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依普利酮在肥厚型心肌病中的抗纤维化作用:一项随机临床试验。

The Antifibrotic Effects of Eplerenone in Hypertrophic Cardiomyopathy: A Randomized Clinical Trial.

作者信息

Papapostolou Stavroula, Iles Leah, O'Brien Jessica, Gutman Sarah J, Ellims Andris, Hare James, Stub Dion, Moir Stuart, Taylor Andrew J

机构信息

Department of Cardiovascular Medicine, The Alfred Hospital, Melbourne, Australia; Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia; Department of Cardiology, Western Health, Melbourne, Australia.

Department of Cardiovascular Medicine, The Alfred Hospital, Melbourne, Australia; Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia.

出版信息

JACC Heart Fail. 2025 Jul;13(7):102415. doi: 10.1016/j.jchf.2025.01.021. Epub 2025 Apr 16.

Abstract

BACKGROUND

Fibrosis plays a central role in hypertrophic cardiomyopathy (HCM), contributing to symptoms via impaired systolic and diastolic function and ventricular arrhythmias.

OBJECTIVES

The aim of this study was to determine if eplerenone has an antifibrotic effect in nonobstructive HCM (resting left ventricular outflow tract gradient <30 mm Hg).

METHODS

This was a randomized, double-blind, placebo-controlled trial of eplerenone in 61 patients with nonobstructive HCM over 12 months. The primary endpoint was native T1 time on cardiac magnetic resonance as an index of diffuse fibrosis. Secondary endpoints included changes in diastolic function.

RESULTS

Thirty patients were randomized to 50 mg eplerenone and 31 to placebo. There was a reduction in native T1 time within the eplerenone group (1,315 ± 134 ms at baseline vs 1,259 ± 92 ms at 12 months; P = 0.041), with no significant change in the placebo group (1,234 ± 28 ms at baseline vs 1,238 ± 70 ms at 12 months; P = 0.854). This represents a 3.7% ± 9% reduction in native T1 with eplerenone compared with a 1.1% ± 9% increase with placebo (P = 0.07). There was no significant change in functional status or markers of diastolic function (such as E/e' ratio or mitral E/A ratio).

CONCLUSIONS

In patients with nonobstructive HCM, there was a reduction in myocardial T1 time with eplerenone, consistent with a reduction in diffuse myocardial fibrosis. Larger and longer trials are needed to confirm this finding and explore whether it translates into improved exercise capacity or a reduction in mortality over time. (Anti-fibrotic role of eplerenone on diffuse myocardial fibrosis and diastolic function in patients with hypertrophic cardiomyopathy; ACTRN12613000065796).

摘要

背景

纤维化在肥厚型心肌病(HCM)中起核心作用,通过收缩和舒张功能受损及室性心律失常导致症状出现。

目的

本研究旨在确定依普利酮对非梗阻性HCM(静息左心室流出道梯度<30 mmHg)是否具有抗纤维化作用。

方法

这是一项针对61例非梗阻性HCM患者的依普利酮随机、双盲、安慰剂对照试验,为期12个月。主要终点是心脏磁共振成像上的固有T1时间,作为弥漫性纤维化的指标。次要终点包括舒张功能的变化。

结果

30例患者被随机分配至依普利酮50 mg组,31例被分配至安慰剂组。依普利酮组的固有T1时间有所降低(基线时为1315±134 ms,12个月时为1259±92 ms;P = 0.041),而安慰剂组无显著变化(基线时为1234±28 ms,12个月时为1238±70 ms;P = 0.854)。与安慰剂组固有T1时间增加1.1%±9%相比,依普利酮使固有T1时间降低了3.7%±9%(P = 0.07)。功能状态或舒张功能标志物(如E/e'比值或二尖瓣E/A比值)无显著变化。

结论

在非梗阻性HCM患者中,依普利酮可使心肌T1时间缩短,这与弥漫性心肌纤维化的减轻一致。需要更大规模、更长时间的试验来证实这一发现,并探索其是否能随着时间推移转化为运动能力的改善或死亡率的降低。(依普利酮对肥厚型心肌病患者弥漫性心肌纤维化和舒张功能的抗纤维化作用;ACTRN12613000065796)

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