Myocardial Fibrosis and Early Intervention in Asymptomatic Patients With Severe Aortic Stenosis: Insights From the EVOLVED Randomized Clinical Trial.

Background

To determine whether midwall myocardial fibrosis burden is associated with adverse clinical outcomes in asymptomatic patients and whether those with more fibrosis derive greater benefit from early intervention.

确定中层心肌纤维化负担是否与无症状患者的不良临床结果有关，以及那些纤维化更多的患者是否从早期干预中获得更大的益处。

DESIGN, SETTING, AND PARTICIPANTS: This post hoc analysis of a randomized clinical trial was conducted between August 2017 and October 2022.

设计、环境和参与者：这项事后分析是基于一项随机临床试验，研究时间从2017年8月至2022年10月。

The trial took place at 24 cardiac centers across the United Kingdom and Australia.

该试验在英国和澳大利亚的24个心脏中心进行。

Participants included asymptomatic patients with severe aortic stenosis and midwall fibrosis on cardiac magnetic resonance.

参与者包括无症状的严重主动脉瓣狭窄患者，他们在心脏磁共振上显示出中层纤维化。

These data were analyzed from October 2024 through June 2025.

这些数据是从2024年10月至2025年6月期间进行分析的。

intervention

Early intervention with transcatheter or surgical aortic valve replacement.

早期干预采用经导管或外科主动脉瓣膜置换术。

main_outcomes_and_measures

Primary outcome was all-cause death or unplanned aortic stenosis-related hospitalization.

主要结果是全因死亡或计划外的主动脉瓣狭窄相关住院。

Secondary outcomes included the individual components of the primary outcome.

次要结果包括主要结果的各个组成部分。

Results

In 224 trial participants (mean [SD] age, 73 [9] years; 63 women and 161 men, and mean [SD] aortic valve peak velocity 4.3 [0.5] m per second) with a median follow-up of 42 months, fibrosis burden (per 1% increase) was associated with an increase in the primary end point (hazard ratio[HR], 1.23; 95% CI, 1.08-1.37) and its component of unplanned aortic stenosis-related hospitalizations (HR, 1.22; 95% CI, 1.03-1.40) but not all-cause death (HR, 1.17; 95% CI, 0.98-1.35).

在224名试验参与者（平均[标准差]年龄为73[9]岁；63名女性和161名男性，平均[标准差]主动脉瓣峰值流速为4.3[0.5]米/秒）中，随访中位数为42个月，纤维化负担（每增加1%）与主要终点事件（风险比[HR]，1.23；95%置信区间[CI]，1.08-1.37）及其组成部分的计划外主动脉瓣狭窄相关住院（HR，1.22；95% CI，1.03-1.40）的增加有关，但与全因死亡（HR，1.17；95% CI，0.98-1.35）无关。

There were no interactions between randomization arm and the midwall fibrosis burden for the primary (P for interaction = .39) or secondary end points.

随机分组与中层纤维化负荷之间对于主要终点（P for interaction = .39）或次要终点没有交互作用。

In patients with high fibrosis burden above the median, the primary end point occurred in 12 of 59 (20%) of those randomized to early intervention and 17 of 53 (32%) of those randomized to guideline-directed conservative management (HR, 0.62; 95% CI, 0.29-1.28).

在纤维化负荷高于中位数的患者中，主要终点在随机分到早期干预的59人中有12人（20%）发生，而在随机分到指南指导的保守管理的53人中有17人（32%）发生（HR, 0.62; 95% CI, 0.29-1.28）。

For the individual components, all-cause death occurred in 9 (15%) and 10 (19%) patients, respectively (HR, 0.84; 95% CI, 0.33-2.07), and unplanned aortic stenosis-related hospitalization in 4 (7%) and 13 (25%) patients respectively (HR, 0.27; 95% CI, 0.08-0.77).

对于各个组成部分，全因死亡分别发生在9名（15%）和10名（19%）患者中（HR, 0.84; 95% CI, 0.33-2.07），以及计划外的主动脉瓣狭窄相关住院分别发生在4名（7%）和13名（25%）患者中（HR, 0.27; 95% CI, 0.08-0.77）。

In patients with low fibrosis burden below the median, there were no differences in the primary outcome (HR, 1.05; 95% CI, 0.39-2.86) or its components between intervention groups.

在纤维化负担低于中位数的患者中，主要结果（HR, 1.05; 95% CI, 0.39-2.86）及其组成部分在干预组之间没有差异。

conclusions_and_relevance

In this study, in asymptomatic patients with severe aortic stenosis, higher midwall fibrosis burden was associated with adverse outcomes.

在这项研究中，对于无症状的重度主动脉瓣狭窄患者，较高的中层纤维化负荷与不良结果相关。

There was no demonstrable heterogeneity by the degree of midwall fibrosis for the treatment effects of early surgical or transcatheter aortic valve replacement compared to clinical surveillance.

与临床监测相比，早期手术或经导管主动脉瓣置换治疗效果的中层纤维化程度无明显异质性。

trial_registration

ClinicalTrials.gov Identifier: NCT03094143.

临床试验注册号：NCT03094143。