Contemporary cohort study in adult patients with infective endocarditis

Contemporary cohort study in adult patients with infective endocarditis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Contemporary cohort study in adult patients with infective endocarditis Mariana Giorgi Barroso Carvalho, Thatyane Veloso Almeida, Nicolas Feijoo, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4854250/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Infective endocarditis (IE) is a severe disease with a high mortality rate. Our aim was to describe a case series of adult patients with definite IE treated at a reference centre for cardiac surgery in Brazil, highlighting their specific characteristics. Methods A retrospective analysis of a prospectively implemented endocarditis database was conducted, including adult patients with definite IE according to the modified Duke criteria from January 2006 to June 2023. The analysis used the International Collaboration on Endocarditis case report form. Statistical analysis was performed using Jamovi®, version 1.2.2. Results There were 502 episodes of IE; the mean patient age ± SD was 48.4 ± 17.2 years. Community-acquired IE occurred in 64.7% of the patients, previous heart surgery was performed in 40.6%, and 39.0% of the patients had previous congestive heart failure (CHF). The main predisposing factors were rheumatic valve disease (RVD, 30.7%), valve prostheses (31.5%), and congenital heart disease (13.9%). Transthoracic and transoesophageal echocardiograms were performed in 85% and 78% of the patients, respectively. Left-sided IE was predominant. Fever occurred in 90.6% of patients, new murmurs in 50.7%, and embolism in 45%. Blood cultures were negative in 33.1% of the patients. The most common pathogens were oral streptococci (15.6%), Staphylococcus aureus (10.0%), and enterococci (12.8%). The main complications were CHF (58%), acute renal failure (32.8%), and splenic embolization (35.2%). Surgery was performed in 83.6% of the patients, and the in-hospital mortality rate was 25%. Conclusions In this centre, left-sided IE predominated, with negative blood cultures. Oral streptococci were the most frequently encountered pathogens and RVD was the main predisposing factor. Surgery was performed frequently, and the mortality rate was higher than that in developed countries but lower than that in developing countries. Infective endocarditis Epidemiology Cohort Study Surgery Mortality Figures Figure 1 Figure 2 Figure 3 Introduction Infective endocarditis (IE) is an infection of the endocardium, the lining surface of the heart chambers, primarily affecting the cardiac valves (native or prosthetic), non-valvular endocardial surfaces, and intracardiac devices. It is a serious condition with high morbidity rates, leading to complications such as heart failure and embolism [ 1 ]. The epidemiology of IE varies depending on host factors and causative agents. In recent decades, despite improvements in diagnostic and therapeutic strategies, the incidence of IE has been increasing worldwide. This increase may be due to longer life expectancy, improved healthcare access, and increased use of cardiac devices and implants [ 1 – 3 ]. Consequently, the epidemiology in high-income countries has significantly shifted, with an increase in older patients affected by IE, prosthetic valve endocarditis (PVE), and device-related endocarditis within this population. However, studies in low- and middle-income countries still highlight rheumatic valve disease (RVD) and uncorrected congenital heart diseases as common predisposing factors [4; 5]. Therefore, the aim of our study was to analyse the epidemiological, clinical, microbiological, echocardiographic characteristics, as well as complications and outcomes of IE over the past 17 years at a tertiary hospital in Rio de Janeiro (Brazil), and to compare these findings with those of other series from low-, middle-, and high-income countries. Methods Study scenario The National Institute of Cardiology (Instituto Nacional de Cardiologia, INC) is a public tertiary care medical centre offering high-complexity cardiology care and cardiac surgery, including heart transplantation and, more recently, lung transplantation, in Rio de Janeiro, Brazil. The institute has 165 beds, 45 of which are adult intensive care beds, and it is a teaching hospital, training cardiology and cardiac surgery residents. Annually, it performs approximately 1,200 surgeries and conducts 50,000 medical outpatient consultations. The Department of Heart Valve Diseases provided an average of 5,989 outpatient consultations annually between 2019 and 2023, with an average of 207 valve surgeries per year during this time span. Study population and study design This was a prospective observational cohort study of consecutive adult patients with IE hospitalised at the INC in Rio de Janeiro, Brazil. The study included only adult patients meeting the definite criteria for IE according to the modified Duke criteria [ 6 ], spanning from 1 January 2006 to 30 June 2023. Study variables were collected using standardised International Collaboration on Endocarditis case report forms as previously described [ 2 ]. Data analysis was conducted post hoc . Variables analysed Data included patient demographics, epidemiological and clinical data, underlying cardiac conditions, comorbidities, and predisposing factors for IE. Clinical manifestations, complications, causative microorganisms, echocardiographic findings, surgeries, and outcomes were assessed. Laboratory parameters such as erythrocyte sedimentation rate, C-reactive protein (CRP) levels, rheumatoid factor, and urinalysis results were obtained. Descriptions of the operative procedures were obtained from electronic and physical notes. Literature review A literature search was conducted using the virtual library databases PubMed and Virtual Health Library (Biblioteca Virtual em Saúde, BVS). The following descriptors were used: ‘endocarditis’, ‘epidemiology’, ‘cohort studies’, and their respective terms in Portuguese. The inclusion criteria were similar to those of epidemiological studies on the topic from the last 10 years (2014–2024), with a minimum sample size of 100 participants, most of whom fulfilled definite IE according to the modified Duke criteria. The exclusion criteria were multicentre studies, studies published more than 10 years ago, and studies with a sample size of less than one 100 participants. The selected manuscripts were included in an Excel spreadsheet (Supplementary Material) and used in the Discussion section. Definitions The definitions of IE were based on the modified Duke criteria, as well as guidelines from the European Society of Cardiology (ESC) in 2015 and 2023 for the management of IE [1; 6–7]. Community-acquired and healthcare-associated IE were defined according to the ESC 2009 guidelines [ 8 ]. Individuals with healthcare-associated IE were categorised as those manifesting IE 48 h after hospital admission or acquired IE through an invasive procedure performed within the past 8 weeks before symptom development [1; 7]. Early PVE was defined as that occurring within 1 year of heart valve surgery and associated with healthcare. Late PVE was defined as occurring 12 or more months after valve implantation. Pacemaker (PM)-and implantable cardioverter defibrillator (ICD)-related IE were considered healthcare-associated if they occurred within 1 year of device insertion [1; 6–7] Minor clinical criteria included fever > 38.0°C, predisposition to IE, and vascular or immunologic phenomena. Major criteria included typical microorganism isolated from two separate blood cultures, evidence of endocardial involvement on echocardiography, and new valvular regurgitation [1; 6]. The diagnosis of definite IE requires two major criteria, or one major and three minor criteria. St. Thomas’ minor criteria were also employed to improve diagnostic yield [ 9 ]. IE was classified as acute, with sudden onset and rapid progression presenting within 1 month; subacute, with symptoms evolving between 1 and 6 months after onset; and chronic, with symptoms persisting for more than 6 months [1; 6–7]. Embolic events were diagnosed clinically and radiologically. All patients with definite IE had systematic imaging techniques performed at the study site, usually contrast-enhanced computed tomography scans, for evaluation of emboli to the central nervous system, abdomen (in left-sided endocarditis), and thorax (in device-related and right-sided endocarditis) [1; 6–7]. Heart failure and comorbidities, such as chronic obstructive pulmonary disease, coronary artery disease, atrial fibrillation, atrial flutter, cerebrovascular disease, systemic arterial hypertension (SAH), chronic kidney disease (CKD), cancer, cirrhosis, connective tissue disease, and HIV were diagnosed based on medical records. Acute kidney injury was defined as a creatinine clearance rate < 60 mL/min/1.73 m 2 [1; 6–7]. Surgical indications were based on the ESC 2005 guidelines [ 10 ] (and its subsequent versions) for the management of IE, including heart failure, uncontrolled infection, vegetation > 10 mm, or evidence of embolic events [ 1 ]. Prior antibiotic use referred to the administration of antibiotics at any time before IE diagnosis [1; 6–7]. Echocardiographic data Transthoracic echocardiography (TTE) was routinely performed in all patients. Transesophageal echocardiography (TEE) was performed to detect cases with negative TTE results, complementary TTE data, and prosthetic and device-related endocarditis. Both TTE and TEE were performed by the echocardiography service at INC. The variables included in the standardised case report form were the presence of vegetation, regurgitation, abscess, leaflet perforation, pseudoaneurysm, and fistulas between the cardiac chambers. Additionally, variables such as ejection fraction, systolic pulmonary artery pressure, and the size of the largest vegetation on its longest axis in millimetres were collected. Microbiological data Peripheral venous blood cultures were collected using sterile techniques, with a minimum of two sets, as per institutional protocol, and incubated for 5 days in the BACTEC 9240 system (BACTEC/ALERT®, BioMérieux, Durham, NC, USA). Bacterial identification and antimicrobial susceptibility testing were performed using an automated VITEK 2 system (BioMérieux). The minimum inhibitory concentrations of vancomycin and daptomycin were determined using the E-test for methicillin-resistant Staphylococcus aureus . A subset of patients had surgically excised valves studied by 16SrRNA sequencing [ 11 ]. Serological and molecular analyses of Coxiella burnetii and Bartonella spp. were performed at the reference laboratory at Fundação Oswaldo Cruz (Laboratório de Hantaviroses e Rickettsioses) in cases of culture-negative endocarditis with strong epidemiological suspicion and no reported history of prior antimicrobial use [ 11 ]. Statistical Analysis Data were stored in a Microsoft Office Excel spreadsheet. Qualitative data were expressed as absolute and relative frequencies. Quantitative data were presented as frequencies, mean ± standard deviation, median, and interquartile range. Statistical analyses were conducted using Jamovi®, version 1.2.2. Statistical significance was set at p < 0.05. Categorical data were described as frequencies and percentages. The normality of the numerical variables was assessed using the Kolmogorov–Smirnov test. Proportions were compared using the chi-squared test. Ethical Aspects This study was approved by the Ethics Committee of INC (approval number, 5.770.094; Certificate of Presentation for Ethical Appreciation, 65137922.7.0000.5272). Informed consent was obtained from each patient or their legal representative, and the study protocol adhered to the ethical guidelines of the Helsinki