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

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

Research question: Is PA accelerometry associated with disease severity, and based on this association, what minimally 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 used for cross-sectional and longitudinal analyses, respectively, (1) to evaluate the association between z scores of PA accelerometry counts per minute (CPMs) and of percentage of time spent in moderate to vigorous PA and disease severity indices 6-minute walk distance (6MWD) z scores, World Health Organization functional class (WHO-FC), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and tricuspid annular plane systolic excursion z scores; and (2) to perform anchor-based MID estimations for CPMs and percentage of time spent in moderate to vigorous PA accelerometry intensity level (%MVPA) z scores, using defined clinical functional impairment levels (6MWD z scores 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 scores and WHO-FC, 6MWD z scores, and NT-proBNP levels. %MVPA z score was associated significantly with WHO-FC and 6MWD z score. 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 to 0.4 CPM z score when anchored to 6MWD z scores, 0.7 CPM z score when anchored to WHO-FC, 0.4 to 0.5 %MVPA z score when anchored to 6MWD z scores, and 0.5 to 0.6 %MVPA z scores when anchored to WHO-FC.

Interpretation: This study underscored 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.