Make Modern Microbiology Matter More in the 2023 European Society of Cardiology Guidelines for the Management of Infective Endocarditis.

The European Society of Cardiology (ESC) 2023 guidelines for the management of infective endocarditis (IE) stress that a multidisciplinary approach is needed to manage patients with IE. In our view, the guidelines do not include the relevant perspectives from modern microbiology. The diagnostic criteria for IE were changed in the ESC 2023 guidelines, and many IE-causing pathogens are either not clearly defined. Moreover, an improved understanding of the relationship between bacterial species and the risk for IE has not been implemented. The guidelines give detailed and, in our view, incorrect instructions about diagnostic testing in blood culture-negative IE without presenting proper evidence. Other important diagnostic aspects, such as the value of repeated blood cultures and incubation time for blood cultures, are not discussed. We believe that a multidisciplinary collaboration that include microbiologists would have improved these guidelines, and we hope for a future harmonization of diagnostic criteria for IE.

Molecular Analysis With 16S rRNA PCR/Sanger Sequencing and Molecular Antibiogram Performed on DNA Extracted From Valve Improve Diagnosis and Targeted Therapy of Infective Endocarditis: A Prospective Study.

BACKGROUND: Molecular analysis (MA) on heart valve (HV) improves the microbiologic diagnosis of infectious endocarditis (IE). The main drawback of MA is the lack of antimicrobial susceptibility information. METHODS: We conducted a prospective cohort observational study of consecutive adult patients from April 2012 to May 2021 who underwent valve surgery at our hospital. The performance of MA, blood cultures (BC) and valve cultures (VC), and the diagnostic and therapeutic impact of MA were evaluated. Molecular antibiogram results were compared to culture-based antimicrobial susceptibility testing (AST). RESULTS: A total of 137 patients with definite IE and 52 patients with no IE were enrolled in the study. Among IE cases BC, VC, and MA were positive in 75 (55%), 30 (22%), and 120 (88%) of IE cases, respectively. Among 62 cases of BC-negative IE (BCNE), 57 achieved diagnosis with MA. MA led to a change of antimicrobial therapy in 92% of BCNE. MA was negative in 100% of patients with no IE. Molecular antibiogram performed on 17 valve specimens that resulted positive for pathogens potential carrier of genes encoding for multidrug resistant mechanisms showed 100% concordance with AST. CONCLUSIONS: MA showed a high specificity and sensitivity in etiological diagnosis of IE. Molecular antibiogram could overcome the major limitation of MA that is the lack of susceptibility testing. We advocate for the inclusion of MA among diagnostic criteria for IE and for a more extensive use of molecular antibiogram when the culture result is negative, and MA is the only positive test.

Blood culture-negative infective endocarditis: are we looking hard enough?

INTRODUCTION: Infective endocarditis is a common cardiac condition, with significant mortality. Blood culture-negative endocarditis is an important subgroup of endocarditis that holds significant morbidity and mortality. METHOD: We performed an updated review of the literature. We searched the databases of Web of Science, MEDLINE, EMBAS and Scopus for the latest clinical guidelines and literature on blood culture negative endocarditis to provide a narrative synthesis of the literature. RESULTS: There is significant heterogeneity in causes and complications of culture-negative infective endocarditis, due to an insensitivity in available clinical diagnostic pathways. Despite significant advances in diagnostic tools, the diagnostic criterion for infective endocarditis (the modified Duke's criterion) remains insensitive to the detection of culture-negative infective endocarditis. CONCLUSION: The natural history of BCNE and our diagnostic resources are changing. It is time our criterion did too. Remembering, BCNE holds significant morbidity and mortality-the absence of organism of culture should not reassure, rather concern clinicians. Every effort should be made to accurately identify organisms.

Outcomes of culture-negative vs. culture-positive infective endocarditis: the ESC-EORP EURO-ENDO registry.

