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.

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.

Non-infectious thrombotic endocarditis associated with chronic rheumatic heart disease and disseminated tuberculosis

Rheumatic heart disease is still common in developing countries and requires prompt intervention to prevent chronic complications. Vegetations in rheumatic heart disease might be due to acute episodes of rheumatic fever itself or due to either infective endocarditis (IE) or Non-infectious thrombotic endocarditis (NITE). Each form of vegetations has specific pathological characteristics on gross and microscopic examination. However, clinically IE and NITE may have overlapping signs and symptoms. A chance of misdiagnosis of NITE as culture-negative infective endocarditis is higher if the former present with infective symptoms like fever. NITE of valves can be due to underlying associated malignant neoplasm, particularly mucinous adenocarcinoma, pneumonia, cirrhosis, autoimmune disorders, and hypercoagulable state. The coexistence of tuberculosis, non-infectious thrombotic endocarditis and rheumatic valvular heart disease was rarely documented in medical literature. We describe a case of chronic rheumatic heart disease with vegetations in the posterior mitral valve leaflet, treated as culture-negative infective endocarditis, which, at autopsy, reveals the presence of Nonbacterial thrombotic endocarditis vegetation over calcified, fibrosed mitral valve leaflets and associated disseminated tuberculosis along with classic pathological sequela findings of chronic rheumatic mitral valvular heart disease in lungs and liver.

Nonbacterial thrombotic endocarditis of a bioprosthetic valve: Questions to ponder before replacement of the valve.

Nonbacterial thrombotic endocarditis (NBTE) of bioprosthetic valves is extremely rare. We report a 67-year-old lady with early bioprosthetic "failure" that at reoperation was proven to be NBTE. The choice of a prosthesis in this condition may have implications for patients' late clinical course.

Chemotherapy-associated nonbacterial thrombotic endocarditis: A radiological mimicker of cardiac amyloidosis requiring histopathologic examination for definitive diagnosis.

Nonbacterial thrombotic endocarditis is a form of a thrombotic angiopathy involving the endothelial lined endocardial surfaces of the heart which includes valves and the chamber walls. Underlying etiologies for nonbacterial thrombotic endocarditis include autoimmune diseases, hypercoagulable states, in the setting of certain malignant neoplasms, and physical injury. The pathogenesis for these processes is that of primary endothelial injury resulting in a thrombotic angiopathy. We present a patient with heart failure being evaluated before hematopoietic stem cell transplantation who had previously been provided with chemotherapy and whose cardiac magnetic resonance imaging reveals findings suggestive of amyloidosis. A subsequent endomyocardial biopsy instead showed nonbacterial thrombotic endocarditis characterized by the endocardium with fibromyxoid thickening and overlying fresh fibrin. This case highlights histopathologic findings of chemotherapy-associated nonbacterial thrombotic endocarditis involving the right ventricle wall of the endocardium, therefore expanding the radiological differential in patients with cardiac magnetic resonance imaging findings suggestive of amyloidosis.

Nonbacterial thrombotic endocarditis as the initial presentation of prostate cancer- a case report.

Nonbacterial thrombotic endocarditis (NBTE) refers to noninfectious vegetations of the heart valves. It is commonly associated with malignancy and autoimmune diseases like systemic lupus erythematosus, Rheumatoid arthritis. Herein, we present Non-bacterial thrombotic endocarditis and Disseminated intravascular coagulation as the initial manifestations of prostate cancer. A 50-yearold gentleman, known case of hypertension and diabetes, presented with a history of recurrent ischaemic strokes, STEMI and a recent diagnosis of infective endocarditis. He had been taking antibiotics for the past 20 days without any improvement. Negative blood cultures in the presence of vegetations on repeat echocardiography led to a suspicion of NBTE. Laboratory investigations were suggestive of Disseminated intravascular coagulation. CT abdomen and pelvis demonstrated enlarged prostate with enlarged pelvic lymph nodes. Prostate specific antigen was raised at more than 100ng/ml. A bone scan showed extensive metastasis. The patient was started on GnRH analogue and bicalutamide. His Disseminated intravascular coagulation resolved and he was subsequently started on anticoagulants. The valvular lesions diminished without any residual dysfunction.

[An autopsy case after endovascular thrombectomy for cardioembolic stroke due to nonbacterial thrombotic endocarditis].

A 73-year-old women visited emergency department because of sudden right hemiplegia. She had a history of duodenum papilla cancer terminal stage and multiple liver metastasis. On admission, diffusion weighted images revealed high intensity area at left middle cerebral artery territory. In addition, 3D-TOF MRA depicted proximal part of the left internal carotid artery. We performed endovascular thrombectomy because low platelet count met contraindication of intravenous recombinant tissue plasminogen activator therapy. Although we could get partial recanalization of middle cerebral artery occlusion after thrombectomy, the patient eventually died due to multiple organ failure. Autopsy findings showed white thrombus on mitral valve and also left middle cerebral artery occluded by similar white thrombus without infective findings. The patient was finally diagnosed with nonbacterial thrombotic endocarditis due to white thrombus on the mitral valve. We should select appropriate mechanical thrombectomy devices with a case of cerebral infarction due to nonbacterial thrombotic endocarditis because its thrombus is often white thrombus and would be hard.

