A new research published in JAMA Cardiology supports the use of genetic testing in individuals with early-onset atrial fibrillation (AF). Genetic testing in early AF finds pathogenic mutations associated to more significant hereditary cardiomyopathy and arrhythmia disorders, according to a study led by Zachary T. Yoneda of Vanderbilt University Medical Center in Nashville, Tennessee, and colleagues.
In the research, disease-associated variants were discovered in 10% of individuals with early-onset AF utilising genetic testing (the percentage was higher if diagnosed before the age of 30 years and lower if diagnosed after the age of 60 years).
At this time, genetic testing for atrial fibrillation is not advised. Recent research has indicated that patients with early-onset AF have uncommon disease-associated variations. In addition, there are new case reports indicating that AF genetic testing has revolutionised clinical treatment.
Early-onset atrial fibrillation can signal a more significant underlying hereditary cardiomyopathy or arrhythmia syndrome.
In light of this, Yoneda and his colleagues wanted to look at the findings of genetic testing for early-onset AF and see how common disease-associated variations in susceptibility genes for hereditary cardiomyopathy and arrhythmia syndromes are in individuals diagnosed with AF before the age of 66.
Patients from an academic medical centre with AF diagnosed before the age of 66 were included in the prospective, observational cohort research, which included whole genome sequencing through the National Heart, Lung, and Blood Institute’s Trans-Omics for Precision Medicine programme.
Rare variations discovered in a panel of 145 genes included on cardiomyopathy and arrhythmia panels used by commercial clinical genetic testing facilities were among those exposed. The researchers evaluated sequencing data using an automated approach followed by a human examination by a team of independent, blinded reviewers.
The primary objective was the categorization of rare variations using criteria developed by the American College of Medical Genetics and Genomics: benign, likely benign, variant of unknown importance, likely pathogenic, or pathogenic.
Genetic testing found 131 individuals (10.1 percent) with a disease-associated variation, 812 (62.8 percent) with a variant of unknown relevance, 92 (7.1 percent) as heterozygous carriers for an autosomal recessive condition, and 258 (20.0 percent) with no susceptibility.
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.
