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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0040" class="elsevierStylePara elsevierViewall">Infections of non-valvular cardiac implantable electronic devices &#40;CIED&#41; &#8211; pacemakers and implantable cardioverter-defibrillator &#40;ICD&#41; or cardiac resynchronization therapy &#40;CRT&#41; devices &#8211; has increased in recent years&#44;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">1&#8211;3</span></a> and now account for around 10&#37; of cases of endocarditis&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">4</span></a> They are associated with significant morbidity and an 8&#46;4-11&#46;6&#37; higher risk of mortality than with non-infectious cardiac device-related complications&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">5&#44;6</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Prevention or early diagnosis and treatment of CIED infection is crucial to survival and to reducing the risk of reinfection&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">7</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">There have been few studies on the subject and only recently has there been discussion of the best therapeutic approach&#46; Current knowledge is based mainly on observational studies and there are as yet no international guidelines&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Epidemiological data on CIED infection in Portugal are almost non-existent&#44; particularly for the Central region of the country&#46; The aim of this study was to review the current state of the art&#44; based on the experience of our center&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Study population</span><p id="par0060" class="elsevierStylePara elsevierViewall">We performed a retrospective analysis of 3158 patients who underwent device implantation in our center between January 2008 and September 2014&#46; Of these&#44; 47 &#40;1&#46;48&#37;&#41; were hospitalized for CIED infection&#46; The diagnosis was established according to the modified Duke criteria&#44; based on the presence of localized pocket infection and&#47;or endocarditis&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Baseline characteristics</span><p id="par0065" class="elsevierStylePara elsevierViewall">The following characteristics of the study population were recorded&#58; age&#44; gender&#44; type of CIED&#44; type of infection&#44; type of implantation &#40;replacement or first implantation&#41;&#44; clinical presentation&#44; known predictors of infection &#40;hypertension&#44; diabetes&#44; oral anticoagulation&#44; immunosuppression&#44; smoking&#44; long-term corticosteroid therapy&#44; chronic renal disease&#44; severe cardiac dysfunction&#44; previous implantation of temporary pacemaker&#44; antibiotic therapy prior to implantation and presence of hematoma following implantation&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Laboratory and imaging parameters</span><p id="par0070" class="elsevierStylePara elsevierViewall">Laboratory parameters at admission and during hospital stay were analyzed&#44; together with the microorganisms isolated and the results of antibiotic susceptibility testing&#44; and the findings of transthoracic &#40;TTE&#41; and transesophageal echocardiography &#40;TEE&#41; if performed&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Therapeutic approach</span><p id="par0075" class="elsevierStylePara elsevierViewall">The initial empiric antibiotic therapy and any change following the results of susceptibility testing were recorded&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">The method of device extraction &#40;percutaneous or surgical&#41;&#44; or the reason for not removing the device&#44; and the timing of new device implantation were also analyzed&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Clinical follow-up</span><p id="par0085" class="elsevierStylePara elsevierViewall">Patients were followed for a mean of 32&#177;22 months &#40;10-54 months&#41;&#46; The events considered during follow-up were rehospitalization due to device infection and mortality&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Statistical analysis</span><p id="par0090" class="elsevierStylePara elsevierViewall">The statistical analysis was performed using SPSS<span class="elsevierStyleSup">&#174;</span> version 20&#46; Continuous variables were expressed as means &#177; standard deviation and categorical variables as relative frequencies&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Results</span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Baseline characteristics</span><p id="par0095" class="elsevierStylePara elsevierViewall">The mean age of the 47 patients admitted for CIED infection was 65&#177;19 years&#44; and 72&#46;3&#37; &#40;n&#61;34&#41; were male&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Most of the devices involved were pacemakers &#40;76&#46;6&#37;&#44; n&#61;36&#41;&#44; followed by ICD &#40;17&#37;&#44; n&#61;8&#41; and CRT devices &#40;6&#46;4&#37;&#44; n&#61;3&#41;&#46; The infection rate was significantly higher in patients with ICD or CRT devices &#40;5&#46;4&#37;&#41; compared to pacemakers &#40;1&#46;21&#37;&#44; p&#61;0&#46;04&#41;&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Sixteen patients &#40;34&#37;&#41; had pocket infection&#44; while the diagnosis was device-related endocarditis in the other 31 &#40;66&#37;&#41;&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Most infections &#40;70&#46;2&#37;&#44; n&#61;33&#41; occurred at least a year after implantation and were classified as late&#44; and after first implantation &#40;63&#46;3&#37;&#44; n&#61;30&#41;&#46; There was a history of hospitalization for CIED infection in 38&#46;3&#37; &#40;n&#61;18&#41;&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Clinical presentation varied&#44; but most patients &#40;76&#46;6&#37;&#44; n&#61;36&#41; presented with local inflammation manifested as redness&#44; warmth and pain&#44; with lead erosion in 42&#46;6&#37; &#40;n&#61;20&#41;&#46; Fever occurred in 59&#46;6&#37; &#40;n&#61;28&#41;&#44; and 25&#46;5&#37; &#40;n&#61;12&#41; reported