Jean-Baptiste Guichard1,2, Feng Xiong1, Xiao-Yan Qi1, Nathalie L'Heureux1, Roddy Hiram1, Jiening Xiao1, Patrice Naud1, Jean-Claude Tardif1, Antoine Da Costa2, Stanley Nattel1,3,4,5. 1. Department of Medicine and Research Center, Montreal Heart Institute and Université de Montréal, 5000 Belanger Street, Montreal H1T 1C8, Quebec, Canada. 2. Department of Cardiology, University Hospital of Saint-Étienne, University Jean Monnet, Saint-Étienne 42000, France. 3. Department of Pharmacology and Therapeutics, McGill University Montreal, Montreal, Canada. 4. Institute of Pharmacology, West German Heart and Vascular Center, Faculty of Medicine, University Duisburg-Essen, Essen, Germany. 5. IHU LIRYC and Fondation Bordeaux Université, Bordeaux, France.
Abstract
AIMS: No studies have assessed the specific contributions of atrial fibrillation (AF)-related atrial vs. associated ventricular arrhythmia to remodelling. This study assessed the roles of atrial arrhythmia vs. high ventricular rate in AF-associated remodelling. METHODS AND RESULTS: Four primary dog-groups (12/group) were subjected to 3-week pacing: 600-b.p.m. atrial tachypacing maintaining AF [AF w/o- atrioventricular block (AVB)]; atrial tachypacing with atrioventricular-node ablation (AF+AVB) and ventricular-demand pacing (80 b.p.m.); 160-b.p.m. ventricular-tachypacing (V160) reproducing the response rate during AF; and sinus rhythm with AVB/ventricular-pacing at 80-b.p.m. (control group). At terminal study, left-atrial (LA) effective refractory period (ERP) was reduced equally in both AF groups (w/o-AVB and AF+AVB). AF-inducibility was increased strongly in AF groups (w/o-AVB and AF+AVB) and modestly in V160. AF duration was significantly increased in AF w/o-AVB but not in AF+AVB or V160. Conduction velocity was decreased in AF w/o-AVB, to a greater extent than in AF+AVB and V160. Atrial fibrous-tissue content was increased in AF w/o-AVB, AF+AVB and V160, with collagen-gene up-regulation only in AF w/o-AVB. Connexin43 gene expression was reduced only in AF w/o-AVB. An additional group of 240-b.p.m. ventricular tachypacing dogs (VTP240; to induce heart failure) was studied: vs. other tachypaced groups, VTP240 caused greater fibrosis, but no change in LA-ERP or AF-inducibility. VTP240 also increased AF duration, strongly decreased left ventricular ejection fraction, and was the only group with LA natriuretic-peptide activation. CONCLUSION: The atrial tachyarrhythmia and rapid ventricular response during AF produce distinct atrial remodelling; both contribute to the arrhythmogenic substrate, providing new insights into AF-related remodelling and novel considerations for ventricular rate-control. Published on behalf of the European Society of Cardiology. All rights reserved.
AIMS: No studies have assessed the specific contributions of atrial fibrillation (AF)-related atrial vs. associated ventricular arrhythmia to remodelling. This study assessed the roles of atrial arrhythmia vs. high ventricular rate in AF-associated remodelling. METHODS AND RESULTS: Four primary dog-groups (12/group) were subjected to 3-week pacing: 600-b.p.m. atrial tachypacing maintaining AF [AF w/o- atrioventricular block (AVB)]; atrial tachypacing with atrioventricular-node ablation (AF+AVB) and ventricular-demand pacing (80 b.p.m.); 160-b.p.m. ventricular-tachypacing (V160) reproducing the response rate during AF; and sinus rhythm with AVB/ventricular-pacing at 80-b.p.m. (control group). At terminal study, left-atrial (LA) effective refractory period (ERP) was reduced equally in both AF groups (w/o-AVB and AF+AVB). AF-inducibility was increased strongly in AF groups (w/o-AVB and AF+AVB) and modestly in V160. AF duration was significantly increased in AF w/o-AVB but not in AF+AVB or V160. Conduction velocity was decreased in AF w/o-AVB, to a greater extent than in AF+AVB and V160. Atrial fibrous-tissue content was increased in AF w/o-AVB, AF+AVB and V160, with collagen-gene up-regulation only in AF w/o-AVB. Connexin43 gene expression was reduced only in AF w/o-AVB. An additional group of 240-b.p.m. ventricular tachypacing dogs (VTP240; to induce heart failure) was studied: vs. other tachypaced groups, VTP240 caused greater fibrosis, but no change in LA-ERP or AF-inducibility. VTP240 also increased AF duration, strongly decreased left ventricular ejection fraction, and was the only group with LA natriuretic-peptide activation. CONCLUSION: The atrial tachyarrhythmia and rapid ventricular response during AF produce distinct atrial remodelling; both contribute to the arrhythmogenic substrate, providing new insights into AF-related remodelling and novel considerations for ventricular rate-control. Published on behalf of the European Society of Cardiology. All rights reserved.
Authors: Jordi Heijman; Henry Sutanto; Harry J G M Crijns; Stanley Nattel; Natalia A Trayanova Journal: Cardiovasc Res Date: 2021-06-16 Impact factor: 10.787