Clinical impact of post-mortem genetic testing in cardiac death and cardiomyopathy

Area of Science:

• Cardiovascular Genetics
• Molecular Autopsy
• Genetic Pathology

Background:

• Post-mortem genetic analysis can clarify cardiac death causes.
• Its value is less defined when cardiac disease is already suspected.
• Cardiomyopathy diagnosis and family implications require further investigation.

Purpose of the Study:

• To assess the feasibility of post-mortem genetic analysis in suspected cardiomyopathy.
• To evaluate the medical impact of these genetic findings on affected families.

Main Methods:

• Targeted sequencing was performed on 35 patients with cardiac death and suspected cardiomyopathy.
• Genetic variants were identified in genes associated with cardiomyopathies, including sarcomeric, desmosomal, lamin A/C, and transthyretin genes.

Main Results:

• Causal variants were identified in 15 out of 35 patients (43% yield).
• Genetic findings enabled predictive testing for relatives (15 families) and informed early therapeutic strategies (5 families).
• Results clarified cardiomyopathy subtypes, identified genetic origins, aided uncertain diagnoses, and facilitated prenatal testing.

Conclusions:

• Post-mortem molecular testing is a valuable addition to family care strategies after cardiac death with suspected cardiomyopathy.
• Genetic findings offer critical insights for relatives beyond conventional autopsy results.
• This approach enhances diagnostic accuracy and family-specific medical management.