feeling general malaise&#44; fatigue&#44; weakness and loss of appetite&#46; Three patients &#40;6&#37;&#41; were admitted with fever of no apparent cause&#44; diagnostic study revealing device-related infection&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Various known predictors of infection were identified in the study population&#58; hypertension &#40;61&#46;7&#37;&#44; n&#61;29&#41;&#44; diabetes &#40;44&#46;7&#37;&#44; n&#61;21&#41;&#44; oral anticoagulation &#40;17&#37;&#44; n&#61;8&#41;&#44; smoking &#40;10&#46;6&#37;&#44; n&#61;5&#41;&#44; long-term corticosteroid therapy &#40;4&#46;3&#37;&#44; n&#61;2&#41;&#44; chronic renal disease &#40;8&#46;5&#37;&#44; n&#61;4&#41; and severe cardiac dysfunction &#40;21&#46;3&#37;&#44; n&#61;10&#41;&#46; No patient had documented hematoma following CIED implantation or a temporary pacemaker prior to implantation of a permanent system&#46; All had received prophylactic therapy with second-generation cephalosporin before device implantation &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Laboratory and imaging parameters</span><p id="par0125" class="elsevierStylePara elsevierViewall">At least two blood samples were taken in all patients and microorganisms were isolated in 57&#46;4&#37; &#40;27 patients&#41;&#44; mainly Gram-positive bacteria&#58; <span class="elsevierStyleItalic">Staphylococcus aureus</span> &#40;eight&#41;&#44; <span class="elsevierStyleItalic">S&#46; epidermidis</span> &#40;13&#41; and <span class="elsevierStyleItalic">S&#46; hominis</span> &#40;two&#41;&#46; Gram-negative microorganisms &#40;<span class="elsevierStyleItalic">Pseudomonas aeruginosa</span>&#41; were identified in four cases&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Echocardiography was performed in 45 patients&#44; all except two with pocket infection&#46; Thirty-seven underwent TTE&#44; complemented by TEE in 12 cases&#46; Vegetations were detected in 14 patients &#40;29&#46;8&#37;&#41;&#44; eight of whom had concomitant tricuspid valve involvement &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Therapeutic approach</span><p id="par0135" class="elsevierStylePara elsevierViewall">Empiric antibiotic therapy with vancomycin was instituted in all patients&#44; associated with gentamicin in 27 patients &#40;57&#37;&#41; who showed evidence of more severe infection&#46; Based on the results of antibiotic susceptibility testing&#44; therapy was adjusted to vancomycin alone in patients with secondary Gram-positive infection and to ciprofloxacin for those in whom <span class="elsevierStyleItalic">Pseudomonas</span> had been isolated&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">The device was extracted in 72&#37; of patients &#40;n&#61;34&#41;&#44; the other 28&#37; &#40;n&#61;13&#41; being treated by medical therapy alone&#46; Extraction was not performed in six patients with endocarditis and in seven with pocket infection&#46; The decision to opt for medical therapy alone was prompted by evidence of localized pocket infection and&#47;or the presence of comorbidities&#46; The extraction procedure was surgical in 14 patients and percutaneous in the remaining cases&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">A new device was implanted in 94&#37; &#40;n&#61;32&#41;&#44; performed within 48 h of extraction in all patients &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#59; the other patients were not indicated for reimplantation&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Clinical follow-up</span><p id="par0150" class="elsevierStylePara elsevierViewall">Four patients &#40;8&#46;5&#37;&#41; died during hospitalization and eight &#40;17&#37;&#41; during follow-up&#44; of whom seven died of cardiovascular cause&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Albeit without statistical significance&#44; there was a tendency for higher in-hospital mortality in patients with endocarditis and in those in whom the device was not removed&#46; The same tendency was not seen with regard to in-hospital mortality&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">There were seven rehospitalizations &#40;14&#46;9&#37;&#41; due to reinfection&#44; mainly in patients with endocarditis&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">No correlation was found between the type of microorganism and mortality or rehospitalization&#46;</p></span></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Discussion</span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Baseline characteristics</span><p id="par0170" class="elsevierStylePara elsevierViewall">There has been considerable growth in the number of devices implanted over the years&#44; accompanied by a significant increase in cases of CIED infection&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">7&#44;8</span></a> This is associated with high morbidity and mortality as well as significant costs<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">9</span></a> and is due not only to the increase in the number of implants but also to more complex devices&#44; a greater number of generator replacements and an aging target population with multiple comorbidities&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">7</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">The rate of CIED infection in our population was comparable to other studies&#44; reported rates varying between 0&#46;5-5&#37;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">10</span></a> and 0&#46;13-19&#46;9&#37; in pacemakers&#44; and 0&#46;0-3&#46;2&#37; in ICD&#47;CRT devices&#44;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">8&#44;11&#8211;13</span></a> higher in more complex devices &#40;dual chamber&#44; larger generators or greater number of leads&#41;&#44; which entail a more lengthy implantation procedure&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Infection may be confined to the pocket or may be systemic&#44; with or without lead or valve endocarditis&#46;<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">14&#8211;16</span></a> Pocket infection can result from manipulation of the pocket during implantation or when the generator or leads erode through the skin&#59; it