AIM: Fatality of infective endocarditis (IE) is high worldwide, and its diagnosis remains a challenge. The objective of the present study was to compare the clinical characteristics and outcomes of patients with culture-positive (CPIE) vs. culture-negative IE (CNIE). METHODS AND RESULTS: This was an ancillary analysis of the ESC-EORP EURO-ENDO registry. Overall, 3113 patients who were diagnosed with IE during the study period were included in the present study. Of these, 2590 (83.2%) had CPIE, whereas 523 (16.8%) had CNIE. As many as 1488 (48.1%) patients underwent cardiac surgery during the index hospitalization, 1259 (48.8%) with CPIE and 229 (44.5%) with CNIE. The CNIE was a predictor of 1-year mortality [hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.04-1.56], whereas surgery was significantly associated with survival (HR 0.49, 95% CI 0.41-0.58). The 1-year mortality was significantly higher in CNIE than CPIE patients in the medical subgroup, but it was not significantly different in CNIE vs. CPIE patients who underwent surgery. CONCLUSION: The present analysis of the EURO-ENDO registry confirms a higher long-term mortality in patients with CNIE compared with patients with CPIE. This difference was present in patients receiving medical therapy alone and not in those who underwent surgery, with surgery being associated with reduced mortality. Additional efforts are required both to improve the aetiological diagnosis of IE and identify CNIE cases early before progressive disease potentially contraindicates surgery.

Malassezia restricta: An Underdiagnosed Causative Agent of Blood Culture-Negative Infective Endocarditis.

BACKGROUND: Infective endocarditis (IE) is a severe disease requiring microbial identification to successfully adapt its treatment. Currently, identification of its etiological microorganism remains unresolved in 5.2% of cases. We aimed to improve IE diagnosis using an ultra-sensitive molecular technique on cardiac samples in microbiologically nondocumented (culture and conventional polymerase chain reaction [PCR]) IE (NDIE) cases. METHODS: Cardiac samples explanted in a tertiary hospital in Lyon, France, from patients with definite IE over a 5-year period were retrospectively analyzed. NDIE was defined as Duke definite-IE associated with negative explorations including cardiac samples culture, bacterial amplification, and serologies. Ultrasensitive molecular diagnosis was achieved using the Universal Microbe Detection kit (Molzym®). Fungal identification was confirmed using 26S-rDNA and internal transcribed spacer amplifications. Fungal infection was confirmed using Grocott-Gromori staining, auto-immunohistochemistry on cardiac samples, and mannan serologies. RESULTS: Among 88 included patients, microbial DNA was detected in all 16 NDIE cases. Bacterial taxa typical of IE etiologies were detected in 13/16 cases and Malassezia restricta in the 3 other cases. In these 3 cases, histological examination confirmed the presence of fungi pathognomonic of Malassezia that reacted with patient sera in an auto-immunohistochemistry assay and cross-reacted with Candida albicans in an indirect immunofluorescent assay. CONCLUSIONS: M. restricta appears to be an underestimated causative agent of NDIE. Importantly, serological cross-reaction of M. restricta with C. albicans may lead to its misdiagnosis. This is of major concern since M. restricta is intrinsically resistant to echinocandins; the reference treatment for Candida-fungal IE.

Bartonella species as a cause of culture-negative endocarditis in South Africa.

Previous reports have highlighted the high prevalence of blood culture negative endocarditis (BCNE) in South Africa. The Tygerberg Endocarditis Cohort (TEC) study is an ongoing prospective cohort study of patients with confirmed or suspected IE presenting to Tygerberg Academic Hospital, Cape Town, South Africa. Current analysis includes patients that presented between November 2019 and August 2020. Forty four (44) patients have been included in this ongoing study. Fourteen of the 44 patients (31.8%) had BCNE. Further analysis of the patients with BCNE identified Bartonella species as the most common causative organism (n=6; 43%). Other causes included Mycoplasma species (n=2). No cause could be identified in 4 of the 44 patients (9%). Bartonella quintana was identified with PCR of valvular tissue as the causative organism in 4 of the 5 patients that underwent urgent surgery. The patients with Bartonella IE (n=6) had an average age of 39 years with equal gender distribution. The common clinical features were clubbing (n=5; 83%), anemia (n=4; 66.6%), haematuria (n=3; 50%), acute on chronic severe regurgitant lesion (n=3; 50%) and acute severe regurgitant lesion (n=2; 33.3%).The aortic valve was involved in 5 of 6 patients. During a mean follow-up period of 251 days after diagnosis, no major adverse events occurred. Bartonella-associated IE is an important cause of BCNE in the Western Cape of South Africa. Imaging findings (in patients with BCNE) of significant valvular destruction with large vegetations on the aortic valve not affected by congenital or rheumatic valve disease should raise the suspicion of Bartonella-associated IE.

