Combination therapy of bosentan, beraprost and HOT improve pulmonary artery hypertension related to congenital heart disease in contraindications for right heart bypass surgery

  • Keijirou Ibuki, Department of Pediatrics, Faculty of Medicine, University of Toyama, Japan
  • Keiichi Hirono, Department of Pediatrics, Faculty of Medicine, University of Toyama, Japan
  • Kazu Saito, Department of Pediatrics, Faculty of Medicine, University of Toyama, Japan
  • Kazuhiro Watanabe, Department of Pediatrics, Faculty of Medicine, University of Toyama, Japan
  • Sayaka Watanabe, Department of Pediatrics, Faculty of Medicine, University of Toyama, Japan
  • Naoki Yoshimura, 1st department of surgery, Faculty of Medicine, University of Toyama, Japan
  • Fukiko Ichida, Department of Pediatrics, Faculty of Medicine, University of Toyama, Japan
  • Toshio Miyawaki, Department of Pediatrics, Faculty of Medicine, University of Toyama, Japan

    • Background: Bosentan, an oral dual endothelin (ET-A/ET-B) receptor antagonist has been shown to be effective in patients with idiopathic PAH and PAH related to connective tissue disease, improving long term quality of life. However, there are few reports so far on the effect of bosentan for increased pulmonary vascular resistance (PVR) in patients with single ventricle (SV) physiology.
    Objective: We examine successful combination therapy of bosentan, beraprost and HOT in five patients with congenital heart disease (CHD) who could not undergo right heart bypass surgery because of PAH initially.
    Methods: All enrolled patients had PAH in World Health Organization (WHO) functional class III related to CHD with or without prior surgical repair with fixed elevated pulmonary vascular resistance.
    Results: Combination therapy successfully reduced PAP and PVR in all cases. Mean PAP and PVR at baseline and after bosentan therapy, respectively, were; mean main PA pressure (mmHg) : 27.0±9.4 to 19.4±14.5 (p<0.05), PVRI (unit/m2): 5.5±2.4 to 1.9±0.8 (p<0.05), PVR/SVR: 0.36±0.19 to 0.06±0.02 (p<0.05). Each patient had improved clinical symptoms and modified New York Heart Association class, from III to II. Bidirectional Glenn was performed in 4 cases, and 3 cases underwent successful Fontan operations.
    Conclusions: Combined therapy with bosentan, beraprost and HOT may widen the surgical options and improve outcome in Fontan candidates. Larger studies with long-term bosentan are needed to assess the optimal doses and possible therapeutic role of bosentan in this population.