can spread to downstream structures via the lead or through blood-borne dissemination from a remote site&#44; or present as isolated bacteremia&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">6&#44;11&#44;17</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">Infections within a year of implantation &#40;early&#41; are probably due to contamination during the procedure&#44; while those occurring after that period &#40;late&#41; are due to external contamination&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">10</span></a> However&#44; the definition of early or late varies&#44; with some centers considering late onset to be six weeks or three months after implantation&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">11</span></a> The time of onset from first implantation is important because it indicates not only the most likely etiological mechanism but also the ease of device extraction&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">11</span></a> Contamination of the pocket during implantation is more common with reintervention procedures and thus infections are more frequent following lead revision&#44;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">8</span></a> which was not the case in our series&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">The variability of presentation means a high index of suspicion is required&#46; Most patients in our population had changes at the implantation site and fever&#46; Besides signs of inflammation at the pocket site or erosion exposing the generator or leads&#44; patients may also present nonspecific symptoms such as fatigue&#44; loss of appetite&#44; fever and chills or other systemic symptoms&#46; Some cases are diagnosed on the basis of fever of no apparent cause in a patient with a CIED&#46; Less common manifestations are pulmonary or systemic embolism&#44; joint pain&#44; spondylitis&#44; pulmonary abscess or pleural effusion&#46;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">11&#44;2</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">Laboratory tests show changes related to systemic inflammation&#44; including changes in white cell count&#44; elevated C-reactive protein and higher erythrocyte sedimentation rate&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">2</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">Various risk factors for CIED infection are mentioned in the literature&#44; many of which were seen in our population&#46; These include diabetes&#44; hypertension&#44; chronic renal disease &#40;particularly in patients under hemodialysis&#41;&#44; long-term corticosteroid use&#44; active malignancy&#44; immunosuppression&#44; oral anticoagulation&#44; heart failure with left ventricular systolic dysfunction&#44; reintervention &#40;commonly due to hematoma&#44; lead dislocation or device replacement&#41;&#44; longer procedure times and more complex devices&#44; implantation via abdominal access or thoracotomy&#44; lack of antibiotic prophylaxis&#44; fever in the 24 h before implantation and less experienced operators&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">18&#8211;21</span></a> Ideally&#44; these risk factors should be controlled in order to reduce the risk of infection&#46; Prophylactic antibiotics prior to implantation are particularly effective in this respect&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">22</span></a> Various observational studies have reported a greater than 50&#37; reduction in CIED infection in patients receiving a single dose of antibiotics prior to the procedure&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">20&#44;21</span></a> These findings are corroborated by a meta-analysis<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">23</span></a> and by the results of a randomized trial in which the use of cefazolin reduced CIED infection from 3&#46;28&#37; to 0&#46;64&#37; &#40;p&#61;0&#46;016&#41; at eight months&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">24</span></a> There is no consensus on the best antibiotic or the duration of therapy&#59; the choice will depend on whether methicillin-resistant <span class="elsevierStyleItalic">Staphylococcus</span> is present&#46; There appears to be no benefit in continuing antibiotic therapy beyond the first dose or in applying antimicrobials or antiseptics to the pocket after implantation&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">25&#8211;28</span></a></p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Laboratory and imagining parameters</span><p id="par0205" class="elsevierStylePara elsevierViewall">At least two blood cultures should be taken&#44; ideally before antibiotic therapy is begun&#46; The latest UK guidelines recommend that three blood cultures should be taken with &#8805;6 h between them&#44; except in the presence of severe sepsis in which two blood cultures should be taken at different times within 1 h&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">28</span></a> Blood cultures should be taken again 48&#8211;72 h after removal of an infected CIED&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">28</span></a> Cultures are less often positive than in cases of valve endocarditis but they are reported in the literature to be positive in 80&#37;&#8211;100&#37; of patients with pacemaker-related endocarditis&#46; At least two blood cultures were taken in all patients in our population and microorganisms were isolated in 57&#37;&#46; The low rate of positive results is probably related to samples being collected after antibiotic therapy&#44; or may be due to slow-growing bacteria in a small number of cases&#46; Besides usual culture in aerobic and anaerobic media&#44; cultures should be performed for fastidious microorganisms&#44; fungi and mycobacteria&#44;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">29</span></a> which was not done in our center&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">In cases of erosion&#44; pocket-site tissue should be sent for culture&#44; but percutaneous aspiration of the device pocket should not be performed as part of the diagnostic evaluation and is considered contraindicated if there is