Metagenomic Analysis of Microdissected Valvular Tissue for Etiological Diagnosis of Blood Culture-Negative Endocarditis.

BACKGROUND: Etiological diagnosis is a key to therapeutic adaptation and improved prognosis, particularly for infections such as endocarditis. In blood culture-negative endocarditis (BCNE), 22% of cases remain undiagnosed despite an updated comprehensive syndromic approach. This prompted us to develop a new diagnostic approach. METHODS: Eleven valves from 10 BCNE patients were analyzed using a method that combines human RNA bait-depletion with phi29 DNA polymerase-based multiple displacement amplification and shotgun DNA sequencing. An additional case in which a microbe was serendipitously visualized by immunofluorescence was analyzed using the same method, but after laser capture microdissection. RESULTS: Background DNA prevented any diagnosis in cases analyzed without microdissection because the majority of sequences were contaminants. Moraxella sequences were dramatically enriched in the stained microdissected region of the additional case. A consensus genome sequence of 2.4 Mbp covering more than 94% of the Moraxella osloensis KSH reference genome was reconstructed with 234X average coverage. Several antibiotic-resistance genes were observed. Etiological diagnosis was confirmed using Western blot and specific polymerase chain reaction with sequencing on a different valve sample. CONCLUSIONS: Microdissection could be a key to the metagenomic diagnosis of infectious diseases when a microbe is visualized but remains unidentified despite an updated optimal approach. Moraxella osloensis should be tested in blood culture-negative endocarditis.

Impact of pre-operative antimicrobial treatment on microbiological findings from endocardial specimens in infective endocarditis.

Treatment of infective endocarditis (IE) should be initiated promptly. This might hamper the chances to identify the causative organism in blood cultures. Microbiological sampling of infected valve in patients undergoing surgery might identify the causative organism. The impact of pre-operative antimicrobial treatment on the yield of valve samples is not known. This study evaluated the impact of the duration of the pre-operative antibiotic treatment on valve culture and 16S rRNA PCR findings from resected endocardial samples. Patients meeting the modified Duke criteria of definite or possible IE and undergoing valve surgery due to IE during 2011-2016 were included from Southern Finland. Eighty-seven patients were included. In patients with shorter than 2 weeks of pre-operative antimicrobial treatment, PCR was positive in 91% (n = 42/46) and valve culture in 41% (n = 19/46) of cases. However, in patients who had 2 weeks or longer therapy before operation, PCR was positive in 53% (n = 18/34) and all valve cultures were negative. In 14% of patients, PCR had a diagnostic impact. In blood-culture negative cases (n = 13), PCR could detect the causative organism in ten patients (77%). These included five cases of Bartonella quintana, one Tropheryma whipplei, and one Coxiella burnetii. Long pre-operative antimicrobial treatment was shown to have a negative impact on microbiological tests done on resected endocardial material. After 2 weeks of therapy, all valve cultures were negative, but PCR was positive in half of the cases. PCR aided in diagnostic work-up, especially in blood culture negative cases.

Bartonella Species, an Emerging Cause of Blood-Culture-Negative Endocarditis.

Since the reclassification of the genus Bartonella in 1993, the number of species has grown from 1 to 45 currently designated members. Likewise, the association of different Bartonella species with human disease continues to grow, as does the range of clinical presentations associated with these bacteria. Among these, blood-culture-negative endocarditis stands out as a common, often undiagnosed, clinical presentation of infection with several different Bartonella species. The limitations of laboratory tests resulting in this underdiagnosis of Bartonella endocarditis are discussed. The varied clinical picture of Bartonella infection and a review of clinical aspects of endocarditis caused by Bartonella are presented. We also summarize the current knowledge of the molecular basis of Bartonella pathogenesis, focusing on surface adhesins in the two Bartonella species that most commonly cause endocarditis, B. henselae and B. quintana. We discuss evidence that surface adhesins are important factors for autoaggregation and biofilm formation by Bartonella species. Finally, we propose that biofilm formation is a critical step in the formation of vegetative masses during Bartonella-mediated endocarditis and represents a potential reservoir for persistence by these bacteria.

