Derk Gwendolyn, Houser Linda, Miner Pamela, Williams Ryan, Moriarty John, Finn Paul, Alejos Juan, Aboulhosn Jamil
Ahmanson/UCLA Adult Congenital Heart Disease, University of California Los Angeles, Los Angeles, Calif, USA.
Congenit Heart Dis. 2015 Jan-Feb;10(1):E11-6. doi: 10.1111/chd.12189. Epub 2014 May 30.
Phosphodiesterase-5 inhibitors have shown to improve cardiac output and functional capacity in Fontan patients. We sought to test the efficacy and safety of endothelin blockade with bosentan in adult patients with Fontan physiology.
Ten patients were enrolled and seven patients completed this single-center open-label clinical trial. Patients were treated with bosentan for 4 months. Cardiac magnetic resonance imaging (MRI), 6-minute walking distance (6MWD), brain natriuretic peptide, and New York Heart Association functional class were compared before and after treatment using paired t-test.
The 6MWD improved by 73 m, from a mean of 435 m (standard deviation [SD] = 92, standard error [SE] = 35) to 508 m (SD = 93, SE = 35) (P = .03). MRI resting aortic flow increased from 3.3 L/minute (SD = 1.27, SE = 0.73) to 4.4 L/minute (SD = 0.9, SE = 0.54) (P = .03). New York Heart Association class was unchanged in three patients, improved in three patients and worsened in one patient. Brain natriuretic peptide, aspartate aminotransferase, and alanine aminotransferase did not change significantly. Of the three patients with elevated baseline bilirubin, two normalized at the completion of the study, while the other was unchanged. Mean duration of therapy was 4.1 ± 0.51 months. Three adverse advents occurred. One patient complained of fatigue and chest pain after 87 days and withdrew from the study. After extensive workup, it was determined that her symptoms were not related to treatment. The second patient suffered palpitations and fatigue after 75 days; no concerning arrhythmias were identified and symptoms improved with increased antiarrhythmic dose. The third patient developed fatigue on therapy and decided to stop therapy; fatigue improved following drug discontinuation. There were no deaths or hospitalizations.
In this cohort of adult patients with Fontan physiology, endothelin blockade with bosentan resulted in improved 6MWD and MRI-derived resting cardiac output, suggesting a positive effect on pulmonary vascular resistance and pulmonary blood flow. Bosentan was well tolerated and hepatic function was not adversely affected.
磷酸二酯酶-5抑制剂已显示可改善Fontan手术患者的心输出量和功能能力。我们旨在测试波生坦内皮素阻断疗法对成年Fontan生理患者的疗效和安全性。
招募了10名患者，7名患者完成了这项单中心开放标签临床试验。患者接受波生坦治疗4个月。使用配对t检验比较治疗前后的心脏磁共振成像（MRI）、6分钟步行距离（6MWD）、脑钠肽和纽约心脏协会功能分级。
6MWD增加了73米，从平均435米（标准差[SD]=92，标准误[SE]=35）增至508米（SD=93，SE=35）（P=0.03）。MRI静息主动脉血流量从3.3升/分钟（SD=1.27，SE=0.73）增至4.4升/分钟（SD=0.9，SE=0.54）（P=0.03）。纽约心脏协会分级在3名患者中未变，3名患者改善，1名患者恶化。脑钠肽、天冬氨酸转氨酶和丙氨酸转氨酶无显著变化。3名基线胆红素升高的患者中，2名在研究结束时恢复正常，另1名未变。平均治疗持续时间为4.1±0.51个月。发生了3例不良事件。1例患者在87天后出现疲劳和胸痛并退出研究。经过全面检查，确定其症状与治疗无关。第2例患者在75天后出现心悸和疲劳；未发现相关心律失常，增加抗心律失常药物剂量后症状改善。第3例患者在治疗时出现疲劳并决定停药；停药后疲劳改善。无死亡或住院情况。
在这组成年Fontan生理患者中，波生坦内皮素阻断疗法使6MWD和MRI得出的静息心输出量增加，提示对肺血管阻力和肺血流量有积极作用。波生坦耐受性良好，肝功能未受到不利影响。
