Unraveling the systemic manifestations of pulmonary arterial hypertension on lean muscle mass

Project Summary While pulmonary arterial hypertension (PAH) is a progressive disease of the pulmonary vasculature associated with high morbidity and mortality, it also has multiple systemic manifestations affecting many organs. There is a growing body of evidence suggesting respiratory and skeletal muscle dysfunction in patients

with PAH; however, loss of muscle mass has not been adequately studied in PAH. Loss of lean mass is increasingly recognized in individuals with chronic conditions and when present, is associated with decreased physical activity and worse outcomes. Our preliminary data shows that almost 42% of patients with PAH

enrolled in a prospective observational cohort had low lean mass and obese individuals had a higher prevalence of low lean mass as compared to individuals with normal weight. Fat depots are metabolically active and produce an array of inflammatory cytokines and adipokines that likely contribute to the muscle loss.

We are proposing a comprehensive evaluation of lean mass in patients with PAH. First, in a prospective cohort of patients with PAH, we will characterize the endophenotype of PAH patients with low lean mass and identify the metabolomic signature of low lean mass which will provide us with insight into novel putative

pathways. We also aim to understand the role of epicardial adipose tissue in the pathogenesis of low lean mass. We will assess the impact of low lean mass on patient-centered outcomes including quality of life, physical activity, and hospitalizations. Second, we will identify radiographic features of muscles on thoracic

non-contrast chest CTs to allow for earlier and easier screening for low lean mass in patients with PAH. Finally, we will conduct a small pilot study to explore the response of adiponectin and muscle oxygenation to a low- resistance exercise intervention in patients with PAH. The results of this study will lay the foundation for

“personalized” interventions trial targeting low lean mass in PAH.