Infective Endocarditis Involving Implanted Cardiac Electronic Devices: JACC Focus Seminar 1/4.

Cardiac implantable electronic device-related infective endocarditis (CIED-IE) encompasses a range of clinical syndromes, including valvular, device lead, and bloodstream infections. However, accurately diagnosing CIED-IE remains challenging owing in part to diverse clinical presentations, lack of standardized definition, and variations in guideline recommendations. Furthermore, current diagnostic modalities, such as transesophageal echocardiography and [18F]-fluorodeoxyglucose positron emission tomography-computed tomography have limited sensitivity and specificity, further contributing to diagnostic uncertainty. This can potentially result in complications and unnecessary costs associated with inappropriate device extraction. Six hypothetical clinical cases that exemplify the diverse manifestations of CIED-IE are addressed herein. Through these cases, we highlight the importance of optimizing diagnostic accuracy and stewardship, understanding different pathogen-specific risks for bloodstream infections, guiding appropriate device extraction, and preventing CIED-IE, all while addressing key knowledge gaps. This review both informs clinicians and underscores crucial areas for future investigation, thereby shedding light on this complex and challenging syndrome.

Strategies to Improve Patient-Centered Care for Drug Use-Associated Infective Endocarditis: JACC Focus Seminar 2/4.

Drug use-associated infective endocarditis (DUA-IE) is a major cause of illness and death for people with substance use disorder (SUD). Investigations to date have largely focused on advancing the care of patients with DUA-IE and included drug use disorder treatment, decisions about surgery, and choice of antibiotics during the period of hospitalization. Transitions from hospital to outpatient care are relatively unstudied and frequently a key factor of uncontrolled infection, continued substance use, and death. In this paper, we review the evidence supporting cross-disciplinary care for people with DUA-IE and highlight domains that need further clinician, institutional, and research investment in clinicians and institutions. We highlight best practices for treating people with DUA-IE, with a focus on addressing health disparities, meeting health-related social needs, and policy changes that can support care for people with DUA-IE in the hospital and when transitioning to the community.

The Clinical Challenge of Prosthetic Valve Endocarditis: JACC Focus Seminar 3/4.

During the past 6 decades, there have been numerous changes in prosthetic valve endocarditis (PVE), currently affecting an older population and increasing in incidence in patients with transcatheter-implanted valves. Significant microbiologic (molecular biology) and imaging diagnostic (fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography) advances have been incorporated into the 2023 Duke-International Society for Cardiovascular Infectious Diseases infective endocarditis diagnostic criteria, thus increasing the diagnostic sensitivity for PVE without sacrificing specificity in validation studies. PVE is a life-threatening disease requiring management by multidisciplinary endocarditis teams in cardiac centers to improve outcomes. Novel surgical options are now available, and an increasing set of patients may avoid surgical intervention despite indication. Selected patients may complete parenteral or oral antimicrobial treatment at home. Finally, patients with prosthetic valves implanted surgically or by the transcatheter approach are candidates for antibiotic prophylaxis before invasive dental procedures.

Recent Insights Into Native Valve Infective Endocarditis: JACC Focus Seminar 4/4.

This focused review highlights the latest issues in native valve infective endocarditis. Native valve disease moderately increases the risk of developing infective endocarditis. In 2023, new diagnostic criteria were published by the Duke-International Society of Cardiovascular Infectious Diseases group. New pathogens were designated as typical, and findings on computed tomography imaging were included as diagnostic criteria. It is now recognized that a multidisciplinary approach to care is vital, and the role of an "endocarditis team" is highlighted. Recent studies have suggested that a transition from intravenous to oral antibiotics in selected patients may be reasonable, and the role of long-acting antibiotics is discussed. It is also now clear that an aggressive surgical approach can be life-saving in some patients. Finally, results of several recent studies have suggested there is an association between dental and other invasive procedures and an increased risk of developing infective endocarditis. Moreover, data indicate that antibiotic prophylaxis may be effective in some scenarios.

