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The incidence of infective endocarditis (IE) has increased globally in the past decades, including in the United States. However, little is known about the differences in trends across states, gender, and age groups within the United States. Using the Global Burden of Disease database, we analyzed the incidence and mortality trends of IE in the United States between 1990 and 2019 using Joinpoint regression analyses, and compared between states, gender, and age groups. The age-standardized incidence rate (ASIR) of IE in the United States increased from 10.2/100,000 population in 1990 to 14.4 in 2019. The increase in ASIR was greater among men than women (45.8% vs 34.1%). The incidence increase was driven by 55+ year-olds (112.7% increase), with rapid increases in the 1990s and early 2000s, followed by a plateau around the mid-2000s. In contrast, the incidence among 5-to-19-year-olds decreased by -36.6% over the 30-year period. The incidence increased among all age groups in the last 5 years of observation (2015 to 2019), with the largest increase in 5-to-19-year-olds (3.3% yearly). The 30-year increase in ASIR was greatest in Utah (66.2%) and smallest in California (30.2%). The overall age-standardized mortality attributable to IE increased in the United States by 126% between 1990 and 2019 versus 19.6% globally. In conclusion, although the overall incidence and mortality of IE increased over the past 30 years in the United States, there are significant differences between regions, gender, and age groups. These findings indicate unevenly distributed disease burden of IE across the nation., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

This study aimed to identify which streptococcal species are closely associated with infective endocarditis (IE) and to evaluate risk factors for mortality in patients with streptococcal IE. We performed a retrospective cohort study of all patients with streptococcal bloodstream infection (BSI) from January 2010 to June 2020 in a tertiary hospital in South Korea. We compared clinical and microbiological characteristics of streptococcal BSIs according to the diagnosis of IE. We performed multivariate analysis to evaluate the risk of IE according to streptococcal species and risk factors for mortality in streptococcal IE. A total of 2,737 patients were identified during the study period, and 174 (6.4%) were diagnosed with IE. The highest IE prevalence was in patients with Streptococcus mutans BSI (33% [9/27]) followed by S. sanguinis (31% [20/64]), S. gordonii (23% [5/22]), S. gallolyticus (16% [12/77]), and S. oralis (12% [14/115]). In multivariate analysis, previous IE, high-grade BSI, native valve disease, prosthetic valve, congenital heart disease, and community-onset BSI were independent risk factors for IE. After adjusting for these factors, S. sanguinis (adjusted OR [aOR], 7.75), S. mutans (aOR, 5.50), and S. gallolyticus (aOR, 2.57) were significantly associated with higher risk of IE, whereas S. pneumoniae (aOR, 0.23) and S. constellatus (aOR, 0.37) were associated with lower risk of IE. Age, hospital-acquired BSI, ischemic heart disease, and chronic kidney disease were independent risk factors for mortality in streptococcal IE. Our study points to significant differences in the prevalence of IE in streptococcal BSI according to species. IMPORTANCE Our study of risk of infective endocarditis in patients with streptococcal bloodstream infection demonstrated that Streptococcus sanguinis, S. mutans, and S. gallolyticus were significantly associated with higher risk of infective endocarditis. However, when we evaluated the performance of echocardiography in patients with streptococcal bloodstream infection, patients with S. mutans and S. gordonii bloodstream infection had a tendency of low performance in echocardiography. There are significant differences in the prevalence of infective endocarditis in streptococcal bloodstream infection according to species. Therefore, performing echocardiography in streptococcal bloodstream infection with a high prevalence of, and significant association with, infective endocarditis is desirable., Competing Interests: The authors declare no conflict of interest.

Multiple episodes of Enterococcus faecalis bacteremia (EfsB) may indicate a relapse and be due to an undiagnosed infective endocarditis (IE). The aims were to study the clinical presentation of patients with EfsB with focus on the risk of recurrent infection and IE, identify potential improvements of the management, and to investigate whether E. faecalis isolates from different episodes in the same patient were identical. In a retrospective study, a cohort of patients with monomicrobial (M) EfsB episodes was analyzed. Clinical data from medical records were collected. Furthermore, blood culture isolates from patients with multiple episodes were subjected to whole genome sequencing and multilocus sequence typing. In 666 episodes of MEfsB, 69 patients with IE and 43 with recurrent infections were found. Patients without IE, but with a following episode diagnosed as IE, were compared to those without a following episode. Variables significantly correlated with IE were long duration of symptoms, growth in all blood cultures, unknown origin of infection, heart murmur, and predisposition for IE. Transesophageal echocardiography, all negative, was done in 4 out of 11 episodes during the first episodes, later diagnosed with IE. In 28 of 31 patients with two or more EfsB episodes, isolates with identical sequence type were found. Episodes of EfsB in patients later diagnosed with IE showed features of IE already during the first episodes, were not adequately evaluated, are due to identical isolates, and most likely represent true relapses. Risk factor analysis should guide the use of echocardiography., (© 2023. The Author(s).)

In this part 1 of a 2-part continuing medical education series, we review the epidemiology and pathophysiology of cardiovascular disease, its association with cutaneous symptoms, and the diagnosis and evaluation of cutaneous features of cardiovascular syndromes, including infective endocarditis, acute rheumatic fever, Kawasaki disease, cholesterol embolization syndrome, lipid disorders, cardiac amyloidosis, and cardiac myxomas. As the incidence and prevalence of cardiovascular diseases increase, dermatologists play an essential role in recognizing the cutaneous manifestations of cardiovascular diseases in order to appropriately connect patients with follow-up care., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2022 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

In patients receiving hemodialysis, infective endocarditis (IE) may present in a similar way to other causes of bacteremia, which may delay early diagnosis and can lead to worse outcomes. In this study, we aimed to identify the risk factors for IE in hemodialysis patients with bacteremia. This study was conducted on all patients diagnosed with IE and receiving hemodialysis between 2005 and 2018 in Salford Royal Hospital. Patients with IE were propensity score matched with similar hemodialysis patients with episodes of bacteremia between 2011 and 2015 (non-IE bacteremic (NIEB)). Logistic regression analysis was used to predict the risk factors associated with infective endocarditis. There were 35 cases of IE, and these were propensity matched with 70 NIEB cases. The median age of the patients was 65 years with a predominance of males (60%). The IE group had higher peak C-reactive protein compared to the NIEB group (median, 253 mg/L vs. 152, p = 0.001). Patients with IE had a longer duration of prior dialysis catheter use than NIEB patients (150 vs. 28.5 days: p = 0.004). IE patients had a much higher 30-day mortality rate (37.1% vs. 17.1%, p = 0.023). Logistic regression analysis showed previous valvular heart disease (OR: 29.7; p < 0.001), and a higher baseline C-reactive protein (OR: 1.01; p = 0.001) as significant predictors for infective endocarditis. Bacteremia in patients receiving hemodialysis through a catheter access should be actively investigated with a high index of suspicion for infective endocarditis, particularly in those with known valvular heart disease and a higher baseline C-reactive protein.

Importance: It is suggested that patients with Cutibacterium acnes endocarditis often present without fever or abnormal inflammatory markers. However, no study has yet confirmed this statement., Objective: To assess the clinical characteristics and outcomes of patients with C acnes endocarditis., Design, Setting, and Participants: A case series of 105 patients presenting to 7 hospitals in the Netherlands and France (4 university hospitals and 3 teaching hospitals) with definite endocarditis according to the modified Duke criteria between January 1, 2010, and December 31, 2020, was performed. Clinical characteristics and outcomes were retrieved from medical records. Cases were identified by blood or valve and prosthesis cultures positive for C acnes, retrieved from the medical microbiology databases. Infected pacemaker or internal cardioverter defibrillator lead cases were excluded. Statistical analysis was performed in November 2022., Main Outcomes and Measures: Main outcomes included symptoms at presentation, presence of prosthetic valve endocarditis, laboratory test results at presentation, time to positive results of blood cultures, 30-day and 1-year mortality rates, type of treatment (conservative or surgical), and endocarditis relapse rates., Results: A total of 105 patients (mean [SD] age, 61.1 [13.9] years; 96 men [91.4%]; 93 patients [88.6%] with prosthetic valve endocarditis) were identified and included. Seventy patients (66.7%) did not experience fever prior to hospital admission, nor was it present at hospitalization. The median C-reactive protein level was 3.6 mg/dL (IQR, 1.2-7.5 mg/dL), and the median leukocyte count was 10.0 × 103/µL (IQR, 8.2-12.2 × 103/µL). The median time to positive blood culture results was 7 days (IQR, 6-9 days). Surgery or reoperation was indicated for 88 patients and performed for 80 patients. Not performing the indicated surgical procedure was associated with high mortality rates. Seventeen patients were treated conservatively, in accordance with the European Society of Cardiology guideline; these patients showed relatively high rates of endocarditis recurrence (5 of 17 [29.4%])., Conclusions and Relevance: This case series suggests that C acnes endocarditis was seen predominantly among male patients with prosthetic heart valves. Diagnosing C acnes endocarditis is difficult due to its atypical presentation, with frequent absence of fever and inflammatory markers. The prolonged time to positivity of blood culture results further delays the diagnostic process. Not performing a surgical procedure when indicated seems to be associated with higher mortality rates. For prosthetic valve endocarditis with small vegetations, there should be a low threshold for surgery because this group seems prone to endocarditis recurrence.