Declaration of 1975 and its modifications. Results Number of cases of definitive IE in adults Between 1 January 2006 and 30 June 2023, our database identified 502 episodes of definite IE in 481 patients (19 patients had two episodes and one patient had three episodes during the study period). The annual distribution of endocarditis cases per year (excluding 2023 as cases were included until June) is depicted in Fig. 1 . General features of the cohort The mean age of the patients in the cohort was 48 ± 17.2 years, with a ratio of approximately two males for each female (327/502, 65.1% vs 175/502, 34.9%). Individuals over 60 years of age accounted for 149/502 (29.7%) of the sample. A total of 260/501 (51.9%) patients were transferred from other centres. Native and prosthetic valve IE occurred in 68.5% and 31.5% of cases, respectively. Early prosthetic valve IE occurred in 59/502 (11.8%) cases and late prosthetic valve IE in 99/502 (19.7%) cases. Community-acquired IE occurred in 324 (64.7%) patients, healthcare-associated nosocomial IE in 128 (25.5%), and healthcare-associated non-nosocomial IE in 49 (9.8%) (Table 1 ). Table 1 Features of definitive IE acquisition in adults, INC, 2006–2023. ACQUISITIONS n/N (%) Community-acquired IE 324/501 (64.7) Nosocomial IE 128/501 (25.5) Healthcare-associated IE 49/499 (9.8) HD-associated IE 54/501 (10.8) Early prosthetic IE 59/501 (11.8) Late prosthetic IE 99/502 (19.7) Device-associated IE 37/502 (7.4) n/N = absolute number of findings/total number of episodes with available data; IE: Infective Endocarditis; HD: Haemodialysis Patients’ medical history and comorbidities In terms of medical history, half of the patients (50.3%) had systemic arterial hypertension, 196 (39.0%) had congestive heart failure (CHF), 107 (21.4%) had CKD, and 40.6% had undergone previous cardiac surgery, mostly vale replacement. The main predispositions for IE were valve prostheses (158/502; 31.5%), RVD in 151/492 (30.7%), congenital heart disease in 70/502 (13.9%), and previous IE in 63 (12.6%) patients (Table 2 ). Table 2. Comorbidities, past medical history, and predisposition for IE in adult patients with definitive IE, INC, 2006-2023. Systemic arterial hypertension 237/471 (50.3) CHF 203/500 (40.6) HF 196/502 (39) CKD 107/507 (21.4) Dyslipidemia 88/448 (19.6) Atrial fibrillation/flutter 87/493 (17.6) Diabetes mellitus 76/502 (15.1) CAD 71/498 (14.3) Cerebrovascular disease 34/502 (6.8) Percutaneous coronary intervention 32/499 (6.4) Myocardial revascularization surgery 25/499 (5) Neoplasia 27/502 (5.4) COPD 19/499 (3.8) HIV/AIDS 7/480 (1.4) Pacemaker 54/502 (10.8) Intracardiac device 13/502 (2.6) Others* 18 (3.8) PREDISPOSITION Prosthesis 158/502 (31.5) RVD 151/492 (30.7) Congenital heart disease 70/502 (13.9) Previous IE 63/501 (12.6) IV drug use 6/502 (1.2) *Others = collagen disease (3/501–0.6%), cirrhosis (5/501–1.0%), immunosuppressive use (10/450–2.2%) n/N = absolute number of findings/total number of episodes with available data. IE = infective endocarditis; CHF: Congestive heart failure; HF: heart failure; CKD: chronic kidney disease; CAD: Coronary artery disease; COPD: chronic obstructive pulmonary disease; HIV: Human Immunodeficiency Virus; AIDS = acquired immunodeficiency syndrome; RVD: rheumatic valve disease; IV: Intravenous. Clinical and laboratory manifestations of IE cases Most endocarditis cases presented acutely (52%), followed by subacute (41.3%) and chronic progression (32/496 cases, 6.4%). The most common clinical-laboratory manifestation of IE was fever in 454/501(90.6%), followed by elevated C-reactive protein (CRP) in 329/455 (72.3%) and presence of new regurgitant murmurs (50.7%). Approximately one-third of the patients had an elevated erythrocyte sedimentation rate 104/328 (31.7%), half had an embolic vascular event (45%), and splenomegaly (19.2%) was also a frequent clinical manifestation. Osler’s nodes, Janeway lesions, and conjunctival haemorrhage were observed in less than 5% of the cases. The clinical manifestations are shown in Fig. 2 . Microbiological characteristics Blood cultures were drawn from 495/502 (98.6%) patients. They were positive in 339/495 (68.5%) patients. Serology was performed in less than 5% of the cases (23/502; 4.6%). Culture-negative IE cases accounted for 33.1% of all blood cultures collected. Among positive blood cultures, oral streptococci and enterococci were the most frequent, followed by S. aureus and coagulase-negative staphylococci. Typical microorganisms such as streptococci of the bovis and HACEK groups ( Haemophilus species, Aggregatibacter species , Cardiobacterium hominis, Eikenella corrodens and Kingella species; Trichosporon s p, Coxiella burnetii; Bartonella henselae ). were infrequent and found in less than 5% of the cases. Non-HACEK gram-negative bacteria were more frequent than in the HACEK group. The aetiology of IE is shown in Fig. 3 . Echocardiographic features TTE was performed in 425/500 (85%) cases, whereas TEE was performed in 390/500 (78%) cases. Regardless of the involvement of native or prosthetic valves, the most frequent location of vegetation was the mitral valve (MV) (221/498, 46.9%) and the aortic valve (189/499, 37.9%). PM or ICD infections were reported in 37/501 (7.4%) cases. The main echocardiographic findings were vegetation (82.9%), MV vegetations 235/501 (46.9%), MV regurgitation (221/498; 44.4%), and aortic valve regurgitation (207/501; 37.9%). Complications of IE observed on echocardiography included abscesses (15.2%), perforation of the valve apparatus (17.2%), and prosthetic valve dehiscence (4.5%). When comparing early and late prosthetic valve IE and native IE, fistulae were found in 2/59 (3.4%), 2/98 (2%), and 19/345 (5.5%) patients, respectively, whereas abscesses were found in 11/59 (18.6%), 24/98 (24.5%), and 41/345 (11.9%) patients, respectively. Early prosthetic dehiscence occurred in 5 of 59 (8.5%) episodes, and in 10 of 95 (10.5%) episodes of late prosthetic IE. The mean pulmonary arterial systolic pressure was 45.9 mmHg. Echocardiographic findings are summarised in Table 3. ECOCARDIOGRAPHIC CHARACTERISTICS n/N (%) Table 3 Echocardiographic findings in adult patients with definite IE, INC, 2006-2023. TTE 425/500 (85) TEE 390/500 (78) New moderate to severe regurgitation Aortic 189/499 (37.9) Mitral 221/498 (44.4) Tricuspid 82/500 (16.4) Pulmonary 2/500 (0.4) Vegetation Frequency of vegetation (%) (82.9) Maximum vegetation size (mm) (48) Aortic valve 207/501 (41.3) Mitral valve 235/501 (46.9) Tricuspid valve 25/501 (5) Pulmonary valve 6/501 (1.2) Chord 10/500 (2) Catheter 3/501 (0.6) Device lead 37/50 (7.4) Myocardial wall 14/501 (2.8) Complications Valve perforation 86 (17.2%) Abscess 76 (15.2%) Cardiac fistula 21/500 (4.2) Prosthetic dehiscence 19/422 (4.5) Quantitative variables EF M = 58.8% (SD: 38) PASP M = 45.9 mmHg (SD: 17,98) n/N = absolute number of findings/total number of episodes with available data; TTE: Transthoracic echocardiogram; TEE: transesophageal echocardiogram; EF: Ejection fraction; PASP: Pulmonary artery systolic pressure; M: mean; SD: standard deviation Complications and outcomes of IE cases Among the complications of IE episodes (Table 4 ), acute heart failure was the most frequent, occurring in more than half of the patients (291/502, 58%), followed by acute renal failure (156/476, 32.8%), central neurological events (131/501, 26.1%), and myocardial or paravalvular abscesses (108/501, 21.6%). Embolization was also frequently seen, with splenic emboli being the most common with 176/500 cases (35.2%), followed by emboli to the central nervous system in 131/501 cases (26.1%). The lungs were affected in 5.4% of all cases and in 10/35 cases (28.5%) of device-related endocarditis. The overall mortality rate was 125/500 (25%) (Table 5 ). Among all the patients, 415 (82.6%) had surgical indications. Of these patients, 347 (83.6%) underwent surgery. Among patients who underwent surgery, the mortality rate was 21.3% (74/347). Among the 68 patients who had a surgical indication but did not operate, 39/68 died (mortality rate: 57.4%). This difference was statistically significant (p < 0.001, chi-squared test). Only 53 patients did not have surgical indications; among them, 10 died, representing a mortality rate of 18.9%. Discussion IE is a severe condition with a high risk of complications and mortality, requiring specialised multidisciplinary management. This study presented a series of 502 episodes of definite IE in adult patients, diagnosed according to the modified Duke criteria, at a federal public hospital in Rio de Janeiro. Few case series of IE have been reported from Brazilian centres [ 12 – 14 ] and other low- and middle-income countries. To facilitate the discussion, we compiled Tables 1 – 4 from the literature (Supplementary Material). Our study revealed a mean patient age of 48 years, consistent with the literature indicating that younger age groups are more commonly affected in the low- and middle-income countries [ 15 – 19 ]. This finding is associated with the frequent presence of rheumatic valvopathy as a predisposing factor, leading to earlier onset of IE [17; 18]. Rheumatic valvopathy was also prevalent in two other Brazilian studies from Southeastern centres [12; 13]. In contrast, a larger IE series by Murdoch et al. [ 2 ], which included 2,781 adults from 58 hospitals across 25 countries from 2000 to 2005, reported a median age of 57.9 years. The EURO-ENDO study [ 20 ], including 3,116 patients from 2016 to 2018, predominantly from European centres, reported a median age of 65 years. Recent case series from European countries have also reported higher mean ages compared to our study [21; 22]. The most common underlying cardiac conditions in this cohort were rheumatic valvopathy (30.7%) and congenital heart disease (13.9%), which is consistent with the literature. Studies from other developing countries, such as French Polynesia [ 23 ], Saudi Arabia [ 18 ], and China [ 17 ] have also highlighted these conditions as significant predispositions for IE. Rheumatic valvopathy was present in 15% of patients in Saudi Arabia [ 18 ], 33% in French Polynesia [ 23 ], and 17% in China [ 17 ] (Supplementary Table 1). Regarding the male-to-female ratio, our study showed a male predominance, similar to studies from East Asia [ 18 ] (67%), Africa [ 19 ] (67.1%), and South America [ 15 ] (68.7%), as well as studies from developed countries [21–22; 24] (Supplementary Table 1). Although IE was once considered a rare disease, the literature has reported a significant increase in cases over time, both in developed and developing countries. Similarly, we found an increasing trend in the number of cases over the study period. This higher incidence is likely related to an increase in high-risk populations, including older adults, individuals with multiple comorbidities, and those undergoing haemodialysis [8; 12; 20]. This trend supports CHF and chronic renal failure as prevalent comorbidities among patients who developed IE at our centre. IE on native valves occurred in 68.5% of patients, with a higher incidence on the aortic and mitral valves, similar to observations in both developed and developing countries [2; 5; 12; 14; 17–18; 20–21; 25]. Prosthetic valve endocarditis accounted for 31.47% of cases, similar to findings in Italy [ 22 ], Saudi Arabia [ 18 ], Turkey [ 26 ], and other Brazilian studies (27.1%; 48.4%) [ 12 – 13 ]. Despite the predominant involvement of native valves, the incidence of prosthetic valve endocarditis has increased, consistent with the rising number of valve surgeries in recent years [ 28 ]. In low- and middle-income countries, the incidence of prosthetic valve endocarditis is significantly lower than that of native valve endocarditis, possibly due to limited access to healthcare and fewer valve replacements [17; 26]. The