no erosion&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">13</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall">Culture of the removed leads offers the possibility of an etiological diagnosis in the majority of cases and is therefore mandatory&#46; Sterile manipulation after removal and rapid submission to the laboratory are essential&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">As found in our population&#44; most infections are monomicrobial&#44;<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">13&#44;30</span></a> involving coagulase-negative staphylococci&#44; mainly <span class="elsevierStyleItalic">S&#46; epidermidis</span> and <span class="elsevierStyleItalic">S&#46; aureus</span>&#46; Only 10-30&#37; are due to other Gram-positive microorganisms like <span class="elsevierStyleItalic">Enterococcus</span>&#44; <span class="elsevierStyleItalic">Streptococcus</span>&#44; and <span class="elsevierStyleItalic">Corynebacterium</span> spp&#46; and <span class="elsevierStyleItalic">Propionibacterium acnes</span>&#44; Gram-negative bacteria such as Enterobacteriaceae and <span class="elsevierStyleItalic">Pseudomonas</span>&#44; atypical bacteria like <span class="elsevierStyleItalic">Nocardia</span> spp&#46;&#44; fungi like <span class="elsevierStyleItalic">Candida</span> and <span class="elsevierStyleItalic">Aspergillus</span> and mycobacterial organisms&#46;<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">12&#44;31</span></a> The increasing incidence of multiresistant microorganisms indicates that many infections are acquired in the hospital environment&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">Infections by <span class="elsevierStyleItalic">S&#46; aureus</span> are more serious and are associated with higher mortality<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">32</span></a> compared to other microorganisms &#40;9&#37; vs&#46; 4&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">31</span></a></p><p id="par0230" class="elsevierStylePara elsevierViewall">The chest X-ray can detect associated lung infection&#44; pulmonary abscess and pleural effusion&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">Echocardiography plays a central role in the diagnosis of CIED infection<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">33</span></a> as it can detect and assess vegetations&#44; which may be located on leads&#44; the tricuspid or other valves or the endocardium&#46; Vegetations do not always appear as masses attached to structures but may present as a filiform structure or as localized thickening of the lead&#44; making diagnosis more difficult&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">TTE has low sensitivity and negative predictive value for detecting vegetations on cardiac devices&#44; while TEE has higher specificity and sensitivity&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">11</span></a> The two modalities are complementary and should both be used as part of an overall assessment&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">33</span></a></p><p id="par0245" class="elsevierStylePara elsevierViewall">The presence of lead-induced echoes&#44; atypical location of vegetations and inadequate acoustic window may produce false negative results&#44; and so the lack of visible vegetations does not rule out CIED infection&#59; when clinical suspicion is high&#44; repeat TEE is warranted within seven days&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">33</span></a></p><p id="par0250" class="elsevierStylePara elsevierViewall">Echocardiographic study should also be performed after device extraction to exclude residual vegetations&#44; particularly of the right ventricle&#44; tricuspid valve&#44; right atrium and superior vena cava&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">29</span></a></p><p id="par0255" class="elsevierStylePara elsevierViewall">Echocardiographic images should be carefully interpreted in the light of the available clinical information&#46; An incidental finding of small masses adhering to leads should be considered in the diagnosis but these may be fibrous tissue or thrombi rather than vegetations&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">13</span></a></p><p id="par0260" class="elsevierStylePara elsevierViewall">Two patients in our population with pocket infection did not undergo echocardiographic study&#44; possibly because in the earlier years of the study period there were no protocols establishing all the diagnostic exams to be performed&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">Other imaging modalities can be used to aid diagnosis&#44; such as <span class="elsevierStyleSup">99m</span>Tc-labeled leukocyte scintigraphy&#44; which can show uptake of the marker in areas of infection in doubtful cases&#46; <span class="elsevierStyleSup">18</span>F-fluorodesoxyglucose positron emission tomography has also been found useful in the diagnosis of CIED infection&#44; but experience is limited and further validation of this method is needed&#46;<a class="elsevierStyleCrossRefs" href="#bib0365"><span class="elsevierStyleSup">34&#44;35</span></a></p><p id="par0270" class="elsevierStylePara elsevierViewall">Suspected pulmonary embolism should be confirmed by thoracic computed tomography angiography or ventilation-perfusion scintigraphy&#46;</p><p id="par0275" class="elsevierStylePara elsevierViewall">Since the Duke criteria were found to be insufficiently sensitive&#44; the modified Duke criteria have been established in order to standardize diagnosis&#44; and now include local signs of infection and pulmonary embolism as major criteria<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">29</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0280" class="elsevierStylePara elsevierViewall">Before the establishment of the modified Duke criteria&#44; others were proposed such as the modified von Reyn criteria or those established by Chamis<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">11</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Therapeutic approach</span><p id="par0285" class="elsevierStylePara elsevierViewall">Antibiotic therapy should be