{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T10:12:14Z","timestamp":1782987134671,"version":"3.54.5"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T00:00:00Z","timestamp":1670544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:p>An extremely dystrophic, premature female infant, born at 25 3\/7 weeks of gestational age (birth weight: 430 g) with severe pulmonary hypertension (PH), was admitted to our neonatal intensive care unit (ICU) requiring cardiorespiratory support, including mechanical ventilation and pulmonary vasodilators such as inhaled nitric oxide (iNO) and continuous intravenous sildenafil infusions. The diagnosis of bronchopulmonary dysplasia (BPD) was made. A hemodynamically relevant, persistent ductus arteriosus (PDA) was surgically ligated after failed pharmacologic PDA closure using indomethacin and ibuprofen. The patient was discharged with an estimated 2\/3 systemic pulmonary artery pressure. One month after hospital discharge, on low-flow oxygen supplementation (0.5 L\/min FiO2 100%), at the corrected age of 16 weeks, she was readmitted to our emergency department with signs of respiratory distress and circulatory decompensation. Echocardiography demonstrated suprasystemic PH. Severe PH persisted despite initiated invasive mechanical ventilation, triple vasodilating therapy [iNO, macitentan, and continuous intravenous (IV) sildenafil], as well as levosimendan, milrinone, and norepinephrine for recompensation from cardiac shock. Thus, we started off-label oral selexipag therapy (oral IP receptor agonist) in the smallest patient reported so far (4 kg body weight). Subsequently, RV systolic pressure decreased to half-systemic, allowing successful weaning of iNO, norepinephrine, and milrinone, and extubation of the patient over 4 days. The infant was discharged 4 weeks after pediatric intensive care unit (PICU) admission in stable cardiorespiratory condition, with an oral, specific, triple antihypertensive PAH-targeted therapy using selexipag, macitentan, and sildenafil as well as oxygen therapy at low-flow (0.5 l\/min) and spironolactone. The first cardiac catheterization at the age of 9 months under aforementioned triple PAH-targeted therapy revealed mild PH with 35% systemic PA pressure (mPAP\/mSAP = 0.35) and isolated pulmonary vein stenosis. A transthoracic biopsy at the age of 12 months confirmed the diagnosis of BPD and further showed pulmonary interstitial glycogenosis and severe pulmonary capillary hemangiomatosis, without involvement of the pulmonary venules (chILD A2, A3, and B4 according to the Deutsch-Classification). The patient is currently in stable cardiorespiratory condition undergoing triple PH-targeted therapy including selexipag. This report highlights the potential benefits of the oral prostacyclin mimetic selexipag as an early add-on PH-targeted drug in chronic PH of infancy (cPHi).<\/jats:p>","DOI":"10.3389\/fcvm.2022.984698","type":"journal-article","created":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T07:38:45Z","timestamp":1670571525000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Case report: Rescue treatment with add-on selexipag in a preterm infant with suprasystemic pulmonary hypertension, pulmonary capillary hemangiomatosis, and isolated pulmonary vein stenosis"],"prefix":"10.3389","volume":"9","author":[{"given":"Hosan","family":"Hasan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klea","family":"Hysko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Jack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Dingemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Wetzke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Hansmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,12,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1164\/rccm.201812-2348OC","article-title":"The diagnosis of bronchopulmonary dysplasia in very preterm infants. an evidence-based approach.","volume":"200","author":"Jensen","year":"2019","journal-title":"Am J Respir Crit Care Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/j.rmed.2017.10.014","article-title":"Bronchopulmonary dysplasia: a review of pathogenesis and pathophysiology.","volume":"132","author":"Kalikkot Thekkeveedu","year":"2017","journal-title":"Respir Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1016\/s0046-8177(98)90280-5","article-title":"Pathology of arrested acinar development in postsurfactant bronchopulmonary dysplasia.","volume":"29","author":"Husain","year":"1998","journal-title":"Hum Pathol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/S1084-2756(02)00193-8","article-title":"Pathology of new bronchopulmonary dysplasia.","volume":"8","author":"Coalson","year":"2003","journal-title":"Semin Neonatol."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-019-0127-7","article-title":"Bronchopulmonary dysplasia.","volume":"5","author":"Thebaud","year":"2019","journal-title":"Nat Rev Dis Primers."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.siny.2022.101351","article-title":"Diagnosis and management of pulmonary hypertension in infants with bronchopulmonary dysplasia.","volume":"27","author":"Levy","year":"2022","journal-title":"Semin Fetal Neonatal Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1038\/s41390-020-0993-4","article-title":"Pulmonary hypertension in bronchopulmonary dysplasia.","volume":"89","author":"Hansmann","year":"2021","journal-title":"Pediatr Res."},{"key":"B8","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1016\/j.healun.2019.06.022","article-title":"2019 updated consensus statement on the diagnosis and treatment of pediatric pulmonary hypertension: the European Pediatric Pulmonary Vascular Disease Network (EPPVDN), endorsed by AEPC, ESPR and ISHLT.","volume":"38","author":"Hansmann","year":"2019","journal-title":"J Heart Lung Transplant."},{"key":"B9","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1164\/rccm.201409-1594OC","article-title":"Early pulmonary vascular disease in preterm infants at risk for bronchopulmonary dysplasia.","volume":"191","author":"Mourani","year":"2015","journal-title":"Am J Respir Crit Care Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1260","DOI":"10.1542\/peds.2007-0971","article-title":"Pulmonary artery hypertension in formerly premature infants with bronchopulmonary dysplasia: clinical features and outcomes in the surfactant era.","volume":"120","author":"Khemani","year":"2007","journal-title":"Pediatrics."