Nonbacterial thrombotic endocarditis NBTE masquerading as culturenegative sepsis

Non-bacterial thrombotic endocarditis (NBTE) masquerading as culture-negative sepsis Deepti Mundkur, Scott Drew, Jian Huang Introduction Non-Bacterial Thrombotic Endocarditis (NBTE) is a rare condition characterized by sterile-platelet thrombi on heart valves of patients with advanced malignancy, SLE or other hypercoagulable states. Although NBTE is often a post-mortem finding and poses a diagnostic challenge, its tendency to cause systemic embolization may provide an opportunity for early recognition and intervention. We report a case of NBTE with suspected lung cancer presenting with renal infarct. Learning objectives 1. Recognize the constellation of findings which suggest the diagnosis of NBTE. 2. Understand the implication of NBTE on overall morbidity and mortality. Case Report A 60 -year-old man presented with constant, non-radiating, right lower quadrant (RLQ) abdominal pain and constipation for 4 days. He was an active smoker with chronic cough and shortness of breath. The remainder of his review of systems was negative. Past Medical History was significant for Hepatitis C, polysubstance dependence, interstitial lung disease, seizure disorder, schizophrenia and chronic leukocytosis with a normal flow cytometry. Physical exam demonstrated that patient was alert, oriented, and normotensive, with tachypnea (25), tachycardia (133), and diffuse lung crackles. Cardiovascular examination was negative for heart murmurs or jugular venous distension. Abdomen was soft, but tender to palpation in the RLQ. Hyperactive bowel sounds were appreciated. On laboratory examination his WBC count was 31, 500. Urinalysis was normal with a negative urine drug screen. CXR showed chronic interstitial markings and mild linear right basilar opacities. Serum lactate concentration was normal. The patient was admitted for sepsis and empirically started on piperacillintazobactam after collecting blood for cultures. Initial Imaging CT abdomen showed bilateral perinephric stranding and wedge shaped right renal infarct. Hospital Course As the sepsis worsened despite negative serial cultures, and absent abdominal/pulmonary source of infection, we then performed TTE on day 4. The sensitivity of TTE is modest (75%); the specificity approaches 100%. (4). TTE was negative but TEE (sensitivity >90%) was warranted in the circumstance of a negative TTE with high clinical suspicion of Infective Endocarditis (IE) due to multiple minor criteria (fever and major arterial emboli) positive for IE. (5) Early TEE examination has been found to improve the prognosis of NTBE. (6) Late TEE (day 8) delayed our diagnosis of valvular vegetations while our patient developed extensive cerebral embolization and DIC, limiting his treatment options and worsening his prognosis. Lesson learned from this case is that, in the presence of early renal infarct, ruling out IE should be a priority despite absence of cardiac murmur/modified Duke’s criteria for diagnosis of IE. Definitive diagnosis of NBTE is by autopsy/surgery. The clinical diagnosis of NBTE relies on strong clinical suspicion in the context of a disease process known to be associated with NBTE (our patient had strongly suspected lung malignancy), the presence of a heart murmur (absent in our patient), the presence of vegetations not responding to antibiotic treatment (present in our patient) and evidence of multiple systemic emboli (renal infarct, cerebral infarction noted in our patient). (7) According to the European Society of Cardiology guidelines: “NTBE is first managed by treating the underlying pathology. If there is no contraindication, these patients should be anticoagulated with unfractionated or LMW heparin or warfarin, although there is little evidence to support this strategy. ” (8) Early TEE could have allowed for initiation of early anticoagulation before patient developed contraindications to anticoagulation. On day 2, the patient developed fever and rising WBC count to 44, 000 with 3 bands. Preliminary blood cultures were negative. He developed hypoxic respiratory failure, was intubated and mechanically ventilated. Bronchoscopy with bronchoalveolar lavage was performed. APLA, ANA, HIV, and Coccidioidomycosis PCR were negative. On day 4, Transthoracic Echocardiography (TTE) was unremarkable. On day 5, Vancomycin was added. BAL did not reveal pulmonary source of infection. Serial blood cultures (X 2) were negative. Serial UA (X 2) and urine culture were negative. On day 6, the patient developed right lower extremity weakness and sustained clonus. Stat CT head demonstrated multiple infarcts in both anterior and posterior circulation. Take-away points • DIC panel was positive with thrombocytopenia of 30, 000. Anticoagulation was not initiated due to significant thrombocytopenia and due to presumed septic embolization. • • On day 7 Metronidazole and Ceftriaxone were started while stopping Zosyn. Transesophageal Echocardiography (TEE) performed on day 8 demonstrated vegetations on the anterior leaflet of the mitral valve concerning for culturenegative endocarditis or NBTE. Antibiotic regimen was changed from Vancomycin, Metronidazole and Ceftriaxone to Ampicillin-Sulbactam, gentamicin and ciprofloxacin to cover culture-negative endocarditis. He rapidly deteriorated clinically with generalized tonic-clonic seizure, and family decided on comfort care. He died on the 15 th day. Autopsy revealed poorly differentiated lung carcinoma, NBTE with multiple brain infarcts, and renovascular fibrin thrombus as the cause of renal infarction. CTPA ruled out pulmonary embolus but showed multiple lung nodules, hilar/mediastinal lymphadenopathy, interstitial lung changes and superimposed emphysema. Discussion This case report highlights the importance of early diagnostic workup to explore potential embolic sources in this patient with a renal infarct found on imaging. Acute pyelonephritis and nephrolithiasis, both closely mimic the clinical presentation of renal infarction. Clinical presentation of our case was not consistent with acute pyelonephritis, although significant leukocytosis warranted empiric antibiotics. Contrast enhanced CT which has 80% sensitivity in diagnosis of embolic renal infarction, demonstrated renal infarct in our patient. (1) It is important to note that patients with renal emboli may have embolization to other organs (1, 2, 3), thus warranting a thorough search for cardioembolic source. Potential for early diagnosis of NBTE in a patient with suspected underlying lung malignancy and renal infarct. 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