Outcomes of post mortem genetic diagnosis in SCD victims and primary prevention of cardiac arrest in relatives: a nationwide multidisciplinary and multicentric collaboration in the Czechia. (11th May 2021)

• Record Type: Journal Article
• Authors: Krebsova, A; Votypka, P; Peldova, P; Rucklova, K; Kulvajtova, M; Pohlova -Kucerova, S; Pilin, A; Gregorova, A; Tavacova, T; Petrkova, J; Dobias, M; Tomasek, P; Macek Jr, M; Janousek, J; Kautzner, J
• Is Part Of: European journal of preventive cardiology. Volume 28:Supplement 1(2021)
• Publication Date: 2021-05-11
• Subjects: Cardiovascular system -- Diseases -- Prevention -- Periodicals; Cardiac patients -- Rehabilitation -- Periodicals; 616.12
• DOI: 10.1093/eurjpc/zwab061.011
• Languages: English
• ISSNs: 2047-4873

Abstract

Abstract: Funding Acknowledgements: Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Supported by Ministry of Health of the Czech Republic Introduction: Post mortem genetic analysis in sudden cardiac death (SCD) represents an important diagnostic tool for the primary prevention of cardiac arrest in victim´s relatives. Purpose: To assess the underlying molecular pathogenesis of SCD in a representative Czech cohort and to evaluate the effects of primary prevention of SCD in genetic relatives. Patients and Methods: Between 2016 and 2020 we have ascertained 100 SCD cases (29 females/71 males; age range 0-52 years). According to autopsy protocols, cases with SCD were divided into categories of sudden arrhythmic death (SADS), sudden unexplained death (in infants; SUD/SUDI), thoracic aortic aneurysm/dissection and cardiomyopathy hypertrophic, arrhythmic, dilated (HCM, ACM, DCM) and sudden infant death syndrome (SIDS). DNA was isolated from post mortem biopsies / relatives blood and subjected to massively parallel sequencing (Illumina, USA) comprising custom-made candidate gene panel (100 genes). Genetic counselling and cardiological examinations were carried out in 245 family members. Results: According to post mortem-established diagnosis, we identified 20 victims with SADS and SUD/SUDI, 11 with HCM and DCM, 19 with ACMG, 8 SIDS cases and 9 acute dissection cases. Most of victims died at sleep or at rest, while only 10/100 victims died during strenuous sport activities. About 50% of SCD victims did not report any apparent cardiac complaints. Highly likely or certain molecular etiology (i.e. based on presence of ACMG.net Class 4 to 5 variants) was disclosed in 19/100 (19%) in RYR2, KCNH2, SCN5A, FLNC (stop), TTN, RBM 20, LMNA/C, PRKAG2, MYBPC3, DSC2, FHL1, TGFBR1 and Col3A1 genes (see Tab). Finally, we identified 52/241 phenotype/genotype positive family members who are at risk of cardiac arrest and were offered corresponding cardiological care. Conclusion: Multidisciplinary cooperation, together with centralized and standardized molecular genetic testing, enables the primary prevention of cardiac arrest in relatives of SCD victims.