Atrial Remodeling in an Ovine Model of Anthracycline-Induced Nonischemic Cardiomyopathy: Remodeling of the Same Sort

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. (J Cardiovasc Electrophysiol, Vol. 22, pp. 175-182, February 2011).