Inflammatory and Vasoactive Mediator Profiles during Valvular Surgery for Infective Endocarditis versus Noninfectious Valvular Heart Disease

Objectives: More than half of Infective endocarditis (IE) patients require cardiac surgery which is associated with high mortality. One of the leading causes of death in IE patients is postoperative multiple organ dysfunction syndrome (MODS). The contamination of blood with bacteria and cell debris during cardiac surgery might stimulate the release of cytokines and vasoactive peptides leading to circulatory failure.

Methods: We planned a monocentric, prospective case-control diagnostic study comparing two groups of patients undergoing cardiac surgery for IE or for non-infectious valvular heart disease (VHD). We measured plasma profiles of cytokines and vasoactive peptides at 7 defined time points in all patients. We used sequential organ failure assessment (SOFA) score to evaluate organ dysfunction. The study is registered in the German Register of Clinical Studies, ID: NCT02727413.

Results: Between May and December 2016 we included 20 patients in each group. Mean age was 65.1 ± 9.9. Both groups showed similar distribution of age and gender. Patients with IE had a higher preoperative EuroSCORE II (18.6 ± 17.4 versus 1.8 ± 1.3), and SOFA score (6.9 ± 2.6 vs 3.8 ± 1.1, p < 0.001) than patients in the control group. Preoperative pro-Adrenomedullin (proADM) was higher in IE patients compared with control group (1.77 vs 0.59, p = 0.017). Preoperative ProADM performed well in predicting mortality in patients with IE (area under the curve for receiver operating characteristic was 0.747). Pro - atrial natriuretic peptide, IL-1-β, IL-6, IL-10, IL-18, TNF-α and Endothelin-I were significantly higher in patients with IE at different time points. The level of proADM, IL-6, IL-10, and TNF-α dramatically increased during cardiopulmonary bypass in IE patients. In-hospital mortality was higher in IE patients (35% vs. 5%; p < 0.001). Incidence of postoperative organ dysfunction was higher in IE patients (SOFA 9.3 ± 3.2 vs. 6.6 ± 1.6, p = 0.014).

Conclusion: Our results show that during endocarditis surgery plasma levels of cytokines and vasoactive peptides are significantly higher compared with surgery for non-endocarditis valvular disease. This difference is associated with higher postoperative morbidity and mortality. This association sets the stage for a prospective randomized study aiming at reducing intraoperative cytokines and vasoactive peptides.