Baddour, Larry M.

AbstractBackgroundGiven the challenges of conventional therapies in managing right‐sided infective endocarditis (RSIE), percutaneous mechanical aspiration (PMA) of vegetations has emerged as a novel treatment option. Data on trends, characteristics, and outcomes of PMA, however, have largely been limited to case reports and case series.Aims:The aim of the current investigation was to provide a descriptive analysis of PMA in the United States and to profile the frequency of PMA with a temporal analysis and the patient cohort.MethodsThe International Classification of Diseases, 10th Revision codes were used to identify patients with RSIE in the national (nationwide) inpatient sample (NIS) database between 2016 and 2020. The clinical characteristics and temporal trends of RSIE hospitalizations in patients who underwent PMA was profiled.ResultsAn estimated 117,955 RSIE‐related hospital admissions in the United States over the 5‐year study period were estimated and 1675 of them included PMA. Remarkably, the rate of PMA for RSIE increased 4.7‐fold from 2016 (0.56%) to 2020 (2.62%). Patients identified with RSIE who had undergone PMA were young (medial age 36.5 years) and had few comorbid conditions (median Charlson Comorbidity Index, 0.6). Of note, 36.1% of patients had a history of hepatitis C infection, while only 9.9% of patients had a cardiovascular implantable electronic device. Staphylococcus aureus was the predominant (61.8%) pathogen. Concomitant transvenous lead extraction and cardiac valve surgery during the PMA hospitalization were performed in 18.2% and 8.4% of admissions, respectively. The median hospital stay was 19.0 days, with 6.0% in‐hospital mortality.ConclusionsThe marked increase in the number of PMA procedures in the United States suggests that this novel treatment option has been embraced as a useful tool in select cases of RSIE. More work is needed to better define indications for the procedure and its efficacy and safety.

Introduction: The association of echocardiographic measurements and subsequent risk of left-sided native valve endocarditis (LS-NVE) is undefined. Aim: To determine if transthoracic echocardiographic (TTE) measurements are associated with the subsequent development of LS-NVE in patients without recognized cardiac predisposing conditions. Methods: Institutional databases were evaluated for adults diagnosed with LS-NVE from 2008 to 2020. Patients with prosthetic valves, cardiovascular implantable electronic devices, intracardiac devices, injection drug use, and recognized predisposing cardiac conditions were excluded. Patients with a TTE performed 6 months to 3 years before developing LS-NVE were included as cases. Controls were patients within the same Mayo Clinic location with a TTE report and were matched in a 1:3 ratio according to age, gender, Charlson Comorbidity Index (CCI), and echocardiography date. Multivariate logistic-regression analyses adjusting significant variables between cohort's were performed. A p-value <0.05 was considered significant. Results: There were 148 cases and 431 matched controls. The median age was 63.8 (IQR: 53.6 - 74.6) years, and 329 (56.8%) patients were males. LS-NVE cases had a higher prevalence of diabetes mellitus (46.6% vs. 30.4%) and chronic kidney disease (46.6% vs. 28.1%) when compared with controls (p<0.001 both). The median CCI score was 3 (IQR: 0-6) for cases and 2 (IQR: 0-6) for controls. After performing adjusted analyses, left ventricular outflow tract velocity (p=0.017), left ventricular ejection fraction (p=0.018), and E: e’ ratio (p=0.050) were associated with the development of LS-NVE ( Figure 1) . Conclusions: Echocardiographic measurements were associated with subsequent LS-NVE development in this preliminary investigation. A larger cohort of LS-NVE patients is needed to validate these findings.

Introduction: Transcatheter aortic valve replacement (TAVR) is a well-recognized treatment for severe aortic stenosis. One potentially life-threatening complication of TAVR is infective endocarditis (IE). There is limited contemporary data on the clinical characteristics and outcomes of patients undergoing TAVR who develop in-hospital IE. Aim: Describe the clinical characteristics and outcomes of patients undergoing TAVR who develop in-hospital IE. Methods: The National Inpatient Sample Database was queried from 2016 to 2020 for relevant ICD-10 procedural and diagnostic codes. Baseline characteristics and in-hospital outcomes of adult (≥18 years) patients undergoing TAVR who developed in-hospital IE were compared to that of patients who did not develop IE. Multivariate logistic-regression analyses adjusting for age, race, gender, and statistically significant comorbidities between cohort's were performed. A p-value <0.05 was considered significant. Results: A total of 314,250 hospitalizations for patients undergoing TAVR were identified. Of them, 1065 (0.3%) developed in-hospital IE. Overall, mean age of IE patients was 70.3 ± 15.0. Patients were predominantly (62%) males and white (79.5%) ( Table 1) . IE patients had a higher risk of in-hospital all-cause mortality (adjusted odds ratio [95% CI]: 2.07 [1.50-2.86]), septic shock (3.73 [2.71-5.13]), acute respiratory failure (2.59 [2.19-3.06]), ischemic stroke (4.4 [3.48-5.51]), acute kidney injury (3.05 [2.61-3.57]), cardiac arrest (2.82 [1.83-4.37] and cardiogenic shock 3.70 [2.98-4.57]). All p values were <0.01. Conclusion: Patients undergoing TAVR who develop in-hospital IE had higher in-hospital complications when compared to those of patients who did not develop IE. Although the rate of in-hospital IE was low, the number of patients identified in the NIS database was sizable and the syndrome deserves investigation due to its associated complications.

