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

Figures

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  Figure 1. Boxplot Comparisons of Metabolites Among Control, rTOF, and PAH Groups Individual metabolites were compared among 3 groups (control [Ctrl], repaired tetralogy of Fallot [rTOF] and pulmonary arterial hypertension [PAH]) in terms of acylcarnitine (top, A and B), branched-chain amino acid (BCAA) metabolites (middle, C to E); and one-carbon metabolites (bottom, F to N). P values are from the pairwise companion from full model, adjusted for age, sex, body surface area, systolic and diastolic blood pressure, heart rate, diabetes, hyperlipidemia, hypertension, and current smoker.

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  Figure 2. Correlation Coefficients Between CMR, Exercise, and Metabolites rTOF and PAH The relationship between CMR parameter, PVo2, and metabolic parameters in rTOF and PAH, respectively. CMR = cardiac magnetic resonance; LVEDV = left ventricular end-diastolic volume; PVo2 = peak oxygen uptake; RV = right ventricle; RVEDV = right ventricular end-diastolic volume; RVEF = right ventricular ejection fraction; RVESV = right ventricular end-systolic volume; RVGLS = right ventricular global longitudinal strain; TAPSE = tricuspid annular plane systolic excursion; other abbreviations as in Figure 1.

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  Figure 3. Utility of Metabolites in Detecting Abnormal Exercise Capacity Receiver-operating characteristic analysis was used to study the discrimination utility of individual metabolites for detecting abnormal exercise capacity using different criteria in rTOF and PAH. (A) % predicted PVo2 ≤65% in rTOF; (B) PVo2 ≤15 mL/kg/min in rTOF; (C) % predicted PVo2 ≤65% in PAH; (D) PVo2 ≤15 mL/kg/min in PAH; (E) VE/VCo2 slope ≥36 in PAH. VE = minute ventilation; VCo2 = carbon dioxide production; other abbreviations as in Figures 1 and 2.

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  Central Illustration. Remodeling, Exercise, and Metabolites in Right Ventricular Pressure and Volume Overload (A) Pulmonary arterial hypertension (PAH) patients with right ventricular (RV) pressure overload have worse exercise capacity in terms of peak oxygen uptake (PVo2), metabolic equivalent, and % predicted PVo2; repaired tetralogy of Fallot (rTOF) patients with RV volume overload have more adverse RV remodeling in terms of increased right ventricular end-diastolic volume (RVEDV) index, RV end-systolic volume index, RVEDV/left ventricular (LV) end-diastolic volume (LVEDV) ratio, and RV/LV mass. (B) rTOF has significantly elevated levels of branched-chain amino acids (BCAAs) (valine, isoleucine, leucine) than PAH. (C) PAH had significantly higher levels of one-carbon metabolites (dimethylglycine, choline and alanine) than rTOF and healthy control subjects. (D) Receiver-operating characteristic (ROC) analysis demonstrated the better discriminative capacity of individual metabolites than right ventricular ejection fraction (RVEF) in predicting abnormal exercise capacity in terms of PVo2.