Cancer-associated non-bacterial thrombotic endocarditis-Clinical series from a single institution.

Premortem clinical presentation of cancer-associated non-bacterial thrombotic endocarditis (Ca-NBTE), therapy, and the clinal course is limited to case reports and small clinical series. An electronic search of Mayo Clinic records (03/31/2002-06/30/2022) with a subsequent manual review was performed to identify adult patients with echocardiographically detected NBTE and active malignancy, excluding those with infectious endocarditis or lupus anticoagulant/antiphospholipid antibodies. In this retrospective cohort study, we analyzed 115 Ca-NBTE patients (mean age 63.2 ± 9.7 years, 66.1% female) involving 71 (61.7%) mitral, 58 (50.4%) aortic, 8 (6.9%) tricuspid, and 1 (0.9%) pulmonary valve. The most common cancer was lung (n = 45 cases (39.1%), followed by pancreatic (n = 19, 16.5%), gynecological (17, 14.8%), gastrointestinal (n = 10, 8.7%), and 10 (8.7%) with hematologic malignancy; 6 patients had two active cancers. Embolic complications at presentation were frequent: 94 (81.7%) brain, 11 splenic, 10 renal, 6 coronary, and 4 to the extremities. Of 104 anticoagulated patients, 60 received low molecular weight heparin, 17 unfractionated heparin, 16 apixaban, 8 warfarin, and 3 rivaroxaban. There were 18 arterial thromboembolisms; the Kaplan-Meier estimates of the incidence at 2 years were consistent with a rate of 15.9% [95% Confidence Interval (CI) 9.9-23.3], including 14 strokes (12.4%, 95%CI, 7.1-19.2), and 8 other arterial emboli (10.5%, 95%CI, 4.7-18.9); there were 10 venous thromboembolisms (8.9%, 95%CI, 4.5-15.0). Fourteen major bleedings occurred (12.8%, 95%CI, 7.3-19.9) and 94 patients died during follow-up (77.9%, 95%CI, 71.1-85.8). Ca-NBTE predominantly affected women with lung adenocarcinoma or digestive tract cancers and manifested by stroke with high mortality and frequent embolic and bleeding complications during anticoagulation therapy.

Nonbacterial Thrombotic Endocarditis Caused by Early-stage Lung Cancer: An Autopsy Case Report.

Nonbacterial thrombotic endocarditis (NBTE) is a manifestation of prothrombotic status observed in patients with malignancy. Most cases are discovered only in the advanced stages. However, cancer in early stages may also induce NBTE development. We herein report an 87-year-old man with NBTE with multiple thromboembolization coexisting with lung cancer in early clinical stage. Autopsy findings revealed platelet- and fibrin-rich vegetations in both the tricuspid and mitral valves without evidence of bacterial infection. NBTE should be considered in cases with occult thromboembolization. Not only the presence of typical vegetation but irregular leaflet thickening should be monitored with careful echocardiographic examinations.

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

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

Non-bacterial thrombotic endocarditis in a patient with COVID.

Non-bacterial thrombotic endocarditis is mainly associated with malignancies and rheumatological diseases. We report the case of mildly symptomatic COVID-19 infection with non-bacterial aortic valve vegetation complicated by transient ischemic attack (TIA) and pulmonary embolism during his hospitalisation. This case emphasised rare life-threatening complications from a hypercoagulable state related to COVID-19 infection. To the best of our knowledge, this is the third case report of non-bacterial endocarditis in a patient with COVID-19 patients as a potential rare complication of COVID-19.

Marantic Endocarditis in Metastatic Lung Adenocarcinoma.

Marantic endocarditis is a rare condition associated with autoimmune disease, malignancy, and hypercoagulable states. It is characterized by sterile friable vegetations composed of fibrin and platelets that confer a high risk of systemic embolism. Here we showcase imaging that led to the diagnosis of an interesting case of marantic endocarditis secondary to metastatic malignancy.

Trivalvular nonbacterial thrombotic endocarditis in a patient with colon adenocarcinoma: a case report.

BACKGROUND: Nonbacterial thrombotic endocarditis is a rare complication of prothrombotic states such as neoplasms that can cause valvular dysfunction and life-threatening complications. Nonbacterial thrombotic endocarditis usually affects the left-sided valves; however, only a minority of cases involving the tricuspid valve have been reported in medical literature. CASE PRESENTATION: The current report describes trivalvular involvement by nonbacterial thrombotic endocarditis in a 54-year-old Azeri female patient with metastatic colorectal carcinoma. This case underlines the necessity of evaluating nonbacterial thrombotic endocarditis as a possible consequence in cancer patients. When thromboembolic events are found in the presence of a hypercoagulable state (such as malignancy) and no growth on blood cultures, nonbacterial thrombotic endocarditis could be suspected as the cause. CONCLUSION: It is critical to achieve early diagnosis in such a setting to initiate treatment plans and prevent further complications rapidly.

