University Medical Center, University of Groningen, Groningen, The Netherlands.
Int J Cardiol. 2010 Oct 29;144(3):373-8. doi: 10.1016/j.ijcard.2009.04.037. Epub 2009 May 21.
Eisenmenger's syndrome (ES) is the most advanced form of pulmonary arterial hypertension related to congenital heart disease. Evolution of pulmonary vascular disease differs markedly between patients with atrial septal defects (ASD) versus ventricular septal defects (VSD), potentially affecting response to treatment. We compared the effects of bosentan and placebo in patients with isolated ASD (ASD subgroup) versus patients with isolated VSD or both defects (VSD subgroup).
Post-hoc analysis of a 16-week, multicenter, randomized, double-blind, placebo-controlled trial was performed. Fifty-four patients (13: ASDs, 36: VSDs, 5: VSD+ASD) were randomized to bosentan 62.5 mg bid for four weeks (uptitrated to 125 mg bid thereafter) or placebo. Main outcome measures were: indexed pulmonary vascular resistance (PVRi), exercise capacity, mean pulmonary artery pressure (mPAP), pulmonary blood flow index (Qpi), and changes in oxygen saturation (SpO₂).
Placebo-corrected median (95% CI) treatment effects on PVRi were -544.0 dyn·s·cm⁻⁵ (-1593.8, 344.7) and -436.4 dyn·s·cm⁻⁵ (-960.0, 167.0) in the ASD and VSD subgroups, respectively. Effects of bosentan on exercise capacity and mPAP were similar in both subgroups. No changes in SpO₂ or Qpi were observed in either bosentan or placebo subgroups.
Improvements in exercise capacity and cardiopulmonary hemodynamics, without desaturation, were observed in ES patients with both ASDs and VSDs. Although not reaching statistical significance, improvements were similar to those in the BREATHE-5 analyses, suggesting that the location of septal defects is not a key determinant of treatment response. These data further support the use of bosentan for the treatment of ES, independent of shunt location.
艾森曼格综合征（ES）是与先天性心脏病相关的肺动脉高压的终末期形式。肺血管疾病的演变在房间隔缺损（ASD）与室间隔缺损（VSD）患者之间有显著差异，这可能会影响治疗反应。我们比较了波生坦和安慰剂在单纯 ASD（ASD 亚组）患者与单纯 VSD 或两种缺陷（VSD 亚组）患者中的作用。
对一项为期 16 周、多中心、随机、双盲、安慰剂对照试验进行了事后分析。54 名患者（13 例 ASD、36 例 VSD、5 例 VSD+ASD）被随机分为波生坦 62.5mg bid 治疗 4 周（此后增至 125mg bid）或安慰剂。主要观察指标为：肺血管阻力指数（PVRi）、运动能力、肺动脉平均压（mPAP）、肺血流指数（Qpi）和血氧饱和度（SpO₂）的变化。
ASD 和 VSD 亚组中，安慰剂校正的中位（95%CI）治疗对 PVRi 的影响分别为-544.0dyn·s·cm⁻⁵（-1593.8，344.7）和-436.4 dyn·s·cm⁻⁵（-960.0，167.0）。波生坦对运动能力和 mPAP 的影响在两个亚组中相似。在波生坦或安慰剂亚组中均未观察到 SpO₂或 Qpi 的变化。
在 ASD 和 VSD 患者中，观察到运动能力和心肺血流动力学的改善，而无低氧血症。尽管未达到统计学意义，但改善情况与 BREATHE-5 分析相似，提示间隔缺损的位置不是治疗反应的关键决定因素。这些数据进一步支持波生坦用于 ES 的治疗，而与分流位置无关。