Blood Culture-Negative Endocarditis, Morocco.

We investigated the microorganisms causing blood culture-negative endocarditis (BCNE) in Morocco. We tested 19 patients with BCNE by serologic methods, molecular methods, or both and identified Bartonella quintana, Staphylococcus aureus, Streptococcus equi, and Streptococcus oralis in 4 patients. These results highlight the role of these zoonotic agents in BCNE in Morocco.

Laboratory Approach to the Diagnosis of Culture-Negative Infective Endocarditis.

Blood-culture negative endocarditis (BCNE) accounts for up to 35% of all cases of infective endocarditis (IE) and is a serious life-threatening condition with considerable morbidity and mortality. Rapid detection and identification of the causative pathogen is essential for timely, directed therapy. Blood-culture negative endocarditis presents a diagnostic and therapeutic challenge. Causes of BCNE are varied including: treatment with antibiotic agents prior to blood culture collection; sub-optimal specimen collection; and/or infection due to fastidious (eg. nutritionally variant streptococci), intracellular (eg. Coxiella burnetii, Bartonella species) or non-culturable or difficult to culture organisms (eg. Mycobacteria, Tropheryma whipplei and fungi); as well as non-infective aetiologies. Here, we review aetiological and diagnostic approaches to BCNE including newer molecular based techniques, with a brief summary of imaging investigation and treatment principles.

Impact of serology and molecular methods on improving the microbiologic diagnosis of infective endocarditis in Egypt.

BACKGROUND: Conventional diagnosis of infective endocarditis (IE) is based mainly on culture-dependent methods that may fail because of antibiotic therapy or fastidious microorganisms. OBJECTIVES: We aimed to evaluate the added values of serological and molecular methods for diagnosis of infective endocarditis. PATIENTS AND METHODS: One hundred and fifty-six cases of suspected endocarditis were enrolled in the study. For each patient, three sets of blood culture were withdrawn and serum sample was collected for Brucella, Bartonella and Coxiella burnetii antibody testing. Galactomannan antigen was added if fungal endocarditis was suspected. Broad range PCR targeting bacterial and fungal pathogens were done on blood culture bottles followed by sequencing. Culture and molecular studies were done on excised valve tissue when available. RESULTS: One hundred and thirty-two cases were diagnosed as definite IE. Causative organisms were detected by blood cultures in 40 (30.3 %) of cases. Blood culture-negative endocarditis (BCNE) represented 69.7 %. Of these cases, PCR followed by sequencing on blood and valvular tissue could diagnose five cases of Aspergillus flavus. Eleven patients with BCNE (8.3 %) were diagnosed as zoonotic endocarditis by serology and PCR including five cases of Brucella spp, four cases of Bartonella spp and two cases of Coxiella burnetii. PCR detected three cases of Brucella spp and two cases of Bartonella spp, while cases of Coxiella burnetii were PCR negative. The results of all diagnostic tools decreased the percentage of non-identified cases of BCNE from 69.7 to 49.2 %. CONCLUSION: Our data underline the role of serologic and molecular tools for the diagnosis of blood culture-negative endocarditis.

Culture-negative endocarditis with multifocal spread and flail mitral valve leaflet: a case report.

