Infective Endocarditis Research Articles

Risk of infective endocarditis in patients with mitral valve prolapse: Systematic review with meta-analysis

AimsInfective endocarditis (IE) is a serious heart valvular condition. While mitral valve prolapse (MVP) has been associated with an increased risk of IE, the magnitude of this association remains poorly quantified. This systematic review aimed to better estimate the risk of developing IE among MVP patients compared with the general population. MethodsMEDLINE, Cochrane Library (CENTRAL) and Web of Science databases were searched electronically to find all the relevant cohort and case-control studies. Pooled estimates of odds ratios (ORs) and 95 % confidence intervals (CIs) were derived by random effects meta-analysis. Heterogeneity was assessed using the I2 test. ResultsA total of six studies were considered eligible, and the obtained results showed that MVP patients had a higher risk of IE when compared to the general population (OR 7.83, 95 % CI 5.11, 12.02; I2 = 0 %). Posterior analysis according to the risk of bias and study design didn't show any significant variations in the direction and magnitude of the effect. ConclusionThe magnitude of increased risk of IE of 7-fold warrants further attention for patients with MVP. Further contemporary studies and prophylaxis studies should be considered.

Molecular epidemiology and clinical characteristics of Staphylococcus aureus bacteremia in Japanese adults

IntroductionStaphylococcus aureus bacteremia (SAB), especially when caused by methicillin-resistant S. aureus (MRSA), is of considerable clinical importance. In recent years, the proportion of MRSA among S. aureus has decreased, and a relative increase in the proportion of methicillin-susceptible S. aureus (MSSA) has been observed. It is therefore necessary to consider both MRSA and MSSA when assessing the microbiological and clinical significance of SAB. Materials and MethodsWe included SAB cases from the Nara Medical University Hospital between January 2015 and February 2017. We performed drug susceptibility testing, toxicity gene analysis, multilocus sequence typing (MLST), and polymerase chain reaction-based open reading frame typing (POT) of stored strains to integrate clinical and bacteriological characteristics. ResultsThere were 90 cases during the experimental period (42 MRSA and 48 MSSA), with 30-day mortality rates of 19% for MRSA and 10.4% for MSSA. Deaths were more frequently complicated by septic shock and disseminated intravascular coagulation. MLST studies showed that ST8, ST764, ST1, and ST15 were prevalent in the MRSA group, whereas ST5, ST188, and ST12 were prevalent in MSSA. Infective endocarditis cases had a long time from onset to the initiation of effective antimicrobials and were all MSSA. MLST and POT results correlated well, and POT appeared to have better discriminatory power. ConclusionsThe severity and mortality of SAB, along with the microbiological characteristics of causative isolates, vary by location and time. Continued studies integrating clinical and microbiological investigations are thus needed.

<i>Ochrobactrum anthropi</i>: a rare case of endocarditis

Ochrobactrum anthropi is an aerobic Gram-negative bacillus, formerly known as “Achromobacter group Vd”. It is increasingly recognized as a potentially problematic, opportunistic, and nosocomial pathogen. Most cases of human diseases due to O. anthropi are associated with central venous catheter line infection; few case reports about infective endocarditis, pancreatic abscess, puncture wound osteochondritis, endophthalmitis, urinary tract infection, meningitis, pelvic abscess, and osteomyelitis are present in the literature. Among the previously stated infections it can cause, infective endocarditis is very rare; only four cases have been described in the literature. Here, we report the case of an immunocompromised man who developed native valve endocarditis with septic cerebral embolization due to O. anthropi.

Experience with expanded use of oritavancin in a tertiary hospital: indications, tolerability and outcomes.

Oritavancin is a lipoglycopeptide antibacterial agent used to treat infections caused by Gram-positive organisms. It is FDA-approved for the treatment of acute bacterial skin and soft tissue infections (ABSSIs) but is increasingly being used off-label to treat invasive bacterial infections such as osteomyelitis, prosthetic joint infection and infective endocarditis. This study describes the clinical outcomes and adverse reactions related to oritavancin. This was a retrospective study conducted over a 5 year period at a tertiary care medical centre. Ninety-five adult patients were included in this study and were followed for 1 year after the last dose of oritavancin. The most common indication for oritavancin at our institution was osteomyelitis, followed by ABSSI. Other indications were vertebral infection, hardware-associated infection, bacteraemia and infective endocarditis. Fourteen percent (13/95) of patients developed an adverse reaction to oritavancin during the study period. Cure with no recurrence up to 1 year after the last dose of oritavancin was achieved in 74% (53/71) of patients, and the treatment failure rate was 19% (14/71 patients). Oritavancin is an effective agent that can be used to treat invasive Gram-positive bacterial infections other than ABSSI. Adverse events requiring drug discontinuation were common.

Outcomes of Enterococcus faecalis infective endocarditis according to MIC of amoxicillin: a multicentric study.

