Doxorubicin-induced cardiomyopathy in an ovine model caused significant atrial remodeling, including increased fibrosis and longer induced atrial fibrillation episodes (16 vs 2 seconds; P=0.04).
In an ovine model of doxorubicin-induced nonischemic cardiomyopathy, significant atrial remodeling occurs similarly to rapid ventricular pacing models, suggesting a common substrate for AF in heart failure.
Absolute Event Rate: 37.1% vs 46.4%
p-value: p=0.003
INTRODUCTION: All preclinical studies of atrial remodeling in heart failure (HF) have been confined to a single model of rapid ventricular pacing. To evaluate whether the atrial changes were specific to the model or represented an end result of HF, this study aimed to characterize atrial remodeling in an ovine model of doxorubicin-induced cardiomyopathy. METHODS AND RESULTS: Fourteen sheep, 7 with cardiomyopathy induced by repeated intracoronary doxorubicin infusions and 7 controls, were studied. The development of HF was monitored by cardiac imaging and hemodynamic parameters. Open chest electrophysiological study was performed using custom-made 128-electrode epicardial plaque assessing effective refractory period (ERP) and conduction velocity. Atrial tissues were harvested for structural analysis. The HF group had demonstrable moderate global HF (left ventricular ejection fraction LVEF: 37.1 vs 46.4%; P = 0.003) and showed the following compared to controls: left atrial dilatation (P = 0.02) and dysfunction (P = 0.005); longer P-wave duration (P < 0.05); higher ERP at all cycle lengths (P ≤ 0.002) and locations (P < 0.001); slower conduction velocity (P < 0.001); increased conduction heterogeneity index (P < 0.001); increased atrial fibrosis (right atrial RA: 5.9 ± 2.6 vs 2.8 ± 0.9%; P < 0.0001, left atrial LA: 3.7 ± 2.2 vs 2.4 ± 1.1%; P = 0.002), and longer induced atrial fibrillation (AF) episodes (16 ± 22 vs 2 ± 3 seconds; P = 0.04). CONCLUSION: In this model of HF, there was significant atrial remodeling characterized by atrial enlargement/dysfunction, increased fibrosis, slowed/heterogeneous conduction, and increased refractoriness associated with more sustained AF. These findings appear the "same sort" to previous models of HF implicating a final common substrate leading to the development of AF in HF.
Lau et al. (Mon,) conducted a other in Anthracycline-induced nonischemic cardiomyopathy (n=14). Doxorubicin-induced cardiomyopathy vs. Controls was evaluated on Left ventricular ejection fraction (p=0.003). Doxorubicin-induced cardiomyopathy in an ovine model caused significant atrial remodeling, including increased fibrosis and longer induced atrial fibrillation episodes (16 vs 2 seconds; P=0.04).
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