Objectives: Viridans group streptococci (VGS) have been previously linked to infective endocarditis (IE) in patients with mitral valve prolapse (MVP). The species identification of VGS is now available in clinical laboratories; however, it has not been examined in MVP IE. Therefore, we detailed the clinical profile, species designations, and antibiotic susceptibility of VGS isolates from patients with MVP IE., Methods: We retrospectively queried all adults with MVP and a definite or possible IE diagnosis seen at medical centers of the Mayo Clinic Enterprise from January 2009 to December 2021. Data, including clinical characteristics, comorbidities, microbiology, and outcomes, were extracted from electronic health records. VGS isolates from patients with MVP and IE were subclassified into mutans, salivarius, anginosus, sanguinis, and mitis groups., Results: A total of 38 patients with MVP with IE due to streptococcal species were included. Overall, median age was 62.4 years and 32% of patients were females. The most prevalent comorbidities were diabetes mellitus (26%), hypertension (21%), heart failure (16%), and malignancy (16%). A total of (37%) patients presented with an embolic event at the time of their IE diagnosis, 27 (66%) required valve surgery, and no patient died within the hospital stay. The Streptococcus mitis group was the predominant (n = 17, 45%) species designation; S. anginosus and S. sanguinis were identified in three (8%) each; S. mutans in two (5%); and S. salivarius in one (3%). Non-VGS streptococcal pathogens included S. agalactiae in three patients (8%), S. equi in two (5%), and S. dysgalactiae and S. bovis in one each (3%). VGS were identified in five (13%) patients, but species designation was not done. No penicillin resistance was identified among the isolates., Conclusion: The S. mitis group was the predominant species in our investigation. Continued evaluation of VGS species should be considered to profile the IE risk based on species identification., Competing Interests: Declarations of competing interest Dr Larry M Baddour: UpToDate, Inc. – royalty payments (authorship duties); Boston Scientific - consultant duties; Roivant Sciences - consultant duties. The other authors have no competing interests to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The epidemiology of infective endocarditis (IE) continues to evolve in areas affected by the opioid epidemic. Understanding the demographics of the disease allows us to better tailor therapy towards this at-risk population. This was an observational study of adults (age ≥ 18) admitted to the University of Kentucky hospital with IE between January 2009 and December 2018. 1,255 patients were included in the final analysis. The mean age was 42 years, 45% were female and injection drug use was seen in 66% of patients. On multivariable analysis, higher Charlson comorbidity indices, left sided, and multivalve involvement were associated with increased mortality, whereas surgical intervention demonstrated a trend towards lower mortality. Our results highlight the alarming increase in injection drug use related IE and the high mortality rates despite therapeutic advances. Patients with left sided IE, multivalve involvement and a higher Charlson comorbidity index had decreased survival., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Infective endocarditis (IE) may present with a broad spectrum of symptoms and signs and several tools can be used for diagnosis. Many protocols can be used for in-hospital and out-patient management. The aim of this study was to assess the clinical features, tools used and outcomes of patients diagnosed with IE in one of the tertiary-care university hospitals., Methods: This study included 90 consecutive patients admitted to the Cardiology Department in a tertiary-care university hospital in Egypt with a diagnosis of IE., Results: The mean age of the studied population was 36.72 years and 76.67% were males. The most common underlying condition was valvular heart disease (48.89%), followed by intravenous drug use (26.67%) and the most common risk factor was smoking (48.89%). The most common clinical presentation was fever (69.67%), followed by dyspnoea (55.56%), and the mean duration from symptom onset until admission was 13.28 ± 9.29 days. Positive cultures were encountered in 45.56% of patients. Surgery was indicated in 91.11% of the patients but it was performed in only 28.89%. Almost a third of patients (34.44%) died in the hospital. After one year of follow up, a further 8.47% of the patients had died, 11.86% had heart failure and 6.78% had undergone a re-do surgery., Conclusions: Nowadays IE tends to affect a younger group of patients and valvular heart disease is the main underlying condition. The mortality rate due to IE is high in developing countries and IE does not have only immediate and short-term complications, its effects extend to a longer period of time.

Background: Cardiac implantable electronic device (CIED)-associated infections are associated with substantial morbidity, mortality, and costs. Guidelines have cited endocarditis as a Class I indication for transvenous lead removal/extraction (TLE) among patients with CIEDs., Objectives: The authors sought to study utilization of TLE among hospital admissions with infective endocarditis using a nationally representative database., Methods: Using the Nationwide Readmissions Database (NRD), 25,303 admissions for patients with CIEDs and endocarditis between 2016 and 2019 were evaluated on the basis of International Classification of Diseases-10th Revision, Clinical-Modification (ICD-10-CM) codes., Results: Among admissions for patients with CIEDs and endocarditis, 11.5% were managed with TLE. The proportion undergoing TLE increased significantly from 2016 to 2019 (7.6% vs 14.9%; P trend < 0.001). Procedural complications were identified in 2.7%. Index mortality was significantly lower among patients managed with TLE (6.0% vs 9.5%; P < 0.001). Presence of Staphylococcus aureus infection, implantable cardioverter-defibrillator, and large hospital size were independently associated with TLE management. TLE management was less likely with older age, female sex, dementia, and kidney disease. After adjustment for comorbidities, TLE was independently associated with significantly lower odds of mortality (adjusted OR: 0.47; 95% CI: 0.37-0.60 by multivariable logistic regression, and adjusted OR: 0.51; 95% CI: 0.40-0.66 by propensity score matching)., Conclusions: Utilization of lead extraction among patients with CIEDs and endocarditis is low, even in the presence of low rates of procedural complications. Lead extraction management is associated with significantly lower mortality, and its use has trended upward between 2016 and 2019. Barriers to TLE for patients with CIEDs and endocarditis require investigation., Competing Interests: Funding Support and Author Disclosures This work was supported by grants from the Michael Wolk Heart Foundation, the New York Cardiac Center, Inc, and the New York Weill Cornell Medical Center Alumni Council. Dr Cheung has received consulting fees from Abbott, Biotronik, and Boston Scientific; has received research grant support from Boston Scientific; and has received fellowship grant support from Abbott, Biosense Webster, Biotronik, Boston Scientific, and Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Patients with cardiac implantable electronic device (CIED) and Staphylococcus aureus bacteraemia (SAB) are at risk of having infective endocarditis (IE). The objectives were to describe a Swedish population-based cohort of patients with CIED and SAB, to identify risk factors, and to construct a predictive score for IE. Patients over 18 years old in the Stockholm Region identified to have SAB in the Karolinska Laboratory database from January 2015 through December 2019 were matched to the Swedish Pacemaker and Implantable Cardioverter-Defibrillator ICD Registry to identify the study cohort. Data were collected from study of medical records. A cohort of 274 patients with CIED and SAB was identified and in 38 episodes (14%) IE were diagnosed, 19 with changes on the CIED, and 35 with changes on the left side of the heart. The risk factors predisposition for IE, community acquisition, embolization, time to positivity of blood cultures, and growth in blood culture after start of therapy in blood cultures were independently associated to IE. A score to identify patients with IE was constructed, the CTEPP score, and the chosen cut-off generated a sensitivity of 97%, specificity of 25%, and a negative predictive value of 98%. The score was externally validated in a population-based cohort of patients with CIED and SAB from another Swedish region. We found that 14% of patients with CIED and SAB had definite IE diagnosed. The CTEPP-score can be used to predict the risk of IE and, when negative, the risk is negligible., (© 2023. The Author(s).)

I n t r o d u c t i o n: Seasonal variation has been observed for bacterial and viral infections (e.g., COVID-19 [1]), but also for numerous cardiac problems. However, little information is available on the seasonality of infectious endocarditis (IE), a rare disease that is usually linked to a bacterial origin. Data from the Polish population are lacking. Materials and M e t h o d s: Our retrospective study focused on the identification of patients with IE, who were hospitalized at the University Hospital in Krakow between 2005-2022. For this purpose, we searched the medical records system using the ICD-10 code. We decided to divide our patients into four groups (winter, spring, summer, autumn), based on the date of admission to the hospital. Comparison of the distribution of IE incidents by season was performed with the ch2 test. R e s u l t s: One hundred and ten patients were included in the study (median age 62.5 years (range 20-94), 72 men (65.45%)). The left native valve IE was diagnosed in 49% of the patients, the prosthetic valve IE in 16%, the right valve IE in 27% and the implantable cardiac electronic devices IE in 12% of the subjects. The outcomes comprised of cardiac surgery (n = 53), embolism (n = 16), death (n = 15) and metastatic infections (n = 5). No differences in the incidence of IE by season were observed. C o n c l u s i o n s: In the preliminary observation of IE cases of patients admitted to the University Hospital in Krakow, Poland no seasonal pattern of IE was detected. Therefore, IE should be taken into account in the differential diagnosis at any time of the year.

Over the last decade, the incidence of infective endocarditis (IE) has increased, with a change in the frequency of causative bacteria. Early evidence has substantially demonstrated the crucial role of bacterial interaction with human platelets, with no clear mechanistic characterization in the pathogenesis of IE. The pathogenesis of endocarditis is so complex and atypical that it is still unclear how and why certain bacterial species will induce the formation of vegetation. In this review, we will analyze the key role of platelets in the physiopathology of endocarditis and in the formation of vegetation, depending on the bacterial species. We provide a comprehensive outline of the involvement of platelets in the host immune response, investigate the latest developments in platelet therapy, and discuss prospective research avenues for solving the mechanistic enigma of bacteria-platelet interaction for preventive and curative medicine.

