Sterile Vegetations Research Articles

Non-bacterial thrombotic endocarditis and pancreatic cancer: A literature review.

e24002 Background: Non-bacterial thrombotic endocarditis (NBTE) is a condition in which sterile vegetations are deposited on the cardiac valves, disrupting their function, and posing a risk for embolic stroke. It is a rare condition with rates in autopsy studies ranging from 0.9-1.6%1, and with some of the highest rates observed in patients with pancreatic cancer (PC).2 A review of PC-associated NBTE was conducted to improve our understanding and recognition of this rare but serious clinical entity. Methods: We performed a literature search in PubMed from database inception to November 2023 pairing keywords “Non-Bacterial Thrombotic Endocarditis”, “NBTE”, “Marantic Endocarditis”, “Sterile Endocarditis”, and “Libman-Sacks Endocarditis” with “Pancreatic Cancer”, “Adenocarcinoma of the Pancreas”, and “Neuroendocrine Pancreatic Cancer”. We also used the search term “Marantic Endocarditis associated with Pancreatic Cancer: A case series”. The database was filtered only for full text, English language, and human species. Results: We reviewed 17 studies and included 19 patients in this review. Diagnostic presentation included cerebral vascular accident (CVA) (n = 8), endocarditis (n = 3), or a thrombotic pathology such as deep venous thrombosis (DVT) or pulmonary embolism (PE) (n =4). NBTE (n = 12) was predominantly diagnosed before pancreatic cancer (n = 5). Echocardiography was positive for vegetations in most specified cases (14/15), blood cultures were negative in all specified cases (12/12), and abdominal imaging was consistent with pancreatic cancer in all specified cases (15/15). Metastatic disease was found in 13 out of 19 cases, with spread to liver (n = 13), lung (n = 2), and the adrenal glands (n = 1). Valvular localization identified mitral valve (n = 13), aortic valve (n = 7), and the tricuspid valve (n = 2). Treatment primarily focused on anticoagulation (n = 17), with low molecular weight heparin (n = 8) being the most common agent followed by unfractionated heparin (n = 6). 14 patients had expired by study publication, with 7 deaths occurring due to complications from pancreatic cancer and 2 occurring due to complications from NBTE. Conclusions: NBTE is a rare condition with non-specific presentation, with some of the highest rates seen in PC. Diagnosis of NBTE should prompt immediate treatment as per guidelines and investigation for an underlying malignancy. In PC, especially with metastatic disease, clinicians should maintain a low threshold to initiate an endocarditis work-up in the presence of neurologic symptoms or evidence of cardiac dysfunction. However, it is also important to note that 31% of NBTE cases occurred in the absence of metastatic PC, suggesting that even patients without advanced disease are at risk. Although NBTE associated with PC remains rare, given the severity of both conditions, clinicians should consider work-up for one disease process in the presence of the other.

Peculiarity of Systemic Lupus Erythematosus with Cardiac Involvement in Case Report and Literature Review

