A national pathway integrating post-mortem genetic testing for sudden cardiac death identified pathogenic variants in 17% of decedents and provided a new diagnosis for 28% of evaluated relatives.
Observational (n=414)
Yes
Does a prospective population pathway integrating post-mortem genetic testing and clinical evaluation improve the identification of inherited cardiac conditions in relatives of sudden cardiac death victims?
A national prospective pathway integrating post-mortem genetic testing and clinical evaluation successfully identified inherited cardiac conditions in 28% of evaluated relatives of sudden cardiac death victims.
BACKGROUND: Sudden cardiac death (SCD) is a major cause of premature and potentially avoidable mortality. Determining whether a SCD was caused by an inherited cardiac condition (ICC) enables identification and appropriate clinical management of at-risk relatives. We report findings from the NHS and Coronial Service Sudden Unexpected Death programme, which established a national pathway aimed at reducing population risk of SCD in England. METHODS: Cases of SCD were included where a coroner's autopsy raised suspicion of an ICC (ages 1-60) or was unable to determine a cause of death (sudden arrhythmic death syndrome SADS) (ages 1-40). Decedent tissue was retained for post-mortem genetic testing, and their relatives were signposted to a new ICC pathway. Where a decedent harboured a pathogenic (P) or likely pathogenic (LP) genetic variant associated with an ICC, relatives were offered predictive genetic testing for that variant. A negative genetic result enabled appropriate discharge, while a positive result triggered clinical evaluation for cardiac disease phenotype. Where no ICC associated P or LP variants were identified in decedents, their relatives underwent clinical evaluation. FINDINGS: Of 107 SCD cases, the most common findings were SADS (35%) and arrhythmogenic cardiomyopathy (15%), while 17% of those tested were found to have P or LP variants. Three-hundred-and-seven relatives subsequently entered the ICC clinic for further evaluation. Diagnostic yield for relatives of decedents with P or LP variants was 47%. Of the 235 relatives who completed ICC evaluation, 28% were provided with a new genetic and/or clinical diagnosis and subsequently managed appropriately. One notable family cluster (n = 24) included 13 individuals (57%) with the KCNH2:c2775dup variant causative of long QT syndrome. INTERPRETATION: Integration of coronial, pathology, genomic, and cardiac services in a prospective population pathway enabled efficient capture and use of genetic and clinical information to reduce population risk of SCD. FUNDING: British Heart Foundation, Cardiac Risk in the Young, NHS England, NIHR.
Wade et al. (Fri,) conducted a observational in Sudden cardiac death (n=414). Post-mortem genetic testing and clinical evaluation pathway was evaluated on Identification of pathogenic or likely pathogenic variants in decedents. A national pathway integrating post-mortem genetic testing for sudden cardiac death identified pathogenic variants in 17% of decedents and provided a new diagnosis for 28% of evaluated relatives.