Genetic Markers of Cardiovascular Disease in Epilepsy

Genetic Markers of Cardiovascular Diseases and the Potential Role in Sudden Unexpected Death in Epilepsy.

Epilepsy is a common condition which affects over 3 million people in the US. Patients with uncontrolled epilepsy have a lifetime risk of sudden unexpected death (SUDEP) of 35%, which is greatest in those under 40 years of age. The exact mechanisms and causes are not understood but can be due to underlying conditions which affect the heart and brain, which may lead to dangerous heart rhythms and death. Some of these conditions which affect heart and brain have an identifiable genetic cause. This study aims to identify known genetic causes of heart rhythm and sudden death related disorders in patients with epilepsy.

Study Overview

• Status: Recruiting
• Conditions: Epilepsy; Syncope; Seizures; Cardiomyopathies; Channelopathy

Detailed Description

The overall goals are to determine whether patients with epilepsy who have the highest risk of SUDEP have an underlying genetic cardiovascular disorder. The investigators are seeking patients with epilepsy who have a high risk of SUDEP identified by using a risk scoring tool called SUDEP-7 and/or have blood-relatives with a history of epilepsy, seizure, cardiac arrest, sudden death, drowning/near-drowning, syncope or heart rhythm disorder. The investigators may also include blood-relatives of patients with epilepsy and invite them to participate by providing a blood sample and/or buccal cells (from a swab or saliva) for genetic testing.

• Study Type: Observational
• Enrollment (Estimated): 600

Contacts and Locations

• Study Contact: Name: Somers CPL Lab; Email: CPL@mayo.edu

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
      • Sub-Investigator: Erik K St. Louis, MD
      • Sub-Investigator: Anwar A Chahal, MD MRCP
      • Sub-Investigator: Michael J Ackerman, MD PhD
      • Sub-Investigator: Peter A Brady, MD FRCP FHRS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Men and women diagnosed with epilepsy or seizures or unexplained syncope and blood relatives.

Description

Inclusion Criteria:

• Adults ages 18 - 50 with a diagnosis of epilepsy or seizures, or syncope or drowning or cardiac arrest or sudden death or an abnormal ECG suggestive of an arrhythmia
• Blood-relatives (Aged 18+) of a patient with a history of epilepsy, seizure, cardiac arrest, sudden death, drowning, syncope or arrhythmia

Exclusion Criteria:

• Those who are unable to provide written consent.
• Prisoners (vulnerable population)
• Seizures secondary to ischemic events
• Traumatic brain injury resulting in seizures
• History of cranial surgery
• History of brain tumor

Study Plan

How is the study designed?

Design Details

• Observational Models: FAMILY_BASED
• Time Perspectives: PROSPECTIVE

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
High SUDEP risk cohort; Patients with epilepsy who have a high SUDEP-7 risk score and/or a blood-relative with epilepsy, seizure, cardiac arrest, sudden death, drowning/near-drowning, syncope or arrhythmia.
Low SUDEP risk cohort; Patients with epilepsy and a low SUDEP-7 score.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Using Next Generation Whole-Exome Sequencing, determine if an underlying genetic cardiac mutation is present in refractory epilepsy patients who are at highest risk of sudden death.	SUDEP-7 is a risk profiling tool, with a score ranging from 0-12. Generally, a score greater than or equal to 3 is considered high risk. The investigators will select participants with a family history of epilepsy, seizures, cardiac arrest, sudden death, drowning, syncope or arrhythmia, as this markedly increases genetic yield. Next Generation Whole-Exome Sequencing will be performed with a focus on known genes implicated in sudden unexpected death syndromes (channelopathies, cardiomyopathies and aortopathies) and autonomic control. Where relevant, blood-relatives may be invited for genomic 'trio' analyses.	3-5 years

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: American Heart Association
• Investigators: Principal Investigator: Virend K. Somers, MD PhD, Mayo Clinic

Study record dates

Study Major Dates

• Study Start: May 1, 2016
• Primary Completion (Estimated): December 1, 2031
• Study Completion (Estimated): December 1, 2031

Study Registration Dates

• First Submitted: June 22, 2016
• First Submitted That Met QC Criteria: July 2, 2016
• First Posted (Estimated): July 7, 2016

Study Record Updates

• Last Update Posted (Actual): November 3, 2026
• Last Update Submitted That Met QC Criteria: October 30, 2026
• Last Verified: October 1, 2026

More Information

Terms related to this study

• Keywords: Sleep; Sudden Cardiac Death; SUDEP; Long QT syndrome; Brugada; Catecholaminergic Polymorphic Ventricular Tachycardia; Sudden Cardiac Arrest; Sudden Unexpected Death in Epilepsy; Ion channel disease
• Additional Relevant MeSH Terms: Cardiac Conduction System Disease; Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Neurobehavioral Manifestations; Death; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Defects, Congenital; Heart Arrest; Death, Sudden; Consciousness Disorders; Unconsciousness; Tachycardia, Ventricular; Tachycardia; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Sudden Unexpected Death in Epilepsy; Cardiomyopathies; Epilepsy; Seizures; Death, Sudden, Cardiac; Long QT Syndrome; Syncope; Channelopathies; Polymorphic Catecholaminergic Ventricular Tachycardia
• Other Study ID Numbers: 15-002420