Journal of Orthopaedic Medicine, Musculoskeletal Research
Role of Inflammatory Pathways in Arterial Fibrillation Initiation and Progression
Abstract
Naeem Hamza, Alwakaa Osama, Edris Abdulrahman, Wajahat Muhammad Mudassir, Ghadri Osama, Mahoney Ruxandra and Zarrin Tigh Nina
Atrial fibrillation (AF) is the most common persistent cardiac rhythm disturbance, and a top cause of stroke, congestive heart failure, dementia, and death. Historically, atrial fibrillation has been considered to have a pathophysiology that involves electrical, structural, and autonomic derangements within the atrial myocardial substrate. However, increasingly over the past twenty years, inflammation has emerged as a key, underlying, and unifying pathophysiologic link between initiation and maintenance of atrial fibrillation. This literature review examines both animal and human studies to illustrate how inflammatory pathways regulate atrial electrical instability, structural fibrinosis, and atrial fibrillation. Various pro-inflammatory cytokines, including interleukin-6, interleukin-1β, tumor necrosis factor-α, and C-reactive protein, have long been linked with atrial fibrillation development, burden, and recurrence, and have direct pathologic effects on various ion channel and calcium-handling mechanisms and gap junction integrity. Stimulation of immune pathways, especially the NLRP3 inflammsome, integrates cell stress, oxidative damage, and atrial mitochondriopathy with persistent atrial arrhythmias. Furthermore, inflammation leads to the activation of fibroblasts and subsequent deposition of extracellular matrix and atrial fibrinosis, which maintains re-entrant atrial arrhythmias and promotes persistent to paroxysmal atrial fibrillation conversion. The anti-inflammatory treatments such as colchicine, corticosteroids, statins, antioxidants, lifestyle changes, and newer molecular therapies focused on IL-6 and NLRP3 signaling pathways are showing varied yet promising results based on the stage and phenotype of patients. There is evidence to totally redefine AF from being simply a cardiac condition to being a systemic inflammatory disease, which can provide promising leads in the future for the prevention and treatment of AF.