The incidence of Enterococcus faecalis infective endocarditis is increasing over time. Data on the impact of minimum inhibitory concentration (MIC) of amoxicillin on treatment outcomes are scarce. The objective of this study was to describe the epidemiology of E. faecalis infective endocarditis and to evaluate whether the MIC of amoxicillin might influence mortality. We retrospectively included all consecutive patients diagnosed with definite E. faecalis infective endocarditis between 2013 and 2020 in 11 French hospitals. We extracted data from the local diagnosis-related group (DRG) database and matched these data with microbiological results. Amoxicillin MIC was determined by Etest strip. The primary endpoints were endocarditis-related mortality and risk factors for endocarditis-related mortality including amoxicillin MIC. A total of 403 patients with definite E. faecalis infective endocarditis were included. Patients were predominantly male (76.4%) with a median age of 74 years (67-82). Embolic complications occurred in 170 (42.1%) patients. Cardiac surgery was performed in 158 (61.5%) patients. The endocarditis-related mortality rate was 28.3% and the median delay between mortality and onset of hospitalization was 24 (9; 41) days. E. faecalis MIC of amoxicillin was available for 246 (61%) patients. The median MIC was 0.5 mg/L (0.4-0.7). Amoxicillin MIC was not found to be associated with in-hospital mortality. None of the variables included in the multivariate model were identified as a risk factor for mortality and there was no correlation between mortality and the duration of treatment for 4 weeks versus 6 weeks. Higher amoxicillin MIC was not a risk factor leading to endocarditis-related mortality in definite E. faecalis infective endocarditis. However, further studies are needed to assess the effect of amoxicillin MIC on relapse.

Clinical Management and Pathophysiology of Infective Endocarditis: An Updated Review of Diagnostic Challenges and Therapeutic Approaches

Infective endocarditis (IE) is a severe and life-threatening condition characterized by infection of the endocardial surface of the heart, primarily affecting the heart valves. Despite advances in diagnostic techniques and antimicrobial therapies, IE remains associated with significant morbidity and mortality due to its complex pathogenesis and clinical variability. This article reviews the most recent developments in the pathophysiology, diagnostic criteria, and management strategies of infective endocarditis. Key issues such as microbial etiology, including common pathogens like Staphylococcus aureus and Streptococcus species, are discussed alongside less frequent organisms and their association with specific patient populations. The article emphasizes the importance of early diagnosis using advanced imaging modalities, such as echocardiography and PET-CT, and laboratory findings, particularly blood cultures. We explore both medical and surgical management strategies, highlighting the role of antibiotic therapy and the indications for valve surgery. A focus is given to the management of complex cases, including prosthetic valve endocarditis and infections in immunocompromised patients. The article aims to provide clinicians with a comprehensive understanding of the evolving landscape of infective endocarditis and its implications for patient outcomes.

Quadricuspid aortic valve with complete heart block: a double whammy

BackgroundDevelopmental abnormalities of aortic valve cusps are relatively common with the bicuspid valve being the most frequently encountered congenital heart disease. However, the quadricuspid aortic valve (QAV) is an exceedingly rare abnormality.Case presentationWe report a case involving a young, otherwise healthy male who presented with non-exertional syncope and was subsequently diagnosed with complete heart block (CHB). Further evaluation revealed the coexistence of a rare quadricuspid aortic valve and CHB. This combination, in the absence of surgery or infective endocarditis, has only been reported once before in the literature.The patient underwent successful permanent pacemaker implantation and continues to be monitored for aortic regurgitation.ConclusionsThe coexistence of a QAV with CHB, in the absence of infective endocarditis or aortic valve surgery, is extremely rare and necessitates careful evaluation and follow-up.

Relapse of infective endocarditis after cardiac implantable electronic device removal compared to a conservative strategy

Abstract Background According to current guidelines, complete removal of cardiac implantable electronic device (CIED) should be considered in patients with valvular infective endocarditis (IE), accounting for the identified pathogen and need for valve surgery (Class IIa recommendation). Unselected longitudinal data are needed to assess this strategy. Purpose To examine IE readmission after IE discharge according to status of CIED removal in patients with conservatively treated IE. Methods Using Danish nationwide registries, we identified patients aged ≥18 years with first-time IE from 2010-2021. We included patients with conservatively treated IE and a CIED, who were alive at IE discharge. Patients who underwent CIED removal during IE admission were compared to those without removal, examining the study outcome of IE readmission within six months after IE discharge. An initial blanking period of 14 days was applied after IE discharge. The Aalen-Johanson estimator and multivariable Cox regression models were used to determine cumulative incidences and adjusted hazard ratios (HRs) of IE readmission according to status of CIED removal, respectively. Results Among 6,843 patients with first-time IE, 5,731 (83.7%) were conservatively treated. Of these, 1,201 (21.0%) had a CIED, of which 205 (17.1%) died during IE admission. Thus, the final study population comprised 996 patients alive at IE discharge. The median age of the study population was 75.5 years (interquartile range [IQR]: 67.9-82.0), and 753 (75.6%) were males. In total, 574 (57.6%) patients underwent CIED removal during IE admission. Patients who underwent CIED removal were younger, compared to patients without CIED removal, 73.1 years (IQR: 65.7-79.1) versus 79.0 years (IQR: 71.3-85.1), respectively. The six-month cumulative incidence of IE readmission was 2.0% (95% confidence interval [CI]: 1.1-3.5%) in patients who underwent CIED removal versus 6.1% (95% CI: 4.0-8.9%) in patients without CIED removal (P-value=0.001) (Figure 1). CIED removal was associated with a significantly lower six-month rate of IE readmission, compared to no CIED removal (HR: 0.36 [95% CI: 0.17-0.77]). Relapse bacteraemia (including IE) with the same microorganism as first-time IE occurred in 2.2% of patients who underwent CIED removal and in 5.4% of patients without CIED removal. Staphylococcus aureus was the most common microorganism in 33.3% of patients with relapse bacteraemia who underwent CIED removal. Conclusions In this nationwide study, the six-month rate of infective endocarditis (IE) readmission was three-fold lower in patients who underwent cardiac implantable electronic device (CIED) removal, compared to patients without CIED removal. The current findings suggest that CIED removal is associated with lower risk of relapse of IE in patients with conservatively treated IE. These results are in line with current guideline recommendations. However, more randomized clinical trial data are needed.

