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.

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.

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.

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.

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.

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.

Malignancy-Associated Non-Bacterial Thrombotic Endocarditis Causing Aortic Regurgitation and Leading to Aortic Valve Replacement.

Described herein is a 48-year-old woman with metastatic ovarian cancer who developed aortic regurgitation considered clinically to be the result of infective endocarditis but operative resection of the three aortic valve cusps disclosed the valve lesions to be typical of non-bacterial thrombotic endocarditis (NBTE). Aortic regurgitation as a consequence of NBTE is rare but at least 9 cases have been reported previously.

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

BACKGROUND: Antiphospholipid 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 PRESENTATION: We 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. CONCLUSIONS: Classically 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.

Nonbacterial thrombotic endocarditis in a patient with gastric cancer and SARS-CoV-2 infection.

Nonbacterial thrombotic endocarditis, formerly known as marantic endocarditis, is a very rare complication of advanced malignancy and other hypercoagulable states in which sterile, fibrin vegetations develop on heart valve leaflets. The most common malignancies associated with this entity are lung, pancreatic and gastric cancer. It has also been described as a presentation of COVID-19, which is known to be frequently complicated with coagulopathy and thromboembolic events. We report the case of a 62 year-old female patient newly diagnosed with stage IV gastric cancer and acute SARS-CoV-2 infection, presenting with confusion and homonymous hemianopsia in the setting of multiple acute ischemic strokes complicating a nonbacterial thrombotic mitral endocarditis. Herein, we discuss the underlying pathophysiology and make the hypothesis that SARS-CoV-2 infection could have participated in the pathogenesis of nonbacterial thrombotic endocarditis in our patient suffering from a gastric cancer.

Non-Bacterial Thrombotic Endocarditis as a Cause of Cryptogenic Stroke in Malignancy.

Non-bacterial thrombotic endocarditis (NBTE) is characterized by the deposition of fibrin and platelet thrombi on previously undamaged heart valves in the absence of bloodstream infection. It is associated with chronic disease states and can present with systemic embolic disease. Here we report a case of NBTE presenting as recurrent strokes in a patient with bladder cancer. Importantly, transthoracic echocardiography has limitations to detecting valvular lesions in NBTE, and providers should consider obtaining transesophageal echocardiography in the setting of high clinical suspicion.

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.