Nonbacterial Thrombotic Endocarditis Research Articles

Systemic thromboembolism from a misdiagnosed non‑bacterial thrombotic endocarditis in a patient with lung cancer: A case report

Thromboembolic events are frequent in patients with cancer, commonly involving the venous and pulmonary circulation. The arterial system is rarely implicated in embolism and, when involved, a cardiogenic origin should always be excluded. In the present study, a case of a patient who developed multiple embolic events concomitantly with the diagnosis of locally-advanced non-small cell lung cancer with high expression levels of programmed death-ligand 1 (PD-L1) in >50% of tumor cells is reported. A cardiac defect interpreted as a patent foramen ovale required low molecular weight heparin administration. Despite the anti-coagulant therapy, before first-line anticancer treatment with pembrolizumab immunotherapy could be administered due to high PD-L1 expression levels, a new hospitalization was required due to the onset of novel ischemic manifestation. New transthoracic and transesophageal echocardiography revealed a previously misdiagnosed vegetation of the mitral valve that caused systemic embolization. The lack of any sign of infection led to the diagnosis of a non-bacterial thrombotic endocarditis (NBTE), whose embolic sprouting gave rise to the widespread ischemic events. No active anticancer treatment was feasible due to the rapid progression of the disease. NBTE can evolve quickly, eventually preventing any chance of treatment targeting the primary cause, which in the present study was lung cancer. If NBTE can be correctly diagnosed sooner then there may be the potential for anticancer therapy that does not worsen the hypercoagulability state, thus improving cancer-associated survival.

Histopathological findings and viral tropism in UK patients with severe fatal COVID-19: a post-mortem study

BackgroundSevere COVID-19 has a high mortality rate. Comprehensive pathological descriptions of COVID-19 are scarce and limited in scope. We aimed to describe the histopathological findings and viral tropism in patients who died of severe COVID-19.MethodsIn this case series, patients were considered eligible if they were older than 18 years, with premortem diagnosis of severe acute respiratory syndrome coronavirus 2 infection and COVID-19 listed clinically as the direct cause of death. Between March 1 and April 30, 2020, full post-mortem examinations were done on nine patients with confirmed COVID-19, including sampling of all major organs. A limited autopsy was done on one additional patient. Histochemical and immunohistochemical analyses were done, and histopathological findings were reported by subspecialist pathologists. Viral quantitative RT-PCR analysis was done on tissue samples from a subset of patients.FindingsThe median age at death of our cohort of ten patients was 73 years (IQR 52–79). Thrombotic features were observed in at least one major organ in all full autopsies, predominantly in the lung (eight [89%] of nine patients), heart (five [56%]), and kidney (four [44%]). Diffuse alveolar damage was the most consistent lung finding (all ten patients); however, organisation was noted in patients with a longer clinical course. We documented lymphocyte depletion (particularly CD8-positive T cells) in haematological organs and haemophagocytosis. Evidence of acute tubular injury was noted in all nine patients examined. Major unexpected findings were acute pancreatitis (two [22%] of nine patients), adrenal micro-infarction (three [33%]), pericarditis (two [22%]), disseminated mucormycosis (one [10%] of ten patients), aortic dissection (one [11%] of nine patients), and marantic endocarditis (one [11%]). Viral genomes were detected outside of the respiratory tract in four of five patients. The presence of subgenomic viral RNA transcripts provided evidence of active viral replication outside the respiratory tract in three of five patients.InterpretationOur series supports clinical data showing that the four dominant interrelated pathological processes in severe COVID-19 are diffuse alveolar damage, thrombosis, haemophagocytosis, and immune cell depletion. Additionally, we report here several novel autopsy findings including pancreatitis, pericarditis, adrenal micro-infarction, secondary disseminated mucormycosis, and brain microglial activation, which require additional investigation to understand their role in COVID-19.FundingImperial Biomedical Research Centre, Wellcome Trust, Biotechnology and Biological Sciences Research Council.

