Association Between TNF-Alpha Levels and Atrial Fibrillation Outcomes: A Systematic Review and Meta-Analysis

Background and objectives Previous studies suggest a link between tumor necrosis factor-alpha (TNF-alpha) levels and atrial fibrillation (AF). However, the nature of this relationship is disputed. To address this, we conducted a study to gather and assess evidence on the association between TNF-alpha and AF prediction. Methodology Studies were systematically searched and collected from four databases and different types of gray literature to cover all available evidence. After the screening, the selected articles’ quality and risk of bias assessment were evaluated. Meta-analysis calculated std. mean difference on the extracted data. Furthermore, heterogeneity, sensitivity, subgroups, and publication bias analyses were assessed. Results Twenty-three studies were included in this systematic review and meta-analysis, comprising a total of 2,369 patients with atrial fibrillation (AF) and 6,091 control participants. Pooled analysis using a random-effects model demonstrated a significant positive association between serum TNF-alpha levels and AF (standardized mean difference SMD = 1.15; 95% CI: 0.57–1.74; P = 0.0001). However, substantial between-study heterogeneity was observed (τ 2 = 1.4060; Cochran’s Q = 947.52; I 2 = 98.82%; P < 0.0001), indicating considerable variability in effect sizes across the included studies. Conclusions Elevated TNF-α levels are significantly associated with the presence of atrial fibrillation. Despite strong overall evidence, substantial heterogeneity and publication bias were observed among studies. These findings support a role for inflammation in AF and highlight the need for more standardized future research.