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Background Although atrial fibrillation (AF) is common in hypertrophic cardiomyopathy (HCM) patients, the relationship between genetic variation and AF has been poorly defined. Characterizing genetic subtypes of HCM and their associations with AF may help to improve personalized medical care. We aimed to investigate the link between sarcomeric gene variation and incident AF in HCM patients. Methods and Results Patients from the multinational Sarcomeric Human Cardiomyopathy Registry were followed for incident AF. Those with likely pathogenic or pathogenic variants in sarcomeric genes were included. The AF incidence was ascertained by review of medical records and electrocardiograms at each investigative site. One thousand forty adult HCM patients, without baseline AF and with likely pathogenic or pathogenic variation in eitherMYH7 (n=296),MYBPC3 (n=659), or thin filament genes (n=85), were included. Compared with patients with variation in other sarcomeric genes, those withMYH7 variants were younger on first clinical encounter at the Sarcomeric Human Cardiomyopathy Registry site and more likely to be probands than theMYBPC3 variants. During an average follow-up of 7.2 years, 198 incident AF events occurred. Patients with likely pathogenic or pathogenic mutations inMYH7 had the highest incidence of AF after adjusting for age, sex, proband status, left atrial size, maximal wall thickness, and peak pressure gradient (hazard ratio, 1.7; 95% CI, 1.1–2.6;P =0.009).Conclusions During a mean follow-up of 7.2 years, new-onset AF developed in 19% of HCM patients with sarcomeric mutations. Compared with other sarcomeric genes, patients with likely pathogenic or pathogenic variation inMYH7 had a higher rate of incident AF independent of clinical and echocardiographic factors.

Incident Atrial Fibrillation Is Associated With MYH7 Sarcomeric Gene Variation in Hypertrophic Cardiomyopathy