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Genetic testing for early-onset AF yields important prognostic information

Reuters Health - 12/05/2022 - Adults with early-onset atrial fibrillation (AF) often have rare genetic variants in cardiomyopathy and arrhythmia genes, and genetic testing can provide useful prognostic information, a new study suggests.

Among 1,293 adults with AF diagnosed before age 66 years who underwent whole-genomic sequencing, disease-associated pathogenic or likely pathogenic (P/LP) rare variants were discovered in 131 (10%).

During a median follow-up of 9.9 years, 219 adults (17%) died.

In univariable analysis, having a P/LP genetic variant was associated with an increased risk of dying from any cause (hazard ratio, 1.5; 95% CI, 1.0 to 2.1; P=0.05) and the association remained significant in multivariable modeling adjusted for relevant cofactors.

Other risk factors for poorer outcome included younger age at AF diagnosis, higher BMI and lower left ventricular ejection fraction (LVEF) at diagnosis.

"Most patients with a history of reduced LVEF at enrollment did not have a disease-associated variant, but among those who did, the mortality rate was 48% during a median 9.9 years of follow-up," report Dr. Zachary Yoneda of Vanderbilt University, in Nashville, Tennessee, and colleagues in JAMA Cardiology.

The mortality rate among adults with preserved LV function and a disease-associated variant was 18% during follow-up.

"These data suggest that there is prognostic value for genetic testing in patients with early-onset AF regardless of ejection fraction at the time of presentation. Future studies are needed to prospectively define whether genetic testing improves clinical outcomes in patients with early-onset AF," the researchers conclude.

Dr. David S. Park, a cardiac electrophysiologist and assistant professor of medicine at NYU Langone's Heart Rhythm Center, in New York, told Reuters Health by email, "Atrial fibrillation is the most common arrhythmia encountered in clinical practice. Advanced age, hypertension, diabetes, coronary heart disease, obesity, sleep apnea, valvular heart disease, and heart failure are associated with the development of atrial fibrillation. However, it is increasingly recognized that genetics plays a role in developing atrial fibrillation, especially if diagnosed at an early age (age < 60 years old)."

"Genetic testing should not be performed in all patients with atrial fibrillation, but it may be considered in patients who present with atrial fibrillation at a young age or have family history of early-onset atrial fibrillation and associated cardiomyopathy, sudden death, or conduction disease (early pacemaker implantation)," said Dr. Park, who was not involved in the study.

The authors of a linked editorial say that while clinical trials are needed to test whether and how management should be altered by genetic risk stratification, "it is reasonable to hypothesize that a higher-risk early-onset AF group may benefit from closer screening and more intensive traditional cardiovascular risk factor modification."

In a higher-risk early-onset AF group, "it will be important to evaluate whether better blood pressure control, including choice of agent, or management of weight or obstructive sleep apnea, can reduce AF and AF-related morbidity and mortality," write Dr. Elizabeth McNally and Dr. Sadiya Khan with Northwestern University Feinberg School of Medicine in Chicago.

"Additional imaging and telemetry surveillance might additionally benefit a gene-positive early-onset AF group. As monitoring capabilities for AF now extend to smart watches and other patient-enabling devices, these trials are even more feasible. Additionally, cascade genetic testing for family members offers additional opportunities for further risk mitigation and ultimately even primary prevention of AF, stroke, and cardiomyopathy," they add.

SOURCE: https://bit.ly/3N9nn68 and https://bit.ly/3N67ZHD JAMA Cardiology, online May 11, 2022.

By Megan Brooks


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