(Postmortem genetic testing in sudden cardiac death victims and genetic screening of relatives at risk in the Czech Republic)

Alice Krebsová; Štěpánka Kučerová; Pavel Votýpka; Petra Peldová; Markéta Kulvajtová; Petra Dohnalová; Matěj Bílek; Veronika Stufka; Kristina Rücklová; Iva Grossová; Hanka Wünschová; Terézia Tavačová; Jana Hašková; Markéta Segeťová; Andrea Gřegořová; Veronika Zoubková; Jana Petřková; Martin Dobiáš; Michal Makuša; Alžběta Blanková; David Veitr; Hynek Řehulka; Ivan Šubrt; A Pilín; Petr Tomášek; Jan Janoušek; Josef Kautzner; Milan Maçek

doi:10.33678/cor.2022.059

Why the study?

Sudden cardiac death in individuals under 40 years is often caused by inherited cardiovascular disease, and postmortem genetic testing with relative screening enables primary prevention.

Does postmortem genetic testing identify the molecular cause of sudden cardiac death in victims aged 0-59 years to facilitate screening of at-risk relatives?

Key Points

To evaluate the diagnostic yield of postmortem cardiogenetic testing in sudden cardiac death victims and assess cardiological cascade screening in their at-risk surviving relatives.
Evaluated 115 sudden death cases (aged 0–59 years, from 110 families) between 2016 and 2021, categorized by autopsy findings into cardiomyopathies, SADS, SUD/SUDI, SIDS, and aortic dissection.
Performed molecular autopsy using next-generation sequencing across 106 victims with suitable postmortem tissue and provided genetic counseling and cardiological evaluations to 328 surviving relatives.
A family history of sudden death, heart failure, or ventricular arrhythmia was documented in 28.6% of families (33/115).
Pathogenic or likely pathogenic variants (class 4 and 5) were identified in 19.8% of analyzed victims (21/106), involving genes such as RYR2, KCNH2, KCNQ1, SCN5A, and FLNC.

Structured PICO

Does postmortem genetic testing identify the molecular cause of sudden cardiac death in victims aged 0-59 years to facilitate screening of at-risk relatives?

P

Population

115 sudden cardiac death victims aged 0-59 years from 110 families, and 328 of their relatives in the Czech Republic.

I

Intervention

Postmortem genetic testing (next-generation sequencing) and cardiological screening of relatives.

O

Outcome

Identification of highly probable or certain molecular cause of disease (class 4 and 5 variants).surrogate

Postmortem genetic testing identified a definitive or highly probable genetic cause in nearly 20% of sudden cardiac death victims aged 0-59, highlighting its value in guiding primary prevention for at-risk relatives.

Implication

May aid family screening after SCD; leaves open need for prospective validation before routine adoption.

Abstract

NĂĄhlĂĄ srdeÄnĂ smrt (SCD) je u jedincĹŻ mladĹĄĂch 40 let velmi Äasto zpĹŻsobena dÄdiÄnĂ˝m kardiovaskulĂĄrnĂm onemocnÄnĂm. Identifikace tÄchto pĹĂpadĹŻ, provedenĂ post mortem genetickĂŠho vyĹĄetĹenĂ a kardiologickĂŠho screeningovĂŠho vyĹĄetĹenĂ pĹĂmĂ˝ch pĹĂbuznĂ˝ch jsou pĹedpokladem k primĂĄrnĂ prevenci srdeÄnĂ zĂĄstavy u pozĹŻstalĂ˝ch. CĂlem prĂĄce je analĂ˝za vĂ˝sledkĹŻ takovĂŠho programu, kterĂ˝ byl zaveden v ÄeskĂŠ republice. Soubor a metodika: V obdobĂ od 2016 do 2021 jsme v rĂĄmci grantovĂŠho projektu ĹeĹĄili celkovÄ 133 pĹĂpadĹŻ nĂĄhlĂŠho ĂşmrtĂ, z nichĹž bylo podrobnĂŠ kardiogenetickĂŠ diagnostice podrobeno 115 ĂşmrtĂ jedincĹŻ ve vÄku 0-59 let, celkem ze 110 rodin. MrtvĂ byli na zĂĄkladÄ pitevnĂ diagnĂłzy rozĹazeni do kategoriĂ dle typu kardiomyopatie (hypertrofickĂĄ, dilataÄnĂ nebo arytmogennĂ), kategorie bez nĂĄlezu strukturĂĄlnĂho onemocnÄnĂ srdce (SADS) nebo bez jasnĂŠho pitevnĂho nĂĄlezu (SUD/SUDI), pĹĂpadnÄ nĂĄhlĂŠ ĂşmrtĂ novorozence (SIDS) a akutnĂ disekce velkĂŠ cĂŠvy. Celkem 328 pĹĂbuznĂ˝ch bylo geneticky konzultovĂĄno a kardiologicky vyĹĄetĹeno. Po informovanĂŠm souhlasu nĂĄsledovala molekulĂĄrnĂ analĂ˝za metodou sekvenovĂĄnĂ novĂŠ generace (Sophia Genetics) celkem u 106 pĹĂpadĹŻ, kde byl k dispozici vhodnĂ˝ materiĂĄl pro analĂ˝zu. VĂ˝sledky: AnamnĂŠza nĂĄhlĂŠho ĂşmrtĂ Äi blĂzkĂ˝ pĹĂbuznĂ˝ se srdeÄnĂm selhĂĄnĂm a/nebo komorovou arytmiĂ byla zaznamenĂĄna v 33/115 pĹĂpadĹŻ (28,6 %) rodin. Velmi pravdÄpodobnĂĄ nebo jistĂĄ molekulĂĄrnĂ pĹĂÄina onemocnÄnĂ (klasifikace 4 a 5) byla nalezena u 21/106 (19,8 %) v genech RYR2, KCNH2, KCNQ1, SCN5A, FLNC,

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Cite This Study

Krebsová et al. (2023) studied this question.

synapsesocial.com/papers/69f14be12811130d0cde2392 https://doi.org/10.33678/cor.2022.059

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(Postmortem genetic testing in sudden cardiac death victims and genetic screening of relatives at risk in the Czech Republic)

Key Points

Structured PICO

Implication

Abstract

Discussion

Cite This Study

(Postmortem genetic testing in sudden cardiac death victims and genetic screening of relatives at risk in the Czech Republic)

Key Points

Structured PICO

Implication

Abstract

Discussion

Cite This Study

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