Author + information
- Received March 26, 2020
- Revision received May 20, 2020
- Accepted May 26, 2020
- Published online July 20, 2020.
- Jean-Baptiste Guichard, MD, PhDa,b,
- Patrice Naud, PhDa,
- Feng Xiong, PhDa,
- Xiaoyan Qi, PhDa,
- Nathalie L’Heureux, DECa,
- Roddy Hiram, PhDa,
- Jean-Claude Tardif, MDa,
- Raymond Cartier, MD, PhDa,
- Antoine Da Costa, MD, PhDb and
- Stanley Nattel, MDa,c,d,e,∗ ()
- aDepartment of Medicine and Research Center Montreal Heart Institute and Université de Montréal, Montréal, Québec, Canada
- bDepartment of Cardiology, University Hospital of Saint-Étienne, University Jean Monnet, Saint-Étienne, France
- cDepartment of Pharmacology and Therapeutics, McGill University Montréal, Montréal, Québec, Canada
- dInstitute of Pharmacology, West German Heart and Vascular Center, Faculty of Medicine, University Duisburg-Essen, Essen, Germany
- eIHU LIRYC and Fondation Bordeaux Université, Bordeaux, France
- ↵∗Address for correspondence:
Dr. Stanley Nattel, Department of Medicine and Research Center Montréal Heart Institute and Université de Montréal, 5000 Belanger Street E, Montréal H1T 1C8, Québec, Canada.
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.
This study was supported by the Canadian Institutes of Health Research (Foundation Grant 148401) and the Heart and Stroke Foundation of Canada (G-16-00012708). Dr. Guichard has received grant support from Abbott Labs. The authors had full access to and take responsibility for the integrity of the data. All authors have read and have agreed to the manuscript as written. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC author instructions page.
- Received March 26, 2020.
- Revision received May 20, 2020.
- Accepted May 26, 2020.
- 2020 American College of Cardiology Foundation
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