Genetic testing may provide useful information in early-onset atrial fibrillation patients: JAMA
USA: The presence of a disease-associated rare variant for an inherited cardiomyopathy or arrhythmia syndrome among patients with early-onset atrial fibrillation (AF) may be associated with increased mortality risk, reveals a recent study. The findings of the study, published in the journal JAMA Cardiology imply that for patients with early-onset AF, genetic testing may provide important prognostic information.
Atrial fibrillation is the most common arrhythmia that affects more than than 33 million people worldwide. AF is associated with increased risk of stroke and all-cause mortality and often co-occurs with or is caused by heart failure (HF).
Early-onset AF patients are enriched for rare variants in cardiomyopathy and arrhythmia genes. However, there is no information on the e clinical significance of these rare variants in patients with early-onset AF. To fill this knowledge gap, Zachary T. Yoneda, Vanderbilt University Medical Center, Nashville, Tennessee, and colleagues aimed to assess the association between rare variants in cardiomyopathy and arrhythmia genes detected in patients with early-onset AF and time to death in a prospective cohort study.
The study included patients with AF diagnosed before 66 years of age who underwent whole-genome sequencing through the National Heart, Lung and Blood Institute's Trans-Omics for Precision Medicine program. Enrollment was done from November 23, 1999, to June 2, 2015. Data analysis was done from February 26 to September 19, 2021.
Exposure was the rare variants identified in a panel of 145 genes that are included in cardiomyopathy and arrhythmia panels used by commercial clinical genetic testing laboratories.
The primary outcome was time to death and was adjudicated from medical records and the National Death Index. The association of disease-associated variants with death risk after adjustment for age at AF diagnosis, sex, race, body mass index, left ventricular ejection fraction, and an interaction term of age at AF diagnosis and disease-associated variant status were evaluated using Multivariable Cox proportional hazards regression.
Based on the study, the researchers reported the following:
- Among 1293 participants (934 [72%] male; median age at enrollment, 56.0 years), disease-associated (pathogenic or likely pathogenic) rare variants were found in 131 (10%).
- During a median follow-up of 9.9 years, 219 participants (17%) died.
- In univariable analysis, disease-associated variants were associated with an increased risk of mortality; the association remained significant in multivariable modeling when adjusted for age at AF diagnosis, sex, race, body mass index, left ventricular ejection fraction, and an interaction term between disease-associated variant status and age at AF diagnosis.
- The interaction demonstrated that disease-associated variants were associated with a significantly higher risk of mortality compared with no disease-associated variant when AF was diagnosed at a younger age.
- Higher body mass index and lower left ventricular ejection fraction were associated with higher mortality risk.
- There were 73 cardiomyopathy-related deaths, 40 sudden deaths, and 10 stroke-related deaths.
- Mortality among patients with the most prevalent genes with disease-associated variants was 26% (10 of 38 patients) for TTN, 33% (6 of 18) for MYH7, 22% (2 of 9) for LMNA, 0% (0 of 10) for MYH6, and 0% (0 of 8) for KCNQ1.
"Our findings indicate that there is a prognostic value for genetic testing in early-onset AF patients irrespective of ejection fraction at the time of presentation," wrote the authors. "There will be requirement of future studies to prospectively define whether genetic testing improves clinical outcomes in patients with early-onset AF."
Reference:
Yoneda ZT, Anderson KC, Ye F, et al. Mortality Among Patients With Early-Onset Atrial Fibrillation and Rare Variants in Cardiomyopathy and Arrhythmia Genes. JAMA Cardiol. Published online May 11, 2022. doi:10.1001/jamacardio.2022.0810
