Department of Pediatric Cardiology and Critical Care, Hannover Medical School, Hannover, Germany.
Division of Pediatric Cardiology, Department of Pediatrics, Medical University of Graz, Graz, Austria.
J Heart Lung Transplant. 2020 Jul;39(7):695-706. doi: 10.1016/j.healun.2020.03.029. Epub 2020 Apr 7.
The European Pediatric Pulmonary Vascular Disease Network (EPPVDN) investigated the safety and efficacy of add-on selexipag, an oral prostacyclin receptor agonist approved for pulmonary arterial hypertension (PAH) in adults, in the largest, exploratory pediatric cohort to date.
This is a prospective observational study of 15 consecutive children with PAH, treated with oral add-on selexipag at 3 centers. Most patients underwent cardiac catheterizations at baseline and median of 8 months follow-up. All patients had clinical, echocardiographic, and N-terminal pro b-type natriuretic peptide studies, including the EPPVDN pediatric pulmonary hypertension (PH) risk score.
There was no death during the use of selexipag. Two of 15 patients ultimately underwent lung transplantation. One patient with heritable PAH died on intravenous treprostinil (off selexipag). The mean right atrial pressure, the ratio of pulmonary arterial pressure (PAP) to systemic arterial pressure (SAP) (mean PAP/mean SAP, diastolic PAP/diastolic SAP: -17%), and transpulmonary pressure gradients (TPG) (mean TPG: -17%; p < 0.01; diastolic TPG: -6 mm Hg; p < 0.05) were improved after the therapy (n = 10). Selexipag therapy was associated with a better right ventricular systolic function (tricuspid annular plane systolic excursion: +14.5%; p < 0.01) and functional class. Improvement was seen in non-invasive and combined invasive/non-invasive PH risk scores (lower risk: +18%-22%, higher risk: -35%-37%; p < 0.05). Overall, the efficacy of selexipag was variable, often with a better response in less sick patients.
Oral selexipag use in children with PAH is well tolerated and safe when closely monitored. Add-on selexipag therapy improved several outcome-relevant variables in about 50% of patients and prevented disease progression in additional 27% of patients. The novel EPPVDN pediatric PH risk score indicated these drug effects properly, can be useful in clinical follow-up, and should be validated in larger prospective studies.
欧洲儿科肺血管疾病网络 (EPPVDN) 调查了添加性塞来昔帕（一种已被批准用于成人肺动脉高压 (PAH) 的口服前列环素受体激动剂）的安全性和疗效，这是迄今为止最大的探索性儿科队列研究。
这是一项前瞻性观察研究，纳入了 3 个中心的 15 例连续的 PAH 患儿，给予口服添加性塞来昔帕治疗。大多数患者在基线和中位数 8 个月的随访时接受了心导管检查。所有患者均进行了临床、超声心动图和 N 末端 pro B 型利钠肽研究，包括 EPPVDN 儿科肺动脉高压 (PH) 风险评分。
在使用塞来昔帕期间无死亡病例。15 例患者中有 2 例最终接受了肺移植。1 例遗传性 PAH 患者在使用静脉注射曲前列尼尔（停用塞来昔帕）时死亡。10 例患者治疗后右心房压、肺动脉压与体动脉压比值（平均 PAP/平均 SAP，舒张 PAP/舒张 SAP：-17%）和跨肺压梯度（平均 TPG：-17%；p < 0.01；舒张 TPG：-6 mmHg；p < 0.05）均有所改善。塞来昔帕治疗与更好的右心室收缩功能（三尖瓣环平面收缩位移：+14.5%；p < 0.01）和心功能分级相关。非侵入性和联合侵入性/非侵入性 PH 风险评分也有所改善（风险降低：+18%-22%；风险升高：-35%-37%；p < 0.05）。总体而言，塞来昔帕在儿童 PAH 中的应用耐受性良好，当密切监测时是安全的。添加性塞来昔帕治疗改善了约 50%患者的多项预后相关变量，并使另外 27%患者的疾病进展得到了预防。新型 EPPVDN 儿科 PH 风险评分适当地指示了这些药物作用，可在临床随访中发挥作用，应在更大的前瞻性研究中进行验证。