incidence of IE in implantable cardiac electronic devices has shown an increasing trend owing to higher device insertion rates, population aging, and increased comorbidities. In this study, it represented approximately 8% of all cases over the past 17 years, a proportion similar to that reported in Argentina, China, and Turkey [15–16; 26] (Supplementary Table 2). The signs and symptoms of IE vary depending on the severity of the infection. The most relevant classical signs and symptoms observed were fever (90.6%) and heart murmur (50.7%), consistent with other studies (Supplementary Table 4). Classic Oslerian manifestations of endocarditis were present in only 3% of patients upon hospital admission, aligning with findings from other Brazilian [ 13 ] and Chinese [ 17 ] studies. Notably, most patients did not exhibit the classic clinical findings traditionally associated with IE. Although embolic manifestations were frequent (45%) in this cohort, other studies reported a lower proportion despite a significant number of cases [13–14; 17; 21; 29; 30]; in our study, emboli were often detected radiologically rather than clinically. This underscores the recommendation for echocardiography in cases of bacteraemia and screening for embolic events, even in asymptomatic patients [ 31 ]. In comparison with published literature from Argentina [ 15 ], China [ 17 ], and the USA [ 32 ], the vegetation rate in our study (82.9%) closely aligns with the rates reported in these studies (80.9%, 86%, and 84.1%, respectively) (Supplementary Table 2). However, the proportion of patients who underwent TEE in this cohort (78%) was significantly higher than that reported in a Chinese study (12.8%). This contrasts with the 2015 ESC guidelines on IE [ 1 ], which recommend performing TEE to exclude perivalvular complications, even if TTE shows findings compatible with IE. The high frequency of TEE in our study reflects the setting of a highly specialised surgical cardiology hospital. The lower utilisation of TEE in other studies may have led to lower detection rates of perivalvular complications such as valve perforation and perivalvular abscess, potentially resulting in diagnostic errors in patients with subtle or early valvular lesions. The number of positive blood cultures in this study was lower than that in studies from developed countries [21; 25; 27; 29] but higher than those from developing countries [ 16 – 18 ], as demonstrated in Supplementary Table 3. Brazilian studies reported blood culture positivity rates of 66.5% [ 12 ], 76.9% [ 13 ], and 76.6% [ 14 ]. The low rate of microbiological detection may be related to antibiotic use before blood culture collection, as previously described by our group, where the rate of prior antibiotic use reached 75% [ 11 ]. Additionally, over half of the patients in our centre were referred from other medical institutions, where antibiotic treatment is often initiated before blood cultures are collected. Oral streptococci were the primary etiological agents used in this study. Likewise, studies from Argentina and China [ 15 – 16 ] show predominance of oral streptococci, in contrast to those in developed countries [25; 27], where S. aureus has become the main aetiology (Supplementary Table 3). The increase in staphylococcus infections is primarily attributed to the high incidence of infections among intravenous drug users [5; 25], patients undergoing haemodialysis [ 25 ], and older patients with comorbidities. However, the proportion of intravenous drug users and octogenarians was low in our cohort compared to developed countries [25; 27; 32]. Notably, poor oral health in patients treated by the Brazilian public health system may contribute to the prevalence of oral streptococci [ 11 , 33 ]. The complications of IE are widespread and can affect multiple organs. Systemic embolization is the most frequent complication included in the Duke diagnostic criteria [ 28 ]. The sites of embolization depend on the affected valves and may involve the spleen, liver, kidneys, lungs, brain, vertebral bodies, and iliac and mesenteric arteries. Left-sided involvement commonly leads to splenic and cerebral emboli, while right-sided involvement causes pulmonary emboli [ 28 ]. Detection of these complications is often hindered by delayed diagnosis [7; 30; 31]. As shown in Supplementary Table 4, embolization was the most frequently reported complication, although not all studies specified the affected areas. All studies reviewed demonstrated a higher incidence of left-sided endocarditis than right-sided endocarditis, resulting in more splenic embolization. Surgery is indicated to prevent progressive and irreversible structural damage and is justified in patients at high risk where cure with antibiotic therapy alone is unlikely and in those who do not have comorbidities or severe complications that make recovery prospects remote [1; 7]. This review revealed that a wide range of patients underwent surgery for IE, from 17.2% in Japan [ 24 ] to 69.7% in Turkey [ 26 ]. Studies from the USA have demonstrated surgical indication rates of approximately 25% [ 25 , 32 ], which are lower than those in our cohort (Supplementary Table 4). Although the USA is a high-income country, intravenous drug abuse has increased substantially, contributing to the predisposition of individuals to IE and the acquisition of more virulent pathogens [ 25 ]. This increase has significant consequences because IE due to S. aureus infection is associated with a higher likelihood of requiring surgical treatment and worse overall outcomes. The study with the lowest surgical indication rate in this review was Japan [ 24 ] (17.2%), which despite also being a high-income country, has an older average population age (69.1 ± 14 years) with multiple comorbidities, often reducing the drive for surgical intervention. Unfortunately, our cohort did not have sufficient power to compare patients who underwent early intervention with those who underwent late surgery. However, our study provided evidence supporting the assumption that surgically treated patients have better outcomes than conservatively managed patients. Early surgery is recommended (and reduces mortality) in cases of IE with complications such as embolic events, CHF, and valvular abscesses [1; 4; 7; 37]. Despite improvements in the diagnostic accuracy, medical therapy, and surgical techniques, IE mortality rates remain relatively high worldwide. In our study, we observed an overall hospital mortality rate of 25%, which is similar to the rates observed in Japan [ 24 ] (26.1%) and Turkey [ 26 ] (22.6%). However, these results were lower than those of other studies, such as French Polynesia [35] (37%) and Spain [ 21 ] (34.7%). This may be due to the younger age of our patients and lower proportion of infections caused by S. aureus . Oral streptococcal species were the most frequently identified microorganisms in our study, which may have contributed to the favourable outcomes. Additionally, early surgery has been reported to improve the prognosis of IE. Thus, early surgery for IE has been increasingly performed in recent years, likely contributing to the gradual decline in IE hospital mortality rates at some centres [ 29 ]. Available studies in Brazil have reported higher mortality rates than ours (Minas Gerais, 32%; São Paulo, 33%; and Rio Grande do Sul, 41.9%) [ 12 – 14 ]. These higher rates may be attributed to differences in patient profiles, with a prevalence of multiple comorbidities, and differences in hospital profiles, as ours is a referral centre in cardiology with a tendency to perform early surgeries [12–14; 23–24]. The main limitation of our study was the retrospective, single-centre nature at a cardiac surgery referral centre, which may not represent the profile of the entire Brazilian and South American healthcare systems. Therefore, our findings cannot be generalised, and the results may have been influenced by this limitation. A significant strength of our study is that it included one of the largest cohorts of adult patients with definite IE, with prospectively collected data, in Latin America. Conclusion This study presents the IE profile and mortality analysis in a large cohort of patients spanning a 17-year period, representing a rare initiative in a middle-income country. Blood culture-negative endocarditis is frequent in young men, while oral streptococci remain the primary etiological agents. The high mortality rate observed in this cohort underscores the importance of studies on IE, as they provide a better understanding of the clinical and microbiological characteristics, as well as factors associated with unfavourable prognosis. This could contribute to the development of improved strategies. Declarations Author Contribution C.C.L was responsible for the concept of the work.M.C., T.A., N.F., R.G.,G.B.,G.C.,W.G.,C.W.,B.Z.,C.C.L acquired dataM.C., T.A., M.G.C.,C.C.L.were responsible for data analysis and interpretation:M.C.,T.A.,C.C.L. drafted the work (text, tables and figures).C.C.L. revised it critically for important intellectual contentAll authors approved the final draft. Acknowledgement We acknowledge Ms. Cyntia Aguiar for technical help as a librarian in the systematic literature search. We also acknowledge all medical and nursing staff who looked after the patients , as well as the supporting staff in the microbiology, radiology and echocardiography departments. Data Availability Data is provided within the manuscript or supplementary information files References Habib G, et al. 2015 ESC guidelines for the management of infective endocarditis. Kardiol Pol. 2015;73(11):963–1027. Murdoch DR, et al. Clinical presentation, etiology, and outcome of infective endocarditis in the 21st century: the International Collaboration on Endocarditis-Prospective Cohort Study. Archives Intern Med vol. 2009;169(5):463–73. 10.1001/archinternmed.2008.603 . Holland TL et al. Sep. Infective endocarditis. Nature reviews. Disease primers vol. 2 16059. 1 2016, 10.1038/nrdp.2016.59 Thuny F et al. Management of infective endocarditis: challenges and perspectives. Lancet. 2012;379(9819):965–975. doi: 10.1016/S0140-6736(11)60755-1. Epub 2012 Feb 7. PMID: 22317840. Baddour LM et al. Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications: A Scientific Statement for Healthcare Professionals from the American Heart Association. Circulation. 2015;132(15):1435-86. 10.1161/CIR.0000000000000296 . Epub 2015 Sep 1. Li JS, et al. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis. 2000;30(4):633–8. 10.1086/313753 . Epub 2000 Apr 3. Victoria D, ESC Scientific Document Group., 2023 ESC Guidelines for the management of endocarditis: Developed by the task force on the management of endocarditis of the European Society of Cardiology (ESC) Endorsed by the European Association for Cardio-Thoracic Surgery (EACTS) and the European Association of Nuclear Medicine (EANM), European Heart Journal, Volume 44, Issue 39, 14 October 2023, Pages 3948–4042, https://doi.org/10.1093/eurheartj/ehad193 Habib G et al. Guidelines on the prevention, diagnosis and treatment of infective endocarditis; the task force on the prevention, diagnosis, and treatment of infective endocarditis of the European society of cardiology. Eur Heart J 2009. Lamas CC, Eykyn SJ. Suggested modifications to the Duke criteria for the clinical diagnosis of native valve and prosthetic valve endocarditis: analysis of 118 pathologically proven cases. Clin Infect Dis. 1997;25(3):713-9. 10.1086/513765 . PMID: 9314466. Horstkotte D, et al. Guidelines on prevention, diagnosis and tre atment of infective endocarditis executive summary; the task force on infective endocarditis of the European society of cardiology. Eur heart J vol. 2004;25(3):267–76. 