Associations Between Right Ventricular Remodeling, Exercise and Circulating Metabolites in Volume and Pressure...

Ventricular pressure and volume overload may induce alterations in myocardial function, exercise capacity, and tissue metabolic pathways.

The authors investigated and compared these changes in pulmonary arterial hypertension (PAH) vs repaired tetralogy of Fallot (rTOF) with residual pulmonary regurgitation, which exemplify pressure- and volume-overloaded states, respectively.

A total of 227 subjects (103 healthy control subjects, 67 rTOF, 57 PAH) identified from an ongoing prospective cohort study all underwent cardiac magnetic resonance (CMR), cardiopulmonary exercise tests (CPET), and serum assays for metabolomic profiling. Measurements included left ventricular end-diastolic volume (LVEDV), right ventricular (RV) end-diastolic volume (RVEDV), right ventricular ejection fraction (RVEF), feature-tracked tricuspid annular plane systolic excursion (TAPSE), and right ventricular global longitudinal strain (RVGLS) on CMR, and peak oxygen uptake (PVo₂) on CPET.

rTOF had significantly higher RV mass index, RVEDV index, RVEDV/LVEDV, and RV/LV mass ratios vs PAH and control subjects. Compared with control subjects, RV functional parameters (RVEF, TAPSE, and RVGLS) were impaired in both rTOF and PAH. Significant decrements in PVo₂ were observed from control subjects to rTOF to PAH. Valine, leucine, and isoleucine levels were elevated in rTOF (but not in PAH), which associated negatively with TAPSE and RVGLS. Choline levels and PVo₂ were associated negatively and positively in rTOF and control subjects, respectively. In PAH, dimethylglycine-which was elevated vs rTOF and control subjects-was associated positively with RVEDV/LVEDV and RV/LV mass, and negatively with RVEF, TAPSE, and RVGLS.

PAH and rTOF exhibited distinct RV remodeling, and PAH, worse exercise tolerance. Differences in circulating branched chain amino acids and one-carbon metabolites were observed among rTOF, PAH, and control subjects.