Ceguera cortical como manifestación inicial de endocarditis trombótica no bacteriana / Cortical blindness as initial manifestation of nonbacterial thrombotic endocarditis

La endocarditis trombótica no bacteriana, antiguamente conocida como endocarditis marántica, es una entidad infrecuente en la que se desarrollan vegetaciones estériles, compuestas por fibrina en las válvulas del corazón. Suele diagnosticarse en el momento de la autopsia o en enfermedades oncológicas avanzadas. Las neoplasias malignas más frecuentemente asociadas con esta entidad son las de pulmón, páncreas, estómago y adenocarcinomas de origen primario desconocido. Es necesario descartar la endocarditis infecciosa y establecer la presencia de vegetaciones valvulares mediante ecocardiografía. Presentamos el caso de una paciente con diagnóstico reciente de adenocarcinoma de estómago en estadio avanzado que presentó ceguera cortical e imágenes compatibles con isquemia cerebral. El ecocardiograma transesofágico mostró dos vegetaciones en válvula mitral. Los hemocultivos fueron negativos. Se enfatiza la importancia de sospechar endocarditis trombótica no bacteriana en enfermos con cáncer y embolismo sistémico.

Nonbacterial thrombotic endocarditis, formerly known as marantic endocarditis, it is an infrequent entity in which sterile, fibrin vegetations develop on heart valve leaflets. It is often diagnosed at the time of autopsy or in late-stage malignancies. The most common malignancies associated with nonbacterial thrombotic endocarditis are lung, pancreatic, gastric cancer and adenocarcinomas of an unknown primary site. Diagnosis requires ruling out infective endocarditis and establishing the presence of valvular vegetations using echocardiography. We report the case of a patient with a recent diagnosis of advanced gastric adenocarcinoma who presented with cortical blindness. The computed tomography was compatible with cerebral ischemia. The transoesophageal echocardiogram showed two vegetations in mitral valve. Blood cultures were negative. We emphasize the importance of suspecting nonbacterial thrombotic endocarditis in patients with cancer and systemic embolism.

[Cortical blindness as initial manifestation of nonbacterial thrombotic endocarditis]. / Ceguera cortical como manifestación inicial de endocarditis trombótica no bacteriana.

Nonbacterial thrombotic endocarditis, formerly known as marantic endocarditis, it is an infrequent entity in which sterile, fibrin vegetations develop on heart valve leaflets. It is often diagnosed at the time of autopsy or in latestage malignancies. The most common malignancies associated with nonbacterial thrombotic endocarditis are lung, pancreatic, gastric cancer and adenocarcinomas of an unknown primary site. Diagnosis requires ruling out infective endocarditis and establishing the presence of valvular vegetations using echocardiography. We report the case of a patient with a recent diagnosis of advanced gastric adenocarcinoma who presented with cortical blindness. The computed tomography was compatible with cerebral ischemia. The transoesophageal echocardiogram showed two vegetations in mitral valve. Blood cultures were negative. We emphasize the importance of suspecting nonbacterial thrombotic endocarditis in patients with cancer and systemic embolism.

Marantic endocarditis: incidental infarcts leading to diagnosis of pancreatic cancer.

Non-bacterial thrombotic endocarditis (NBTE) is a well-described phenomenon associated with malignancies due to hypercoaguable state. In the setting of pancreatic cancer, NBTE is more commonly diagnosed postmortem. We describe a case of a man who was diagnosed with pancreatic carcinoma after incidental finding of NBTE. Imaging incidentally revealed multiple strokes, bilateral renal and splenic infarcts, while subsequent workup for cardioembolic source demonstrated a 1.1×0.7 cm mitral valve vegetation. As multiple blood cultures were sterile and patient lacked clinical signs of infection, an underlying malignancy was suspected. CT abdomen demonstrated a dilated pancreatic duct, MRI showed a 2.8×2.2 cm pancreatic head mass. Endoscopic biopsy of the mass revealed pancreatic adenocarcinoma. Other than NBTE, there were no other clinical or laboratory findings to clearly suggest pancreatic cancer. Thus, incidental discovery of this mitral valve vegetation led to the diagnosis of pancreatic malignancy.

Nonbacterial Thrombotic Endocarditis Presenting with Leg Pain and a Left Atrial Mass Lesion.

Systemic lupus erythematosus (SLE) is a major cause of nonbacterial thrombotic endocarditis (NBTE) associated with intracardiac sterile vegetations. It is rare for vegetations to present as an atrial tumor. This report describes a 48-year-old female with SLE and antiphospholipid syndrome complicated by recurrent thrombosis on anticoagulation. A large left atrial mass lesion was detected on echocardiography during a work-up for leg burning. Infective endocarditis could not be confirmed, and hence left atrial mass lesion was the most likely diagnosis. The patient was managed surgically and the pathology report revealed fibrin networks in a pattern similar to that of thrombosis, characteristic of NBTE.