Systemic lupus erythematosus (SLE, or lupus) is a condition in which the immune system attacks healthy cells and tissues throughout the body, it is characterized by aberrant activity of the immune system, leading to variable clinical symptoms. Case: A Moroccan 54 years old women presented a progressive dyspnea associated with palpitations with a history of hyperthyroidism, a pericardial effusion of great abundance punctured, the remainder of the diagnostic workup had revealed lupus erythematosus. The echocardiography found a global hypocontractility with an ejection fraction at 25%, a dilated atrial mass and mitral regurgtitaion, moderate aortic regurgitation with an image of vegetation on the non-coronary cusp, right ventricular dysfunction. Laboratory investigations revealed bycitopenia with high inflammatory markers, a renal dysfunction test result. Immunological tests showed a high positive antinuclear antibodies ans DNA antibodies. While hospitalization the patient presented a constrictive chest pain , the electrocardiogram showed an st segment elevation in the inferior derivation in relation with a coronary spasm.Three days later the patient presented a sudden neurological deficit type of right hemiparesis with facial paralysis and aphasia, the emergency MRI objectified a cortical frontotemporal stroke, in the acute phase, patient was thrombolysed by metalysis , finally the diagnosis of vasculitis of the central nervous system (CNS) was retained with ischemic and hemorrhagic lesions in favor of lupus vasculitis of the CNS . Discussion: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that may affect several different organs(5) , the underlying pathophysiologic mechanism remains unknown, new autoantibodies, such as antibodies to DNA , antibodies to extractable nuclear antigens , and anticardiolipin antibodies, were recognized as causative of clinical subsets of lupus(5) SLE is an unpredictable disease, it is characterized by alternating periods of remission and exacerbation and by a wide variety of clinical manifestations that may affect any organ. The case of our patient with SLE involved: cardiac type of lupus myopericadtitis in biventricular dysfunction with LVEF: 25%, , Normochromic normocytic anemia with positive coombs test and lymphopenia and thrombocytopenia ; lupus nephropathy satde IV ; Cerebral vasculitis. Cytopenias are common in patients with lupus, and moderate to severe lymphopenia is associated with high disease activity and organ damage. Up to 50% of patients with SLE have evidence of renal disease at presentation (10) Lupus end-stage kidney disease is associated with worse survival among dialysis and transplant patients. The risk for ischemic stroke is higher in patient with SLE. Stroke affects 3–20% of patients with SLE and usually occurs within the first 5 years of the diagnosis(13,14). The main Cardiovascular diseases of SLE are valvular heart diseases associated with Libman-Sacks disease lesions, sterile vegetations, serositis associated with pericardial disease. African-American patients are at increased risk for development of myocarditis(20); low ejection fraction is detected in the majority of the patients (25)Our patient had an ejection fraction around 25% . The most characteristic valvulopathy of SLE is Libman- Sacks endocarditis (LSE), which mainly affects the left cardiac valves (22) . Non-steroidal anti-inflammatory drugs (NSAIDs) are considered as the first choice in mild cases with minimal pericardial effusion (28) Corticosteroids should be used in refractory cases with or without antimalarials. Corticosteroids in combination with immunosuppressives (25) Cyclophosphamide and intravenous immunoglobulins (IVIGs) have been shown to improve cardiac function and mortality (30), in addition to the medical treatment of Heart failure. Conclusion: Diagnosis of SLE can be challenging and while several classification criteria have been posed, their utility in the clinical setting is still a matter of debate. Despite several agents shown to be efficacious in the treatment of SLE, the disease still poses significant morbidity and mortality risk in patients.

Nonbacterial thrombotic endocarditis of mitral valve associated with a lymphoproliferative malignancy: case report and literature review

BackgroundNon-bacterial thrombotic endocarditis (NBTE) is a rare condition marked by sterile vegetations on cardiac valves, often linked to rheumatologic diseases, autoimmune disorders, and advanced solid malignancies. An early diagnosis and treatment of the associated clinical condition are mandatory, although they do not usually eliminate valvular vegetations, making anticoagulation essential to prevent embolic events. Despite variability, the prognosis of NBTE is usually unfavorable due to recurrent embolic events and the severity of the primary condition, typically advanced cancer.Case presentationWe present a case of a 57 years-old male who presented to the emergency department with a 5-day history of painful bilateral digital edema and color change episodes (from pallor to cyanosis). Physical examination revealed erythrocyanosis in the distal extremities, prompting consideration of secondary Raynaud syndrome.Despite medical therapy, progressive digital ischemia led to multiple finger amputations. During etiological investigation, anticoagulation tests and autoimmune analysis yielded negative results. A transesophageal echocardiogram was performed, revealing an irregular hyperechogenic mass on the anterior leaflet of the mitral valve without valve dysfunction, and a thoracic computed tomography scan with contrast showed an enlarged right paratracheal lymph node. Histopathological analysis from a transthoracic needle biopsy of the paratracheal lymph node revealed diffuse large B-cell lymphoma. The patient underwent aggressive R-CHOP chemotherapy, achieving a favorable complete response.ConclusionThis is a particular case involving the occurrence of NBTE and Raynaud phenomenon as the initial paraneoplastic manifestations in a previously healthy young man. Reports of NBTE associated with lymphoproliferative conditions are quite rare, with fewer than ten cases described in the literature. To our knowledge, this is the first case of NBTE specifically associated with diffuse large B-cell lymphoma.

