Metabolic profiling of in vivo right ventricular function and exercise performance in pulmonary arterial hypertension
Catherine E. Simpson, Julie Coursen, Steven Hsu, Ethan Gough, Robert Harlan, Aurelie Roux, Susan Aja, David R. Graham, Matthew J. Kauffman, Karthik Suresh, Ryan J. Tedford, Todd M. Kolb, Stephen C. Mathai, Paul M. Hassoun, Rachel L. Damico
Abstract
In this cohort of patients with pulmonary arterial hypertension (PAH), we investigate metabolomic associations with comprehensive right ventricular (RV) functional measurements derived from multibeat RV pressure-volume loop analysis. Our results show that tryptophan metabolism, particularly the kynurenine pathway, is linked to intrinsic RV function and PAH pathobiology. Findings also highlight the importance of arginine bioavailability in the cardiopulmonary system's response to exercise stress. Metabolite profiles selected via unbiased analysis outperformed N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) in predicting load-independent measures of RV function at rest and cardiopulmonary system performance under stress. Overall, this work suggests the potential for select metabolites to function as disease-specific biomarkers, offers insights into PAH pathobiology, and informs discovery of potentially targetable RV-centric pathways.