The Lead Episode 88:Ablation for Atrial Fibrillation in Patients With Rare Pathogenic Variants in Cardiomyopathy and Arrhythmia Genes-JACC Electrophysiology (visual aid)

JACC Electrophysiology (visual aid)

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This study investigates the efficacy of atrial fibrillation (AF) ablation in patients with rare pathogenic variants in genes associated with cardiomyopathy and arrhythmia. The researchers conducted a prospective, observational cohort study involving 1,366 participants who underwent AF catheter ablation and whole exome sequencing. The main objective was to compare the recurrence of arrhythmias after ablation between patients with genetic variants and those without.<br /><br />Findings revealed that 8% of participants had pathogenic or likely pathogenic (P/LP) variants in cardiomyopathy or arrhythmia genes. However, the presence of these variants was not statistically associated with an increased risk of recurrence in multivariable analyses. Specific gene groups were evaluated: P/LP variants in the arrhythmogenic left ventricular cardiomyopathy (ALVC) group, particularly LMNA, were linked to a significantly higher recurrence risk, whereas variants in genes associated with dilated cardiomyopathy (such as TTN), hypertrophic cardiomyopathy, and channelopathies showed no significant increase in recurrence risk.<br /><br />For individual genes, the study found that LMNA variants were associated with a higher recurrence risk, but TTN, MYBPC3, MYH7, and KCNH2 variants were not. This suggests that AF ablation is generally effective for most patients with these genetic backgrounds, except those with ALVC gene variants who have a heightened risk.<br /><br />The study underscores the complexity of ablation outcomes based on genetic profiles and suggests a nuanced approach: while many rare pathogenic CM and arrhythmia variants do not negatively affect ablation outcomes, those with LMNA variants need closer management due to higher recurrence risks. As genetic testing becomes more accessible for patients with AF, these findings can inform clinical decisions, particularly when considering AF ablation in genetically diverse patients. Further research with larger sample sizes is needed to refine these conclusions and guide personalized AF treatment strategies.

Keywords

atrial fibrillation

AF ablation

cardiomyopathy

arrhythmia

genetic variants

LMNA

recurrence risk

whole exome sequencing

personalized treatment

clinical decisions