Relative contribution of imaging techniques for the contemporary diagnosis of infective endocarditis: a single-center experience

Abstract Introduction In developed countries, the incidence of infective endocarditis (IE) is up to 6 cases per 100,000 individuals and in-hospital mortality rates are reported to reach 30%. The diagnostic recommendations for IE have been revised in the new ESC guidelines emphasizing the use of transesophageal echocardiography (TEE) and advanced imaging techniques (computed tomography [CT], magnetic resonance [MR], positron emission tomography [PET] and white blood cell scintigraphy [WBC-SPECT]). Aims This research aims to investigate the practical applicability of established clinical guidelines in a real-world population with suspected IE. Methods We reviewed the hospital database from 06/2021 to 06/2023 using the international classification of disease codification (ICD-10) for IE. Only patients admitted to Cardiology or Cardiac Surgery departments were included. Diagnosis of IE was defined according to the modified Duke criteria. Firstly, we identified individuals in whom diagnosis was performed by clinical presentation, blood cultures and transthoracic echocardiogram (TTE). Subsequently, we identified those who required further imaging diagnostic investigation. Results A total of 63 patients were included [mean age 64 ±14 years; 76% male (n=48)]. Native IE was diagnosed in 53 (84%) patients, prosthetic IE in 7 (11%) and cardiac implantable electronic devices-related IE in 3 (5%). A total of 26 (41%) patients had at least one predisposing risk factor, 48 (76%) presented with fever, 24 (38%) suffered an embolic event and 1 (2%) had an immunological phenomenon. Out of 49 positive blood cultures (78%), typical microorganisms consistent with IE were isolated in 25 (78%) of samples: 13 (34%) staphylococcus aureus, 10 (26%) oral streptococci, 9 (24%) enterococcus faecalis, 5 (13%) streptococcus gallolyticus and 1 (3%) HACEK group. Overall, in 22 (34%) patients, a definitive diagnosis of IE was established by means of clinical presentation, blood cultures and TTE. In the remaining, TEE was performed in 86% (n=36). Of those, a definite diagnosis was established in 52% (n=22). Brain and whole-body imaging upgraded the diagnosis from possible to definite in 3 (5%) patients. In the one patient in which a comprehensive clinical evaluation including TTE and TEE rejected IE, the diagnosis was ultimately established by means of PET. The median time from admission to the definite/possible diagnosis of IE was 6 (IQR 2-17) days. A total of 47 (75%) patients underwent surgery, with the most frequent indications being heart failure 46% (n=21) and uncontrolled infection 28% (n=13). Time from diagnosis to surgery was 10 (2-19) days, hospital length of stay was 45 (35-70) days and in-hospital mortality 21%. Conclusion Clinical presentation, blood cultures and TTE plus TEE established the definite or possible diagnosis of IE in most patients with suspected IE. Advanced imaging techniques allowed the establishment of definite diagnosis in only 6% of patients.

Infective endocarditis - characteristics and long-term outcomes in patients with congenital heart disease are distinct from those without congenital heart disease

