Genetic Testing Identifies Greater Inherited Sudden Cardiac Arrest Risk in Younger Individuals

Detecting inherited risk remains challenging, especially in individuals without obvious structural heart disease. A better understanding of how genetic susceptibility varies by age could help refine testing strategies for at-risk families. A new study shows that pathogenic variants associated with SCA are more common in younger individuals than in older adults.

Cedars-Sinai Medical Center’s Smidt Heart Institute (Los Angeles, CA, USA) analyzed the genetic architecture of SCA using whole genome sequencing (WGS) of individuals who experienced the event. WGS is a method that maps a person’s entire genetic code, enabling systematic detection of rare, damaging variants. The research highlights the need for broad genetic assessment to identify individuals and families at elevated risk.

The team examined blood samples from more than 3,000 people with SCA drawn from two community-based cohorts: the ongoing Oregon Sudden Unexpected Death Study and the Ventura Prediction of Sudden Death in Multi-Ethnic Communities study, spanning Portland, Oregon, and Ventura County, California. Investigators focused on rare, deleterious variants across 15 genes in which loss of normal function can increase the likelihood of SCA. They report that the prevalence of damaging variants decreases progressively with age.

Pathogenic variants were detected in 10% of individuals aged 29 years and younger, 7% of those 30–49 years, 4% of those 50–69 years, and 3% of those 70 years and older. In older adults, SCA more commonly reflects coronary artery narrowing or occlusion rather than a primary genetic arrhythmia substrate, according to the investigators. The authors note that SCA is fatal in 90% of cases. Findings were published in JACC: Clinical Electrophysiology, and the investigators indicated that additional research could uncover further genes implicated in SCA.

“If you have a family member who suffered sudden cardiac arrest, it is important to undergo genetic testing to determine if you harbor a genetic variant that increases your risk of sudden cardiac arrest or other heart conditions. For people who carry a variant linked to sudden cardiac arrest, a cardiologist can prescribe medications or lifestyle changes that can decrease the chances of experiencing this dangerous event,” said Evan Kransdorf, MD, Ph.D., assistant professor of Cardiology in the Smidt Heart Institute and first author of the study.

“This study is more representative of the U.S. population than other studies because it includes data from two communities rather than data from people already being seen at a medical center,” said Sumeet Chugh, MD, director of the Center for Cardiac Arrest Prevention at the Smidt Heart Institute and senior author of the study.

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Cedars-Sinai Medical Center’s Smidt Heart Institute