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

IF 14.8 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
John W Ostrominski, Brian L Claggett, Michael Jerosch-Herold, Anna Axelsson Raja, Sharlene M Day, Mark W Russell, Kenneth Zahka, Alexandre C Pereira, Steven D Colan, Anne M Murphy, Charles Canter, Richard G Bach, Matthew T Wheeler, Joseph W Rossano, Anjali T Owens, Luisa Mestroni, Matthew R G Taylor, Amit R Patel, Ivan Wilmot, Jonathan H Soslow, Jason R Becker, Neal K Lakdawala, Henning Bundgaard, Jose D Vargas, Carolyn Y Ho
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引用次数: 0

Abstract

Importance: Valsartan has been shown to attenuate phenotypic progression among individuals with early-stage sarcomeric hypertrophic cardiomyopathy (HCM). Myocardial tissue characterization by cardiac magnetic resonance (CMR) imaging may enhance mechanistic insights, but whether valsartan influences these parameters remains uncertain.

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

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. 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.

Interventions: 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).

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

Results: Overall, 137 of 178 VANISH participants (77.0%) underwent CMR imaging at baseline and year 2. Among these participants, mean (SD) age was 23 (10) years, and 51 participants (37.2%) were female. Baseline characteristics and CMR parameters were well balanced between treatment groups. Higher LGE, iECV, and iICV at baseline were associated with higher cardiac biomarker levels and more pronounced cardiac remodeling. 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. Similarly, valsartan appeared to reduce decline in right ventricular volumes. 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).

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

Trial registration: ClinicalTrials.gov Identifier: NCT01912534.

缬沙坦与早期肥厚性心肌病的心脏重构:VANISH随机临床试验心脏磁共振亚研究。
重要性:缬沙坦已被证明可以减轻早期肌瘤性肥厚性心肌病(HCM)患者的表型进展。心肌组织特征的心脏磁共振(CMR)成像可能增强机理的见解,但是否缬沙坦影响这些参数仍不确定。目的:探讨缬沙坦对早期肌瘤性HCM患者心肌结构、功能及组织参数的影响。设计、环境和参与者:这项预先指定的VANISH(缬沙坦用于减轻早期肉瘤性肥厚性心肌病疾病演变)随机临床试验的CMR亚研究评估了缬沙坦与安慰剂对心肌结构、功能和组织参数的治疗效果,该试验于2014年4月至2019年7月在17个国际站点进行。年龄在8 - 45岁的早期HCM患者(年龄在8 - 45岁之间,无症状或症状最小)符合入选条件。干预措施:安慰剂或缬沙坦治疗(80mg /天,儿童体重):主要结局和措施:主要结局是基线和第2年之间CMR参数的平均变化,包括指数胞外体积(iECV),指数胞内体积(iICV)和晚期钆增强(LGE)。使用多变量混合效应线性回归模型评估基线和第2年CMR参数组间平均差异。结果: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CMR成像。在这些参与者中,平均(SD)年龄为23(10)岁,51名参与者(37.2%)为女性。治疗组间基线特征和CMR参数平衡良好。基线时较高的LGE、iECV和iICV与较高的心脏生物标志物水平和更明显的心脏重构相关。在基线和第2年之间,缬沙坦似乎增加左室(LV)舒张末期容积指数(平均差值[MD], 3.3 mL/m2;95% ci, 0.4-6.2;P = .03),提示治疗获益,但对左室质量指数无显著影响(MD, -2.9 g/m2;95% CI, -6.1 ~ 0.2;P = .07)或左室射血分数。同样,缬沙坦似乎可以减轻右心室容积的下降。缬沙坦似乎显著降低iICV进展(MD, -5.0 mL/m2;95% CI, -9.7 ~ -0.4;P = .03),但不影响iECV (MD, 0.0 mL/m2;95% CI, -1.4 ~ 1.3;P = 0.95)或LGE进展(MD, 0.5%;95% CI, -0.4 ~ 1.3;p = .30)。结论和相关性:这些发现增强了缬沙坦在早期HCM中的作用机制,显示了对双室重构和心肌细胞内体积的潜在益处。需要进一步研究确定缬沙坦对HCM进展的细胞机制。试验注册:ClinicalTrials.gov标识符:NCT01912534。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
JAMA cardiology
JAMA cardiology Medicine-Cardiology and Cardiovascular Medicine
CiteScore
45.80
自引率
1.70%
发文量
264
期刊介绍: JAMA Cardiology, an international peer-reviewed journal, serves as the premier publication for clinical investigators, clinicians, and trainees in cardiovascular medicine worldwide. As a member of the JAMA Network, it aligns with a consortium of peer-reviewed general medical and specialty publications. Published online weekly, every Wednesday, and in 12 print/online issues annually, JAMA Cardiology attracts over 4.3 million annual article views and downloads. Research articles become freely accessible online 12 months post-publication without any author fees. Moreover, the online version is readily accessible to institutions in developing countries through the World Health Organization's HINARI program. Positioned at the intersection of clinical investigation, actionable clinical science, and clinical practice, JAMA Cardiology prioritizes traditional and evolving cardiovascular medicine, alongside evidence-based health policy. It places particular emphasis on health equity, especially when grounded in original science, as a top editorial priority.
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