Predictive Role of Metabolic Profiling in Rivaroxaban Efficacy for Thrombus Lysis in Atrial Fibrillation

Figures

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  Figure A1. The area under receiver operating characteristic (ROC) curve for two variables selected based on PLS-DA algorithm was 0.90, with a specificity of 75% and a sensitivity of 86% for the prediction of thrombus resolution. The most frequently selected variables for the model were C6-DC (100%), iC5-OH (50%), and lysine (50%).

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  Figure 1. Concentration of rivaroxaban in plasma of patients (n = 15) treated with standard (1 × 20 mg) and modified dose (2 × 15 mg). * p = 0.0468, ** p = 0.0090 (Wilcoxon matched-pairs test).

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  Figure 2. Concentration of rivaroxaban in the plasma of patients effectively (n = 7) and non-effectively (n = 8) treated with a modified dose (2 × 15 mg). No statistically significant differences were observed between the two groups (3 h: Mann–Whitney U test; 12 h, 24 h: Student’s t-test). The concentrations tended to be higher in responders compared to non-responders, especially at 12 h and 24 h post-administration. However, it is important to emphasize that all concentrations were within the recommended concentration ranges set by the International Council for Standardization in Hematology [13] and the European Heart Rhythm Association [14].

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  Figure 3. Heatmap of 24 compounds that differed significantly between patients effectively (n = 7) (green) and non-effectively (n = 8) (red) treated with a modified dose of rivaroxaban. The deeper the blue color, the lower the level of the metabolite. The deeper the red color, the higher the level. The metabolites with similar abundance patterns across the samples were clustered together, and patients with similar metabolic fingerprints were also grouped into clusters. DG: diglyceride; C5-DC: glutarylcarnitine; FA: fatty acid; PE: phosphatidylethanolamine; 3Hyp: 3-hydroxyproline; 4Hyp: 4hydroxyproline.

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  Figure 4. (a) Partial least squares-discriminant analysis (PLS-DA) and (b) VIP scores. Cross-validated PLS-DA score plot comparing metabolite profiles of 7 patients with effective treatment (group “resolution”) and 8 patients with ineffective treatment (group “persistent”), both receiving a modified rivaroxaban dose, shows the separation based on treatment results. The p-value based on permutation testing is 0.04. Light red and green ellipses represent 95% confidence intervals. Colored dots represent individual samples. The percentages given along the x and y axes are the scores of components 1 and 2, respectively.