A Contemporary 20-Year Cleveland Clinic Experience of Nonbacterial Thrombotic Endocarditis: Etiology, Echocardiographic Imaging, Management, and Outcomes

BackgroundNonbacterial thrombotic endocarditis, or marantic endocarditis, is rare. Contemporary data on the etiology, echocardiographic evaluation, and management of nonbacterial thrombotic endocarditis are limited. MethodsA single-center retrospective cohort study was performed. Electronic medical records and echocardiographic records were searched for patients ages ≥18 years with a confirmed diagnosis of nonbacterial thrombotic endocarditis between January 1999 and November 2019. Demographic, echocardiographic, and management data were collected. ResultsOf 600,577 transthoracic echocardiograms (TTEs) and 89,264 transesophageal echocardiograms (TEEs), 42 patients had nonbacterial thrombotic endocarditis (mean age: 54 ± 14.5 years; 66.7% were female). The median duration of follow-up was 8.2 (interquartile range 3.3-24.4) months. Seventeen patients (40.5%) had malignancy, 33.3% had systemic lupus erythematosus, and 35.7% had antiphospholipid antibody syndrome. Stroke was the most common presentation (59.5%).TTE enabled the diagnosis in 19 cases (45.2%), compared with TEE, which identified the condition in 33 of 34 (97.1%) cases in which it was utilized. Three-dimensional echocardiography was performed in 17 TEEs. The most common valves involved were mitral (61.9%), and aortic (23.8%) valves. Thirty-two patients were managed with anticoagulation. Ten patients underwent surgery. Sixteen (38.1%) patients died, most of whom had a diagnosis of advanced malignancy. ConclusionIn a contemporary 20-year cohort, TTE and TEE played important roles in diagnosis, with superior diagnostic performance of TEE for nonbacterial thrombotic endocarditis. Mortality was high, and advanced malignancy portended a worse prognosis. Management in most cases was therapeutic anticoagulation. In select cases, surgery provided favorable outcomes.

Non-Bacterial Thrombotic Endocarditis: A Presentation of COVID-19.

The SARS-CoV-2 virus is a newly emergent pathogen first identified in Wuhan, China, and responsible for the COVID-19 global pandemic. In this case report we describe a manifestation of non-bacterial thrombotic endocarditis with continuous peripheral embolization in a COVID-19-positive patient. The patient responded well to high-dose LMWH treatment with cessation of the embolic process.LEARNING POINTSRaising awareness of possible complications of COVID-19.To highlight the importance of the careful consideration of and dosage of anticoagulation in non-bacterial thrombotic endocarditis.

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.

A Case of Nonbacterial Thrombotic Endocarditis Following Immune Checkpoint Inhibitor Treatment for Lung Adenocarcinoma

A Case of Nonbacterial Thrombotic Endocarditis Following Immune Checkpoint Inhibitor Treatment for Lung Adenocarcinoma

Adult-onset Still's disease accompanying noninfective endocarditis.

Adult-onset Still's disease can develop valve lesions. Since AOSD may complicate valvular lesion, differentiation of endocarditis in patients with AOSD is required.

Long-term follow-up of antiphospholipid syndrome: real-life experience from a single center.

The objective of this paper is to assess the prevalence of the main clinical manifestations and laboratory features at disease onset and during the ensuing 10years of a large cohort of patients with antiphospholipid syndrome (APS) from a single center. The study included all consecutive APS patients followed longitudinally in our center from 2003 to 2013. Descriptive statistics for demographics, clinical and laboratory features and mortality were performed. A total of 160 patients were included. Most of them, 128 (78.8%), were women and the mean (SD) age at diagnosis was 39.1 (14.0) years. The majority of them, 104 (65.0%), had primary APS, 36 (22.5%) had APS associated with systemic lupus erythematous, and 20 (12.5%) had APS associated with other autoimmune disease. During the study period, thrombotic events occurred in 27 (16.9%) patients, the most common being strokes, nonbacterial thrombotic endocarditis and deep venous thrombosis. Regarding obstetric morbidity, 18 women (14.3%) became pregnant and 90% of pregnancies succeeded in having live births. The most common obstetric complication was early pregnancy loss (15% of pregnancies). Prematurity (11.1% of live births) and intrauterine growth restriction (5.6% of live births) were the most frequent fetal morbidities. Ten (6.3%) patients died and the most frequent causes of death were severe thrombosis, hemorrhage, and cancer. Three (0.9%) cases of catastrophic APS occurred. The survival probability at 10 years was 93.8%. Patients with APS develop significant morbidity and mortality despite current treatment. It is imperative to identify prognostic factors and therapeutic measures to prevent these complications.

