Takemoto Yoshio, Ramirez Rafael J, Kaur Kuljeet, Salvador-Montañés Oscar, Ponce-Balbuena Daniela, Ramos-Mondragón Roberto, Ennis Steven R, Guerrero-Serna Guadalupe, Berenfeld Omer, Jalife José
Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Tajimi, Japan; Department of Internal Medicine, Center for Arrhythmia Research, University of Michigan, Ann Arbor, Michigan.
Department of Internal Medicine, Center for Arrhythmia Research, University of Michigan, Ann Arbor, Michigan.
J Am Coll Cardiol. 2017 Dec 12;70(23):2893-2905. doi: 10.1016/j.jacc.2017.10.014.
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.
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.
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).
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.
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.
醛固酮抑制剂依普利酮（EPL）已被证明可降低收缩性心力衰竭患者心房颤动（AF）的发生率，但其机制尚不清楚。
本研究假设，在无心力衰竭的情况下，通过减少心房扩张和纤维化，依普利酮还可减轻房颤负担并防止房颤持续。
作者对34只心房快速起搏（13±1周）的绵羊进行了一项随机对照研究。从快速起搏开始，他们比较了每日口服依普利酮（n = 19）与安慰剂（SP）治疗（n = 15）的效果。终点是连续7天持续房颤（n = 29）或完成23周快速起搏（n = 5）。
依普利酮显著降低了房颤进展过程中左心房扩张增加的速率。与接受安慰剂治疗的绵羊心房相比，接受依普利酮治疗的绵羊心房平滑肌肌动蛋白蛋白、胶原蛋白III表达、心房间质纤维化和细胞肥大较少。然而，依普利酮并未改变在接受安慰剂治疗时观察到的房颤诱导的主导频率和离子通道密度增加的速率，而是使26%的动物发生持续性房颤的时间延长。它还降低了颤动传导程度、房颤诱发率和房颤负担。
在绵羊模型中，依普利酮可减轻纤维化和心房扩张，改变房颤诱发率和房颤复杂性，并使26%的动物向持续性房颤转变的时间延长，但它不能预防房颤诱导的电重构或房颤持续。结果突出了结构重构作为减轻房颤负担的核心上游靶点，以及预防电重构以避免房颤持续的必要性。
