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Observational Study
. 2020 Apr;7(4):462-473.
doi: 10.1002/acn3.51017. Epub 2020 Mar 24.

Cardiac arrhythmias in Dravet syndrome: an observational multicenter study

Sharon Shmuely  1   2 , Rainer Surges  3   4 , Robert M Helling  1 , W Boudewijn Gunning  1 , Eva H Brilstra  5 , Judith S Verhoeven  6 , J Helen Cross  7 , Sanjay M Sisodiya  2   8 , Hanno L Tan  9   10 , Josemir W Sander  1   2   8 , Roland D Thijs  1   2   11
Affiliations
Observational Study

Cardiac arrhythmias in Dravet syndrome: an observational multicenter study

Sharon Shmuely et al. Ann Clin Transl Neurol. 2020 Apr.

Abstract

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); peri-ictal 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.

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Conflict of interest statement

RS reports personal fees from UCB Pharma, EISAI, Cyberonics, Bial, Desitin, and LivaNova, RS is member of the editorial board of Epilepsy and Behavior and Epilepsia Open. JWS reports personal fees from UCB and Zogenix, grants from UCB, Eisai, UCB, GW Pharma. JWS's current position is endowed by the Epilepsy Society, he is a member of the Editorial Board of the Lancet Neurology and receives research support from the Marvin Weil Epilepsy Research Fund. JHC reports grants from GW Pharma, Zogenix, Marinius, Vitaflo, Nutricia, and National Institute for Health Research Biomedical Centre at Great Ormond Street Hospital for Children NHS Foundation trust. SS reports personal fees from UK Epilepsy Society. BG reports personal fees from GW Pharmaceuticals, Zogenix, and OVID/Takeda. RDT reports personal fees from UCB, GSK, Theravance, Novartis and Medtronic and grants from Nuts OHRA Foundation, Medtronic, AC Thomson Foundation and The Netherlands Organisation for Health Research and Development (ZonMW). RDT is a member of the editorial board of Seizure, Epilepsia and Clinical Autonomic Research. The remaining authors have no conflicts of interest relevant to this research.

Figures

Figure 1
Figure 1
Study flowchart.
Figure 2
Figure 2
Hours ECG, number of recorded seizures, and proportion unreported seizures for each Dravet syndrome case.
Figure 3
Figure 3
Box plots of peri‐ictal heart rates in convulsive seizures of the Dravet syndrome and historical epilepsy control groups. T1 = time of seizure onset; T2 = seizure end; T3 = two minutes after T2; T4 = 5 min after T2; * significance P < 0.05. Median (solid line), mean (plus sign), interquartile interval (box), minimum, maximum (whiskers, 1.5 IQR), and suspected outliers (dots) are shown. Generalized estimating equation linear models were used to compare heart rates between the groups, correcting for within‐subject correlation and seizure onset from sleep or wakefulness.
Figure 4
Figure 4
Heart rate curve during a convulsive seizure of a 14‐year‐old girl with Dravet syndrome from 1 min prior to seizure onset to 5 min after seizure end. T1 = time of seizure onset; T2 = seizure end; T3 = 2 min after T2; T4 = 5 min after T2.
See this image and copyright information in PMC

References

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