Biomarkers for endocardial vegetations diagnosis and prognosis: preliminary data from the BEEP STUDY

Background The diagnosis of infective endocarditis (IE) requires the integration of clinical findings, microbiological analyses, and diagnostic tests. Both transthoracic and transesophageal echocardiography (TOE) play a crucial role. However, the current diagnostic criteria lack specific biomarkers for endocardial vegetations diagnosis and prognosis. In endocardial processes, pathogen proliferation triggers a local and systemic inflammatory response mediated by pro-inflammatory cytokines, which in turn activate oxidative stress mediators. Purpose To evaluate whether patients with clinically suspected infective endocarditis (IE) present higher levels of biomarkers of oxidative stress and platelet activation compared to patients without vegetations or local infection. Secondary aim was to investigate a possible association of these biomarkers with embolic events. Methods Patients with a clinical indication for TOE due to suspected infective endocarditis were invited to participate in the study. Those who provided informed consent underwent blood sampling on the same day as the TOE for the analysis of oxidative stress markers and platelet activation, (hydrogen peroxide (H2O2), soluble serum NOX2, thromboxane B2 (TxB2), and P-selectin). Based on imaging findings, patients were classified as VEG+ (vegetation detected) or VEG− (no vegetation detected). Patients who had received empirical intravenous antibiotic therapy in a hospital setting for more than 7 days were excluded. A control group of patients with pneumonia (P) was recruited for comparison. Results 100 patients were recruited: 32 VEG+, 28 VEG−, and 40 P. Statistically significant differences were found in marker concentrations between the groups. The mean concentrations of H2O2, soluble NOX2, P-selectin, and TxB2 were higher in VEG+ compared to VEG− and P patients [respectively, p = 0.017, p = 0.001, p < 0.001, p < 0.001] (Figure 1 and Table 1). A linear regression analysis showed a statistically significant correlation between NOX2 and the other two markers: P-selectin (p < 0.001) and TxB2 (p < 0.001). Among the 32 VEG+ patients, 37% experienced embolic events. A univariate analysis showed that NOX2 and TxB2 were associated with embolic events [p = 0.036; p = 0.034]. Conclusions These preliminary data indicate that VEG+ patients exhibit higher levels of oxidative stress and platelet activation biomarkers compared to those without vegetations or localized infections. These biomarkers were also associated with embolic events. The findings suggest a potential role for these markers in supporting the diagnosis of infective endocarditis in uncertain cases, as well as their possible predictive value. Validation in a larger, multicenter cohort is needed to confirm these results.