10.1016/j.ehj.2003.11.008 . Lamas CC, Fournier PE, Zappa M, et al. Diagnosis of blood culture-negative endocarditis and clinical comparison between blood culture-negative and blood culture-positive cases. Infection. 2016;44:459–66. https://doi.org/10.1007/s15010-015-0863-x . Siciliano RF, et al. Community-acquired culture-negative endocarditis: clinical characteristics and risk factors for mortality. Int J Infect Dis. 2014;25:191–5. Nunes MCP, et al. Outcomes of infective endocarditis in the current era: Early predictors of a poor prognosis. Int J Infect Dis. 2018;68:102–7. Tagliari AP, et al. Infective endocarditis profile, prognostic factors and in-hospital mortality: 6-year trends from a tertiary university center in South America. J Card Surg. 2020;35(8):1905–11. Kazelian LR, Gagliardi JA, Napoli Llobera ME, Lespada MI, Beck MA, Cianciulli TF. Experiencia en endocarditis infecciosa a lo largo de 30 años en un hospital de Buenos Aires [Experience in infective endocarditis over 30 years in a hospital in Buenos Aires]. Med (B Aires). 2021;81(6):939–45. Spanish.PMID: 34875591. Zhu W, Zhang Q, Zhang J. The changing epidemiology and clinical features of infective endocarditis: A retrospective study of 196 episodes in a teaching hospital in China. BMC Cardiovasc Disord. 2017;17(1):113. 10.1186/s12872-017-0548-8 . PMID: 28482820; PMCID: PMC5422999. Wu Z, Chen Y, Xiao T, et al. Epidemiology and risk factors of infective endocarditis in a tertiary hospital in China from 2007 to 2016. BMC Infect Dis. 2020;20:428. Barry M, Bari SA, Akhtar MY, Al Nahdi F, Erlandez R, Al Khushail A, Al Hebaishi Y. Clinical and Microbiological Characteristics of Infective Endocarditis at a Cardiac Center in Saudi Arabia. J Epidemiol Glob Health. 2021;11(4):435–43. Epub 2021 Nov 4. PMID: 34735715; PMCID: PMC8664328. Pecoraro AJK, Pienaar C, Herbst PG. et alCauses of infective endocarditis in the Western Cape, South Africa: a prospective cohort study using a set protocol for organism detection and central decision making by an endocarditis. teamBMJ Open. 2021;11:e053169. 10.1136/bmjopen-2021-053169 . Habib G, et al. Clinical presentation, aetiology and outcome of infective endocarditis. Results of the ESC-EORP EURO-ENDO (European infective endocarditis) registry: a prospective cohort study. Eur heart J vol. 2019;40(39):3222–32. Ballesta AIP, Vázquez EG, Gómez JG. Infective endocarditis treated in a secondary hospital: epidemiological, clinical, microbiological characteristics and prognosis, with special reference to patients transferred to a third level hospital. Rev Esp Quimioterapia. 2022; 35 (1): 35–42. Espanha. 10.37201/req/092.2021 Pallotto C, Martinelli L, Baldelli F, Bucaneve G, Cecchini E, Malincarne L, Pasticci MB. Aspetti epidemiologici e clinici delle endocarditi infettive in un Ospedale Universitario di medie dimensioni dell'Italia centrale: analisi di 232 casi [Trends in infective endocarditis in a medium-sized University Hospital in Italy: analysis of 232 cases]. Infez Med. 2014;22(2):124–31. Italian. PMID: 24955799. Blanchard V, et al. Infective endocarditis in French Polynesia: Epidemiology, treatments and outcomes. Arch Cardiovasc Dis. 2020;113(4):252–62. 10.1016/j.acvd.2019.12.007 . Epub 2020 Feb 15. PMID: 32070729. Hase R, Otsuka Y, Yoshida K, Hosokawa N. Profile of infective endocarditis at a tertiary-care hospital in Japan over a 14-year period: characteristics, outcome and predictors for in-hospital mortality. Int J Infect Dis. 2015;33:62–6. Epub 2015 Jan 7. PMID: 2. Liaqat W, et al. Epidemiologic and clinical characteristics of infective endocarditis: a single-center retrospective study in the Bronx. New York Infect. 2022;50(5):1349–61. 10.1007/s15010-022-01846-3 . Epub 2022 May 25. Agus HZ, et al. Characterization, epidemiological profile and risk factors for clinical outcome of infective endocarditis from a tertiary care centre in Turkey. Infect Dis (Lond). 2019;51(10):738–44. Epub 2019 Jul 31. PMID: 31364901. Holland DJ, Simos PA, Yoon J, Sivabalan P, Ramnarain J, Runnegar NJ. Infective Endocarditis: A Contemporary Study of Microbiology, Echocardiography and Associated Clinical Outcomes at a Major Tertiary Referral Centre. Heart Lung Circ. 2020;29(6):840–50. Epub 2019 Aug 2. PMID: 31402124. Mutagaywa RK et al. Infective endocarditis in developing countries: An update. Frontiers in cardiovascular medicine. 2022; 9:1007118. https://doi.org/10.3389/fcvm.2022.1007118 Kim JH, Lee HJ, Ku NS, Lee SH, Lee S, Choi JY, Yeom JS. Infective endocarditis at a tertiary care hospital in South Korea. Heart. 2021;107(2):135–41. Acibuca A, Yilmaz M, Okar S, Kursun E, Acilar O, Tekin A, Demiroglu YZ, Muderrisoglu IH. An epidemiological study to define the recent clinical characteristics and outcomes of infective endocarditis in southern Turkey. Cardiovasc J Afr. 2021 Jul-Aug 23;32(4):188–192. 10.5830/CVJA-2021-009 . Epub 2021 Apr 7. PMID: 33830167; PMCID: PMC8756046. Monteiro TS, et al. Asymptomatic and symptomatic embolic events in infective endocarditis: associated factors and clinical impact. Brazilian J Infect diseases: official publication Brazilian Soc Infect Dis vol. 2017;21(3):240–7. Kashef MA, Friderici J, Hernandez-Montfort J, Atreya AR, Lindenauer P, Lagu T. Quality of Care of Hospitalized Infective Endocarditis Patients: Report from a Tertiary Medical Center. J Hosp Med. 2017;12(6):414–20. 10.12788/jhm.2746 . PMID: 28574530; PMCID: PMC6005201. Bergan EH, et al. Impact of improvement in preoperative oral health on nosocomial pneumonia in a group of cardiac surgery patients: a single arm prospective intervention study. Intensive care Med vol. 2014;40(1):23–31. 10.1007/s00134-013-3049-y . Tables Tables 4 and 5 are available in the Supplementary Files section. Additional Declarations No competing interests reported. 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16:53:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4854250/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4854250/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":63126754,"identity":"0ad1462a-170c-482d-a706-525e964f702d","added_by":"auto","created_at":"2024-08-23 12:24:53","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":36776,"visible":true,"origin":"","legend":"\u003cp\u003eNumber of cases of infective endocarditis per year, INC 2006-2022\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4854250/v1/6b628484740169048668491a.png"},{"id":63126757,"identity":"dc482d2a-e4c6-4701-b668-29f1dac25f3a","added_by":"auto","created_at":"2024-08-23 12:24:54","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":26817,"visible":true,"origin":"","legend":"\u003cp\u003eClinical-laboratory manifestations of IE in adult patients with definite IE, INC, 2006-2023\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4854250/v1/8b27f324366297889e29a233.png"},{"id":63126759,"identity":"2c064486-c2a0-4e05-bf03-96d8f47a1033","added_by":"auto","created_at":"2024-08-23 12:24:59","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":68219,"visible":true,"origin":"","legend":"\u003cp\u003eCausative agents in 502 episodes of definite IE in adult patients, INC, 2006-2023.\u003c/p\u003e\n\u003cp\u003eCNS: coagulase-negative staphylococci; GNB: Gram-Negative bacteria; Other GP: \u003cem\u003eAbiotrophia defectiva\u003c/em\u003e (2); \u003cem\u003eCorynebacterium diphtheriae\u003c/em\u003e (2); \u003cem\u003eCorynebacterium amycolatum\u003c/em\u003e (1); \u003cem\u003eCutibacterium acnes\u003c/em\u003e (1); \u003cem\u003eGemella morbillorum\u003c/em\u003e (3); \u003cem\u003eGemella bergeri\u003c/em\u003e (1); \u003cem\u003eGranulicatella spp\u003c/em\u003e (4); \u003cem\u003eKocuria kristinae\u003c/em\u003e (1); \u003cem\u003eListeria monocytogenes\u003c/em\u003e (1); \u003cem\u003eStreptococcus agalactiae\u003c/em\u003e (3); \u003cem\u003eStreptococcus pneumoniae\u003c/em\u003e (2); \u003cem\u003eStreptococcus pyogenes\u003c/em\u003e (1). Others: HACEK (5): \u003cem\u003eHaemophilus species, Aggregatibacter species\u003c/em\u003e, \u003cem\u003eCardiobacterium hominis, Eikenella corrodens and Kingella species; Trichosporon s\u003c/em\u003ep (2), \u003cem\u003eCoxiella burnetii (2); Bartonella henselae\u003c/em\u003e(2).\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-4854250/v1/310b156afdb7683712184e95.png"},{"id":63127664,"identity":"40dee6ca-edce-442a-8e56-5288c1fc9d18","added_by":"auto","created_at":"2024-08-23 12:33:08","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":784169,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4854250/v1/d824f567-28d8-43ad-8e01-3870d34a221d.pdf"},{"id":63126756,"identity":"e00e594f-782b-4981-b739-a01d08119a2d","added_by":"auto","created_at":"2024-08-23 12:24:53","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":16268,"visible":true,"origin":"","legend":"","description":"","filename":"Tables4and5.docx","url":"https://assets-eu.researchsquare.com/files/rs-4854250/v1/12d64818e0d577182fff299e.docx"},{"id":63126755,"identity":"2857a627-0c00-4d9e-9590-7585c1312000","added_by":"auto","created_at":"2024-08-23 12:24:53","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":46271,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTables.docx","url":"https://assets-eu.researchsquare.com/files/rs-4854250/v1/15ee25c218ded7508b09613b.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Contemporary cohort study in adult patients with infective endocarditis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eInfective endocarditis (IE) is an infection of the endocardium, the lining surface of the heart chambers, primarily affecting the cardiac valves (native or prosthetic), non-valvular endocardial surfaces, and intracardiac devices. It is a serious condition with high morbidity rates, leading to complications such as heart failure and embolism [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe epidemiology of IE varies depending on host factors and causative agents. In recent decades, despite improvements in diagnostic and therapeutic strategies, the incidence of IE has been increasing worldwide. This increase may be due to longer life expectancy, improved healthcare access, and increased use of cardiac devices and implants [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eConsequently, the epidemiology in high-income countries has significantly shifted, with an increase in older patients affected by IE, prosthetic valve endocarditis (PVE), and device-related endocarditis within this population. However, studies in low- and middle-income countries still highlight rheumatic valve disease (RVD) and uncorrected congenital heart diseases as common predisposing factors [4; 5].\u003c/p\u003e \u003cp\u003eTherefore, the aim of our study was to analyse the epidemiological, clinical, microbiological, echocardiographic characteristics, as well as complications and outcomes of IE over the past 17 years at a tertiary hospital in Rio de Janeiro (Brazil), and to compare these findings with those of other series from low-, middle-, and high-income countries.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy scenario\u003c/h2\u003e \u003cp\u003e The National Institute of Cardiology (Instituto Nacional de Cardiologia, INC) is a public tertiary care medical centre offering high-complexity cardiology care and cardiac surgery, including heart transplantation and, more recently, lung transplantation, in Rio de Janeiro, Brazil. The institute has 165 beds, 45 of which are adult intensive care beds, and it is a teaching hospital, training cardiology and cardiac surgery residents. Annually, it performs approximately 1,200 surgeries and conducts 50,000 medical outpatient consultations. The Department of Heart Valve Diseases provided an average of 5,989 outpatient consultations annually between 2019 and 2023, with an average of 207 valve surgeries per year during this time span.