Real World Difference After Changing Medication From Nonselective to Selective Endothelin Receptor Antagonist in Stable Eisenmenger Syndrome
Real World Difference After Changing Medication From Nonselective to Selective Endothelin Receptor Antagonist in Stable Eisenmenger Syndrome
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