Insights into sudden cardiac death: exploring the potential relevance of non-diagnostic autopsy findings

Area of Science:

• Cardiology
• Forensic Pathology
• Genetics

Background:

• Unexplained sudden cardiac death (SCD) in individuals under 65 may be linked to inherited cardiogenetic diseases.
• Autopsy findings in SCD cases can guide clinical evaluation of at-risk relatives towards specific inherited heart conditions.
• The role of non-diagnostic autopsy abnormalities in SCD requires further investigation.

Purpose of the Study:

• To investigate the relevance of non-diagnostic pathological abnormalities of indeterminate causality in sudden cardiac death (SCD).
• To determine the association between uncertain autopsy findings and cardiogenetic diagnoses in unexplained SCD cases.
• To compare the diagnostic yield of clinical phenotyping in relatives of SCD cases with normal versus non-diagnostic autopsy findings.

Main Methods:

• Clinical cardiac phenotyping was performed on 346 at-risk relatives from 98 unexplained SCD cases (aged 1-64 years).
• SCD cases were categorized into true sudden arrhythmic death syndrome (SADS) with normal autopsies and uncertain sudden unexplained death (SUD) with non-diagnostic findings.
• Relatives were evaluated for inherited cardiomyopathies and primary arrhythmia syndromes.

Main Results:

• A cardiogenetic diagnosis was established in 24.5% of families.
• The proportion of families with a cardiogenetic diagnosis was similar for uncertain SUD (20%) and true SADS (31%).
• Unexplained SCD cases were significantly more likely to have at least one uncertain autopsy finding compared to controls.

Conclusions:

• Primary arrhythmia syndromes are the predominant familial cardiogenetic diagnoses in both uncertain SUD and true SADS cases.
• Non-diagnostic or uncertain histological findings in SCD autopsies are associated with underlying genetic causes but lack definitive causative status.
• At-risk relatives of individuals with uncertain SUD should undergo thorough evaluation for both ion channel disorders and cardiomyopathies.