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStudy population and study design\u003c/h2\u003e \u003cp\u003eThis was a prospective observational cohort study of consecutive adult patients with IE hospitalised at the INC in Rio de Janeiro, Brazil. The study included only adult patients meeting the definite criteria for IE according to the modified Duke criteria [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], spanning from 1 January 2006 to 30 June 2023. Study variables were collected using standardised International Collaboration on Endocarditis case report forms as previously described [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Data analysis was conducted \u003cem\u003epost hoc\u003c/em\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eVariables analysed\u003c/h2\u003e \u003cp\u003eData included patient demographics, epidemiological and clinical data, underlying cardiac conditions, comorbidities, and predisposing factors for IE. Clinical manifestations, complications, causative microorganisms, echocardiographic findings, surgeries, and outcomes were assessed. Laboratory parameters such as erythrocyte sedimentation rate, C-reactive protein (CRP) levels, rheumatoid factor, and urinalysis results were obtained. Descriptions of the operative procedures were obtained from electronic and physical notes.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eLiterature review\u003c/h2\u003e \u003cp\u003eA literature search was conducted using the virtual library databases PubMed and Virtual Health Library (Biblioteca Virtual em Sa\u0026uacute;de, BVS). The following descriptors were used: \u0026lsquo;endocarditis\u0026rsquo;, \u0026lsquo;epidemiology\u0026rsquo;, \u0026lsquo;cohort studies\u0026rsquo;, and their respective terms in Portuguese. The inclusion criteria were similar to those of epidemiological studies on the topic from the last 10 years (2014\u0026ndash;2024), with a minimum sample size of 100 participants, most of whom fulfilled definite IE according to the modified Duke criteria. The exclusion criteria were multicentre studies, studies published more than 10 years ago, and studies with a sample size of less than one 100 participants. The selected manuscripts were included in an Excel spreadsheet (Supplementary Material) and used in the \u003cspan refid=\"Sec21\" class=\"InternalRef\"\u003eDiscussion\u003c/span\u003e section.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eDefinitions\u003c/h2\u003e \u003cp\u003e The definitions of IE were based on the modified Duke criteria, as well as guidelines from the European Society of Cardiology (ESC) in 2015 and 2023 for the management of IE [1; 6\u0026ndash;7].\u003c/p\u003e \u003cp\u003eCommunity-acquired and healthcare-associated IE were defined according to the ESC 2009 guidelines [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Individuals with healthcare-associated IE were categorised as those manifesting IE 48 h after hospital admission or acquired IE through an invasive procedure performed within the past 8 weeks before symptom development [1; 7]. Early PVE was defined as that occurring within 1 year of heart valve surgery and associated with healthcare. Late PVE was defined as occurring 12 or more months after valve implantation. Pacemaker (PM)-and implantable cardioverter defibrillator (ICD)-related IE were considered healthcare-associated if they occurred within 1 year of device insertion [1; 6\u0026ndash;7]\u003c/p\u003e \u003cp\u003eMinor clinical criteria included fever\u0026thinsp;\u0026gt;\u0026thinsp;38.0\u0026deg;C, predisposition to IE, and vascular or immunologic phenomena. Major criteria included typical microorganism isolated from two separate blood cultures, evidence of endocardial involvement on echocardiography, and new valvular regurgitation [1; 6]. The diagnosis of definite IE requires two major criteria, or one major and three minor criteria. St. Thomas\u0026rsquo; minor criteria were also employed to improve diagnostic yield [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIE was classified as acute, with sudden onset and rapid progression presenting within 1 month; subacute, with symptoms evolving between 1 and 6 months after onset; and chronic, with symptoms persisting for more than 6 months [1; 6\u0026ndash;7].\u003c/p\u003e \u003cp\u003eEmbolic events were diagnosed clinically and radiologically. All patients with definite IE had systematic imaging techniques performed at the study site, usually contrast-enhanced computed tomography scans, for evaluation of emboli to the central nervous system, abdomen (in left-sided endocarditis), and thorax (in device-related and right-sided endocarditis) [1; 6\u0026ndash;7].\u003c/p\u003e \u003cp\u003eHeart failure and comorbidities, such as chronic obstructive pulmonary disease, coronary artery disease, atrial fibrillation, atrial flutter, cerebrovascular disease, systemic arterial hypertension (SAH), chronic kidney disease (CKD), cancer, cirrhosis, connective tissue disease, and HIV were diagnosed based on medical records. Acute kidney injury was defined as a creatinine clearance rate\u0026thinsp;\u0026lt;\u0026thinsp;60 mL/min/1.73 m\u003csup\u003e2\u003c/sup\u003e [1; 6\u0026ndash;7].\u003c/p\u003e \u003cp\u003eSurgical indications were based on the ESC 2005 guidelines [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] (and its subsequent versions) for the management of IE, including heart failure, uncontrolled infection, vegetation\u0026thinsp;\u0026gt;\u0026thinsp;10 mm, or evidence of embolic events [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePrior antibiotic use referred to the administration of antibiotics at any time before IE diagnosis [1; 6\u0026ndash;7].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eEchocardiographic data\u003c/h2\u003e \u003cp\u003eTransthoracic echocardiography (TTE) was routinely performed in all patients. Transesophageal echocardiography (TEE) was performed to detect cases with negative TTE results, complementary TTE data, and prosthetic and device-related endocarditis. Both TTE and TEE were performed by the echocardiography service at INC. The variables included in the standardised case report form were the presence of vegetation, regurgitation, abscess, leaflet perforation, pseudoaneurysm, and fistulas between the cardiac chambers. Additionally, variables such as ejection fraction, systolic pulmonary artery pressure, and the size of the largest vegetation on its longest axis in millimetres were collected.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eMicrobiological data\u003c/h2\u003e \u003cp\u003ePeripheral venous blood cultures were collected using sterile techniques, with a minimum of two sets, as per institutional protocol, and incubated for 5 days in the BACTEC 9240 system (BACTEC/ALERT\u0026reg;, BioM\u0026eacute;rieux, Durham, NC, USA). Bacterial identification and antimicrobial susceptibility testing were performed using an automated VITEK 2 system (BioM\u0026eacute;rieux). The minimum inhibitory concentrations of vancomycin and daptomycin were determined using the E-test for methicillin-resistant \u003cem\u003eStaphylococcus aureus\u003c/em\u003e.\u003c/p\u003e \u003cp\u003eA subset of patients had surgically excised valves studied by 16SrRNA sequencing [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Serological and molecular analyses of \u003cem\u003eCoxiella burnetii\u003c/em\u003e and \u003cem\u003eBartonella\u003c/em\u003e spp. were performed at the reference laboratory at Funda\u0026ccedil;\u0026atilde;o Oswaldo Cruz (Laborat\u0026oacute;rio de Hantaviroses e Rickettsioses) in cases of culture-negative endocarditis with strong epidemiological suspicion and no reported history of prior antimicrobial use [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eData were stored in a Microsoft Office Excel spreadsheet. Qualitative data were expressed as absolute and relative frequencies. Quantitative data were presented as frequencies, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, median, and interquartile range. Statistical analyses were conducted using Jamovi\u0026reg;, version 1.2.2. Statistical significance was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05. Categorical data were described as frequencies and percentages. The normality of the numerical variables was assessed using the Kolmogorov\u0026ndash;Smirnov test. Proportions were compared using the chi-squared test.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eEthical Aspects\u003c/h2\u003e \u003cp\u003eThis study was approved by the Ethics Committee of INC (approval number, 5.770.094; Certificate of Presentation for Ethical Appreciation, 65137922.7.0000.5272). Informed consent was obtained from each patient or their legal representative, and the study protocol adhered to the ethical guidelines of the Helsinki Declaration of 1975 and its modifications.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\n \u003ch2\u003eNumber of cases of definitive IE in adults\u003c/h2\u003e\n \u003cp\u003eBetween 1 January 2006 and 30 June 2023, our database identified 502 episodes of definite IE in 481 patients (19 patients had two episodes and one patient had three episodes during the study period). The annual distribution of endocarditis cases per year (excluding 2023 as cases were included until June) is depicted in Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\n \u003ch2\u003eGeneral features of the cohort\u003c/h2\u003e\n \u003cp\u003eThe mean age of the patients in the cohort was 48\u0026thinsp;\u0026plusmn;\u0026thinsp;17.2 years, with a ratio of approximately two males for each female (327/502, 65.1% vs 175/502, 34.9%). Individuals over 60 years of age accounted for 149/502 (29.7%) of the sample. A total of 260/501 (51.9%) patients were transferred from other centres.\u003c/p\u003e\n \u003cp\u003eNative and prosthetic valve IE occurred in 68.5% and 31.5% of cases, respectively. Early prosthetic valve IE occurred in 59/502 (11.8%) cases and late prosthetic valve IE in 99/502 (19.7%) cases. Community-acquired IE occurred in 324 (64.7%) patients, healthcare-associated nosocomial IE in 128 (25.5%), and healthcare-associated non-nosocomial IE in 49 (9.8%) (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u0026nbsp;\u003c/p\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eFeatures of definitive IE acquisition in adults, INC, 2006\u0026ndash;2023. \u003cstrong\u003eACQUISITIONS\u003c/strong\u003e \u003cstrong\u003en/N\u003c/strong\u003e \u003cstrong\u003e(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCommunity-acquired IE\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e324/501 (64.7)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNosocomial IE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e128/501 (25.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHealthcare-associated IE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e49/499 (9.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHD-associated IE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e54/501 (10.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEarly prosthetic IE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e59/501 (11.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLate prosthetic IE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e99/502 (19.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDevice-associated IE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e37/502 (7.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\"\u003e\u003cem\u003en/N\u0026thinsp;=\u0026thinsp;absolute number of findings/total number of episodes with available data; IE: Infective Endocarditis; HD: Haemodialysis\u003c/em\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\n \u003ch2\u003ePatients\u0026rsquo; medical history and comorbidities\u003c/h2\u003e\n \u003cp\u003eIn terms of medical history, half of the patients (50.3%) had systemic arterial hypertension, 196 (39.0%) had congestive heart failure (CHF), 107 (21.4%) had CKD, and 40.6% had undergone previous cardiac surgery, mostly vale replacement.