Abstract Background Patients with congenital heart disease (CHD) form a high-risk niche among patients considered at high-risk of infective endocarditis (IE). Their life-long exposure to the risk of IE, starting from birth, necessitates a nuanced approach to both prevention and treatment strategies. However, comprehensive data from an unselected nationwide cohort, including children, are lacking. Purpose This study sets out to compare characteristics and associated outcomes among patients with IE with and without CHD. Methods Using nationwide registries, all Danish patients diagnosed with IE from 1977-2021 were identified and stratified on whether they had a diagnosis of CHD, regardless of its complexity. Characteristics prior to and during admission as well as associated outcomes (i.e., in-hospital mortality, 1-year mortality, and 10-year mortality, and IE recurrence) were compared between groups. Results In total, 14,040 patients were diagnosed with IE from 1977-2021 including 895 (6.4%) with a diagnosis of CHD. Patients with versus without CHD were significantly younger at time of IE diagnosis (median age 38.8 years [IQR 21.2-56.4 years] versus 70.7 years [IQR 58.8-78.9 years], Figure 1) and less comorbid. Patients with versus without CHD were hospitalized due to IE for a similar period of time but more often underwent cardiac surgery during admission (44.9% versus 21.3%). The IE-related bacteremia was significantly different between groups: the most common bacteriemia in relation to IE was Streptococci (29.9%) in patients with CHD and Staphylococcus Aureus (29.9%) in patients without CHD. Patients with CHD were associated with a significantly lower risk of in-hospital mortality (6.4% versus 19.8%), 1-year mortality (10.5% versus 32.4%) and 10-year mortality (21.3% versus 58.7%) compared with those without CHD. The 10-year incidence of IE recurrence was similar among groups (p-value 0.5). Conclusions Patients with CHD who develop IE are distinctive from patients with IE without CHD in terms of characteristics as well as long-term outcomes. Notably, our findings stress a key point: the majority of children and adolescents with IE have a CHD. These unselected findings should help guide future preventive strategies, diagnosis, and management.

Role of negative transthoracic echocardiography in excluding infective endocarditis

Abstract Background Recent guidelines suggest an extensive role of transesophageal echocardiography (TOE) in the diagnostic work-up for suspected infective endocarditis (IE). However, the negative predictive value of transthoracic echocardiography (TTE) remains poorly investigated. Purpose The purpose of our study was to evaluate the accuracy of TTE in ruling out IE in order to avoid unnecessary TOE, a more invasive and expensive diagnostic exam. Methods We reviewed data of 637 consecutive patients referred to our laboratory of echocardiography with a suspected diagnosis of IE who underwent TOE within 14 days of TTE (median 4.4 days; interquartile range 2.4-7.4). For each patient we obtained age, sex, blood culture results, complete blood count, blood chemistry, evidence of systemic embolism or pulmonary embolism, and presence of moderate/severe heart valve disease, congenital heart disease, valve prostheses and intracardiac devices. Patients with initial doubtful findings at TOE were referred for a follow-up TOE after one week and/or 18F fluorodeoxyglucose positron emission tomography computed tomography to achieve a definitive clinical diagnosis. Patients in whom a clear diagnosis of IE could not be achieved (n=7) were considered to have the disease. Results Of the 637 patients enrolled, 375 had negative TTE for IE (59%). TOE was positive and doubtful for IE in 44 (12%) and 29 (8%) of these patients, respectively. After further assessment, a final diagnosis of IE was achieved in 56 patients (15%). Variables associated with IE at univariable analysis included presence of valve prostheses (p<0.001), systemic or pulmonary embolism (p<0.001), lower platelet count (p=0.003), positive blood culture (p=0.005), aortic valve regurgitation (p=0.02), aortic valve stenosis (p=0.03) and mitral regurgitation (p=0.03). At multivariable logistic regression, independent predictors of IE (OR=odds ratio; CI=confidence interval) included evidence of systemic or pulmonary embolism (OR 17.75, 95% CI 6.66-47.3, p<0.001), bioprosthetic heart valves (OR 2.93, 95% CI 1.31-6.53 p=0.023) and lower platelet count (OR 0.995, 95% CI 0.991-0.998, p=0.003). Among the subgroup of patients (n=183, 49%) with no evidence of embolism, no bioprosthetic valve and platelet count >190,000/mL (median value), IE was diagnosed in 11 patients only (6%). Conclusions In our study, a negative TTE in the subgroup of patients with suspected IE showing platelet count >190,000/mL and absence of embolism and valvular bio-prosthesis, had a negative predictive value for IE of 94%, suggesting that, in this subset of patients, TOE can initially be delayed and performed only if clinical suspicion continues to remain high.

Epidemiological profile and mortality of infective endocarditis over the past decade: a systematic review and meta-analysis of 133 studies comprising 132,355 cases

Abstract Background Understanding the epidemiology of infective endocarditis (IE) is crucial in the context of an aging population, increased comorbidities, and the heightened occurrence of healthcare-associated cases. Comprehensive data on causative agents, affected valves, and associated mortality are essential for current clinical practice. Methods This systematic review was conducted according to the PRISMA guidelines. A random effects model meta-analysis was conducted. Eligible studies reporting outcomes on IE were identified through a search of the PubMed/Medline database from 2010 to 2021. Results One hundred-thirty-three studies with 132,584 patients from six continents were included in the analysis. The most common causative agents of IE were Staphylococci species in 36% of cases, followed by Streptococci species in 26% of cases and Enterococci species in 10% of cases. Of the studies providing further speciation, the predominant species was Staphylococcus aureus with an incidence of 29%, followed by Viridans Streptococcus with an incidence of 12%. We found an in-hospital/30-day mortality of 17% (CI: 16%-19%) from 109 studies worldwide. In the subgroup analysis, the highest mortality rates were observed in Latin America 33% (CI: 28%-38%) and Africa 25% (CI: 21%-30%), while the lowest mortality rates were reported in Oceania 13% (CI: 8%-19%), followed by North America 14% (CI: 11%-18%), Asia 15% (CI: 12%-18%), and Europe 17% (CI: 16%-19%). The aortic valve was affected in 46% of cases, followed by the mitral valve in 43%. Tricuspid valve IE and multivalvular IE were identified in 7% and 14% of the cases, respectively. Conclusion Our study highlights the shift in epidemiological profile of IE over the last decade with S. aureus identified as the most common causative microorganism of IE in almost one third of cases. IE remains a highly morbid and fatal condition with high mortality rates even in tertiary and high-expertise centers worldwide. While left-sided IE is by far more common, right-sided IE and multivalvular IE are not rare entities and should be considered early in the differential of patients presenting with suspected IE to decrease the risk of future complications.Global burden of infective endocarditis.

