Elsevier

The Lancet

Volume 379, Issue 9815, 11–17 February 2012, Pages 537-546
The Lancet

Articles
Clinical features of paediatric pulmonary hypertension: a registry study

https://doi.org/10.1016/S0140-6736(11)61621-8Get rights and content

Summary

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.

Introduction

Pulmonary hypertension with increased pulmonary vascular resistance is associated with substantial morbidity and mortality. The most recent clinical classification defines five pulmonary hypertension groups, with pulmonary arterial hypertension (PAH) being group 1 (the full classification is provided in the webappendix).1 PAH can be idiopathic (IPAH), heritable (HPAH), or associated with conditions (APAH) such as congenital heart disease and can present at any age. It is a rare disease with incidence and prevalence estimates of 2–3 per million and 25–50 per million, respectively.

Without treatment, median survival after diagnosis of IPAH or HPAH has been reported as 2·8 years in adults, but survival in children might be worse.2 Clinical trials and registries have led to substantial progress in treatment of this disorder in adults.2, 3, 4, 5, 6 Although pathobiology and clinical features share similarities in children and adults, paediatric pulmonary hypertension could well differ from adult disease.7, 8, 9 Adult studies alone cannot provide a basis for optimum care for children. However, paediatric pulmonary hypertension is insufficiently characterised. The Tracking Outcomes and Practice in Pediatric Pulmonary Hypertension (TOPP) registry is a global, prospective, observational study designed to provide information about demographics, course, treatment, and outcomes in paediatric pulmonary hypertension.10

Section snippets

Study design

TOPP is a centre-based, comprehensive registry, which was initiated on Jan 31, 2008. Enrolled patients undergo assessment, treatment, and follow-up according to the judgment of their physicians. No specific therapy or follow-up protocols are part of TOPP. Patients in clinical trials are eligible. Patients were enrolled from 31 centres in 19 countries in five continents (sites and investigators are listed at the end of the report). Patients with pulmonary hypertension caused by left-heart

Results

From Jan 31, 2008, to Feb 15, 2010, 456 patients were enrolled. Enrolment of prevalent and incident patients was stopped at one site on Feb 10 and Aug 19, of 2009, respectively, to prevent overrepresentation of that site. Enrolment of prevalent patients at all other sites was stopped on May 22, 2009, to prevent such patients accounting for more than two-thirds of the total. No further predefined restriction rules were required.

Of the 456 patients in the all-patients cohort, 362 (79%) met all

Discussion

Overall, about half the children enrolled with confirmed pulmonary hypertension had a history of congenital heart disease, which was regarded as causative for the PAH in most cases. In the most recent classification of pulmonary hypertension, a specific threshold for increased pulmonary vascular resistance was abandoned as a criterion for PAH.11 Flow-associated pulmonary hypertension due to large left-to-right systemic-to-pulmonary shunts might have normal pulmonary capillary wedge pressure and

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