\u003c/p\u003e\n \u003cp\u003eThe main predispositions for IE were valve prostheses (158/502; 31.5%), RVD in 151/492 (30.7%), congenital heart disease in 70/502 (13.9%), and previous IE in 63 (12.6%) patients (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\"\u003e\u003cstrong\u003eTable 2.\u0026nbsp;\u003c/strong\u003eComorbidities, past medical history, and predisposition for IE in adult patients with definitive IE, INC, 2006-2023.\u003c/div\u003e\n \u003ctable id=\"Taba\" border=\"1\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSystemic arterial hypertension\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e237/471 (50.3)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCHF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e203/500 (40.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e196/502 (39)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCKD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e107/507 (21.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDyslipidemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e88/448 (19.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAtrial fibrillation/flutter\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e87/493 (17.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiabetes mellitus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76/502 (15.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCAD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e71/498 (14.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCerebrovascular disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34/502 (6.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePercutaneous coronary intervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32/499 (6.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMyocardial revascularization surgery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25/499 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNeoplasia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27/502 (5.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCOPD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19/499 (3.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHIV/AIDS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7/480 (1.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePacemaker\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e54/502 (10.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIntracardiac device\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13/502 (2.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOthers*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18 (3.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePREDISPOSITION\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eProsthesis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e158/502 (31.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRVD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e151/492 (30.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCongenital heart disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e70/502 (13.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrevious IE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e63/501 (12.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIV drug use\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6/502 (1.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\"\u003e\u003cem\u003e*Others\u0026thinsp;=\u0026thinsp;collagen disease (3/501\u0026ndash;0.6%), cirrhosis (5/501\u0026ndash;1.0%), immunosuppressive use (10/450\u0026ndash;2.2%)\u003c/em\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003e\u003cem\u003en/N\u0026thinsp;=\u0026thinsp;absolute number of findings/total number of episodes with available data. IE\u0026thinsp;=\u0026thinsp;infective endocarditis; CHF: Congestive heart failure; HF: heart failure; CKD: chronic kidney disease; CAD: Coronary artery disease; COPD: chronic obstructive pulmonary disease; HIV: Human Immunodeficiency Virus; AIDS\u0026thinsp;=\u0026thinsp;acquired immunodeficiency syndrome; RVD: rheumatic valve disease; IV: Intravenous.\u003c/em\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\n \u003ch2\u003eClinical and laboratory manifestations of IE cases\u003c/h2\u003e\n \u003cp\u003eMost endocarditis cases presented acutely (52%), followed by subacute (41.3%) and chronic progression (32/496 cases, 6.4%).\u003c/p\u003e\n \u003cp\u003eThe most common clinical-laboratory manifestation of IE was fever in 454/501(90.6%), followed by elevated C-reactive protein (CRP) in 329/455 (72.3%) and presence of new regurgitant murmurs (50.7%). Approximately one-third of the patients had an elevated erythrocyte sedimentation rate 104/328 (31.7%), half had an embolic vascular event (45%), and splenomegaly (19.2%) was also a frequent clinical manifestation. Osler\u0026rsquo;s nodes, Janeway lesions, and conjunctival haemorrhage were observed in less than 5% of the cases. The clinical manifestations are shown in Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\n \u003ch2\u003eMicrobiological characteristics\u003c/h2\u003e\n \u003cp\u003eBlood cultures were drawn from 495/502 (98.6%) patients. They were positive in 339/495 (68.5%) patients. Serology was performed in less than 5% of the cases (23/502; 4.6%). Culture-negative IE cases accounted for 33.1% of all blood cultures collected. Among positive blood cultures, oral streptococci and enterococci were the most frequent, followed by \u003cem\u003eS. aureus\u003c/em\u003e and coagulase-negative staphylococci. Typical microorganisms such as streptococci of the bovis and HACEK groups (\u003cem\u003eHaemophilus species, Aggregatibacter species\u003c/em\u003e, \u003cem\u003eCardiobacterium hominis, Eikenella corrodens and Kingella species; Trichosporon s\u003c/em\u003ep, \u003cem\u003eCoxiella burnetii; Bartonella henselae\u003c/em\u003e). were infrequent and found in less than 5% of the cases. Non-HACEK gram-negative bacteria were more frequent than in the HACEK group. The aetiology of IE is shown in Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec18\" class=\"Section2\"\u003e\n \u003ch2\u003eEchocardiographic features\u003c/h2\u003e\n \u003cp\u003eTTE was performed in 425/500 (85%) cases, whereas TEE was performed in 390/500 (78%) cases. Regardless of the involvement of native or prosthetic valves, the most frequent location of vegetation was the mitral valve (MV) (221/498, 46.9%) and the aortic valve (189/499, 37.9%). PM or ICD infections were reported in 37/501 (7.4%) cases. The main echocardiographic findings were vegetation (82.9%), MV vegetations 235/501 (46.9%), MV regurgitation (221/498; 44.4%), and aortic valve regurgitation (207/501; 37.9%). Complications of IE observed on echocardiography included abscesses (15.2%), perforation of the valve apparatus (17.2%), and prosthetic valve dehiscence (4.5%). When comparing early and late prosthetic valve IE and native IE, fistulae were found in 2/59 (3.4%), 2/98 (2%), and 19/345 (5.5%) patients, respectively, whereas abscesses were found in 11/59 (18.6%), 24/98 (24.5%), and 41/345 (11.9%) patients, respectively. Early prosthetic dehiscence occurred in 5 of 59 (8.5%) episodes, and in 10 of 95 (10.5%) episodes of late prosthetic IE. The mean pulmonary arterial systolic pressure was 45.9 mmHg. Echocardiographic findings are summarised in Table 3.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eECOCARDIOGRAPHIC CHARACTERISTICS\u003c/strong\u003e \u003cem\u003en/N\u003c/em\u003e (%)\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\"\u003e\u003cstrong\u003eTable 3\u0026nbsp;\u003c/strong\u003eEchocardiographic findings in adult patients with definite IE, INC, 2006-2023.\u003c/div\u003e\n \u003ctable id=\"Tabb\" border=\"1\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTTE\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e425/500 (85)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTEE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e390/500 (78)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eNew moderate to severe regurgitation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAortic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e189/499 (37.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMitral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e221/498 (44.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTricuspid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e82/500 (16.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePulmonary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2/500 (0.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eVegetation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFrequency of vegetation (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(82.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMaximum vegetation size (mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(48)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAortic valve\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e207/501 (41.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMitral valve\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e235/501 (46.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTricuspid valve\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25/501 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePulmonary valve\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6/501 (1.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChord\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10/500 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCatheter\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3/501 (0.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDevice lead\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37/50 (7.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMyocardial wall\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14/501 (2.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eComplications\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eValve perforation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e86 (17.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAbscess\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76 (15.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCardiac fistula\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21/500 (4.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eProsthetic dehiscence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19/422 (4.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eQuantitative variables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eM\u0026thinsp;=\u0026thinsp;58.8% (SD: 38)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePASP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eM\u0026thinsp;=\u0026thinsp;45.9 mmHg (SD: 17,98)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\"\u003e\u003cem\u003en/N\u0026thinsp;=\u0026thinsp;absolute number of findings/total number of episodes with available data; TTE: Transthoracic echocardiogram; TEE: transesophageal echocardiogram; EF: Ejection fraction; PASP: Pulmonary artery systolic pressure; M: mean; SD: standard deviation\u003c/em\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec19\" class=\"Section2\"\u003e\n \u003ch2\u003eComplications and outcomes of IE cases\u003c/h2\u003e\n \u003cp\u003eAmong the complications of IE episodes (Table \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e), acute heart failure was the most frequent, occurring in more than half of the patients (291/502, 58%), followed by acute renal failure (156/476, 32.8%), central neurological events (131/501, 26.1%), and myocardial or paravalvular abscesses (108/501, 21.6%). Embolization was also frequently seen, with splenic emboli being the most common with 176/500 cases (35.2%), followed by emboli to the central nervous system in 131/501 cases (26.1%). The lungs were affected in 5.4% of all cases and in 10/35 cases (28.5%) of device-related endocarditis.