Background Data on national trends in mortality due to infective endocarditis (IE) in the United States are limited. Methods and Results Utilizing the multiple causes of death data from the Centers for Disease Control and Prevention's Wide‐Ranging Online Data for Epidemiologic Research database from 1999 to 2020, IE and substance use were identified using the International Classification of Diseases, Tenth Revision, Clinical Modification codes. Between 1999 and 2020, the IE‐related age‐adjusted mortality rates declined. IE‐related crude mortality accelerated significantly in the age groups 25–34 years (average annual percentage change, 5.4 [95% CI, 3.1–7.7]; P <0.001) and 35–44 years (average annual percentage change, 2.3 [95% CI, 1.3–3.3]; P <0.001), but remained stagnant in those aged 45–54 years (average annual percentage change, 0.5 [95% CI, −1.9 to 3]; P =0.684), and showed a significant decline in those aged ≥55 years. A concomitant substance use disorder as multiple causes of death in those with IE increased drastically in the 25–44 years age group ( P <0.001). The states of Kentucky, Tennessee, and West Virginia showed an acceleration in age‐adjusted mortality rates in contrast to other states, where there was predominantly a decline or static trend for IE. Conclusions Age‐adjusted mortality rates due to IE in the overall population have declined. The marked acceleration in mortality in the 25‐ to 44‐year age group is a cause for alarm. Regional differences with acceleration in IE mortality rates were noted in Kentucky, Tennessee, and West Virginia. We speculate that this acceleration was likely due mainly to the opioid crisis that has engulfed several states and involved principally younger adults.