Manifestations of Prosthetic Valve Endocarditis: Lessons From Multimodality Imaging and Pathological Correlation.

Heart valve replacement has steadily increased over the past decades due to improved surgical mortality, an aging population, and the increasing use of transcatheter valve technology. With these developments, prosthetic valve complications, including prosthetic valve endocarditis, are increasingly encountered. In this review, we aim to characterize the manifestations of prosthetic valve endocarditis using representative case studies from our institution to highlight the advances and contributions of modern multimodality imaging techniques.

Healthcare exposures and associated risk of endocarditis after open-heart cardiac valve surgery.

BACKGROUND: Infective endocarditis (IE) following cardiac valve surgery is associated with high morbidity and mortality. Data on the impact of iatrogenic healthcare exposures on this risk are sparse. This study aimed to investigate risk factors including healthcare exposures for post open-heart cardiac valve surgery endocarditis (PVE). METHODS: In this population-linkage cohort study, 23,720 patients who had their first cardiac valve surgery between 2001 and 2017 were identified from an Australian state-wide hospital-admission database and followed-up to 31 December 2018. Risk factors for PVE were identified from multivariable Cox regression analysis and verified using a case-crossover design sensitivity analysis. RESULTS: In 23,720 study participants (median age 73, 63% male), the cumulative incidence of PVE 15 years after cardiac valve surgery was 7.8% (95% CI 7.3-8.3%). Thirty-seven percent of PVE was healthcare-associated, which included red cell transfusions (16% of healthcare exposures) and coronary angiograms (7%). The risk of PVE was elevated for 90 days after red cell transfusion (HR = 3.4, 95% CI 2.1-5.4), coronary angiogram (HR = 4.0, 95% CI 2.3-7.0), and healthcare exposures in general (HR = 4.0, 95% CI 3.3-4.8) (all p < 0.001). Sensitivity analysis confirmed red cell transfusion (odds ratio [OR] = 3.9, 95% CI 1.8-8.1) and coronary angiogram (OR = 2.6, 95% CI 1.5-4.6) (both p < 0.001) were associated with PVE. Six-month mortality after PVE was 24% and was higher for healthcare-associated PVE than for non-healthcare-associated PVE (HR = 1.3, 95% CI 1.1-1.5, p = 0.002). CONCLUSIONS: The risk of PVE is significantly higher for 90 days after healthcare exposures and associated with high mortality.

Incidence of Bacteremia, Infective Endocarditis, or Prosthetic Joint Infection in Dermatologic Surgery: A Systematic Review.

BACKGROUND: Prophylactic antibiotic therapy is widely used in dermatologic surgery to prevent surgical site infections and bacteremia, which can lead to prosthetic joint infections (PJI) and infective endocarditis (IE) in high-risk populations. OBJECTIVE: To evaluate the incidence of bacteremia, PJI, and IE after dermatologic surgery and assess the current evidence for antibiotic prophylaxis. MATERIALS AND METHODS: A search of the computerized bibliographic databases was performed using key terms from the date of inception to March 21, 2021. Data extraction was performed independently by 2 data extractors. RESULTS: The review resulted in 9 publications that met inclusion criteria, including 5 prospective cohort studies and 4 case reports or case series. The prospective studies reported a wide range of bacteremia incidence (0%-7%) after dermatologic surgery. No cases of PJI resulting directly from cutaneous surgery were identified, and only 1 case series reported IE after various skin procedures. CONCLUSION: These findings suggest a low rate of bacteremia and a lack of direct evidence linking dermatologic surgery to PJI or IE. The scarcity of published data on this topic is a limitation, highlighting the need for further research, particularly randomized controlled trials, to guide antibiotic prophylaxis recommendations.

Infective Endocarditis in Patients Addicted to Injected Opioid Drugs.

