Clinical Course, Treatment Outcome, Cellular, and Molecular Biology Findings in Cases of Infective Endocarditis Caused by Various Microorganisms Among Cardiac Surgery Patients. Summary of the Doctoral Thesis
Authors:   ,   Rīga Stradiņš University, Meidrops Kristiāns 
Published: May 2024

Infective endocarditis is a life-threatening disease characterized by microorganism-induced damage to the endocardium. There can be several potential causative microorganisms, although some are more commonly detected than others. Consequently, the aetiology, manifestations, course, and outcome of the disease can vary. Regardless of the aetiology, the most common reasons why patients are at risk are uncontrolled systemic or local infection, systemic or pulmonary vegetation embolism, and heart failure caused by valve damage. It has long been believed that bacteraemia and existing endothelial damage play a major role in the pathogenesis of infective endocarditis. Therefore, the diagnosis of infective endocarditis is also based on the detection of the pathogen in the blood and imaging studies that demonstrate endocardial involvement in the process. With the advancement of technology, diagnostic and research possibilities have expanded. As a result, potentially new significant elements in the pathogenesis of infective endocarditis have emerged, enabling more accurate diagnosis, prediction of unfavorable outcomes and risk factors, as well as increased treatment effectiveness. In this doctoral thesis, the clinical course, treatment outcomes, cellular and molecular biology findings in cases of infective endocarditis caused by various microorganisms in cardiac surgical patients were identified. An analysis of data from patients operated on in Latvia was conducted, including identification of the most common causative agents, risk factors, and outcomes. Analysis of the excised valves was performed morphologically using light microscopy and electron microscopy. Neutrophilic leukocyte activation markers were identified using immunohistochemistry, indicating neutrophilic leukocyte and neutrophil extracellular trap involvement in the pathogenesis process. Overall, the intrahospital mortality for operated patients with infective endocarditis was 11.2 %, but the long-term prognosis was 21.7 % after one year and 28.7 % after three years. Perivalvular infection prevalence was independently associated with an increased risk of intrahospital mortality. None of the laboratory indicators were independently prognostic for intrahospital mortality. There were no statistically significant differences between the blood culture-positive and negative endocarditis groups in terms of intrahospital mortality, intrahospital and intensive care unit stay, as well as three-year mortality. The most commonly encountered microorganism in the blood culture-positive endocarditis group was S. aureus. It was associated with significantly higher intrahospital mortality (RR coefficient of 3.332 and 4.408 in univariate and multivariate analyses, respectively) compared to other disease-causing microorganisms. Unlike E. faecalis, S. aureus is also associated with worse long-term prognosis in patients with infective endocarditis after cardiac surgery. In cases of blood culture-negative endocarditis 16S rRNA Next-Generation Sequencing is a useful technology for diagnosing the causative agent. Among blood culture-negative infective endocarditis cases, a large portion of the causative agents are Bartonella spp. These patients more frequently have a history of alcoholism, higher creatinine and BNP levels, lower ejection fraction of the left ventricle, lower glucose levels, leukocyte and platelet counts. There were differences in Bartonella spp. and non-Bartonella spp. infective endocarditis valvular vegetation morphology. On the contrary of control group patients’ cardiac valves a high level of neutrophilic leukocyte activation markers was observed. When compared, marker expression was significantly higher in non-Bartonella spp. infective endocarditis patients group. Research project was supported by the European Social Fund and Latvian state budget within project No 8.2.2.0/20/I/004 “Support for involving doctoral students in scientific research and studies” at Rīga Stradiņš University; Research project was supported by Rīga Stradiņš University PhD grant; Research project was supported by Pauls Stradiņš Clinical University Hospital Scientific Institute grant. The Doctoral Thesis was developed at Rīga Stradiņš University and Pauls Stradiņš Clinical University Hospital, Latvia. Defence: at the public session of the Promotion Council of Clinical Medicine of Rīga Stradiņš University on 23 May 2024 at 15.00 in the Hippocrates Lecture Theatre, 16 Dzirciema Street, Rīga Stradiņš University and remotely via online platform Zoom. 3.2 ClinicalMedicine; Sub-Sector – Surgery. Keywords: infective endocarditis; microorganisms; 16S rRNA NGS; Bartonella spp.; neutrophilic leukocytes.