Nonbacterial Thrombotic Endocarditis Research Articles

A case series of non-bacterial thrombotic endocarditis associated with gynecological malignancies

Background: Ischemic stroke secondary to NBTE is a rare complication of systemic malignancies. Although previously reported in gynecological cancers, this occurrence is infrequent. Furthermore, stroke pre-dating the gynecological malignancy diagnosis has rarely been reported. Methods: Case presentations and literature review. Results: Case1: A 48-year-old woman presented with acute dysarthria and left facial weakness caused by a right middle cerebral artery (MCA) infarct. Mitral valve vegetations were found on a transthoracic echocardiogram (TTE). A malignancy screen uncovered a pelvic endometrial adenocarcinoma. Case 2: A 49-year-old woman developed acute right hand weakness. A CT head scan showed a left pre-central gyrus infarct. Her TEE revealed aortic valve vegetations. An ovarian neoplasm was then discovered. Case 3: A 36-year-old woman with a known diagnosis of cervical squamous cell carcinoma developed acute left-sided weakness secondary to a right MCA stroke. Aortic valve vegetations were seen on TTE. Conclusions: We have reported three cases of NBTE where the underlying malignancy was gynecological. In the first two cases, the malignancy was discovered while investigating for the stroke mechanism, while the third had a known underlying malignancy. This series highlights the need to consider gynecological malignancies as an underlying cause of stroke in young women; and that the ischemic event can occur prior to the malignancy diagnosis.

Diagnostic yield of echocardiography in cancer patients with ischemic stroke.

The yield of echocardiography in cancer patients with acute ischemic stroke is unknown. We identified adult patients with active systemic cancer diagnosed with acute ischemic stroke at a tertiary-care cancer center from 2005 through 2009 who underwent transthoracic (TTE) or transesophageal echocardiography (TEE). Two neurologists independently reviewed all clinical data, including TTE and TEE reports, and adjudicated whether echocardiographic studies revealed a definite or possible source of stroke according to pre-defined criteria. Patients were classified as having suspected cardioembolic strokes if imaging showed embolic-appearing infarcts in more than one vascular territory. Among 220 patients with cancer and ischemic stroke who underwent echocardiography, 216 (98%) had TTE and 37 (17%) had TEE. TTE revealed a definite source in 15 (7%, 95% CI 4-10%) patients and a possible source in 42 (19%, 95% CI 14-25%), while TEE revealed a definite source in 10 (27%, 95% CI 12-42%) patients and a possible source in 14 (38%, 95% CI 21-54%). In 92 patients with suspected cardioembolic strokes who underwent TTE, 6 (7%, 95% CI 1-12%) had a definite source, including 4 with marantic endocarditis, and 20 (22%, 95% CI 13-30%) had a possible source. Twenty-one of these patients also underwent TEE, which demonstrated a definite or possible source in 16 (76%, 95% CI 56-96%) patients, including marantic endocarditis in 4 (19%). The yield of TTE for detecting marantic endocarditis and other cardiac sources of stroke in cancer patients is low, but TEE may provide a higher yield in targeted patients.

In-hospital stroke recurrence and stroke after transient ischemic attack: frequency and risk factors.

We aimed to assess the risk of recurrent ischemic events during hospitalization for stroke or transient ischemic attack (TIA) with optimal current management and to identify associated risk factors. We performed a retrospective analysis of all patients treated for acute ischemic stroke or TIA in 3 stroke units between 2010 and 2013. Recurrent stroke was defined as new persisting (≥24 hours) neurological deficit occurring >24 hours after the index event and not attributable to other causes of neurological deterioration. Cox proportional hazard regression identified risk factors associated with recurrent stroke. The study included 5106 patients. During a median length of stay of 5 days (interquartile range, 4-8), stroke recurrence (or stroke after TIA) occurred in 40 patients (0.8%) and was independently associated with history of TIA, symptomatic carotid stenosis (≥70%), or other determined etiology. Patients with recurrent stroke and other determined etiology had cervical arterial dissection (n=2), primary angiitis of the central nervous system (n=1), giant cell arteritis (n=1), and lung cancer with nonbacterial thrombotic endocarditis (n=1). In patients with initial TIA or minor stroke (National Institutes of Health Stroke Scale ≤5) recurrence was associated additionally with pneumonia after the inciting ischemic event but before stroke recurrence. Patients with initial stroke and aphasia had a lower stroke recurrence rate and there were no recurrences in patients with lacunar stroke. Recurrence was associated with significantly higher in-hospital mortality (17.5% versus 3.1%; P<0.001). In-hospital stroke recurrence was low with optimal current management. Patients with a history of TIA, severe symptomatic carotid stenosis, or uncommon causes of stroke were at higher risk. Pneumonia was associated with a higher risk of stroke recurrence in patients with initial TIA or minor stroke but not in the overall population studied. Aphasia may bias the detection rate by concealing new neurological symptoms.

