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Zeemering, Stef; Isaacs, Aaron; Winters, Joris; Maesen, Bart; Bidar, Elham; Dimopoulou, Christina; Guasch, Eduard; Batlle, Montserrat; Haase, Doreen; Hatem, Stephane N.; Kara, Mansour; Kääb, Stefan; Mont, Lluis; Sinner, Moritz F.; Wakili, Reza; Maessen, Jos; Crijns, Harry J. G. M.; Fabritz, Larissa; Kirchhof, Paulus; Stoll, Monika and Schotten, Ulrich (2022): Atrial fibrillation in the presence and absence of heart failure enhances expression of genes involved in cardiomyocyte structure, conduction properties, fibrosis, inflammation, and endothelial dysfunction. In: Heart Rhythm, Vol. 19, No. 12: pp. 2115-2124

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BACKGROUND Little is known about genome-wide changes in the atrial transcriptome as a cause or consequence of atrial fibrillation (AF), and the effect of its common and clinically relevant comorbidity-heart failure (HF). OBJECTIVE The purpose of this study was to explore candidate disease processes for AF by investigating gene expression changes in atrial tissue samples from patients with and without AF, stratified by HF. METHODS RNA sequencing was performed in right and left atrial appendage tissue in 195 patients undergoing open heart surgery from centers participating in the CATCH-ME consortium (no history of AF, n = 91;paroxysmal AF, n = 53;persistent/permanent AF, n = 51). Analyses were stratified into patients with/without HF (n = 75/120) and adjusted for age, sex, atrial side, and a combination of clinical characteristics. RESULTS We identified 35 genes associated with persistent AF compared to patients without a history of AF, both in the presence or absence of HF (false discovery rate <0.05). These were mostly novel associations, including 13 long noncoding RNAs. Genes were involved in regulation of cardiomyocyte structure, conduction properties, fibrosis, inflammation, and endothelial dysfunction. Gene set enrichment analysis identified mainly inflammatory gene sets to be enriched in AF patients without HF, and gene sets involved in cellular respiration in AF patients with HF. CONCLUSION Analysis of atrial gene expression profiles identified numerous novel genes associated with persistent AF, in the presence or absence of HF. Interestingly, no consistent transcriptional changes were associated with paroxysmal AF, suggesting that AF-induced changes in gene expression predominate other changes.

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