Gene sequencing may identify rare pathogenic DNA variants or likely pathogenic variants in a "small but potentially important" population of adults suffering from sudden cardiac death, according to a study published Nov. 11 in the Journal of the American College of Cardiology, which will be presented during AHA 2019 in Philadelphia, PA.

Amit V. Khera, MD, MSc, et al., performed whole exome sequencing in 600 adults with onset sudden cardiac death and 600 matched controls from 106,098 participants of six prospective cohort studies. Observed DNA variants in any of the 49 genes with known association to cardiovascular disease were then classified as pathogenic or likely pathogenic. Then, in an independent population of 4,525 asymptomatic adults in a prospective cohort study, Khera et al., performed whole genome sequencing and determined the number of pathogenic or likely pathogenic variants.

Results showed that among the 1,200 sudden cardiac death cases and controls, 5,178 genetic variants were identified and 14 variants were classified as pathogenic or likely pathogenic. Further, the 14 variants were present in 15 individuals who had suffered sudden cardiac death, "corresponding to a pathogenic variant prevalence of 2.5 percent in cases and 0 percent in controls (p<0.0001)." In addition, among the participants of the prospective cohort study group, "41 (0.9 percent) carried a pathogenic or likely pathogenic variant and these individuals had 3.24-fold higher risk of cardiovascular death over a median follow-up of 14.3 years (p=0.02)."

The authors conclude that "gene sequencing confirms significant enrichment of pathogenic variants in sudden cardiac death cases as compared to controls, and such variants are present in approximately 1 percent of asymptomatic adults free of known cardiovascular disease." They add that moving forward, "these results lay the scientific foundation for the integration of gene sequencing to identify asymptomatic individuals with pathogenic variants into routine clinical practice, with the ultimate goal of preventing a sudden cardiac death tragedy that might have been anticipated."

Clinical Topics: Arrhythmias and Clinical EP, SCD/Ventricular Arrhythmias

Keywords: AHA Annual Scientific Sessions, AHA19, Exome, Prevalence, Follow-Up Studies, Prospective Studies, Death, Sudden, Cardiac, DNA

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