Right ventricular marantic endocarditis

A 68-year-old female presented with chest pain and breathlessness. She had breast carcinoma treated 17 years ago, with further surgical excision for recurrence 7 years ago. Computerised tomography (CT) demonstrated bi-lateral pulmonary embolism, with extensive lymphadenopathy and lung metastases. She was treated with therapeutic heparin. Echocardiography revealed a right ventricular mass attached to the tricuspid valve chordae (Fig. 1; Videos 1 and 2), which could be thrombus, marantic or infective vegetation. Blood cultures were negative. Lymph node biopsy showed malignant cells, likely of breast origin. Despite therapeutic anti-coagulation, echocardiogram 3 weeks after initial presentation demonstrated enlargement of the original mass and an additional mass (Fig. 1; Videos 3 and 4), implying that these were most probably marantic. We retrospectively reviewed the CT performed at first presentation, which also demonstrated the original right ventricular mass (Fig. 1). She died from recurrent embolic cerebrovascular events, confirmed on MRI, within a month from initial presentation. In advanced stages of malignancy, marantic endocarditis or non-bacterial thrombotic endocarditis can develop in hypercoagulable states. It has a rapidly progressive course, with embolisation of vegetations to other organs. The sterile vegetations consist of fibrin and platelets (1, 2). Patients should be anti-coagulated. In terminal cases, surgery rarely alters the final outcome (2, 3). Figure 1 (A and B) Right ventricular mass (arrowed) attached to the tricuspid valve chordae apparatus on echocardiography, in apical four-chamber view, and modified parasternal right ventricular inflow view respectively; (C and D) repeat echocardiogram demonstrating ... Video 1 The initial right ventricular mass attached to the tricuspid valve chordae apparatus on echocardiography, in modified parasternal right ventricular inflow view. Download Video 1 via http://dx.doi.org/10.1530/ERP-14-0066-v1 Download Video 1 Video 2 The initial right ventricular mass attached to the tricuspid valve chordae apparatus on echocardiography, in apical four-chamber view. Download Video 2 via http://dx.doi.org/10.1530/ERP-14-0066-v2 Download Video 2 Video 3 Repeat echocardiogram demonstrating enlargement of the original mass and an additional mass, in modified parasternal right ventricular inflow view. Download Video 3 via http://dx.doi.org/10.1530/ERP-14-0066-v3 Download Video 3 Video 4 Repeat echocardiogram demonstrating enlargement of the original mass and an additional mass, in apical four-chamber view. Download Video 4 via http://dx.doi.org/10.1530/ERP-14-0066-v4 Download Video 4

Nonbacterial Thrombotic Endocarditis in Association with Metastatic Mucin-Secreting Adenocarcinoma in Heart

Nonbacterial thrombotic endocarditis (NBTE) is characterized by the deposition of thrombi on cardiac valves in the absence of bloodstream bacterial infection. It is usually associated with advanced stage malignancy and chronic debilitating diseases. We present an autopsy case report of a 45-year-old man with NBTE in association with metastatic mucin-secreting adenocarcinoma involving the heart.

Synchronous Ovarian and Endometrial Endometrioid Adenocarcinoma Presenting with Nonbacterial Thrombotic Endocarditis and Pulmonary Thromboembolism: Adenocarcinoma with Thrombotic Events

Introduction. Nonbacterial thrombotic endocarditis (NBTE) is a rare manifestation of hypercoagulability in patients with malignant neoplasms. Case Report. A fifty-six-year-old woman presented to the emergency service; the clinical workup revealed deep vein thrombosis in right leg and bilateral massive PTE. As the abdominal sections on the spiral CT revealed a giant pelvic mass of ovarian origin, she was referred to our hospital's gynecologic oncology department. She was scheduled for surgery under enoxaparin. She described numbness on one side of her face. Cranial imaging findings revealed acute ischemic cerebral lesions and transesophageal echocardiogram showed vegetation on the aortic cusp. Under anticoagulation treatment, she underwent hysterectomy with bilateral salpingo-oophorectomy and infracolic omentectomy. After tumor resection, her neurological symptoms dissolved with aggressive anticoagulant treatment. Pathology result was synchronous endometrial and ovarian adenocarcinoma. Discussion. NBTE is a rare condition often associated with advanced malignancies. Peripheral embolism and venous thrombosis are complications that have been associated with NBTE due to hypercoagulable state. These disorders could be resistant to routine anticoagulant treatment. In case of a thrombotic complication due to ovarian malignancy, surgical resection of the primary tumor may increase the effect of anticoagulant treatment.

