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Inflammation and the pathogenesis of atrial fibrillation

Key Points

  • Inflammation and its associated immune response are involved in the initiation and maintenance of atrial fibrillation (AF)

  • AF can further promote inflammation, which contributes to the clinical phenomenon of 'AF begets AF'

  • Inflammatory pathways contribute to both electrical and structural atrial remodelling and thrombogenesis in patients with AF

  • The mechanisms and dynamic changes that underlie the inflammatory responses in different clinical scenarios of AF should be determined to enable the development of specific, individualized anti-inflammatory strategies

  • Therapies that target specific inflammatory cascades might be potential therapeutic strategies for the prevention of AF

Abstract

Atrial fibrillation (AF) is the most common cardiac arrhythmia. However, the development of preventative therapies for AF has been disappointing. The infiltration of immune cells and proteins that mediate the inflammatory response in cardiac tissue and circulatory processes is associated with AF. Furthermore, the presence of inflammation in the heart or systemic circulation can predict the onset of AF and recurrence in the general population, as well as in patients after cardiac surgery, cardioversion, and catheter ablation. Mediators of the inflammatory response can alter atrial electrophysiology and structural substrates, thereby leading to increased vulnerability to AF. Inflammation also modulates calcium homeostasis and connexins, which are associated with triggers of AF and heterogeneous atrial conduction. Myolysis, cardiomyocyte apoptosis, and the activation of fibrotic pathways via fibroblasts, transforming growth factor-β and matrix metalloproteases are also mediated by inflammatory pathways, which can all contribute to structural remodelling of the atria. The development of thromboembolism, a detrimental complication of AF, is also associated with inflammatory activity. Understanding the complex pathophysiological processes and dynamic changes of AF-associated inflammation might help to identify specific anti-inflammatory strategies for the prevention of AF.

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Figure 1: Sources of inflammation in patients with atrial fibrillation.
Figure 2: Inflammatory cell regulation in lone and postoperative AF.
Figure 3: HSPs in atrial fibrillation.
Figure 4: Inflammatory cells and mediators of inflammation modulate cardiac electrophysiology and structural properties.
Figure 5: The pathophysiological link between inflammation and thrombogenesis.

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Acknowledgements

This authors were supported in part by the Ministry of Science and Technology, Taiwan (NSC102-2325-B-010-005, NSC-101-2321-B-075–004, and NSC102-2911-I-008-001).

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Hu, YF., Chen, YJ., Lin, YJ. et al. Inflammation and the pathogenesis of atrial fibrillation. Nat Rev Cardiol 12, 230–243 (2015). https://doi.org/10.1038/nrcardio.2015.2

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