Navigating Complex Diagnoses in Oncology

CardioNerds (Dr. Rick Ferraro and Dr. Dan Ambinder) join Dr. Sahar Samimi and Dr. Lorraine Mascarenhas from Baylor College of Medicine, Houston, Texas, at the Houston Rodeo for some tasty Texas BBQ and a tour of the lively rodeo grounds to discuss an interesting case full of clinical pearls involving a patient with nonbacterial thrombotic endocarditis (NBTE). Expert commentary is provided by Dr. Basant Arya. Episode audio was edited by CardioNerds Intern Dr. Bhavya Shah.

We discuss a case of a 38-year-old woman with advanced endometrial cancer who presents with acute abdominal pain, found to have splenic and renal infarcts, severe aortic regurgitation, and persistently negative blood cultures, ultimately diagnosed with nonbacterial thrombotic endocarditis (NBTE). We review the definition and pathophysiology of NBTE in the context of malignancy and hypercoagulability, discuss initial evaluation and echocardiographic findings, and highlight important management considerations. Emphasis is placed on the complexities of anticoagulation choice, the role of valvular surveillance, and the need for coordinated, multidisciplinary care.  

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Pearls- Nonbacterial Thrombotic Endocarditis

1. Eliminate the Usual Suspects. NBTE is a diagnosis of exclusion! Always rule out infective endocarditis (IE) first with serial blood cultures and serologic tests. 

2. More than Meets the Echo. Distinguishing NBTE from culture-negative endocarditis can be tricky. Look beyond the echo—focus on clinical context (underlying malignancy, autoimmune issues) and lab findings to clinch the diagnosis. 

3. TEE for the Win… Mostly. While TEE is more sensitive than TTE, NBTE vegetations can be sneaky and may embolize quickly. Don’t hesitate to use advanced imaging (i.e., cardiac MRI, CTA) or repeat imaging if you still suspect NBTE. 

4. Choose your champion. In cancer-associated NBTE, guideline recommendations for anticoagulation choice are lacking. Consider DOACs and LMWH as agents of choice, but ultimately use shared decision-making to guide management. 

5. No obvious trigger? Go hunting for hidden malignancies or autoimmune disorders. A thorough workup is essential to uncover the driving force behind NBTE. 

Check out this state-of-the-art review for a comprehensive, one-stop summary of NBTE: European Heart Journal, 46(3), 236–245. Please note that the figures and tables referenced in the following notes are adapted from this review. 

notes- Nonbacterial Thrombotic Endocarditis

Notes were drafted by Dr. Sahar Samimi. 

1. What is nonbacterial thrombotic endocarditis (NBTE)?  

• NBTE, previously known as marantic endocarditis, is a rare condition in which sterile vegetations form on heart valves.¹ 

• It occurs most commonly in association with malignancies and autoimmune conditions (i.e, antiphospholipid antibody syndrome or systemic lupus erythematosus).¹ In addition, NBTE has been reported in association with COVID-19 infection, burns, sepsis, and indwelling catheters.² 

• Precise mechanisms remain unclear, but an interplay of endothelial injury, hypercoagulability, hypoxia, and immune complex deposition contributes to the formation of these sterile vegetations. ¹ 

2. How do we diagnose NBTE? 

• Physicians should have a high level of suspicion for NBTE in at-risk patients (e.g., with active malignancy) who present with recent or recurrent embolic events (i.e., stroke, splenic, renal, or mesenteric infarct, and acute coronary syndrome).¹ 

• Once vegetations are observed, the diagnosis of NBTE is focused on ruling out IE, followed by looking for the underlying etiology, if not already evident.¹ A focused clinical assessment, including a thorough history, physical exam, and relevant microbiological and serological tests, should aim to rule out IE using the modified Duke criteria.³ 

• Persistently negative blood cultures after adequate sampling increase the likelihood of NBTE but do not exclude culture-negative endocarditis. Vegetations found in patients with risk factors raise the suspicion for NBTE, whereas signs of systemic infection—such as ongoing fever, recent antibiotic exposure, or potential zoonotic sources—may point instead toward CNE.¹ 

