Comparison of Atrial Remodeling Caused by Sustained Atrial Flutter Versus Atrial Fibrillation

J Am Coll Cardiol. 2020 Jul 28;76(4):374-388. doi: 10.1016/j.jacc.2020.05.062.

Abstract

Background: Atrial flutter (AFL) and atrial fibrillation (AF) are associated with AF-promoting atrial remodeling, but no experimental studies have addressed remodeling with sustained AFL.

Objectives: This study aimed to define the atrial remodeling caused by sustained atrial flutter (AFL) and/or atrial fibrillation (AF).

Methods: Intercaval radiofrequency lesions created a substrate for sustained isthmus-dependent AFL, confirmed by endocavity mapping. Four groups (6 dogs per group) were followed for 3 weeks: sustained AFL; sustained AF (600 beats/min atrial tachypacing); AF superimposed on an AFL substrate (AF+AFLs); sinus rhythm (SR) with an AFL substrate (SR+AFLs; control group). All dogs had atrioventricular-node ablation and ventricular pacemakers at 80 beats/min to control ventricular rate.

Results: Monitoring confirmed spontaneous AFL maintenance >99% of the time in dogs with AFL. At terminal open-chest study, left-atrial (LA) effective refractory period was reduced similarly with AFL, AF+AFLs and AF, while AF vulnerability to extrastimuli increased in parallel. Induced AF duration increased significantly in AF+AFLs and AF, but not AFL. Dogs with AF+AFLs had shorter cycle lengths and substantial irregularity versus dogs with AFL. LA volume increased in AF+AFLs and AF, but not dogs with AFL, versus SR+AFLs. Optical mapping showed significant conduction slowing in AF+AFLs and AF but not AFL, paralleling atrial fibrosis and collagen-gene upregulation. Left-ventricular function did not change in any group. Transcriptomic analysis revealed substantial dysregulation of inflammatory and extracellular matrix-signaling pathways with AF and AF+ALs but not AFL.

Conclusions: Sustained AFL causes atrial repolarization changes like those in AF but, unlike AF or AF+AFLs, does not induce structural remodeling. These results provide novel insights into AFL-induced remodeling and suggest that early intervention may be important to prevent irreversible fibrosis when AF intervenes in a patient with AFL.

Keywords: atrial fibrillation; atrial flutter; atrial remodeling; fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atrial Fibrillation* / complications
  • Atrial Fibrillation* / pathology
  • Atrial Fibrillation* / physiopathology
  • Atrial Flutter* / complications
  • Atrial Flutter* / pathology
  • Atrial Flutter* / physiopathology
  • Atrial Remodeling*
  • Catheter Ablation / methods
  • Dogs
  • Electrocardiography / methods
  • Fibrosis / etiology
  • Fibrosis / pathology
  • Fibrosis / prevention & control
  • Heart Atria* / pathology
  • Heart Atria* / physiopathology

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