Marantic Endocarditis and Lung Adenocarcinoma with Brain Metastasis: A Diagnostic Conundrum

Neurological symptoms such as headache and blurring of vision could be a manifestation of an underlying lung adenocarcinoma. The objective of this case report is to unveil the possible differentials and processes involved in the diagnosis of marantic endocarditis. A 57-year old male with blurring of vision and brain CT revealing multiple abscesses, sterile on culture, was treated as per guidelines. However, the patient had recurrent complaints that reinforced recurrent admissions and the patient was found to be COVID-19 positive during the pandemic when a routine test was performed in the emergency department. Suspicious lesions on the chest X-ray were further scrutinised and the patient was diagnosed with lung adenocarcinoma. To further investigate the sterile cultures in the brain, a cardiologist’s opinion was taken and a transthoracic echocardiogram was done, which was unremarkable. The increased suspicion for non-infective endocarditis necessitated a transoesophageal echocardiogram, which was positive for vegetations on the aortic valve. The patient was treated with anticoagulants and chemotherapy. In conclusion, in patients with CT findings of abscesses and sterile cultures, it is crucial to investigate the possible differentials in a meticulous fashion, as there could be an undiagnosed lung cancer in a non-smoker and there is a rare possibility of a sterile vegetation on the aortic valve, as was seen in the authors’ case.

Dynamics of a Staphylococcus aureus infective endocarditis simulation model.

Infective endocarditis (IE) is a serious infection of the inner surface of heart, resulting from minor lesions in the endocardium. The damage induces a healing reaction, which leads to recruitment of fibrin and immune cells. This sterile healing vegetation can be colonized during temporary bacteremia, inducing IE. We have previously established a novel in vitro IE model using a simulated IE vegetation (IEV) model produced from whole venous blood, on which we achieved stable bacterial colonization after 24 h. The bacteria were organized in biofilm aggregates and displayed increased tolerance toward antibiotics. In this current study, we aimed at further characterizing the time course of biofilm formation and the impact on antibiotic tolerance development. We found that a Staphylococcus aureus reference strain, as well as three clinical IE isolates formed biofilms on the IEV after 6 h. When treatment was initiated immediately after infection, the antibiotic effect was significantly higher than when treatment was started after the biofilm was allowed to mature. We could follow the biofilm development microscopically by visualizing growing bacterial aggregates on the IEV. The findings indicate that mature, antibiotic‐tolerant biofilms can be formed in our model already after 6 h, accelerating the screening for optimal treatment strategies for IE.

Cancer-associated non-bacterial thrombotic endocarditis

This paper reviews the current evidence on the pathogenesis, clinical manifestations, diagnosis and management of cancer-associated non-bacterial thrombotic endocarditis (NBTE). NBTE is an underdiagnosed condition characterized by sterile valvular vegetations composed of platelets and fibrin which are susceptible to systemic embolization. Cancer is a leading cause of NBTE and should be excluded in NBTE cases without a clear etiology. Malignancies most frequently associated with NBTE are mucin-releasing adenocarcinomas of the lung, ovary, biliary system, pancreas, breast and stomach. NBTE carries a high risk of arterial thromboembolism, while cardiac valvular dysfunction is much less frequent. NBTE appears to be an important underdiagnosed cause of cancer-associated embolic stroke of undetermined source. Characteristics associated with cancer-associated NBTE include elevated D-dimer, visceral infarcts, cerebral infarcts in multiple vascular territories, transcranial doppler microembolic signals, disseminated cancer and adenocarcinoma histology. Transesophageal echocardiography is the diagnostic test of choice, and all suspected cases should be evaluated for the presence of elevated D-dimers and disseminated intravascular coagulation. Long-term anticoagulation with low molecular weight heparin should be strongly considered, and surgical intervention is usually not needed. Underlying cancer must be diagnosed swiftly (if previously undiagnosed) and anti-cancer treatment should be initiated as soon as possible. The paucity of data regarding all aspects of NBTE, and the severe clinical consequences of untreated NBTE, are an urgent call for future research.

