Evaluation of cardiac repolarization indices in well-controlled partial epilepsy: 12-Lead ECG findings

doi:10.1016/j.eplepsyres.2010.04.008

Epilepsy Research

Volume 90, Issues 1–2, June 2010, Pages 157-163

https://doi.org/10.1016/j.eplepsyres.2010.04.008 Get rights and content

Summary

Purpose

To evaluate the cardiac repolarization indices in terms of QT intervals in patients with well-controlled partial epilepsy.

Methods

Seventy-six adult patients with well-controlled partial epilepsy and 66 healthy controls were enrolled into the study. 12-Lead ECGs were obtained from all participants. Corrected QT (QTc) intervals including maximum QTc (QTmaxc), minimum QTc (QTminc) and QTc dispersion (QTcd) were calculated.

Results

QTmaxc and QTcd intervals were significantly longer in the epilepsy group when compared to control group (439 ± 27 ms vs. 422 ± 25 ms, p < 0.001 and 55 ± 18 ms vs. 41 ± 18 ms, p < 0.001). The proportion of patients with pathologically prolonged QTcd intervals (>50 ms) was significantly higher in the epilepsy group (25 of 76 vs. 7 of 66, p = 0.002). QTmaxc was significantly correlated with age (β = 0.29, p = 0.012) after adjusting for gender, body mass index and duration of epilepsy. No correlation was observed between the duration of epilepsy and any of the QT intervals. There were no significant differences between the subgroups regarding QT intervals according to the etiology of the seizures (symptomatic/cryptogenic), being on mono- or polytherapy and treatment regimens (carbamazepine/non-carbamazepine).

Conclusion

The results highlight the importance of cardiac evaluation even in patients with well-controlled epilepsy. 12-lead ECG recordings might help to uncover serious cardiovascular events.

Introduction

The recognition of a causal relationship between seizures and cardiac deaths has led to a considerable interest in seizure-related cardiac abnormalities. Available data suggest that patients with epilepsy are subject to potentially serious cardiac rhythm abnormalities not only during seizures but also during the interictal period (Ryvlin et al., 2006, Scorza et al., 2008). It is probable that cardiac repolarization pathologies during and between seizures play a potential role in sudden cardiac death (Stollberger and Finsterer, 2004, Ryvlin et al., 2006, Scorza et al., 2008). As fatal arrhythmias can be encountered even in patients without an underlying cardiac disease, being familiar to cardiac repolarization indices in epileptic patients will be beneficial (Schuele, 2009).

Previous studies suggest that epilepsy patients have an increased risk for sudden cardiac death (Nei, 2009, Neufeld et al., 2009, Surges et al., 2009). However to the best of our knowledge, cardiac repolarization abnormalities based on 12-lead ECG recordings have not been documented previously in adult patients with well-controlled partial epilepsy. Therefore we investigated this particular patient population and speculated that these pathologies might also occur in individuals with well-controlled partial epilepsy and possibly predispose them to life-threatening arrhythmias.

Section snippets

Subjects

This prospectively designed study was conducted in Neurology and Cardiology Departments of Selcuk University Meram School of Medicine with the approval of the Institutional Ethics Committee. Informed consent was obtained from all participants. The study population included 76 patients and 66 healthy controls. The groups were well matched for age, gender and body mass index (BMI), all of which are known to influence the cardiac repolarization indices (Tran et al., 2001, Bezante et al., 2007, Li

Statistics

Continuous variables were expressed as mean ± SD. Dichotomous variables were tested with Pearson's chi-square test. The two-sided independent samples t-test was used to test the significance of the differences between the groups. For multiple testing, the Bonferroni–Holm test was used. Simple relations between age, epilepsy duration and cardiac repolarization indices were studied by using the Pearson correlation, whereas multiple stepwise regressions were performed to control for confounders.

