Leukocytes in atrial fibrillation: mechanisms and therapeutics

Area of Science:

• Cardiology
• Immunology
• Electrophysiology

Background:

• Atrial fibrillation (AF) is a prevalent arrhythmia linked to significant morbidity and mortality.
• While not primarily an immune disorder, leukocytes increasingly show influence on AF substrate vulnerability.
• Evidence suggests various leukocyte populations contribute to AF initiation, maintenance, and complications.

Purpose of the Study:

• To review the multifaceted roles of different leukocyte populations in atrial fibrillation.
• To explore the mechanisms by which leukocytes impact AF pathophysiology.
• To discuss immune-targeted therapies for AF and challenges in clinical translation.

Main Methods:

• Literature review summarizing clinical, translational, and experimental evidence.
• Outline of core electrophysiologic mechanisms of AF.
• Discussion of leukocyte influence via atrial recruitment, immune remodeling, NETs, and fibrosis.

Main Results:

• Specific leukocyte types (neutrophils, monocytes, macrophages, B-cells, T-cells, mast cells) are implicated in AF.
• Leukocytes affect AF through atrial recruitment, electrical remodeling, thromboinflammation, and fibrosis.
• Context-specific roles of leukocytes identified in postoperative, cardiometabolic, and persistent AF.

Conclusions:

• Leukocytes are key modulators of AF pathophysiology, impacting initiation, maintenance, and complications.
• Immune-targeted therapies show promise but face challenges in clinical translation due to heterogeneity.
• Further research is needed to optimize timing, patient selection, and endpoints for immune-based AF treatments.