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.

Treatment with a Direct Oral Anticoagulant for Nonbacterial Thrombotic Endocarditis.

We herein report a case of nonbacterial thrombotic endocarditis (NBTE) in a patient with previously undiagnosed lung cancer. A 62-year-old woman presented to our hospital with multiple cerebral infarctions. There was no evidence of valvular heart disease or vegetations. Whole-leg ultrasonography revealed deep vein thrombosis of the left peroneal vein. We administered direct oral anticoagulants (DOACs) for a presumed diagnosis of paradoxical embolisms caused by patent foramen ovale. Unfortunately, she experienced further embolization and died. At a postmortem examination, she was diagnosed with NBTE and metastatic adenocarcinoma of the lung. Our experience with this patient suggests that DOACs may be an insufficient treatment for NBTE.

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

BACKGROUND: Nonbacterial thrombotic endocarditis, or marantic endocarditis, is rare. Contemporary data on the etiology, echocardiographic evaluation, and management of nonbacterial thrombotic endocarditis are limited. METHODS: A 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. RESULTS: Of 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. CONCLUSION: In 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.

Fungal endocarditis with heart valve replacement and atrial fibrillation posing a treatment challenge: A case report.

RATIONALE: Fungal endocarditis (FE) is a rare disease, in which antifungal treatment is necessary. When FE is complicated with prosthetic heart valve and/or atrial fibrillation, the coadministration of antifungal agents and warfarin is inevitable. We report a case of rheumatic heart disease with atrial fibrillation who developed FE following prosthetic heart valve replacement. The international normalized ratio (INR) increased significantly during the antifungal treatment with fluconazole. A discussion of the antifungal strategy in FE patients with prosthetic heart valves and/or atrial fibrillation and the interaction between antifungal agents and warfarin was performed. PATIENT CONCERNS: A 54-year-old Chinese woman experienced intermittent fevers, aphemia, and weakness in her right extremities. Her temperature was 38.7°C, and there was atrial fibrillation with heart rate 110 times/min. Neurological examination revealed that she had drowsiness, Broca aphasia, right central facial paralysis, and hemiplegia (Medical Research Council scale, upper limb grade 0, lower limb grade II). DIAGNOSES: Multiple infarction on magnetic resonance imaging and the occlusion of left middle cerebral artery suggested the occurrence of cerebral embolism. The presence of Candida parapsilosis in the results of 4 blood cultures and the existence of valve vegetation in the reexamination of echocardiogram supported the diagnosis of FE. INTERVENTIONS: The patient was given antifungal therapy with fluconazol. The INR increased dramatically on the 9th day of antifungal treatment, and subcutaneous bruising occurred at the intravenous infusion site. The antagonist of vitamin K1 was used and warfarin was reduced to a smaller dosage. The antifungal agent was replaced with caspofungin. OUTCOMES: Her speech improved significantly, and the muscle strength of her paralyzed side reached the Medical Research Council scale of grade IV. She continued to receive caspofungin for antifungal treatment with relatively stable INR and waited for heart valve surgery. LESSONS: The choice of antifungal agents is often a big challenge for FE patients, especially when they need warfarin for anticoagulation. It is better to administer a low dose of warfarin while carefully monitoring the INR or choose the antifungal drugs with little or no effect on warfarin.

Nonbacterial Thrombotic Endocarditis Due to Primary Gallbladder Malignancy with Recurrent Stroke Despite Anticoagulation: Case Report and Literature Review.

Nonbacterial thrombotic endocarditis (NBTE) associated with malignancy is rare; its infrequency and similarity to other diagnoses make it a significant diagnostic challenge. A 63-year-old woman on rivaroxaban for prior deep vein thrombosis presented with left upper extremity weakness and left facial droop with imaging demonstrating multiple strokes. Echocardiograms revealed mitral and aortic valve vegetations. The patient was switched to apixaban and started on vancomycin and ceftriaxone for presumed culture-negative endocarditis. Despite continuing apixaban, her hospital course was complicated by new acute embolic infarcts. Workup confirmed non-mucinous metastatic biliary adenocarcinoma. The patient was placed on a heparin drip then switched to low molecular weight heparin without further embolic events and was discharged to a rehabilitation facility in stable condition with plans for chemotherapy as an outpatient. These clinical, imaging, and histologic findings were consistent with a rare case of NBTE associated with primary non-mucinous gallbladder malignancy complicated by recurrent strokes in which direct oral anticoagulants did not provide adequate anticoagulation.

A case of tricuspid valve non-bacterial thrombotic endocarditis presenting as pulmonary embolism in a patient with antiphospholipid antibody syndrome.

A 47-year-old woman with a medical history of Raynaud's phenomenon presented with fever, cough and shortness of breath. She was found to have left lower lobe consolidation and pleural effusion and was treated as a case of pneumonia. During the hospital course, her respiratory status worsened, and she was intubated on the third hospital day. To investigate the high A-a gradient, a Computerized Tomographic Pulmonary Embolism (CTPE) study was done which identified a large left lower pulmonary artery embolism. She was also found to have a new murmur, and an echocardiogram demonstrated a large lesion on tricuspid valve. However, multiple sets of her blood cultures came back consistently negative. Alternative diagnoses for culture-negative endocarditis were considered, and a full set of rheumatological workup was done. Laboratory tests were suggestive of antiphospholipid syndrome, hence the diagnosis of tricuspid valve Libman-Sacks endocarditis was made.

