JAMA study supports the use of genetic testing for patients with early-onset atrial fibrillation
USA: The results from a recent study in the journal JAMA Cardiology support the use of genetic testing in patients with early-onset atrial fibrillation (AF). The study by Zachary T. Yoneda, Vanderbilt University Medical Center, Nashville, Tennessee, and colleagues found that genetic testing in early AF identifies pathogenic variants linked to more serious inherited cardiomyopathy and arrhythmia syndromes.
In the study, disease-associated variant, by using genetic testing, was identified in 10% of patients with early-onset AF (the percentage was higher if diagnosed before the age of 30 years and lower if diagnosed after the age of 60 years).
Currently, genetic testing is not recommended for atrial fibrillation. However, recent studies have suggested that early-onset AF patients have rare disease-associated variants. Also, there are emerging case reports in which genetic testing for AF has changed clinical management.
Early-onset atrial fibrillation can be the initial manifestation of a more serious underlying inherited cardiomyopathy or arrhythmia syndrome.
Against the above background, Yoneda and the team aimed to examine the results of genetic testing for early-onset AF and addressed the question of what is the prevalence of disease-associated variants in susceptibility genes for inherited cardiomyopathy and arrhythmia syndromes in patients diagnosed with AF before 66 years of age.
The prospective, observational cohort study enrolled patients from an academic medical center who had AF diagnosed before 66 years of age, and underwent whole genome sequencing through the National Heart, Lung, and Blood Institute's Trans-Omics for Precision Medicine program.
Exposures included rare variants identified in a panel of 145 genes that are included on cardiomyopathy and arrhythmia panels used by commercial clinical genetic testing laboratories. Using an automated process followed by a manual review by a panel of independent, blinded reviewers, the researchers analyzed sequencing data.
The primary outcome was classification of rare variants using American College of Medical Genetics and Genomics criteria: benign, likely benign, variant of undetermined significance, likely pathogenic, or pathogenic.
Among 1293 participants (934 [72.2%] male; median age at enrollment, 56 years; median age at AF diagnosis, 50 years), genetic testing identified 131 participants (10.1%) with a disease-associated variant, 812 (62.8%) with a variant of undetermined significance, 92 (7.1%) as heterozygous carriers for an autosomal recessive disorder, and 258 (20.0%) with no suspicious variant.
Key findings of the study include:
- The likelihood of a disease-associated variant was highest in participants with AF diagnosed before the age of 30 years (20 of 119 [16.8%]) and lowest after the age of 60 years (8 of 112 [7.1%]).
- Disease-associated variants were more often associated with inherited cardiomyopathy syndromes compared with inherited arrhythmias.
- The most common genes were TTN (n = 38), MYH7 (n = 18), MYH6 (n = 10), LMNA (n = 9), and KCNQ1 (n = 8).
The researchers concluded, "in our cohort study genetic testing identified a disease-associated variant in 10% of patients with early-onset AF (the percentage was higher if diagnosed before the age of 30 years and lower if diagnosed after the age of 60 years)." "Most pathogenic/likely pathogenic variants are in genes associated with cardiomyopathy. These results support the use of genetic testing in early-onset AF."
Yoneda ZT, Anderson KC, Quintana JA, et al. Early-Onset Atrial Fibrillation and the Prevalence of Rare Variants in Cardiomyopathy and Arrhythmia Genes. JAMA Cardiol. Published online September 08, 2021. doi:10.1001/jamacardio.2021.3370