Diagnostic yield in victims of sudden cardiac death and their relatives Benjamin Lautrup Hansen 1 *, Elisabeth Mu ¨ tze Jacobsen 1 , Amalie Kjerrumgaard 1 , Jacob Tfelt-Hansen 1,2 , Bo Gregers Winkel 1 , Henning Bundgaard 1† , and Alex Hørby Christensen 1,3† 1 Department of Cardiology, Rigshospitalet, University Hospital of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark; 2 Department of Forensic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; and 3 Department of Cardiology, Herlev-Gentofte, Copenhagen University Hospital, Copenhagen, Denmark Received 13 November 2019; editorial decision 18 February 2020; accepted 25 February 2020; online publish-ahead-of-print 20 April 2020 Aims International guidelines recommend cardiogenetic screening in families with sudden cardiac death (SCD) if the sus- pected cause is an inherited cardiac disease. The aim was to assess the diagnostic yield of inherited cardiac diseases in consecutively referred SCD families. ................................................................................................................................................................................................... Methods and results In this single-centre retrospective study, we consecutively included families referred to our tertiary unit between 2005 and 2018 for screening due to SCD. Following evaluation of premortem medical records and postmortem findings for the proband, the families underwent a guideline-based screening protocol. Relatives were followed and cardiovascular events registered. In total, 304 families with 695 relatives were included. In probands, mean age at death was 39 years (75% males) and in relatives mean age at screening was 35 years (47% males). The proband- diagnosis was established through autopsy findings (n = 89), genetic analyses (n = 7), or based on premortem find- ings (n = 21). In the remaining 187 families with borderline/no diagnosis in the proband, screening of relatives yielded a diagnosis in 26 additional families. In total, an inherited cardiac disease was identified in 143 out of 304 families (47%). In relatives, 73 (11%) were diagnosed. Arrhythmogenic right ventricular cardiomyopathy (n = 16) was the most common diagnosis. During follow-up (mean 5.5 years), a low rate of serious cardiac events was ob- served (no SCD events). ................................................................................................................................................................................................... Conclusion Forty-seven percent of SCD families were diagnosed. Eleven percent of the screened relatives received a definite diagnosis and were offered treatment according to guidelines. A low rate of serious cardiovascular events was ob- served among SCD relatives.                                                                                                                                                                                                                     Keywords Sudden cardiac death • Inherited cardiac disease • Inherited arrhythmia • Molecular autopsy • Family screening Introduction Sudden cardiac death (SCD) is defined as a sudden and unex- pected non-traumatic death caused by cardiac or unknown cause. 1 A Danish nationwide study 2 from 2014 reported that approxi- mately 11% of deaths in the age group 1–49 years were SCD and the annual rate of SCD in this age group was 8.6 per 100 000 persons (300 SCD events per year). Since the death is sudden, unexpected and often without prodromal symptoms, several different pre-symptomatic screening methods have been suggested for prevention. Due to the inherited nature of a considerable fraction of underlying diseases associated with SCD in the young, 3 guidelines for detection of at-risk relatives recommend a compre- hensive postmortem analysis focusing on the diagnosis in the SCD victim 4 followed by a phenotype-driven evaluation of the rela- tives. 5 Although autopsy is key, the autopsy rate in sudden unex- pected death in Denmark is 68% in the age group 1–35 years, decreasing to 44% in the age group 36–49 years. * Corresponding author. Tel: þ45 81271128. E-mail address: benjamin.lautrup.hansen.01@regionh.dk † The last two authors shared last authorship. Published on behalf of the European Society of Cardiology. All rights reserved. V C The Author(s) 2020. For permissions, please email: journals.permissions@oup.com. Europace (2020) 22, 964–971 CLINICAL RESEARCH doi:10.1093/europace/euaa056 Channelopathies and cardiomyopathies Downloaded from https://academic.oup.com/europace/article/22/6/964/5821388 by guest on 20 August 2022