Cell-free mitochondrial DNA may predict the risk of post-operative complications and outcomes in surgical aortic valve replacement patients

Figures

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  Fig. 1. Cf-mtDNA levels intra- and post-operatively in AVR patients. A representative TapeStation profile of total cfDNA from a single patient across the observation period (baseline to 18 h post-surgery) presented in fluorescence intensity (on the Y axis). Each line represents the relative size and abundance of cfDNA fragments throughout the sampling period. The widest variance and peak average size of cfDNA fragments (red) is observed following cardioplegia delivery (a). Plasma levels were significantly increased from the time of cardioplegia delivery until 18 hours’ post-surgery, peaking at the end of cardiopulmonary bypass (b). Data are expressed as mean number of copies ± SD over time. Significance was assessed across all time intervals using ANOVA. Binary comparisons from baseline were calculated using the Wilcoxon U-test. ***p < 0.001 compared to baseline. B, baseline (dark blue); ST, sternotomy (orange); C, cardioplegia delivery (dark green); End, end of cardiopulmonary bypass (red); 6 h (light blue), 12 h (light green), 18 h (purple) post ICU admission.

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  Fig. 2. Normalized gene counts for TNFα, IL1β, IL8, IL10, IL18, CCL5/RANTES, CD40L, NFκB, TLR9, PF4 and NLRP3 in leukocytes of AVR patients. Levels of IL10, IL1β, NFκB and NLRP3 rise post-surgery and are significantly increased over time, from baseline to 18 h post ICU admission. In contrast levels of TNFα, IL8, IL18, CCL5/RANTES, CD40L, PF4 and TLR9 are reduced following surgery, with an overall significant decrease from baseline to 18 h post ICU admission. Data are presented as mean ± SD over time. Significance was assessed across all time intervals using ANOVA. Binary comparisons from baseline were calculated using the Wilcoxon U-test. *p < 0.05, **p < 0.01, ***p < 0.001 compared to baseline. B, baseline; ST, sternotomy; C, cardioplegia delivery; End, end of cardiopulmonary bypass.

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  Fig. 3. Levels of inflammatory markers in plasma of AVR patients adjusted for haematocrit. Cytokines TNFα, IL6, IL1β, CD40L, IL18, chemokine (IL8) and platelet activation marker P-Selectin were increased post-surgery whereas IL10 levels start to increase during the procedure. All were found to be significantly increased over time from baseline to 18 h post ICU admission. A decrease in inflammatory markers, consistent with attenuation of inflammation in response to procedural characteristics is visible following cardioplegia delivery (C). Data are presented as mean ± SD over time. Significance was assessed across all time intervals using ANOVA. Binary comparisons from baseline were calculated using the Wilcoxon U-test. ***p < 0.001 compared to baseline. B, baseline; ST, sternotomy; C, cardioplegia delivery; End, end of cardiopulmonary bypass.

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  Fig. 4. Relative gene expression data and levels of neutrophil activation markers in plasma of AVR patients. a, Normalized expression of the neutrophil activation markers NE, MPO and MMP8 is increased following CPB initiation, with peak levels occurring at the end of cardiopulmonary bypass. b, A corresponding peak in secreted levels of NE and MPO which are major regulators of the inflammatory response to CPB and indicators of neutrophil activation, is apparent at the end of cardiopulmonary bypass. Data are presented as mean ± SD over time. Significance was assessed across all time intervals using ANOVA. Binary comparisons from baseline were calculated using the Wilcoxon U-test. ***p < 0.001 compared to baseline. B, baseline; ST, sternotomy; C, cardioplegia delivery; End, end of cardiopulmonary bypass.