IJCS | Volume 33, Nº1, January / February 2019

19 Lott Bezerra et al. Insulin use and infective endocarditis Int J Cardiovasc Sci. 2020;33(1):14-21 Original Article In our sample, mortality was higher in diabetic patients, when compared to non-diabetic ones, 35.29% of mortality in diabetics and 21.1% in non-diabetic patients, with no statistical difference (p = 0.221), as reported by Wallace et al. 10 with 36% and 16% andMoreno et al. 9 with 31% and 15%. That is in disagreement with the results of Chrillo et al. 7 and Movahed et al., 8 who indicated an association between DM and the outcome of IE. When we attempted to separate the diabetic patients between those who used or did not use insulin, mortality persisted without a statistically significant difference between the two groups, as demonstrated by Olmos et al. 11 On the other hand, Duval et al. 12 obtained a different result, showing that insulin use was a strong and independent predictor of mortality in IE. According to Wang, 31 the higher mortality rate observed in insulin users reported by Duval et al. 12 occurred because generally there is a higher prevalence of complications in patients with DM, such as coronary artery disease, renal failure, among others. In our sample, the groups of diabetic patients who were insulin users and non-insulin users were similar regarding these characteristics and therewas no difference in the outcome, which may corroborate the hypothesis by Wang, 31 i.e., that the clinical evolution is more related to the state of vulnerability associated with DM complications. It is also possible that the type of treatment implemented is a determinant for prognosis, but this variable was not collected in our study and it was not possible to evaluate whether there was any difference between the groups. We observed specific and relevant characteristics of the IE in insulin users in comparison to the other patients, related to the high prevalence of IE by S. aureus and the involvement of the tricuspid valve. In the study by Duval et al., 12 S. aureus also represented the majority of insulin users, but the statistical significance was only observed when the entire Staphylococcus spp genus was considered. As for the results of Olmos et al,¹¹ which studied only cases of left-chamber IE, S. aureus was also more prevalent, with 27.6% of cases, but there was no statistical significance. From the point of view of valvular involvement, the higher prevalence of IE in the tricuspid valve was not consistent with the findings of Duval et al., 12 since there was no statistical significance in relation to this variable. It should be noted that in the study by Olmos et al., 11 patients with right-chamber IE were excluded from the sample, which makes this comparison impossible and also raises the question whether this fact could have underestimated the proportion of IE caused by S. aureus among insulin users in their study. It can be observed that the higher prevalence of IE by S. aureus and the significant tricuspid involvement among insulin users are similar characteristics to what is described in IE observed in intravenous drug users, a known and well established risk factor for IE. Our results showed 57.1% of IE by S. aureus in insulin users, whereas this rate has already been described in the literature as ranging from 64.2% to 82% among intravenous drug users. 1,30,32,33 Regarding the tricuspid valve involvement, 32,34 rates have been reported as raging from 44% to 46% among intravenous drug users, and a rate of 33.3% was observed in the present study, which is in contrast with that observed in the general population, with 10% in our sample and 7% in South America, according to Murdoch et al. 1 Study limitations The present study has several limitations regarding its retrospective design. First, the difficulty in obtaining some information that would be relevant for sample characterization. It was not possible to obtain information on specific characteristics of non-diabetic patients, such as the proportion of patients with health-care related IE 28 , which would attenuate the bias of the comparison of the S. aureus proportion in this group of patients. It was possible to collect specific characteristics in diabetic patients, but the criterion of previous hospitalization related to health-care related IE 28 was not used. It was not possible to control for the quality, interval and location of blood collection for cultures, and sometimes the information on how many samples showed bacterial growth was not reported and, therefore, it is believed that some positive blood cultures, especially those in the ones that showed growth of coagulase-negative Staphylococcus , the result may be due to contamination. Blood culture was not performed in 34 patients, which received empirical treatment or who had already started antibiotic therapy at the health services that referred them. It was not possible to collect data regarding the time of DM, glycemic control and quality of IE treatment received, whether surgical or not, which are information that directly reflect the prognosis of these patients. Additionally, the sample size may be considered insufficient, since there is a considerable difference between the number of non-diabetic and diabetic patients

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