Geerdink Lianne M, Bertram Harald, Hansmann Georg
Department of Pediatric Cardiology and Critical Care, Hannover Medical School, Hannover, Germany.
Pulm Circ. 2017 Apr-Jun;7(2):551-554. doi: 10.1177/2045893217703369. Epub 2017 May 12.
Pulmonary arterial hypertension (PAH) is a complex disease with a poor prognosis. Selexipag is a selective prostacyclin receptor agonist with vasodilatory, anti-proliferative, anti-inflammatory, and pro-angiogenic properties. However, no clinical data on its therapeutic use in children with PAH are currently available. Here, we report the case of a 12-year-old girl who presented in World Health Organization (WHO) functional class III and right ventricular (RV) failure with recurrent syncope, dizziness, and progressive fatigue for two years. Cardiac catheterization revealed severe precapillary PAH: mean right atrial pressure (RAP) = 10-13 mmHg, right ventricular end-diastolic pressure (RVEDP) = 13 mmHg, left ventricular end-diastolic pressure (LVEDP) = 7 mmHg, mean pulmonary arterial pressure (PAP) = 81 mmHg, and mean aorta ascendens pressure = 89 mmHg. The pulmonary vascular resistance index (PVRi) was 25.2 WU × m. An oral combination therapy was started with a phosphodiesterase type 5 inhibitor (sildenafil 3 × 20 mg) and an endothelin-1 receptor antagonist (bosentan 2 × 62.5 mg). No significant clinical/hemodynamic improvement was seen after nine months of dual therapy, so that the patient was transferred to our institution. We agreed upon the off-label add-on use of oral selexipag. Within ten days, we up-titrated selexipag to a final (max. adult) dose of 1600 mcg twice daily. After six months, the patient had: (1) decrease in PVR index, pulmonary artery acceleration time, RAP, RVEDP, right atrial/RV size; (2) re-gain of vasoreactivity; and (3) improvement of cardiac index, 6-minute walking distance, functional class, body weight, and CAMPHOR score. Our encouraging results suggest the consideration of off-label use of oral selexipag in children with severe PAH, preferably in a protocol-driven prospective study.
肺动脉高压（PAH）是一种预后不良的复杂疾病。司来帕格是一种选择性前列环素受体激动剂，具有血管舒张、抗增殖、抗炎和促血管生成特性。然而，目前尚无关于其在儿童PAH治疗中应用的临床数据。在此，我们报告一例12岁女孩的病例，该女孩表现为世界卫生组织（WHO）功能分级III级和右心室（RV）衰竭，伴有反复晕厥、头晕和进行性疲劳达两年。心导管检查显示严重的毛细血管前PAH：平均右心房压（RAP）=10 - 13 mmHg，右心室舒张末期压力（RVEDP）=13 mmHg，左心室舒张末期压力（LVEDP）=7 mmHg，平均肺动脉压（PAP）=81 mmHg，平均升主动脉压=89 mmHg。肺血管阻力指数（PVRi）为25.2 WU×m。开始口服联合治疗，使用5型磷酸二酯酶抑制剂（西地那非3×20 mg）和内皮素-1受体拮抗剂（波生坦2×62.5 mg）。双联治疗9个月后未见明显临床/血流动力学改善，因此患者转至我院。我们同意超说明书使用口服司来帕格。在十天内，我们将司来帕格剂量上调至最终（最大成人）剂量每日两次，每次1600 mcg。六个月后，患者出现：（1）PVR指数、肺动脉加速时间、RAP、RVEDP、右心房/RV大小降低；（2）恢复血管反应性；（3）心脏指数、6分钟步行距离、功能分级、体重和CAMPHOR评分改善。我们令人鼓舞的结果表明，对于重度PAH儿童，可考虑超说明书使用口服司来帕格，最好在一项方案驱动的前瞻性研究中进行。
