Related Experiment Videos
[Atrial fibrillation: pathophysiology]
Wolfgang Schoels1, Alexander Bauer, Ruediger Becker
1Abteilung Innere Medizin III, Medizinische Universitätsklinik Heidelberg. Wolfgang_Schoels@med.uni-heidelberg.de
Insights
Atrial fibrillation pathophysiology is evolving beyond random reentrant circuits. New evidence suggests focal triggers and organized activation patterns are key in this common arrhythmia.
Area of Science:
- Cardiology
- Electrophysiology
- Molecular Biology
Context:
- Classical models of atrial fibrillation (AF) pathophysiology relied on multiple, random reentrant circuits.
- Recent findings challenge these traditional concepts, necessitating updated understanding.
- Atrial remodeling, driven by intracellular calcium overload and gene expression changes, plays a crucial role.
Purpose:
- To review and synthesize current understanding of atrial fibrillation pathophysiology.
- To integrate recent findings with classical theories on reentrant circuits.
- To explore alternative mechanisms, including focal activity and organized activation patterns.
Summary:
- Atrial fibrillation pathophysiology is shifting from a purely random reentrant circuit model.
- Evidence supports the role of single meandering circuits, focal triggers, and spatio-temporal periodicity.
- Atrial remodeling, influenced by calcium handling and gene regulation, is a critical substrate.
- A subset of atrial fibrillation cases appears to be focally induced, supported by ablation studies.
Impact:
- This review refines the understanding of atrial fibrillation mechanisms.
- It highlights the importance of focal triggers and organized patterns in AF.
- The findings may inform novel therapeutic strategies targeting specific AF substrates.
Background:
Although several classical studies seemed to provide clear ideas on the pathophysiology of atrial fibrillation, current concepts have to be modified on the basis of more recent findings.
Reentrant Circuits:
Based on the findings of Garrey and of Moe & Abildskov, atrial fibrillation has long been considered as the prototype of an arrhythmia being caused by multiple, random reentrant circuits, the number of which would determine the stability of the reentrant process. Local refractory and conduction properties would determine the size of individual circuits, a hypothesis quite convincing with respect to refractoriness, but so far hard to prove with respect to conduction. The finding that rapid atrial rates shorten atrial refractory periods and reverse rate adaptation (atrial remodeling) has coined the phrase "atrial fibrillation begets atrial fibrillation", indicating that any atrial tachyarrhythmia modifies the substrate in a way that favors reentry. With intracellular calcium overload being the initial trigger, down-regulation of genes encoding for calcium channels seems to primarily account for atrial remodeling. Primarily neglected concepts on the pathophysiology of atrial fibrillation suggesting single, meandering circuits or focal activity have regained attention. Atrial fibrillation as a random phenomenon is questioned not only by the dominant role of the left atrium for the maintenance of the arrhythmia, but also by most recent data demonstrating a spatio-temporal periodicity in activation patterns. Finally, ablation studies have provided convincing evidence that there is a subset of patients with focal or at least focally induced atrial fibrillation.