Sota-ES - Sotatercept in Patients With Congenital Heart Disease and Eisenmenger´s Syndrome

Inclusion Criteria: * Age ≥18 years * Congenital heart disease with Eisenmenger syndrome (known unrepaired atrial septal defect, and/or ventricular septal defect, and/or patent ductus arteriosus; patients with anomalous pulmonary venous drainage will not be considered) * Eisenmenger syndrome defined as right-to-left or bi-directional shunt with a mPAP \>25 mmHg, PAWP \< 15 mmHg, and PVR \>5 WU * In patients with pre-tricuspid shunt, the consideration of Eisenmenger syndrome requires one of the following: Systemic arterial O2 saturation (SaO2) at rest \<88% and more than 70%, and/or SaO2 \<80% during 6MWT, and secondary erythrocytosis (Hb \> 15.0 g/dl for females and 16.0 g/dl for males) * On stable doses of background PAH therapy\* and diuretics (i.e., patient-individual dose goal for each therapy achieved) for ≥30 days * 6-minute walking distance \>100 m * WHO-FC II or III * Written informed consent Exclusion Criteria: * Age \<18 years * Diagnosis of pulmonary hypertension groups 2, 3, 4, or 5 * Hospitalization or change in PAH background therapies within 30 days prior to screening (changes in dose of diuretics or parenteral prostanoids \[\<10% change in infusion rate over the preceding 3 months\] are allowed) * Uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure \>160 mmHg or sitting diastolic blood pressure \>100 mmHg during screening visit after a period of rest * Baseline systolic blood pressure \<90 mmHg at screening * Left ventricular systolic dysfunction (LVEF 40%) * Restrictive lung disease with a TLC \< 60% AND demonstration of more than mild fibrosis on chest CT prior to enrolment (note that patients with congenital heart disease may have thoracic cage deformities \[e.g. pectus\] that may lead to thoracic cage restriction in the absence of parenchymal lung disease). * Obstructive lung disease (FEV1 \< 60% pred. and FEV1/FVC \<60%) * Chronic thromboembolic disease (intermediate or high probability) on V/Q scan and evidence of distal thromboembolism on CT angiography (note that proximal in-situ thrombosis is a known complication of Eisenmenger's and will not be considered an exclusion criterion - such patients may be reviewed centrally for inclusion) * Significant liver disease (Child II or III) * Any of the following clinical laboratory values at the screening visit: * Estimated glomerular filtration rate (eGFR) \<30 mL/min/m2 (as defined by the Modification of Diet in Renal Disease \[MDRD\] equation) * Serum alanine aminotransferase, aspartate aminotransferase, or total bilirubin levels \>3 × ULN (bilirubin criterion waived if there is a documented history of Gilbert's syndrome) * Baseline platelet count \<50,000/µl (\<50.0 x 109/L) at screening * Documented episodes of previous repetitive hyperviscosity syndrome * History of haemoptysis within 12 months prior to screening, and/or repeated severe epistaxis (≥ 1 episode per month) * Uncorrected iron deficiency (iron stores must be normal defined as a Ferritin \> 100 and transferrin saturation \[TSAT\] ≥ 20%) * Recent (\< 3 months) enrolment into a rehabilitation program * Untreated sleep disordered breathing with an AHI \> 10. Patients with sleep apnea will need to have been on CPAP or BiPAP for 3 months prior to enrolment. * Prior or current exposure to sotatercept or luspatercept * Treatment by phlebotomy within 1 month prior to screening * Participation in another interventional study * Pregnant (serum B-HCG) or lactating women