Specific metabolite profiles may reveal right ventricular (RV) functional measurements of people with pulmonary arterial hypertension (PAH) as accurately as invasive pressure-volume loop analysis, as well as predict RV response to exercise, according to an article published in the American Journal of Physiology-Lung Cellular and Molecular Physiology.

For this study, the researchers recruited 23 patients with PAH from a tertiary care center and performed rest and exercise right heart catheterization with multibeat pressure-volume loop analysis. Pulmonary arterial blood samples were taken both at rest and during exercise.

The study authors then performed mass spectrometry-based targeted metabolomics and used sparse partial least squares regression to identify metabolic associations with hemodynamics as well as the general measures of RV function. The profiles of metabolites obtained were compared with pro-B-type natriuretic peptide (BNP) measurements to ensure the correct modeling of ventriculoatrial parameters. 

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According to the results, the concentration of 13 metabolites changed with increased physical exercise. These were the metabolites reflecting an increase in arginine bioavailability, precursors of catecholamine and nucleotide synthesis, and branched-chain amino acids.

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Increased arginine bioavailability at rest was found to predict better hemodynamics and pressure-flow relationships during periods of physical activity. People with severe PAH had a greater increase in arginine bioavailability during exercise in comparison with those with a less serious form of the disease.

Moreover, there was an association between kynurenine pathway metabolism and compromised ventriculoatrial coupling, worse RV diastolic function, decreased RV contractility, diminished RV contractility with exercise, and RV dilation with exercise.

“In addition to offering pathobiological insights, our findings underscore the potential for select metabolites to function as disease‐specific biomarkers. Metabolite combinations outperformed NT‐proBNP, the current clinical gold standard marker, for predicting most hemodynamic and RV functional variables,” Simpson and colleagues emphasized.

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“Improvements in model accuracy were most robust for prediction of variables associated with intrinsic RV function, such as relaxation and contractility, and RV exercise performance,” they said.

The functional state of the right heart ventricle is the main indicator of survival in PAH patients. Reliable indicators of its function could predict disease outcomes and help with choosing the best treatment option.  


Simpson CE, Coursen J, Hsu S, et al. Metabolic profiling of in vivo right ventricular function and exercise performance in pulmonary arterial hypertension. Am J Physiol Lung Cell Mol Physiol. Published online April 18, 2023. doi:10.1152/ajplung.00003.2023