Impact of Age and Gender on Diagnosing Inherited Cardiac Disorders in SADS

Overview

This study evaluated 760 sudden arrhythmic death syndrome (SADS) cases to determine how age and sex affect diagnostic outcomes using familial evaluation (FE) and molecular autopsy (MA). Diagnostic yield was up to 45% when combining FE and MA, with females and younger decedents showing higher likelihood of inherited cardiac condition diagnoses, especially long QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT).

Background

Sudden arrhythmic death syndrome (SADS) refers to sudden unexplained deaths despite thorough post-mortem and toxicology. It accounts for a significant proportion of sudden deaths in young individuals. Familial evaluation and molecular autopsy are recommended to identify inherited cardiac conditions (ICCs) such as LQTS, Brugada syndrome, and CPVT, which can inform risk in surviving relatives. Prior studies have not fully explored how age and sex influence diagnostic yield in SADS cases.

Data Highlights

Key Findings

• The overall diagnostic yield for inherited cardiac conditions was 37% with familial evaluation and 9% with molecular autopsy alone.
• Combining familial evaluation and molecular autopsy increased diagnostic yield to 45%.
• Diagnostic likelihood of LQTS and CPVT decreased significantly with increasing age at death.
• Females had a higher diagnostic yield than males in both familial evaluation and molecular autopsy cohorts.
• Females were notably more likely to be diagnosed with LQTS via molecular autopsy compared to males.
• The highest diagnostic yields for LQTS and CPVT were observed in children and adolescents.

Clinical Implications

Clinicians should consider age and sex when evaluating families after a SADS death, as younger decedents and females have higher likelihood of inherited arrhythmia syndromes. A combined approach using both familial evaluation and molecular autopsy maximizes diagnostic yield. This personalized strategy can better identify at-risk relatives and guide preventative interventions.

Conclusion

A combined familial and molecular diagnostic approach following SADS deaths yields up to 45% diagnosis of inherited cardiac conditions, with younger age and female sex associated with higher diagnostic rates, particularly for LQTS and CPVT. Tailoring evaluation based on these factors enhances detection and family risk stratification.

References

1. O. Weizman et al. 2023 -- Sudden arrhythmic death syndrome: are we missing the clues in women?