Impact of mandatory preoperative dental screening on infective endocarditis in patients undergoing surgical valve replacement

Abstract Background Guidelines recommend preoperative dental screening (PDS) prior to surgical valve replacement (SVR) to reduce risk of prosthetic valve infective endocarditis (IE). However, limited data support these recommendations. Purpose Investigate the effect of mandatory PDS on risk of IE in patients undergoing SVR. Methods A total of 1,207 patients undergoing SVR in Western-Denmark from 2020 to 2022 were included in this observational study. Patients were considered based on two applied PDS practices: mandatory PDS (MPDS), and no routine referral PDS (NPDS). Outcome data were retrieved from Danish registries and adjudicated using medical records. The primary endpoint was incidence of IE. Secondary endpoints were all-cause mortality, and the composite endpoint of IE and all-cause mortality. Key endpoints were also analyzed in a propensity score-matched (PSM) population. Results Of 805 patients in the MPDS, 93% (n=751) underwent subsequent PDS, compared to 5% (n=21) among 402 patients in the NPDS. Patients in the MPDS were older with higher rates of coexisting co-morbidities. During a median follow-up of 2.6 years (interquartile range 1.9-3.2 years), 3.3% (n=40) developed IE. The yearly incidence IE rate was higher in MPDS compared with NPDS (1.5% vs. 0.7%; p=0.08). All-cause mortality rate was higher in the MPDS (2-year mortality of 6.2% vs 2.3%, p=0.02) as well as the composite endpoint (p<0.01). Differences in IE rates, all-cause mortality, but not composite endpoint were abolished in 370 propensity score-matched patients. Conclusion Risk of IE was low regardless of PDS practice. MPDS prior to surgery did not alter the risk of IE or all-cause mortality in patients undergoing left-sided SVR in Denmark.Kaplan-Meier plot

A novel murine wire injury based infectious endocarditis model aggravates aortic valve stenosis

Abstract Background With mortality rates up to 40% under optimal medical treatment, infectious endocarditis (IE) remains one of the deadliest infectious diseases worldwide. In the early stages of IE, diagnosis and treatment initiation are often difficult and research is limited due to unreliable models. Most murine IE models rely on permanent prosthetic wire placement and i.v. bacterial injection, thus making it inadequate to study IE pathophysiology with the aim to reflect the course of disease in humans. Purpose To develop a reproducible murine IE model, based on aortic valve injury preceding intravenous S. aureus bacterial challenge. Methods Using a wire-injury model we induced endothelial lesions. 72h after wire injury (WI), we performed intravenous bacterial challenge using S. aureus. Echocardiography was performed to confirm bacterial vegetations and assess valvular function. Cross sections of valvular leaflets were prepared for scanning electron microscopy (SEM). Macrophage, neutrophil and S. aureus-specific immunofluorescence staining was performed and visualized by immunofluorescence microscopy. Bacterial cultivation was performed from peripheral blood and valve tissue. Systemic immune response was analyzed using flow cytometry. Results WI induced endothelial damage in all mice verified using scanning electron microscopy imaging. The combination of wire injury and injection of 10^5 and 10^6 colonies-forming-units (CFU) S. aureus reliably caused IE validated via in vivo echocardiography as well as S.aureus immunofluorescence staining and SEM imaging. Mice undergoing bacterial challenge responded with significant neutrophilia in the blood. Using 10^6 CFU S. aureus was associated with an increased mortality, liver and kidney abscess formation due to systemic bacterial spreading compared to 10^5 CFU. Peak velocity across the aortic valve and aortic valve leaflet thickness as markers for aortic valve stenosis were increased in IE compared to WI only mice. Aortic regurgitation was more prevalent after bacterial challenge mediating increased left ventricular volumes, meanwhile ejection fraction was not altered. Immunofluorescence staining revealed a pro-inflammatory milieu including increased macrophage and neutrophil infiltration in IE compared to WI only mice. Conclusion In vivo echocardiography and ex vivo histological staining revealed reliable IE induction using our new model with S. aureus concentrations of 10^5 CFU. The additional bacterial challenge causes a more severe aortic valve stenosis compared to WI only mice, potentially due to an observed increase in valvular inflammation.Fig 1 Scanning electron microscopy after

