In this study, the investigator will evaluate the treatment effects and safety, patient compliance of Ambrisentan in Eisenmenger syndrome in PAH patients who have been previously treated with Bosentan.

Endothelin receptor antagonist is an established class of targeted therapy for pulmonary arterial hypertension (PAH). Nonselective ERA, Bosentan was the first approved ERA for PAH. Selective ERA, Ambrisentan was also approved for PAH treatment consequently. Although non-selective and selective ERA are both effective in clinical trials, there is no direct comparison for non-selective and selective ERA. Furthermore, approval study for both non-selective and selective ERA did not include the PAH associated with congenital heart disease (PAH-CHD) with significant shunt including Eisenmenger syndrome. Approval study for Ambrisentan;ARIES-1 and ARIES-2 trials also did not include the PAH-CHD In Korea, Bosentan was approved in 2003 and Ambrisentan was approved in 2009 for idiopathic PAH. Bosentan was also approved for PAH-CHD, however, Amrisentan was not because of limited data for PAH-CHD. Therefore, Bosentan was the only ERA covered by public health insurance since 2018 for PAH-CHD. Recently, Amrisentan was also approved for PAH associated with congenital heart disease including Eisenmger syndrome. And, there is a need for changing medication from double pill medication to once-daily dose medication because of patient's compliance.

PAH associated with CHD includes the group with significant shunt vs without shunt (s/p corrected state). When there is a shunt flow, change in pulmonary vascular resistance (PVR) and cardiac output can be a modulator of shunt flow, thus impact of pulmonary vasodilator on hemodynamics can be different from PAH without shunt. However, there is a limited data for changing ERA from non-selective to selective ERA. Our patients population can be interesting study group to understand the clinical response to changing between ERA because they are uniformly treated with non-selective ERA to selective ERA, Bosentan to Ambrisentan.

In this study, the investigators will evaluate the treatment effects and safety, patient compliance of Ambrisentan in Eisenmenger syndrome in PAH patients who have been previously treated with Bosentan.

1. Inclusion Criteria

   • Age at least 18 years

   • Patient who was scheduled to change Ambrisentan from Bosentan (prospective arm) or who already changed to Ambrisentan from Bosentan (retrospective arm)

   • Presence of cyanosis with < 95 % arterial oxygen saturation (measured by transcutaneous pulse oximetry) or documented during exercise test (6 minute walk distance test or CPT stress test)

   • Bosentan treatment more than 3months before changing to Ambrisentan and stable medication dosage for 1 month before changing medication

   • Presence of PAH as diagnosed by invasive methods with Rp:Rs > 0.75 measured at rest or diagnosed by echocardiography with TR Vmax > 3.5m/s and bidirectional or right to left shunt.

   • One of the following diagnosis:

     i) non-corrected large congenital shunting defect at atrial, ventricular or arterial level: Partial anomalous venous return, atrial septal defect, ventricular septal defect, atrioventricular cushion defect, persistent ductus arteriosus, or a combination of these.

   ii) Surgically corrected shunting defect (diagnoses as above) with significant residual defect iii) Other diagnoses with univentricular physiology/haemodynamics.

2. Exclusion Criteria

   • pregnancy or lactation
   • women of child-bearing age who are sexually active without practicing reliable methods of contraception
   • any disease or impairment that, in the opinion of the investigator, excludes a subject from participation
   • substance abuse (alcohol, medicines, drugs)
   • acute decompensated heart failure within 7 days before the invasive procedure
   • significant anemia (Hb < 9.0 g/dl)
   • decompensated symptomatic polycythaemia
   • significant impairment of hepatic function (Child Pugh class C)
   • Significant left ventricular diseases (LV EF < 45%)
   • significant valvular diseases other than tricuspid or pulmonary regurgitation ( mitral or aortic valvular impairment more than moderate degree)
   • pericardial constriction
   • history of stroke, myocardial infarction or life-threatening arrhythmia within 6 months before screening
   • bronchopulmonary dysplasia or other chronic severe lung diseases
   • history of significant pulmonary embolism (in situ thromboembolism with optimal anticoagulation can be enrolled)
   • other relevant diseases (e.g. HIV infection)
   • trisomy 21
   • Unstable medication, recent changes in dosage regimen
   • Other medication with vascular action

• Patient who was scheduled to change Ambrisentan from Bosentan (prospective arm) or who already changed to Ambrisentan from Bosentan (retrospective arm)
• Presence of cyanosis with < 95 % arterial oxygen saturation (measured by transcutaneous pulse oximetry) or documented during exercise test (6 minute walk distance test or CPT stress test)