wave (29, 11%). Children with normal ECGs had shorter epilepsy duration as compared to those with ECG abnormalities (46 [18-91] months vs. 73 [32-128 months], p = 0.004). A multivariable logistic regression model demonstrated that increasing epilepsy duration was independently associated with the presence of ECG abnormalities (OR=1.09, 95% CI=1.02-1.16, p = 0.008), adjusted for seizure frequency, generalized tonic-clonic/focal to bilateral tonic-clonic seizures as the predominant seizure type, and number of channel-modifying anti-seizure medications. Increasing epilepsy duration was also independently associated with the presence of ST/T wave abnormalities (OR=1.09, 95% CI=1.01-1.16, p = 0.017), adjusted for the same covariates.
CONCLUSIONS: Increasing epilepsy duration is independently associated with the presence of minor ECG abnormalities. Additional studies are needed to evaluate whether this finding may represent a manifestation of the \"epileptic heart\".

BACKGROUND: Sudden death is the leading cause of mortality in medically refractory epilepsy. Middle-aged persons with epilepsy (PWE) are under investigated regarding their mortality risk and burden of cardiovascular disease (CVD).
METHODS: Using UK Biobank, we identified 7786 (1.6%) participants with diagnoses of epilepsy and 6,171,803 person-years of follow-up (mean 12.30 years, standard deviation 1.74); 566 patients with previous histories of stroke were excluded. The 7220 PWE comprised the study cohort with the remaining 494,676 without epilepsy as the comparator group. Prevalence of CVD was determined using validated diagnostic codes. Cox proportional hazards regression was used to assess all-cause mortality and sudden death risk.
RESULTS: Hypertension, coronary artery disease, heart failure, valvular heart disease, and congenital heart disease were more prevalent in PWE. Arrhythmias including atrial fibrillation/flutter (12.2% vs 6.9%; P < 0.01), bradyarrhythmias (7.7% vs 3.5%; P < 0.01), conduction defects (6.1% vs 2.6%; P < 0.01), and ventricular arrhythmias (2.3% vs 1.0%; P < 0.01), as well as cardiac implantable electric devices (4.6% vs 2.0%; P < 0.01) were more prevalent in PWE. PWE had higher adjusted all-cause mortality (hazard ratio [HR], 3.9; 95% confidence interval [CI], 3.01-3.39), and sudden death-specific mortality (HR, 6.65; 95% CI, 4.53-9.77); and were almost 2 years younger at death (68.1 vs 69.8; P < 0.001).
CONCLUSIONS: Middle-aged PWE have increased all-cause and sudden death-specific mortality and higher burden of CVD including arrhythmias and heart failure. Further work is required to elucidate mechanisms underlying all-cause mortality and sudden death risk in PWE of middle age, to identify prognostic biomarkers and develop preventative therapies in PWE.

BACKGROUND: Sudden cardiac arrest results from cardiac electrical instability and is 3-fold more frequent in patients with chronic epilepsy than in the general population. We hypothesized that focal to bilateral tonic-clonic seizures (FTBTCS) would acutely impact T-wave alternans (TWA), a marker of cardiac electrical instability linked to an elevated risk for sudden cardiac death, more than focal seizures (FS) [focal aware seizures (FAS) and focal with impaired awareness seizures (FIAS)], due to their greater sympathetic stimulation of the heart. Since stress has been shown to cause significant TWA elevations in patients with heart disease, we also hypothesized that the early days of an inpatient admission to an epilepsy monitoring unit (EMU) would be associated with higher TWA levels compared to later hospital days in patients with chronic epilepsy, presumably due to stress.
METHODS: We analyzed the acute effects of seizures [FAS, FIAS, FTBTCS, and nonepileptic seizures (NES)] and day of hospital stay on TWA in 18 patients admitted to the EMU using high-resolution wireless electrocardiographic (ECG) patch monitors.
RESULTS: A total of 5 patients had FTBTCS, 7 patients had FS (2 FAS, 5 FIAS), and 3 patients had NES only during the index hospital stay. Four patients did not have any electroclinical seizures or NES. FTBTCS resulted in marked acute increases in ictal TWA from baseline (2 ± 0.3 µV) to ictal maximum (70 ± 6.1 µV, p < 0.0001), the latter exceeding the 60 µV cut point defined as severely abnormal. By comparison, while FAS and FIAS also provoked significant increases in TWA (from 2 ± 0.5 µV to 30 ± 3.3 µV, p < 0.0001), maximum ictal TWA levels did not reach the 47 µV cut point defined as abnormal. Heart rate increases during FTBTCS from baseline (62 ± 5.8 beats/min) to ictal maximum (134 ± 8.6 beats/min, an increase of 72 ± 7.2 beats/min, p < 0.02) were also greater (p = 0.014) than heart rate increases during FS (from 70 ± 5.2 beats/min to 118 ± 6.2 beats/min, an increase of 48 ± 2.6 beats/min, p < 0.03). In 3 patients with NES, TWA rose mildly during the patients\' typical episodes (from 2 ± 0.6 µV to 14 ± 2.6 µV, p < 0.0004), well below the cut point of abnormality, while heart rate increases were observed (from 75 ± 1.3 to 112 ± 8.7 beats/min, an increase of 37 ± 8.9 beats/min, p = 0.03). Patients with EEG-confirmed electroclinical seizures recorded while in the EMU exhibited significantly elevated interictal TWA maxima (61 ± 3.4 µV) on EMU admission day which were similar in magnitude to ictal maxima seen during FTBTCS (70 ± 6.1 µV, p = 0.21). During subsequent days of hospitalization, daily interictal TWA maxima showed gradual habituation in patients with both FS and FTBTCS but not in patients with NES only.
CONCLUSIONS: This is the first study to our knowledge demonstrating that FTBTCS acutely provoke highly significant increases in TWA to levels that have been associated with heightened risk for sudden cardiac death in other patient populations. We speculate that mortality temporally associated with FTBTCS may, in some cases, be due to sudden cardiac death rather than respiratory failure. In patients with EEG-confirmed epilepsy, hospital admission is associated with interictal TWA maxima that approach those seen during FTBTCS, presumably related to stress during the early phase of hospitalization compared to later in the hospitalization, indicating cardiac electrical instability and potential vulnerability to sudden cardiac death related to stress independent of temporal relationships to seizures. The elevated heart rates observed acutely with seizures and on hospital Day 1 are consistent with a hyperadrenergic state and the effect of elevated sympathetic output on a vulnerable cardiac substrate, a phenomenon termed \"the Epileptic Heart.\"