},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2021.648972","article-title":"Long-term outcomes of bronchopulmonary dysplasia under two different diagnostic criteria: a retrospective cohort study at a chinese tertiary center.","volume":"9","author":"Sun","year":"2021","journal-title":"Front Pediatr."},{"key":"B12","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1038\/s41372-022-01374-w","article-title":"Extremely premature infants born at 23-25 weeks gestation are at substantial risk for pulmonary hypertension.","volume":"42","author":"Sallmon","year":"2022","journal-title":"J Perinatol."},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2018.07.035","article-title":"The impact of pulmonary hypertension in preterm infants with severe bronchopulmonary dysplasia through 1 year.","volume":"203","author":"Lagatta","year":"2018","journal-title":"J Pediatr."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1111\/eci.13571","article-title":"Off-label use of PAH-targeted medications approved for adults and their financial coverage by health insurances are vital for children with pulmonary hypertension.","volume":"51","author":"Hansmann","year":"2021","journal-title":"Eur J Clin Invest."},{"key":"B15","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1016\/j.healun.2020.03.029","article-title":"Selexipag for the treatment of children with pulmonary arterial hypertension: first multicenter experience in drug safety and efficacy.","volume":"39","author":"Hansmann","year":"2020","journal-title":"J Heart Lung Transplant."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2020-1209","article-title":"Patent ductus arteriosus of the preterm infant.","volume":"146","author":"Hamrick","year":"2020","journal-title":"Pediatrics."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1718","DOI":"10.21037\/cdt-20-483","article-title":"Cardiac catheterization in pulmonary hypertension: doing it right, with a catheter on the left.","volume":"10","author":"Hansmann","year":"2020","journal-title":"Cardiovasc Diagn Ther."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1016\/j.jacc.2015.10.102","article-title":"The need for comprehensive cardiac catheterization in children with pulmonary hypertension.","volume":"67","author":"Hansmann","year":"2016","journal-title":"J Am Coll Cardiol."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01913-2018","article-title":"Haemodynamic definitions and updated clinical classification of pulmonary hypertension.","volume":"53","author":"Simonneau","year":"2019","journal-title":"Eur Respir J."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1120","DOI":"10.1164\/rccm.200703-393OC","article-title":"Diffuse lung disease in young children: application of a novel classification scheme.","volume":"176","author":"Deutsch","year":"2007","journal-title":"Am J Respir Crit Care Med."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-015-0339-1","article-title":"Categorizing diffuse parenchymal lung disease in children.","volume":"10","author":"Griese","year":"2015","journal-title":"Orphanet J Rare Dis."},{"key":"B22","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1111\/ppe.12444","article-title":"Identification of gaps in the current knowledge on pulmonary hypertension in extremely preterm infants: a systematic review and meta-analysis.","volume":"32","author":"Arjaans","year":"2018","journal-title":"Paediatr Perinat Epidemiol."},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1177\/2045894019878598","article-title":"Diminished right ventricular function at diagnosis of pulmonary hypertension is associated with mortality in bronchopulmonary dysplasia.","volume":"9","author":"Altit","year":"2019","journal-title":"Pulm Circ."},{"key":"B24","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1053\/j.semperi.2018.05.006","article-title":"Patent ductus arteriosus, its treatments, and the risks of pulmonary morbidity.","volume":"42","author":"Clyman","year":"2018","journal-title":"Semin Perinatol."},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2015.06.054","article-title":"Neurodevelopmental outcomes of premature infants treated for patent ductus arteriosus: a population-based cohort study.","volume":"167","author":"Janz-Robinson","year":"2015","journal-title":"J Pediatr."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0100-2017","article-title":"Chronic interstitial lung disease in children.","volume":"27","author":"Griese","year":"2018","journal-title":"Eur Respir Rev."},{"key":"B27","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1111\/j.1365-2559.1978.tb01734.x","article-title":"Capillary haemangiomatosis of the lungs.","volume":"2","author":"Wagenvoort","year":"1978","journal-title":"Histopathology."},{"key":"B28","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1016\/j.ccm.2016.04.014","article-title":"Pulmonary capillary hemangiomatosis and pulmonary veno-occlusive disease.","volume":"37","author":"Chaisson","year":"2016","journal-title":"Clin Chest Med."},{"key":"B29","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1002\/ppul.10245","article-title":"Congenital pulmonary capillary hemangiomatosis: report of two cases and review of the literature.","volume":"36","author":"Oviedo","year":"2003","journal-title":"Pediatr Pulmonol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.jacc.2004.02.033","article-title":"Pathologic assessment of vasculopathies in pulmonary hypertension.","volume":"43","author":"Pietra","year":"2004","journal-title":"J Am Coll Cardiol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1518","DOI":"10.1183\/13993003.00026-2016","article-title":"Pulmonary veno-occlusive disease.","volume":"47","author":"Montani","year":"2016","journal-title":"Eur Respir J."}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2022.984698\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T07:38:48Z","timestamp":1670571528000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2022.984698\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,9]]},"references-count":31,"alternative-id":["10.3389\/fcvm.2022.984698"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2022.984698","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,9]]},"article-number":"984698"}}