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Heart rate variability (HRV), in particular, reduced low frequency power (LFP), appears to be a biomarker for sudden unexpected death in epilepsy (SUDEP) when measured while individuals with epilepsy are awake, according to a study published online on December 14 in Neurology.

“Low HRV strongly predicts an increased risk of sudden death in heart disease patients and all-cause mortality in older adults,” wrote lead author Orrin Devinsky, MD, FAAN, an epileptologist and director of the Comprehensive Epilepsy Center at NYU Langone Health, and colleagues. “In epilepsy cohorts, reduced interictal HRV is associated with drug resistance and epilepsy chronicity and predicts less favorable outcomes after epilepsy surgery. We postulated that HRV could help identify patients at high risk for SUDEP who might benefit from more intensive epilepsy management interventions and risk mitigation strategies such as nocturnal monitoring.”

To determine the association between short-term heart rate variability and a patient’s risk of SUDEP, the researchers compared HRV in 31 SUDEP cases and 56 living epilepsy controls. The participants came from nine tertiary epilepsy monitoring units in Australia, Spain, New York, Pennsylvania, Ohio, Connecticut, and Maryland, making it the largest SUDEP biomarker study to date.

The cohort included patients admitted for video-EEG monitoring (VEM) between January 1, 2003, and December 31, 2014, and who subsequently died of SUDEP. Patients between 6 months and 65 years of age with at least one electroclinical seizure recorded during their VEM admission were included in the study. The study authors analyzed a five-minute interictal segment of stable ECG in both sleep and wakefulness conditions for each participant.

Of those who had died of SUDEP, the study authors found significantly reduced LFP during wakefulness. These patients also exhibited a shorter follow-up duration from their VEM admission compared with the epilepsy controls, with the time to SUDEP decreasing as LFP decreased. They found that each 1 percent incremental reduction in normalized LFP conferred a 2.7 percent decrease in the time to SUDEP.

The researchers noted that increased HFP in sleep in SUDEP was associated with increased duration of survival, indicating its cardioprotective role. The findings are particularly exciting, the study authors wrote, because HRV—a simple diagnostic measure of cardiac autonomic function—is inexpensive and readily available.

“Integration of HRV as a biomarker for SUDEP into multimodal risk stratification models may improve identification of patients at greatest SUDEP risk, allowing implementation of targeted interventions to mitigate this risk,” the study authors concluded.

Funding for the study was provided by Finding A Cure for Epilepsy and Seizures and the Australian National Health and Medical Research Council.

Dr. Daniel Friedman reported support from The Epilepsy Study Consortium, Axcella, Biogen, Cerevel, Crossject, Engage Pharmaceuticals, Lundbeck, Pfizer, SK Life Science, Xenon, Zynerba, Eisai and Neurelis Pharmaceuticals, Medtronics, Eisai, the Epilepsy Foundation, Centers for Disease Control and Prevention, National Institute of Neurological Disorders and Stroke, Empatica, Epitel, UCB, Neuropace, and Oxford University Press.

Dr. Shobi Sivathamboo reported support from a Bridging Postdoctoral Fellowship from Monash University, the Victorian Medical Research Acceleration Fund, Kaoskey, and Optalert.

Dr. Orrin Devinsky reported support from Finding a Cure for Epilepsy and Seizures, the National Institute of Neurological Disorders and Stroke, National Institute of Mental Health, Multidisciplinary University Research Initiatives, Centers for Disease Control and Prevention, and National Science Foundation.

SOURCE: NeurologyToday.com by Stephanie Specht

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