initiated early&#46; In the light of current knowledge of the causal agents involved&#44; antibiotic coverage for Gram-positive methicillin-resistant bacterial strains is recommended&#44; vancomycin being the most commonly used drug&#46; This should be combined with coverage for Gram-negative bacteria in patients with sepsis&#46; Therapy should be adjusted appropriately following confirmation of the microorganism involved&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">13</span></a></p><p id="par0290" class="elsevierStylePara elsevierViewall">The duration of antibiotic therapy varies after device extraction&#44; ranging from two weeks in cases of pocket infection to 4-6 weeks in cases of confirmed endocarditis&#44; especially if blood cultures remain positive&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">13</span></a></p><p id="par0295" class="elsevierStylePara elsevierViewall">Treatment with antibiotic therapy alone&#44; without device extraction&#44; is associated with frequent reinfection and higher mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">36</span></a> Various studies have shown that there is a particularly high risk in <span class="elsevierStyleItalic">S&#46; aureus</span> bacteremia&#44; even in the absence of visible CIED infection&#44; and so device removal is recommended&#46;<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">12&#44;32</span></a> In cases of Gram-negative bacteremia&#44; the risk of device infection appears to be low&#44; and thus extraction is not mandatory unless there is reinfection after appropriate antibiotic therapy&#46;<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">12&#44;36</span></a></p><p id="par0300" class="elsevierStylePara elsevierViewall">Together with antibiotic therapy&#44; complete device removal is essential&#44; irrespective of the extent of infection&#46; The only exception in some guidelines is antibiotic therapy alone with an agent with activity against staphylococci for 8-10 days for superficial or incisional infection&#44; if there is no involvement of the device&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">12</span></a> Conservative treatment is often ineffective and is associated with high mortality &#40;31-66&#37;&#44; as opposed to 13-21&#37; with combined treatment&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">6&#44;37</span></a> Device removal should be performed early rather than after a period of antibiotic therapy&#46;</p><p id="par0305" class="elsevierStylePara elsevierViewall">In our population we opted not to remove the device in some patients with localized pocket infection only and in others with multiple comorbidities at high risk during the extraction procedure&#46; To date there have been no rehospitalizations for reinfection in these cases&#59; however&#44; there was a tendency for higher in-hospital mortality in patients who did not undergo device removal&#46;</p><p id="par0310" class="elsevierStylePara elsevierViewall">The extraction procedure is more difficult in the case of late-onset infections&#44; and carries a higher risk of complications due to the formation of fibrocollagenous tissue&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">11</span></a></p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Reimplantation of a new device</span><p id="par0315" class="elsevierStylePara elsevierViewall">Reimplantation should not be an automatic decision and the original indication for the device should be reassessed&#46; According to the literature replacement is not indicated in around one third of patients with a diagnosis of CIED infection&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">13</span></a> When reimplantation is needed&#44; it should be performed on the contralateral side or by epicardial implantation&#46; There are no randomized trials to guide the timing of reimplantation&#59; this depends on the type of infection&#44; the presence of positive blood cultures&#44; and the pathogen involved&#46; Patients with no evidence of endocarditis and positive blood cultures can be reimplanted if repeat blood cultures after CIED removal remain negative for 72 h&#46; In the event of valve infection&#44; reimplantation should not be performed until at least 14 days after the first negative blood cultures after CIED removal&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">13</span></a> Patients who are pacemaker dependent are a real challenge in terms of the extraction approach&#46; Implantation of a temporary pacing system enables completion of antibiotic therapy&#44; thus reducing the risk of infection of the new device&#44; but the rate of complications such as dislocation or infection of the temporary lead and right ventricular perforation is significant&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">38</span></a> An alternative is to implant a new conventional system at the same time or an epicardial system&#46; A new and increasingly popular approach that provides a bridge of 10-15 days of antibiotic therapy prior to implantation of a new device consists of implantation of an active-fixation right-ventricular lead via the jugular vein that is sutured to the skin and connected to a VVI generator placed in an antimicrobial envelope and covered with an adhesive dressing&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">39</span></a></p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Clinical follow-up</span><p id="par0320" class="elsevierStylePara elsevierViewall">Mortality in our series was similar to that reported in the literature&#58; 4-10&#37; in-hospital and 15-20&#37; at one year&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">13</span></a> It is higher at one year in cases of healthcare-associated infection&#44; multiresistant staphylococcal infection&#44;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">6</span></a> concomitant valve involvement and medical therapy alone&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">2</span></a></p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Areas of uncertainty</span><p id="par0325" class="elsevierStylePara elsevierViewall">As stated above&#44; randomized trials are needed to