Fig. 3: Proteomic alterations associated with NYHA class in IE.

A Heatmap showing the association between NYHA class and 13 adverse events. B Scatter plot showing the correlation between proteins and NYHA class (colored by significance). C Venn diagram illustrating 21 proteins correlated with NYHA class (R < − 0.2, p < 0.05) and belonging to the pathways enriched in MEturquoise. D, E Heatmap and bar chart showing the 21 protein expression profiles and their histologic origin enrichment results. F Boxplots delineating the distribution of 6 CBMs. The central line represents the median, the box indicates the interquartile range (IQR), and whiskers extend to 1.5 × IQR, with outliers as individual points. G Scatter plot depicting the correlation between NYHA class and age. The error band represents the 95% CI of the regression line. H–K Volcano and bar plots showing the DEPs and dysregulated pathways enriched by these DEPs. L Heatmap showing the downregulated plasma and vegetation proteins in NYHA class IV. M Stacked bar plots showing the association between NYHA class and mitral and tricuspid valve surgeries. N, O Scatter plot showing the correlations of vegetation proteins with mitral valve surgery (N) and PTPRF (O). P Bubble chart showing significant pathways enriched by proteins correlated with PTPRF (R > 0.2, p < 0.05). Q Heatmap showing the complement, serine protease inhibitors, and HDL-related proteins in Cohort 2. Bar plot (left) showing the correlation between the proteins and NYHA class. R Scatter plot showing the correlation between NYHA class and ALB, AST, and DBIL levels in Cohort 2. S Schematic diagram summarizing the potential mechanisms by which liver dysfunction affects IE deterioration. Pearson’s two-sided χ² test was used for figures (A and M); two-sided Pearson’s correlation (WGCNA-derived) for (B and C); and two-sided Spearman’s correlation for (G, N–R), with p-values adjusted for FDR (*p < 0.05, **p < 0.01, ***p < 0.001). For (F, H, and J), unpaired two-sided Wilcoxon tests were used to compare NYHA class IV (n = 60) with NYHA class II and III (n = 134). Source data are provided as Source Data files.