BACKGROUND: Persons who inject drugs and require surgery for infective endocarditis have 2 potentially lethal diseases. Current postoperative rehabilitation efforts seem ineffective in preventing loss to follow-up, injection drug use relapse (relapse), and death. OBJECTIVES: The purpose of this study was to characterize drug use, psychosocial issues, surgical outcome, and postoperative addiction management, as well as loss to follow-up, relapse, and mortality and their risk factors. METHODS: From January 2010 to June 2020, 227 persons who inject drugs, age 36 ± 9.9 years, underwent surgery for infective endocarditis at a quaternary hospital having special interest in developing addiction management programs. Postsurgery loss to follow-up, relapse, and death were assessed as competing risks and risk factors identified parametrically and by machine learning. CIs are 68% (±1 SE). RESULTS: Heroin was the most self-reported drug injected (n = 183 [81%]). Psychosocial issues included homelessness (n = 56 [25%]), justice system involvement (n = 150 [66%]), depression (n = 118 [52%]), anxiety (n = 104 [46%]), and post-traumatic stress disorder (n = 33 [15%]). Four (1.8%) died in-hospital. Medication for opioid use disorder prescribed at discharge increased from 0% in 2010 to 100% in 2020. At 1 and 5 years, conditional probabilities of loss to follow-up were 16% (68% CI: 13%-22%) and 59% (68% CI: 44%-65%), relapse 32% (68% CI: 28%-34%) and 79% (68% CI: 74%-83%), and mortality 21% (68% CI: 18%-23%) and 68% (68% CI: 62%-72%). Younger age, heroin use, and lower education level were predictors of relapse. CONCLUSIONS: Infective endocarditis surgery can be performed with low mortality in persons who inject drugs, but addiction is far more lethal. Risk of loss to follow-up and relapse require more effective addiction strategies without which this major loss to society will continue.

Treatment of cardiac implantable electronic device endocarditis in pacemaker-dependent patients utilizing a percutaneous aspiration system.

With the increasing use of cardiac implantable electronic devices, the number of patients with cardiac implantable electronic device-related endocarditis is also rising. The treatment of this type of endocarditis is a challenging clinical task, in particular if device removal is required in patients who are pacemaker dependent. This video tutorial describes a treatment strategy for cardiac implantable electronic device-related endocarditis involving the tricuspid valve in pacemaker-dependent patients. The proposed treatment strategy consists of implanting an epicardial pacemaker via a minimally invasive subxiphoid approach, percutaneous aspiration of tricuspid valve vegetations and complete transvenous explantation of the infected cardiac implantable electronic device system using advanced lead extraction tools.

Prognosis of prosthetic valve infective endocarditis due to Streptococcus spp., a retrospective multi-site study to assess the impact of antibiotic treatment duration.

PURPOSE: The duration of antibiotic treatment for prosthetic valve endocarditis caused by Streptococcus spp. is largely based on clinical observations and expert opinion rather than empirical studies. Here we assess the impact of a shorter antibiotic duration. OBJECTIVES: To assess the impact of antibiotic treatment duration for streptococcal prosthetic valve endocarditis on 12-month mortality as well as subsequent morbidity resulting in additional cardiac surgical interventions, and rates of relapse and reinfection. METHODS: This retrospective multisite (N= 3) study examines two decades of data on patients with streptococcal prosthetic valve endocarditis receiving either 4 or 6 weeks of antibiotics. Overall mortality, relapse, and reinfection rates were also assessed for the entire available follow-up period. RESULTS: The sample includes 121 patients (median age 72 years, IQR [53; 81]). The majority (74%, 89/121) received a ß-lactam antibiotic combined with aminoglycoside in 74% (89/121, median bi-therapy 5 days [1; 14]). Twenty-eight patients underwent surgery guided by ESC-guidelines (23%). The 12-month mortality rate was not significantly affected by antibiotic duration (4/40, 10% in the 4-week group vs 3/81, 3.7% in the 6-week group, p=0.34) or aminoglycoside usage (p=0.1). Similarly, there were no significant differences between the 2 treatment groups for secondary surgical procedures (7/40 vs 21/81, p=0.42), relapse or reinfection (1/40 vs 2/81 and 2/40 vs 5/81 respectively). CONCLUSIONS: Our study found no increased adverse outcomes associated with a 4-week antibiotic duration compared to the recommended 6-week regimen. Further randomized trials are needed to ascertain the optimal duration of treatment for streptococcal endocarditis.

