Heart rate variability in epilepsy: A potential biomarker of <scp>sudden unexpected death in epilepsy</scp> risk

Myers, Kenneth A.; Bello-Espinosa, Luis; Symonds, Joseph D.; Zuberi, Sameer M.; Clegg, Robin; Sadleir, Lynette G.; Buchhalter, Jeffrey; Scheffer, Ingrid E.

doi:10.1111/epi.14438

Cited by 122 publications

(91 citation statements)

References 37 publications

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“…90 Recently, one group showed that heart rate variability was decreased among cases of SUDEP versus individuals with epilepsy, indicating autonomic dysfunction. 8 This was consistent with earlier evidence of a correlation between SUDEP risk and lower RMSSD (Root Mean Square of Successive Differences), reflecting depressed vagal modulation of heart rate variability. 91 However, other studies comparing suspected SUDEP cases with matched epilepsy controls revealed no difference in resting ECG measures or heart rate variability.…”

Section: Clinical Significance Of Altered Cardiac Ion Channel Expresupporting

confidence: 91%

“…Similarly, QTc dispersion (variability) was found to incrementally increase the risk of sudden cardiac death . Recently, one group showed that heart rate variability was decreased among cases of SUDEP versus individuals with epilepsy, indicating autonomic dysfunction . This was consistent with earlier evidence of a correlation between SUDEP risk and lower RMSSD (Root Mean Square of Successive Differences), reflecting depressed vagal modulation of heart rate variability .…”

Section: Clinical Significance Of Altered Cardiac Ion Channel Expresssupporting

confidence: 79%

“…As with ictal studies, interictal prolongation of the QTc interval has been reported, especially among individuals with poor seizure control . Elevated sympathetic tone and decreased parasympathetic tone are also evident upon interrogation of heart rate variability, with a more severe dysautonomia noted in cases of SUDEP . Furthermore, echocardiographic features of systolic and diastolic dysfunction highlight the functional consequences of myocardial damage secondary to repetitive ictal activity .…”

Section: Introductionmentioning

confidence: 95%

“…6 Elevated sympathetic tone and decreased parasympathetic tone are also evident upon interrogation of heart rate variability, with a more severe dysautonomia noted in cases of SUDEP. 7,8 Furthermore, echocardiographic features of systolic and diastolic dysfunction highlight the functional consequences of myocardial damage secondary to repetitive ictal activity. [9][10][11] Together, these abnormalities may reflect a degree of underlying cardiac pathology in epilepsy.…”

Section: Introductionmentioning

confidence: 99%

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Acquired cardiac channelopathies in epilepsy: Evidence, mechanisms, and clinical significance

O’Brien

Todaro

et al. 2019

Epilepsia

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There is growing evidence that cardiac dysfunction in patients with chronic epilepsy could play a pathogenic role in sudden unexpected death in epilepsy (SUDEP). Recent animal studies have revealed that epilepsy secondarily alters the expression of cardiac ion channels alongside abnormal cardiac electrophysiology and remodeling. These molecular findings represent novel evidence for an acquired cardiac channelopathy in epilepsy, distinct from inherited ion channels mutations associated with cardiocerebral phenotypes. Specifically, seizure activity has been shown to alter the messenger RNA (mRNA) and protein expression of voltage‐gated sodium channels (Nav1.1, Nav1.5), voltage‐gated potassium channels (Kv4.2, Kv4.3), sodium‐calcium exchangers (NCX1), and nonspecific cation‐conducting channels (HCN2, HCN4). The pathophysiology may involve autonomic dysfunction and structural cardiac disease, as both are independently associated with epilepsy and ion channel dysregulation. Indeed, in vivo and in vitro studies of cardiac pathology reveal a complex network of signaling pathways and transcription factors regulating ion channel expression in the setting of sympathetic overactivity, cardiac failure, and hypertrophy. Other mechanisms such as circulating inflammatory mediators or exogenous effects of antiepileptic medications lack evidence. Moreover, an acquired cardiac channelopathy may underlie the electrophysiologic cardiac abnormalities seen in chronic epilepsy, potentially contributing to the increased risk of malignant arrhythmias and sudden death. Therefore, further investigation is necessary to establish whether cardiac ion channel dysregulation similarly occurs in patients with epilepsy, and to characterize any pathogenic relationship with SUDEP.

