Center for Congenital Heart Diseases, Beatrix Children's Hospital
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Physical Activity in Pediatric Pulmonary Arterial Hypertension Measured by Accelerometry: A Candidate Clinical Endpoint
- Published on July 15, 2017
Background Although the six-minute walk distance is well established as a clinically relevant endpoint for adults with pulmonary arterial hypertension (PAH), this endpoint is less applicable to infants and children who may be unable to participate in such testing. Thus, there is a critical need to develop and validate means of assessing activity levels in younger populations that can be applied to clinical trial design. Accelerometry has previously been used in adults and children to measure physical activity, but whether accelerometry correlates with disease severity and outcomes in pediatric PAH remains unknown.
Methods and Results Children with PAH were recruited from the Dutch National Network for Pediatric Pulmonary Hypertension. These subjects were age- and sex-matched to controls without hemodynamically relevant cardiac disease recruited from the Beatrix Children’s Hospital outpatient Cardiology Clinic, with 2 controls to every 1 pulmonary hypertension patient. Children were asked to wear the ActiGraph wGT3X accelerometer for 7 days on the right hip during all awake time. Vector magnitude counts per minute were defined as the primary accelerometer outcome, and physical activity intensity was defined as the secondary accelerometer outcome. Physical activity measures were then correlated with patient characteristics, WHO functional class, six minute walk distance (for children aged 7 years or older), serum NT-pro BNP levels, and pulmonary hypertension medication use.
Twenty-nine children with PAH and 60 age- and sex-matched control children completed the accelerometry study. PAH subjects included 4 children (14%) under 5 years of age, and 3 children (10%) with Down syndrome; most children were WHO functional class II or III. Six minute walk distance was unavailable in 9 PAH children (31%) due to young age or developmental disorder. Average wear time per day was similar between PAH and control children, and there was no significant day-to-day variance in vector magnitude counts.
Average vector magnitude counts per minute were significantly lower in children with PAH compared to controls. Additionally, children with PAH were significantly less likely to engage in moderate or vigorous physical activity. Time spent in moderate or vigorous physical activity inversely correlated with WHO functional class in all children. Vector magnitude counts also correlated inversely with WHO functional class in univariate analysis, but lost significance when corrected for age and diagnosis. In a post hoc Cox regression analysis, lower vector magnitude counts were associated with a shorter time to PAH-related hospitalization, and less time spent in higher activity levels was associated with worse outcome.
Conclusions Accelerometry is a feasible measure of physical activity, even in young children with PAH who would otherwise be incapable of completing classic measures such as six-minute walk distance. Physical activity levels measured by accelerometry are significantly decreased among children with PAH. Activity correlated well with clinical disease severity markers, and may correlate with outcomes. Additional validation in larger studies may help to identify age-related normal values for activity. Finally, use of accelerometry for tracking individual activity levels in response to changes in therapy may be beneficial for assessing treatment effects. Accelerometry should be considered as a clinically meaningful endpoint in pediatric PAH, and may be useful to implement in future trial design as an adjunct to six-minute walk testing, particularly for younger children or those with developmental disabilities.
- Zijlstra WMH 1
- Ploegstra MJ 1
- Vissia-Kazemier T 1
- Roofthooft MTR 1
- Sarvaas GDM 1
- Bartelds B 1
- Rackowitz A 1
- van den Heuvel F 1
- Hillege HL 2
- Plasqui G 3
- Berger RMF 1
Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
Maastricht University Medical Center, University of Maastricht, Maastricht, the Netherlands
American Journal of Respiratory and Critical Care Medicine