By Dr Jonathan Shurlock
A Canadian group led by Steffany Grondin at the Montreal Heart Institute have explored the role of genetic testing for patients suffering with unexplained cardiac arrest. The group rationalised the need for further testing in the context of an important proportion of non-coronary cardiac arrests remaining unexplained.
Data were collected from consenting survivors of unexplained cardiac arrest from the Cardiac Arrest Survivor with Preserved Ejection fraction Registry (CASPER), 228 participants were included. 77 were female (34%) and age at arrest was 39 ± 12 years. Participants were enrolled between 2004 and 2018.
Whole-exome sequencing was applied to samples from each participant, including 184 target genes in order to attempt to identify pathogenic (P) or likely pathogenic (LP) variants. P/LP variants were identified in 23 participants (10%), which the authors suggest increased the proportion of explained causes of cardiac arrest from 9% overall with phenotyping, to 18% when combined with whole-exome sequencing. Of the 23 identified P/LP variants, 13 were located on genes associated with cardiomyopathy. The group also performed sub-group analysis to further qualify the identified genetic variants, the full details of which can be found in the paper.
The authors argue for the role of systematic genetic testing of patients with unexplained cardiac arrest, using whole-exome sequencing in addition to phenotyping. They further suggest that the higher prevalence of genetic variants associated with cardiomyopathy, in the absence of a previous diagnosis, is suggestive of what they call ‘concealed cardiomyopathy’ as a mechanism for cardiac arrest.
Importantly there is frequent appearance of variants with uncertain significance, as is often seen with whole-exome/genome-wide sequencing.
Read full article here: https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehac145/6555814
Reference
- Steffany Grondin, Brianna Davies, Julia Cadrin-Tourigny, Christian Steinberg, Christopher C. Cheung, et a. Importance of genetic testing in unexplained cardiac arrest. European Heart Journal, 2022;, ehac145, https://doi.org/10.1093/eurheartj/ehac145
