Sudden cardiac death: forensic investigation and its implications for cardiovascular risk stratification and prevention

Abstract

Sudden cardiac death (SCD) remains a major global cause of mortality and is often the first manifestation of previously unrecognized cardiovascular disease. Despite advances in clinical cardiology, a substantial proportion of cases remain undiagnosed during life, underscoring the crucial role of forensic investigation in determining the cause of death and informing preventive strategies. This review provides a comprehensive overview of the forensic approach to SCD, highlighting the integration of scene investigation, autopsy, histopathology, toxicology, and molecular analyses within a standardized diagnostic workflow. Conventional autopsy continues to be the diagnostic cornerstone for identifying structural, ischemic, and inflammatory cardiac diseases, with coronary artery disease predominating in older individuals and cardiomyopathies and channelopathies representing major causes in younger populations. However, approximately 10%-15% of cases remain autopsy-negative and require advanced diagnostic approaches. Molecular autopsy, particularly through next-generation sequencing, has significantly improved the identification of heritable arrhythmogenic disorders, facilitating familial cascade screening and targeted preventive interventions. Emerging technologies, including postmortem imaging, immunohistochemistry, artificial intelligence, and multi-omics approaches, improve the detection of subtle pathological changes, although their routine implementation remains limited. Beyond cause-of-death determination, forensic investigation provides valuable epidemiological data and contributes to cardiovascular risk stratification by identifying undiagnosed disease substrates and inherited risk factors. Combining forensic, molecular, and population-level data strengthens the link between postmortem investigation and preventive cardiology, supporting more effective strategies to reduce the burden of SCD.

Keywords

Sudden cardiac death / forensic pathology / molecular autopsy / cardiovascular risk stratification / cardiomyopathies / channelopathies / artificial intelligence / preventive cardiology

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