Investigating a Potential Link Between Inflammation and Cardiac Arrhythmia

Researchers investigated how immune cells in human epicardial adipose tissue (EAT) contribute to atrial fibrillation (AF), revealing a potential link between inflammation and cardiac arrhythmia according to research published in Nature Cardiovascular Research. 

Inflammation plays a key role in the formation of AF substrate, leading to electrical and structural remodeling of the atrium and increased vulnerability to AF. EAT has been implicated in the development of AF, with studies showing that EAT volume and inflammation are associated with the presence, severity, and recurrence of AF. The exact immune structure and cellular characterization of EAT in AF remain unclear.

The study examined the significance of immune infiltrate in the EAT of AF patients. Flow cytometry found an increase in tissue-resident memory T (TRM) cells in AF patients compared to controls. TRM cells are a specialized subset of memory T cells that remain in peripheral tissues long term. Through cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) and T cell receptor (TCR) sequencing, 2 transcriptionally distinct CD8+ TRM cells influenced by AF were identified in the EAT.

A total of 153 participants undergoing open heart surgery were recruited for the study, with a mean age of 66.1 years and a mean body mass index (BMI) of 28.2 kg/m2, 75% of whom were male. Participants were classified into 2 groups based on their preoperative ECG rhythm: AF or SR, with 31 participants excluded from the study due to developing postoperative AF. Patients with AF were older, more likely to undergo valve surgery, and showed higher levels of TRM cells in their EAT compared to those in sinus rhythm (SR). This increase in TRM cells was independent of risk factors and correlated with interferon gamma (IFN-γ) and interleukin 17 (IL-17) production, suggesting a potential pathological role in the development of AF.

EAT is a risk factor and independent predictor of AF incidence and recurrence after ablation. In this study, researchers found that TRM cells, a subset of memory T cells in tissue, were significantly elevated in the EAT of patients with AF. These cells showed a high degree of expansion and could impair cardiomyocyte calcium handling. The presence of TRM cells positively correlated with the production of proinflammatory cytokines known to be implicated in AF risk. TRM cells in EAT may play a role in AF pathogenesis and could serve as a predictive biomarker of disease persistence.

Reference
Vyas V, Sandhar B, Keane JM, et al. Tissue-resident memory T cells in epicardial adipose tissue comprise transcriptionally distinct subsets that are modulated in atrial fibrillation. Nat Cardiovasc Res. 2024;3:1067–1082. doi: 10.1038/s44161-024-00532-x