Strategy for clinical evaluation and screening of sudden cardiac death relatives

Area of Science:

• Cardiology
• Genetics
• Forensic Pathology

Background:

• Sudden cardiac death (SCD) is frequently the initial presentation of underlying heart disease, particularly in younger individuals.
• Hereditary cardiac diseases, often with autosomal-dominant inheritance, place first-degree relatives at significant risk (50%) of developing similar conditions.
• Effective screening of at-risk relatives is essential for reducing SCD incidence.

Purpose of the Study:

• To emphasize the importance of establishing the cause of death in young SCD cases for targeted family screening and counseling.
• To advocate for systematic autopsies in SCD cases to guide appropriate screening protocols for relatives.
• To highlight the diagnostic value of autopsy, even in cases with negative findings or no autopsy, through clinical and genetic evaluations.

Main Methods:

• Review of current practices and challenges in evaluating young SCD cases.
• Advocacy for systematic autopsy performance in SCD.
• Proposal of an algorithm for diagnostic evaluation of relatives of young SCD victims, incorporating clinical examination and selective genetic screening.
• Discussion of the role of molecular autopsy in identifying genetic causes of SCD.

Main Results:

• Systematic autopsies provide crucial findings for selecting optimal screening programs for relatives.
• Negative autopsy findings, while challenging, can suggest specific inherited cardiac diseases without structural changes.
• In cases lacking autopsy or with negative results, clinical examinations and genetic screening can identify likely diagnoses in over 50% of families.
• A proposed algorithm aids in narrowing diagnostic possibilities for relatives of young SCD victims.

Conclusions:

• Establishing the cause of death through systematic autopsies is vital for effective family screening and prevention of SCD.
• Even without autopsy, a combination of thorough clinical evaluation and targeted genetic testing can diagnose the cause of SCD in a significant proportion of families.
• There is a need for consensus on routine SCD evaluation, postmortem testing ethics, and legal frameworks.
• Molecular autopsy represents a valuable tool in the comprehensive evaluation of young SCD cases and their at-risk relatives.