\u003c/p\u003e\n \u003cp\u003eThe overall mortality rate was 125/500 (25%) (Table \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e). Among all the patients, 415 (82.6%) had surgical indications. Of these patients, 347 (83.6%) underwent surgery. Among patients who underwent surgery, the mortality rate was 21.3% (74/347). Among the 68 patients who had a surgical indication but did not operate, 39/68 died (mortality rate: 57.4%). This difference was statistically significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, chi-squared test). Only 53 patients did not have surgical indications; among them, 10 died, representing a mortality rate of 18.9%.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIE is a severe condition with a high risk of complications and mortality, requiring specialised multidisciplinary management. This study presented a series of 502 episodes of definite IE in adult patients, diagnosed according to the modified Duke criteria, at a federal public hospital in Rio de Janeiro. Few case series of IE have been reported from Brazilian centres [\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e] and other low- and middle-income countries. To facilitate the discussion, we compiled Tables \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e from the literature (Supplementary Material). Our study revealed a mean patient age of 48 years, consistent with the literature indicating that younger age groups are more commonly affected in the low- and middle-income countries [\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e]. This finding is associated with the frequent presence of rheumatic valvopathy as a predisposing factor, leading to earlier onset of IE [17; 18]. Rheumatic valvopathy was also prevalent in two other Brazilian studies from Southeastern centres [12; 13]. In contrast, a larger IE series by Murdoch et al. [\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e], which included 2,781 adults from 58 hospitals across 25 countries from 2000 to 2005, reported a median age of 57.9 years. The EURO-ENDO study [\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e], including 3,116 patients from 2016 to 2018, predominantly from European centres, reported a median age of 65 years. Recent case series from European countries have also reported higher mean ages compared to our study [21; 22]. The most common underlying cardiac conditions in this cohort were rheumatic valvopathy (30.7%) and congenital heart disease (13.9%), which is consistent with the literature. Studies from other developing countries, such as French Polynesia [\u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e], Saudi Arabia [\u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e], and China [\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e] have also highlighted these conditions as significant predispositions for IE. Rheumatic valvopathy was present in 15% of patients in Saudi Arabia [\u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e], 33% in French Polynesia [\u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e], and 17% in China [\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e] (Supplementary Table\u0026nbsp;1).\u003c/p\u003e\n\u003cp\u003eRegarding the male-to-female ratio, our study showed a male predominance, similar to studies from East Asia [\u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e] (67%), Africa [\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e] (67.1%), and South America [\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e] (68.7%), as well as studies from developed countries [21\u0026ndash;22; 24] (Supplementary Table\u0026nbsp;1).\u003c/p\u003e\n\u003cp\u003eAlthough IE was once considered a rare disease, the literature has reported a significant increase in cases over time, both in developed and developing countries. Similarly, we found an increasing trend in the number of cases over the study period. This higher incidence is likely related to an increase in high-risk populations, including older adults, individuals with multiple comorbidities, and those undergoing haemodialysis [8; 12; 20]. This trend supports CHF and chronic renal failure as prevalent comorbidities among patients who developed IE at our centre.\u003c/p\u003e\n\u003cp\u003eIE on native valves occurred in 68.5% of patients, with a higher incidence on the aortic and mitral valves, similar to observations in both developed and developing countries [2; 5; 12; 14; 17\u0026ndash;18; 20\u0026ndash;21; 25]. Prosthetic valve endocarditis accounted for 31.47% of cases, similar to findings in Italy [\u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e], Saudi Arabia [\u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e], Turkey [\u003cspan class=\"CitationRef\"\u003e26\u003c/span\u003e], and other Brazilian studies (27.1%; 48.4%) [\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e]. Despite the predominant involvement of native valves, the incidence of prosthetic valve endocarditis has increased, consistent with the rising number of valve surgeries in recent years [\u003cspan class=\"CitationRef\"\u003e28\u003c/span\u003e]. In low- and middle-income countries, the incidence of prosthetic valve endocarditis is significantly lower than that of native valve endocarditis, possibly due to limited access to healthcare and fewer valve replacements [17; 26]. The incidence of IE in implantable cardiac electronic devices has shown an increasing trend owing to higher device insertion rates, population aging, and increased comorbidities. In this study, it represented approximately 8% of all cases over the past 17 years, a proportion similar to that reported in Argentina, China, and Turkey [15\u0026ndash;16; 26] (Supplementary Table\u0026nbsp;2).\u003c/p\u003e\n\u003cp\u003eThe signs and symptoms of IE vary depending on the severity of the infection. The most relevant classical signs and symptoms observed were fever (90.6%) and heart murmur (50.7%), consistent with other studies (Supplementary Table\u0026nbsp;4). Classic Oslerian manifestations of endocarditis were present in only 3% of patients upon hospital admission, aligning with findings from other Brazilian [\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e] and Chinese [\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e] studies. Notably, most patients did not exhibit the classic clinical findings traditionally associated with IE. Although embolic manifestations were frequent (45%) in this cohort, other studies reported a lower proportion despite a significant number of cases [13\u0026ndash;14; 17; 21; 29; 30]; in our study, emboli were often detected radiologically rather than clinically. This underscores the recommendation for echocardiography in cases of bacteraemia and screening for embolic events, even in asymptomatic patients [\u003cspan class=\"CitationRef\"\u003e31\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eIn comparison with published literature from Argentina [\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e], China [\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e], and the USA [\u003cspan class=\"CitationRef\"\u003e32\u003c/span\u003e], the vegetation rate in our study (82.9%) closely aligns with the rates reported in these studies (80.9%, 86%, and 84.1%, respectively) (Supplementary Table\u0026nbsp;2). However, the proportion of patients who underwent TEE in this cohort (78%) was significantly higher than that reported in a Chinese study (12.8%). This contrasts with the 2015 ESC guidelines on IE [\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e], which recommend performing TEE to exclude perivalvular complications, even if TTE shows findings compatible with IE. The high frequency of TEE in our study reflects the setting of a highly specialised surgical cardiology hospital. The lower utilisation of TEE in other studies may have led to lower detection rates of perivalvular complications such as valve perforation and perivalvular abscess, potentially resulting in diagnostic errors in patients with subtle or early valvular lesions.\u003c/p\u003e\n\u003cp\u003eThe number of positive blood cultures in this study was lower than that in studies from developed countries [21; 25; 27; 29] but higher than those from developing countries [\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e], as demonstrated in Supplementary Table\u0026nbsp;3. Brazilian studies reported blood culture positivity rates of 66.5% [\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e], 76.9% [\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e], and 76.6% [\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e]. The low rate of microbiological detection may be related to antibiotic use before blood culture collection, as previously described by our group, where the rate of prior antibiotic use reached 75% [\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e]. Additionally, over half of the patients in our centre were referred from other medical institutions, where antibiotic treatment is often initiated before blood cultures are collected. Oral streptococci were the primary etiological agents used in this study. Likewise, studies from Argentina and China [\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e] show predominance of oral streptococci, in contrast to those in developed countries [25; 27], where \u003cem\u003eS. aureus\u003c/em\u003e has become the main aetiology (Supplementary Table 3). The increase in staphylococcus infections is primarily attributed to the high incidence of infections among intravenous drug users [5; 25], patients undergoing haemodialysis [\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e], and older patients with comorbidities. However, the proportion of intravenous drug users and octogenarians was low in our cohort compared to developed countries [25; 27; 32]. Notably, poor oral health in patients treated by the Brazilian public health system may contribute to the prevalence of oral streptococci [\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e33\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eThe complications of IE are widespread and can affect multiple organs. Systemic embolization is the most frequent complication included in the Duke diagnostic criteria [\u003cspan class=\"CitationRef\"\u003e28\u003c/span\u003e]. The sites of embolization depend on the affected valves and may involve the spleen, liver, kidneys, lungs, brain, vertebral bodies, and iliac and mesenteric arteries. Left-sided involvement commonly leads to splenic and cerebral emboli, while right-sided involvement causes pulmonary emboli [\u003cspan class=\"CitationRef\"\u003e28\u003c/span\u003e]. Detection of these complications is often hindered by delayed diagnosis [7; 30; 31]. As shown in Supplementary Table\u0026nbsp;4, embolization was the most frequently reported complication, although not all studies specified the affected areas. All studies reviewed demonstrated a higher incidence of left-sided endocarditis than right-sided endocarditis, resulting in more splenic embolization.