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

Background Atrial fibrillation (AF) results from a complex interaction of inflammatory, metabolic, structural, and genetic mechanisms. In patients with chronic heart failure (CHF), permanent AF confers a worse prognosis. Although inflammation is implicated in both HFpEF progression and AF pathogenesis, the relationship among systemic inflammation, atrial remodeling, metabolic dysregulation, and epigenetic modulation remains incompletely clarified. Methods We performed a cross-sectional, case–control study including 82 consecutive CHF patients with permanent AF and 82 CHF patients in sinus rhythm, matched for major cardiovascular risk factors. Serum inflammatory cytokines (IL-6, IL-8, TNF-α, CRP), metabolic and renal indices, and circulating microRNAs (miR-1-3p, miR-21-5p, miR-26a-5p) were quantified. Transthoracic echocardiography, including left atrial strain (PALS), was used to assess atrial and ventricular remodeling. Results Patients with AF were significantly older and showed more advanced atrial remodeling (higher LAVI, reduced PALS), increased relative wall thickness, and lower ejection fraction. AF patients also exhibited impaired renal function (lower eGFR, higher microalbuminuria/ACr/PCr) and elevated inflammatory markers (CRP, IL-6, IL-8, NT-proBNP). In multivariate logistic regression, LAVI, PALS, microalbuminuria, ACr, and PCr emerged as independent predictors of AF (all p < 0.05). No significant differences were observed in the expression of circulating miRNAs between groups. Conclusions Permanent AF in CHF is associated with advanced atrial remodeling, renal impairment, and systemic inflammation. Left atrial strain and renal biomarkers outperform circulating inflammatory cytokines and miRNAs in predicting AF, reinforcing the concept of AF as the clinical manifestation of an underlying atrial myopathy within a “systemic cardio-metabolic inflammatory continuum”. Longitudinal studies are warranted to determine whether targeting inflammation and endothelial dysfunction may slow atrial remodeling and AF progression.