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

Abstract

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. 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? 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. 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. 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.