Association of Fontan Pathophysiology With Plasma Bile Acids

Figures

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  Central Illustration. Association of Fontan Pathophysiology With Plasma Bile Acids Assessment of Fontan patients and healthy controls from time of recruitment. This included body composition and frailty assessment, cardiopulmonary exercise testing, noninvasive hemodynamic assessment (pre- and post-exercise), nontargeted metabolomics, plasma bile acid measurement and correlation of total and individual bile acid components with other parameters.

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  Figure 1. Metabolomics of Fontan Patients and Healthy Controls Principal component analysis scores plot (A), and partial least square-discriminant analysis scores plot (B) of fontan patients compared to healthy controls (B). (C) Volcano plot of metabolomics data. X- and Y-axis present the log 2 (ratio) and −log10 (corrected P value), respectively. Red color denotes the metabolites with significant difference (P < 0.05 and a fold change >4). (D) Clustered Heatmap depicting differential abundance of metabolites between Fontan patients and healthy controls. each column represents a sample and each row represents a metabolite. The red and blue colors correspond to high or low metabolite levels, respectively. (E) Correlation Heatmap depicting metabolite-metabolite correlations (Pearson correlation) of 58 metabolites that were significantly different between Fontan patients and healthy controls.

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  Figure 2. Bile Acids Analysis, Their Distribution on the Spectrum of Hydrophobicity–Hydrophilicity and Individual Elevated BA in Fontan Patients and Healthy Controls (A) Seventy-five bile acids measured in each Fontan patient and healthy control (red–healthy subject; green–Fontan patient). (B) Bile acid concentration differences between Fontan patients and healthy subjects; bile acids are described by their spectrum of Hydrophobicity–Hydrophilicity. Significantly elevated bile acids in Fontan patients are described in green color. (C) Total (75) and the 17 significantly elevated bile acids in fontan patients.

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  Figure 3. Bile Acids and Their Correlation With Demographics, Frailty, Exercise Capacity, and Hemodynamic Parameters The relationship between demographic, frailty, exercise capacity, hemodynamic parameters, and the total as well as individual 75 bile acids. Presence of dot signifies a significant correlation. purple color describes a positive relationship, whereas orange color describes a negative association.

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  Figure 4. DehydroLithocholic Acid Level and Its Correlation With Age, Body Composition, Exercise Capacity, and Hemodynamic Parameters The relationship between dehydro lithocholic acid concentration with (A) age, (B) skeletal muscle mass, (C) VO2max (%), (D) SI (at rest), (E) CI (at rest), and (F) CPI (at rest). Blue color represent Fontan patient, and red color represent heathy subject. CI = cardiac index; CPI = cardiac power index; SI = stroke index; VO2max = maximal oxygen consumption.