2018 年第 5 期 第 13 卷

诊断性治疗左向右分流型先天性心脏病合并重度肺动脉高压中靶向药物的应用及手术适应证的选择

Application of targeted drugs in diagnostic treatment of severe pulmonary hypertension associated with left-to-right shunt congenital heart disease and its values in surgical indication selection

作者：王执一景小勇杨学勇李刚苏俊武刘迎龙范祥明

英文作者：

单位：100029首都医科大学附属北京安贞医院小儿心脏中心

英文单位：

关键词：先天性心脏病；肺动脉高压；靶向药物；诊断性治疗

英文关键词：

• 摘要：

• 目的    评估靶向药物在诊断性治疗左向右分流型先天性心脏病合并重度肺动脉高压患者手术适应证选择中的临床价值。方法    回顾性分析2011年1月至2017年6月首都医科大学附属北京安贞医院收治的左向右分流型先天性心脏病合并重度肺动脉高压患者55例。在强心利尿药物治疗的基础上，联合应用波生坦诊断性治疗，并通过右心导管检查、超声心动图和经皮血氧饱和度（SpO2）改善情况评估波生坦治疗效果欠佳患者，联合应用皮下/静脉输注前列环素类药物（曲前列尼尔）治疗后，再次评估是否符合手术指征，对符合手术指征患者行外科手术根治，对术后残存肺动脉高压和不符合手术指征患者长期联合控制肺动脉高压药物治疗并进行远期超声心动图随访。结果    本研究中单用波生坦患者32例（58.2%），治疗后SpO2水平由86%～94%［（91.5±2.2）%］上升至95%～99%［（97.1±1.7）%］。序贯联合靶向药物治疗患者23例（41.8%），经联合用药后12例患者SpO2水平由70%～94%［（89.4±8.2）%］上升至95%～99%［（96.6±2.1）%］；4例复杂畸形患者SpO2水平由68%～79%［（72.1±4.3）%］上升至82%～91%［（86.0±6.0）%］，平均上升水平(17.7±3.4)%；另有7例患者SpO2水平用药后仍维持在78%～92%［（89.1±5.3）%］，目前继续靶向药物治疗。经诊断性治疗后48例（87.3%）患者行外科根治手术治疗，无围术期死亡，术后恢复良好；7例（12.7%）患者未达手术指征继续靶向药物治疗。全组手术患者随访3～6个月，6例患者肺动脉压力恢复正常，37例患者降至轻中度肺动脉高压，5例患者术后残存重度肺动脉高压。结论    诊断性治疗通过强心利尿药物加上靶向药物的联合治疗，对传统意义上不符合手术指征的患者提供了可能根治手术的机会，同时对术后残存肺动脉高压和不符合手术指征的患者降低肺动脉压力、改善生活质量也有着重要意义。

• 【Abstract】Objective    To evaluate the value of targeted drugs in diagnostic treatment and surgical indication selection for left-to-right shunt congenital heart disease patients with severe pulmonary hypertension. Methods    Clinical data of 55 left-to-right shunt congenital heart disease patients with severe pulmonary hypertension were reviewed from January 2011 to June 2017 in Beijing Anzhen Hospital, Capital Medical University. All patients were treated with bosentan on the basis of cardiotonic and diuretic agents; patients with no significant response to bosentan had subcutaneous/intravenous infusion of prostacyclin drug（treprostinil）. Patients who showed surgical indications after diagnostic treatment had radical operation; patients without surgical indications and patients with residual pulmonary hypertension after operation were treated with long-term drug therapy and had regular echocardiography reexamination. Results    Thirty-two patients(58.2%) had bosetan monotherapy; the level of SpO2 increased from 86%-94%［（91.5±2.2）%］ to 95%-99%［（97.1±1.7）%］ after treatment. Twenty-three patients（41.8%） had sequential targeted drug therapy; the level of SpO2 in 12 patients increased from 70%-94%［（89.4±8.2）%］ to 95%-99%［（96.6±2.1）%］ after treatment; the level of SpO2 in 4 patients with complex congenital heart disease increased from 68%-79% ［（72.1±4.3）%］ to 82%-91%［（86.0±6.0）%］ and the average rise level was (17.7±3.4)%; the level of SpO2 in 7 patients remained at 78%-92%［（89.1±5.3）%］ after treatment. Forty-eight patients(87.3%) had surgical radical operation after diagnostic treatment without perioperative death and recovered well; 7 patients(12.7%) continued to be treated with target drugs. All patients were followed up for 3-6 months; pulmonary artery pressure recovered to normal in 6 patients; 37 patients recovered to mild-to-moderate pulmonary hypertension; 5 patients had residual severe pulmonary hypertension after surgery. Conclusion    Diagnostic treatment with combination of cardio-diuretic agents and targeted drugs provide patients who do not conform to surgical indications with opportunity and possibility to have radical surgery, and it is of great significance to reduce postoperative residual pulmonary artery pressure and improve the quality of life.

  【Key word】Congenital heart disease；Pulmonary hypertension；Targeted drugs；Diagnostic treatment

  【Fund program】National Natural Science Foundation of China（81600383）； High Level Health Technical Personnel Training Project of Beijing Health System（2015-3-051）