Background: Infective endocarditis (IE) remains major cause of morbidity and mortality in adult congenital heart disease (ACHD). Limited data exists on ACHD with IE in Central and South-Eastern European (CESEE) countries. The aim of this study is to characterize contemporary management and assess outcomes of ACHD with IE in CESEE region., Methods: Data on ACHD patients with IE from 9 tertiary centres in 9 different CESEE countries between 2015 and 2020 was included. Baseline demographics, clinical presentation, indication for surgery, outcomes, hospital and all-cause-1-year mortality were studied., Results: A total of 295 ACHD patients (mean age 40 ± 14 years) with IE were included. Median time from symptoms onset to establishing diagnosis was 25 (11-59) days. The majority of patients (203, 68.8%) received previous empiric oral antibiotic therapy. The highest incidence of IE was observed on native and left sided valves, 194(65.8%) and 204(69.2%), respectively. More than half had a vegetation size ≥10 mm (164, 55.6%); overall 138 (46.8%) had valve complications and 119 (40.3%) had heart failure. In-hospital mortality was 26 (8.8%)., Conclusion: There is clear delay in establishing IE diagnosis amongst ACHD patients in CESEE countries. Adequate diagnosis is hampered by common prescription of empiric antibiotics before establishing formal diagnosis. Hence, patients commonly present with associated complications requiring surgery. Hospital treatment and survival are, nevertheless, comparable to other Western European countries. Improved awareness and education of patients and medical profession regarding IE preventive measures, risks, signs, and symptoms are urgently needed. Empiric antibiotic prescription before blood cultures are taken must be omitted., Competing Interests: Declaration of Competing Interest No conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Transcatheter aortic valve implantation-related infective endocarditis (TAVI-IE) is a well-recognised and serious complication following TAVI. The purpose of this study was to describe the clinical characteristics, microorganism spectrum, and outcomes of TAVI-IE in an Irish context., Methods: A prospective registry was used to assess the baseline demographics, procedural variables, and clinical outcomes of patients undergoing TAVI between 2009 and 2020 at two tertiary referral Irish Hospitals., Results: A total of 733 patients underwent TAVI during the study period. During a follow-up duration of 1,949 person-years (median 28 months), TAVI-IE occurred in 17 (2.3%) patients. The overall incidence was 0.87 per 100 person-years and the median time from TAVI to presentation with IE was 7 months [IQR: 5-13 months]. In those who developed TAVI-IE, the mean age was 78.7 years, 70.5% were male, and there was a trend towards more permanent pacemaker implantations post-TAVI (17.6% vs. 5.86%; p = 0.08). The dominant culprit microorganisms were streptococci (41.1%) and four (23.5%) cases were attributed to dental seeding. Major complications of TAVI-IE included one (5.8%) stroke, one (5.8%) in-hospital death, and two (11.7%) urgent surgical aortic valve replacements. The Kaplan-Meier estimate of survival at 1-year was 82% (95% CI = 55-95)., Conclusions: This Irish cohort of TAVI-IE exhibited a similar incidence and time to presentation compared to prior international registries; however, the 1-year mortality rate was comparatively lower. The need for rigorous dental clearance pre-TAVI and maintenance of dental health post-TAVI is underscored by the high prevalence of oral streptococcus species in this cohort., (© 2022. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Objectives: This study aimed to investigate the demographic differences amongst patients diagnosed with infective endocarditis (IE), predictors of adverse events, and the association between clinical decision-making and adverse health outcomes amongst patients with IE., Design: A retrospective cross-sectional study was conducted using the New South Wales (NSW) Admitted Patient Data Collection (APDC) from the Centre for Health Record Linkage (CHeReL)., Participants: All patients (N=18,044) from 2001 to 2020 in New South Wales who received a diagnosis of IE using ICD-10-AM diagnostic code 133.0 were included., Methods: Categorical variables were compared using the chi-square test or Fisher's exact test, while the t-test was used for continuous variables. The association between clinical decision-making and adverse health outcomes amongst patients with IE were examined via generalised linear mixed models., Results: Sex, age, birthplace and referral impacted clinical decision-making, in-hospital death and severity of the disease. Women experienced a higher risk of death and fewer escalations of care. Admission and mortality increased with age, with those aged 60 years and above responsible for 60.8% of hospitalisations. Despite octogenarians making up one-fifth of admissions and having the worst mortality rate (15.1%), they experienced only one in 10 intensive care (ICU) admissions. Overseas-born patients had fewer escalations of care and experienced less severe disease if referred by a medical practitioner. One out of 10 admissions that resulted in a hospital death were given non-emergency status, and one in two ICU patients died in hospital., Conclusions: Sex, age, place of birth, and clinical decision-making were important predictors of severe disease and death in hospital, lending weight that health care clinical decisions may adversely impact health outcomes for populations of interest., (Copyright © 2022 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Prosthetic valve endocarditis (PVE) remains a serious condition with a high mortality rate. Precise identification of the PVE-associated pathogen/s and their virulence is essential for successful therapy and patient survival. The commonly described PVE-associated pathogens are staphylococci, streptococci, and enterococci, with Staphylococcus aureus being the most frequently diagnosed species. Furthermore, multi-drug resistance pathogens are increasing in prevalence and continue to pose new challenges mandating a personalized approach. Blood cultures in combination with echocardiography are the most common methods to diagnose PVE, often being the only indication, it exists. In many cases, the diagnostic strategy recommended in the clinical guidelines does not identify the precise microbial agent, and frequently, false-negative blood cultures are reported. Despite the fact that blood culture findings are not always a good indicator of the actual PVE agent in the valve tissue, only a minority of re-operated prostheses are subjected to microbiological diagnostic evaluation. In this review, we focus on the diversity and the complete spectrum of PVE-associated bacterial, fungal, and viral pathogens in blood and prosthetic heart valve, their possible virulence potential, and their challenges in making a microbial diagnosis. We are curious to understand if the unacceptable high mortality of PVE is associated with the high number of negative microbial findings in connection with a possible PVE. Herein, we discuss the possibilities and limits of the diagnostic methods conventionally used and make recommendations for enhanced pathogen identification. We also show possible virulence factors of the most common PVE-associated pathogens and their clinical effects. Based on blood culture, molecular biological diagnostics, and specific valve examination, better derivations for the antibiotic therapy as well as possible preventive intervention can be established in the future., Competing Interests: Conflict of interest: There is no conflicts of interest of the authors who worked on this publication., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Echocardiography is the primary imaging modality for diagnosis of infective endocarditis (IE) in prosthetic valve endocarditis (PVE) including IE after transcatheter aortic valve implantation (TAVI). This study aimed to evaluate the characteristics and clinical outcomes of patients with absent compared with evident echocardiographic signs of TAVI-IE., Methods: Patients with definite TAVI-IE derived from the Infectious Endocarditis after TAVI International Registry were investigated comparing those with absent and evident echocardiographic signs of IE defined as vegetation, abscess, pseudo-aneurysm, intracardiac fistula, or valvular perforation or aneurysm., Results: Among 578 patients, 87 (15.1%) and 491 (84.9%) had absent (IE-neg) and evident (IE-pos) echocardiographic signs of IE, respectively. IE-neg were more often treated via a transfemoral access with a self-expanding device and had higher rates of peri-interventional complications (eg, stroke, major vascular complications) during the TAVI procedure (P < .05 for all). IE-neg had higher rates of IE caused by Staphylococcus aureus (33.7% vs 23.2%; P = .038) and enterococci (37.2% vs 23.8%; P = .009) but lower rates of coagulase-negative staphylococci (4.7% vs 20.0%, P = .001). IE-neg was associated with the same dismal prognosis for in-hospital mortality in a multivariate binary regression analysis (odds ratio: 1.51; 95% confidence interval [CI]: .55-4.12) as well as a for 1-year mortality in Cox regression analysis (hazard ratio: 1.10; 95% CI: .67-1.80)., Conclusions: Even with negative echocardiographic imaging, patients who have undergone TAVI and presenting with positive blood cultures and symptoms of infection are a high-risk patient group having a reasonable suspicion of IE and the need for an early treatment initiation., Competing Interests: Potential conflicts of interest. N. M. reports personal fees from Edwards Lifesciences (payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events), Medtronic (payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events), Biotronik, Novartis, Sanofi Genzyme, AstraZeneca, Pfizer, Bayer, Abbott (payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events), Abiomed, and Boston Scientific (consulting and payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events), outside the submitted work. J. R.-C. has received institutional research grants from Edwards Lifesciences, Medtronic, and Boston Scientific. V. P. received research grants from Boston Scientific, Medtronic, and Microport. A. L. reports personal fees from Medtronic, Abbott, Edwards Lifesciences, Boston Scientific, AstraZeneca, Novartis, Pfizer, Abiomed, Bayer, and Boehringer, outside the submitted work. H. C. H. has received institutional research grants from Abbott, Boston Scientific, Edwards Lifesciences, and Medtronic and consulting fees from Edwards Lifesciences and Medtronic. H. L. B. reports lecture fees from Edwards Lifesciences, outside the submitted work. J.-M. S. reports speaker’s honoraria from Abbott, Boston Scientific, Edwards Lifesciences, and Medtronic and research grants from Boston Scientific, Edwards Lifesciences, and Medtronic, outside the submitted work. W.-K. K. reports proctor/speaker’s fees/advisory board participation from Abbott, Boston Scientific, Edwards Lifesciences, Medtronic, Meril Life Sciences, and ShockWave Medical, outside the submitted work. L. S. has received consultant fees and/or institutional research grants from Abbott, Boston Scientific, Medtronic, and SMT. O. H. reports personal fees from Boston Scientific and payments from Abbott. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To define the frequency and characteristics of acute neurologic complications in children hospitalised with infective endocarditis and to identify risk factors for neurologic complications., Study Design: Retrospective cohort study of children aged 0-18 years hospitalised at a tertiary children's hospital from 1 January, 2008 to 31 December, 2017 with infective endocarditis., Results: Sixty-eight children met Duke criteria for infective endocarditis (43 definite and 25 possible). Twenty-three (34%) had identified neurologic complications, including intracranial haemorrhage (25%, 17/68) and ischaemic stroke (25%, 17/68). Neurologic symptoms began a median of 4.5 days after infective endocarditis symptom onset (interquartile range 1, 25 days), though five children were asymptomatic and diagnosed on screening neuroimaging only. Overall, only 56% (38/68) underwent neuroimaging during acute hospitalisation, so additional asymptomatic neurologic complications may have been missed. Children with identified neurologic complications compared to those without were older (48 versus 22% ≥ 13 years old, p = 0.031), more often had definite rather than possible infective endocarditis (96 versus 47%, p < 0.001), mobile vegetations >10mm (30 versus 11%, p = 0.048), and vegetations with the potential for systemic embolisation (65 versus 29%, p = 0.004). Six children died (9%), all of whom had neurologic complications., Conclusions: Neurologic complications of infective endocarditis were common (34%) and associated with mortality. The true frequency of neurologic complications was likely higher because asymptomatic cases may have been missed without screening neuroimaging. Moving forward, we advocate that all children with infective endocarditis have neurologic consultation, examination, and screening neuroimaging. Additional prospective studies are needed to determine whether early identification of neurologic abnormalities may direct management and ultimately reduce neurologic morbidity and overall mortality.

