Abstract 17762: Temporal Evolution of Atrial Remodeling and Atrial Arrhythmogenesis During Tachycardiomyopathic Heart Failure Development
Introduction: Heart failure (HF) is a common cause of atrial fibrillation (AF). Both changes in Ca2+ handling and tissue fibrosis have been implicated but the role of these and other mechanisms are poorly understood. This study assessed the temporal relationships among components of left atrial (LA) remodeling and arrhythmogenesis during HF development.
Methods: HF was induced by ventricular tachypacing (VTP, 240 bpm) in dogs for 0 h (CTL), 12 h, 24 h, 1 wk or 2 wks (n=5/group). We performed echocardiography, 1 h Holter ECG recordings and EP studies in vivo and Ca2+ transient (Indo1 AM) and action potential (AP) recordings on isolated cardiomyocytes.
Results: Hemodynamic indices show progressive HF with decreased left ventricular (LV) systolic pressure (P), increased LV end diastolic P (EDP) and LAP reaching statistical significance at 1 wk VTP (Fig. A). Echo showed a similar pattern, with increased LA area and reduced FS after 1 wk VTP vs. CTL (13.5±1.1 cm2 vs 9.5±0.9 cm2, 25±2.5% vs. 35±2.7% respectively; p<0.05). The time course of fibrosis paralleled that of HF development (B). AP duration (APD) increased within 24 h (C), accompanied by prolonged LA effective refractory period (ERP, D) and increased Ca2+ transient amplitude (CaT, E). The development of DAD-related triggered activity (TA, F) was slower than that of CaTs, indicating that increased CaTs are insufficient to cause TA. The development of spontaneous atrial tachyarrhythmias (G) paralleled TA; and induced AF duration (H) paralleled HF and fibrosis development.
Conclusions: VTP-induced HF causes rapid changes in Ca2+ transients, APD and ERP. Triggered activity develops more slowly, implicating additional factors like ryanodine receptor dysfunction, and correlates with spontaneous ectopy. The AF-maintaining substrate is related to HF severity and tissue fibrosis. These results indicate that HF causes an evolving pattern of remodeling and arrhythmogenesis and provide insights into underlying mechanisms.
- © 2010 by American Heart Association, Inc.