Infectious endocarditis, aspects on pathogenesis, diagnosis and prognosis

Abstract: The incidence of infectious endocarditis (IE) is estimated to 5.9/100.000 inhabitants and year. In recent years there has been an improvement in prognosis mainly due to more sensitive echocardiographic methods and surgery in the acute phase of the infection. However the mortality rate is still between 10-20% with an even higher mortality in IE caused by Staphylococcus aureus (SA). In this thesis some aspects of pathogenesis, diagnosis and prognosis have been studied. In paper I, a retrospective study started 1994 the Duke criteria were applied to 83 patients who in 88 episodes had been examined by transesophageal echocardiography (TEE) for IE. In 49 episodes no treatment was given, all these episodes were classified as rejected. In 39 episodes the patients were treated, 26 definite, 11 possible and 2 rejected episodes. The Duke criteria were well adapted to use in clinical routine and valuable both in excluding patients without IE and identifying patients with IE. In paper II thirty-four patients with 35 episodes of IE were followed prospectively with repeated TEE examinations (at diagnosis, discharge and follow-up 5 months later). The use of TEE for the diagnosis was found to be valuable as the high sensitivity and resolution enabled the diagnosis of small vegetations (< 5 mm) in 9/35 episodes and the identification of indications for surgery in 8/35 at the first TEE. The size of the vegetations decreased significantly during treatment. The repeated TEE examinations did not detect any previously unknown complications or influence the treatment. In paper III, a retrospective study of the period from 1994 to 2000 the in-hospital and longterm mortality of injecting drug-users (IDU) and non-IDU patients was compared. In this study 195 IE episodes, 60 in IDUs and 135 non-IDUs were included. The episodes were classified by the Duke criteria and 145 definite episodes were analysed in detail. The favourable prognosis in right-sided IE was confirmed with no in-hospital mortality in 29 episodes in IDUs, and long-term mortality rate as IDUs in general. The in-hospital mortality did not differ between IDUs and non-IDUs but IDUs with left-sided IE had a higher long-term mortality rate than non-IDUs with left-sided IE and IDUs with right-sided IE. This excess mortality was explained by the poor long-term survival of operated IDUs. In paper IV the internalization of S aureus in endothelial cells was studied as this might be one explanation for the difficulty in treating IE caused by SA. In an experimental model the rate of internalization of S aureus in cultured endothelial cells was compared to the rate in human heart valve biopsies and umbilical cord veins. The internalization rate into biopsies was significantly diminished by a factor 300 1000 compared to cultured cells. Furthermore we studied the role of Fibronectin Binding Protein (FnBP) on internalization into biopsies. In cultured endothelial cells we could confirm the vital role of FnBP for internalization but not so in the biopsies. This raises the question if internalization is of less importance in vivo than in vitro.