An epidemiological update on infective endocarditis: a two-decade retrospective longitudinal analysis

Abstract Background Infective endocarditis (IE) is a rare yet serious condition affecting the heart valves and the endocardium. Despite advances in management, IE's incidence is on the rise, maintaining a mortality rate similar to that of the late 20th century. Notably, there has been a notable shift in the risk-factor profile, transitioning from traditional factors such as rheumatic heart disease and poor dental health to more iatrogenic causes such as prosthetic heart valves, cardiac devices, foreign body implants, haemodialysis, and immunosuppression. This shift impacts microbiological and imaging diagnosis. Purpose While IE has been extensively studied in the past, the evolving landscape prompts an epidemiological re-evaluation of vulnerable patient populations and the challenges in current diagnostic parameters. Our primary objective is to examine the trends in microbiological and imaging diagnostics over two decades and to compare them across native valve endocarditis (NVE), prosthetic valve endocarditis (PVE), and cardiac implantable electronic device-related IE (CIED-IE). Methods We conducted a retrospective analysis of longitudinal data encompassing 912 patients admitted with either a possible or definite IE diagnosis between 2001 and 2023. Results The incidence of IE increased over the study duration (p<0.01) with octogenarians most affected (21%). Iatrogenic risk factors were associated with nearly two-thirds (63%) of patients diagnosed with IE, while traditional risk factors were evident in almost one-eighth (13%). Blood culture-negative endocarditis increased over the study duration (81% versus73%, p<0.01) and Staphylococcus aureus (29%, p<0.01) became the dominant pathogen over Viridans Streptococcus (14%, p=0.001). Imaging with transthoracic (56% in 2004 versus 75% in 2023) and transoesophageal echocardiography (57% in 2004 versus 79% in 2023) had an increasing contribution in the diagnosis of IE over the two decades. The subgroup analysis found PVE and CIED-IE were more likely to have negative blood cultures (OR=3.7, CI [1.2-6.8] & OR=4.9, CI [1.3-8]) compared to NVE (OR=0.04, CI [0.02-0.8]). PVE and CIED-IE were more likely to have inconclusive imaging (OR=3.7, CI [1.2-6.6] & OR=2.2, CI [0.07-7.8]) compared to NVE (OR=0.63, CI [0.3-3.2]). Complications of stroke were higher in PVE (OR=3.5, CI [0.89-10]) compared to NVE which also had a lower stroke rate (OR=.16, CI [.04-.73]). PVE had more valvular insufficiency (OR=2.1, CI [0.6-4]) compared to NVE (OR=1.2, CI [0.9-6]). The 12-month mortality was no different across the entities (OR=0.3, CI [0.5-7.7] & OR=.49, CI [0.14-1.8] & OR=0.85, CI [0.3-2.4]). Conclusion Our study underscores the evolving nature of IE, now predominantly a healthcare-related disease. Diagnostic challenges persist due to the heterogeneity of the disease, with the emergence of distinct entities such as PVE and CIED-IE.Graphs: Blood culture & echocardiographyForest plot: NVE vs PVE vs CIED-IE

Mild intracerebral bleeding does not adversely affect survival and neurological outcome of surgical therapy for left-sided infective endocarditis

Abstract Background Intracerebral bleeding (IB) is a serious condition that requires increased attention and has implications for treatment options. For patients with infective endocarditis (IE), current guidelines recommend postponing surgery if IB is present. IB can be classified into four relevant groups (following European Cooperative Acute Stroke Study and Heidelberger Bleeding classification): hemorrhagic transformation (HT) 1 and 2, and parenchymal hemorrhage (PH) 1 and 2. PH2 is the only IB with neurological deterioration. These classifications were originally introduced for stroke patients following thrombolysis but without IE. The hypothesis tested in our study is that IB may influence IE treatment and thus outcome. Method Patients were retrospectively identifyied who were operated for left-sided IE, neuroradiologists re-evaluated and classified preoperative cerebral imaging for any IB. Outcome was quantified using the modified Rankin score (mRS), and mRS were extracted from the patients’ hospital chart at admission and by follow-up telephone call (FU), also including mortality. To ensure that the influence of IB was comparable, patients with IB (IB+) were propensity matched (EuroScore 2, Charlson Comorbidity Index, C-reactive protein; nearest neighbor match) to patients without IB (IB-) who also received surgical IE therapy. All IB+ patients underwent a careful risk-benefit analysis before therapy. Results Of 286 consecutive patients (January 2015 - November 2022) operated for left-sided IE, 36 had IB (65±13 years, 26% female): 11 with HT1, 9 with HT2, 8 with PH1, and 8 with PH2. These patients were matched with 36 operated IB- patients. Survival analysis showed no overall effect of IB+ vs. IB- (p = 0.112, 95% CI of hazard ratio was 0.246-1.243 vs. 0.709-3.572). Although there was no effect of IB on survival in the mild IB subgroup (HT1/2, Figure A), there was a difference in patients with severe IB (PH1/2) with less survival in IB+ (Figure B). Neurological outcome (ΔmRS) showed an effect of IB grade in the two-way ANOVA analysis (p = 0.029). Intergroup comparison showed a significantly better outcome for IB- (vs. IB+) in the PH2 subgroup (p = 0.034), but not in other subgroups. For all groups, the mean ΔmRS for IB+ was 1.1±1.6 vs. 0.70±1.4 for IB- (p = 0.256). The mean FU time was 2.6±2.1 years. Conclusion In patients operated for left-sided IE, mild IB did not affect survival or neurological outcome. In the more severe forms of IB, i.e. PH1 and PH2, survival was less favorable compared to matched controls. Furthermore, we observed a difference in neurological outcome in patients with severe IB. Thus, surgical therapy of left-sided IE should be avoided in patients with severe IB, whereas we can add evidence to the safety of surgical therapy in mild IB. Therefore, we recommend regular assessment of the degree of IB in such patients.Figure