Cerebral infarction related to nonbacterial thrombotic endocarditis in a middle-aged woman with uterine adenomyosis: A case report.

RATIONALE: Few isolated case reports and case series have reported arterial and venous thromboembolism related to adenomyosis; however, the underlying mechanism remains unclear. PATIENT CONCERNS: A 47-year-old woman presented with dizziness, nausea, vomiting, and loss of consciousness after red blood cell transfusion. She was being treated for menorrhagia and severe anemia. DIAGNOSES: Magnetic resonance imaging showed multiple infarctions in right cerebellum and bilateral frontal, parietal, and occipital lobes. Echocardiography performed during the evaluation for the source of emboli revealed multiple echogenic masses on the tricuspid aortic valve. There was no evidence of infection, and the masses on the aortic valve were diagnosed as nonbacterial thrombotic endocarditis. The levels of autoimmune antibodies and tumor markers except for carbohydrate antigen 19-9 and cancer antigen 125 were within the normal range. Uterine ultrasound showed a large adenomyosis. The patient was diagnosed with multiple cerebral and cerebellar infarctions due to nonbacterial thrombotic endocarditis, and hormone therapy and anticoagulation with warfarin were initiated. INTERVENTIONS: The patient did not develop recurrent infarction during anticoagulant therapy; however, menorrhagia worsened requiring total hysterectomy. OUTCOMES: The patient did not experience recurrent infarction despite the absence of anticoagulant therapy during the 3-year follow-up period. LESSONS: The present case adds to the limited number of previously reported cases and supports that, albeit rare, adenomyosis can be associated with embolic infarction and suggests that nonbacterial thrombotic endocarditis might be the link between adenomyosis and embolic infarction.

Multimodality imaging in marantic endocarditis associated with cancer: a multicentric cohort study.

AIMS: We aimed to assess the role of multimodality imaging (MMI) in the diagnosis of marantic endocarditis (ME) associated with cancers and to describe the clinical characteristics, management, and outcome of these patients. METHODS AND RESULTS: In a retrospective multicentric study including four tertiary centres for the treatment of endocarditis in France and Belgium, patients with a diagnosis of ME were included. Demographic, MMI [echocardiography, computed tomography (CT), and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT)], and management data were collected. Long-term mortality was analysed. Between November 2011 and August 2021, 47 patients with a diagnosis of ME were included. Mean age was 65 ± 11 years. ME occurred in 43 cases (91%) on native valves. Vegetations were detected by echocardiography in all cases and in 12 cases (26%) by CT. No patient had an increased cardiac 18F-FDG valve uptake. The most common cardiac valve involved was aortic (34 cases, 73%). Twenty-two patients (46%) had a known cancer before ME, and 25 cases (54%) were diagnosed thanks to multimodality imaging. 18FDG PET/CT was performed in 30 patients (64%) and allowed a new diagnosis of cancer in 14 patients (30%). Systemic embolism was frequent (40 patients, 85% of cases). Forty-one patients (87%) were treated medically with anticoagulation therapy. One-year mortality was 55% (26 patients). CONCLUSION: ME remains associated with a high risk of complications and death.

Recurrent embolic strokes due to antiphospholipid syndrome and non-bacterial thrombotic endocarditis in a patient with basal cell carcinoma.

BACKGROUND: Non-Bacterial Thrombotic Endocarditis (NBTE) is a common form of aseptic thrombotic endocarditis that primarily affects mitral valves and less frequently aortic valves. NBTE is caused by systemic inflammatory reactions. This condition induces valve thickening or attached sterile mobile vegetation. NBTE is mostly asymptomatic; however, major clinical manifestations result from systemic emboli rather than valve dysfunction. When significant damage occurs, valvular insufficiency or stenosis can appear and promote heart failure occasionally requiring valve replacement surgery. NBTE is associated with hypercoagulable states, systemic lupus erythematous (SLE), antiphospholipid syndrome, or malignancies. CASE PRESENTATION: We report successful biological aortic valve replacement surgery including cardiopulmonary bypass for a 78-year-old man with NBTE and voluminous vegetation on the aortic valve inducing moderate aortic insufficiency and acute heart failure. The histopathological analysis of the valve sample showed myxoid degeneration, fibrous remodeling, and partial necrosis without any bacteria, thus indicating marantic endocarditis. Initially, the patient presented to the emergency department with an acute stroke. He was already using Apixaban treatment for a history of atrial fibrillation and cardioembolic stroke. Because of the recurrence of stroke and appearance of aortic vegetation, the investigations were extended. The antiphospholipid antibodies were positive without any indication of bacterial endocarditis. The malignancy screening was positive for basal cell carcinoma (BCC). The surgery and postoperative course were uneventful, and the patient was discharged with vitamin K antagonists (VKA). To our knowledge, NBTE with such a volume is rare and its apparent association with BCC has not been previously reported. CONCLUSION: Outside of SLE and antiphospholipid syndrome, NBTE is a rare and underdiagnosed disease associated with thromboembolic events. Adequate anticoagulation is a cornerstone of its treatment. Anticoagulation management during perioperative care and valve surgery deserves specific attention and helps to protect the patient from embolic complications. In the case of stroke and thromboembolic events of unclear cause or suspected NBTE, echocardiography and thrombophilia assessments including an immunological workup are recommended.