\u003c/p\u003e\n\u003cp\u003eSurgery is indicated to prevent progressive and irreversible structural damage and is justified in patients at high risk where cure with antibiotic therapy alone is unlikely and in those who do not have comorbidities or severe complications that make recovery prospects remote [1; 7]. This review revealed that a wide range of patients underwent surgery for IE, from 17.2% in Japan [\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e] to 69.7% in Turkey [\u003cspan class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eStudies from the USA have demonstrated surgical indication rates of approximately 25% [\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e32\u003c/span\u003e], which are lower than those in our cohort (Supplementary Table\u0026nbsp;4). Although the USA is a high-income country, intravenous drug abuse has increased substantially, contributing to the predisposition of individuals to IE and the acquisition of more virulent pathogens [\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e]. This increase has significant consequences because IE due to \u003cem\u003eS. aureus\u003c/em\u003e infection is associated with a higher likelihood of requiring surgical treatment and worse overall outcomes. The study with the lowest surgical indication rate in this review was Japan [\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e] (17.2%), which despite also being a high-income country, has an older average population age (69.1\u0026thinsp;\u0026plusmn;\u0026thinsp;14 years) with multiple comorbidities, often reducing the drive for surgical intervention.\u003c/p\u003e\n\u003cp\u003eUnfortunately, our cohort did not have sufficient power to compare patients who underwent early intervention with those who underwent late surgery. However, our study provided evidence supporting the assumption that surgically treated patients have better outcomes than conservatively managed patients. Early surgery is recommended (and reduces mortality) in cases of IE with complications such as embolic events, CHF, and valvular abscesses [1; 4; 7; 37].\u003c/p\u003e\n\u003cp\u003eDespite improvements in the diagnostic accuracy, medical therapy, and surgical techniques, IE mortality rates remain relatively high worldwide. In our study, we observed an overall hospital mortality rate of 25%, which is similar to the rates observed in Japan [\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e] (26.1%) and Turkey [\u003cspan class=\"CitationRef\"\u003e26\u003c/span\u003e] (22.6%).\u003c/p\u003e\n\u003cp\u003eHowever, these results were lower than those of other studies, such as French Polynesia [35] (37%) and Spain [\u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e] (34.7%). This may be due to the younger age of our patients and lower proportion of infections caused by \u003cem\u003eS. aureus\u003c/em\u003e. Oral streptococcal species were the most frequently identified microorganisms in our study, which may have contributed to the favourable outcomes. Additionally, early surgery has been reported to improve the prognosis of IE. Thus, early surgery for IE has been increasingly performed in recent years, likely contributing to the gradual decline in IE hospital mortality rates at some centres [\u003cspan class=\"CitationRef\"\u003e29\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eAvailable studies in Brazil have reported higher mortality rates than ours (Minas Gerais, 32%; S\u0026atilde;o Paulo, 33%; and Rio Grande do Sul, 41.9%) [\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e]. These higher rates may be attributed to differences in patient profiles, with a prevalence of multiple comorbidities, and differences in hospital profiles, as ours is a referral centre in cardiology with a tendency to perform early surgeries [12\u0026ndash;14; 23\u0026ndash;24].\u003c/p\u003e\n\u003cp\u003eThe main limitation of our study was the retrospective, single-centre nature at a cardiac surgery referral centre, which may not represent the profile of the entire Brazilian and South American healthcare systems. Therefore, our findings cannot be generalised, and the results may have been influenced by this limitation. A significant strength of our study is that it included one of the largest cohorts of adult patients with definite IE, with prospectively collected data, in Latin America.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study presents the IE profile and mortality analysis in a large cohort of patients spanning a 17-year period, representing a rare initiative in a middle-income country. Blood culture-negative endocarditis is frequent in young men, while oral streptococci remain the primary etiological agents.\u003c/p\u003e \u003cp\u003eThe high mortality rate observed in this cohort underscores the importance of studies on IE, as they provide a better understanding of the clinical and microbiological characteristics, as well as factors associated with unfavourable prognosis. This could contribute to the development of improved strategies.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eC.C.L was responsible for the concept of the work.M.C., T.A., N.F., R.G.,G.B.,G.C.,W.G.,C.W.,B.Z.,C.C.L acquired dataM.C., T.A., M.G.C.,C.C.L.were responsible for data analysis and interpretation:M.C.,T.A.,C.C.L. drafted the work (text, tables and figures).C.C.L. revised it critically for important intellectual contentAll authors approved the final draft.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe acknowledge Ms. Cyntia Aguiar for technical help as a librarian in the systematic literature search. We also acknowledge all medical and nursing staff who looked after the patients , as well as the supporting staff in the microbiology, radiology and echocardiography departments.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eData is provided within the manuscript or supplementary information files\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eHabib G, et al. 2015 ESC guidelines for the management of infective endocarditis. Kardiol Pol. 2015;73(11):963\u0026ndash;1027.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMurdoch DR, et al. Clinical presentation, etiology, and outcome of infective endocarditis in the 21st century: the International Collaboration on Endocarditis-Prospective Cohort Study. Archives Intern Med vol. 2009;169(5):463\u0026ndash;73. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1001/archinternmed.2008.603\u003c/span\u003e\u003cspan address=\"10.1001/archinternmed.2008.603\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHolland TL et al. Sep. Infective endocarditis. Nature reviews. Disease primers vol. 2 16059. 1 2016, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/nrdp.2016.59\u003c/span\u003e\u003cspan address=\"10.1038/nrdp.2016.59\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThuny F et al. Management of infective endocarditis: challenges and perspectives. Lancet. 2012;379(9819):965\u0026ndash;975. doi: 10.1016/S0140-6736(11)60755-1. Epub 2012 Feb 7. 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Infect Dis (Lond). 2019;51(10):738\u0026ndash;44. Epub 2019 Jul 31. PMID: 31364901.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHolland DJ, Simos PA, Yoon J, Sivabalan P, Ramnarain J, Runnegar NJ. Infective Endocarditis: A Contemporary Study of Microbiology, Echocardiography and Associated Clinical Outcomes at a Major Tertiary Referral Centre. Heart Lung Circ. 2020;29(6):840\u0026ndash;50. Epub 2019 Aug 2. PMID: 31402124.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMutagaywa RK et al. Infective endocarditis in developing countries: An update. Frontiers in cardiovascular medicine. 2022; 9:1007118. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3389/fcvm.2022.1007118\u003c/span\u003e\u003cspan address=\"10.3389/fcvm.2022.1007118\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim JH, Lee HJ, Ku NS, Lee SH, Lee S, Choi JY, Yeom JS. Infective endocarditis at a tertiary care hospital in South Korea. Heart. 2021;107(2):135\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAcibuca A, Yilmaz M, Okar S, Kursun E, Acilar O, Tekin A, Demiroglu YZ, Muderrisoglu IH. An epidemiological study to define the recent clinical characteristics and outcomes of infective endocarditis in southern Turkey. 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J Hosp Med. 2017;12(6):414\u0026ndash;20. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.12788/jhm.2746\u003c/span\u003e\u003cspan address=\"10.12788/jhm.2746\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 28574530; PMCID: PMC6005201.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBergan EH, et al. Impact of improvement in preoperative oral health on nosocomial pneumonia in a group of cardiac surgery patients: a single arm prospective intervention study. Intensive care Med vol. 2014;40(1):23\u0026ndash;31. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00134-013-3049-y\u003c/span\u003e\u003cspan address=\"10.1007/s00134-013-3049-y\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 4 and 5 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Infective endocarditis, Epidemiology, Cohort Study, Surgery, Mortality","lastPublishedDoi":"10.21203/rs.3.rs-4854250/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4854250/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e \u003cp\u003eInfective endocarditis (IE) is a severe disease with a high mortality rate. Our aim was to describe a case series of adult patients with definite IE treated at a reference centre for cardiac surgery in Brazil, highlighting their specific characteristics.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003e A retrospective analysis of a prospectively implemented endocarditis database was conducted, including adult patients with definite IE according to the modified Duke criteria from January 2006 to June 2023. The analysis used the International Collaboration on Endocarditis case report form. Statistical analysis was performed using Jamovi\u0026reg;, version 1.2.2.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThere were 502 episodes of IE; the mean patient age\u0026thinsp;\u0026plusmn;\u0026thinsp;SD was 48.4\u0026thinsp;\u0026plusmn;\u0026thinsp;17.2 years. Community-acquired IE occurred in 64.7% of the patients, previous heart surgery was performed in 40.6%, and 39.0% of the patients had previous congestive heart failure (CHF). The main predisposing factors were rheumatic valve disease (RVD, 30.7%), valve prostheses (31.5%), and congenital heart disease (13.9%). Transthoracic and transoesophageal echocardiograms were performed in 85% and 78% of the patients, respectively. Left-sided IE was predominant. Fever occurred in 90.6% of patients, new murmurs in 50.7%, and embolism in 45%. Blood cultures were negative in 33.1% of the patients. The most common pathogens were oral streptococci (15.6%), \u003cem\u003eStaphylococcus aureus\u003c/em\u003e (10.0%), and enterococci (12.8%). The main complications were CHF (58%), acute renal failure (32.8%), and splenic embolization (35.2%). Surgery was performed in 83.6% of the patients, and the in-hospital mortality rate was 25%.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusions\u003c/b\u003e\u003c/p\u003e \u003cp\u003eIn this centre, left-sided IE predominated, with negative blood cultures. Oral streptococci were the most frequently encountered pathogens and RVD was the main predisposing factor. Surgery was performed frequently, and the mortality rate was higher than that in developed countries but lower than that in developing countries.\u003c/p\u003e","manuscriptTitle":"Contemporary cohort study in adult patients with infective endocarditis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-23 12:24:47","doi":"10.21203/rs.3.rs-4854250/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4dc6cc19-7dcd-41b5-a794-97032b9cdaa9","owner":[],"postedDate":"August 23rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-08-23T12:24:50+00:00","versionOfRecord":[],"versionCreatedAt":"2024-08-23 12:24:47","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4854250","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4854250","identity":"rs-4854250","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}