BACKGROUND The aldosterone inhibitor eplerenone (EPL) has been shown to reduce the incidence of atrial fibrillation (AF) in patients with systolic heart failure, but the mechanism is unknown. OBJECTIVES This study hypothesized that by reducing atrial dilation and fibrosis in the absence of heart failure, EPL also reduces AF burden and prevents AF perpetuation. METHODS The authors conducted a randomized controlled study in 34 sheep that were atrially tachypaced (13 ± 1 week). They compared daily oral EPL (n = 19) versus sugar pill (SP) treatment (n = 15) from the start of tachypacing. The endpoint was a continuous 7-day stretch of persistent AF (n = 29) or completion of 23 weeks tachypacing (n = 5). RESULTS EPL significantly reduced the rate of left atrial dilation increase during AF progression. Atria from EPL-treated sheep had less smooth muscle actin protein, collagen-III expression, interstitial atrial fibrosis, and cell hypertrophy than SP-treated sheep atria did. However, EPL did not modify the AF-induced increase in the rate of dominant frequency and ion channel densities seen under SP treatment, but rather prolonged the time to persistent AF in 26% of animals. It also reduced the degree of fibrillatory conduction, AF inducibility, and AF burden. CONCLUSIONS In the sheep model, EPL mitigates fibrosis and atrial dilation, modifies AF inducibility and AF complexity, and prolongs the transition to persistent AF in 26% of animals, but it does not prevent AF-induced electrical remodeling or AF persistence. The results highlight structural remodeling as a central upstream target to reduce AF burden, and the need to prevent electrical remodeling to avert AF perpetuation.

中文翻译：

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依普利酮可减轻心房颤动负担而不阻止心房电重构

背景 醛固酮抑制剂依普利酮 (EPL) 已被证明可以降低收缩性心力衰竭患者的房颤 (AF) 发生率，但其机制尚不清楚。目标 本研究假设，通过在没有心力衰竭的情况下减少心房扩张和纤维化，EPL 还可以减少 AF 负担并防止 AF 持续存在。方法 作者对 34 只心房超速（13 ± 1 周）绵羊进行了一项随机对照研究。他们比较了从快速起搏开始时每日口服 EPL（n = 19）与糖丸（SP）治疗（n = 15）。终点是持续 7 天的持续性 AF（n = 29）或完成 23 周快速起搏（n = 5）。结果 EPL 显着降低了 AF 进展过程中左心房扩张的速度。与 SP 处理的绵羊心房相比，EPL 处理的绵羊心房的平滑肌肌动蛋白、胶原蛋白 III 表达、间质心房纤维化和细胞肥大较少。然而，EPL 没有改变在 SP 治疗下看到的 AF 诱导的主频率和离子通道密度速率的增加，而是延长了 26% 动物持续性 AF 的时间。它还降低了纤颤传导的程度、AF 诱导性和 AF 负担。结论 在绵羊模型中，EPL 减轻了纤维化和心房扩张，改变了 AF 诱导性和 AF 复杂性，并延长了 26% 动物向持续性 AF 的过渡，但它不能防止 AF 诱导的电重构或 AF 持续性。结果突出了结构重塑作为减少 AF 负担的中央上游目标，