Long-term outcome of children with newly diagnosed pulmonary arterial hypertension: results from the global TOPP registry

Abstract

Background and Aims The Tracking Outcomes and Practice in Pediatric Pulmonary Hypertension (TOPP) registry is a global network established to gain insights into the disease course and long-term outcomes of pediatric pulmonary arterial hypertension (PAH). Previously published cohorts in pediatric PAH are obscured by survival bias due to the inclusion of both prevalent (previously diagnosed) and incident (newly diagnosed) patients. The current study aims to describe long-term outcome and its predictors in pediatric PAH, exclusively of newly diagnosed patients. Methods and Results 531 children with confirmed pulmonary hypertension, aged ≥3 months and <18 years were enrolled in the real-world TOPP registry at 33 centers in 20 countries, from 2008 to 2015. Of these, 242 children with newly diagnosed PAH with at least one follow-up visit were included in the current outcome analyses. During long-term follow-up, 42 (17.4%) children died, 9 (3.7%) underwent lung transplantation, 3 (1.2%) atrial septostomy and 9 (3.7%) Potts shunt palliation (event rates: 6.2, 1.3, 0.4, and 1.4 events per 100 person-years, respectively). One, 3-, and 5-year survival free from adverse outcome was 83.9%, 75.2% and 71.8%, respectively. Overall, children with open (unrepaired or residual) cardiac shunts had the best survival rates. Younger age, worse World Health Organization functional class and higher pulmonary vascular resistance index were identified as independent predictors of long-term adverse outcome. Younger age, higher mean right atrial pressure and lower systemic venous oxygen saturation were specifically identified as independent predictors of early adverse outcome (within 12 months after enrolment). Conclusions This comprehensive analysis of survival from time of diagnosis in a large exclusive cohort of children newly diagnosed with PAH describes current era outcome and its predictors.

Younger age at initiation of subcutaneous treprostinil is associated with better response in pediatric Group 1 pulmonary arterial hypertension

“…Predicting which patients will respond to TRE, and to what degree, remains challenging, and there are few studies to guide risk stratification. Age is not a well‐defined prognostic factor in this patient population, as both younger and older age have been shown to be associated with worse outcomes 11,12 . A limited number of studies have demonstrated that early hemodynamic improvement after starting prostacyclin therapy is associated with long‐term freedom from adverse events (AE), and others have shown that a higher indexed pulmonary vascular resistance (PVRi) at the time of starting therapy to be a risk‐factor for death 11,13–16 …”

Application of a modified clinical classification for pulmonary arterial hypertension associated with congenital heart disease in children: emphasis on atrial septal defects and transposition of the great arteries. An analysis from the TOPP registry

“…Whereas differences in disease severity and survival between PAH-CHD groups defined as per the Nice CHD classification have been demonstrated in adults (13), the prognostic value of this classification in children remains to be proven. A recent analysis from the Tracking Outcomes and Practice in Pediatric Pulmonary Hypertension (TOPP) registry showed that patients with an open shunt (whether unrepaired or residual) had a better survival than all the other categories of PAH (14). However, no analysis of the different PAH-CHD subgroups was performed.…”