Nonbacterial Thrombotic Endocarditis: Presentation, Pathophysiology, Diagnosis and Management.

Initially described in 1936, non-bacterial thrombotic endocarditis (NBTE) is a rare entity involving sterile vegetations on cardiac valves. These vegetations are usually small and friable, typically associated with hypercoagulable states of malignancy and inflammatory diseases such as systemic lupus erythematosus. Diagnosis remains challenging and is commonly made post-mortem although standard clinical methods such as echocardiography (transthoracic and transesophageal) and magnetic resonance imaging may yield the clinical diagnosis. Prognosis of NBTE is poor with very high morbidity and mortality usually related to the serious underlying conditions and high rates of systemic embolization. Therapeutic anticoagulation with unfractionated heparin has been described as useful for short term prevention of recurrent embolic events in patients with NBTE but there are no guidelines for management of this disease.

Bacteriophages Combined With Subtherapeutic Doses of Flucloxacillin Act Synergistically Against Staphylococcus aureus Experimental Infective Endocarditis.

BackgroundThe potential of phage therapy for the treatment of endovascular Staphylococcus aureus infections remains to be evaluated.Methods and ResultsThe efficacy of a phage cocktail combining Herelleviridae phage vB_SauH_2002 and Podoviriae phage 66 was evaluated against a methicillin‐sensitive S. aureus strain in vitro and in vivo in a rodent model of experimental endocarditis. Six hours after bacterial challenge, animals were treated with (1) the phage cocktail. (2) subtherapeutic flucloxacillin dosage, (3) combination of the phage cocktail and flucloxacillin, or (4) saline. Bacterial loads in cardiac vegetations at 30 hours were the primary outcome. Secondary outcomes were phage loads at 30 hours in cardiac vegetations, blood, spleen, liver, and kidneys. We evaluated phage resistance 30 hours post infection in vegetations of rats under combination treatment. In vitro, phages synergized against S. aureus planktonic cells and the cocktail synergized with flucloxacillin to eradicated biofilms. In infected animals, the phage cocktail achieved bacteriostatic effect. The addition of low‐dose flucloxacillin elevated bacterial suppression (∆ of −5.25 log10 colony forming unit/g [CFU/g] versus treatment onset, P<0.0001) and synergism was confirmed (∆ of −2.15 log10 CFU/g versus low‐dose flucloxacillin alone, P<0.01). Importantly, 9/12 rats given the combination treatment had sterile vegetations at 30 hours. In vivo phage replication was partially suppressed by the antibiotic and selection of resistance to the Podoviridae component of the phage cocktail occurred. Plasma‐mediated inhibition of phage killing activity was observed in vitro.ConclusionsCombining phages with a low‐dose standard of care antibiotic represents a promising strategy for the treatment of S. aureus infective endocarditis.

Novel human invitro vegetation simulation model for infective endocarditis.

Infective endocarditis (IE) is a heart valve infection with high mortality rates. IE results from epithelial lesions, inducing sterile healing vegetations consisting of platelets, leucocytes, and fibrin that are susceptible for colonization by temporary bacteremia. Clinical testing of new treatments for IE is difficult and fast models sparse. The present study aimed at establishing an invitro vegetation simulation IE model for fast screening of novel treatment strategies. A healing promoting platelet and leucocyte-rich fibrin patch was used to establish an IE organoid-like model by colonization with IE-associated bacterial isolates Staphylococcus aureus, Streptococcus spp (S.mitis group), and Enterococcus faecalis. The patch was subsequently exposed to tobramycin, ciprofloxacin, or penicillin. Bacterial colonization was evaluated by microscopy and quantitative bacteriology. We achieved stable bacterial colonization on the patch, comparable to clinical IE vegetations. Microscopy revealed uneven, biofilm-like colonization of the patch. The surface-associated bacteria displayed increased tolerance to antibiotics compared to planktonic bacteria. The present study succeeded in establishing an IE simulation model with the relevant pathogens S.aureus, S.mitis group, and E.faecalis. The findings indicate that the IE model mirrors the natural IE process and has the potential for fast screening of treatment candidates.