A Marantic Endocarditis Complicating a Metastatic Gastric Adenocarcinoma Initially Resistant to Low-molecular Weight Heparin: A Case Report

Background: Marantic endocarditis is a rare paraneoplastic syndrome which results from an hypercoagulate state. It can be associated with several tumors, particularly gastric cancer, and histology of adenocarcinoma. Mucines secreted by adenocarcinoma contribute to the activation of the coagulation pathway. Case presentation: We present the case of a patient with a marantic endocarditis complicating a metastatic gastric adenocarcinoma. He was hospitalised for a thoracic pain. At the physical examination, we found swelling, redness, and warmth of the right lower limb, suspected for a deep vein thrombosis that was confirmed at the echo doppler ultrasound. CT scan documented a severe bilateral pulmonary embolism, a splenic infarction, and multiple liver metastases. Laboratory tests were normal. Despite a Low-Molecular Weight Heparin (LMWH) treatment, the patient presented a cerebral stroke, confirmed at the MRI. Trans-thoracic echocardiography found a small vegetation of the mobile end of the mitral valve with a normal left ventricular contractile function. LMWH was switched by continuous intravenous Unfractionated Heparin (UFH). PET scan showed multiple liver metastases and a pathological gastric hypermetabolism. Liver biopsy confirmed a metastasis of a HER-2 negative gastric adenocarcinoma. Because of the stop of heparin treatment during this procedure, the patient presented a new brain stroke. A systemic palliative chemotherapy was started by FOLFOX-4 regimen and it is now ongoing. Conclusion: The particularity of this case relies on the impossibility to initially switch UFH by another anticoagulant treatment. Chemotherapy represents the only possibility to decrease mucine production and thrombi formation.

Hypercoagulability in Malignancy and a Rare Case of Embolıc Stroke as a Consequence of Nonbacterial Thrombotic Endocarditis in Ovarian Clear Cell Carcınoma

Hypercoagulability in Malignancy and a Rare Case of Embolıc Stroke as a Consequence of Nonbacterial Thrombotic Endocarditis in Ovarian Clear Cell Carcınoma

Stroke : Highlights of Selected Articles

<i>Stroke</i> : Highlights of Selected Articles

Cryptogenic subtype predicts reduced survival among cancer patients with ischemic stroke.

Cryptogenic stroke is common in patients with cancer. Autopsy studies suggest that many of these cases may be because of marantic endocarditis, which is closely linked to cancer activity. We, therefore, hypothesized that among patients with cancer and ischemic stroke, those with cryptogenic stroke would have shorter survival. We retrospectively analyzed all adult patients with active systemic cancer diagnosed with acute ischemic stroke at a tertiary care cancer center from 2005 through 2009. Two neurologists determined stroke mechanisms by consensus. Patients were diagnosed with cryptogenic stroke if no specific mechanism could be determined. The diagnosis of marantic endocarditis was restricted to patients with cardiac vegetations on echocardiography or autopsy and negative blood cultures. Patients were followed until July 31, 2012, for the primary outcome of death. Kaplan-Meier statistics and the log-rank test were used to compare survival between patients with cryptogenic stroke and patients with known stroke mechanisms. Multivariate Cox proportional hazard analysis evaluated the association between cryptogenic stroke and death after adjusting for potential confounders. Among 263 patients with cancer and ischemic stroke, 133 (51%) were cryptogenic. Median survival in patients with cryptogenic stroke was 55 days (interquartile range, 21-240) versus 147 days (interquartile range, 33-735) in patients with known stroke mechanisms (P<0.01). Cryptogenic stroke was independently associated with death (hazard ratio, 1.64; 95% confidence interval, 1.25-2.14) after adjusting for age, systemic metastases, adenocarcinoma histology, and functional status. Cryptogenic stroke is independently associated with reduced survival in patients with active cancer and ischemic stroke.

The Search for Cryptogenic Stroke, A Case of Marantic Endocarditis

Nonbacterial thrombotic endocarditis (NBTE) is rare and undoubtedly an under-recognized cause of cryptogenic stroke. Its diagnosis relies on a high index of clinical suspicion, particularly in patients with previous malignancy. We present a case of a young woman, with three neurologic events occurring in rapid succession over three weeks, ultimately resulting in her death. The echo imaging findings here appear relatively benign compared to the catastrophic consequences, and speaks of the aggressive fibrin and platelet deposition that can embolize widely in this condition, confirmed on the postmortem examination. We discuss the details of NBTE aiming to increase awareness while assessing patients with undetermined systemic embolization.

