Structural remodeling in atrial fibrillation

Abstract

Atrial fibrillation occurs and maintains itself in the context of a morphologically and functionally altered atrial substrate that can be induced by stressors such as underlying diseases (cardiac or noncardiac) or aging. The resultant structural remodeling is a slow process that progressively affects myocytes and the myocardial interstitium, and takes place from as early as the first days of atrial tachyarrhythmia. The left atrium, and particularly its posterior wall, is the location where remodeling is concentrated to the greatest extent. The mechanisms that underlie the remodeling process in atrial fibrillation have not yet been completely elucidated, although experimental and clinical investigations have indicated a number of signaling systems, inflammation, oxidative stress, atrial stretching and ischemia as factors involved in the cascade of events that leads to atrial fibrillation. The aim of this Review is to provide a comprehensive overview of the morphological changes that characterize the fibrillating atrial myocardium at histological and ultrastructural levels, and the established and hypothetical pathogenetic mechanisms involved in structural remodeling. This article also highlights the emerging therapies being developed to prevent progression of atrial fibrillation.

Cardiac mast cells cause atrial fibrillation through PDGF-A–mediated fibrosis in pressure-overloaded mouse hearts

“…Recent electrophysiological evidence has indicated that the triggering ectopic foci act on predisposing substrates to initiate single-or multiple-circuit reentry, leading to AF (2). The most important histopathological change in AF is atrial fibrosis (3,4). Accumulation of ECM proteins has been documented in biopsied specimens of atrium from patients with AF (5), and experimental studies using animal models have indicated that interstitial deposition of dense ECM proteins causes separation between bundles of atrial myocytes and disturbs cell-to-cell impulse propagation (3,4).…”

“…The most important histopathological change in AF is atrial fibrosis (3,4). Accumulation of ECM proteins has been documented in biopsied specimens of atrium from patients with AF (5), and experimental studies using animal models have indicated that interstitial deposition of dense ECM proteins causes separation between bundles of atrial myocytes and disturbs cell-to-cell impulse propagation (3,4). In addition, atrial fibrosis potentially exaggerates myocardial ischemia by hampering oxygen diffusion and alters the electrophysical and biomechanical properties of atrial myocytes, allowing the initiation and perpetuation of AF (4).…”

Serial N-Terminal Pro Brain Natriuretic Peptide Assessments in Predicting New-Onset Atrial Fibrillation in ST Elevation Myocardial Infarction Patients who Undergo Primary Percutaneous Coronary Intervention

“…Furthermore, atrial dysfunction, atrial ischemia, pericarditis, congestive heart failure due to ischemia, atrial reverse remodeling and enhanced sympathetic tone may also play an important role in AF in the setting of STEMI [20][21][22][23][24]. An increased sympathetic tone in STEMI patients is associated with worse outcome after 2 years [25].…”

Can We Predict Electroanatomical Remodeling of Left Atrium in Patients With Non-Valvular Atrial Fibrillation by Transforming Growth Factor-βand Tissue Inhibitor of Metalloproteinase-1?

“…Accumulation of ECM proteins has been documented in biopsy specimens of the LA from patients with AF, 9 and experimental studies using animal models have indicated that interstitial deposition of dense ECM proteins causes separation of the bundles of atrial myocytes and disturbs cell-to-cell impulse propagation. 8 Dense and disorganized collagen deposition with apoptosis or necrosis of cardiomyocytes reduces the voltage of the contact atrial electrogram and enlarges the LA volume; that is, electroanatomical remodeling.…”