Outcome of Stroke Patients with Cancer and Nonbacterial Thrombotic Endocarditis.

Background and PurposeNonbacterial thrombotic endocarditis (NBTE) is a cause of stroke in cancer. However, clinical characteristics and outcomes in stroke patients with cancer-associated NBTE are not well known.MethodsWe included consecutive patients with stroke and active cancer over a 9-year period who underwent echocardiography. We retrospectively compared clinical characteristics and presence of metastasis between patients with NBTE, those with cryptogenic etiologies, and those with determined etiologies. We also investigated mortality and stroke events during the 6-month follow-up.ResultsAmong the 245 patients, 20 had NBTE, 96 had cryptogenic etiologies, and 129 had determined etiologies. Metastasis was seen in all 20 patients (100%) with NBTE, 69.8% in patients with cryptogenic etiology, and 48.8% in patients with or determined etiology. During the 6-month follow-up, 127 patients (51.8%) developed stroke and/or died (death in 110 [44.9%] and stroke events in 55 [22.4%]). Patients with NBTE showed significantly higher mortality (80%) and stroke occurrence (50%) than those with cryptogenic etiologies (mortality 54.2%, stroke 25.0%, log-rank P=0.006) and determined etiologies (mortality 32.6%, stroke 16.3%, log-rank P<0.001). In a multivariate Cox proportional hazard analysis, the presence of NBTE was independently associated with composite outcomes of mortality and stroke events (hazard ratio, 1.941; 95% confidence interval, 1.052 to 3.690).ConclusionsNBTE should be suspected as a potential cause of stroke in patients with metastatic cancer. Patients with NBTE have a high risk of recurrent stroke and mortality. Future studies are necessary to determine strategies to reduce stroke recurrence in patients with NBTE.

Non-infective endocarditis

### Learning objectives Endocarditis is defined as inflammation of the endocardium, the lining of the cardiac chambers and valves, and characterised by vegetations, most commonly caused by infection with bacteria...

RAGING REGURGITATION RAISES SPECTER OF MYSTERIOUS ENDOCARDITIS

Libman-Sacks endocarditis is a nonbacterial thrombotic endocarditis (NBTE) associated with anti-cardiolipin positive systemic lupus erythematosus and anti-phospholipid antibody syndrome. Lesions typically affect the mitral and aortic valves leading to regurgitation. A 44-year-old woman with Crohn's

AN ECHOGENIC MASS ON A BIOPROSTHETIC MITRAL VALVE

Nonbacterial thrombotic endocarditis (NBTE) is often diagnosed postmortem concurrently with an underlying hypercoagulable state, such as systemic lupus erythematosus or malignancy. In-vivo diagnosis is usually prompted by clinical symptoms from systemic embolization with a multimodality approach

Cholangiocarcinoma Manifesting as Non-Bacterial Thrombotic Endocarditis in a Young Patient

Cholangiocarcinoma Manifesting as Non-Bacterial Thrombotic Endocarditis in a Young Patient

Non-Bacterial Thrombotic Endocarditis: A Manifestation of Lung Cancer

Non-bacterial thrombotic endocarditis (NBTE) is characterized by vegetations on cardiac valves consisting of fibrin and platelet aggregates that are devoid of inflammation or bacteria. Diagnosis is often challenging and is aided by a high index of suspicion. These factors are reflected by the case of a 53 year old woman with a history of recurrent idiopathic deep vein thrombosis (DVT) prior to presentation at our institution to which she was admitted because of right upper extremity numbness and weakness.