Objectives: A proportion of blaZ gene-positive methicillin-susceptible Staphylococcus aureus (MSSA) strains exhibits the cefazolin inoculum effect (CInE). Its clinical impact remains uncertain but could compromise the use of cefazolin in high-burden infections. To date, no study has been conducted in France or in Europe. We aimed to assess the prevalence of CInE and its association with blaZ beta-lactamase and S. aureus protein A (spa) types, and to assess the clinical outcomes in cefazolin-treated patients for infective endocarditis whose strain exhibited a CInE., Methods: This was a French single-center retrospective study of 51 MSSA strains from patients of the Nantes endocarditis prospective cohort, conducted between 2013 and 2018., Results: Cefazolin MIC 50 at high inoculum was 2 mg/L (IQR 1-2). CInE was found in 17.6 % of tested strains. Among blaZ-positive strains (n = 44), type A beta-lactamase was predominant (n = 25, 57 %). Thirty-seven S. aureus protein A (spa) types were found. No statistical association was shown between blaZ or spa types and CInE. CInE was neither associated with a higher rate of persistent bacteremia (25 % vs 56.3 %, p = 0.58) nor with clinical failure in patients treated with cefazolin, in comparison to patients with no CInE strain (25 % vs 56.3 %, p = 0.58)., Conclusion: The cefazolin inoculum effect was found in a substantial number of Staphylococcus aureus strains; however, minimum inhibitory concentrations remained globally low. CInE was not associated with a higher proportion of clinical failure on treatment., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Objectives: To determine the causative organisms, clinical features and outcome of canine infective endocarditis in the UK., Materials and Methods: Medical records of three veterinary referral hospitals were searched for dogs with infective endocarditis between December 2009 and December 2019. Signalment, clinical signs, causative organism, valve affected, treatment and survival data were recorded., Results: Seventy-seven cases with possible or definite infective endocarditis (according to the modified Duke criteria) were included. The majority were large breed (40/77 - 51.9%). There were 47 of 77 (61%) male dogs and the mean age was 7.3 ±3 years. A causative organism was identified in 26 of 77 (33.8%) cases. The most common organisms were Escherichia coli (7/27 - 25.9%), Pasteurella spp. (5/27 - 18.5%), Staphylococcus spp. (4/27 - 14.8%) and Corynebacterium spp. (4/27 - 14.8%). Bartonella spp. were not detected in any patients. The mitral valve was most commonly affected (48/77 - 62.3%). Clinical features were non-specific, with lethargy being the most common clinical sign observed (53/77 - 68.8%). Fifty-three dogs (68.8%) survived to discharge. The median survival time post discharge was 425 days (2 to 3650 days). The development of congestive heart failure was associated with a poorer outcome. Cardiac troponin concentration, antithrombotic use and the development of thromboembolism or arrhythmias were not significantly associated with outcome., Clinical Significance: Some dogs with infective endocarditis that survive to discharge can have a long lifespan. The inability to detect an underlying organism is common and Bartonella spp. may be a less prevalent cause of canine infective endocarditis in the UK than in the USA., (© 2022 The Authors. Journal of Small Animal Practice published by John Wiley & Sons Ltd on behalf of British Small Animal Veterinary Association.)

Background: Infective endocarditis (IE) in pediatric patients is a severe cardiac disease and its actual epidemiology and clinical outcome in Switzerland is scarcely studied., Methods: Retrospective nationwide multicenter data analysis of pediatric IE in children (<18 years) between 2011 and 2020., Results: 69 patients were treated for definite (40/69;58%) or possible IE (29/69;42%). 61% (42/69) were male. Diagnosis was made at median 6.4 years (IQR 0.8-12.6) of age with 19 patients (28%) during the first year of life. 84% (58/69) had congenital heart defects. IE was located on pulmonary (25/69;35%), mitral (10/69;14%), tricuspid (8/69;12%) and aortic valve (6/69;9%), and rarely on ventricular septal defect (VSD;4/69;6%) and atrial septal defect (ASD;1/69;1%). In 22% (16/69) localization was unknown. 70% (48/69) had postoperative IE, with prosthetic material involved in 60% (29/48; right ventricular to pulmonary artery conduit (24), VSD (4), ASD (1)). Causative organisms were mostly Staphylococci spp. (25;36%) including Staphylococcus aureus (19;28%), and Streptococci spp. (13;19%). 51% (35/69) suffered from severe complications including congestive heart failure (16;23%), sepsis (17;25%) and embolism (19;28%). Staphylococcus aureus was found as a predictor of severe complications in univariate and multivariate analysis (p = 0.02 and p = 0.033). In 46% (32/69) cardiac surgery was performed. 7% (5/69) died., Conclusions: IE in childhood remains a severe cardiac disease with relevant mortality. The high morbidity and high rate of complications is associated with Staphylococcus aureus infections. Congenital heart defects act as a risk factor for IE, in particular the high number of cases associated with prosthetic pulmonary valve needs further evaluation and therapeutic alternatives., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Congenital Heart Disease (CHD) predisposes to Infective Endocarditis (IE), but data about characterization and prognosis of IE in CHD patients is scarce., Methods: The ESC-EORP-EURO-ENDO study is a prospective international study in IE patients (n = 3111). In this pre-specified analysis, adult CHD patients (n = 365, 11.7%) are described and compared with patients without CHD (n = 2746) in terms of baseline characteristics and mortality., Results: CHD patients (73% men, age 44.8 ± 16.6 years) were younger and had fewer comorbidities. Of the CHD patients, 14% had a dental procedure before hospitalization versus 7% in non-CHD patients (p < 0.001) and more often had positive blood cultures for Streptococcus viridans (16.4% vs 8.8%, p < 0.001). As in non-CHD patients, IE most often affected the left-sided valves. For CHD patients, in-hospital mortality was 9.0% vs 18.1% in non-CHD patients (p < 0.001), and also, during the entire follow-up of 700 days, survival was more favorable (log-rank p < 0.0001), even after adjustment for age, gender and major comorbidities (Hazard Ratio (HR) 0.68; 95%CI 0.50-0.92). Within the CHD population, multivariable Cox regression revealed the following effects (HR and [95% CI]) on mortality: fistula (HR 6.97 [3.36-14.47]), cerebral embolus (HR 4.64 [2.08-10.35]), renal insufficiency (HR 3.44 [1.48-8.02]), Staphylococcus aureus as causative agent (HR 2.06 [1.11-3.81]) and failure to undertake surgery when indicated (HR 5.93 [3.15-11.18])., Conclusions: CHD patients with IE have a better outcome in terms of all-cause mortality. The observed high incidence of dental procedures prior to IE warrants further studies about the current use, need and efficacy of antibiotic prophylaxis in CHD patients., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The optimal treatment strategy for intravenous drug users (IVDU) with infective endocarditis (IE) is controversial. We therefore sought to investigate outcomes among IVDUs after surgery for IE., Methods: We retrospectively reviewed all 192 consecutive patients who underwent an operation for IE between 2005 and 2016 in the Helsinki University Hospital. Forty-seven patients (24.5%) were IVDUs and 145 (75.5%) were non-IVDUs. Mortality and reinfection and reoperation rates were evaluated., Results: IVDUs were younger (29.9 vs. 63.8 years, p  < 0.001) and had less cardiovascular risk factors and lower EuroSCORE II (4.3 vs. 7.3%, p  < 0.001), but Staphylococcus aureus infection (66.0 vs. 23.4%, p  < 0.001), tricuspid valve endocarditis (34.0 vs. 2.8%, p  < 0.001), and liver disease (63.8 vs. 2.8%, p  < 0.001) occurred more often in IVDUs than in non-IVDUs. Thirty-day mortality of IVDUs was 8.5% and that of non-IVDUs was 6.9% ( p  = 0.711). Survival of IVDUs at 5 years was 70.8 ± 7.4% and survival of non-IVDUs was 67.9 ± 4.7% ( p  = 0.678). Relative to an age- and sex-matched general population, IVDUs had 58.6 (95% confidence interval [CI]: 33.7-101.9; p  < 0.001) and non-IVUD 4.4 (95% CI: 3.1-6.2; p  < 0.001) standardized mortality ratio. IVDUs had a higher reinfection rate at 5 years (25.8 ± 7.7% vs. 3.0 ± 1.7%, p  < 0.001) and a higher early reoperation rate than non-IVDUs (10.6 vs. 1.4%, p  = 0.003)., Conclusions: IVDUs and non-IVDUs had comparable survival at 5 years, but IVDUs had a very significantly increased risk of death in comparison to an age- and sex-matched general population. IVDUs had higher reinfection and early reoperation rates. Survival was poor after medically treated reinfection., Competing Interests: None declared., (Thieme. All rights reserved.)

The increase of intravenous drug use has led to an increase in right-sided infective endocarditis and its complications including septic pulmonary embolism. The objective of this study was to compare the outcomes of tricuspid valve (TV) operations in patients with drug-use infective endocarditis (DU-IE) complicated by septic pulmonary emboli (PE). Hospitalizations for DU-IE complicated by septic PE were identified from the National Inpatient Sample from 2002 to 2019. Outcomes of patients who underwent TV operations were compared with medical management. The primary outcome was the incidence of major adverse cardiovascular events (MACEs), defined as in-hospital mortality, myocardial infarction, stroke, cardiogenic shock, or cardiac arrest. An inverse probability of treatment weighted analysis was utilized to adjust for the differences between the cohorts. A total of 9,029 cases of DU-IE with septic PE were identified (mean age 33.6 years), of which 818 patients (9.1%) underwent TV operation. Surgery was associated with a higher rate of MACE (14.5% vs 10.8%, p <0.01), driven by a higher rate of cardiogenic shock (6.1% vs 1.2%, p <0.01) but a lower rate of mortality (2.7% vs 5.7%, p <0.01). Moreover, TV operation was associated with an increased need for permanent pacemakers, blood transfusions, and a higher risk of acute kidney injury. In the inverse probability treatment weighting analysis, TV operation was associated with an increased risk for MACE driven by a higher rate of cardiogenic shock and cardiac arrest, but a lower rate of mortality when compared with medical therapy alone. In conclusion, TV operations in patients with DU-IE complicated by septic PE are associated with an increased risk for MACE but a decreased risk of mortality. Although surgical management may be beneficial in some patients, alternative options such as percutaneous debulking should be considered given the higher risk., (Copyright © 2022. Published by Elsevier Inc.)