TH6. DUPLICATION ORDER OF GENES ASSOCIATED WITH ATTENTION DEFICIT HYPERACTIVITY DISORDER IN HUMANS

Implantable cardiac devices are widely used devices that serve several purposes. Complications from devices are not uncommon and include localized or systemic infections, device-related endocarditis, and device malfunction leading to serious outcomes, including death. Another possible complication that has been reported in the literature is thrombus formation on the device leads. We present a rare case of large thrombi forming on the leads of an implantable cardioverter defibrillator leading to lead fracture and device malfunction. After the device alerted for malfunction, the patient underwent a transesophageal echocardiogram which demonstrated masses on the right atrium and ventricle. He subsequently had a right atrial exploration and lead extraction which revealed large thrombi on the leads which histologically were identified as sterile vegetations.

Ураження ендокарда як дебют системного червоного вовчака, власне спостереження й огляд літератури

Системний червоний вовчак (СЧВ) — хронічне автоімунне захворювання, що характеризується запаленням і пошкодженням багатьох систем органів. Залучення серця при СЧВ — одне з багатьох можливих проявів цього поліморфного захворювання і спостерігається у більше ніж 50 % таких пацієнтів, зачіпаючи всі структурні компоненти серця. Ураження ендокарда при СЧВ є досить рідкісним, але водночас складним клінічним проявом для правильної інтерпретації його нозологічної приналежності. Це пов’язано, з одного боку, з нетиповістю цього ураження в межах СЧВ, коли пацієнти звертаються до кардіологів, терапевтів, кардіохірургів, отримуючи тільки симптоматичну, як в нашому клінічному випадку, допомогу. З іншого боку, використовуючи нові класифікаційні критерії СЧВ, можна з великою часткою визначеності верифікувати цю патологію і почати адекватну базисну терапію, здатну привести до стійкої клініко-лабораторної ремісії і запобігти залученню в процес інших органів і систем. У нашій роботі подано клінічне спостереження дебюту СЧВ з ураження клапанів, пізньої діагностики та нозологічної верифікації вовчакового ендокардиту (ендокардиту Лібмана — Сакса). Проведено огляд літератури з ведення пацієнтів із небактеріальним тромботичним ендокардитом (НБТЕ), обумовленим формуванням стерильних вегетаций на серцевих клапанах без будь-яких ознак інфекції у зв’язку з пошкодженням ендотелію в умовах гіперкоагуляції. Найчастіші причини НБТЕ — СЧВ, антифосфоліпідний синдром та злоякісні новоутворення. Перебіг НБТЕ зазвичай безсимптомний, і цей стан часто є випадковою знахідкою при обстеженні або при розтині. Вегетації частіше локалізовані на клапанах лівих відділів серця (мітральний і рідше аортальний), але можуть бути вражені й інші клапани. Типові клінічні прояви обумовлені емболією. Лікування таких пацієнтів засноване на застосуванні антикоагулянтної терапії і лікуванні основного захворювання, хоча проспективних досліджень не проводилося.

