Sudden Arrhythmic Death During Exercise: A Post-Mortem Genetic Analysis

Area of Science:

• Cardiology
• Genetics
• Forensic Pathology

Background:

• Sudden cardiac death (SCD) is an unexpected death within 1 hour of symptom onset, often during exercise.
• Myocardial infarction is a common cause, but some SCD cases, especially in young individuals, are attributed to cardiomyopathies or remain unexplained.
• Genetic alterations are increasingly recognized as potential underlying causes of fatal arrhythmias in these cases.

Purpose of the Study:

• To investigate genetic predispositions in a cohort of individuals who experienced sudden cardiac death during exercise.
• To identify genetic variants in cases with structurally normal hearts classified as arrhythmogenic death.

Main Methods:

• Analysis of 52 post-mortem samples from individuals under 50 years old with negative autopsies.
• Utilized next-generation sequencing to screen genes associated with sudden cardiac death.

Main Results:

• The cohort exhibited a 12:1 male prevalence, with half of deaths in the 41-50 age group.
• Running was the most frequent exercise activity (46.15%).
• Identified 83 rare variants in 37 samples (71.15%), with 36.14% classified as deleterious, present in 53.84% of cases.

Conclusions:

• Comprehensive genetic analysis can identify potentially causative variants in sudden cardiac death during exercise.
• Many identified genetic variants currently hold indeterminate significance, requiring further investigation for clinical translation.
• Genetic screening aids in detecting causative variants and identifying at-risk family members.