determine the best approach to various issues&#44; including the duration of antibiotic therapy&#44; the timing of device reimplantation&#44; and the type and duration of antibiotic prophylaxis&#46;</p><p id="par0330" class="elsevierStylePara elsevierViewall">Further studies are also required on patients with positive blood cultures but no other evidence of endocarditis&#44; in order to standardize treatment&#46;</p><p id="par0335" class="elsevierStylePara elsevierViewall">The role of leadless pacemakers and subcutaneous ICDs should also be investigated as results indicate a lower rate of infection with these devices&#46;</p></span></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Limitations</span><p id="par0340" class="elsevierStylePara elsevierViewall">The study has the following limitations&#58; this was a single-center series with a short follow-up&#59; collection of material during the extraction procedure was not systematic&#59; TTE was not performed in all patients&#59; and the device was not removed in all patients with indication for extraction&#46;</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Conclusion</span><p id="par0345" class="elsevierStylePara elsevierViewall">CIED infection is a serious&#44; potentially life-threatening complication&#46; Although guidelines exist&#44; the approach to these patients has yet to be standardized&#44; even in centers treating a large volume of cases&#59; this is particularly true of prophylactic therapy prior to implantation&#44; and treatment of infection when diagnosed&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">23</span></a> Protocols covering the diagnosis and treatment of CIED infection are required&#46;</p><p id="par0350" class="elsevierStylePara elsevierViewall">The rate of infections in our center was similar to that reported in the literature&#44; and most were late-onset infection of pacemakers&#46; Clinical presentation varied&#44; but in most cases Gram-positive microorganisms were isolated&#46; There were no CIED infection-related rehospitalizations or deaths during follow-up&#46;</p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Ethical disclosures</span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Protection of human and animal subjects</span><p id="par0355" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study&#46;</p></span><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0185">Confidentiality of data</span><p id="par0360" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of their work center on the publication of patient data&#46;</p></span><span id="sec0130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0190">Right to privacy and informed consent</span><p id="par0365" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article&#46;</p></span></span><span id="sec0135" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0195">Conflicts of interest</span><p id="par0370" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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    "fechaRecibido" => "2015-10-09"
    "fechaAceptado" => "2015-12-20"
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          "clase" => "keyword"
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          "palabras" => array:5 [
            0 => "Cardiac device"
            1 => "Pacemaker"
            2 => "Cardiac defibrillator"
            3 => "Resynchronization device"
            4 => "Endocarditis"
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          "palabras" => array:5 [
            0 => "Dispositivos card&#237;acos"
            1 => "<span class="elsevierStyleItalic">Pacemakers</span>"
            2 => "Cardiodesfibrilhador implant&#225;veis"
            3 => "Dispositivos de ressincroniza&#231;&#227;o"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The incidence of cardiac implantable electronic device infections has increased significantly over the years and they are associated with significant morbidity and mortality&#46; The epidemiology in the Central region of Portugal is not known&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objective</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">To characterize cardiac implantable electronic device infections through a retrospective study of 3158 patients admitted to our center between January 2008 and September 2014 and to review the subject in the light of the current state of the art&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The infection rate was 1&#46;48&#37; &#40;pacemakers 1&#46;21&#37;&#44; cardiac defibrillator&#47;resynchronization devices 5&#46;40&#37;&#41;&#46; The study population consisted of 47 patients with a mean age of 65&#177;19 years&#44; predominantly male &#40;72&#46;3&#37;&#41;&#46; Infections were mainly of pacemakers&#44; the main device implanted in our population &#40;n&#61;2954&#41;&#44; and most occurred late after first implantation&#46; Clinically&#44; most patients presented with fever and local inflammation&#46; Blood cultures identified mainly Gram-positive microorganisms&#46; Empiric antibiotic therapy with vancomycin was instituted in all patients&#44; associated with gentamicin in 57&#37;&#46; The device was extracted in the majority of cases &#40;72&#37;&#41;&#46; During follow-up &#40;32&#177;22 months&#41; eight patients died &#40;17&#37;&#41;&#44; seven of cardiovascular cause &#40;15&#37;&#41;&#44; and seven were readmitted with device infection &#40;15&#37;&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Our rate of infection was low&#44; similar to other published series&#44; with a higher rate in cardiac defibrillator&#47;resynchronization devices&#46; After standard treatment with antibiotic therapy and device extraction&#44; the prognosis was good&#46;</p></span>"
        "secciones" => array:4 [
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            "identificador" => "abst0005"