Nephrotic syndrome associated with Libman–Sacks endocarditis as a first manifestation of systemic lupus

Libman–Sacks endocarditis is a rare cardiac manifestation of systemic lupus erythematosus, in which there is sterile vegetation in the heart valves with a significant risk of infective endocarditis. Patient aged 29, presents with a deep nephrotic syndrome, associated with microscopic hematuria, we find in his history a notion of inflammatory arthritis of the ankles, wrists and knees, with alteration of the general state in a long-term febrile context, associated with a chronic inflammatory left subpalpebral cellulitis. The patient was in average general condition, asthenic, with exertional dyspnoea, oedema of the lower limbs rising to the legs and the cardiac examination found a significant murmur at the aorto-mitral focus. Biologically: a deep nephrotic syndrome was found. Inflammatory syndrome with PRC at 80 mg and SR at +++. Inflammatory anaemia and lymphopenia. An echocardiography done, finds a mitro-aortic valve thickening, with the presence of fine vegetations on the aortic side of the posterior sigmoid, in addition to an important mitral and aortic leak. The immunological work-up was strongly positive for antiphospholipid syndrome with IgG anti-cardiolipin antibodies (+), IgG anti-B2GP1 antibodies (+), antinuclear factor antibodies (+) with a speckled appearance; a renal biopsy was performed and was consistent with lupus glomerulonephritis. High-dose corticosteroids combined with double antibiotic therapy significantly improved the patient's clinical and biological parameters. Our observation is quite exceptional because cardiac involvement usually occurs years after the onset of SLE, but in this observation the onset is quite nasty, first in a male subject, associating renal involvement, endocarditis and SAPL. Treatment was based on a combination of antibiotics, corticoids and synthetic antimalarials.

Evaluation of 99mTechnetium-Vancomycin Imaging Potential in Experimental Rat Model for the Diagnosis of Infective Endocarditis.

Infective endocarditis (IE) is an infection of the heart's endocardial surface. In recent years, nuclear imaging methods have gained importance in the diagnosis of IE. The present study aims to investigate the imaging potential of 99mTc-labeled vancomycin (99mTc-Vancomycin) as a new agent that would enable the diagnosis of IE in its early stages when it is difficult to diagnose or has small vegetation in the experimental rat model. 99mTc-Vancomycin scintigraphy was evaluated for its accumulation in IE with Staphylococcus aureus performed in an experimental rat model. Serial planar scintigraphic and biodistribution analysis of infected vegetations are compared to rats with sterile vegetations. The heart was identified as an infected organ, the liver was identified as a non-infected organ and the heart/liver uptake ratio (T / NT ratio) was compared between infective endocarditis and sterile endocarditis groups. Planar scintigrams (in vivo measurements) showed more uptake in the heart of rats in the infective endocarditis group compared to the uptake in the heart of rats in the sterile endocarditis group, but this difference was not statistically significant (p>0.05). From the ex vivo measurements, the 99mTc-Vancomycin heart uptake increased significantly (p = 0.016), liver uptake was significantly decreased (p = 0.045) and the T/NT ratio was significantly higher (p = 0.014) in the infective endocarditis group compared to the sterile endocarditis group. In this experimental study, 99mTc-Vancomycin scintigraphy ensured the detection of ex vivo infected tissue in a rat model of IE. In addition, the absence of significant 99mTc-Vancomycin uptake in the sterile endocarditis group indicates that this agent targeted the infected tissue instead of the sterile inflammatory tissue. Finally, this agent should also be evaluated with animal- specific imaging devices.

Aortic valve surgery for aortic regurgitation caused by Libman-Sacks endocarditis in a patient with primary antiphospholipid syndrome: a case report