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Section: Clinical Significance Of Altered Cardiac Ion Channel Expresupporting

confidence: 91%

Section: Clinical Significance Of Altered Cardiac Ion Channel Expresssupporting

confidence: 79%

Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Acquired cardiac channelopathies in epilepsy: Evidence, mechanisms, and clinical significance

O’Brien

Todaro

et al. 2019

Epilepsia

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“…It is possible to find numerous works in which these signals are used to detect stress, emotions, and activity in the literature. The ECG signal is used in some papers such as [23], where the obtained results suggest that positive emotions lead to alterations in HRV, which may be beneficial in some illness treatment [19,31,32].…”

mentioning

confidence: 99%

Activity Recognition Using Wearable Physiological Measurements: Selection of Features from a Comprehensive Literature Study

Mohíno-Herranz

Gil-Pita

Rosa-Zurera

et al. 2019

Sensors

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Activity and emotion recognition based on physiological signal processing in health care applications is a relevant research field, with promising future and relevant applications, such as health at work or preventive care. This paper carries out a deep analysis of features proposed to extract information from the electrocardiogram, thoracic electrical bioimpedance, and electrodermal activity signals. The activities analyzed are: neutral, emotional, mental and physical. A total number of 533 features are tested for activity recognition, performing a comprehensive study taking into consideration the prediction accuracy, feature calculation, window length, and type of classifier. Feature selection to know the most relevant features from the complete set is implemented using a genetic algorithm, with a different number of features. This study has allowed us to determine the best number of features to obtain a good error probability avoiding over-fitting, and the best subset of features among those proposed in the literature. The lowest error probability that is obtained is 22.2%, with 40 features, a least squares error classifier, and 40 s window length.

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Cardiac arrhythmias in Dravet syndrome: an observational multicenter study

Shmuely

Surges

Helling

et al. 2020

Ann Clin Transl Neurol

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Objectives: We ascertained the prevalence of ictal arrhythmias to explain the high rate of sudden unexpected death in epilepsy (SUDEP) in Dravet syndrome (DS). Methods: We selected cases with clinical DS, ≥6 years, SCN1A mutation, and ≥1 seizure/week. Home-based ECG recordings were performed for 20 days continuously. Cases were matched for age and sex to two epilepsy controls with no DS and ≥1 major motor seizure during video-EEG. We determined the prevalence of peri-ictal asystole, bradycardia, QTc changes, and effects of convulsive seizures (CS) on heart rate, heart rate variability (HRV), and PR/QRS. Generalized estimating equations were used to account for multiple seizures within subjects, seizure type, and sleep/wakefulness. Results: We included 59 cases. Ictal recordings were obtained in 45 cases and compared to 90 controls. We analyzed 547 seizures in DS (300 CS) and 169 in controls (120 CS). No asystole occurred. Postictal bradycardia was more common in controls (n = 11, 6.5%) than cases (n = 4, 0.7%; P = 0.002). Peri-ictal QTc-lengthening (≥60ms) occurred more frequently in DS (n = 64, 12%) than controls (n = 8, 4.7%, P = 0.048); pathologically prolonged QTc was rare (once in each group). In DS, interictal HRV was lower compared to controls (RMSSD P = 0.029); periictal values did not differ between the groups. Prolonged QRS/PR was rare and more common in controls (QRS: one vs. none; PR: three vs. one). Interpretation: We did not identify major arrhythmias in DS which can directly explain high SUDEP rates. Peri-ictal QTc-lengthening was, however, more common in DS. This may reflect unstable repolarization and an increased propensity for arrhythmias. 462

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Heart rate variability in epilepsy: A potential biomarker of sudden unexpected death in epilepsy risk

Cited by 122 publications

References 37 publications

Acquired cardiac channelopathies in epilepsy: Evidence, mechanisms, and clinical significance

Acquired cardiac channelopathies in epilepsy: Evidence, mechanisms, and clinical significance

Activity Recognition Using Wearable Physiological Measurements: Selection of Features from a Comprehensive Literature Study

Cardiac arrhythmias in Dravet syndrome: an observational multicenter study

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