Left ventricular free-wall rupture: An unusual presentation of non-bacterial thrombotic endocarditis.

Non-bacterial thrombotic endocarditis (NBTE) is a rare, often asymptomatic, condition. A 55-year-old woman presented with hemiparesis, facial palsy and chest pain. After urgent investigation, she was referred as a case of type A aortic dissection complicated by tamponade, myocardial infarction and stroke. Review of her imaging identified haemopericardium but no dissection, and emergency surgery proceeded considering her unstable condition. She underwent an emergency repair of left-ventricular free-wall rupture and excision of an aortic valve vegetation. Postoperative investigations confirmed a diagnosis of NBTE in the setting of a plexiform neurofibroma, and she was discharged 9 weeks later with residual neurological symptoms. This case poses a previously unreported acute presentation of NBTE and highlights the complexities in its diagnosis and management.

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.

A New Insight Into Nonbacterial Thrombotic Endocarditis: A Systematic Review of Cases.

BACKGROUND: Nonbacterial thrombotic endocarditis is characterized by the presence of organized thrombi on cardiac valves, often associated with hypercoagulable states. There is a paucity of data regarding the predictors of mortality in patients with nonbacterial thrombotic endocarditis. Our primary aim was to identify predictors of in-hospital mortality in patients with nonbacterial thrombotic endocarditis. METHODS: A systematic literature review of all published cases and case series was performed until May 2018 according to Preferred Reporting Items for Systematic Review and Meta-analyses statement guidelines. We applied random forest machine learning model to identify predictors of in-patient mortality in patients with nonbacterial thrombotic endocarditis. RESULTS: Our search generated a total of 163 patients (mean age, 46 ± 17 years; women, 69%) with newly diagnosed nonbacterial thrombotic endocarditis. The in-hospital mortality rate in the study cohort was 30%. Among the patients who died in the hospital, initial presentation of pulmonary embolism (12.2 vs. 2.6%), splenic (38.7 vs. 10.5%), and renal (40.8 vs. 9.6%) infarcts were higher compared to patients alive at the time of discharge. Higher rates of malignancy (71.4 vs. 39.4%, P = .0003) and lower rates of antiphospholipid syndrome (8.1 vs. 48.2%, P = .0001) were noted in deceased patients. Random forest machine learning analysis showed that older age, presence of antiphospholipid syndrome, splenic infarct, renal infarct, peripheral thromboembolism, pulmonary embolism, myocardial infarction, and mitral valve regurgitation were significantly associated with increased risk of in-hospital mortality. CONCLUSION: Patients admitted with nonbacterial thrombotic endocarditis have a high rate of in-hospital mortality. Factors including older age, presence of antiphospholipid syndrome, splenic/renal infarct, lower limb thromboembolism, pulmonary embolism, myocardial infarction, and mitral valve regurgitation were significantly associated with increased risk of in-hospital mortality in patients with nonbacterial thrombotic endocarditis.

Reversibility of valve regurgitation due to cancer-related non-bacterial thrombotic endocarditis after switching direct oral anticoagulation for heparin.

Non-bacterial thrombotic endocarditis (NBTE) is a rare condition related to a state of hypercoagulability in advanced neoplastic disease. Most of the time, arterial thromboembolic event precedes the diagnosis of NBTE. We report here a case of NBTE responsible for multiple ischaemic strokes, which leads to the diagnosis of metastatic pancreatic adenocarcinoma. Aortic and mitral valvular regurgitations secondary to NBTE appeared within 6 weeks despite therapeutic anticoagulation with direct oral anticoagulant (DOAC) in stroke prevention of paroxysmal atrial fibrillation. Bivalvular regurgitations resolved 8 weeks after therapeutic switch to low-molecular-weight heparin (LMWH) and chemotherapy. DOACs are a possible alternative to LMWH for the prevention of venous thromboembolism in patients with active neoplasia. There is a lack of evidence for a clinical efficiency for the prevention of arterial thromboembolism in NBTE. We propose here a short review of the efficacy of anticoagulant therapy for the prevention of arterial thromboembolism in NBTE.