            "titulo" => "Introduction"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introdu&#231;&#227;o</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">O n&#250;mero de infe&#231;&#245;es associadas com dispositivos card&#237;acos tem aumentado exponencialmente ao longo dos anos&#46; Estas infe&#231;&#245;es associam-se a elevada morbimortalidade&#46; A sua epidemiologia na regi&#227;o centro do pa&#237;s n&#227;o &#233; conhecida&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Objetivo e m&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Pretende-se caracterizar a nossa popula&#231;&#227;o de doentes com infe&#231;&#245;es de dispositivo atrav&#233;s dum estudo retrospetivo&#44; incluindo 3158 doentes consecutivos que implantaram dispositivos no nosso centro&#44; entre janeiro de 2008 e setembro de 2014&#44; e realizar uma revis&#227;o do tema &#224; luz do estado da arte&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">A taxa de infe&#231;&#227;o na nossa popula&#231;&#227;o foi de 1&#44;48&#37; &#40;<span class="elsevierStyleItalic">pacemakers</span> 1&#44;21&#37;&#44; desfibrilhadores e dispositivos de ressincroniza&#231;&#227;o 5&#44;40&#37;&#41;&#46; A popula&#231;&#227;o inicial era constitu&#237;da por 47 doentes&#46; Tinham idade m&#233;dia de 65<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>19 anos e predom&#237;nio do g&#233;nero masculino &#40;72&#44;3&#37;&#41;&#46; Foram predominantemente infe&#231;&#245;es em <span class="elsevierStyleItalic">pacemakers</span>&#44; ap&#243;s primeira implanta&#231;&#227;o e com surgimento tardio&#46; A apresenta&#231;&#227;o cl&#237;nica foi variada&#44; apresentando-se a maioria com febre e altera&#231;&#245;es inflamat&#243;rias locais&#46; Identificaram-se nas hemoculturas&#44; predominantemente&#44; microrganismos gram positivos&#46; A antibioterapia emp&#237;rica inicial realizada foi vancomicina associada a gentamicina em 57&#37; dos casos&#59; extra&#231;&#227;o do dispositivo foi realizada em 72&#37;&#46; Durante o seguimento &#40;32<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>22 meses&#41; morreram oito doentes &#40;17&#37;&#41;&#44; sete dos quais de causa cardiovascular &#40;15&#37;&#41; e verificaram-se sete reinternamentos por reinfe&#231;&#227;o &#40;15&#37;&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclus&#227;o</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">A taxa de infe&#231;&#227;o &#233; baixa e semelhante a outras s&#233;ries&#44; sendo superior em desfibrilhadores e dispositivos de ressincroniza&#231;&#227;o&#46; Ap&#243;s a admiss&#227;o inicial para tratamento antibi&#243;tico<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>extra&#231;&#227;o&#44; o progn&#243;stico foi bastante favor&#225;vel&#46;</p></span>"
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            "titulo" => "Objetivo e m&#233;todos"
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      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Fernandes A&#44; Cassandra M&#44; Trigo J&#44; et al&#46; Endocardite de dispositivos&#44; revis&#227;o com base na experi&#234;ncia de um centro&#46; Rev Port Cardiol&#46; 2016&#59;35&#58;351&#8211;358&#46;</p>"
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          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">CRT&#58; cardiac resynchronization therapy device&#59; ICD&#58; implantable cardioverter-defibrillator&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Infection rate&#44; &#37;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Pacemaker</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">ICD&#47;CRT</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Type of infection&#44; &#37; &#40;n&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Late-onset&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">70&#46;2 &#40;33&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>First implantation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">63&#46;3 &#40;30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Previous infection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">38&#46;3 &#40;18&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Pocket infection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">72 &#40;34&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Endocarditis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">28 &#40;13&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Type of device&#44; &#37; &#40;n&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Pacemaker&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">76&#46;6 &#40;36&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>ICD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17 &#40;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>CRT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&#46;4 &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Clinical presentation&#44; &#37; &#40;n&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Signs of local inflammation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">76&#46;6 &#40;36&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Fever&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">59&#46;6 &#40;28&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Erosion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">42&#46;6 &#40;20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Systemic symptoms&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25&#46;5 &#40;12&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Fever of no apparent cause&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&#46;4 &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Embolic events&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;3 &#40;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Predictors of infection&#44; &#37; &#40;n&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Antibiotic prophylaxis prior to implantation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">100 &#40;47&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hypertension&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">61&#46;7 &#40;29&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Diabetes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">44&#46;7 &#40;21&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Severe cardiac dysfunction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">21&#46;3 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Oral