Institutionen för medicin, Huddinge Sjukhus / Department of Medicine at Huddinge University Hospital
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