1. Heart Rate Variability in Patients with SCN Mutations and SUDEP
Ken Myers MD PhD FRCPC (Paeds Neuro)
Epilepsy Fellow – Austin Health, University of Melbourne

2. Faculty/Presenter Disclosure
Faculty: Ken Myers
Relationships with commercial interests: None.

3. Disclosure of Commercial Support
This program has not received financial or in-kind support from any commercial entities.
Potential for conflict of interest: None.

4. Mitigating Potential Bias
N/A

5. Heart Rate Variability
Various measures, including standard deviation over time or beat-to-beat variability
Common measure of beat-to-beat variability is root mean square of successive differences (rMSSD)
Typically, calculated automatically from Holter monitor or other cardiac monitoring device

6. Physiologic Significance
Parasympathetic
Sympathetic
HRV

7. Clinical Utility of HRV
Lower HRV values predictive of mortality in post-MI, CHF, and elderly (1-3)
HRV is lower in people with epilepsy, independent of medications
HRV even lower in Dravet syndrome (4)
HRV is disproportionately increased in sleep (5)
Kleiger et al 1987; (2) Nolan et al 1998; (3) Tsuji et al 1994;
(4) Delogu et al 2011; (5) Sivakumar et al 2016

8. HRV and SUDEP
HRV abnormalities hypothesized to explain SUDEP as partly due to autonomic dysregulation
2 cases demonstrated altered HRV prior to sudden death during VEM
HRV as a risk factor for SUDEP unclear

9. Hypothesis
Baseline HRV is lower in people with SCN-related epilepsy who die of SUDEP

10. How?

11. Methods
Reviewed EEGs of patients with SCN gene mutations and age-matched controls with refractory epilepsy
Manually extracted interbeat intervals from ECG derivation for 5 minute periods awake and in light sleep (if available)
Calculated rMSSD (primary outcome variable) and ratio of awake to sleep rMSSD

12. Results
31 patients with SCN mutations (30 SCN1A, 1 SCN2A), 20 of whom had sleep on EEG
Median age 7 years (range 6 months to 44 years)
2 definite SUDEP, 1 possible SUDEP*
* Nashef et al 2012

13. Results rMSSD Wilcoxon Rank Sum test Awake Sleep * p < 0.02
SCN Mutation Control
Wilcoxon Rank Sum test

14. Results * rMSSD Wilcoxon Rank Sum test * p < 0.02 Non-SUDEP SUDEP
SCN Mutation
Wilcoxon Rank Sum test

15. Results * rMSSD Sleep:Waking Ratio Wilcoxon Rank Sum test * p = 0.05
Non-SUDEP SUDEP
SCN Mutation
Wilcoxon Rank Sum test

16. Conclusions
No statistically significant difference in HRV between patients with SCN-related epilepsy when compared to other refractory epilepsy patients
HRV may have clinical utility as a biomarker of SUDEP risk

17. Acknowledgements Patients and families Alberta Children’s Hospital/
University of Calgary
Luis Bello-Espinosa
Robin Clegg
Jeffrey Buchhalter
Austin Health/
University of Melbourne
Ingrid Scheffer
Royal Hospital for Sick Children/
University of Glasgow
Joe Symonds
Sameer Zuberi

18. Interval between EEG and SUDEP
EEG at 14 years, died at 16 years
EEG at 20 months, died at 22 months
EEG at 17 months, died at 7.5 years

19. Age-HRV Relationship

20. SUDC during VEM