Patient characteristics

The demographics of the subjects are shown in Table 1. Cranial neuroimaging (8 patients had CT and 68 patients had MRI) was available in all individuals in the patient population. Twenty-seven of the patients (35.5%) had an abnormal neuroimaging; the etiologies included cerebral infarct (n = 6), posttraumatic encephalomalasia (n = 5), mesial temporal sclerosis (n = 4), venous angioma (n = 4), intracranial mass (n = 3), hamartoma (n = 2), cavernous angioma (n = 2) and neurosarcoidosis (n = 1). Thirty-two

Discussion

In this study we present four major findings: (i) in epileptic patients QTmaxc and QTcd intervals are significantly longer when compared to the individuals in the control group, (ii) the proportion of individuals who display pathologic QTcd intervals are significantly higher in the epilepsy group, (iii) while increased age is associated with longer QTcd intervals, there are no correlations between any of the QT intervals with the duration of the disease, (iv) etiology of the seizures

Conclusion

Albeit the limitations of our study include the lack of the evaluation of autonomic functions and AEDs in detail, the results highlight the importance of cardiac evaluation even in patients with well-controlled epilepsy. Routine electrocardiographic evaluations may uncover serious cardiovascular pathologies and may be helpful in preventing adverse cardiovascular events in epilepsy patients.