Introduction: Blood culture-negative infective endocarditis is the condition in which a causative organism cannot be identified after inoculation of at least three samples using standard blood-culture systems for 7 days. It has a low reported incidence of about 2.5-31%. Causes may be infectious or non-infectious; use of prior antibiotic therapy is usually the leading factor. Case presentation: The authors present a case of true culture-negative endocarditis involving the mitral valve, with multiple foci of spread including brain, spleen, liver, and Intervertebral disc, which remained persistent despite treatment with intravenous broad-spectrum antibiotics on an inpatient and outpatient basis but eventually improved after upgrading alternative broad-spectrum antibiotic for an extended duration. The patient had complications in the form of a flail mitral valve with persistent mitral regurgitation, requiring mitra-clip placement. Discussion: Positive blood culture is one of the major diagnostic criteria to establish infective endocarditis. Patients may have persistent negative cultures due to previous antibiotic use, the presence of fastidious organisms, or the use of inappropriate techniques or media. Involvement of a multidisciplinary team, use of multimodal investigations, and appropriate antibiotic stewardship are crucial. Extended duration of treatment and upgrading antibiotics can be helpful next steps in highly suspicious cases. With multifocal spread as in our case, it further becomes challenging to control and treat the infection as it is frequently connected with higher morbidity and mortality. Conclusion: Blood culture-negative endocarditis is an entity that can present with early complications. It is diagnostically and therapeutically challenging to treat such patients. Multimodal approaches for early diagnosis and appropriate treatment are crucial owing to its high morbidity and mortality.

Innovative Management of Blood Culture-Negative Endocarditis With Pulmonary Septic Emboli in a Patient With a Biventricular Pacemaker and Implantable Cardioverter Defibrillator (BiV-ICD) and Psychosocial Stressors: A Case Report.

Blood culture-negative endocarditis (BCNE) poses significant diagnostic and therapeutic challenges and is associated with notable morbidity and mortality. When presented concurrently with other comorbidities, these challenges and the chances of morbidity and mortality significantly increase. This case presents right-sided BCNE accompanied by pulmonary cavitary lesions in a patient with a history of supraventricular tachycardias (SVT), a biventricular pacemaker and implantable cardioverter-defibrillator (BiV-ICD), alcohol use, and anticoagulant noncompliance. The patient missed follow-up appointments for six months after the death of his wife, leading to increased alcohol use and noncompliance with medications. During this period, his home monitoring device was offline. Once reconnected, it detected several episodes of SVT and ventricular tachycardia (VT), prompting a wellness check. He presented to the cardiology clinic with shortness of breath and a cough producing brown-tinged sputum. Evaluation revealed cavitary lesions in the lingula and left lower lobe, a vegetation on his tricuspid valve, and vegetations on his endocardial leads, despite negative blood cultures. Tuberculosis testing was negative, while sputum cultures were positive for Haemophilus influenzae. After ruling out other possible infectious causes of the cavitary lesions, septic emboli were suspected as the cause. Broad-spectrum antibiotics were begun and surgical intervention was done to replace the tricuspid valve and remove the endocardial leads. This procedure was complicated by fibrosis of the leads at the coronary sinus, necessitating their cutting at the superior vena cava and leaving them inside the patient until laser therapy could be performed for their removal. The patient's history of bradycardia and SVTs required the ongoing use of a pacemaker. Inventory discrepancy during the placement of the new pacemaker epicardial leads lead to complications warranting an alternative approach to lead implantation. A traditionally used epicardial lead was placed on the right ventricle for pacing, and an innovative technique was employed to place an endocardial lead on the right atrium epicardium for sensing. This case underscores the importance of thorough evaluation and collaborative management strategies to optimize outcomes for patients with concomitant cardiac and pulmonary pathologies, particularly in the context of underlying psychosocial stressors. Additionally, it demonstrates solutions to challenges that can arise during surgery and presents an alternative lead placement technique for physicians who have only one epicardial lead available after removing infected endocardial leads. This is illustrated by the innovative use of an endocardial lead as an epicardial sensing lead.

Identifying risk factors for blood culture negative infective endocarditis: An international ID-IRI study.

