Evaluation of genetic-molecular causes of Out-of-Hospital Cardiac Arrest - from patients to families: the GenetiCA study

Out-of-hospital cardiac arrest (OHCA) is a public health priority. In patients aged≤50years, inherited arrhythmogenic and structural heart diseases represent a leading etiology, yet existing evidence is largely derived from small, selected cohorts, and population-based estimates of genetic contribution to OHCA in young are still lacking. a multicenter, prospective observational study enrolling all patients aged≤50 years who experience a medically-caused OHCA in Lombardy Region (Italy). (ClinicalTrials.gov NCT06844851). Blood samples will be collected in the pre-hospital by Emergency Medical System during Advanced Life Support. Genetic analysis will be performed using Next-Generation Sequencing with a comprehensive multigene panel targeting inherited arrhythmogenic syndromes and cardiomyopathies. Pre-hospital clinical data, environmental air pollution data and clinical outcomes will be collected. Family members of probands carrying pathogenic(P), likely-pathogenic(LP), or uncertain variants will be offered genetic counseling and clinical evaluation. The primary outcome will be to determine the prevalence of inherited arrhythmogenic and structural cardiomyopathies among young OHCA cases in this geographic area. Secondary outcomes will assess regional variability, associations with initial rhythm, sex, environmental pollution, and survival according to genetic findings. Expected results: Based on the regional OHCA registry (LombardiaCaRe), approximately 575 resuscitated young OHCA cases are expected annually. P/LP variants are anticipated in 15–25% of cases, corresponding to 86–144 individuals/year. GenetiCA study will provide the first population-based assessment of inherited cardiac diseases among young OHCA patients within an entire geographic region. It aims to clarify the genetic burden of OHCA, support targeted family screening with potential implications for public health policies.