Sudden cardiac death and the role of postmortem genetic testing in unexplained cases

Sudden cardiac death (SCD) is accountable for 10-20% of deaths in Europe. While inherited and acquired structural heart disease underlie a considerable proportion, many SCDs remain unexplained after conventional autopsy. Lack of structural cardiac abnormalities in sudden death points towards the possibility of inherited heart disease, yet to manifest in observable changes. In fact, 70 % of SCDs in the young are potentially inherited, and causes may be familial hypercholesterolemia, cardiomyopathies, and primary arrhythmias syndromes. Early diagnosis of occult hereditary conditions and initiation of tailored prevention is key in risk reduction of SCD in relatives of deceased individuals. Postmortem genetic testing is recommended in potential inherited causes of SCD, with novel data showing the technique enables detection of concealed cardiomyopathies and channelopathies. Yet widespread implementation is impeded by a number of challenges, including lack of awareness among clinicians of the value of postmortem genetics. Current guidelines from the European Society of Cardiology (ESC) and the American Heart Association (AHA) advise both post-mortem genetic testing of the SCD victim with a potential inherited cause of death and testing of first-degree relatives to prevent future SCDs. Furthermore, it is recommended that specialists interpret findings, and that family evaluation takes place in multidisciplinary collaboration between cardiologists, pathologists, geneticists, and counsellors. This review provides a summary of contemporary knowledge on SCD, outlines guidelines for general forensic management and use of post-mortem genetic testing - including its interpretation, advantages, and challenges - and finally describes standard procedures for investigations of relatives to the deceased individual.