441 An Atypical Case of Marantic Endocarditis in Undiagnosed Antiphospholipid Syndrome

Marantic endocarditis (ME) is difficult to differentiate from infective endocarditis (IE) [[1]Bussani R. F DE-G Pesel G. Zandona L. Sinagra G. Grassi S. et al.Overview and Comparison of Infectious Endocarditis and Non-infectious Endocarditis: A Review of 814 Autoptic Cases.In vivo (Athens, Greece). 2019; 33: 1565-1572PubMed Google Scholar]. We demonstrate an atypical case of ME presenting as an independently-mobile mass and severe MR. A 57-year-old man presented with a right parietal stroke secondary to mitral valve(MV) endocarditis. Past history was significant for a provoked pulmonary embolus. Family history was insignificant. Transthoracic (TTE) and transoesophageal echocardiogram revealed a 1.1x0.6cm independently-mobile MV vegetation with severe mitral regurgitation (MR) and normal left atrium size. He was clinically euvolaemic. Empiric antibiotics were commenced. Inflammatory markers were normal and blood cultures negative. He was considered for MV surgery. Preoperative coagulation studies revealed an incidental elevated activated partial thromboplastin time (APTT) (77s) which did not correct with mixing studies. Thrombophilia screen demonstrated high anti-cardiolipin >2024 and beta-2-glycoprotein-1 antibodies >6100. A diagnosis of ME due to presumed antiphospholipid syndrome (APLS) was established. Multidisciplinary decision was made to trial anticoagulation with warfarin over surgery. TTE at 4 months demonstrated resolution of the vegetation with mild mitral incompetence. While rare(prevalence 0.9-1.6%), ME is associated with high morbidity and mortality [[2]Gundersen H. Moynihan B. An Uncommon Cause of Stroke: Non-bacterial Thrombotic Endocarditis.Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association. 2016; 25: e163-e164Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar]. Causes of ME can be inflammatory, autoimmune or malignant [[3]Ahmed S. Jani P. Yamani M.H. Ailawadhi S. Alegria V.R. Ailawadhi M. Marantic Endocarditis Associated With T-Cell Large Granular Lymphocytic Leukemia: First Report of Its Occurrence With a Lymphoproliferative Malignancy in Adults.Journal of oncology practice. 2018; 14: 625-627Crossref PubMed Scopus (2) Google Scholar]. ME commonly affects the MV [[4]Murtaza G. Iskandar J. Humphrey T. Adhikari S. Kuruvilla A. Lupus-Negative Libman-Sacks Endocarditis Complicated by Catastrophic Antiphospholipid Syndrome.Cardiology research. 2017; 8: 57-62Crossref PubMed Google Scholar] and presents with embolic phenomena [[5]Deppisch L.M. Fayemi A.O. Non-bacterial thrombotic endocarditis: clinicopathologic correlations.American heart journal. 1976; 92: 723-729Crossref PubMed Scopus (122) Google Scholar]. ME vegetations typically attach firmly to valve leaflets and move with them compared to independently-mobile infective vegetations [[6]Bouma W. Klinkenberg T.J. van der Horst I.C. Wijdh-den Hamer I.J. Erasmus M.E. Bijl M. et al.Mitral valve surgery for mitral regurgitation caused by Libman-Sacks endocarditis: a report of four cases and a systematic review of the literature.Journal of cardiothoracic surgery. 2010; 5: 13Crossref PubMed Scopus (59) Google Scholar]. Significant valvular regurgitation is rare. Surgical treatment in ME is seldom required with the mainstay treatment being therapeutic anticoagulation [[6]Bouma W. Klinkenberg T.J. van der Horst I.C. Wijdh-den Hamer I.J. Erasmus M.E. Bijl M. et al.Mitral valve surgery for mitral regurgitation caused by Libman-Sacks endocarditis: a report of four cases and a systematic review of the literature.Journal of cardiothoracic surgery. 2010; 5: 13Crossref PubMed Scopus (59) Google Scholar]. Our case highlights the value of a multidisciplinary approach to endocarditis and importance of a thorough history and scrutiny of investigations.