Aims: Infective endocarditis (IE) is a life-threatening disease associated with high mortality and morbidity worldwide. We sought to determine how socioeconomic factors might influence its epidemiology, clinical presentation, investigation and management, and outcome, in a large international multicentre registry., Methods and Results: The EurObservational Programme (EORP) of the European Society of Cardiology EURO-ENDO (European Infective Endocarditis) registry comprises a prospective cohort of 3113 adult patients admitted for IE in 156 hospitals in 40 countries between January 2016 and March 2018. Patients were separated in three groups, according to World Bank economic stratification [group 1: high income (75.6%); group 2: upper-middle income (15.4%); group 3: lower-middle income (9.1%)]. Group 3 patients were younger [median age (interquartile range, IQR): group 1, 66 (53-75) years; group 2, 57 (41-68) years; group 3, 33 (26-43) years; P < 0.001] with a higher frequency of smokers, intravenous drug use, and human immunodeficiency virus infection (all P < 0.001) and presented later [median (IQR) days since symptom onset: group 1, 12 (3-35); group 2, 19 (6-54); group 3, 31 (12-62); P < 0.001] with a higher likelihood of developing congestive heart failure (13.6%, 11.1%, and 22.6%, respectively; P < 0.001) and persistent fever (9.8%, 14.2%, and 27.9%, respectively; P < 0.001). Among 2157 (69.3%) patients with theoretical indication for cardiac surgery, surgery was performed less frequently in group 3 patients (75.5%, 76.8%, and 51.3%, respectively; P < 0.001), who also demonstrated the highest mortality (15.0%, 23.0%, and 23.7%, respectively; P < 0.001)., Conclusion: Socioeconomic factors influence the clinical profile of patients presenting with IE across the world. Despite younger age, patients from the poorest countries presented with more frequent complications and higher mortality associated with delayed diagnosis and lower use of surgery., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims of the Study: Numerous studies from different countries have contributed to an improved understanding of blood culture-negative infective endocarditis. However, little is known about its epidemiology and microbiology in Switzerland. We aimed to assess the epidemiology and microbiology of blood culture-negative endocarditis at the University Hospital Zurich, Switzerland., Methods: We screened all patients hospitalised between 1997 and 2020 with possible or definite endocarditis at our institution. Thereof, we identified all cases with blood culture-negative endocarditis and retrospectively retrieved patient characteristics, microbiological, histopathological, radiographic and surgical data from medical records., Results: Among 861 patients screened, 66 (7.7%) cases of blood culture-negative endocarditis were identified. Thereof, 31 cases could be microbiologically documented or not documented (n = 30), and in five cases a non-infectious aetiology was confirmed. Endocarditis predominantly affected men (77%) and the left heart (79%); predisposing factors were prosthetic valves (42%), congenital heart disease (35%) and prior endocarditis (14%). The most common reasons for negative blood cultures were antibiotic treatment prior to blood culture sampling (35%), fastidious and slow growing microorganisms (30%) and definite non-infective endocarditis (8%). Coxiella burnetii and Bartonella spp. were the most common fastidious bacteria identified. In addition to serology, identification of causative microorganisms was possible by microbiological and/or histopathological analysis of tissue samples, of which polymerase chain reaction testing (PCR) of the 16S ribosomal RNA proved to be most successful., Conclusions: The present study provides a detailed analysis of blood culture-negative endocarditis over a time span of more than 20 years in Zurich, Switzerland. Antibiotic treatment prior to blood collection, and fastidious and slow growing organisms were identified as main reasons for sterile blood cultures. Typical culture-negative bacteria were mainly found by PCR and/or culture of tissue samples.

Aims: The incidence of infective endocarditis related to cardiac implantable electronic devices (CIEDs) has gradually increased. The risk associated with dental procedures in patients with CIED implantation and the need for prevention of infective endocarditis remain unclear. The present study investigated the incidence and risk of infective endocarditis associated with invasive dental procedures in patients with CIEDs., Methods and Results: We analysed a nationwide population-based cohort of patients with CIEDs who underwent dental procedures. We performed a self-controlled case series analysis and evaluated the incidence rate ratio of infective endocarditis 3 months after dental procedures. Of a total of 62 019 patients who underwent CIED implantation, 32 536 patients underwent at least one dental procedure during follow-up, and the mean number of dental procedures was 3.4 per patient. They were 152 infections with an incidence of 445 per 100 000 person-years in the dental procedure period and 500 events at an incidence of 255 per 100 000 person-years in the non-dental procedure period. The CIED-related infective endocarditis in the dental procedure period occurred significantly more frequently than during non-dental procedure periods (odds ratio, 1.75; 95% confidence interval, 1.48-2.05; P < 0.001). The mean time interval from dental procedure to infective endocarditis was 59.6 ± 47.3 days., Conclusion: Invasive dental procedures are associated with an increased risk of infective endocarditis in those who underwent CIED implantation. Appropriate preventive therapy might be needed in these patients., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Current guidelines on the management of infective endocarditis (IE) recommend follow-up blood cultures (FUBCs) to identify persistent bacteraemia, as this has prognostic value and guides treatment decisions. While persistent bacteraemia frequently occurs in Staphylococcus aureus bacteraemia and IE, its prevalence and impact in non-staphylococcal IE is largely unknown. We determined prevalence and prognostic value of persistent bacteraemia in non-staphylococcal IE., Methods: We conducted a retrospective analysis of all patients diagnosed with definite non-staphylococcal endocarditis according to the modified Duke Criteria in two university hospital endocarditis registries We determined the prevalence and prognostic value of persistent bacteraemia., Results: Of the included 159 patients 70 (44%) had prosthetic valve endocarditis (PVE). A median number of two [IQR 1-3] FUBCs were taken during the first week, with 134/159 (84%) having at least one FUBC in the first four days. Seven patients (4,4%) had persistent bacteraemia 48 h after start of antibiotic treatment: 5/70 patients (7.1%) with PVE and 2/89 (2.2%) with native valve endocarditis. Among 97 patients with streptococcal IE, nine patients with HACEK IE and six patients with Cutibacterium IE, no persistent bacteraemia was observed. Enterococcus faecalis was the causative microorganism in five patients with persistent bacteraemia, the other two had non-HACEK Gram-negative endocarditis., Conclusion: Persistent bacteraemia in non-staphylococcal endocarditis was rare. It was more frequently observed in PVE and was restricted to more resilient microorganisms such as enterococci and non-HACEK Gram-negative bacteria. Routine collection of FUBCs in patients with streptococcal endocarditis has a low yield and may require re-evaluation., Competing Interests: Declaration of Competing Interest The authors declared they do not have anything to disclose regarding conflict of interest with respect to this manuscript., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Infective endocarditis (IE) is associated with marked morbidity and mortality in the United States and parallels the opioid pandemic. Few studies explore this interaction and its effect on clinical outcomes. We analyzed contemporary patients admitted with IE to determine predictors of readmission in the United States. The 2017 National Readmission Database was used to identify index admissions in adults with the diagnosis of IE, based on the International Classification of Disease, 10th Revision codes. The primary outcome of interest was 30-day readmission. Secondary outcomes were mortality, hospital charges, and predictors of hospitalization readmission. Of 40,413 index admissions for IE, 5,558 patients (13.8%) were readmitted within 30 days. Patients who were readmitted were younger (55 ± 20 vs 61 ± 19 years, p <0.001) and more likely to have end-stage renal disease (12.2% vs 10.5%, p <0.001), hepatitis C virus (19.4% vs 12.6%, p <0.001), HIV (1.8% vs 1.2%, p = 0.001), opioid abuse (23.9% vs 15%, p <0.001), cocaine use (7.3% vs 4.4%, p <0.001), and other substance abuse (8.5 vs 5.6, p <0.001). Patients readmitted were less likely to have diabetes mellitus (27.8% vs 29.4%, p = 0.01), hypertension (56.9% vs 64%, p <0.001), heart failure (37.7% vs 40%, p <0.001), chronic kidney disease (31.2% vs 32%, p <0.001), and peripheral vascular disease (3.6% vs 4.6%, p = 0.001). The median cost of index admission for the total cohort was $84,325 (39,922 to 190,492). After adjusting for age, diabetes mellitus, heart failure, hypertension, and end-stage renal disease, opioid abuse (odds ratio [OR] 1.34; 95% confidence interval [CI] 1.23 to 1.46; p <0.001), cocaine use (OR 1.32; 95% CI 1.17 to 1.48; p <0.001), other substance abuse (OR 1.16; 95% CI 1.04 to 1.30; p = 0.008), and hepatitis C virus (OR 1.32; 95% CI 1.21 to 1.43; p <0.001) correlated with higher odds of 30-day readmission. These factors may present targets for future intervention., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Purpose: Neurological complications following infective endocarditis (IE) directly contribute to long-term morbidity. We examined the risk factors for different neurological complications of left-sided IE., Methods: Using a database of consecutive adults admitted to a health system with left-sided IE from 2015 to 2019, the frequency of cerebral infarcts, intraparenchymal hemorrhage, cerebral microbleeds (CMB), mycotic aneurysm, and encephalopathy was determined. Variables with significant differences comparing each neurological complication (p < 0.1) were entered into regression models along with age to determine predictors., Results: 211 patients with mean age 54 (±18) years, and 69 (33%) females were included. Infarcts were found in 118 (56%) patients, intraparenchymal hemorrhage was found in 17 (8%) patients, CMB were found in 58 (27%) patients, mycotic aneurysms were found in 22 (10%) patients, and encephalopathy occurred in 16 (8%) patients. In multivariable models, vegetation size ≥15 mm was associated with a higher risk of infarcts (aOR 2.26, 95% CI (1.12-4.57)), and the presence of a mycotic aneurysm was a risk factor for intraparenchymal hemorrhage (aOR 18.79, 95% CI (3.97-88.97)). Prosthetic valves (aOR 2.89, 95% CI (1.11-7.54)) and Staphylococcus aureus infection (aOR 3.50, 95% CI (1.08-11.36)) were associated with CMB. No risk factors emerged as predictors of encephalopathy., Conclusions: Large vegetation size is associated with stroke in patients with IE. Mycotic aneurysms are found at a higher frequency in young patients and are the primary cause of intraparenchymal hemorrhage. CMB may be related to prosthetic valves and Staphylococcus aureus infection., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022. Published by Elsevier B.V.)

