波生坦治疗儿童先天性心脏病相关肺动脉高压的疗效观察

Outcome of oral bosentan in children with congenital heart disease associated pulmonary arterial hypertension

目的评价非选择性内皮素受体拮抗剂波生坦用于儿童先天性心脏病（CHD）相关肺动脉高压（PAH）治疗的临床效果。方法32例具备用药指征的CHD患儿接受口服波生坦治疗，其中18例为左向右分流，男10例，女8例，年龄2个月至15岁；14例为功能性单心室（FSV），男8例，女6例，年龄5个月至15岁。术前90d至术后8年开始口服波生坦治疗，用药后定期随访，评估临床效果和药物不良反应。结果左向右分流患儿口服波生坦后1、2、3个月肺动脉压（mm Hg，1mm Hg=0．133kPa）分别为57±26、52±31、46±22，均明显低于用药前（74±15，均P〈0．05）；用药后3个月心功能分级明显改善（Ⅳ、Ⅲ、Ⅱ级构成比分别为55．6％、33．3％、11．1％比o、16．7％、83．3％，P〈0．01）。其中7例8—15岁患儿用药后3个月6min步行距离较用药前明显增加[（497±56）比（424±31）m，P〈0．01）]。FSV组患儿末次随访（用药2～5个月）经皮血氧饱和度比用药前明显提高[（86±5）％比（78±6）％，P〈0．01]；心功能分级明显改善（Ⅳ、Ⅲ、Ⅱ级构成比分别为0、21．4％、71．5％比35．7％、42．9％、21．4％，P〈0．01）；颜面部水肿和胸腔积液发生率明显降低（均为7．1％比57．1％，均P〈0．05），未发现因服用波生坦而发生的明显不良反应。结论波生坦用于治疗儿童CHD相关PAH是安全的。对左向右分流患儿可有效降低术后肺动脉压，改善心功能分级和活动耐量；对FSV患儿可改善血氧饱和度和心功能，降低肺血管阻力增高所致并发症的发生率。

Objective To investigate the outcome of dual endothelin receptor antagonist bosentan in children with congenital heart disease （CHD） associated pulmonary arterial hypertension （PAH）. Methods A total of 32 children were recruited into this prospective and observational study. Among them, there were 18 cases with left-to-right shunt and 14 cases with elevated pulmonary vascular resistance （ PVR ） in functional single ventricle （FSV）. All the cases were treated with oral bosentan, initialed from 90 days before or 8 years after operation, and were followed up periodically to analyze the clinical outcome and monitor its side effects. Results In the left-to-right shunt group, pulmonary arterial pressure （PAP） was measured at （57 ±26） , （52 ±31 ） and （46 ±22） mm Hg after oral bosentan therapy at 1, 2 and 3 months respectively. The measurements significantly decreased as compared with the pre-dosing level of （74 ± 15 ） mm Hg （P 〈 0.05）. After a 3-months therapy of bosentan, World Health Organization functional class （ WHO FC） improved significantly （P 〈 0.01 ）. In the elder cases, the 6-minute walking distance after a 3- month bosentan therapy significantly increased as compared with the pre-dosing level, i.e. （497 ± 56） vs （424 ± 31 ） m （P 〈 0.05）. In the FSV group, as compared with the pre-dosing level, the transcutaneous oxygen saturation increased significantly in the last follow-up during bosentan exposure, i.e. （ 86 ± 5 ） % vs （78 ±6）% （P〈0.01）. WHO FC improved significantly （P 〈0. 01 ） and the incidence of facial edema and pleural effusion was significant lower （P 〈0.05） in the last follow-up for the treatment group. Patients tolerated bosentan well and no significant rise in hepatic transaminases was observed. Conclusions Bosentan is safe in treating CHD associated PAH in children. In left-to-right shunt cases, oral bosentan can reduce PAP and improve both WHO FC and exercise capacity. And it can also improve WHO FC and transcutaneous oxygen saturation in FSV and reduces the occurrence of elevated PVR-related complications.