Bowater Sarah E, Weaver Rebekah A, Thorne Sara A, Clift Paul F
University Hospital Birmingham Foundation NHS Trust, Birmingham, United Kingdom.
Congenit Heart Dis. 2012 May-Jun;7(3):243-9. doi: 10.1111/j.1747-0803.2012.00635.x. Epub 2012 Feb 20.
Adult patients with a Fontan circulation tend to have diminished exercise capacity. The principal objective of this study was to investigate the safety of the endothelin receptor antagonist bosentan in Fontan patients, and, secondarily, to assess effects on cardiovascular performance, New York Heart Association functional classification (NYHA FC), and ventricular function.
A 6-month prospective, single-center, pilot, safety study of bosentan in Fontan patients. Setting. Adult Congenital Heart Disease referral center.
All patients ≥18 years old with a Fontan circulation and in NYHA FC ≥II were invited to enroll. Interventions. Patients started on 62.5 mg bid of bosentan, uptitrating to 125 mg bid after 2 weeks.
Safety was assessed by the incidence of anticipated and unanticipated adverse events during the 6-month study period; specifically those relating to hepatic, renal, or hematological dysfunction as measured by monthly blood tests. Other outcome measures included cardiopulmonary exercise test, 6-minute walk distance test, Borg dyspnea index, NYHA FC, and ventricular function parameters using transthoracic echocardiography.
Of the eight patients enrolled, six completed the study. Two patients withdrew from the study (one for non-trial related reasons, one due to adverse events). No clinically significant adverse events relating to bosentan therapy occurred during this study and, in particular, no significant abnormalities in hepatic function tests were observed. Three patients reported transient adverse events. Improvements in NYHA FC and systolic ventricular function were observed after 6 months of bosentan treatment.
The small number of patients with a Fontan circulation in our study was able to tolerate bosentan for 6 months. The safety and tolerability of bosentan in a larger patient population remains unknown. The results presented here justify further investigation in larger studies.
患有Fontan循环的成年患者运动能力往往会下降。本研究的主要目的是调查内皮素受体拮抗剂波生坦在Fontan患者中的安全性，其次是评估其对心血管功能、纽约心脏协会功能分级（NYHA FC）和心室功能的影响。
一项针对Fontan患者使用波生坦的为期6个月的前瞻性、单中心、试点安全性研究。地点：成人先天性心脏病转诊中心。
邀请所有年龄≥18岁、患有Fontan循环且NYHA FC≥II级的患者入组。干预措施：患者开始服用波生坦62.5mg，每日两次，2周后增至125mg，每日两次。
通过6个月研究期间预期和意外不良事件的发生率评估安全性；具体而言，通过每月血液检测评估与肝、肾或血液系统功能障碍相关的不良事件。其他观察指标包括心肺运动试验、6分钟步行距离试验、Borg呼吸困难指数、NYHA FC以及使用经胸超声心动图测量的心室功能参数。
入组的8名患者中，6名完成了研究。2名患者退出研究（1名因非试验相关原因，1名因不良事件）。本研究期间未发生与波生坦治疗相关的具有临床意义的不良事件，特别是未观察到肝功能检查有明显异常。3名患者报告了短暂的不良事件。波生坦治疗6个月后，NYHA FC和心室收缩功能有所改善。
我们研究中患有Fontan循环的患者数量较少，但能够耐受波生坦6个月。波生坦在更大患者群体中的安全性和耐受性仍然未知。此处呈现的结果证明有必要在更大规模的研究中进一步探究。