Epidemiology and temporal trends of infective endocarditis between 2006 and 2018 at a tertiary referral center

Abstract Introduction Despite modern diagnostics, targeted antibiotic therapy and surgical treatment the mortality rate of infective endocarditis (IE) remains high. In developed countries both the risk factors and pathogens have changed. Objective and methods In our retrospective study we analyzed the clinical and microbiological characteristics, short- and long-term all-cause mortality, and temporal trends of consecutive patients admitted with IE between 2006 and 2018. Results We included 537 cases in our study, the mean age was 55.9 ± 16.5 years (72.2% male). 325 (60.5%) cases were native left-sided IE, 14 (3%) cases were right-sided IE, 130 (24%) cases were prosthetic valve IE, 62 (11.5%) cases were intracardiac device-related IE and 6 (1%) other cases. The most common microorganisms were Staphylococci (n=175; 33%), including 104 cases of methicillin-sensitive Staphylococcus aureus (MSSA), 27 cases of methicillin-resistant Staphylococcus aureus (MRSA) and 44 cases of coagulase-negative Staphylococci. Streptococcus species were identified in 141 cases (26%), Enterococcus species in 88 cases (16%) and 72 cases (13%) were classified as blood culture-negative IE. In-hospital all-cause mortality was 14%, mortality at six months was 27%, at one-year was 31%, and at five-year was 45%. The incidence of MSSA infections increased over time (p=0.024), while coagulase-negative Staphylococci (p<0.001), and Streptococci (p=0.047) infections decreased. None of the observed mortality rates showed significant change over the study period. Predictors of mortality were advanced age (HR 1.37; p<0.001), impaired renal function (HR: 1.03; p<0.001), reduced ejection fraction on admission (HR 1.38; p<0.001), stroke (HR 1.74; p=0.001), and MRSA infection compared to Streptococci (HR 2.56; p=0.002). Conclusion During the observed 13-year period Staphylococci were the most common pathogens, with an increasing incidence of MSSA infection in our tertiary center. The mortality rate of IE remained high and showed no improvement over time.

Infective endocarditis on percutaneous aortic valve prosthesis: incidence, characteristics and comparison with endocarditis on surgically implanted aortic bioprostheses

Abstract Background Transcatheter aortic valve replacement (TAVR) has become a first-line therapeutic measure in patients with severe aortic stenosis, especially in selected patients who present a very high surgical risk; nevertheless, this technique is becoming increasingly widespread even among patients with a lower surgical risk. Infective endocarditis (IE) is an infrequent but very serious complication in patients undergoing TAVR implantation. The aforementioned generalization of this technique means that more and more patients are at risk of developing this complication which, in addition, seems to have some particularities with respect to endocarditis in other patients. Purpose The aim of our study was to analyze the incidence, clinical characteristics and mortality of IE in patients with TAVR, comparing them with IE in patients with surgically implanted prostheses (SAVR). Methods Observational, single-center, prospective cohort study including all cases of IE diagnosed and prospectively followed up in our center from 2008 to 2022, according to Duke or ESC diagnostic criteria, depending on the era. We identified cases of IE in patients with TAVR in this period and compared their characteristics with endocarditis in patients with surgical aortic prostheses. Results In our center 10 cases of IE have been diagnosed in patients with TAVR. Since 2008 this procedure has been successfully performed in 778 patients, which gives an incidence of 1.29% compared to 1.68% of its surgical counterpart with a total of 24 cases of IE. The clinical characteristics of these patients are shown in the table. With the exception of mean age (p= 0.006), there were no significant differences between the two groups. In approximately half of the cases the diagnosis was made early after valve replacement (<1 year after replacement). With respect to the causative microorganisms, the most prevalent agent was enterococci, followed by coagulase-negative staphylococci and staphylococcus aureus; in 17% of patients with SAVR the causative agent was not identified. The clinical evolution was similar in both groups, with a high proportion of severe complications and 50% of cardiac complications in the TAVR group. Half of the patients had a surgical indication at diagnosis, but only 50% underwent surgery. There were also no differences in mortality, which, nevertheless, was high, around 30%. Conclusions Despite the differences in mean age, no significant differences were found between the two groups. IE is an infrequent but serious complication in patients with prosthetic valves, with a high rate of serious complications and mortality regardless of its management.Baseline characteristics of patients