Infective Endocarditis After Transcatheter Versus Surgical Aortic Valve Replacement.

BACKGROUND: Scarce data are available comparing infective endocarditis (IE) following surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR). This study aimed to compare the clinical presentation, microbiological profile, management, and outcomes of IE after SAVR versus TAVR. METHODS: Data were collected from the "Infectious Endocarditis after TAVR International" (enrollment from 2005 to 2020) and the "International Collaboration on Endocarditis" (enrollment from 2000 to 2012) registries. Only patients with an IE affecting the aortic valve prosthesis were included. A 1:1 paired matching approach was used to compare patients with TAVR and SAVR. RESULTS: A total of 1688 patients were included. Of them, 602 (35.7%) had a surgical bioprosthesis (SB), 666 (39.5%) a mechanical prosthesis, 70 (4.2%) a homograft, and 350 (20.7%) a transcatheter heart valve. In the SAVR versus TAVR matched population, the rate of new moderate or severe aortic regurgitation was higher in the SB group (43.4% vs 13.5%; P < .001), and fewer vegetations were diagnosed in the SB group (62.5% vs 82%; P < .001). Patients with an SB had a higher rate of perivalvular extension (47.9% vs 27%; P < .001) and Staphylococcus aureus was less common in this group (13.4% vs 22%; P = .033). Despite a higher rate of surgery in patients with SB (44.4% vs 27.3%; P < .001), 1-year mortality was similar (SB: 46.5%; TAVR: 44.8%; log-rank P = .697). CONCLUSIONS: Clinical presentation, type of causative microorganism, and treatment differed between patients with an IE located on SB compared with TAVR. Despite these differences, both groups exhibited high and similar mortality at 1-year follow-up.

Features of infective endocarditis in a contemporary cohort of persons who inject drugs: a matched comparison analysis of long-term prognostic factors.

The objective of the study was to assess the short- and long-term mortality of infective endocarditis (IE) among people who inject drugs (PWID). Using prospectively collected data on hospitalized patients (years 2000 through 2021) with IE, PWID were identified and included in this study. Survival analysis was performed to analyze short- and long-term mortality and study their risk factors among PWID and a matched group of non-intravenous drug users (N-IDU). In a study of 485 patients admitted for IE, 55 (11%) of them were PWID. These PWID patients were 1:1 age- and sex- matched to an N-IDU group (N = 55 per group). Both groups had similar baseline comorbid conditions, including congestive heart failure, type 2 diabetes, and neoplastic diseases. However, PWID were more likely to have HCV co-infection (62% vs 16%, respectively, p < 0.001) and advanced liver disease/cirrhosis (52% vs 7.9%, respectively, p < 0.001). IE in PWID more often affected the tricuspid valve (42% vs 22%, respectively, p = 0.024) and presented with more embolic events (66% vs 35%, respectively, p < 0.01). S. aureus was the primary cause of IE in PWID (44% vs 21%, respectively, p = 0.01). After adjusting for other variables, PWID (HR = 2.99, 95% CI [1.06, 8.43], p = 0.038) and valve bioprosthetic replacement (HR = 5.37, 95% CI [1.3, 22.1], p = 0.02) were independently associated with increased mortality risk, whereas IE caused by tricuspid valve infection was associated with reduced mortality risk (HR = 0.25, 95% CI [0.06, 0.97], p = 0.046). In this cohort, PWID had increased risk of long-term mortality after hospital discharge for IE, when compared to matched N-IDU with similar baseline characteristics. The reasons behind the significant increase in mortality warrant further investigation.

Epidemiologic and Clinical Characteristics of Marantic Endocarditis: A Systematic Review and Meta-analysis of 416 Reports.

