Beneficial Effect of Oral Bosentan in Children with Pulmonary Arterial Hypertension Associated with Congenital Heart Disease

  • Limin Zhu, Department of cardiovascular surgery, Shanghai Children’s Medical Center, Medical college of Shanghai Jiaotong University, China
  • Zhuoming Xu, Department of cardiovascular surgery, Shanghai Children’s Medical Center, Medical college of Shanghai Jiaotong University, China
  • Xiaoman Cai, Department of cardiovascular surgery, Shanghai Children’s Medical Center, Medical college of Shanghai Jiaotong University, China
  • Gang Ji, Department of cardiovascular surgery, Shanghai Children's Medical Center, Medical college of Shanghai Jiaotong University, China
  • Jinfen Liu, Department of cardiovascular surgery, Shanghai Children’s Medical Center, Medical college of Shanghai Jiaotong University, China
  • Zhaokang Su, Department of cardiovascular surgery, Shanghai Children’s Medical Center, Medical college of Shanghai Jiaotong University, China

    • Background—Pulmonary arterial hypertension associated with congenital heart disease (CHD-PAH) is a progressive and fatal disease. Endothelin is a mediator of PAH. Bosentan, an oral dual endothelin receptor antagonist, improves hemodynamics and exercise capacity in adults with PAH; however, limited data are available on its effects in children.
    Objective: To examine mid-term safety and efficacy of bosentan in children with increased pulmonary vascular resistance (PVR) because of CHD. For observation only, an open-label bosentan arm was included.
    Interventions: Bosentan was given as2-4 mg/kg orally twice daily. Children were treated for a mean of 3.4 months (range 1–6 months).
    Main outcome measures: WHO functional class, echocardiographic findings, Oxygen saturation, 6-minute walk distance (6MWD) and liver enzymes were analyzed.
    Results: At the cutoff date, 18 patients (10 male) were included (Table). The median age was 3.5 years (range 2 months-15 years). Pulmonary arterial pressure decreased compared with baseline 22.18%, 29.20%, 29.63% at 1 month, 2 months and 3 months of treatment, respectively (p< 0.05 for each) The 6MWD, and WHO FC improved significantly (Figure1,2). Bosentan was discontinued in 1 patient, and another patient died during follow-up. Patients tolerated bosentan well and no significant rise in liver transaminases was seen.
    Conclusions: Oral Bosentan is safe and well tolerated in children with CHD-PAH. It appears to improve. to improve hemodynamics and exercise capacity after 3 months of therapy.