P691 New onset severe mitral regurgitation in oncological patient: when the disease progresses

Abstract Nonbacterial thrombotic endocarditis is frequently diagnosed in postmortem autopsies. However, in some patients with systemic diseases it is diagnosed in the context of multiple embolic events, so a high degree of clinical suspicion must be maintained to offer the best treatment to these patients. We report a case of a 59-year-old woman with diagnosis of stage IV lung adenocarcinoma in the context of first episode of cardiac tamponade requiring urgent pericardiocentesis. She was admitted to the emergency department for an acute ischemic stroke, so antiplatelet therapy was started and chemotherapy discontinued. After few weeks, she required new admission due to progression of the oncological disease and bilateral pulmonary thromboembolism secondary to deep vein thrombosis of the lower extremities. Given the progression of the disease, it was decided not to return to chemotherapy and to start anticoagulant therapy with low molecular weight heparin. A transthoracic echocardiogram (TTE) was requested, which highlighted a thickened mitral valve with severe mitral regurgitation, not present in the TTE performed one year before. She was asymptomatic, without fever, with repeatedly negative blood cultures and absence of infectious markers. A new TTE was repeated 4 weeks later, beeing under antiplatelet and anticoagulant treatment, observing a greater thickening of both mitral leaflets with nodular image on the anterior mitral leaflet, persisting a severe mitral regurgitation. Given the low probability of infective endocarditis, these findings were attributed to a nonbacterial thrombotic endocarditis in the context of a progressive malignant disease. Nonbacterial thrombotic endocarditis is characterized by the presence of sterile vegetations formed by the accumulation of platelets and fibrin. It is associated with neoplastic processes (specially with mucinous adenocarcinomas) as well as with autoimmune, rheumatologic and infectious processes. These vegetations tend to produce multiple systemic embolizations, which usually manifests as the first symptom. Patients do not usually present murmurs in the physical examination, nor fever, and blood cultures are negative. It is necessary to complete the study with a TTE, where the left valves tend to be affected more frequently (mitral valve in 2/3 of the cases). In case of doubt, the study should be completed with a TEE, although neither of these techniques differentiates infectious vegetations from thrombotic ones. Treatment consists of treating the underlying cause and starting anticoagulation with heparin to prevent new embolisms. In some isolated cases the surgical treatment of this entity has been proposed. Conclusion presence of nonbacterial thrombotic endocarditis should be suspected in all patients with multiple embolisms and concomitant systemic disease. Study must be completed with a TTE/TEE and anticoagulant treatment should be started. Abstract P691 Figure. A: Mitral valve 1 year before. B: now

P1243 Nonbacterial thrombotic endocarditis (NBTE) of the aortic valve: incidental finding in hospitalized patients with advanced heart failure

Abstract Background The presence of small mobile masses on the ventricular side of the aortic valves in the absence of valvular regurgitation and signs of systemic inflammation has been previously described as marantic endocarditis and is now referred to as nonbacterial thrombotic endocarditis (NBTE). It is thought to be associated with endothelial dysfunction and procoagulative status, as is the case of acute decompensated heart failure (HF). Case description We present a series of three male patients, with similar clinical characteristics, who were admitted for acute decompensated HF. All three patients had chronic HF, due to non-ischemic dilated cardiomyopathy with severe biventricular dysfunction, with resynchronization therapy, with elevated natriuretic peptides and previous HF hospitalizations in the past year requiring prolonged intravenous treatments. Other clinical, biological criteria for the definition of advanced HF were also met. All patients were under chronic anticoagulation treatment using a direct oral anticoagulant because of persistent atrial fibrillation. Thorough echocardiographic evaluation (both transthoracic and transoesophageal ultrasound) identified small mobile masses on the ventricular side of the aortic valves, centrally, on the line of cusp coaptation, with only minor central regurgitation. The lack of progression of valve lesion and the absence of gross signs of inflammation (no fever, normal hemoleucogram, normal CRP, repeated negative blood cultures) on serial examinations during several weeks follow-up allowed for the exclusion of infective endocarditis. In one case we also identified a left atrial appendage thrombus and presumably thrombotic masses attached to right side pacing leads. No clinically systemic embolic events were identified. Conclusion We consider this to be an incidental finding in the given subclinical prothrombotic and inflammatory predisposing milieu of advanced chronic HF and the increasing high quality echocardiography imaging. Its clinical significance is still unknown, while differential diagnosis from subacute or chronic endocarditis relies largely on clinical judgment.

