Measurements of cell-free DNA during- and post- cardiopulmonary bypass predict postoperative outcomes

Background: Cardiopulmonary bypass (CPB) induces a systemic inflammatory response, which correlates with poorer patient outcomes. The cellular dynamics of immune activation and end-organ injury have not been accurately described due to the lack of sufficient temporal and cellular resolution.

Methods: We recruited patients that undergo valve operations and controls in a single center. Cellular turnover and end-organ injury was evaluated by analyzing the epigenetic signature of plasma cell-free (cf) DNA, collected at multiple time points before, during, and after surgery.

Results: We recruited 14 patients. The mean age was 58.6 ±15.9. The median bypass time was 110 minutes (67-113), and the median cross clamp time was 77.5 minutes (42-96). We detected a significant increase in total cfDNA levels starting 10 minutes after initiation of bypass (log2(fold-change) = 6.1, p-value = 0), a 10-fold decline at POD1 (p=4x10-7), and a recurrent increase at POD3 (9.5x10-6). The levels of cardiomyocyte cfDNA increased as early as 10 minutes after initiation of bypass and remained high as late as POD3. The levels kidney cfDNA were found to increase 40 minutes after initiation of bypass (log2(fold-change) = 5, p = 0.004) and remained high until POD3. The levels of kidney cfDNA correlated with endothelial cfDNA (R=0.74, p = 1.5e-10). Postoperative edema correlated with a rise in endothelial cfDNA as early as 10 minutes after initiation of bypass. T cells were the most sensitive immune cells to CPB.

Conclusion: This is the first report of the of the early cellular dynamics following the use of CPB. An early, bypass-dependent, endothelial damage correlates with renal injury and postoperative edema and might serve as a novel marker for post-operative outcomes. Cardiomyocyte death is ongoing even at POD3. The study is ongoing and updated results will be presented in the conference, together with validations which are currently at work.