Post-mortem toxicology analysis in a young sudden cardiac death cohort.

Risk of sudden cardiac death (SCD) increases with age, and several studies have examined the impact of different drugs on cardiovascular function. However, few studies have integrated epidemiological drug consumption data and genetic background in the context of cardiac death. We performed a retrospective population-based study in forensic sudden death cases from a 9-year period in Catalonia. The young cohort included 924 cases 18-50 years old, 566 of which had a cardiac cause of death. Complete autopsy, toxicological, and histopathological studies were performed. Molecular autopsy using next-generation sequencing was performed in nearly 400 cardiac cases. Cases related with fatal acute intoxication were excluded. Drug consumption prevalence was similar between forensic cases of cardiac and non-cardiac origin (62.5% versus 69.5%), with the exception of alcohol, which was more prevalent in the cardiac group than in the non-cardiac group (23.3% versus 17.1%). Individuals in the toxicology-positive group were carriers of more rare genetic variants and were significantly younger than the toxicology-negative group. Psychopharmacological drugs were identified in 22.3% of cardiac cases, and molecular autopsy identified an association between antiepileptic drugs or caffeine and pathogenic or likely pathogenic variants in arrhythmogenic genes. Specific substances could therefore play an essential role as triggers of SCD in genetically predisposed young people.