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Pulmonary arterial hypertension in children after neonatal arterial switch operation
  1. Willemijn MH Zijlstra1,
  2. Ola Elmasry2,
  3. Shari Pepplinkhuizen1,
  4. D Dunbar Ivy3,
  5. Damien Bonnet4,
  6. Paul Luijendijk1,
  7. Marilyne Lévy4,
  8. Jose Luis Gavilan5,
  9. Alba Torrent-Vernetta6,
  10. Alberto Mendoza7,
  11. Maria Jesus del Cerro8,
  12. Shahin Moledina2,
  13. Rolf MF Berger1
  1. 1Center for Congenital Heart Diseases, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
  2. 2Great Ormond Street Hospital for Children, London, UK
  3. 3Children's Hospital Colorado, Aurora, Colorado, USA
  4. 4M3C-Necker, Hôpital Necker Enfants Malades, Université Paris Descartes, Paris, France
  5. 5Virgen del Rocio University Hospital, Seville, Spain
  6. 6Vall d'Hebrón University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain
  7. 7Doce de Octubre University Hospital, Madrid, Spain
  8. 8Ramon y Cajal University Hospital, Madrid, Spain
  1. Correspondence to Willemijn MH Zijlstra, Center for Congenital Heart Diseases, Department of Pediatric Cardiology, Beatrix Children's Hospital, University Medical Center Groningen, P.O. Box 30.001, Groningen 9700 RB, The Netherlands; w.m.h.zijlstra{at}


Objectives Paediatric pulmonary arterial hypertension (PAH) after neonatal arterial switch operation (ASO) for transposition of the great arteries (TGA) is a clinically recognised entity with an estimated incidence of 0.6%–1.0%. Nevertheless, a clinical characterisation is lacking. We present an international cohort of children with PAH after neonatal ASO for TGA and describe epidemiology and clinical course.

Methods Data were collected of children with PAH after neonatal ASO (≤6 weeks after birth) for simple TGA without residual shunt defects, identified in four national paediatric PAH networks in Europe and one US referral centre.

Results Twenty-five children were identified between 1989 and 2014. In 17 children (68%), PAH was detected <1 year after ASO. In the remaining children, PAH was detected after median 64 months (IQR 19.5, 94.5). Nineteen children (96%) received PAH-targeted therapies. During follow-up after ASO (median 5.2 years), eight children died, four underwent lung transplantation and two received a Potts shunt. 1-year and 5-year Potts shunt- and transplantation-free survival after ASO was 100% and 73%. From first PAH detection, this was 100% and 58%, respectively, which did not differ between children with early (<1 year after ASO) or late PAH detection.

Conclusions The occurrence of PAH after ASO for TGA represents a specific association. PAH onset may be early or late after ASO, with similar fatal course from first PAH detection. Mechanisms leading to PAH in this association are unknown, but may include abnormal prenatal pulmonary haemodynamics and/or genetic susceptibility. Routine, lifelong follow-up for children who undergo ASO for TGA should include screening for PAH.

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  • Contributors WMHZ and RMFB designed the study, collected data, analysed and interpreted data and drafted the manuscript. OE, SP, DI, DB, PL, ML, JLG, AT-V, AM, MJdC and SM contributed to the conception and design of the study, the data collection or analysis and interpretation of data, revised the draft of the manuscript critically for important intellectual content and finally approved the submitted manuscript.

  • Funding This research was supported by the Sebald Fund, The Frederick and Margaret L Weyerhaeuser Foundation, The Jayden de Luca Foundation and the Association pour la Recherche en Cardiologie du Foetus à l'Adulte. The REHIPED Registry is supported by unrestricted educational grants from Actelion, Ferrer, GlaxoSmithKline and Pfizer.

  • Competing interests SM has acted as a consultant to Actelion Pharmaceuticals and Bayer HealthCare. DB has acted as a consultant to Actelion Pharmaceuticals, Novartis, Pfizer, Lilly and Bayer HealthCare. The University of Colorado contracts with Actelion, Bayer, Gilead, Lilly, Pfizer and United Therapeutics for consultancy activities of DDI. The University Medical Center Groningen contracts with Actelion, Bayer, GlaxoSmithKline, Lilly and Pfizer for advisory board and steering committee activities of RMFB. All other authors have nothing to disclose.

  • Ethics approval Institutional Review Boards of the constituent/participating registries.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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