Characterisation of paediatric pulmonary hypertensive vascular disease from the PPHNet Registry

Abstract

BackgroundThere are limited data about the range of diseases, natural history, age-appropriate endpoints and optimal care for children with pulmonary hypertension (PH), including the need for developing high quality patient registries of children with diverse forms of PH to enhance care and research.ObjectiveTo characterise the distribution and clinical features of diseases associated with pediatric PH, including natural history, evaluation, therapeutic interventions and outcomes, as defined by the WSPH Classification.Methods1475 patients were enrolled into a multisite registry across the Pediatric Pulmonary Hypertension Network (PPHNet), comprised of 8 interdisciplinary PH programs.ResultsWSPH Groups 1 (PAH) and 3 (lung disease) were the most common primary classifications (45% and 49% of subjects, respectively). The most common Group 3 conditions were BPD and CDH. Group 1 disease was predominantly associated with congenital heart disease (60%) and idiopathic (23% of Group 1 cases). In comparison with Group 1, Group 3 subjects had better disease resolution (HR=3.1, p<0.001), tended to be younger at diagnosis (0.3 (0.0,0.6) versus 1.6 (0.1,6.9) years (median (IQR); p<0.001), and were more often male (57% versus. 45%, p<0.001). Down syndrome (DS), the most common genetic syndrome in the registry, constituted 11% of the entire PH cohort.ConclusionsWe find a striking proportion of pediatric PH patients with Group 3 disorders, reflecting the growing recognition of PH in diverse developmental lung diseases. Greater precision of clinical phenotyping based on disease-specific characterization may further enhance care and research of pediatric PH.

Building a dedicated pediatric pulmonary hypertension program: A consensus statement from the pediatric pulmonary hypertension network

“…Pediatric PH programs now include care for a large number of children with PH associated with lung disease (WSPH Group 3), which represents nearly 50% of subjects enrolled in the PPHNet Registry 5 . This finding underscores the advances in neonatal care allowing survival of premature infants with bronchopulmonary dysplasia and congenital diaphragmatic hernia, as well as a growing awareness of rare developmental lung diseases.…”

“…This finding underscores the advances in neonatal care allowing survival of premature infants with bronchopulmonary dysplasia and congenital diaphragmatic hernia, as well as a growing awareness of rare developmental lung diseases. This also highlights the need for developing multidisciplinary teams, including cardiologists, neonatologists, pulmonologists, intensivists, and others, to optimize outcomes 2,3,5,9 . In addition, a team approach is necessary to enhance the continuity of inpatient and outpatient care with a seamless transition to chronic ambulatory care with pediatric subspecialty providers and then ultimately for transition on to adult PH providers 1,2,10 …”

“…Each member site is led by a primary investigator or site director to support the mission of the PPHNet in clinical care, education, training, advocacy, and high‐quality research to push the field of pediatric PH forward 2 . In this way, the PPHNet differs from the PHA in its focus on NIH research for pediatrics, including the development of the largest single registry of pediatric patients with PH 4–8 . Another focus includes collaborative authoring of practice guidelines, multicenter reviews, and consensus statements.…”

Genotypes and Phenotypes: A Review of Pulmonary Hypertension in Genetic Syndromes

“…11 The largest pediatric registry study to date is from the North American Pediatric PH Network (PPHNet) Registry, which found that 17% of the 1475 patient cohort had a genetic syndrome. 12 These patients' pulmonary vascular disease was classified as World Symposium on Pulmonary Hypertension (WSPH) group 1 (PAH), group 3 (associated with lung disease), or group 5 (multifactorial PH), which likely reflects the high prevalence of both CHD and/or lung disease within these diverse genetic syndromes. 12 While the field is rapidly gaining more understanding of the clinical features of PH-associated genetic variants, there is a paucity of data about the impact of the other genetic syndromes on pulmonary vascular disease phenotype and response to therapies.…”

“…12 These patients' pulmonary vascular disease was classified as World Symposium on Pulmonary Hypertension (WSPH) group 1 (PAH), group 3 (associated with lung disease), or group 5 (multifactorial PH), which likely reflects the high prevalence of both CHD and/or lung disease within these diverse genetic syndromes. 12 While the field is rapidly gaining more understanding of the clinical features of PH-associated genetic variants, there is a paucity of data about the impact of the other genetic syndromes on pulmonary vascular disease phenotype and response to therapies. This review aims to present the available data about PH associated with multisystem genetic syndromes, with focus on chromosomal abnormalities, single-gene-related syndromes, and heterogeneous disease.…”