BackgroundAntiphospholipid syndrome is an antibody mediated pro-thrombotic state leading to various arterial and venous thromboses. The syndrome can be either primary or secondary to other autoimmune diseases, commonly systemic lupus erythematosus. Cardiac involvement, in particular valvular disease is common in patients with antiphospholipid syndrome, occurring in about a third of these patients. Valvular diseases associated with antiphospholipid syndrome often occur as valve thickening and non-bacterial vegetation or Libman-Sacks endocarditis. Deposits of antiphospholipid immunoglobulin and complement components are commonly observed in the affected valves, suggesting an inflammatory process resulting in valvular vegetation and thickening. Libman-Sacks endocarditis has a high propensity towards mitral valve, although haemodynamically significant valvular dysfunction is rare.Case presentationWe present a successful aortic valve replacement with cardiopulmonary bypass in a 48 years old lady with antiphospholipid syndrome, who has severe aortic regurgitation as a result of Libman-sacks endocarditis. Antiphospholipid antibodies were positive and the clinical data showed both negative cultures and infective parameters. Surgically resected vegetations revealed sterile fibrinous and verrucous vegetations on aortic valve. Valve replacement and the course of cardiopulmonary bypass was uneventful, and the patient was discharged well.ConclusionsClassically Libman-Sacks endocarditis is often and more commonly associated with autoimmune diseases such as systemic lupus erythematosus, although it can occur in both primary and secondary antiphospholipid syndrome. It is not a common entity, and it is a frequent underestimated disease as most clinicians do not routinely screen for valvular lesion in patients with antiphospholipid syndrome unless they are symptomatic. However, due to its high prevalence of cardiac involvement, clinicians should have a high index of suspicion in the attempt to minimize cardiovascular and haemodynamic complications. Valve surgery in patients with antiphospholipid syndrome carries considerable early and late morbidity and mortality, usually caused by thromboembolic and bleeding events. The perioperative anticoagulation management and haemostatic aspect of antiphospholipid syndrome present an exceptional challenges to clinicians, surgeons, anaesthetists and laboratory personnel.

Non-bacterial thrombotic endocarditis manifested by ventricular fibrillation in a patient with low grade ovarian carcinoma: case report and literature review

BackgroundNon-bacterial thrombotic endocarditis (NBTE) is a rare form of endocarditis notably described in patients with advanced malignancy and auto-immune diseases. It is characterized by the formation of sterile, fibrin-containing vegetations on cardiac endothelium, in the absence of positive blood cultures. It is predominantly located on the mitral- and aortic valve (AV). Vegetations in NBTE are prone to embolize. Trousseau syndrome (TS) is defined as unexplained thrombotic events that precede the diagnosis of malignancy.Case summaryA 49-year-old pre-menopausal woman with a history of visual disturbances, recurrent deep vein thrombosis (DVT) with concurrent pulmonary emboli (PE), and uterine myomas with dysfunctional uterine bleeding was resuscitated for ventricular fibrillation. While echocardiography revealed vegetations on the AV, blood cultures remained negative. Additional work-up for the aetiology of sterile vegetations revealed a low-grade ovarian carcinoma. Cardiac analysis showed evidence of myocardial infarction in the absence of coronary atherosclerosis as a cause for ventricular fibrillation.DiscussionUnexplained thrombotic events (venous, arterial, or both) warrant further investigation, e.g., with regard to TS. NBTE is a potential source of thromboembolism in TS and a rare ante-mortem finding, which prompts additional investigation of the underlying cause. In our patient, a triad of (suspected) (i) arterial/systemic embolization (i.e. visual disturbances, splenic infarction, coronary embolism), (ii) peripheral thrombophlebitis/hypercoagulability (i.e. DVT and PE), and (iii) malignancy (i.e. gynaecological abnormalities) raised suspicion of NBTE in the setting of TS. Early diagnosis and treatment of NBTE is of importance due to the high incidence of embolization, with possible fatal outcome.

Marantic Endocarditis Associated with COVID-19: A Rare Case Report of a Potentially Deadly Disease.

COVID-19 has caused a major global pandemic, with high morbidity and mortality.One of the complications of COVID-19 infection is a hypercoagulable state.To the best of our knowledge, we present only the second case of marantic endocarditis in a patient with COVID-19, in the hope of raising awareness among physicians of this potential rare association.