Outcomes of infective endocarditis in patients with end-stage renal disease and dialysis in Spain: a population-based study

Abstract Background Patients with end-stage renal disease (ESRD), particularly those undergoing dialysis, have a significantly higher risk of developing infective endocarditis (IE) compared to the general population. ESRD is not only related to a higher risk of infection, but also to a worse prognosis in IE. However, most data regarding the epidemiology and outcomes of patients with ESRD and IE is derived from noncontemporary population-based studies with limited clinical variables and lack of complete microbiological information, or from retrospective single-center cohorts. Purpose The aim is to describe the clinical characteristics and outcome of patients with IE and ESRD in Spain, compared to patients without ESRD, and to investigate potential differences between patients undergoing dialysis and the rest of patients with ESRD. Methods Retrospective observational population-based study. A total of 9,008 episodes of IE between 2016 and 2019 were analysed using information from the Spanish Minimum Basic DataSet. 428 patients had ESRD, of whom 332 were undergoing dialysis. A multivariable and multilevel logistic model was developed to evaluate the association of different variables with in-hospital mortality in ESRD patients. Results Compared to patients without ESRD, those with ESRD were younger, had more comorbidities, and had a higher incidence of Staphylococcus aureus (31.8% vs. 18.4%; p <0.001) and coagulase-negative staphylococci infections (19.2% vs. 14%; p =0.006). In terms of in-hospital complications, septic shock was more frequent in patients with ESRD (12.1% vs. 8.9%; p=0.007). Furthermore, ESRD patients underwent cardiac surgery less frequently than patients without ESRD (12.6% vs. 19.6%; p <0.001) and had significantly higher in-hospital mortality (33.4% vs. 26.9%; p =0.003). When comparing patients undergoing dialysis with the rest of ESRD patients, it was observed that those on dialysis had more comorbidities and a higher proportion of Staphylococcus aureus infections (36.1% vs. 16.7%; p <0.001). No differences were found in observed in-hospital mortality between patients on dialysis and the rest of ESRD patients. The multilevel analysis revealed that dialysis was not an independent risk factor for in-hospital mortality in patients with ESRD. Cardiac surgery was also not independently associated with higher in-mortality in ESRD patients. Conclusions Patients with ESRD and IE have a different clinical and microbiological profile than other patients with IE. Moreover, they undergo cardiac surgery less frequently and have significantly higher in-hospital mortality. Dialysis treatment and cardiac surgery were not independent risk factors for mortality in ESRD patients with IE.

Transcatheter valve replacement as rescue treatment for heart failure in infective endocarditis. A multinational series.

Abstract Background Transcatheter valve replacement (TVR) could be a therapeutic alternative for refractory heart failure in patients with infective endocarditis (IE) unsuitable for open surgery. However, evidence of tis use in this scenario is limited to isolated case reports. Purpose We aimed to describe the clinical characteristics and outcome of IE patients in whom a TVR was performed during the active phase of infection in a multinational case series. Methods This retrospective study was conducted in 23 referral hospitals for IE and TVR procedure in 8 countries. All consecutive adult patients (≥18 y) with definite IE in whom a TVR was performed during antimicrobial treatment of within the 3 three months after its withdrawal were included. The inclusion period was between July 2011 and July 2023. Baseline, IE-related, TVR-related, outcome and follow-up (min. 3 months) variables were collected. Results Forty-five patients [median age 74 years (IQR 64 – 82), 35 males (78%), median Charlson comorbidity index 6 (4 – 7) points] were included in the study: 42 aortic TVR, 2 mitral TVR and 1 tricuspid TVR. In 20 patients (44%) TVR was performed on a native valve and in 25 on a prosthetic valve. The most frequent microorganisms causing IE were streptococci (n=16, 36%), staphylococci (n=13, 29%) and enterococci (n=5, 11%). Acute heart failure was present in 41 (91%). Of them, 23 (51%) developed acute pulmonary oedema or cardiogenic shock. The main reasons for excluding open surgery were: high surgical risk [n=39, 87%; median EuroSCORE 17 (9 – 28)] and technical impossibility (n=3, 7%). TVR was performed during antimicrobial treatment in 27 cases (60%) [median 25 (13 – 54) days after initiation] and within the first three months after its completion in 18 (40%) [median 25 (17 – 68) days after discontinuation]. Four patients (9%) died during admission. Over a median follow-up of 10 (6 -30) months, 7/41 patients (17%) died and there were 2/41 (5%) relapses, one of which required open valve replacement surgery 17 days after TVR procedure. Two other patients underwent open surgery due to paravalvular leaks (11 and 44 days after TVR). All cases of relapse and open surgery occurred when TVR was performed during antibiotic treatment. Conclusion TVR could be an option as rescue treatment for heart failure in selected IE patients unsuitable for open surgery. This represents a paradigm shift in the management of IE and may change the natural history of the disease in patients who would otherwise die.