Cells, Volume 14, Issue 17, 31 5 2025, Pages 1357 Heart Failure Impacts Endothelial Cell Responses to Cardiac Surgery on Cardiopulmonary Bypass. Papazisi O, Postma RJ, Dirven RJ, Beeres SLMA, Berendsen RR, Arbous SM, Klautz RJM, van Vessem ME, Bijkerk R, Lindeman JHN, Palmen M, van Zonneveld AJ
Patients with heart failure with a reduced ejection fraction (HFrEF) are at an increased risk of developing postoperative hemodynamic instability and vasoplegia after surgery on cardiopulmonary bypass (CPB). Potentially pre-existing endothelial cell (EC) alterations due to chronic HF influence EC responses to cardiac surgery and might be responsible for the altered vascular responsiveness observed postoperatively. In this study, well-described EC activation markers were measured in blood samples collected pre- and perioperatively at four time points from HFrEF and control patients undergoing cardiac surgery on cardiopulmonary bypass (CPB). Circulating levels of Angiopoietin 2 (ANG2), von Willebrand Factor (vWF), and soluble P-selectin were measured using ELISA. Additionally, we investigated the responses of the cultured EC to patient-derived plasma through morphological profiling and mitochondrial functional assays. In total, 36 patients were included (67 (61-71) years, 78% male). HFrEF patients had higher baseline ANG2 and vWF levels when compared to controls. Both markers peaked during the first postoperative day. A pronounced increase in vWF was seen in controls after CPB. Ex vivo EC responses to patient-derived plasma showed distinct morphological differences between the two groups at baseline. A mitochondrial analysis indicated alterations in function and morphology for both groups after CPB. In conclusion, HFrEF patients exhibit a dampened EC response to cardiac surgery on CPB. Stable circulating factors in HFrEF plasma are responsible for inducing EC stress. Moreover, the mitochondrial function is highly affected postoperatively. This pre-existing mitochondrial and EC dysfunction predispose HFrEF patients to postoperative hemodynamic instability.
