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

Stef Zeemering, Aaron Isaacs, Joris Winters, Bart Maesen, Elham Bidar, Christina Dimopoulou, Eduard Guasch, Montserrat Batlle, Doreen Haase, Stéphane N Hatem, Mansour Kara, Stefan Kääb, Lluis Mont, Moritz F Sinner, Reza Wakili, Jos Maessen, Harry J G M Crijns, Larissa Fabritz, Paulus Kirchhof, Monika StollUlrich Schotten*

*Corresponding author for this work

Research output: Contribution to journalComment/Letter to the editorAcademicpeer-review


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: To explore candidate disease processes for atrial fibrillation, we investigated 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) and persistent/permanent AF (n=51)). Analyses were stratified into patients with and 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 non-coding 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.

CONCLUSIONS: Analysis of atrial gene expression profiles identified numerous novel genes associated with persistent AF, in 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.

Original languageEnglish
Pages (from-to)2115-2124
Number of pages10
JournalHeart Rhythm
Issue number12
Early online date22 Aug 2022
Publication statusPublished - Dec 2022

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