Heart Abnormalities Unlikely Behind Sudden Unexpected Deaths in Dravet, Study Says
Heart abnormalities are unlikely to be the reason behind the high rate of Sudden Unexpected Death in Epilepsy (SUDEP) in people with Dravet syndrome, a new study suggests, though further research is needed.
The study, “Cardiac arrhythmias in Dravet syndrome: an observational multicenter study,” was published in the Annals of Clinical and Translational Neurology.
SUDEP is the term for when a person with epilepsy, who is otherwise healthy, dies unexpectedly without an obvious cause. People with Dravet have a high risk of early epilepsy‐related death, of up to 15% by the age of 20. SUDEP is estimated to cause up to half of deaths in this patient population.
The underlying cause of SUDEP in people with Dravet is unclear, but multiple interconnecting factors are likely at play. Better understanding these factors could aid in the development of strategies to help prevent SUDEP.
Studies in mice have suggested that SUDEP might be related to heart rhythm abnormalities (arrhythmias). However, it’s unclear whether these findings might also translate to human disease.
The new study reports findings from a clinical trial (NCT02415686) in which people with Dravet wore electrocardiogram (ECG or EKG) devices to monitor their heartbeats. The devices were worn daily and continuously recorded data.
The study included 45 participants with Dravet (51% female, average age 19 years), representing 19,174 hours of EKG data, during which a total of 547 seizures occurred. The median number of recorded seizures per participant was seven (range 1–69).
For each Dravet patient, researchers identified two people who were similar in age and sex to serve as controls. The controls were identified from an EKG database and all had epilepsy unrelated to Dravet syndrome. Among 90 controls, 169 seizures were recorded, with a median of one seizure per control (range 1–8).
The most common seizure type recorded in the study was convulsive, followed by tonic.
Researchers looked for seizure-associated heart abnormalities that were more common among the Dravet patients than the controls. Such abnormalities could explain the comparatively high rate of SUDEP in Dravet.
Although some of the findings may warrant further study, the researchers found that none of the seizure-associated heart abnormalities could account for the comparatively high SUDEP rate in Dravet.
“Our analysis did not suggest any major peri‐ictal [seizure-related] cardiac arrhythmias which directly explain high SUDEP rates,” in Dravet syndrome, the researchers wrote.
Nonetheless, a few notable differences were found between the groups. For instance, seizure-related abnormally slow heart rate (bradycardia) was significantly more prevalent in the controls than in those with Dravet (6.5% vs. 0.7% of seizures).
Conversely, seizure-related QTc lengthening was more common in patients with Dravet (12%) than controls (4.7%). The heart works in cycles of pump, reset, pump again, reset again — conceptually, QTc lengthening refers to this cycle taking longer than normal. This lengthening has been linked to heart problems, though whether it plays a role in SUDEP is unclear from the available data.
The researchers also noted significantly lower heart rate variability (HRV) during seizures in patients with Dravet than controls. HRV is simply the variability in time from one heart beat to the next.
“Prospective data to determine whether QTc lengthening and decreased HRV can predict SUDEP risk in [Dravet syndrome] is warranted,” the researchers wrote, noting that “A 10‐year follow‐up of our cohort and additional analyses in case some succumbed to SUDEP will be performed.”