Inflammatory Activation, Epigenetic Signature and Morpho-Structural Alteration in a Cohort of Patients With Chronic Heart Failure and Permanent Atrial Fibrillation: A Cross-Sectional Study

Background Atrial fibrillation (AF) is a complex disorder involving inflammatory, morpho-structural, and genetic factors. Emerging evidence suggests inflammation plays a pivotal role in AF initiation, maintenance, and outcomes. Methods We conducted a cross-sectional case-control study to assess whether, among patients with chronic heart failure (CHF) and permanent AF, serum inflammatory cytokines, metabolic parameters, epigenetic factors, and echocardiographic markers of structural remodeling are interrelated. Eighty-two consecutive CHF patients with permanent AF and 82 CHF patients with sinus rhythm and no AF history were enrolled from the Internal Medicine and Stroke Care Unit at “P. Giaccone” Hospital, Palermo, between January 2020 and May 2022. Results AF patients were older and exhibited higher left atrial volume index (LAVI), reduced left atrial (LA) strain, increased relative wall thickness (RWT), and lower ejection fraction (EF%). Renal markers, including estimated glomerular filtration rate (eGFR) and microalbuminuria, were significantly different. Inflammatory markers such as C-reactive protein (CRP), interleukin 6 (IL-6), interleukin 8 (IL-8), and NT-proBNP were elevated in the AF group. Multivariable logistic regression identified LAVI, LA strain, microalbuminuria, albumin/creatinine ratio (ACr), and protein/creatinine ratio (PCr) as independent predictors of AF. Correlation analyses demonstrated strong associations between echocardiographic, inflammatory, and renal parameters. No significant differences in circulating miRNAs were observed. Conclusions These findings highlight the intricate interconnection between atrial remodeling, renal dysfunction, and systemic inflammation in AF pathogenesis. A better understanding of these mechanisms may inform future risk stratification strategies and support the development of more effective, targeted therapies in patients with CHF.