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People with epilepsy (PWE) are at increased risk for premature death due to many factors. Sudden unexpected death in epilepsy (SUDEP) is among the most important causes of death in these individuals and possibly, sudden cardiac death (SCD) in epilepsy is also as important. The possibility of concurrent derangement in electrical and mechanical cardiac function, which could be a marker of early cardiac involvement in PWE, has not been investigated in that population.
Electrical dispersion indices (T-wave peak to T-wave end, TpTe; QT dispersion, QTd; QT interval corrected for heart rate, QTc) were analyzed in patients with pharmacoresistant temporal lobe epilepsy and compared to a control group. The electromechanical relationship between those indices and echocardiographic parameters were further assessed in PWE.
In 19 PWE and 21 controls, we found greater TpTe and QTd in PWE (TpTe: 91.6 ± 16.4 ms vs. 65.2 ± 12.1 ms, p < 0.0001; and QTd: 45.3 ± 13.1 ms vs. 19 ± 6.2 ms, p < 0.0001, respectively). QTc was similar between PWE and controls (419.2 ± 31.4 ms vs. 435.1 ± 31.4 ms, p = 0.12). In multivariate linear regression, TpTe, QTc, and epilepsy duration were related to left ventricular mass; QTc was associated with left atrial volume; QTc, the number of seizures per month, epilepsy duration and antiseizure medication explained 81% of E/A mitral wave Doppler ratio.
This is the first report to demonstrate concurrent electrical dispersion and diastolic dysfunction in PWE. These noninvasive biomarkers could prove useful in early detection of the “Epileptic Heart” condition.
QT interval alterations in epilepsy: A thorough investigation between epilepsy subtypes
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Cardiac disturbances and rhythm abnormalities which potentially lead sudden unexpected death in epilepsy, have been extensively studied in focal epilepsies. However, studies including generalized epilepsies are scarce and it is not clear whether electrocardiogram parameters reflecting vulnerability to ventricular arrhythmias differ between these groups.
Medical records of patients who were followed in epilepsy department of a tertiary center between October 2015 and September 2016 were retrospectively reviewed. 66 generalized and 64 focal epilepsy patients with eligible electrophysiological data were analyzed. QTc interval, QTcd and other electrocardiographic indices were compared between patients with focal vs generalized epilepsy. Another analysis was performed in order to disclose any difference between patients with epilepsy (n:130) and psychogenic non-epileptic seizures. A two-tailed p value < 0.05 was considered significant.
There was no difference in terms of QTc and QTcd between patients with focal and generalized epilepsy [median: 406 ms vs 404 ms, p = 0.119; and median: 46 ms vs 44 ms, p = 0.497, respectively]. However patients with epilepsy were found to have longer QTc and QTcd when compared to ones with psychogenic non-epileptic seizures (p = 0.035 and p < 0.001, respectively).
Current findings demonstrate that patients with epilepsy have longer QTc and QTcd than patients with pure psychogenic non-epileptic seizures. Since there was no difference between patients with focal and generalized epilepsy; QTc interval, QTcd and potential susceptibility to cardiac arrhythmias as a result, could be a consequence of epilepsy itself regardless of origin.
Evaluation of QT dispersion in epileptic patients and its association with SUDEP risk
2022, Epilepsy Research
Mortality in epileptic patients was attributed to sudden unexpected death in epilepsy (SUDEP). The precise pathophysiology of SUDEP is not fully understood, yet prolongation of ventricular repolarization particularly QTc interval suggested to be one of the contributing risk factor for SUDEP.
We aimed at evaluation of QTc and QT dispersion (QTD) in patients with epilepsy (both refractory and well-controlled epilepsy) and their association with the epileptic severity and sudden unexplained death (SUDEP) risk.
The study included eighty epileptic patients (40 controlled epileptic patients and 40 refractory epileptic patients) compared to thirty non-epileptic volunteers as the control group (patients with history of cardiovascular comorbidities or exposure to antiarrhythmic drugs were excluded from the study). All participants were subjected to clinical evaluation including detailed epileptic history with assessment of SUDEP 7 risk, severity scale, 12 leads surface ECG to measure QTc & QTD, 24 h Holter monitoring to assess heart rate variability (HRV) parameters.
Controlled and refractory epileptic patients demonstrated increased average QTc and QTD values compared to control group (450.1 ± 18.9 vs. 412.3 ± 12.3 ms, p < 0.0001, 452.1 ± 19.0 vs. 412.3 ± 12.3 ms, p < 0.0001 respectively) (45.6 ± 14.9 vs. 15.4 ± 6.8 ms, p < 0.001, 70.6 ± 18.1 vs. 15.4 ± 6.8 ms, p < 0.0001 respectively). Refractory epileptic patients had a significantly higher incidence of abnormal QTD > 50 ms compared to controlled epileptic patients (32.5% vs. 90%, p < 0.005). Refractory epileptic patients with generalized form had significantly higher severity scale in addition to significantly impaired rMSSD and pNN50 compared to those with focal form (1072.7 ± 722.7 vs. 429.1 ± 180.4, p < 0.03, 17.11 ± 4.6 vs. 26.4 ± 7.9 ms, p < 0.004 and 2.9 ± 1.8 vs. 7.8 ± 4.1%, p < 0.003 respectively). Among refractory epileptic patients, the duration of epilepsy, rMSSD and QTD significantly correlated with SUDEP-7 risk (r² =0.199, p < 0.005, r² =0.623, p < 0.0001 and r²⁼0.44, p < 0.0001 respectively).
The current study stands out the importance of evaluating QTc and QTD in 12-lead ECG recordings in epileptic patients and signifying their association with SUDEP-7 risk among refractory epileptic patients.
Interictal cardiac repolarization abnormalities in people with epilepsy
2018, Epilepsy and Behavior
Citation Excerpt :
In contrast, Locati et al. [38] in their study on QTc prolongation, reported that 70% of the patients were women but it was presented earlier in men. In people with epilepsy, contradictory results are found regarding the correlation of pathological QTc dispersion (QTcd) and QT interval with advancing age [13–15]. In our patients, age was an independent significant risk factor for QTc prolongation (for every one-year increase in age, the risk of QTc prolongation increased by 2.7%).
The occurrence of cardiac electrical abnormalities such as repolarization disorders in patients with epilepsy was previously documented and may, in part, clarify the mechanism of sudden unexpected death in those patients. The aim of this study was to investigate the frequency of cardiac repolarization disorders among patients with epilepsy and whether specific demographic- or disease-related features were associated with their occurrence.
This cross-sectional study was carried out on 1000 subjects with epilepsy who were compared with age- and sex-matched 2500 subjects without epilepsy. Clinical assessment, which included careful history taking and examination, was carried out for all participants in addition to resting 12-lead electrocardiogram (ECG) recording. Electrocardiograms were reviewed by experienced cardiologists. Electrocardiogram intervals were measured, and morphological abnormalities were identified using standard guidelines.
Repolarization abnormalities were found in 142 (14.2%) patients with epilepsy. A statistically significant elevation in percentage of corrected QT interval (QTc) prolongation (both severe and borderline) among patients with epilepsy compared with controls was documented (8.4% vs 2%, P < 0.001). Epilepsy increased the likelihood of hosting prolonged QTc more than 4 times (95% confidence interval: 3.175–6.515; odds ratio: 4.548; P < 0.001). Affected patients were significantly older (95% confidence interval: 1.012–1.044; odds ratio: 1.027; P = 0.001), and the abnormality was significantly more prevalent among those with poor seizure control (95% confidence interval: 1.103–2.966; odds ratio: 1.809; P = 0.019). On the other hand, early repolarization (ER) pattern and Brugada type ECG pattern (BP) were significantly more prevalent in subjects without epilepsy.
Corrected QT interval prolongation (both severe and borderline) was more prevalent among patients with epilepsy, especially if uncontrolled or elderly. Electrocardiogram should be established as a part of the diagnostic workup of epilepsy in order to identify such electrocardiographic abnormality.
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The systemic consequences of seizure activity can be significant. An understanding of specific cardiorespiratory or other systemic consequences, their relations to seizure activity, and contributions to severe outcomes, such as sudden death, depends upon measurements of a variety of systemic parameters. We review a number of approaches to monitoring cardiorespiratory and other systemic physiology during seizures, and the specific animal models that have been developed to access these measures. Pharmacological strategies to manipulate measurements and postmortem measurements are also discussed. The range of results presented highlight the value of the animal model as a tool that can be manipulated to explore fundamental questions about the impact of seizures on the body.
Determining factors of electrocardiographic abnormalities in patients with epilepsy: A case-control study
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Citation Excerpt :
Additionally, more prolonged QTc values were also observed in the post-ictal period (ECG 2 h after a seizure) of a pediatric population with epilepsy (Kändler et al., 2005). A long list of medications are implicated in prolonging QT, including anesthetics, antibiotics, antidepressants, antipsychotics, lithium, CNS stimulants, bronchodilators, antihistamines, anti-arrhythmics, antineoplasics, and also ketogenic diet (Best et al., 2000; Dogan et al., 2010). Among our patients, more prolonged QTc was independently associated with AEDs polytherapy.
Sudden unexpected death in epilepsy (SUDEP) is a major cause of mortality in young patients with epilepsy (PWE). Although its mechanisms are still poorly understood, they may include cardiorespiratory dysfunction. Standard 12-lead electrocardiograms (ECGs) were obtained from 62 consecutive patients (aged 18–66y) with a definite diagnosis of epilepsy, without seizures at the day of ECG, and 57 healthy controls matched for sex, age and body mass index (BMI). All ECGs were evaluated by a blinded board-certified cardiologist. Patients with symptomatic focal epilepsy represented 90.3% (N = 56), of whom 56.4% (N = 35) had temporal lobe epilepsy, with a mean duration of 22.02 ± 14.96 years of epilepsy. We observed more prolonged P-wave (p < 0.0001) and PR interval (p = 0.01) in patients than in controls. Additionally, longer QT intervals (p < 0.01), pathologic QT dispersion (p < 0.01) and left atrial overload (p < 0.01) were more common in PWE. Multiple linear regression analysis evidenced age, gender and polytherapy as factors associated with altered ECG. Therefore, routine ECG should be requested in PWE, especially for males, increasing age and in polytherapy. Findings such as longer PR and QT interval, and pathologic QT dispersion, may reflect cardiac structural changes and/or autonomic nervous system dysfunction and indicate a risk for SUDEP.