Background: Our aim was to compare pediatric infective endocarditis (IE) with the clinical profile and outcomes of IE in adults., Methods: Prospective multicenter registry in 31 Spanish hospitals including all patients with a diagnosis of IE from 2008 to 2020., Results: A total of 5590 patients were included, 49 were <18 years (0.1%). Congenital heart disease (CHD) was present in 31 children and adolescents (63.2%). Right-sided location was more common in children/adolescents than in adults (46.9% vs. 6.3%, P < 0.001). Pediatric pulmonary IE was more frequent in patients with CHD (48.4%) than in those without (5.6%), P = 0.004. Staphylococcus aureus etiology tended to be more common in pediatric patients (32.7%) than in adults (22.3%), P = 0.082. Heart failure was less common in pediatric patients than in adults, due to the lower rate of heart failure in children/adolescents with CHD (9.6%) with respect to those without CHD (44.4%), P = 0.005. Inhospital mortality was high in both children, and adolescents and adults (16.3% vs. 25.9%; P = 0.126)., Conclusions: Most IE cases in children and adolescents are seen in patients with CHD that have a more common right-sided location and a lower prevalence of heart failure than patients without CHD. IE in children and adolescents without CHD has a more similar profile to IE in adults., Impact: Infective endocarditis (IE) in children and adolescents is often seen in patients with congenital heart disease (CHD). Right-sided location is the most common in patients with CHD and heart failure is less common as a complication compared with patients without CHD. Infective endocarditis (IE) in children/adolescents without CHD has a more similar profile to IE in adults. In children/adolescents without CHD, locations were similar to adults, including a predominance of left-sided IE. Acute heart failure was the most frequent complication, seen mainly in adults, and in children/adolescents without CHD., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Recently, five North American studies have reported 471 persons who injected drugs intravenously (PWID) (25.34%) out of a total of 1858 patients with infective endocarditis (IE) and three European studies have reported 263 PWID out of 1225 patients with IE (21.46%). Both in North America and Europe the mean age of PWID with IE was 32-38 years and 41-44 years, respectively. Both in North America and in Europe Staphylococcus aureus was the leading cause of IE in PWID (67.30% and 66.15%, respectively). IE involves the tricuspid valve in 90% of cases and mitral and/or aortic valves in less than 15% of cases; the mortality rate is 2.0-2.5%. In North America and in Europe, streptococci caused IE in 10.61% and 10.64% of PWID, respectively, enterococci in 6.58% and 9.50%. Other etiologies accounted for 1-2%. Almost 6% of North American cases and almost 10% of European cases were polymicrobial. New episodes (25-32%) were mostly reinfections (up to 86.4%). PWID's in-hospital mortality was not significantly different from non-PWID's. Ten-year survival of PWID and non-PWID with IE was comparable in an American surgical study (69.5% vs 68.7%) and significantly different in a British study (43.8% vs 83.5%).

Background: Scarce data exist about early infective endocarditis (IE) after trans-catheter aortic valve replacement (TAVR)., Objective: The objective was to evaluate the characteristics, management, and outcomes of very early (VE) IE (≤ 30 days) after TAVR., Methods: This multicenter study included a total of 579 patients from the Infectious Endocarditis after TAVR International Registry who had the diagnosis of definite IE following TAVR., Results: Ninety-one patients (15.7%) had VE-IE. Factors associated with VE-IE (vs. delayed IE (D-IE)) were female gender (p = 0.047), the use of self-expanding valves (p < 0.001), stroke (p = 0.019), and sepsis (p < 0.001) after TAVR. Staphylococcus aureus was the main pathogen among VE-IE patients (35.2% vs. 22.7% in the D-IE group, p = 0.012), and 31.2% of Staphylococcus aureus infections in the VE-IE group were methicillin-resistant (vs. 14.3% in the D-IE group, p = 0.001). The second-most common germ was enterococci (34.1% vs. 24.4% in D-IE cases, p = 0.05). VE-IE was associated with very high in-hospital (44%) and 1-year (54%) mortality rates. Acute renal failure following TAVR (p = 0.001) and the presence of a non-enterococci pathogen (p < 0.001) were associated with an increased risk of death., Conclusion: A significant proportion of IE episodes following TAVR occurs within a few weeks following the procedure and are associated with dismal outcomes. Some baseline and TAVR procedural factors were associated with VE-IE, and Staphylococcus aureus and enterococci were the main causative pathogens. These results may help to select the more appropriate antibiotic prophylaxis in TAVR procedures and guide the initial antibiotic therapy in those cases with a clinical suspicion of IE. Very early infective endocarditis after trans-catheter aortic valve replacement. VE-IE indicates very early infective endocarditis (≤30 days post TAVR). D-IE indicates delayed infective endocarditis., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Current guidelines recommend either ampicillin plus ceftriaxone (AC) or amoxicillin/ampicillin plus gentamicin (AG) with an equivalent class IB recommendation in Enterococcus faecalis endocarditis. However, previous observational studies suggest that AC might be favourable in terms of adverse events., Objectives: To investigate whether AC is non-inferior to AG, and if it is associated with less adverse events., Methods: In June 2021, a systematic literature search using the databases PubMed/MEDLINE, CDSR, CENTRAL, CCAs, EBM Reviews, Web of Science and LILACS was conducted by two independent reviewers. Studies were considered eligible if (P) patients included were ≥ 18 years of age and had IE with E. faecalis, (I) treatment with AC was compared to (C) treatment with AG and (O) outcomes on in-hospital mortality, nephrotoxicity and adverse events requiring drug withdrawal were reported. Odds ratios and 95% confidence intervals were calculated using random-effects models with the Mantel-Haenszel method, the Sidik-Jonkman estimator for τ 2 and the Hartung-Knapp adjustment., Results: Treatment with AC was non-inferior to AG, as depicted by no significant differences in-hospital mortality, 3-month mortality, relapses or treatment failure. Furthermore, AC was associated with a lower prevalence of nephrotoxicity (OR 0.45 [0.26-0.77], p = 0.0182) and drug withdrawal due to adverse events (OR 0.11 [0.03-0.46], p = 0.0160) than AG., Conclusions: Treatment with AC was non-inferior to treatment with AG, and it was associated with a reduced prevalence of nephrotoxicity and drug withdrawal due to adverse events. Thus, combination therapy with AC appears favourable over AG in patients with E. faecalis IE., (© 2021. The Author(s).)

Background: Streptococcus bovis/equinus complex (SBSEC) comprise several species and subspecies and is a common cause of infective endocarditis (IE). S. gallolyticus subsp. gallolyticus ( Sg gallolyticus ) accounts for a majority of SBSEC IE, but the risk of IE for other subspecies is largely unknown. We aimed to investigate the clinical presentation of bacteraemia, and proportion of patients with IE in bacteraemia with the most common subspecies., Methods: A retrospective cohort study of SBSEC-bacteraemia identified in clinical laboratory databases, in Skåne Region, Sweden, 2003-2018. Bacteraemia with Sg gallolyticus, S. gallolyticus subsp. pasteurianus ( Sg pasteurianus ) , S. lutetiensis and S. infantarius subsp. infantarius ( Si infantarius ) were included. Subspecies was identified by whole genome sequencing. Medical charts were reviewed according to a predetermined protocol, IE was defined by the criteria from European Society of Cardiology., Results: In total, 210 episodes of SBSEC-bacteraemia were included. Definite IE was identified in 28/210 (13%) episodes. Of these, 7/28 (25%) were prosthetic valve-IE, 1/28 (4%) related to a cardiovascular implantable electronic device and 10/28 (36%) required heart valve surgery. The proportions of IE among different subspecies were: Sg gallolyticus 17/52 (33%), Si infantarius 5/31 (16%) , Sg pasteurianus 4/83 (5%) and S. lutetiensis 2/44 (5%) ( p  < 0.001). Sg pasteurianus and S. lutetiensis were more often associated with intra-abdominal- and polymicrobial infection., Conclusion: The proportion of IE in SBSEC-bacteraemia varies substantially depending on subspecies. Echocardiography should always be considered in bacteraemia with Sg gallolyticus and Si infantarius , and can sometimes be omitted in bacteraemia with Sg pasteurianus and S. lutetiensis .

Introduction: The prevalence and impact of pulmonary embolism (PE) in patients with lead-related infective endocarditis undergoing transvenous lead extraction (TLE) are unknown., Methods: Twenty-five consecutive patients with vegetations ≥10 mm at transoesophageal echocardiography were prospectively studied. Contrast-enhanced chest computed tomography (CT) was performed before (pre-TLE) and after (post-TLE) the lead extraction procedure., Results: Pre-TLE CT identified 18 patients (72%) with subclinical PE. The size of vegetations in patients with PE did not differ significantly from those without (median 20.0 mm [interquartile range: 13.0-30.0] vs. 14.0 mm [6.0-18.0], p = 0.116). Complete TLE success was achieved in all patients with 3 (2-3) leads extracted per procedure. There were no postprocedure complications related to the presence of PE and no differences in terms of fluoroscopy time and need for advanced tools. In the group of positive pre-TLE CT, post-TLE scan confirmed the presence of silent PE in 14 patients (78%). There were no patients with new PE formation. Large vegetations (≥20 mm) tended to increase the risk of post-TLE subclinical PE (odds ratio 5.99 [95% confidence interval (CI): 0.93-38.6], p = 0.059). During a median 19.4 months follow-up, no re-infection of the implanted system was reported. Survival rates in patients with and without post-TLE PE were similar (hazard ratio: 1.11 [95% CI: 0.18-6.67], p = 0.909)., Conclusion: Subclinical PE detected by CT was common in patients undergoing TLE with lead-related infective endocarditis and vegetations but was not associated with the complexity of the procedure or adverse outcomes. TLE procedure seems safe and feasible even in patients with large vegetations., (© 2022 The Authors. Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