anticoagulation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17 &#40;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Smoking&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&#46;6 &#40;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Chronic renal disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&#46;5 &#40;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Long-term corticosteroid therapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;3 &#40;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hematoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Temporary pacemaker&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Follow-up&#44; &#37; &#40;n&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>In-hospital mortality&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&#46;5 &#40;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Mortality during follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17 &#40;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Reinfection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14&#46;9 &#40;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">TEE&#58; transesophageal electrocardiography&#59; TTE&#58; transthoracic echocardiography&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Blood cultures&#44; &#37; &#40;n&#41; &#40;100&#37;&#44; n&#61;47&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">57&#46;4 &#40;27&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Microorganism isolated&#44; &#37; &#40;n&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Staphylococcus aureus</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17&#46;0 &#40;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">S&#46; epidermidis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">27&#46;7 &#40;13&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">S&#46; hominis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;2 &#40;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Pseudomonas aeruginosa</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&#46;5 &#40;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Echocardiography &#40;n&#61;45&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>TTE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>TEE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Lead vegetations&#44; &#37; &#40;n&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">29&#46;8 &#40;14&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>TTE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>TEE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Valve involvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17 &#40;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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        "etiqueta" => "Table 3"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">1&#46; Definitive infective endocarditis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Pathological criteria</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Microorganisms demonstrated by culture or histologic examination of a vegetation&#44; a vegetation that has embolized&#44; or an intracardiac abscess specimen&#59; or&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Microorganisms demonstrated by culture of the lead tip&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Clinical criteria&#58; 2 major or 1 major and 3 minor or 5 minor&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Major</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Blood culture positive for infective endocarditis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Typical microorganisms from two separate blood cultures&#44; defined as follows&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Microorganisms consistent with endocarditis in two blood cultures drawn &#8805;12 h apart&#44; or&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>All of three blood cultures or a majority of four separate cultures&#44; with first and last sample drawn at least 1 h apart&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Evidence of endocardial involvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Vegetations on echocardiogram&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Intracardiac mobile masses on leads or on the endocardium in contact with leads&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Abscess in contact with leads&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Minor</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Fever &#40;&#62;38<span class="elsevierStyleHsp" style=""></span>&#176;C&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Vascular phenomena&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Alternate diagnosis generally apparent&nbsp;\t\t\t\t\t\t\n
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          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">von Reyn criteria&#46;</p>"
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                    ]
                  ]
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                    0 => array:2 [
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                            0 => "J&#46;C&#46; Deharo"
                            1 => "A&#46; Quatre"
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                            0 => "F&#46; Victor"
                            1 => "C&#46; De Place"
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                            0 => "T&#46; Kleemann"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "C&#46; Romeyer-Bouchard"
                            1 => "A&#46; Costa"
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                  ]
                  "host" => array:1 [
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                      "doi" => "10.1093/eurheartj/ehp421"
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                    0 => array:2 [
                      "titulo" => "Cardiac device-related endocarditis&#58; epidemiology&#44; pathogenesis&#44; diagnosis and treatment &#8211; a review"
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