Association between Inflammation and New-Onset Atrial Fibrillation in Acute Coronary Syndromes

Abstract

Acute coronary syndrome (ACS) is a complex clinical syndrome that encompasses acute myocardial infarction (AMI) and unstable angina (UA). Its underlying mechanism refers to coronary plaque disruption, with consequent platelet aggregation and thrombosis. Inflammation plays an important role in the progression of atherosclerosis by mediating the removal of necrotic tissue following myocardial infarction and shaping the repair processes that are essential for the recovery process after ACS. As a chronic inflammatory disorder, atherosclerosis is characterized by dysfunctional immune inflammation involving interactions between immune (macrophages, T lymphocytes, and monocytes) and vascular cells (endothelial cells and smooth muscle cells). New-onset atrial fibrillation (NOAF) is one of the most common arrhythmic complications in the setting of acute coronary syndromes, especially in the early stages, when the myocardial inflammatory reaction is at its maximum. The main changes in the atrial substrate are due to atrial ischemia and acute infarcts that can be attributed to neurohormonal factors. The high incidence of atrial fibrillation (AF) post-myocardial infarction may be secondary to inflammation. Inflammatory response and immune system cells have been involved in the initiation and development of atrial fibrillation. Several inflammatory indexes, such as C-reactive protein and interleukins, have been demonstrated to be predictive of prognosis in patients with ACS. The cell signaling activation patterns associated with fibrosis, apoptosis, and hypertrophy are forms of cardiac remodeling that occur at the atrial level, predisposing to AF. According to a recent study, the presence of fibrosis and lymphomononuclear infiltration in the atrial tissue was associated with a prior history of AF. However, inflammation may contribute to both the occurrence/maintenance of AF and its thromboembolic complications.

Keywords: acute coronary syndrome; atrial fibrillation; inflammation.

Figure 1

Major components of atrial remodeling. The inflammatory process promotes the production of pro-inflammatory cytokines (IL-6, IL-8, TNF-α, and IFN-γ) contributing to both structural and electrical remodeling. Inflammatory cytokines induce structural remodeling by activation of cardiac fibroblasts, leading to apoptosis and atrial fibrosis. Stimulated by inflammatory status, RAAS increases the production of Angiotensin II and TGF-β, which assess the secretion of more cytokines, maintaining inflammation. Among ROS, Angiotensin II contributes to abnormal Ca²⁺ handling, resulting in a decreased action potential duration and electrical remodeling. Abbreviations: AF—atrial fibrillation; ROS—reactive oxygen species.

Figure 2

Mechanism of CRP in inflammation. Stimulated by IL-6, hepatocytes release CRP molecules and activate the classic complement pathway. By binding Factor H, the alternative pathway is inhibited and, therefore, the inactivation of C3b to iC3b promotes phagocytosis. Abbreviations: CRP—C reactive protein.