Background: Blood culture-negative endocarditis (BCNE) is a diagnostic challenge, therefore our objective was to pinpoint high-risk cohorts for BCNE. Methods: The study included adult patients with definite endocarditis. Data were collected via the Infectious Diseases International Research Initiative (ID-IRI). The study analysing one of the largest case series ever reported was conducted across 41 centers in 13 countries. We analysed the database to determine the predictors of BCNE using univariate and logistic regression analyses. Results: Blood cultures were negative in 101 (11.65 %) of 867 patients. We disclosed that as patients age, the likelihood of a negative blood culture significantly decreases (OR 0.975, 95 % CI 0.963-0.987, p < 0.001). Additionally, factors such as rheumatic heart disease (OR 2.036, 95 % CI 0.970-4.276, p = 0.049), aortic stenosis (OR 3.066, 95 % CI 1.564-6.010, p = 0.001), mitral regurgitation (OR 1.693, 95 % CI 1.012-2.833, p = 0.045), and prosthetic valves (OR 2.539, 95 % CI 1.599-4.031, p < 0.001) are associated with higher likelihoods of negative blood cultures. Our model can predict whether a patient falls into the culture-negative or culture-positive groups with a threshold of 0.104 (AUC±SE = 0.707 ± 0.027). The final model demonstrates a sensitivity of 70.3 % and a specificity of 57.0 %. Conclusion: Caution should be exercised when diagnosing endocarditis in patients with concurrent cardiac disorders, particularly in younger cases.

Paws and Pathogens: A Multidisciplinary Approach Through Bartonella henselae Endocarditis and Hepatosplenic T-Cell Lymphoma.

Bartonella species are gram-negative coccobacilli that are globally recognized as significant pathogens causing zoonotic infections. Among Bartonella species, B. henselae, B. quintana, and B. bacilliformis are prominent pathogens causing infections in humans, often manifesting as infective endocarditis. Bartonella endocarditis can pose diagnostic challenges due to its indolent presentation and limitations of standard microbiological culture techniques to identify the organism. We report a case of a 23-year-old male, who initially presented with the manifestations of hepatosplenic T-cell lymphoma, later diagnosed with blood culture-negative endocarditis caused by B. henselae. The patient had a complicated clinical course including pancytopenia, hepatosplenomegaly, and severe aortic valve regurgitation. Despite negative blood cultures, diagnostic clues included persistent fevers and bicuspid aortic valve with abscess. High Bartonella IgG titers (>1:800) supported the diagnosis. This case underscores the importance of considering Bartonella species in patients with suspected endocarditis, particularly in those with predisposing factors and negative blood cultures. Diagnosis relies heavily on serologic assays due to low sensitivity of conventional culture methods. Treatment involves a multidisciplinary approach with antibiotics and surgical intervention for optimal outcomes. Timely recognition and management are crucial to mitigate the high mortality associated with Bartonella endocarditis, and we hope this article offers insight for clinicians.

A 'Decrescendo' in a Woman With Ascending Paralysis: A Diagnostic Challenge.

Guillain-Barre Syndrome (GBS) is an autoimmune condition that causes muscular weakness and can be potentially life-threatening if not identified early. GBS is diagnosed definitively by cerebrospinal fluid (CSF) analysis and electromyographic (EMG) studies. Identifying illnesses that may have triggered GBS is crucial, as they could affect the course of the disease. Our patient was a 27-year-old woman who developed lower extremity weakness a few days after being treated for a dental abscess. Laboratory and imaging studies ruled out central nervous system (CNS) lesions, myelopathies, and metabolic causes. Diagnosis was difficult due to inconclusive initial investigations, refusal of lumbar puncture, and delayed availability of EMG studies. Additionally, there were no identifiable triggers to support GBS as a diagnosis. During the hospital course, the patient developed tachycardia with new electrocardiogram (EKG) changes. A transthoracic echocardiogram (TTE) showed suspicious vegetation, and a transesophageal echocardiogram (TEE) confirmed severe mitral regurgitation. The new valvular lesions and autonomic dysfunction with worsening lower extremity weakness increased our suspicion of GBS. Intravenous immunoglobulin (IVIG) was administered empirically, but she developed bulbar symptoms, prompting admission to the intensive care unit (ICU). A lumbar puncture performed at this time was negative for albumino-cytological dissociation and CNS infections.  Signs of sepsis with valvular lesions raised concerns for infective endocarditis (IE). Due to recent treatment with antibiotics for dental abscess, a negative blood culture was a confounding factor in Duke's criteria, delaying the diagnosis of IE. Infectious disease experts suggested empirical treatment for suspected blood culture-negative infective endocarditis (BCNE) and valvular abscess. She was transferred to a cardiothoracic care facility for valvular surgery evaluation. EMG studies identified the patient's condition as the acute motor sensory axonal neuropathy (AMSAN) variant of GBS. The patient's antibodies tested positive for Campylobacter jejuni (C. Jejuni) immunoglobulin G (IgG). Since this indicates a past infection, it is uncertain whether C. Jejuni triggered the patient's GBS. However, new valvular vegetation and acute-onset lower extremity weakness make us hypothesize that BCNE may have triggered GBS.