Purpose: High mortality and a limited performance of valvular surgery are typical features of infective endocarditis (IE) in octogenarians, even though surgical treatment is a major determinant of a successful outcome in IE., Methods: Data from the prospective multicentre ESC EORP EURO-ENDO registry were used to assess the prognostic role of valvular surgery depending on age., Results: As compared to < 80 yo patients, ≥ 80 yo had lower rates of theoretical indication for valvular surgery (49.1% vs. 60.3%, p < 0.001), of surgery performed (37.0% vs. 75.5%, p < 0.001), and a higher in-hospital (25.9% vs. 15.8%, p < 0.001) and 1-year mortality (41.3% vs. 22.2%, p < 0.001). By multivariable analysis, age per se was not predictive of 1-year mortality, but lack of surgical procedures when indicated was strongly predictive (HR 2.98 [2.43-3.66]). By propensity analysis, 304 ≥ 80 yo were matched to 608 < 80 yo patients. Propensity analysis confirmed the lower rate of indication for valvular surgery (51.3% vs. 57.2%, p = 0.031) and of surgery performed (35.3% vs. 68.4%, p < 0.0001) in ≥ 80 yo. Overall mortality remained higher in ≥ 80 yo (in-hospital: HR 1.50[1.06-2.13], p = 0.0210; 1-yr: HR 1.58[1.21-2.05], p = 0.0006), but was not different from that of < 80 yo among those who had surgery (in-hospital: 19.7% vs. 20.0%, p = 0.4236; 1-year: 27.3% vs. 25.5%, p = 0.7176)., Conclusion: Although mortality rates are consistently higher in ≥ 80 yo patients than in < 80 yo patients in the general population, mortality of surgery in ≥ 80 yo is similar to < 80 yo after matching patients. These results confirm the importance of a better recognition of surgical indication and of an increased performance of surgery in ≥ 80 yo patients., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Objectives: To describe the clinical features and outcomes of infective endocarditis (IE) in pregnant women who do not inject drugs., Methods: A multinational retrospective study was performed at 14 hospitals. All definite IE episodes between January 2000 and April 2021 were included. The main outcomes were maternal mortality and pregnancy-related complications., Results: Twenty-five episodes of IE were included. Median age at IE diagnosis was 33.2 years (IQR 28.3-36.6) and median gestational age was 30 weeks (IQR 16-32). Thirteen (52%) patients had no previously known heart disease. Sixteen (64%) were native IE, 7 (28%) prosthetic and 2 (8%) cardiac implantable electronic device IE. The most common aetiologies were streptococci (n = 10, 40%), staphylococci (n = 5, 20%), HACEK group (n = 3, 12%) and Enterococcus faecalis (n = 3, 12%). Twenty (80%) patients presented at least one IE complication; the most common were heart failure (n = 13, 52%) and symptomatic embolism other than stroke (n = 4, 16%). Twenty-one (84%) patients had surgery indication and surgery was performed when indicated in 19 (90%). There was one maternal death and 16 (64%) patients presented pregnancy-related complications (11 patients ≥1 complication): 3 pregnancy losses, 9 urgent Caesarean sections, 2 emergency Caesarean sections, 1 fetal death, and 11 preterm births. Two patients presented a relapse during a median follow-up of 3.1 years (IQR 0.6-7.4)., Conclusions: Strict medical surveillance of pregnant women with IE is required and must involve a multidisciplinary team including obstetricians and neonatologists. Furthermore, the potential risk of IE during pregnancy should never be underestimated in women with previously known underlying heart disease., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: A few years after the publication of the British guidelines, national recommendations were published by the Swedish Medical Products Agency in October 2012, promoting the cessation of antibiotic prophylaxis in dentistry for the prevention of infective endocarditis (IE). The aim of this study was to evaluate whether the incidence of oral streptococcal IE increased among high-risk individuals after October 2012., Methods: This nationwide cohort study included all adult individuals (>17 years) living in Sweden from January 2008 to January 2018, with a diagnose code or surgical procedure code indicating high risk of IE. Cox proportional hazard models were performed to calculate adjusted ratios of oral streptococcal IE before and after October 2012 between high-risk individuals and references., Results: This study found no increased incidence of oral streptococcal IE among high-risk individuals during the 5 years after the cessation, compared with before. Hazard rate ratios were 15.4 (95% confidence interval [CI]: 8.3-28.5) before and 20.7 (95% CI: 10.0-42.7) after October 2012 for prevalent high-risk individuals. Corresponding ratios for incident high-risk individuals were 66.8 (95% CI: 28.7-155.6) and 44.6 (95% CI: 22.9-86.9). Point estimates for interaction with time period were 1.4 (95% CI: .6-3.5) and 0.8 (95% CI: .5-1.3) for prevalent and incident high-risk individuals, respectively., Conclusion: The results suggest that the current Swedish recommendation not to administer antibiotic prophylaxis for the prevention of IE in dentistry has not led to an increased incidence of oral streptococcal IE among high-risk individuals., Competing Interests: Potential conflicts of interest. The authors have no competing interests to declare. No author has a potential conflict of interest or funding source. All authors have completed the Unified Competing Interest form (available on request from the corresponding author) and declare: no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. C. K. W. reports being an unpaid Board member for the Swedish Society of Oral and Maxillofacial Surgery., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America.)

Aims: To determine the prognosis of patients treated for infective endocarditis (IE) according to their healthcare pathway. To assess how the ESC guidelines are implemented concerning the performance of transoesophageal echocardiography, the use of antibiotic therapy, and the performance of valve surgery; and to compare the epidemiological profile of IE according to the type of centres in which the patients are hospitalized., Methods and Results: In a prospective multicentric study including 22 hospitals in the South-East of France, 342 patients were classified into three groups according to their healthcare pathway: 119 patients diagnosed and taken care entirely in a reference centre or hospital with cardiac surgery [Referral Center (RC) group], 111 patients diagnosed and initially taken care in a non-RC (NRC), then referred in a centre including cardiac surgery [transferred to the Referral Center (TRC) group] and 112 patients totally taken care in the NRC (NRC group). One-year mortality was 26% (88 deaths) and was not significantly different between Groups 1 and 2 (20 vs. 21%, P = 0.83). Patients in the NRC group had a higher mortality (37%) compared with patients in the RC and TRC groups (P < 0.001). ESC guidelines were not implemented similarly depending on the healthcare pathway (P = 0.04). Patients in the NRC group were significantly older (P < 0.001) and had more comorbidities (P < 0.001) than patients treated in referral centres., Conclusion: Prognosis of patients with IE is influenced by their healthcare pathway. Patients treated exclusively in NRC have a worse prognosis than patients treated in referral or surgical centres., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Antibiotic prophylaxis (AP) before invasive dental procedures (IDPs) is recommended to prevent infective endocarditis (IE) in those at high IE risk, but there are sparse data supporting a link between IDPs and IE or AP efficacy in IE prevention., Objectives: The purpose of this study was to investigate any association between IDPs and IE, and the effectiveness of AP in reducing this., Methods: We performed a case-crossover analysis and cohort study of the association between IDPs and IE, and AP efficacy, in 7,951,972 U.S. subjects with employer-provided Commercial/Medicare-Supplemental coverage., Results: Time course studies showed that IE was most likely to occur within 4 weeks of an IDP. For those at high IE risk, case-crossover analysis demonstrated a significant temporal association between IE and IDPs in the preceding 4 weeks (OR: 2.00; 95% CI: 1.59-2.52; P = 0.002). This relationship was strongest for dental extractions (OR: 11.08; 95% CI: 7.34-16.74; P < 0.0001) and oral-surgical procedures (OR: 50.77; 95% CI: 20.79-123.98; P < 0.0001). AP was associated with a significant reduction in IE incidence following IDP (OR: 0.49; 95% CI: 0.29-0.85; P = 0.01). The cohort study confirmed the associations between IE and extractions or oral surgical procedures in those at high IE risk and the effect of AP in reducing these associations (extractions: OR: 0.13; 95% CI: 0.03-0.34; P < 0.0001; oral surgical procedures: OR: 0.09; 95% CI: 0.01-0.35; P = 0.002)., Conclusions: We demonstrated a significant temporal association between IDPs (particularly extractions and oral-surgical procedures) and subsequent IE in high-IE-risk individuals, and a significant association between AP use and reduced IE incidence following these procedures. These data support the American Heart Association, and other, recommendations that those at high IE risk should receive AP before IDP., Competing Interests: Funding Support and Author Disclosures This study was funded by a research grant from the Delta Dental of Michigan Research Committee and Renaissance Health Service Corporation. The views expressed in this publication are those of the authors and do not necessarily represent those of the funders. The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review or approval of the manuscript; or the decision to submit the manuscript for publication. Profs Thornhill, Lockhart, and O’Gara have received support from the Delta Dental Research and Data Institute for this work. Dr Dayer has received support in the last 3 years from Biotronik that was unconnected to the submitted work; and was a consultant to the review committee that produced the 2015 update to NICE clinical guideline 64 on prophylaxis against infective endocarditis. Prof Prendergast has received unrestricted research and educational grants from Edwards Lifesciences; has received lecture fees from Abbott, Anteris, and Edwards Lifesciences; and has received consultancy fees from and serves on the Scientific Advisory Board for Anteris and Microport (all unconnected to the submitted work); was a member of the Task Force on the Prevention, Diagnosis and Treatment of Infective Endocarditis of the European Society of Cardiology (ESC) that produced the 2009 ESC guidelines; and acted as an external advisor to the committee that produced NICE clinical guideline 64 on Prophylaxis Against Infective Endocarditis in March 2008. Dr Lockhart is a member of the writing committee reviewing the current AHA guidelines on antibiotic prophylaxis to prevent infective endocarditis. Drs Lockhart and Baddour were members of the AHA Committee on Rheumatic Fever, Endocarditis and Kawasaki Disease, and were involved in producing both the 2007 and 2021 AHA guidelines on prevention of infective endocarditis. Dr O’Gara has received support in the last 3 years from Medtronic, Edwards Scientific, and the National Heart, Lung, and Blood Institute that was unconnected to the submitted work. Dr Baddour has received royalty payments (authorship duties) from UpToDate, Inc; and has received consulting fees from Boston Scientific, Botanix Pharmaceuticals, and Roivant Sciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Infective endocarditis (IE) following transcatheter aortic valve replacement (TAVR) has been associated with a dismal prognosis. However, scarce data exist on IE perivalvular extension (PEE) in such patients., Methods: This multicenter study included 579 patients who had the diagnosis of definite IE at a median of 171 (53-421) days following TAVR. PEE was defined as the presence of an intracardiac abscess, pseudoaneurysm, or fistula., Results: A total of 105 patients (18.1%) were diagnosed with PEE (perivalvular abscess, pseudoaneurysm, fistula, or a combination in 87, 7, 7, and 4 patients, respectively). A history of chronic kidney disease (adjusted odds ratio [ORadj], 2.08; 95% confidence interval [CI]: 1.27-3.41; P = .003) and IE secondary to coagulase-negative staphylococci (ORadj, 2.71; 95% CI: 1.57-4.69; P < .001) were associated with an increased risk of PEE. Surgery was performed at index IE episode in 34 patients (32.4%) with PEE (vs 15.2% in patients without PEE, P < .001). In-hospital and 2-year mortality rates among PEE-IE patients were 36.5% and 69.4%, respectively. Factors independently associated with an increased mortality were the occurrence of other complications (stroke post-TAVR, acute renal failure, septic shock) and the lack of surgery at index IE hospitalization (padj < 0.05 for all)., Conclusions: PEE occurred in about one-fifth of IE post-TAVR patients, with the presence of coagulase-negative staphylococci and chronic kidney disease determining an increased risk. Patients with PEE-IE exhibited high early and late mortality rates, and surgery during IE hospitalization seemed to be associated with better outcomes., Competing Interests: Potential conflicts of interest. J. R.-C. has received institutional research grants from Edwards Lifesciences, Medtronic, and Boston Scientific. V. P. has received institutional research grants from Medtronic, Boston Scientific, and Microport. D. T. has received consulting fees from Abbott Vascular, Boston Scientific, Edwards Lifesciences, and Medtronic. H. C. H. has received institutional research grants from Abbott, Boston Scientific, Edwards Lifesciences, and Medtronic and consulting fees from Edwards Lifesciences and Medtronic. J. G. W. has received consulting fees from Edwards Lifesciences and St. Jude Medical. R. M. has received research grants from Edwards Lifesciences, Medtronic, Abbott, Capricor, and St. Jude Medical; has served as a proctor for Edwards Lifesciences; and has received consulting fees from Medtronic. F. S. de B. has received honoraria from Medtronic and Edwards Lifesciences for symposium speeches and proctoring cases. S. L. has received consulting fees from Edwards Lifesciences. H. Le B. has received lecture fees from Edwards Lifesciences outside the submitted work. J. M. S. has received speaker honoraria from Abbott, Boston Scientific, Edwards Lifesciences, and Medtronic and research grants from Boston Scientific, Edwards Lifesciences, and Medtronic outside the submitted work. K. W.-K. has received personal fees from Boston Scientific, Edwards Lifesciences, Abbott, Medtronic, and Meril outside the submitted work. S. S. reports grants to their institution from Edwards Lifesciences, Medtronic, Boston Scientific, and Abbott and has received personal fees from Boston Scientific, BTG, and Teleflex outside the submitted work. O. H. has received personal fees from Boston Scientific and payments from Abbott. N. M. has received personal fees from Edwards Lifesciences, Medtronic, Biotronik, Novartis, Sanofi Genzyme, AstraZeneca, Pfizer, and Bayer outside the submitted work. All remaining authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background Most published reports describing outcomes of patients with cardiovascular implantable electronic device-related infective endocarditis (CIED-IE) are single-center studies with small patient sample sizes. The goal of this study was to utilize population-based data to assess trends in CIED-IE hospitalization and to compare outcomes between patients hospitalized with CIED-IE, prosthetic valve endocarditis (PVE), and native valve endocarditis (NVE). Methods and Results A query of the National (Nationwide) Inpatient Sample (NIS) database between 2003 and 2017 identified 646 325 patients hospitalized with infective endocarditis in the United States of whom 585 974 (90%) had NVE, 27 257 (4.2%) had CIED-IE, and 26 111 (4%) had PVE. There was a 509% increase in CIED-IE hospitalizations in the United States from 2003 to 2017 ( P trend<0.001). In-hospital mortality and length of stay associated with CIED-IE decreased during the study period from 15% and 20 days in 2003 to 9.7% and 19 days in 2017 ( P trend=0.032 and 0.018, respectively). The in-hospital mortality rate was lower in patients hospitalized with CIED-IE (9.2%) than in patients with PVE (12%) and NVE (12%). Length of stay was longest in the CIED-IE group (17 compared with 14 days for both NVE and PVE). Hospital costs were highest for the CIED-IE group ($56 000 compared with $37 000 in NVE and $45 000 in PVE). Conclusions Despite the fact that the number of comorbidities per patient with CIED-IE increased during the study period, mortality rate and hospital length of stay decreased. The mortality rate was significantly lower for patients with CIED-IE than for patients with NVE and PVE. Patients with CIED-IE had the longest lengths of stay and highest hospital costs.

