法舒地尔治疗先天性心脏病相关性重度肺动脉高压短期疗效观察

Short-term effects of fasudil on patients with severe pulmonary arterial hypertension secondary to congenital heart disease

目的探讨法舒地尔治疗先天性心脏病相关性重度肺动脉高压短期应用的有效性及安全性。方法人选2011年1月-2012年8月我科住院的先天性心脏病相关性重度肺动脉高压患者，法舒地尔60mg静脉滴注，每天2次，连续用药14d后观察6分钟步行距离、血流动力学参数、超声心动图指标以及血浆N末端脑钠尿肽前体（NT—proBNP）变化情况。结果共纳入21（男4，女17）例患者，年龄16—54（32±14）岁；用药14d后6分钟步行距离由（445±49）m显著增加至（471±40）m，差异有统计学意义；且WHO肺动脉高压心功能分级显著改善（P〈0．05）。血浆NT—proBNP亦明显下降，从（788±623）pg／ml降低至（464±393）pg／ml（P〈0．05）。右房平均压从（6．1±2．3）mmHg降低至（5．2±1．8）mmHg（P〈0．05）；右向左分流量从（23±16）％明显减少至（18±16）％（P〈0．05）；而肺动脉平均压、肺血管阻力、体肺循环血流量比值、体肺循环阻力比值、股动脉氧饱和度、心脏指数等指标虽无显著统计学差异，但较用药前均有所改善，仅体循环压力及阻力均无统计学差异。结论法舒地尔短期内应用可显著提高先天性心脏病相关重度肺动脉高压患者的运动耐量、WHO肺动脉高压心功能分级，有效改善肺动脉高压的血流动力学指标，而且安全性与耐受性良好。

AIM To investigate the short-term efficacy and safety of fasudil （a Rho kinase inhibitor） monotherapy in patients with severe pulmonary arterial hypertension （PAH） secondary to congenital heart disease （CHD）. METHODS Enrolled in the study were 21 patients with severe PAH secondary to CHD from January 2011 to August 2012 in our Department. All patients were given basic drug treatment for PAH and then continuously given fasudil 60 mg i.v. twice a day for 14 days. After fasudil treatment, changes were observed in the 6-min walking distance according to all relevant hemodynamic parameters （including pulmonary arterial pressure, left to right and right to left shunt volume, pulmonary vascular resistance, systemic and pulmonary blood flow, systemic pressure, systemic vascular resistance, and car- diac output and femoral arterial blood oxygen saturation） , anatomy parameters （including each chamber size and left ventrieular ejection fraction） and plasma brain natriuretic peptide and liver and kidney func- tions after medication. RESULTS After continuous administration of fasudil for 14 days, the 6-min walking distance increased dramatically from （445 ± 490） m to （471 ± 40） m, with significant statistical difference. WHO cardiac functions improved significantly （P 〈 0.05）. Compared with baseline, plasma NT-proBNP significantly decreased from （788 ± 622.61 ） pg/ml to （464 ± 392.80 ） pg/ml （P = 0. 043）, with significant statistical difference. Compared with baseline, mean right atrial pressure decreased from （6. 12 ±2. 26） mmHg to （5.2 ± 1.84） mmHg （P 〈0.05） and right to left shunt volume significantly reduced from （22. 9 ± 16. 21）% to （18. 3 ± 15.98）% （P 〈0. 05）. No significant difference was observed in mean pulmonary artery pressure, pulmonary vascular resistance, systemic and pulmonary blood flow ratio, systemic and pulmonary vascular resistance ratio, femoral arterial oxygen saturation and cardiac indexes, but all improved to some extent. No statistical differences were found in systemic arterial pressure and systemic vascular resistance and no obvious changes were seen in liver and kidney functions. CONCLUSION Short-term treatment of fasudil is safe and well tolerated and can effectively improve exercise capacity and hemodynamic parameters in patients with severe pulmonary arterial hypertension secondary to CHD.