Young Sudden Cardiac Death in Athletes – Genetics, screening controversies, and prevention

Abstract

Background and Objectives: Sudden cardiac death (SCD) in young athletes remains a devastating event with significant prevention potential through genetic understanding and screening strategies. This systematic review synthesizes current evidence on genetic factors, screening controversies, and prevention approaches for SCD in athletes under 35 years. Methods: We conducted a comprehensive systematic review following PRISMA guidelines, searching PubMed, Embase, Cochrane Library, and Web of Science from 2000-2025. Studies examining genetic causes, screening methods, and prevention strategies for athletic SCD were included. Random-effects meta-analysis was performed where appropriate, with quality assessment using Newcastle-Ottawa Scale. Results: Of 3,847 identified records, 127 studies involving 47,892 athletes from 34 countries were included. Pathogenic variants were identified in 56.5% of SCD cases, with sarcomere protein variants (33.7%) being most common, showing strongest association with structural heart disease (OR 4.7, 95% CI: 3.2-6.9). Comprehensive screening protocols detected conditions in 16.1 per 1000 athletes versus 3.8 per 1000 with basic screening. European programs demonstrated superior detection rates (16.8‰) but higher false-positive rates (8.7%) compared to American approaches (4.2‰ detection, 2.1% false-positive). Meta-analysis of ECG-inclusive screening showed pooled sensitivity of 73.4% (95% CI: 65.2-80.8%). Intervention strategies reduced SCD risk by 85% (HR 0.15, 95% CI: 0.09-0.25), with 5-year event-free survival of 98% versus 87% in controls. Conclusions: Genetic factors contribute substantially to athletic SCD, with population-specific variations requiring tailored approaches. Comprehensive screening significantly improves detection rates despite increased false-positives. Evidence-based interventions dramatically reduce SCD risk, supporting implementation of systematic screening and risk-stratified management protocols