AIMS No studies have assessed the specific contributions of atrial fibrillation (AF)-related atrial versus associated ventricular arrhythmia to remodeling. This study assessed the roles of atrial arrhythmia versus high ventricular… Click to show full abstract
AIMS No studies have assessed the specific contributions of atrial fibrillation (AF)-related atrial versus associated ventricular arrhythmia to remodeling. This study assessed the roles of atrial arrhythmia versus high ventricular rate in AF-associated remodeling. METHODS AND RESULTS Four primary dog-groups (12/group) were subjected to 3-week pacing: 600-bpm atrial-tachypacing maintaining AF (AF w/o-AVB); atrial-tachypacing with atrioventricular-node ablation (AF+AVB) and ventricular-demand pacing (80-bpm); 160-bpm ventricular-tachypacing (V160) reproducing the response-rate during AF; and sinus rhythm with AVB/ventricular-pacing at 80-bpm (CTL). 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 upregulation only in AF w/o-AVB. Connexin43 gene-expression was reduced only in AF w/o-AVB. An additional group of 240-bpm ventricular tachypacing dogs (VTP240; to induce heart failure) was studied: versus 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. CONCLUSIONS The atrial tachyarrhythmia and rapid ventricular response during AF produce distinct atrial remodeling; both contribute to the arrhythmogenic substrate, providing new insights into AF-related remodeling and novel considerations for ventricular rate-control. TRANSLATIONAL PERSPECTIVE AF often produces a rapid and irregular arrhythmia in both the atria and ventricles. This study evaluates the contributions of AF-induced atrial versus ventricular arrhythmia to atrial remodeling. Each component produced discrete features: AF-induced atrial arrhythmia caused accelerated repolarization and abbreviated refractoriness, strongly increased vulnerability to AF-induction by premature ectopic beats, conduction slowing and moderate atrial fibrosis; whereas ventricular arrhythmia slightly increased vulnerability, slowed conduction and induced moderate fibrosis without affecting repolarization/refractoriness,. Combined atrial and ventricular arrhythmia abbreviated refractoriness, strongly increased vulnerability and fibrosis and greatly increased AF stability/duration. This work suggests that in the absence of ventricular rate control, the rapid ventricular response can cause AF-promoting atrial remodeling without overt heart failure; further research is needed to clarify the clinical relevance of these findings.
               
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