Circulating intermediate monocytes and toll-like receptor 4 correlate with low-voltage zones in atrial fibrillation

Heart Vessels. 2020 Dec;35(12):1717-1726. doi: 10.1007/s00380-020-01647-4. Epub 2020 Jun 10.


Inflammation has been suggested to play a key role in the pathogenesis of atrial fibrillation (AF). Our hypothesis was that this inflammation, mediated by intermediate monocytes and toll-like receptor 4 (TLR4), causes the formation and expansion of low-voltage zones (LVZs). Prior to ablation, the monocyte subsets of 78 AF patients and TLR4 expression of 66 AF patients were analyzed via a flow cytometric analysis. Based on the CD14/CD16 expression, the monocytes were divided into three subsets: classical, intermediate, and non-classical. At the beginning of the ablation session, voltage mapping was performed. LVZs were defined as all bipolar electrogram amplitudes of < 0.5 mV. Correlations between the flow cytometric analysis results and presence of LVZs, as well as the total area of the LVZ, were examined. Patients with LVZs clearly had a higher proportion of intermediate monocytes (10.0 ± 3.6% vs. 7.2 ± 2.7%, p < 0.001) than those without LVZs. TLR4 was much more frequently expressed in the intermediate monocytes than other two monocyte subsets (p < 0.001). Moreover, the TLR4 expression level in intermediate monocytes correlated positively with the total area of the LVZs (r = 0.267, p = 0.030), especially in patients with paroxysmal AF (r = 0.365, p = 0.015). The intermediate monocytes and TLR4 expression positively correlated with LVZs in AF patients.

Keywords: Atrial fibrillation; Inflammation; Intermediate monocytes; Low-voltage zones; Toll-like receptor 4.

Publication types

  • Observational Study

MeSH terms

  • Action Potentials*
  • Aged
  • Atrial Fibrillation / blood*
  • Atrial Fibrillation / diagnosis
  • Atrial Fibrillation / physiopathology
  • Biomarkers / blood
  • Female
  • GPI-Linked Proteins / blood
  • Heart Rate*
  • Humans
  • Inflammation / blood*
  • Inflammation / diagnosis
  • Inflammation Mediators / blood*
  • Lipopolysaccharide Receptors / blood
  • Male
  • Middle Aged
  • Monocytes / metabolism*
  • Prospective Studies
  • Receptors, IgG / blood
  • Toll-Like Receptor 4 / blood*


  • Biomarkers
  • CD14 protein, human
  • FCGR3B protein, human
  • GPI-Linked Proteins
  • Inflammation Mediators
  • Lipopolysaccharide Receptors
  • Receptors, IgG
  • TLR4 protein, human
  • Toll-Like Receptor 4