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

TY - JOUR

T1 - 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

AU - Zeemering, Stef

AU - Isaacs, Aaron

AU - Winters, Joris

AU - Maesen, Bart

AU - Bidar, Elham

AU - Dimopoulou, Christina

AU - Guasch, Eduard

AU - Batlle, Montserrat

AU - Haase, Doreen

AU - Hatem, Stéphane N

AU - Kara, Mansour

AU - Kääb, Stefan

AU - Mont, Lluis

AU - Sinner, Moritz F

AU - Wakili, Reza

AU - Maessen, Jos

AU - Crijns, Harry J G M

AU - Fabritz, Larissa

AU - Kirchhof, Paulus

AU - Stoll, Monika

AU - Schotten, Ulrich

N1 - Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.

PY - 2022/12

Y1 - 2022/12

N2 - 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.

AB - 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.

KW - Humans

KW - Atrial Fibrillation

KW - Myocytes, Cardiac

KW - Heart Failure

KW - Fibrosis

KW - Inflammation/genetics

U2 - 10.1016/j.hrthm.2022.08.019

DO - 10.1016/j.hrthm.2022.08.019

M3 - SCORING: Journal article

C2 - 36007727

VL - 19

SP - 2115

EP - 2124

JO - HEART RHYTHM

JF - HEART RHYTHM

SN - 1547-5271

IS - 12

ER -