Abstract Background The 2023 Duke-ISCVID criteria for IE were recently introduced to improve classification of IE for research and clinical purposes (Table 1). We compared the diagnostic accuracy of the new criteria with the 2000 modified Duke criteria, the 2015 European Society of Cardiology (ESC) criteria and a clinically adjudicated reference standard by a panel of international experts on IE.Table 1:Overview of changes in criteria from 2000 modified Duke to 2023 Duke-ISCVIDAdapted from: Fowler et al, Clinical Infectious Diseases, 2023 Methods The study population consisted of consecutively enrolled patients suspected to have IE and discussed by the IE team of the Amsterdam University Medical Center (AMC) between October 2016 and March 2021. A panel of international experts on IE assigned a final diagnosis, which served as the reference standard. We compared the definite classification of the 2023 Duke-ISCVID criteria against this reference standard. We also evaluated accuracy of the new criteria, excluding data obtained from cardiac surgery and pathology (“Clinical Criteria”). Lastly, we quantified the added value of the proposed changes to the criteria, and compared the 2023 Duke-ISCVID to previous criteria using the McNemar test. We performed sensitivity analyses in patients who underwent cardiac surgery and patients who underwent TEE. Results 595 patients with suspected IE were included, of whom 399 (67%) were adjudicated as having IE. 111 patients (19%) had prosthetic valve IE, 48 (8%) had cardiac implantable electronic device IE. The 2023 Duke-ISCVID criteria were more sensitive than the modified Duke or ESC criteria (84.2 vs 74.9 vs 80%,respectively, p &lt; 0.001 for ISCVID vs ESC criteria) without significant loss of specificity (Table 2). After excluding cardiac surgery/pathology results, the 2023 Duke-ISCVID Clinical Criteria also had significantly better sensitivity than the modified Duke and ESC criteria, again without losing specificity. The changes in the 'major microbiological' and 'imaging' criteria had the most impact (Figure 1). Findings were robust in sensitivity analyses (Table 3). When classifying ‘definite’ and ‘possible’ IE as a positive test, the 2023 Duke-ISCVID criteria had 99% sensitivity compared to the reference standard, but specificity decreased to 21%.Table 2:Diagnostic accuracy of modified Duke, ESC and Duke-ISCVID criteria Sensitivity and specificity are against the reference standard (adjudication panel). The Clinical Criteria classification is the Duke-ISCVID classification when results from surgery or post-mortem studies are not used to determine classification.Table 3:Sensitivity analyses of accuracy of Duke-ISCVID criteria In the Definite + Possible analysis, patients with possible IE according to the Duke-ISCVID criteria were also considered as having IE. All comparisons are against the reference standard (adjudication panel). Conclusion In this cohort, the 2023 Duke-ISCVID criteria represent a significant advance in the diagnostic classification of patients suspected of IE. Added value of new Duke-ISCVID criteria compared to modified Duke criteria Each point (red square for sensitivity, blue circle for specificity) provides the diagnostic accuracy measure for the 2000 modified Duke Criteria with addition of a specific change from the Duke-ISCVID criteria. The horizontal bars represent the 95% confidence interval for the point estimate. The top points represent the modified Duke criteria without addition, the bottom points are the complete Duke-ISCVID criteria. Disclosures Larry M. Baddour, MD, Boston Scientific: Advisor/Consultant|Roivant Sciences: Advisor/Consultant Arnold S. Bayer, MD, Akagera Medicines: Grant/Research Support|ContraFect Corporation: Grant/Research Support Emanuele Durante Mangoni, MD,, PhD, Advanz pharma: Advisor/Consultant|Advanz pharma: Grant/Research Support|Advanz pharma: Honoraria|Angelini: Grant/Research Support|Angelini: Honoraria|Genentech: Advisor/Consultant|Genentech: Board Member|Genentech: Honoraria|Infectopharm: Grant/Research Support|Menarini: Board Member|Menarini: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Board Member|Pfizer: Grant/Research Support|Pfizer: Honoraria|Roche: Advisor/Consultant|Roche: Board Member|Roche: Honoraria Thomas L. Holland, MD, Aridis: Advisor/Consultant|Basilea Pharmaceutica: Advisor/Consultant|Karius: Advisor/Consultant|Lysovant: Advisor/Consultant Adolf W. Karchmer, MD, Karius: Grant/Research Support|Up To Date: Honoraria Vance G. Fowler, MD, MHS, Amphliphi Biosciences, Integrated Biotherapeutics; C3J, Armata, Valanbio; Akagera, Aridis, Roche, Astra Zeneca: Advisor/Consultant|Genentech, Regeneron, Deep Blue, Basilea, Janssen;: Grant/Research Support|Infectious Diseases Society of America: Honoraria|MedImmune, Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Merck; Medical Biosurfaces; Locus; Affinergy; Contrafect; Karius;: Grant/Research Support|Novartis, Debiopharm, Genentech, Achaogen, Affinium, Medicines Co., MedImmune, Bayer, Basilea, Affinergy, Janssen, Contrafect, Regeneron, Destiny,: Advisor/Consultant|Sepsis diagnostic: Patent pending|UpToDate: Royalties|Valanbio and ArcBio: Stock Options

Abstract Background Patent foramen ovale (PFO) can be identified in about 20-25% of the adult population and may result in variable degrees of left-to-right and right-to-left intracardiac shunting. The association between PFO and pyogenic brain abscess remains poorly understood. The current study aimed to compare the clinical characteristics and outcomes of pyogenic brain abscess in patients with and without PFO. Methods All adults with pyogenic brain abscess seen at Mayo Clinic from 1/1/2009-12/31/2021 who underwent either transesophageal echocardiography (TEE) or transthoracic echocardiography (TTE) with agitated saline shunt (bubble) study were included. Results A total of 222 patients developed pyogenic brain abscess during the study period; 148 (66.7%) patients were excluded due to unknown PFO status. Among 74 remaining patients, PFO was detected in 30 (40.5%) patients; 25 by TEE and 5 by TTE with bubble study (Figure 1). The prevalence of cryptogenic brain abscess (unable to identify the source of abscess) was significantly higher in patients with PFO as compared to those without PFO (53.3% versus 18.2%, p=0.002). Patients with PFO had a larger abscess size (25 mm [IQR 15.8-37.5] versus 15.5 mm [IQR 10.0-28.0], p=0.038). However, multiple abscesses were more common in the group without PFO (43.2% versus 20.0%, p=0.038). Additionally, patients with PFO had less documented bloodstream infection. There were no differences between other clinical characteristics and one-year, all-cause mortality between two groups. Conclusion These findings provide critical insights into the likely association between PFO and cryptogenic brain abscess; additional investigation is warranted. Disclosures Larry M. Baddour, MD, Boston Scientific: Advisor/Consultant|Roivant Sciences: Advisor/Consultant

