Clinical features of paediatric pulmonary hypertension: a registry study

Abstract

Background: Paediatric pulmonary hypertension, is an important cause of morbidity and mortality, and is insufficiently characterised in children. The Tracking Outcomes and Practice in Pediatric Pulmonary Hypertension (TOPP) registry is a global, prospective study designed to provide information about demographics, treatment, and outcomes in paediatric pulmonary hypertension.

Methods: Consecutive patients aged 18 years or younger at diagnosis with pulmonary hypertension and increased pulmonary vascular resistance were enrolled in TOPP at 31 centres in 19 countries from Jan 31, 2008, to Feb 15, 2010. Patient and disease characteristics, including age at diagnosis and at enrolment, sex, ethnicity, presenting symptoms, pulmonary hypertension classification, comorbid disorders, medical and family history, haemodynamic indices, and functional class were recorded. Follow-up was decided by the patients' physicians according to the individual's health-care needs.

Findings: 362 of 456 consecutive patients had confirmed pulmonary hypertension (defined as mean pulmonary artery pressure ≥25 mm Hg, pulmonary capillary wedge pressure ≤12 mm Hg, and pulmonary vascular resistance index ≥3 WU/m(-2)). 317 (88%) patients had pulmonary arterial hypertension (PAH), which was idiopathic [IPAH] or familial [FPAH] in 182 (57%), and associated with other disorders in 135 (43%), of which 115 (85%) cases were associated with congenital heart disease. 42 patients (12%) had pulmonary hypertension associated with respiratory disease or hypoxaemia, with bronchopulmonary dysplasia most frequent. Finally, only three patients had either chronic thromboembolic pulmonary hypertension or miscellaneous causes of pulmonary hypertension. Chromosomal anomalies, mainly trisomy 21, were reported in 47 (13%) of patients with confirmed disease. Median age at diagnosis was 7 years (IQR 3-12); 59% (268 of 456) were female. Although dyspnoea and fatigue were the most frequent symptoms, syncope occurred in 31% (57 of 182) of patients with IPAH or FPAH and in 18% (eight of 45) of those with repaired congenital heart disease; no children with unrepaired congenital systemic-to-pulmonary shunts had syncope. Despite severe pulmonary hypertension, functional class was I or II in 230 of 362 (64%) patients, which is consistent with preserved right-heart function.

Interpretation: TOPP identifies important clinical features specific to the care of paediatric pulmonary hypertension, which draw attention to the need for paediatric data rather than extrapolation from adult studies.

Funding: Actelion Pharmaceuticals.

Conflict of interest statement

Conflicts of interest

All authors or their institutions have received travel costs to visit executive board or investigator meetings related to the TOPP-registry from the Association for Pediatric Pulmonary Hypertension. GR has been a consultant for the Association for Pediatric Pulmonary Hypertension. RMFB has been a consultant for Actelion Pharmaceuticals, GlaxoSmithKline, Novartis, and United Therapeutics; his institution has received or has grants pending from Actelion Pharmaceuticals and Pfizer; and has received lecture fees from Actelion Pharmaceuticals. MB has been a consultant and board member for Actelion Pharmaceuticals, Pfizer, Bayer, Novartis, Eli Lilly, and GlaxoSmithKline; has received grants from Bayer and lecture fees from Actelion Pharmaceuticals, Pfizer, and Bayer; and has developed educational material for Actelion Pharmaceuticals. GER has been a consultant for Bayer, Bristol-Myers Squibb, Johnson & Johnson, Pfizer, Actelion Pharmaceuticals, Daiichi-Sankyo, Sanofi-Aventis, Boehringer Ingelheim, GlaxoSmithKline, and Takeda R&D; and has received writer’s fees from Bristol-Myers Squibb, Daiichy Sankyo, Bayer, and Sanofi-Aventis. DDI has been a consultant for Actelion Pharmaceuticals, Gilead, United Therapeutics, and Pfizer; and has received grants from Gilead and developed educational material for United Therapeutics. ZCJ has been a consultant and board member for Pfizer, GlaxoSmithKline, Actelion Pharmaceuticals, United Therapeutics, and Bayer; has received grants from Actelion Pharmaceuticals, Bayer, Pfizer, and United Therapeutics; and has received lecture fees from Actelion Pharmaceuticals and Bayer. RJB has been a consultant for Actelion Pharmaceuticals, Eli Lilly, GlaxoSmithKline, Gilead, Merck, Novartis, Bayer, and Pfizer. TH, IS-N, and DB declare that they have no conflicts of interests.

Copyright © 2012 Elsevier Ltd. All rights reserved.