Valsartan and Cardiac Remodeling in Early-Stage Hypertrophic Cardiomyopathy: The VANISH Randomized Clinical Trial Cardiac Magnetic Resonance Substudy.

Myocardial tissue characterization by cardiac magnetic resonance (CMR) imaging may enhance mechanistic insights, but whether valsartan influences these parameters remains uncertain.

心脏磁共振（CMR）成像对心肌组织特征的表征可能会增强机制洞察力，但 Valsartan 是否影响这些参数仍不确定。

Background

To evaluate the treatment effects of valsartan on myocardial structure, function, and tissue parameters in early-stage sarcomeric HCM.

评估缬沙坦对早期肌原纤维性肥厚型心肌病（HCM）心肌结构、功能和组织参数的治疗效果。

DESIGN, SETTING, AND PARTICIPANTS: This prespecified CMR substudy of the VANISH (Valsartan for Attenuating Disease Evolution in Early Sarcomeric Hypertrophic Cardiomyopathy) randomized clinical trial evaluated treatment effects of valsartan vs placebo on myocardial structure, function, and tissue parameters and was conducted from April 2014 through July 2019 at 17 international sites.

设计、环境和参与者：这是VANISH（缬沙坦减缓早期肌原纤维性肥厚型心肌病疾病进展）随机临床试验的预先设定的心脏磁共振成像（CMR）子研究，评估了缬沙坦与安慰剂相比对心肌结构、功能和组织参数的治疗效果。该研究于2014年4月至2019年7月在17个国际地点进行。

Individuals aged 8 to 45 years with early-stage HCM aged between 8 and 45 years and with no or minimal symptoms were eligible for inclusion.

年龄在8至45岁之间，患有早期肥厚型心肌病（HCM），且无症状或症状轻微的个体符合纳入标准。

Methods

Treatment with placebo or valsartan (80 mg per day for children weighing <35 kg, 160 mg per day for children weighing ≥35 kg, or 320 mg per day for adults aged 18 years or older).

接受安慰剂或缬沙坦治疗（对于体重<35公斤的儿童，每天80毫克；对于体重≥35公斤的儿童，每天160毫克；或对于18岁及以上的成人，每天320毫克）。

main_outcomes_and_measures

The primary outcome was mean change in CMR parameters between baseline and year 2, including indexed extracellular volume (iECV), indexed intracellular volume (iICV), and late gadolinium enhancement (LGE).

主要结果是基线与第2年之间CMR参数的平均变化，包括索引细胞外体积（iECV）、索引细胞内体积（iICV）和晚期钝增强（LGE）。

Mean between-group differences in CMR parameters between baseline and year 2 were evaluated using multivariable mixed-effects linear regression models.

使用多变量混合效应线性回归模型评估了基线与第2年之间CMR参数的组间平均差异。

Results

Overall, 137 of 178 VANISH participants (77.0%) underwent CMR imaging at baseline and year 2.

总体而言，178名VANISH参与者中有137名（77.0%）在基线和第2年接受了心脏磁共振成像（CMR）检查。

Among these participants, mean (SD) age was 23 (10) years, and 51 participants (37.2%) were female.

在这些参与者中，平均年龄（标准差）为23（10）岁，51名参与者（37.2%）为女性。

Baseline characteristics and CMR parameters were well balanced between treatment groups.

基线特征和心肌磁共振参数在治疗组之间得到了良好的平衡。

Higher LGE, iECV, and iICV at baseline were associated with higher cardiac biomarker levels and more pronounced cardiac remodeling.

基线时更高的晚期钝增强（LGE）、心肌细胞外体积（iECV）和心肌细胞内体积（iICV）与更高的心脏生物标志物水平和更明显的结构性心脏重塑有关。

Between baseline and year 2, valsartan appeared to increase left ventricular (LV) end-diastolic volume index (mean difference [MD], 3.3 mL/m2; 95% CI, 0.4-6.2; P = .03), suggesting treatment benefit, but did not significantly impact LV mass index (MD, -2.9 g/m2; 95% CI, -6.1 to 0.2; P = .07) or LV ejection fraction.

在基线和第2年之间，缬沙坦似乎增加了左心室舒张末期容积指数（平均差异[MD]，3.3 mL/m2；95%置信区间[CI]，0.4-6.2；P = .03），表明治疗有益，但对左心室质量指数（MD，-2.9 g/m2；95% CI，-6.1至0.2；P = .07）或左心室射血分数没有显著影响。

Similarly, valsartan appeared to reduce decline in right ventricular volumes.

同样，缬沙坦似乎减少了右心室容积的下降。

Valsartan appeared to significantly reduce iICV progression (MD, -5.0 mL/m2; 95% CI, -9.7 to -0.4; P = .03), but did not impact iECV (MD, 0.0 mL/m2; 95% CI, -1.4 to 1.3; P = .95) or LGE progression (MD, 0.5%; 95% CI, -0.4 to 1.3; P = .30).

缬沙坦似乎显著降低了iICV进展（MD，-5.0 mL/m2；95% CI，-9.7至-0.4；P = .03），但对iECV（MD，0.0 mL/m2；95% CI，-1.4至1.3；P = .95）或LGE进展（MD，0.5%；95% CI，-0.4至1.3；P = .30）没有影响。

conclusions_and_relevance

These findings enhance mechanistic insights into the effect of valsartan in early-stage HCM, showing potential benefits on biventricular remodeling and myocardial intracellular volume.

这些发现增强了对缬沙坦在早期HCM中作用机制的理解，显示了其在双心室重塑和心肌细胞内体积方面的潜在益处。

Further research to identify cellular mechanisms of valsartan on HCM progression is needed.

需要进一步研究以确定缬沙坦对肥厚型心肌病进展的细胞机制。

trial_registration

ClinicalTrials.gov Identifier: NCT01912534.

ClinicalTrials.gov 注册号：NCT01912534。