Background: People who inject drugs and have infective endocarditis have a high risk of recurrent infective endocarditis and death. We aimed to characterize clinical factors associated with mortality and assess the probability of infective endocarditis recurrence in the presence of death as a competing risk., Methods: A retrospective cohort study was conducted of people who inject drugs, identified between April 5, 2007 and March 15, 2018 with the Modified Duke Criteria for definite infective endocarditis. Fine-Gray sub-distribution and Cox proportional hazards modeling were conducted to determine variables associated with the rate of infective endocarditis recurrence and mortality, respectively., Results: Of the 310 patients with infective endocarditis who inject drugs, 236 experienced a single episode and 74 experienced recurrent episodes. Peripherally inserted central catheter misuse was associated with an increased rate of infective endocarditis recurrence (sub-distribution hazard ratio 2.41; 95% confidence interval [CI], 1.17-4.98; P = .02) and mortality (hazard ratio [HR] 2.44; 95% CI, 1.15-5.17; P = .02). Non-right-sided infection, peripheral intravenous therapy, and intensive care unit admission were also associated with increased mortality. Oral therapy (HR 0.38; 95% CI, 0.16-0.91; P = .03), outpatient treatment (HR 0.39; 95% CI, 0.19-0.82; P = .01), and inpatient referral to addiction services (HR 0.39; 95% CI, 0.22-0.70; P = .002) were associated with a decrease in mortality., Conclusions: Patients who misuse their peripherally inserted central catheter are at higher risk of recurrent infective endocarditis and death. Avoidance of peripherally inserted central catheter lines and use of intravenous peripheral therapy did not reduce mortality, but oral therapy was associated with reduced risk. Inpatient addiction services referral is important., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Infective endocarditis (IE) typically occurs in patients with underlying cardiac conditions (UCC). Little is known about IE in patients without UCC. We aimed to describe the clinical, microbiological and imaging characteristics, management, and in-hospital mortality of IE patients without UCC., Methods: We analysed the data of patients with definite IE included in an observatory between 1st January 2009 and 31st December 2019. We described patients without UCC compared to those with UCC., Results: Of 1502 IE patients, 475 (31.6%) had no UCC. They were younger (median 64.0 [19.0-101.0] vs. 70.0 [18.0-104.0] years, p  < .001), more often on chronic haemodialysis (5.5% vs. 2.7%, p  = .008), and had more often malignancy (22.5% vs. 17.3%, p  = .017), immune deficiency (10.3% vs. 6.4%, p  = .008), and an indwelling central venous line (14.5% vs. 7.0%, p  < .001). They more often developed cerebral complications (34.7% vs. 27.5%, p  = .004) and extracerebral embolism (48.6% vs. 36.1%, p  < .001). Causative microorganisms were less often coagulase negative staphylococci (5.9% vs. 10.8%, p  = .002) or enterococci (10.3% vs. 15.0%, p  = .014) and more often group D streptococci (14.1% vs. 10.0%, p  = .020). Vegetations were more common (92.8% vs. 77.0%, p  < .001) and larger (14.0 [1.0-87.0], vs. 12.0 [0.5-60.0] mm, p  = .002). They had more valve perforation or valve regurgitation (67.4% vs. 53.0%, p  < .001) and underwent valve surgery more often (53.5% vs. 36.3%, p  < .001). In-hospital mortality did not significantly differ between groups., Conclusion: Patients with IE and no UCC were younger than those with UCC, had specific comorbidities and portals of entry, and a more severe disease course.

Background: Outcomes after transcatheter aortic valve replacement (TAVR) and infectious diseases may vary according to sex., Methods: This multicentre study aimed to determine the sex differences in clinical characteristics, management, and outcomes of infective endocarditis (IE) after TAVR. A total of 579 patients (217 women, 37.5%) who had the diagnosis of definite IE following TAVR were included retrospectively from the Infectious Endocarditis After TAVR International Registry., Results: Women were older (80 ± 8 vs 78 ± 8 years; P = 0.001) and exhibited a lower comorbidity burden. Clinical characteristics and microbiological profiles were similar between men and women, but culture-negative IE was more frequent in women (9.9% vs 4.3%; P = 0.009). A high proportion of patients had a clinical indication for surgery (54.4% in both groups; P = 0.99), but a surgical intervention was performed in a minority of patients (women 15.2%, men 20.3%; P = 0.13). The mortality rate at index IE hospitalisation was similar in both groups (women 35.4%, men 31.7%; P = 0.37), but women exhibited a higher mortality rate at 2-year follow-up (63% vs 52.1%; P = 0.021). Female sex remained an independent risk factor for cumulative mortality in the multivariable analysis (adjusted HR 1.28, 95% CI 1.02-1.62; P = 0.035). After adjustment for in-hospital events, surgery was not associated with better outcomes in women., Conclusions: There were no significant sex-related differences in the clinical characteristics and management of IE after TAVR. However, female sex was associated with increased 2-year mortality risk., (Copyright © 2022 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

North America is facing an opioid epidemic and growing illicit drug supply, contributing to growing numbers of injection drug use-related infective endocarditis (IDU-IE). Patients with IDU-IE have high early and late mortality. Patients with IDU-IE more commonly present with right-side IE compared with those with non-IDU IE, and a majority are a result of Streptococcus aureus. Although most patients can be successfully managed with intravenous antibiotic treatment, surgery is often required in part owing to high relapse rates, potential treatment biases, and more aggressive pathophysiology in some. Multidisciplinary management as endocarditis teams, including not only cardiologists and cardiac surgeons, but also infectious disease specialists, drug addiction experts, social workers, neurologists, and neurosurgeons, is essential to best manage substance use disorder and facilitate safe discharge to home and society. Structural and population-level interventions, such as harm-reduction programs, are necessary to reduce IDU-IE relapse rates in the community and other IDU-related health concerns, such as overdoses. In this review, we describe the pathophysiologic, clinical, surgical, social, and ethical characteristics of IDU-IE and their management. We present the most recent clinical guidelines for this condition and discuss existing gaps in knowledge to guide future research, practice changes, and policy interventions., (Copyright © 2022 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)