Cerebral Infarcts by Nonbacterial Thrombotic Endocarditis Associated with Adenomyosis: A Case Report.

We report a case of multiple embolic cerebral infarcts associated with nonbacterial thrombotic endocarditis (NBTE) in a patient with adenomyosis. The patient presented with dysarthria, left perioral sensory change, and left-hand weakness. Magnetic resonance imaging revealed multiple vascular territory infarctions involving the bilateral cerebellum and the right precentral gyrus. Magnetic resonance angiography was normal. d-Dimer, carbohydrate antigen (CA) 19-9, and CA125 levels were elevated. Abdominal and pelvic computed tomography with iodine contrast enhancement revealed a huge adenomyosis with left ovarian cyst. Transesophageal echocardiography (TEE) with agitated saline injection test demonstrated shaggy vegetation at the coapting edge of both mitral leaflets and mitral regurgitation. A diagnosis of NBTE was established and treatment with anticoagulation was initiated. Two weeks later, the thrombi reduced significantly on follow-up TEE and transthoracic echocardiography. The patient underwent an abdominal hysterectomy with bilateral salpingo-oophorectomy, and pathological specimens confirmed adenomyosis. The possibility that adenomyosis can be associated with NBTE suggests one of the underlying thromboembolic mechanisms in adenomyosis. Clinicians should be aware of the potential thromboembolic risk of adenomyosis. Further reporting of similar cases is needed to confirm the thromboembolic mechanism.

Nonbacterial Thrombotic Endocarditis Complicated by Cerebral Infarction in a Patient with Adenomyosis with High Serum CA125 Level; A Case Report.

We report a case of a 48-year-old woman with multiple cerebral infarctions caused by nonbacterial thrombotic endocarditis (NBTE) because of adenomyosis with high serum carbohydrate antigen (CA)125 level. Transesophageal echocardiography (TEE) showed a vegetation, 4 mm in diameter, adjacent to the anterior leaflet of the mitral valve on day 2. Soluble CA125 level was elevated to 901 U/mL. Intravenous infusion of unfractionated heparin sodium was started. On day 35, TEE revealed reduction of the vegetation in size, 2 mm in diameter. On day 38, she was transferred to the hospital for further rehabilitation. CA125 is a transmembrane mucin that contributes to the progression of epithelial ovarian cancer. It is important to keep in mind that adenomyosis with abnormally high serum CA125 level may be at high risk of NBTE.

Thrombocytopaenia and neutropaenia associated with daptomycin USE.

Daptomycin is a lipopeptide antibiotic active against gram-positive bacteria indicated for the treatment of complicated skin and skin structure infections and Staphylococcus aureus bloodstream infections, including endocarditis. Thrombocytopaenia, but not neutropaenia, is described as a possible or probable adverse effect in the product information. Up to now, two case reports of daptomycin-induced thrombocytopaenia have been published and a single case of neutropaenia associated with prolonged daptomycin use. We report a case of simultaneous thrombocytopaenia and neutropaenia associated with prolonged daptomycin use for a culture-negative endocarditis.

Antiphospholipid antibody-associated non-infective mitral valve endocarditis successfully treated with medical therapy.

Non-bacterial endocarditis lesions associated with antiphospholipid antibodies (aPLs) in the absence of other criteria for antiphospholipid syndrome or systemic lupus erythematosus is termed an aPL-associated cardiac valve disease. Evidence regarding the management of this condition is sparse. A rare case is described of a 20-year-old female who presented with an incidental finding of 'vegetations on a heart valve'. Echocardiography revealed mitral valve leaflet thickening and echodensities with moderate mitral regurgitation. She had an elevated partial thromboplastin time that did not correct with a mixing study, and elevated levels of antiocardiolipin antibodies. Hence, a diagnosis of aPL-associated cardiac valve disease was made, and the patient commenced on warfarin, hydroxychloroquine, and a short course of oral prednisone. At one year after diagnosis the patient remained symptom-free, and follow up echocardiography revealed resolution of the vegetations with minimal mitral regurgitation. Further evidence is needed to guide the therapy of this rare condition.

Current issues in the diagnosis and management of blood culture-negative infective and non-infective endocarditis.

Diagnosis and management of blood culture-negative endocarditis constitute a formidable clinical challenge and a systemic approach is necessary for a successful outcome. Blood cultures are negative in endocarditis due mainly to preceding antibiotic administration or to fastidious slow-growing organisms. Less so, non-infective endocarditis is a paraneoplastic manifestation or may occur in association with autoimmune diseases. When the clinical diagnosis is contemplated and cultures and serologies are negative, histologic and molecular examination of the removed valve tissue may confirm the diagnosis. Treatment with antibiotics is often warranted and valve replacement remains appropriate for patients with heart failure or irreversible structural damage.