Chapter 12 - Neurologic complications of nonbacterial thrombotic endocarditis

Endocarditis is an inflammatory or infective condition affecting the cardiac valves or endocardium, often associated with serious neurological sequelae. Nonbacterial thrombotic endocarditis (NBTE)-referred to as degenerative, Libman-Sachs, marantic, verrucous, or terminal endocarditis-is a serious but rare cause of valvular heart disease characterized by deposition of sterile vegetations of fibrin and platelet aggregates on the cardiac valves, eventually resulting in life-threatening embolization of these thrombi to the brain, limbs, or visceral organs. NBTE may complicate a heterogeneous group of chronic conditions, predominantly connective tissue and autoimmune disorders, malignancies, and diseases associated with hypercoagulability states. NBTE usually affects the native rather than prosthetic valves, and unlike infective endocarditis (IE), sparing the involved valve function without its destruction. Compared to those seen in IE, vegetations in NBTE are small and friable, thus may easily be dislodged leading to systemic thromboembolism with devastating morbidities and mortality. There are no diagnostic criteria for NBTE, and antemortem diagnosis is challenging. The condition should be suspected in patients with thromboembolic events and vegetations on the cardiac valves on echocardiographic or cardiac imaging studies, in the absence of underlying infection, especially in disorders predisposing to coagulopathy. Early recognition and prompt treatment of the primary underlying disorder is essential. Anticoagulation with heparin or heparinoid products is recommended to prevent recurrent embolism. Surgical intervention is not indicated except in selected patients with life-threatening recurrent embolism.

Editors' note: Neurologic complications of coronavirus infections.

Editors' note: Neurologic complications of coronavirus infections.

Reader response: Neurologic complications of coronavirus infections.

Dr Nath's timely editorial1 lists the neurologic complications of coronavirus infections. On behalf of coauthors, I highlight 5 patients with large artery stroke in the 2003 severe acute respiratory syndrome (SARS) outbreak in Singapore, arising from SARS-CoV-1 virus infection.2 Of 206 patients, 48 required intensive care and 32 died. Four of the 5 patients with stroke were critically ill and 3 died. The strokes were deemed thromboembolic. At autopsy, 1 patient had occipital lobe infarction, sterile vegetations in multiple valves, deep venous thrombosis, and pulmonary embolism; this prompted low-molecular-weight heparin (LMWH) use in subsequent critically ill patients with SARS. Nevertheless, a significant number of patients suffered venous thromboembolism, despite adequate treatment with LMWH.3 Three patients received intravenous immunoglobulin (IVIg) empirically, which might have contributed to stroke. The induction of hfgl2 prothrombinase gene by SARS-CoV-1 in experiments raised the possibility of a direct prothrombotic effect of that coronavirus.4 Only 8 patients underwent autopsy; therefore, more strokes may have gone undiagnosed. It is easy to miss stroke in critically ill patients who are heavily sedated and paralyzed. With increasing anecdotal reports ([journals.lww.com/neurotodayonline][1]), and the use of IVIg in desperately ill patients with COVID-19,5 we reiterate vigilance against strokes and thrombotic complications in critically ill coronavirus infected patients. [1]: https://journals.lww.com/neurotodayonline

Embolic Showering from Non-Bacterial Thrombotic Endocarditis and Adenocarcinoma of the Lung.

Non-bacterial thrombotic endocarditis (NBTE) is a paraneoplastic phenomenon with sterile vegetations. It is associated with adenocarcinoma and can shower emboli, which can be the presenting symptom. A 44-year-old woman with adenocarcinoma of the lung presented with chest pain, left hand weakness, and ataxia due to repeated embolic showering from NBTE to the central nervous system (CNS) and spleen. NBTE is a rare condition that should be on the differential diagnosis in patients with culture-negative endocarditis and a history of adenocarcinoma. Differentiating non-bacterial thrombotic endocarditis (NBTE) from infective endocarditis can be a diagnostic challenge due to slow growing organisms; laboratory findings that suggest NBTE include the lack of leucocytosis, normal C-reactive protein, negative blood culture sets, and positive antiphospholipid antibodies.Serial transesophageal echocardiogram (TEE) should be performed if suspicion of valvular vegetations is high despite the initial TEE showing no vegetations.The mainstay treatment of NBTE is anticoagulation and addressing the underlying condition.