Nonbacterial thrombotic endocarditis (NBTE) is a distinctive condition marked by the presence of aseptic fibrin depositions on cardiac valves due to hypercoagulability and endocardial damage. There is a scarcity of large cohort studies clarifying factors associated with morbidity and mortality of this condition. A systematic literature review was performed utilizing the PubMed, Embase, Cochrane, and Web-of-Science databases to retrieve case reports and series documenting cases of NBTE from inception until September-2022. A descriptive analysis of basic characteristics was carried out, followed by multivariate regression analysis to identify risk factors associated with morbidity and mortality. A total of 416 case reports and series were identified, of which 450 patients were extracted. The female-to-male ratio was around 2:1 with an overall sample median age of 48 (interquartile range [IQR]:34-61). Stroke-like symptoms were the most common presentation and embolic phenomena occurred in 70% of cases, the majority of which were due to stroke. Cancer was associated with higher embolic complications (aOR:6.38, 95% CI = 3.75-10.83, p < 0.01) in comparison to other NBTE etiologies, while age, sex, and vegetation size were not (p > 0.05). All-cause in-hospital mortality was 36%, with cancer etiology being associated with higher mortality: 56% (aOR:3.64, 95% CI = 1.57-8.43, p < 0.01) in comparison to other NBTE etiologies:19%. A significant decrease in NBTE mortality was seen in recent years in comparison to admissions that occurred during the 20th century (aOR:0.07, 95% CI = 0.04-0.15, p < 0.01). While there has been an observed improvement in overall in-hospital mortality rates for patients admitted with NBTE in recent years, it is important to note that cases associated with a cancer etiology are still linked to high morbidity and mortality during hospitalization.

Prosthetic Valve Endocarditis After Aortic Valve Replacement With Bovine Versus Porcine Bioprostheses.

BACKGROUND: Whether a bovine or porcine aortic valve bioprosthesis carries a higher risk of endocarditis after aortic valve replacement is unknown. The aim of this study was to compare the risk of prosthetic endocarditis in patients undergoing aortic valve replacement with a bovine versus porcine bioprosthesis. METHODS AND RESULTS: This nationwide, population-based cohort study included all patients who underwent surgical aortic valve replacement with a bovine or porcine bioprosthesis in Sweden from 1997 to 2018. Regression standardization was used to account for intergroup differences. The primary outcome was prosthetic valve endocarditis, and the secondary outcomes were all-cause mortality and early prosthetic valve endocarditis. During a maximum follow-up time of 22 years, we included 21 022 patients, 16 603 with a bovine valve prosthesis and 4419 with a porcine valve prosthesis. The mean age was 73 years, and 61% of the patients were men. In total, 910 patients were hospitalized for infective endocarditis: 690 (4.2%) in the bovine group and 220 (5.0%) in the porcine group. The adjusted cumulative incidence of prosthetic valve endocarditis at 15 years was 9.5% (95% CI, 6.2%-14.4%) in the bovine group and 2.8% (95% CI, 1.4%-5.6%) in the porcine group. The absolute risk difference between the groups at 15 years was 6.7% (95% CI, 0.8%-12.5%). CONCLUSIONS: The risk of endocarditis was higher in patients who received a bovine compared with a porcine valve prosthesis after surgical aortic valve replacement. This association should be considered in patients undergoing both surgical and transcatheter aortic valve replacement.

Prosthetic Valve Endocarditis After Aortic Valve Replacement: Differences Between Biological and Mechanical Prostheses.

