People who carry rare genetic variants linked to cardiomyopathy, a disease impacting the heart muscle, are more likely to develop atrial fibrillation, according to results from the UK Biobank and the All of Us cohort.
Writing in JAMA Cardiology, the researchers report that the presence of cardiomyopathy-associated pathogenic or likely pathogenic variants increased the risk of atrial fibrillation 2-fold and early atrial fibrillation 5-fold.
Atrial fibrillation occurs when an abnormal heart rhythm causes irregular electrical signals in the upper part of the heart and can lead to more severe symptoms such as blood clots, stroke, heart failure, or cardiomyopathy.
“The prevalence of atrial fibrillation in patients with hypertrophic cardiomyopathy is 20% to 30%, which is 4- to 6-fold higher than similarly aged-matched patients in the general population,” explained Sharlene Day, MD, an associate professor at the University of Pennsylvania Perelman School of Medicine, and colleagues in an accompanying editorial published in the same journal.
“More recently, atrial fibrillation has been recognized as an early phenotypic manifestation of cardiomyopathy, possibly reflecting the presence of an atrial myopathy preceding detectable ventricular remodeling.”
In this study, researchers in Boston and Amsterdam analyzed data from 393,768 and 193,232 participants of the UK Biobank and U.S.-based All of Us cohort, respectively. The average age of the participants was 65 years, and 44,182 people across the two cohorts had atrial fibrillation. Genetic sequence data from the participants were also investigated to look for pathogenic or likely pathogenic variants in 26 genes linked to cardiomyopathy.
Genetic variants linked to cardiomyopathy were twice as common in people in the two cohorts with atrial fibrillation versus those without. Similarly, these variants were five times as common in people with early-onset atrial fibrillation before the age of 45 years.
The cumulative rate of heart failure and cardiomyopathy in people in the two biobanks who had atrial fibrillation was higher than in those without, at 18% vs 3%, respectively. The risk of this combined endpoint was also increased in people with atrial fibrillation who also carried a cardiomyopathy variant by 60% compared with non-carriers with atrial fibrillation.
The results suggest that although these cardiomyopathy-associated variants are relatively rare, they are linked to worse cardiovascular outcomes in people who carry them, which may warrant some selective genetic testing of people with atrial fibrillation, particularly if it is early in onset.
“Their findings also highlight the increasing need for genetic counselors embedded in cardiology practices and an expanded availability of specialized cardiovascular genetics clinics,” commented Day and co-authors.
“Future research is needed to test whether preemptive deployment of guideline-directed therapy for patients with atrial fibrillation harboring a cardiomyopathy variant could reduce the likelihood of developing adverse ventricular remodeling and heart failure.”