Recurrent Stroke In 34 Year-Old, Unusual Presentation of Non-Bacterial Endocarditis

Factor V Leiden (FVL) and prothrombin G20210A (PGM) mutations are the most frequent genetic risk factors involved in deep venous thrombosis in Caucasians. Being heterozygous for both seems to increase the risk of venous events but it is not well established if the association increases the risk of arterial thrombosis or other thrombotic events. We present a case of recurrent stroke caused by non-bacterial thrombotic endocarditis (NBTE) in a 34-year-old Caucasian man heterozygous for both FVL and PGM. His diagnosis of NBTE was confirmed with pathology in the absence of other causes of NBTE.

P630 Recovery of non-bacterial thrombotic endocarditis and severe aortic regurgitation in a young patient with acute promyelocytic leukemia

Abstract Introduction Non-bacterial thrombotic endocarditis (NBTE) is characterised by non-infectious vegetations on the cardiac valves and is typically seen in patients with malignancies or systemic lupus erythematosus. Risk of thromboembolic events is high and treatment of choice consists of anticoagulation, if feasible, as well as treatment of the underlying disease. Severe valvular dysfunction is rarely seen and in these cases, surgical valve replacement is usually performed. Case presentation A 28-year old female patient presented with left-sided hemiparesis persisting for several hours. Angio-CT scan of the brain revealed a branch occlusion of the middle cerebral artery with a correlating infarct core and without an area of penumbra. Blood tests showed decreased thrombocyte levels (45 x109/l). Given the thrombocytopenia and the time between the onset of symptoms and presentation, no thrombolysis was administered. A subsequently performed transoesophageal echocardiography for diagnostic work-up of cardioembolic sources of stroke revealed a right ventricular thrombus and vegetations on the aortic valve causing severe aortic regurgitation with a holodiastolic flow reversal in the descending aorta (Fig. 1 (a) and (b) showing a large central coaptation defect). There were no of signs of infection or inflammation and blood cultures remained negative, thus infectious endocarditis was unlikely. A bone marrow biopsy led to the diagnosis of acute promyeolocytic leukemia (PML). Despite the inherent high risk of bleeding due to PML, anticoagulation with unfractionated heparin was initiated and treatment with prednisolone, all-trans retinoic acid and arsenic trioxide was started. After three weeks of therapy aortic valve vegetation size decreased considerably leading to dramatic reduction of aortic regurgitation (Fig. 1 (c) and (d)). No further embolic event or bleeding occurred. Conclusion This case is remarkable in many aspects. First, PML typically causes bleeding complications whereas NBTE is characterised by a high risk of thromboembolic events. Thus, the decision to start or not to start anticoagulation is challenging. Second, NBTE, unlike infectious endocarditis, rarely causes severe valvular dysfunction and reported treatment in most cases consisted of surgical valve replacement or repair. However, in this case, conservative treatment alone led to almost complete resolution of valvular vegetations and of aortic regurgitation. We conclude that conservative treatment of severe valvular disease in the setting of NBTE should be strongly considered, especially given the small number of cases reported worldwide. Abstract P630 Figure. Fig.1

Thrombectomy and Thrombolysis by Catheter Through Right Gastroepiploic Vein of Acute Superior Mesenteric Venous Thrombosis with Peritoneal Signs

Thrombectomy and Thrombolysis by Catheter Through Right Gastroepiploic Vein of Acute Superior Mesenteric Venous Thrombosis with Peritoneal Signs