Incidence and Outcomes of Children with Idiopathic Pulmonary Arterial Hypertension - Results from a Bi-National Population Based Study

Childhood idiopathic pulmonary arterial hypertension (IPAH) is a rare disease. Population-based incidence and long-term outcomes are not well described. We describe the incidence and outcomes of this population using a bi-national multicenter registry. The Pediatric Pulmonary Hypertension Registry (PPHR) is a collaboration between 9 Australian and New Zealand centers from 1/1/2002 to 12/31/2013. Children 3 months to 18 years at diagnosis of IPAH were included with retro- and prospective data entry. Participating center institutional review boards approval and informed consent were obtained. Population-based incidence was calculated. Primary study end-points were death or lung transplantation, with secondary end-point of parenteral prostanoid-free survival. Forty-three patients, 12 with family history of IPAH, satisfied entry criteria for PPHR; median [IQR] age at diagnosis 8.7 years [4.8, 14] and 51% were female. Overall bi-national childhood IPAH incidence was 6.4 per 10 million person-years, with a peak incidence in the 10-14yo age group (8.7 per 10 million person-years). Almost all patients were symptomatic at diagnosis, with 31/42 (74%) WHO class II or III, and 8/42 (19%) WHO class IV. Targeted pulmonary vasodilator therapy was commenced in all but 4/43 (9%) patients in the cohort, and parenteral prostenoid used in 15/43 (35%) patients. Of 43 PPHR patients, 17 (40%) achieved the combined end-point of death/transplantation, with median [IQR] follow-up 3.3 years [0.44, 5.9]. Transplantation-free survival was 83% (95%CI 68-92%) 1 year after diagnosis and 56% (37-70%) at 5 years. Freedom from parenteral prostanoid, death and transplantation was 68% (95%CI 43-84%) at 1 year, 44% (21-65%) at 2 years and 31% (12-53%) at 5 years in the eligible PPHR population. Demographic, symptomatology, echocardiographic and hemodynamic parameters were assessed for association with death/transplantation in univariable analysis. Of these, only female gender (p=0.039) and elevated mean RAP (p=0.041) demonstrated an association. Incidence of IPAH in childhood is 6.4 per 10 million patient-years. In the current era, death or transplantation rates remain high despite the use of targeted vasodilator therapy.