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Importance of Genetic Testing in Unexplained Cardiac Arrest
Quick Takes
- Among 228 unexplained cardiac arrest survivors, whole-exome sequencing identified a pathogenic or likely pathogenic genetic variant in arrhythmia or cardiomyopathy genes in 10% of cases.
- When added to phenotyping, genetic testing increased the proportion of “explained” cases from 9%–18%.
Study Questions:
What is the yield and clinical utility of genetic testing in unexplained cardiac arrest (UCA) using whole-exome sequencing?
Methods:
Survivors of UCA requiring external defibrillation were included from the CASPER registry (Cardiac Arrest Survivor with Preserved Ejection fraction Registry). Following advanced clinical testing at baseline, the likely etiology of cardiac arrest was assessed thorough genetic testing. Whole-exome sequencing was performed, followed by assessment of rare variants in previously reported cardiovascular disease genes.
Results:
The study included 228 UCA survivors (mean age at arrest, 39 ± 13 years). The likely genetic etiology of cardiac arrest was determined in 21/228 (9%) cases. The proportion of “explained” cases was 9% with phenotyping alone and 18% when combining phenotyping with whole-exome sequencing. Interestingly, 13 (57%) of the 23 P/LP variants identified were located in genes associated with cardiomyopathy in the absence of a diagnosis of cardiomyopathy at the time of arrest.
Conclusions:
Genetic testing identifies a disease-causing variant in 10% of UCA survivors. The majority of disease-causing variants were located in cardiomyopathy-associated genes, highlighting the arrhythmogenic potential of such variants in the absence of an overt cardiomyopathy diagnosis.
Perspective:
Despite diagnostic testing following an UCA, a large share of noncoronary cardiac arrest cases remain unexplained. So far, guidelines do not support the role of genetic testing in the absence of inherited arrhythmia or cardiomyopathy. It remains arguable what the role of comprehensive genetic testing in unselected patients surviving an UCA is. In this study, 6% of cardiac arrest survivors without a cardiomyopathy phenotype carried a probable or likely probable variant in a cardiomyopathy gene. This suggests that some victims of UCA have “concealed” cardiomyopathy.
Clinical Topics: Acute Coronary Syndromes, Arrhythmias and Clinical EP, Cardiovascular Care Team, Heart Failure and Cardiomyopathies, Prevention, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure
Keywords: Acute Coronary Syndrome, Arrhythmias, Cardiac, Cardiomyopathies, Genetic Testing, Heart Arrest, Heart Failure, Phenotype, Secondary Prevention, Stroke Volume, Whole Exome Sequencing
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