Postmortem genetic analysis following sudden cardiac death : Background, approach, and future

Abstract

Sudden cardiac death (SCD) is defined as an unexpected, nontraumatic death with apossible cardiac or unknown cause. The lowest incidence is observed in infancy and childhood (1per 100,000), and the incidence is approximately 50per 100,000 in the middle-aged population, reaching aplateau around the age of 80 (200 per100,000). While most SCD cases occur in older people with coronary artery disease, there is apredominance of monogenetic and polygenetic diseases in the young. Postmortem genetic analysis (molecular autopsy) using next-generation sequencing reveals adefinite pathogenic genetic alteration, which can explain SCD of young patients in near 20% of the cases. Hence, postmortem genetic analysis has become an important tool to unravel the inheritable cause of death. Furthermore, early identification of apathogenic genetic sequence variant in the deceased is crucial to reduce risk in relatives due to preventive personalized measures. Postmortem genetic analysis forms together with the clinical assessment the basis for early identification of at-risk relatives. Anew guideline for the management of ventricular arrhythmias and prevention of sudden death was recently published by the European Society of Cardiology. The new recommendations give genetic testing, also in deceased patients amuch higher priority reflecting increasing relevance of genetic testing for diagnostic evaluation, risk stratification and prevention.