Endocarditis marántica como presentación de cáncer de páncreas: caso clínico / Non-bacterial thrombotic endocarditis: report of one case

Marantic or nonbacterial thrombotic endocarditis is characterized for the presence of vegetations formed by a meshwork of fibrin and other cellular material similar a blood clot, without the presence of microorganisms. It is often related with tumors and chronic inflammatory states. We report a 49 years old female with a history of weight loss and asthenia, presenting with multiple cerebrovascular attacks and fever. Blood cultures were negative and the fever did not subside with antibiotic treatment. Trans esophageal echocardiogram showed a mitral valve vegetation and thickening of the free edge of both leaflets. In search of the etiology of such a case, a primary pancreatic cancer with distant metastases was found. We cannot rule out the differential diagnosis with bacterial endocarditis with negative blood cultures, although the clinical context supports a non-infectious etiology.

[Non-bacterial thrombotic endocarditis. Report of one case]. / Endocarditis marántica como presentación de cáncer de páncreas. Caso clínico.

Marantic or nonbacterial thrombotic endocarditis is characterized for the presence of vegetations formed by a meshwork of fibrin and other cellular material similar a blood clot, without the presence of microorganisms. It is often related with tumors and chronic inflammatory states. We report a 49 years old female with a history of weight loss and asthenia, presenting with multiple cerebrovascular attacks and fever. Blood cultures were negative and the fever did not subside with antibiotic treatment. Trans esophageal echocardiogram showed a mitral valve vegetation and thickening of the free edge of both leaflets. In search of the etiology of such a case, a primary pancreatic cancer with distant metastases was found. We cannot rule out the differential diagnosis with bacterial endocarditis with negative blood cultures, although the clinical context supports a non-infectious etiology.

Porcine models of non-bacterial thrombotic endocarditis (NBTE) and infective endocarditis (IE) caused by Staphylococcus aureus: a preliminary study.

BACKGROUND AND AIM OF THE STUDY: Non-bacterial thrombotic endocarditis (NBTE) and, in particular, infective endocarditis (IE), are serious and potentially life-threatening diseases. An increasingly important agent of human IE is Staphylococcus aureus, which typically causes an acute endocarditis with high mortality. The study aim was to evaluate the pig as a model for non-bacterial as well as S. aureus-associated endocarditis, as these models would have several advantages compared to other laboratory animal models. METHODS: Fourteen animals underwent surgery with placement of a plastic catheter in the left side of the heart. Six of the pigs did not receive a bacterial inoculation and were used to study the development of NBTE. The remaining eight pigs were inoculated intravenously once or twice with S. aureus, 10(5)-10(7) cfu/kg body weight. Two bacterial strains were used: S54F9 (porcine) and NCTC8325-4 (human). Clinical examination, echocardiography and bacterial blood cultures were used to diagnose and monitor the development of endocarditis. Animals were euthanized at between two and 15 days after catheter placement, and tissue samples were collected for bacteriology and histopathology. RESULTS: Pigs inoculated with 10(7) cfu/kg of S. aureus strain S54F9 developed clinical, echocardiographic and pathologic signs of IE. All other pigs, except one, developed NBTE. Serial blood cultures withdrawn after inoculation were positive in animals with IE, and negative in all other animals. CONCLUSION: S. aureus endocarditis was successfully induced in pigs with an indwelling cardiac catheter after intravenous inoculation of 10(7) cfu/kg of S. aureus strain S54F9. The model simulates typical pathological, clinical and diagnostic features seen in the human disease. Furthermore, NBTE was induced in all but one of the pigs without IE. Thus, the pig model can be used in future studies of the pathogenesis, diagnosis and therapy of NBTE and S. aureus endocarditis.

Marantic endocarditis - A not so benign entity.

Marantic, verrucous or nonbacterial thrombotic endocarditis, is characterised by the deposition of an amorphous mixture of fibrin and platelets onto heart valves. Although not commonly a cause of death in forensic practice, it may be associated with systemic embolisation. This was observed in a 60-year-old woman who suddenly collapsed and was found at autopsy to have a poorly differentiated adenocarcinoma of the lung with vegetations from marantic endocarditis on the mitral valve and embolisation with infarcts in the left kidney, the spleen, the right occipital cortex of the brain and the left ventricle of the heart. Death was due to coronary artery embolism from marantic endocarditis associated with an undiagnosed adenocarcinoma of the lung. Although marantic endocarditis is more common in hospital autopsies than in forensic cases, it can have lethal complications that result in sudden and unexpected death. Histories of debilitating disease and/or arterial thromboembolic episodes necessitate meticulous examination of the cardiac valves with careful serial sectioning of the major epicardial coronary arteries and histologic sampling of both ventricles.