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Usefulness of Genetic Testing in Sudden Cardiac Arrest Survivors With or Without Previous Clinical Evidence of Heart Disease


Abstract

Genetic testing in survivors of sudden cardiac arrest (SCA) with a suspicious cardiac phenotype is considered clinically useful, whereas its value in the absence of phenotype is disputed. We aimed to evaluate the clinical utility of genetic testing in survivors of SCA with or without cardiac phenotype. Sixty unrelated SCA survivors (median age: 34 [interquartile range 20 to 43] years, 82% male) without coronary artery disease were included: 24 (40%) with detectable cardiac phenotype (Ph(+)SCA) after the SCA event and 36 (60%) with no clear cardiac phenotype (Ph(-)SCA). The targeted exome sequencing was performed using the TruSight-One Sequencing Panel (Illumina). Variants in 185 clinically relevant cardiac genes with minor allele frequency <1% were analyzed. A total of 32 pathogenic or likely pathogenic variants were found in 27 (45%) patients: 17 (71%) in the Ph(+)SCA group and 10 (28%) in the Ph(-)SCA group. Sixteen (67%) Ph(+)SCA patients hosted mutations congruent with the suspected phenotype, in which 12 (50%) were cardiomyopathies and 4 (17%) channelopathies. In Ph(-)SCA cases, 6 (17%) carried a mutation in cardiac ion channel genes that could explain the event. The additional 4 (11%) mutations in this group, could not explain the phenotype and require additional studies. In conclusion, cardiac genetic testing was positive in nearly 2/3 patients of the Ph(+)SCA group and in 1/6 of the Ph(-)SCA group. The test was useful in both groups to identify or confirm an inherited heart disease, with an important impact on the patient care and first-degree relatives at risk.

Abstract

Genetic testing in survivors of sudden cardiac arrest (SCA) with a suspicious cardiac phenotype is considered clinically useful, whereas its value in the absence of phenotype is disputed. We aimed to evaluate the clinical utility of genetic testing in survivors of SCA with or without cardiac phenotype. Sixty unrelated SCA survivors (median age: 34 [interquartile range 20 to 43] years, 82% male) without coronary artery disease were included: 24 (40%) with detectable cardiac phenotype (Ph(+)SCA) after the SCA event and 36 (60%) with no clear cardiac phenotype (Ph(-)SCA). The targeted exome sequencing was performed using the TruSight-One Sequencing Panel (Illumina). Variants in 185 clinically relevant cardiac genes with minor allele frequency <1% were analyzed. A total of 32 pathogenic or likely pathogenic variants were found in 27 (45%) patients: 17 (71%) in the Ph(+)SCA group and 10 (28%) in the Ph(-)SCA group. Sixteen (67%) Ph(+)SCA patients hosted mutations congruent with the suspected phenotype, in which 12 (50%) were cardiomyopathies and 4 (17%) channelopathies. In Ph(-)SCA cases, 6 (17%) carried a mutation in cardiac ion channel genes that could explain the event. The additional 4 (11%) mutations in this group, could not explain the phenotype and require additional studies. In conclusion, cardiac genetic testing was positive in nearly 2/3 patients of the Ph(+)SCA group and in 1/6 of the Ph(-)SCA group. The test was useful in both groups to identify or confirm an inherited heart disease, with an important impact on the patient care and first-degree relatives at risk.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Cardiology
04 Faculty of Medicine > Cardiocentro Ticino
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Cardiology and Cardiovascular Medicine
Language:English
Date:15 June 2019
Deposited On:17 Oct 2019 08:18
Last Modified:29 Jul 2020 11:11
Publisher:Elsevier
ISSN:0002-9149
OA Status:Green
Publisher DOI:https://doi.org/10.1016/j.amjcard.2019.02.061
PubMed ID:30975432

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