Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Apr 21;10(9):1806.
doi: 10.3390/jcm10091806.

Diagnostic Yield of Genetic Testing in Sudden Cardiac Death with Autopsy Findings of Uncertain Significance

Mercedes Iglesias  1 , Tomas Ripoll-Vera  1 , Consuelo Perez-Luengo  2 , Ana Belen García  2 , Susana Moyano  3 , Juan Carlos Canos  3 , Juan Carlos Borondo  3 , Jorge Alvarez  1 , Damian Heine-Suñer  4 , Bernardino Barcelo  5
Affiliations

Diagnostic Yield of Genetic Testing in Sudden Cardiac Death with Autopsy Findings of Uncertain Significance

Mercedes Iglesias et al. J Clin Med. .

Abstract

Background: Sudden death (SD) in the young usually has an underlying genetic cause. In many cases, autopsy reveals unspecific and inconclusive results, like idiopathic left ventricular hypertrophy (LVH), nonsignificant coronary atherosclerosis (CA), and primary myocardial fibrosis (PMF). Their pathogenicity and their relation to SD cause is unknown. This study aims to evaluate the diagnostic yield of genetic testing in these cases.

Methods: SD cases, between 1 and 50 years old, with findings of uncertain significance (idiopathic LVH, nonsignificant CA and PMF) on autopsy were evaluated prospectively, including information about medical and family history and circumstances of death. Genetic testing was performed.

Results: In a series of 195 SD cases, we selected 31 cases presenting idiopathic LVH (n = 16, 51.61%), nonsignificant CA (n = 17, 54.84%), and/or PMF (n = 24, 77.42%) in the autopsy. Mean age was 41 ± 7.2 years. Diagnostic yield of genetic test was 67.74%, considering variants of unknown significance (VUS), pathogenic variants (PV) and likely pathogenic variants (LPV); 6.45% including only PV and LPV. Structural genes represented 41,93% (n = 13) of cases, while 38,7% (n = 12) were related to channelopathies.

Conclusion: Molecular autopsy in SD cases between 1 and 50 years old, with findings of uncertain significance, has a low diagnostic yield, being VUS the most frequent variant observed.

Keywords: autopsy; genetic testing; sudden death.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Flow chart of study cohort. SD, sudden death. SUDS, sudden unexpected death syndrome. IC, ischemic cardyomyopathy. LVH, left ventricular hypertrophy. CA, coronary atherosclerosis.
Figure 2
Figure 2
Macroscopic examination of the heart of a sudden death decedent showing left ventricular hypertrophy (above); histological analysis of the heart of another sudden death decedent at 60× showing the presence of myocardial fibrosis in the absence of disarray (below).
Figure 3
Figure 3
Molecular autopsy results. VUS, variant of unknown significance; PV, pathogenic variant; LPV, likely pathogenic variant.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Priori S.G., Blomstrom-Lundqvist C., Mazzanti A., Blom N., Borggrefe M., Camm J., Elliott P.M., Fitzsimons D., Hatala R., Hindricks G., et al. 2015 ESC Guidelines for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Association for European Paediatric and Congenital Cardiology (AEPC) Eur. Heart J. 2015;36:2793–2867. - PubMed
    1. Bezzina C.R., Lahrouchi N. Genetics of Sudden Cardiac Death. Circ. Res. 2015;116:1919–1936. doi: 10.1161/CIRCRESAHA.116.304030. - DOI - PubMed
    1. Semsarian C., Ingles J. Sudden cardiac death in the young: The molecular autopsy and a practical approach to surviving relatives. Eur. Heart J. 2015;36:1290–1296. doi: 10.1093/eurheartj/ehv063. - DOI - PubMed
    1. Chugh S.S. Sudden cardiac death in 2017: Spotlight on prediction and prevention. Int. J. Cardiol. 2017;237:2–5. doi: 10.1016/j.ijcard.2017.03.086. - DOI - PMC - PubMed
    1. Bagnall R.D., Weintraub R.G. A prospective study of sudden cardiac death among children and young adults. N. Engl. J. Med. 2016;374:2441–2452. doi: 10.1056/NEJMoa1510687. - DOI - PubMed

LinkOut - more resources