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Evaluation of cardiac repolarization indices in well-controlled partial epilepsy: 12-Lead ECG findings

Summary

Purpose

Methods

Results

Conclusion

Introduction

Section snippets

Subjects

Statistics

Patient characteristics

Discussion

Conclusion

Int. J. Cardiol.

Prog. Cardiovasc. Dis.

Seizure

Epilepsy Behav.

Am. J. Cardiol.

Epilepsy Res.

Electroencephalogr. Clin. Neurophysiol.

J. Electrocardiol.

Epilepsy Res.

Epilepsy Res.

Clinics (Sao Paulo)

Epilepsy Res.

Seizure

Seizure

Seizure

Seizure

Increased QT dispersion in epileptic children

Acta Paediatr.

Interictal cardiovascular autonomic responses in patients with temporal lobe epilepsy

Epilepsia

Comparison of formulae for heart rate correction of QT interval in exercise electrocardiograms

Pacing Clin. Electrophysiol.

Individual patterns of QT/RR relationship

Card Electrophysiol. Rev.

An analysis of time relations of electrocardiograms

Heart

Biliopancreatic diversion reduces QT interval and dispersion in severely obese patients

Obesity (Silver Spring)

Lengthening of corrected QT during epileptic seizures

Epilepsia

Cardiac effects of carbamazepine therapy

Minerva Cardioangiol.

Rufinamide: pharmacology, clinical trials, and role in clinical practice

Int. J. Clin. Pract.

Proposal for revised classification of epilepsies and epileptic syndromes

Epilepsia

Assessment of ventricular repolarization from body-surface ECGs in humans

QT dispersion: an indicator of arrhythmia risk in patients with long QT intervals

Br. Heart J.

Primidone in the treatment of the long QT syndrome: QT shortening and ventricular arrhythmia suppression

Ann. Intern. Med.

Collagen accumulation in heart ventricles as a function of growth and aging

Cardiovasc. Res.