Kauferstein Silke, Beckmann Britt-Maria
Institut für Rechtsmedizin, Zentrum für plötzlichen Herztod und familiäre Arrhythmiesyndrome, Universitätsklinikum Frankfurt, Kennedyallee 104, 60590, Frankfurt, Deutschland.
Partner Site Rhein-Main, DZHK (German Centre for Cardiovascular Research), Frankfurt, Deutschland.
Herzschrittmacherther Elektrophysiol. 2024 Mar;35(1):31-38. doi: 10.1007/s00399-023-00986-9. Epub 2024 Jan 10.
Sudden cardiac death (SCD) is defined as an unexpected, nontraumatic death with a possible cardiac or unknown cause. The lowest incidence is observed in infancy and childhood (1 per 100,000), and the incidence is approximately 50 per 100,000 in the middle-aged population, reaching a plateau around the age of 80 (200 per 100,000). While most SCD cases occur in older people with coronary artery disease, there is a predominance of monogenetic and polygenetic diseases in the young.
Postmortem genetic analysis (molecular autopsy) using next-generation sequencing reveals a definite 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 a pathogenic 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. A new 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 a much higher priority reflecting increasing relevance of genetic testing for diagnostic evaluation, risk stratification and prevention.
心源性猝死（SCD）被定义为意外的、非创伤性死亡，其病因可能是心脏原因或不明原因。婴儿期和儿童期的发病率最低（每10万人中1例），中年人群的发病率约为每10万人中50例，在80岁左右达到高峰（每10万人中200例）。虽然大多数SCD病例发生在患有冠状动脉疾病的老年人中，但年轻人中主要是单基因和多基因疾病。
使用下一代测序进行的死后基因分析（分子尸检）揭示了明确的致病性基因改变，这可以解释近20%的年轻患者的SCD。因此，死后基因分析已成为揭示可遗传死亡原因的重要工具。此外，早期识别死者中的致病性基因序列变异对于通过预防性个性化措施降低亲属的风险至关重要。
死后基因分析与临床评估共同构成了早期识别高危亲属的基础。欧洲心脏病学会最近发布了一项关于室性心律失常管理和猝死预防的新指南。新建议给予基因检测，包括对死者的检测更高的优先级，这反映了基因检测在诊断评估、风险分层和预防中的相关性日益增加。
