Association between preoperative peripheral blood mononuclear cell gene expression profiles, early postoperative organ function recovery potential and long-term survival in advanced heart failure patients undergoing mechanical circulatory support

Figures

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  Fig 1. Organ function and outcomes. (A) Organ function and outcomes of 29 patients across five time points. Out of 29 AdHF-patients undergoing MCS-surgery, 17 patients had organ function improvement from preoperative day -1 (TP1) to day 8 (TP5) (Group I) and 12 patients had no organ function improvement (Group II). Each black line represents one 1-year survivor while each red line represents one 1-year non-survivor. In each group, non-survivors are shown in red. (B) Out of 29 AdHF-patients undergoing MCS-surgery, 17 patients improved (Group I, upper right quadrant) and 12 patients did not improve (Group II, remaining 3 quadrants) from day -1 (TP1) to day 8 (TP5). Each large dark bullet represents one patient who died within one year. Absence of improvement of either score was associated with reduced 1-year survival.

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  Fig 2. Kaplan-Meier 1-year survival in Group I vs. Group II. In the 17 patients who improved (Group I = Functional recovery = Organ function improving = Low Risk) vs. the 11 patients who did not improve (Group II = No functional recovery = Organ function not improving = High Risk), the time-to-event Kaplan-Meier survival analysis suggested that the significantly elevated risk (log rank test p = 0.00182) of death in Group II continued over the 1-year period following MCS-surgery.

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  Fig 3. Overlap of significant genes associated with organ function improvement and survival benefit. (A) Hierarchical clustering of significant genes day -1 (TP1). Left: The Volcano plot of 28 genes, which are differentially expressed between Group I and Group II. Right: Hierarchical clustering of the 28 candidate genes for the prediction test demonstrates the differential gene expression between Group I and Group II. (B) Hierarchical clustering of genes associated with survival benefit. Left: The Volcano plot of 105 genes, which are differentially expressed between Group I and Group II. Right: Hierarchical clustering of the 105 candidate genes for the prediction test demonstrates the differential gene expression between Group I = Survival, Group II = Non-survival. (C) Overlap genes from both improvement group and 1-year survival outcome. Left: Venn-Diagram shows the 28 DEGs identified in the comparison by improvement score (red) and the Right shows the 105 DEGs identified by comparing 1-Year Survival (blue). Twelve DEGs were shared across the two comparisons. Right: The 12 overlap genes (see text for details).

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  Fig 4. Prediction biomarker development rationale. Preoperative clinical heart failure/organ function severity scores (INTERMACS class, SOFA median score, MELD-XI median score) and demographics (age, gender) did not reliably discriminate postoperative organ function improvement (ROC, 95% confidence interval) and long term survival (Cox Proportional Hazard Model, 95% confidence interval). In contrast, the PBMC-GEP correlates well with postoperative organ function improvement and long term survival.