Abstract Background Limited research has focused on bloodstream infection (BSI) in patients with arterial grafts. This study aims to describe the incidence and outcomes of BSI after arterial aneurysm repair in a population-based cohort. Methods The expanded Rochester Epidemiology Project (e-REP) was used to analyze aneurysm repairs in adults (aged ≥18 years) residing in 8 counties in southern Minnesota from January 2010 to December 2020. Electronic records were reviewed for the first episode of BSI following aneurysm repair. BSI patients were assessed for vascular graft infection (VGI) and followed for all-cause mortality. Results During the study, 643 patients had 706 aneurysm repairs: 416 endovascular repairs (EVARs) and 290 open surgical repairs (OSRs). Forty-two patients developed BSI during follow-up. The 5-year cumulative incidence of BSI was 4.7% (95% confidence interval [CI], 3.0%–6.4%), with rates of 4.0% (95% CI, 1.8%–6.2%) in the EVAR group and 5.8% (95% CI, 2.9%–8.6%) in the OSR group (P = .052). Thirty-nine (92.9%) BSI cases were monomicrobial, 33 of which were evaluated for VGI. VGI was diagnosed in 30.3% (10/33), accounting for 50.0% (8/16) of gram-positive BSI cases compared to 11.8% (2/17) of gram-negative BSI cases (P = .017). The 1-, 3-, and 5-year cumulative post-BSI all-cause mortality rates were 22.2% (95% CI, 8.3%–34.0%), 55.8% (95% CI, 32.1%–71.2%), and 76.8% (95% CI, 44.3%–90.3%), respectively. Conclusions The incidence of BSI following aneurysm repair was overall low. VGI was more common with gram-positive compared to gram-negative BSI. All-cause mortality following BSI was high, which may be attributed to advanced age and significant comorbidities in our cohort.

(1) Background: Coagulase-negative staphylococci (CoNS) are an important group of organisms that can cause bloodstream infection (BSI) and infective endocarditis (IE). The prevalence of IE in patients with BSI due to different CoNS species, however, has received limited attention; (2) Methods: A retrospective study of adults with monomicrobial CoNS BSI who had undergone echocardiography and a risk factor analysis was done to determine the most common CoNS species that cause definite IE; (3) Results: 247 patients with CoNS BSI were included in the investigation; 49 (19.8%) had definite IE, 124 (50.2%) possible IE, and 74 (30.0%) BSI only. The latter two entities were grouped in one category for further analysis. The most common species in CoNS BSI was Staphylococcus epidermidis (79.4%) and most patients (83.2%) had possible IE/BSI only. 59.1% of patients with BSI due to S. lugdunensis had definite IE. The majority of CoNS were healthcare-associated/nosocomial bacteremia. Multivariable analysis demonstrated that valve disease (p = 0.002) and a foreign cardiovascular material (p < 0.001) were risk factors associated with definite IE. Patients with S. lugdunensis BSI had an 8-fold higher risk of definite IE than did those with S. epidermidis BSI and nearly a 13-fold higher risk than did patients with BSI due to other species of CoNS (p = 0.002); (4) Conclusions: The prevalence of definite IE in patients with BSI due to different CoNS species was significant. CoNS bacteremia, particularly with S. lugdunensis, confers a significant risk of IE, particularly in patients with a valve disease or intravascular foreign body material and should not be immediately dismissed as a contaminant.

Abstract Background In contrast to bloodstream infection due to a variety of bacteria in patients with cardiovascular implantable electronic devices (CIED), there are limited data regarding candidemia and risk of CIED infection. Methods All patients with candidemia and a CIED at Mayo Clinic Rochester between 2012 and 2019 were reviewed. Cardiovascular implantable electronic device infection was defined by (1) clinical signs of pocket site infection or (2) echocardiographic evidence of lead vegetations. Results A total of 23 patients with candidemia had underlying CIED; 9 (39.1%) cases were community onset. None of the patients had pocket site infection. The duration between CIED placement and candidemia was prolonged (median 3.5 years; interquartile range, 2.0–6.5). Only 7 (30.4%) patients underwent transesophageal echocardiography and 2 of 7 (28.6%) had lead masses. Only the 2 patients with lead masses underwent CIED extraction, but device cultures were negative for Candida species. Two (33.3%) of 6 other patients who were managed as candidemia without device infection subsequently developed relapsing candidemia. Cardiovascular implantable electronic device removal was done in both patients and device cultures grew Candida species. Although 17.4% of patients were ultimately confirmed to have CIED infection, CIED infection status was undefined in 52.2%. Overall, 17 (73.9%) patients died within 90 days of diagnosis of candidemia. Conclusions Although current international guidelines recommend CIED removal in patients with candidemia, the optimal management strategy remains undefined. This is problematic because candidemia alone is associated with increased morbidity and mortality as seen in this cohort. Moreover, inappropriate device removal or retention can both result in increased patient morbidity and mortality.