Long-Chain Acylcarnitines and Monounsaturated Fatty Acids Discriminate Heart Failure Patients According to Pulmonary Hypertension Status

Figures

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  Figure 1. Principal component analysis identified distinct metabolic patterns in PH-HF (n = 33) and noPH-HF (n = 27) and segregated HF patients from healthy subjects (n = 72). A total of 55 variables were included in the analysis and comprised usual biochemical parameters as well as various metabolites measured by a combination of MS-based metabolomics approach targeting fatty acids, acylcarnitines, organic acids and amino acids. For the segregation between healthy subjects (controls) and HF patients, principal component 1 (PC1) and principal component 2 (PC2) accounted for 15.7% and 10.1% of the total variation, respectively. Controls are identified in red, noPH-HF in green and PH-HF in blue. Biplot analysis merging PCA plot and loadings plot identified the most potent metabolites in segregating controls (red) and noPH-HF (green) with PC1 and PC2 accounting for 11.9% and 9.3% respectively, and controls (red) and PH-HF (blue) with PC1 and PC2 accounting for 16.8% and 11.9% respectively. The corresponding loading scores in PC1 and PC2 for both analyses are reported in Table S1.

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  Figure 2. Acylcarnitines and fatty acids circulating levels are differentially affected in PH-HF (n = 33) and noPH-HF (N = 27) compared to controls (N = 72). Box plots represent top discriminant FA-related metabolites identified using the PCA analysis in the comparison noPH-HF (green) vs. controls (red) and PH-HF (blue) vs. controls. Shown are semi-quantitative analyses of (A) acylcarnitines reported as MS signal ratio normalized to standard, and the quantitative analysis of (B) saturated FA, (C) MUFA, and (D) PUFA. In the boxplots, rectangles represent the SD, the segment inside the rectangle the median and the whiskers above and below the maximum and minimum. * p < 0.05, ** p < 0.01, *** p < 0.001 compared to controls; $ p < 0.05, $$ p < 0.01 PH-HF vs. noPH-HF. Other more commonly measured metabolites are shown in Figure S1.

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  Figure 3. Acylcarnitines and fatty acids significantly correlate with NT-proBNP in PH-HF but not in noPH-HF patients. Pearson correlation analysis between NT-proBNP and (A) acylcarnitines, (B) FA (MUFA and PUFA) in noPH-HF (black) or PH-HF (blue) patients. The dotted lines indicate the 95% confidence intervals.