Abstract
Atrial fibrillation (AF) can present as persistent or permanent forms with each exhibiting distinct pathological features. This study explores the gene signatures associated with cardiac and immune cells in persistent and permanent AF compared to sinus rhythm controls. We performed a meta-analysis to combine independent microarray and RNA sequencing (RNAseq) datasets for both persistent and permanent AF left atrial tissue. Cell type abundances were inferred using Cibersort and CibersortX, and gene set enrichment analysis was performed using ShinyGo. In persistent AF, a significant reduction in atrial cardiomyocytes and smooth muscle cells, along with an increase in fibroblasts, myeloid cells and pericytes was observed. Permanent AF showed increased endothelial cell and pericyte abundance. Immune cell analysis revealed altered abundances in five cell types in persistent AF, particularly an increase in neutrophils, which was not observed in permanent AF. Pathway analysis identified enriched neutrophil activation and degranulation in persistent AF, while permanent AF was enriched in extracellular matrix organization and angiogenesis pathways. In conclusion, this study highlights distinct and complex immune and cellular dynamics between chronic AF, where persistent AF has heightened immune cell infiltration and neutrophil activity which contribute to sustaining AF, whereas permanent AF shows inflammation returning to baseline but enhanced tissue remodelling and angiogenesis.