Senescent CD8+ T cells were independently associated with atrial fibrillation prevalence (OR 2.876, P<0.05) and postprocedural recurrence (HR 22.955, P<0.0001).
Cohort
Are senescent CD8+ T cells associated with atrial fibrillation prevalence and postprocedural recurrence?
Senescent CD8+ T cells are significantly associated with AF prevalence and postprocedural recurrence, potentially driving proarrhythmic calcium handling abnormalities via IFN-γ secretion.
Effect estimate: OR 2.876 (prevalence); HR 22.955 (recurrence)
p-value: p=<0.05 (prevalence); <0.0001 (recurrence)
AIMS: Immune cell alterations may play a role in the development of atrial fibrillation (AF). Our objective was to comprehensively characterize immune cells in AF, and investigate the potential mechanisms. METHODS AND RESULTS: Single-cell RNA sequencing and multicolour flow cytometry revealed that T cells constituted the most significant subset alterations in AF, and senescent CD8+ T cells were AF-associated subset. Senescent CD8+ T cells increased in both peripheral veins (P < 0.0001) and the left atria (P < 0.05) in patients with AF compared to non-AF control. Senescent CD8+ T cells were independently associated with AF prevalence (odds ratio = 2.876, P < 0.05) and postprocedural recurrence (hazard ratio = 22.955, P < 0.0001) using a cross-sectional study and a subsequent prospective cohort study. Senescent CD8+ T cells secreted an increased amount of interferon (IFN)-γ, which induces Ca2+ handling abnormalities in human induced pluripotent stem cell-derived atrial cardiomyocytes, and translated into an increased susceptibility to AF assessed by heart optical mapping. CONCLUSIONS: An increased amount of senescent CD8+ T cells may be a hallmark of the immune senescence phenotype in AF and potentially serve as a valid biomarker for assessing prevalence and postprocedural recurrence of AF. By connecting immune senescence with electrophysiological disturbances in AF, this research provides a potential mechanism for the involvement of senescent CD8+ T cells in proarrhythmic calcium disorders and suggests novel avenues for developing new immune-modulatory and senolytic therapies for AF.
Li et al. (Wed,) conducted a cohort in Atrial fibrillation. Senescent CD8+ T cells vs. Non-AF control was evaluated on AF prevalence and postprocedural recurrence (OR 2.876 (prevalence); HR 22.955 (recurrence), p=<0.05 (prevalence); <0.0001 (recurrence)). Senescent CD8+ T cells were independently associated with atrial fibrillation prevalence (OR 2.876, P<0.05) and postprocedural recurrence (HR 22.955, P<0.0001).