Bacterial Culture-Negative Acute Infective Endocarditis With Vegetation in Native Bicuspid Aortic Valve.

A 51-year-old male with a past medical history of bicuspid aortic valve, hypertension, and anterior cerebral artery stroke of unclear etiology three months earlier, presented to the Emergency Department with progressive shortness of breath, hemoptysis, and night sweats. The patient's echocardiogram revealed a mobile mass greater than 1.0 cm in diameter on the bicuspid aortic valve, which was not present on the echocardiogram three months prior, during his stroke workup. Per modified Duke's criteria, this patient was found to have 'definite' infective endocarditis despite persistently negative blood cultures. The patient underwent urgent surgical aortic valve replacement and a ventricular septal defect was noted that was not seen on prior imaging. The patient was discharged on intravenous antibiotics and warfarin. The patient was able to return to his normal functional status weeks after surgery, and is continuing to exercise without limitation. This case provides an example of patients with bicuspid aortic valves having an increased propensity for developing infective endocarditis. While also highlighting the interesting intra-operative images and presentation of acute culture-negative endocarditis with vegetation, and the subsequent repair, treatment, and recovery.

Case report: Novel three-dimensional echocardiographic methods mapping aortic root pseudoaneurysm secondary to blood culture-negative endocarditis with bicuspid aortic valve involvement.

Background: Infective endocarditis (IE), though uncommon, is a potentially lethal disease. Blood culture-negative endocarditis (BCNIE) accounts for 2.5%-31% of all cases of IE and can lead to life-threatening complications, including aortic root pseudoaneurysm. It is associated with considerable diagnostic and therapeutic dilemmas. TrueVue and TrueVue Glass include the latest two technologies applied in advanced three-dimensional echocardiography, which allow for novel photorealistic images of cardiac structures, and provide abundant previously unavailable diagnostic information. Herein, based on a series of novel three-dimensional echocardiographic methods, we report a case of BCNIE with aortic valve involvement, leading to aortic valve perforation and prolapse, and developing into a giant aortic root pseudoaneurysm. Case summary: In this study, we presented a case of a 64-year-old man exhibiting symptoms of intermittent fever, asthenia, and dyspnea following light exertion. Physical examination, laboratory tests, and electrocardiograms were suspected of IE, though the results of blood cultures were exactly negative. Three-dimensional transthoracic echocardiography, as well as a series of novel advanced techniques, was adopted to clearly visualize the lesions of the aortic valve and aortic root. However, despite active medical treatment modalities, the patient eventually suffered from a sudden, unexpected death 5 days later. Conclusion: BCNIE with aortic valve involvement and development into a giant aortic root pseudoaneurysm is a rare and serious clinical event. In addition, TrueVue and TrueVue Glass offer unprecedented photographic stereoscopic images, enhancing the diagnostic performance of such structural heart diseases.

A Rare Case of Bartonella henselae Infective Endocarditis Causing an Embolic Cerebrovascular Accident.

Bartonella is a facultative intracellular Gram-negative aerobic rod that is an important cause of culture-negative endocarditis that only accounts for 3% of all infective endocarditis (IE) cases. Throughout the literature, there have been very few documented cases of an embolic stroke caused by Bartonella henselae (B. henselae) IE. Following a comprehensive review of the literature, it appears that only a small number of articles have reported on the correlation between cerebrovascular accidents (CVAs) and Bartonella IE. Here, we present a case of a 42-year-old male with a cerebral embolic event as a complication of B. henselae IE.