AIMS: Prosthetic valve endocarditis (PVE) is the most severe form of infective endocarditis associated with a high mortality rate. Whether PVE affects biological and mechanical aortic valves to the same extent remains controversial. This study aimed to compare the incidence of re-intervention because of PVE between bioprosthetic and mechanical valves. METHODS: Patients undergoing isolated surgical aortic valve replacement (AVR) or combined AVR in a single cardiac surgery centre between January 1998 and December 2019 were analysed. All patients who underwent re-intervention because of PVE were identified. The primary endpoint was the rate of explants. Freedom from re-intervention and variables associated with re-intervention were analysed using Cox regression analysis including correction for competing risk. RESULTS: During the study period, 5,983 aortic valve prostheses were implanted, including 3,620 biological (60.5%) and 2,363 mechanical (39.5%) prostheses. The overall mean follow-up period was 7.3±5.3 years (median, 6.5; IQR 2.9-11.2 years). The rate of re-intervention for PVE in the biological group was 1.5% (n=54) compared with 1.7% (n=40) in the mechanical group (p=0.541). Cox regression analysis revealed that younger age (HR 0.960, 95% CI 0.942-0.979; p<0.001), male sex (HR 2.362, 95% CI 1.384-4.033; p=0.002), higher creatinine (HR 1.002, 95% CI 0.999-1.004; p=0.057), and biological valve prosthesis (HR 2.073, 95% CI 1.258-3.414; p=0.004) were associated with re-intervention for PVE. After correction for competing risk of death, biological valve prosthesis was significantly associated with a higher rate of re-intervention for PVE (HR 2.011, 95% CI 1.177-3.437; p=0.011). CONCLUSIONS: According to this single-centre, observational, retrospective cohort study, AVR using biological prosthesis is associated with re-intervention for PVE compared to mechanical prosthesis. Further investigations are needed to verify these findings.

Root-commando operation with a modified self-assembled aortic root conduit for endocarditis after sutureless aortic valve replacement.

We present a case of a Staphylococcus epidermidis early prosthetic valve endocarditis after minimally invasive sutureless aortic valve replacement. The patient developed a root abscess with a fistula, severe mitral and periprosthetic regurgitations, with a large mitral vegetation and a residual patent foramen ovale. The surgical approach consisted of a redo median sternotomy, explantation of a sutureless aortic prosthesis, resection of an intervalvular fibrosa and anterior mitral leaflet and debridement of an aortic root-left ventricle outflow tract abscess. These procedures were followed by a root-commando procedure with mitral and aortic root placement using a self-assembled mechanical aortic root conduit. The technique used is an alternative to a root-commando procedure performed with an allograft or a Medtronic Freestyle bioprosthesis. The same technique can be utilized with a commercially available stented bioprosthesis.

A high throughput microphysiological model of prosthetic valve endocarditis for investigating factors that influence bacterial adhesion under fluid shear stress.

Prosthetic heart valves are associated with almost one quarter of cases of infective endocarditis, a rare but serious condition with a staggering 25 % mortality rate. Without the endothelium of native valves, the risk of infection is exacerbated for implanted devices exposed to blood. There are currently no physiologically relevant in vitro or animal models of prosthetic valve endocarditis (PVE). Of particular importance, Staphylococcus aureus, a common agent of PVE, has demonstrated enhanced binding to blood plasma proteins (e.g., fibrinogen) and exposed matrix under fluid shear stress (FSS). An in vitro platform that mimics the multiple physiological determinants for S. aureus adhesion to prosthetic valve materials would facilitate the discovery of new treatments to minimize PVE. To this end, we developed a first-of-its-kind microphysiological model of PVE to study the effects of several key variables (endothelial cell coverage, fibrinogen deposition, surface treatments, and FSS) on S. aureus adhesion to bioprosthetic material surfaces. Our model demonstrated that viable endothelial monolayers diminished the deposition of fibrinogen and that fibrinogen was required for the subsequent adhesion of S. aureus to the bioprosthetic surface model. Next, we examined factors that affected endothelial cell coverage, such as FSS and glutaraldehyde, a common chemical treatment for bioprosthetic materials. In particular, glutaraldehyde treatment obstructed endothelialization of otherwise biocompatible collagen-coated surfaces, further enabling fibrinogen and S. aureus deposition. In future work, this model could impact multiple research areas, such as screening candidate bioprosthetic valve materials and new surface treatments to prevent PVE and further understanding host-pathogen interactions.