Physical Activity and Its Association with Traditional Outcome Measures in Pulmonary Arterial Hypertension

Rationale Limitation of physical activity is a common presenting complaint for patients with pulmonary arterial hypertension (PAH). Physical activity is thought to be determined by cardiopulmonary function, yet there are limited data that investigate this relationship. Objective We aimed to study the relationship between right ventricular function and daily activity and its impact on health-related quality of life (HRQoL) in PAH. Methods Baseline data for 55 patients enrolled in PHANTOM, an ongoing multicenter randomized controlled trial of anastrozole in PAH were used. Post-menopausal women and men were eligible and underwent six-minute walk testing, echocardiography and completed HRQoL questionnaires. Each patient wore an accelerometer for 7-days. Multivariable linear regression models were used to study the association between tricuspid annular plane systolic excursion (TAPSE) and vector magnitude counts, and between daily activity and HRQoL. Principal component analysis and K-means clustering were used to identify activity-based phenotypes. K-nearest neighbors' classification was applied to an independent cross-sectional cohort from the University of Pennsylvania. Results The mean age of patients in PHANTOM was 61 years. 67% were women with idiopathic PAH as the most common etiology. A 0.4 cm increase in TAPSE was associated with an increase in daily vector magnitude counts (s:34000, 95%CI:900-67000, p=0.004) after adjustment for age, sex, body mass index, etiology of PAH and wear time. A 1-standard deviation increase in vector magnitude counts was associated with higher six-minute walk distance (s: 56.1 meters, 95%CI:28.6-83.7, p<0.001) and lower emPHasis-10 scores (s:-3.3, 95%CI:0.3-6.4, p=0.03). Three activity phenotypes, low, medium, and high, were identified. The most active phenotype had greater six-minute walk distances (p=0.001) and lower emPHasis-10 scores (p=0.009) after adjustment for age, sex, body mass index, WHO functional class and parenteral prostacyclin use. Phenotypes of physical activity were reproduced in the second cohort and were independently associated with six-minute walk distance. Conclusion Better right ventricular systolic function was associated with increased levels of activity in PAH. Increased daily activity was associated with greater six-minute walk distance and better HRQoL. Distinct activity-based phenotypes may be helpful in risk stratification of PAH patients or provide novel endpoints for clinical trials.