Physical Activity Measured by Hip-Anchored Accelerometry in Pediatric Pulmonary Hypertension: Association with Disease Severity & Estimation of Minimal Important Differences.

Background: Pediatric pulmonary hypertension (PH) is a severe incurable disease with poor prognosis. In pediatric PH, trial design is hampered by the absence of age-appropriate trial endpoints. This study evaluated physical activity (PA) measured by hip-anchored accelerometry as a potential trial endpoint in pediatric PH.

Research questions: Is PA-accelerometry associated with disease severity, and based on this association, what minimal important differences (MIDs) correspond to meaningful changes in disease severity in pediatric PH?

Study design and methods: Accelerometer outputs from 54 children with hemodynamically confirmed PH were analyzed. Univariable linear regression and mixed effect models were respectively used for cross sectional and longitudinal analyses 1) to evaluate the association between Z-scores of PA-accelerometry counts per minute (CPM-Z) and of % of time spent in moderate or vigorous physical activity (%MVPA-Z) and disease severity indices 6-minute walk-distance Z-scores (6MWD-Z), World Health Organization functional class (WHO-FC), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and tricuspid annular plane systolic excursion Z-scores (TAPSE-Z) and 2) to perform anchor-based MID estimations for CPM-Z and %MVPA-Z, using defined clinical functional impairment levels (6MWD-Z and WHO-FC) as reference anchors.

Results: When assessing the association between disease severity and PA-accelerometry cross-sectionally, we found significant associations between CPM-Z and WHO-FC, 6MWD-Z and NT-proBNP. %MVPA-Z was significantly associated with WHO-FC and 6MWD-Z. In longitudinal analysis, these associations were confirmed throughout the disease course. MID estimations, expressed in Z-score units, resulted in mean MIDs of 0.3-0.4 CPM-Z when anchored to 6MWD-Z, 0.7 CPM-Z when anchored to WHO-FC, 0.4-0.5 %MVPA-Z when anchored to 6MWD-Z and 0.5-0.6 %MVPA-Z when anchored to WHO-FC.

Interpretation: This study underscores the robust relationship between PA-accelerometry and disease severity in children with PH and fills a critical gap in pediatric PH trial design and evaluation of treatment efficacy by providing anchor-based MID-estimates for hip-anchored PA-accelerometry.