Undergraduate Research Assistant UNC Chapel Hill Chapel Hill, North Carolina, United States
Introduction/Rationale: Mast cells reside in cardiac tissue and release inflammatory mediators upon IgE-mediated activation. While mast cells have been implicated in cardiac remodeling, the relationship between IgE and arrhythmias remains unexplored. We hypothesized that elevated IgE is associated with increased atrial fibrillation (AF) risk and that IgE-dependent mast cell activation promotes cardiac inflammation and sympathetic remodeling.
Methods: We performed a propensity-matched cohort study using TriNetX comparing patients with elevated IgE (>1000 IU/mL) versus normal IgE ( < 100 IU/mL), matched on 29 covariates. The primary outcome was incident AF/flutter over 5 years. In parallel, C57BL/6J mice were sensitized to peanut allergen and fed peanut for 4 weeks. Hearts were analyzed for mast cell density, inflammatory cytokines, tyrosine hydroxylase (TH) as a sympathetic nerve marker, and sinoatrial node (SAN) macrophage infiltration.
Results: After matching, 54,007 patients per cohort were analyzed (mean age 29). Elevated IgE was associated with increased AF risk (1.54% vs 1.25%; OR 1.24, 95% CI 1.12-1.37, p< 0.0001). In mice, sensitization increased cardiac mast cells 3-fold (p < 0.01), an effect absent in IgE-deficient mice. Notably, much of the increase in mast cells was observed in or near cardiac ganglia and conducting system, key locations in the development or arrhythmia. Sensitized mice demonstrated elevated cardiac IL-1α, IL-6, IL-13, and TNFα. TH staining revealed 7-fold increased right atrial sympathetic nerve density (1.5% vs 0.2% area, p< 0.001). CD68 immunostaining showed increased macrophage infiltration within the SAN of sensitized animals.
Conclusion: Elevated IgE is associated with increased AF risk in young adults. IgE-dependent mast cell activation drives cardiac inflammation, sympathetic hyperinnervation, and SAN inflammation. These findings identify allergic sensitization as a novel arrhythmia risk factor with therapeutic implications.
