Heart Failure Impacts Endothelial Cell Responses to Cardiac Surgery on Cardiopulmonary Bypass

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.