Concomitant presentation of myocarditis and non-bacterial thrombotic endocarditis in a patient with granulomatosis with polyangiitis

Granulomatosis with polyangiitis (GPA) is a necrotizing vasculitis. The etiology of the disease is not completely known. In this report, we describe a 47-year-old male who presented with ongoing dyspnea. He is a known case of GPA for 3 years based on skin biopsy and positive antineutrophil cytoplasmic antibody. The electrocardiogram showed changes suggestive for myocarditis. A transthoracic and trans esophageal echocardiogram revealed left ventricular systolic dysfunction, thickened left atrial and ventricular wall and vegetation on mitral valve. Blood cultures were negative. Myocarditis and nonbacterial thrombotic endocarditis (NBTE) were diagnosed. As far as we know, NBTE is a rare manifestation of GPA and its presentation with myocarditis is not reported to date. This case indicates the uncommon manifestations of GPA and notifies the importance of performing echocardiography in order to prevent life threatening cardiac complications of the disease.

A Case Series Of Non-Bacterial Thrombotic Endocarditis Associated With Gynecological Malignancies (P6.248)

A Case Series Of Non-Bacterial Thrombotic Endocarditis Associated With Gynecological Malignancies (P6.248)

Infective and non-infective endocarditis in critically ill patients: a clinical–pathological study

The aims of this study are to estimate the incidence, the outcome and the associated risk factors of infective and non-infective endocarditis (IE and NIE, respectively) in intensive care unit (ICU) patients. We studied the post-mortem findings and the clinical data of the patients who died in our ICU between 1996 and 2010. Of the 765 reviewed autopsies, 21 patients (2.7%) presented cardiac vegetations. These cases consisted of 12 IEs and 9 NIEs. Three patients with IE had a mechanical prosthetic valve, and in 11 cases invasive devices had been used. Multiple peripheral embolisms were discovered at autopsy. In particular, the brain appeared to be more affected in patients with IE, while pulmonary embolisms were commonly associated with NIE. Blood cultures were positive in nine patients with IE. The imaging diagnostics (transthoracic and transesophageal echocardiography) which were seldom performed in both groups, proved to be of little help. As a consequence, an IE was correctly diagnosed before death in three patients (25%) and suspected in two other cases (17%), while a NIE was diagnosed before death in one patient alone. In conclusions, critically ill patients admitted to general ICUs, multiple factors related both to the underlying conditions and to performed procedures can facilitate the occurrence of IE and NIE making, at the same time, their diagnosis challenging. Many cases, in fact, are diagnosed only at autopsy. Yet again, post-mortem examination proves to be an invaluable tool for the evaluation of diagnostic accuracy in critical care.

Middle cerebral artery infarction in a cancer patient: a fatal case of Trousseau's syndrome

Trousseau's syndrome is defined as any unexplained thrombotic event that precedes the diagnosis of an occult visceral malignancy or appears concomitantly with a tumour. This report describes a young, previously healthy man diagnosed to have an acute middle cerebral arterial ischaemic stroke and lower-limb deep vein thrombosis, who subsequently succumbed to pulmonary arterial embolism. During the course of his illness, he was diagnosed to have a malignant pleural effusion secondary to an occult adenocarcinoma. This report highlights the need for a high degree of suspicion for occult malignancy and non-bacterial thrombotic endocarditis in young (<60 years old) ischaemic stroke patients with no identifiable conventional cardiovascular risks. In selected patients, transoesophageal echocardiography is the diagnostic investigation of choice, since transthoracic imaging is not sensitive. Screening tests for serum tumour markers and prompt heparinisation of these patients are suggested whenever ischaemic stroke secondary to malignancy-induced systemic hypercoagulability is suspected.

Nonbacterial Thrombotic Endocarditis in a Patient with Bowel Infarction due to Mesenteric Vein Thrombosis.

Ante mortem cases of venous thrombosis in patients with nonbacterial thrombotic endocarditis (NBTE) have not yet been reported. We describe a rare case of NBTE in a patient with mesenteric vein thrombosis. A healthy 37-year-old man with abdominal pain and fever underwent emergency small bowel resection due to bowel ischemia resulting from mesenteric vein thrombosis. Transthoracic echocardiography revealed multiple mobile masses attached to the anterior leaflet of the mitral valves and their chordae tendineae. On suspicion of infective endocarditis, the cardiac masses were excised through open-heart surgery. However, pathologic reviews were compatible with NBTE. The patient was stable after the cardiac surgery and was treated with warfarin. Laboratory and imaging findings regarding his hypercoagulable condition were all negative.

