To our knowledge, this is the first and to date the largest study showing significant correlations between causative bacteria and IE manifestations detected by ECHO. In this cohort of 570 patients from the SRIE, we found that patients with S. aureus were more likely to have tricuspid valve vegetation but less likely to have aortic valve vegetation. Furthermore, S. aureus-linked IE was more common among patients with a history of IV drug abuse but less so among patients with prosthetic valves. Correlations were found between CoNS and the presence of a perivalvular abscess and aortic valve vegetation. CoNS as an agent was more common among patients with more than one manifestation on ECHO, but less common among patients with a history of IV drug abuse, although it should be noted that there were relatively few patients with CoNS (n = 29, 5%). Patients with E. faecalis infections were more likely to have aortic valve vegetation. Patients with CoNS or E. faecalis infections were also more likely to have aortic valve vegetation, regardless of whether they had native or prosthetic aortic valves. Significant correlations were seen between group B streptococcal infections and mitral valve vegetation and between HACEK- and CIED-associated IE.Correlations between specific bacterial infections and IE manifestations detected by ECHO have been reported previously [10, 11]. Trifunovic et al. could not show any correlations between specific IE manifestations and certain etiologies in their study of 246 patients with IE, even though their main findings were that S. aureus and gram-negative bacteria caused large vegetations, CoNS caused destructive leaflet lesions, CoNS and gram-negative bacteria caused perivalvular extension of the infective process, and that gram-negative bacteria were correlated with multiple manifestations in the same patient . Those results were consistent with our findings that CoNS infections were correlated with perivalvular abscesses (extension of the infective process). Furthermore, we found that S. aureus infections were correlated with tricuspid valve IE, which is supported by Bonetti et al. in their study of 274 patients with IE .
In our analysis of the most common bacteria causing IE, S. aureus was present in 47% of all patients and was also the only strain that was significantly correlated with in-hospital mortality. These findings are in line with studies showing that S. aureus is the most common bacterium causing IE in industrialized countries, and that it has higher mortality rates than IE caused by other pathogens [3, 12, 15, 16]. Furthermore, in our study, Streptococcus species were also common (28%), as was seen in studies presenting a high and increasing prevalence of streptococci in general, but more specifically viridans group streptococci and S. bovis [17, 18]. In addition, we found that the presence of a perivalvular abscess, a serious IE manifestation of tissue destruction, was correlated with in-hospital mortality. Similar results were reported by Lauridsen et al. who showed that perivalvular abscess and valve perforation independently predicted 1-year mortality in patients with left-sided native valve S. aureus-linked endocarditis .SurgeryIn our study, 28% of patients underwent surgical treatment, slightly less than the 31% of Swedish patients with IE who underwent surgical treatment in 2017 . This lower percentage in our cohort might be explained by the large proportion of patients with a history of IV drug abuse (29%). Patients with aortic or mitral valve vegetation, CIED-associated endocarditis, or a perivalvular abscess more often underwent surgical treatments. None of the bacteria in our analyses were correlated with surgical treatment of IE. It has been argued whether S. aureus should be listed as an absolute indication for surgical treatment, as it often causes severe IE with the presence of emboli or abscesses, and/or severe valvular engagement, but the current recommendations promote individual evaluation of patients for decisions on using surgical treatments [6, 20, 21]. This individualized approach was adopted in decision-making at KUH.
Prosthetic valves and CIED-linked IE
It has been reported that prosthetic valve IE and CIED-linked IE are becoming more frequent . In our study, there was no difference in the prevalence of CIED-associated IE and prosthetic valve IE between the two 5-year periods, although it should be noted that there were only a few patients with CIED-linked IE and prosthetic valve IE. These cases can be challenging to diagnose, especially with TTE because of its relatively low resolution and shading from the prosthesis or chordae tendinae; thus, TEE is highly recommended [2, 17, 22]. The respective sensitivities for diagnosing native IE and prosthetic valve IE are approximately 96% and 70% with TTE and 96% and 92% for TEE, respectively . The correlations between the incidences of prosthetic valve IE and E. faecalis infection found in our study differ from previous reports. S. aureus and CoNS infections have been described as common etiological factors for prosthetic valve IE .IV drug abuseKUH has a special ward for addicts with infections, with an uptake area covering Stockholm County Council (approximately 2.3 million inhabitants), which might contribute to the relatively high presence of IV drug abuse among endocarditis patients at KUH. Studies of patients with IE in the USA in 2012–2013 showed a lower incidence of IV drug abuse among IE patients (6.5–7.8% of the IE patients had IV drug abuse) than in our results (29% of the patients had a history of IV drug abuse), although recent US and European studies have noted that the presence of IV drug abuse is generally increasing among patients with IE [23, 24]. S. aureus was the most common bacterial strain among patients with IE and a history of IV drug abuse, which is consistent with previous studies [23-25].
Although there were significantly more men than women in our study (~2:1), we found no gender differences in IE etiology, which is consistent with earlier studies in which the ratio of men to women was typically higher than 2:1 [26, 27]. Previous work has evaluated the differences in etiology and manifestations, but with ambiguous results. For instance, Aksoy et al. showed that women were more likely to have vegetations on CIED and men were more commonly infected with CoNS , while Sambola et al. showed that mitral valve IE and aortic valve IE were more common among men, but the etiology did not differ between genders . In our study, men were more likely to have aortic valve IE, which could possibly be explained by the higher presence of bicuspid aortic valves among men, and the known higher risk of developing IE in bicuspid versus tricuspid aortic valves . The rates of in-hospital mortality and surgical treatment for IE in our study did not differ between men and women, which does not accord with previous reports indicating that women have higher mortality and receive surgical treatment to a lesser extent compared with men . In our cohort, the in-hospital mortality rate was low (7%), which contrasts with previously reported rates of 15–20% [29, 30]. This might be explained by the relatively low age of the patients (mean age 58.2 years) in our study.
Diagnosis of IE manifestations
TEE has been reported to have high sensitivity for the diagnosis of IE, ranging between 90% and 100%, as well as a high negative predictive value of 86–97% [22, 31]. Moreover, it has been shown that ECHO findings did not differ between patients who underwent ECHO early (<2 days) or late (³2 days) after starting antibiotic treatment for IE . We found IE manifestations most frequently on the mitral valve (n = 222, 36%), followed by the aortic valve (n = 214, 34%) and the tricuspid valve (n = 117, 19%). Our results resemble those of a study involving 68 autopsies of patients with IE, which reported that 35% of patients had mitral valve IE, 26% had aortic valve IE, and 5% had tricuspid valve IE . Our results are also consistent with a multicenter study of 1055 patients in Europe and the USA, showing that the most common ECHO manifestations among patients with IE were on the mitral valve followed by the aortic valve .
The SRIE includes variables on IE manifestation, such as vegetation localization, but not the size or numbers of vegetations. Nor does it include detailed information on comorbidity, for example, a history of heart failure, other diseases, or results from blood tests such as glucose and brain natriuretic peptide levels, which are valuable for the analysis of predisposition for bacteria or specific IE manifestations. Furthermore, we could not assess how many days after initiating antibiotic treatment ECHO was conducted. In addition, it would be interesting to analyze patients with IE with a more unusual etiology, such as infections with gram-negative bacteria and fungi; however, this was not possible in our cohort as there were very few cases with these infective agents.