乌地那非对 FUEL 研究参与者单心室大小和功能的超声心动图指标的影响。
Impact of Udenafil on Echocardiographic Indices of Single Ventricle Size and Function in FUEL Study Participants.
机构信息
Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO (M.V.D.M.).
Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA (D.J.G., S.M.P.).
出版信息
Circ Cardiovasc Imaging. 2022 Nov;15(11):e013676. doi: 10.1161/CIRCIMAGING.121.013676. Epub 2022 Nov 15.
BACKGROUND
The FUEL trial (Fontan Udenafil Exercise Longitudinal) demonstrated statistical improvements in exercise capacity following 6 months of treatment with udenafil (87.5 mg po BID). The effect of udenafil on echocardiographic measures of single ventricle function in this cohort has not been studied.
METHODS
The 400 enrolled participants were randomized 1:1 to udenafil or placebo. Protocol echocardiograms were obtained at baseline and 26 weeks after initiation of udenafil/placebo. Linear regression compared change from baseline indices of single ventricle systolic, diastolic and global function, atrioventricular valve regurgitation, and mean Fontan fenestration gradient in the udenafil cohort versus placebo, controlling for ventricular morphology (left ventricle versus right ventricle/other) and baseline value.
RESULTS
The udenafil participants (n=191) had significantly improved between baseline and 26 weeks visits compared to placebo participants (n=195) in myocardial performance index (=0.03, adjusted mean difference [SE] of changes between groups -0.03[0.01]), atrioventricular valve inflow peak E (=0.009, 3.95 [1.50]), and A velocities (=0.034, 3.46 [1.62]), and annular Doppler tissue imaging-derived peak e' velocity (=0.008, 0.60[0.23]). There were no significant differences in change in single ventricle size, systolic function, atrioventricular valve regurgitation severity, or mean fenestration gradient. Participants with a dominant left ventricle had significantly more favorable baseline values of indices of single ventricle size and function (lower volumes and areas, E/e' ratio, systolic:diastolic time and atrioventricular valve regurgitation, and higher annular s' and e' velocity).
CONCLUSIONS
FUEL participants who received udenafil demonstrated a statistically significant improvement in some global and diastolic echo indices. Although small, the changes in diastolic function suggest improvement in pulmonary venous return and/or augmented ventricular compliance, which may help explain improved exercise performance in that cohort.
REGISTRATION
URL: https://clinicaltrials.gov; Unique Identifier: NCT02741115.
背景
FUEL 试验（Fontan 乌地那非运动纵向研究）表明，在接受乌地那非（87.5mg 口服，每日两次）治疗 6 个月后，运动能力有统计学上的改善。在该队列中，尚未研究乌地那非对单心室功能的超声心动图测量的影响。
方法
400 名入选的参与者按 1:1 随机分为乌地那非组或安慰剂组。在开始使用乌地那非/安慰剂后 26 周时获得方案超声心动图。线性回归比较了乌地那非组与安慰剂组在单心室收缩、舒张和整体功能、房室瓣反流以及平均 Fontan 窗格梯度的基线指数从基线的变化，控制心室形态（左心室与右心室/其他）和基线值。
结果
与安慰剂组（n=195）相比，乌地那非组（n=191）在基线至 26 周的随访中，心肌运动指数（=0.03，调整后的组间变化平均差值[SE]为-0.03[0.01]）、房室瓣流入峰值 E（=0.009，3.95[1.50]）和 A 速度（=0.034，3.46[1.62]）以及瓣环多普勒组织成像衍生的峰值 e'速度（=0.008，0.60[0.23]）均有显著改善。单心室大小、收缩功能、房室瓣反流严重程度或平均窗格梯度无显著差异。左心室占主导地位的参与者单心室大小和功能指数的基线值（较低的容积和面积、E/e'比值、收缩期：舒张期时间和房室瓣反流以及较高的瓣环 s'和 e'速度）有显著更优。
结论
接受乌地那非治疗的 FUEL 参与者在一些整体和舒张超声心动图指标上表现出统计学上的显著改善。尽管变化较小，但舒张功能的改变提示肺静脉回流和/或心室顺应性增强，这可能有助于解释该队列运动能力的提高。
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