Multiple Hypercoagulability Disorders at Presentation of Non-Small-Cell Lung Cancer

Hypercoagulability disorders are commonly encountered in clinical situations in patients with a variety of cancers. However, several hypercoagulability disorders presenting as first symptoms or signs in cancer patients have rarely been reported. We herein described a case of a woman with adenocarcinoma of the lung presenting with deep vein thrombosis, nonbacterial thrombotic endocarditis, recurrent cerebral embolic infarction, and heart failure.

Aerococcus christensenii native aortic valve subacute bacterial endocarditis (SBE) presenting as culture negative endocarditis (CNE) mimicking marantic endocarditis

This is a case report of an adult who presented with apparent culture negative endocarditis (CNE) thought to be marantic endocarditis due to a B-cell lymphoproliferative disorder. This was a most perplexing case and was eventually diagnosed as subacute bacterial endocarditis (SBE) due to a rare slow growing organism. Against the diagnosis of SBE was the lack of fever, hepatomegaly, peripheral manifestations and microscopic hematuria. Also, against a diagnosis of SBE was another explanation for the patient's abnormal findings, e.g., elevated ferritin levels, elevated α1/α2 globulins on SPEP, an elevated alkaline phosphatase, flow cytometry showing B-lymphocytes expressing CD5, and a bone lesion in the right iliac. Findings compatible with both SBE and marantic endocarditis due to a B-cell lymphoproliferative disorder included an elevated ESR, and splenomegaly. Blood cultures eventually became positive during hospitalization. We report a case of native aortic valve (AV) subacute bacterial endocarditis (SBE) due to Aerococcus christensenii mimicking marantic endocarditis due to a B-cell lymphoproliferative disorder. To the best of our knowledge, this is the first reported case of native AV SBE due to A. christensenii presenting as marantic endocarditis.

Ischemic Stroke in Patients with Solid Gynecologic Tract Tumors and Coagulopathy

Aim: Patients with gynecological neoplasms often suffer ischemic stroke. This study aimed to clarify the underlying mechanisms of ischemic stroke in patients with gynecological tract tumors. Methods: We retrospectively reviewed 6 patients with gynecologic tumors and hypercoagulability who were being treated for acute ischemic stroke between 2006 and 2012. Diffusion-weighted magnetic resonance imaging (DW-MRI), cardiovascular risk factors including plasma D-dimer levels, and histologic examination of the patients' solid tumors were performed. All 6 patients underwent transesophageal echocardiography (TEE) for nonbacterial thrombotic endocarditis (NBTE) and paradoxical embolism. Results: All 6 patients showed elevated plasma D-dimer levels. In 1 patient, paradoxical embolism was diagnosed. In the remaining 5 patients, DW-MRI scans showed numerous lesions in multiple vascular territories, and in 4 of these 5 patients, TEE demonstrated vegetations on the mitral valve, leading to the diagnosis of NBTE. Interestingly, 2 of these 4 patients had benign uterine tumors, whereas the other 2 had ovarian cancer. Conclusions: NBTE was the main etiology for ischemic stroke in patients with gynecologic tract tumors and coagulopathy. Both malignant and benign tumors of the gynecologic tract can cause NBTE.

Systemic inflammatory response and local cytokine expression in porcine models of endocarditis

The knowledge of systemic inflammation and local cytokine expression in porcine endocarditis models is limited, though it could provide valuable information about the pathogenesis and comparability to human endocarditis. Analyses of bacteriology and hematology were performed on blood samples from pigs with non-bacterial thrombotic endocarditis (NBTE, n = 11), Staphylococcus aureus infective endocarditis (IE, n = 2), animals with S. aureus sepsis without endocarditis (n = 2) and controls (n = 2). Furthermore, immunohistochemistry was used to examine the local expression of IL-1β and IL-8. Bacterial blood cultures were continuously positive in IE pigs from inoculation to euthanasia, and negative in all other pigs at all times. The total white blood cell counts and total neutrophil counts were massively elevated in pigs with IE. Local IL-1β and IL-8 expression in IE pigs were moderate to high, and high, respectively. In addition, slight local expression of IL-1β and IL-8 was present in some NBTE pigs. In the IE model, both the systemic inflammatory response and the high local expression of IL-8 were comparable to the human disease. Furthermore, the results indicate IL-1β and IL-8 as important contributors in the endocarditis pathogenesis.