Electrical, contractile and structural remodeling during atrial fibrillation

Abstract

The natural history of atrial fibrillation (AF) is characterized by a gradual worsening with time. The recent finding that AF itself produces changes in atrial function and structure has provided a possible explanation for the progressive nature of this arrhythmia. Electrical remodeling (shortening of atrial refractoriness) develops within the first days of AF and contributes to an increase in stability of AF. However, 'domestication of AF' must also depend on a 'second factor' since the persistence of AF continues to increase after electrical remodeling has been completed. Atrial contractile remodeling (loss of contractility) leads to a reduced atrial transport function after cardioversion of AF. An important clinical consequence is that during several days after restoration of sinus rhythm, the risk of atrial thrombus formation is still high. In addition, the reduction of atrial contractility during AF may enhance atrial dilatation which may add to the persistence of AF. Tachycardia-induced structural remodeling takes place in a different time domain (weeks to months). Myolysis probably contributes to the loss of atrial contractile force. Although it might explain the loss of efficacy of pharmacological cardioversion and the development of permanent AF, the role of structural remodeling in the progression of AF is still unclear. Atrial structural remodeling also occurs as a result of heart failure and other underlying cardiovascular diseases. The associated atrial fibrosis might explain intra-atrial conduction disturbances and the susceptibility for AF. Thus, both AF itself and the underlying heart disease are responsible for the development of the arrhythmogenic substrate. New strategies for prevention and termination of AF should be build on our knowledge of the mechanisms and time course of AF-induced atrial remodeling.

2012 HRS/EHRA/ECAS Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation: Recommendations for Patient Selection, Procedural Techniques, Patient Management and Follow-up, Definitions, Endpoints, and Research Trial Design

“…20,151,152 The transition likely reflects progressive structural and electrophysiological remodeling in both atria, making the sources of the arrhythmia more stable by fundamental mechanisms that have been incompletely explored. 153,154,155,156 …”

“…167 At the molecular scale are dynamics changes in the genome, the transcriptome, and the signaling pathways underlying the generation of profibrotic molecules 168 ; cellular changes involve interactions among the various cardiac cells, including myocytes, fibroblasts or myofibroblasts, and inflammatory cells such as macrophages and neutrophils 169 ; and tissue changes relate to the dynamics of scar, angiogenesis, electrical conduction, and contractility. 153 Fibrosis can certainly act as an electrically insulating obstacle. Profibrotic stimuli promote differentiation of fibroblasts into activated myofibroblasts, which electronically couple to myocytes in vitro 20,150,151,152 ; whether this occurs to a significant extent in AF atria in vivo remains uncertain.…”

“…13,153,154,190 A number of ion channel modifications underlying such electrical changes have been described in animal models and humans. 17,190,191,192 A recent study 158 used a clinically relevant ovine model of intermittent RA tachypacing and demonstrated that, after the first AF episode, the dominant excitation frequency (DF) increased gradually during a 2-week period in both LA and RA until it stabilized at a time that coincided with the onset of persistent AF.…”

“…Over time, AF progresses from a trigger-driven to a more substrate-mediated arrhythmia due to structural remodeling of the atria. 153,243 Ablative therapy is therefore aimed at either eliminating the trigger initiating AF or modifying the arrhythmogenic substrate. The most commonly employed ablation strategy consists of electrical isolation of the PVs by creation of circumferential lesions around the right and the left PV.…”

The Effects of Wenxin Keli on P-Wave Dispersion and Maintenance of Sinus Rhythm in Patients with Paroxysmal Atrial Fibrillation: A Meta-Analysis of Randomized Controlled Trials

“…Electrical remodelling could shorten atrial refractoriness and contributes to an increase in the stability of AF. Atrial structural remodelling occurs as a result of heart failure and other underlying cardiovascular diseases [29, 30]. The ionic mechanisms underlying this arrhythmogenic process have been elucidated by a number of patch clamp experiments in isolated atrial cells from animal models and patients in chronic AF.…”