Abstract 18311: Metabolomic Signatures of Right Ventricular-Pulmonary Vascular Dysfunction
Impaired performance of the right ventricular-pulmonary vascular (RV-PV) unit is an important determinant of reduced exercise capacity, morbidity and mortality. We sought to determine comprehensive plasma metabolite signatures of RV-PV dysfunction.
Methods/Results: We studied subjects who underwent incremental cycle ergometry cardiopulmonary exercise testing with simultaneous hemodynamic monitoring to evaluate the etiology of dyspnea on exertion. In derivation and validation groups (n=71 and n=52, respectively) we performed multi-site blood sampling from the pulmonary and radial arteries to determine plasma concentrations of 130 metabolites using targeted liquid chromatography/mass spectrometry. Indicators of abnormal RV-PV function (i.e. elevated resting right atrial pressure, mean pulmonary arterial pressure [mPAP], pulmonary vascular resistance [PVR], as well as PVR and PAP-flow response [PQ] during exercise) were associated with levels of multiple groups of metabolites (Table), including arginine- nitric oxide (NO) pathway intermediates, indicators of oxidative stress, TCA cycle metabolites, and indoleamine 2,3-dioxygenase (IDO)-dependent tryptophan metabolites (TMs). Higher levels of IDO-TMs were the leading predictors of resting mPAP and PVR and exercise PVR and PQ. Transpulmonary release of IDO-TMs localized metabolic changes to the pulmonary circulation. Multivariate regression adjusting for age, gender, BMI, cystatin C, and NT-BNP did not attenuate the relationship between IDO-TMs and indices of RV-PV dysfunction.
Conclusion: Metabolic profiling identified signatures of RV-PV dysfunction. These signatures consisted of metabolites known to be associated with RV-PV dysfunction (i.e. NO pathway intermediates, indicators of oxidative stress) and metabolites not previously associated with RV-PV dysfunction (i.e. TCA cycle metabolites and IDO-TMs), which represent potential novel biomarkers of RV-PV dysfunction.
- © 2012 by American Heart Association, Inc.