• New diagnostic techniques, including specialized serology and metagenomic sequencing, have significantly enhanced our ability to detect elusive pathogens in CNE.¹ 

3. How should imaging be approached in suspected NBTE? 

• In cases of suspected endocarditis, guidelines from the American College of Cardiology, the American Heart Association, and the European Society of Cardiology recommend starting the assessment with a TTE to visualize potential valvular vegetations. ^4,5 

• TTE is less sensitive than TEE, particularly for detecting smaller vegetations < 5 mm that are often associated with NBTE. Therefore, a subsequent TEE is recommended due to its superior ability to detect subtle valvular abnormalities. ^4,5 

• Echocardiographic features of vegetations alone do not reliably distinguish NBTE from IE; hence, clinical context, along with laboratory and microbiological findings, is crucial for accurate diagnosis. ¹ 

• Uncertainty may remain following a TEE or in cases where TEE is not feasible. In such situations, advanced imaging techniques like cardiac MRI and CT scanning are emerging tools for more detailed cardiac tissue characterization. ¹ 

4. What are the management strategies for NBTE? 

• NBTE’s complexity necessitates a multidisciplinary treatment strategy, with each patient’s prognosis shaped by individual clinical factors. ¹ 

• Primary therapy involves anticoagulation, alongside targeted management of malignancy or autoimmune disorder driving the hypercoagulable state. ¹ 

• While the criteria for surgical intervention are similar to those used in IE, surgery generally has a more limited role in NBTE. ¹ 

5. What factors into choosing the anticoagulation agent? 

• Anticoagulation outcomes in NBTE can vary greatly: some patients have vegetations resolve, while others experience disease progression to new valves despite therapy.¹ 

• Because NBTE-specific evidence remains sparse, the underlying clinical context primarily guides the choice of anticoagulant: 

• Multiple case reports describe DOAC failure with recurrent embolization in patients with cancer and NBTE. ^6-8 

• LMWH remains a mainstay for patients with cancer or when patients experience thrombotic complications on DOACs. ¹ 

• Warfarin is the preferred anticoagulant among patients with thrombotic antiphospholipid syndrome. ⁹ 

• The duration of anticoagulation should take into consideration the status of the underlying disease, the presence of valvular lesions on follow-up imaging, and an individualized assessment of risks and benefits. ¹ 

References – Nonbacterial Thrombotic Endocarditis

1. Ahmed O, King NE, Qureshi MA, et al. Non-bacterial thrombotic endocarditis: a clinical and pathophysiological reappraisal. European Heart Journal. 2025;46(3):236-49. 

2. Balata D, Mellergård J, Ekqvist D, et al. Non-bacterial thrombotic endocarditis: a presentation of COVID-19. European journal of case reports in internal medicine. 2020;7(8).  

3. Li JS, Sexton DJ, Mick N, et al. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis 2000;30: 633–8.  

4. Otto CM, Nishimura RA, Bonow RO, et al. 2020 ACC/AHA guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol 2021;77:e25–197.  

5. Vahanian A, Beyersdorf F, Praz F, et al.; ESC/EACTS Scientific Document Group. 2021 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J. 2022 Feb 12;43(7):561-632.  

6. Mantovani F, Navazio A, Barbieri A, Boriani G. A first described case of cancer- associated non-bacterial thrombotic endocarditis in the era of direct oral anticoagulants. Thromb Res 2017;149:45–7.  

7. Panicucci E, Bruno C, Ferrari V, Suissa L. Recurrence of ischemic stroke on direct oral anticoagulant therapy in a patient with marantic endocarditis related to lung cancer. J Cardiol Cases 2021;23:242–5. 

8. Shoji MK, Kim JH, Bakshi S, et al. Nonbacterial thrombotic endocarditis due to primary gallbladder malignancy with recurrent stroke despite anticoagulation: case report and literature review. J Gen Intern Med 2019;34:1934–40.  

9. Khairani CD, Bejjani A, Piazza G, et al. Direct oral anticoagulants vs vitamin K antagonists in patients with antiphospholipid syndromes: meta-analysis of randomized trials. J Am Coll Cardiol 2023;81:16–30. 

Case Media

TTE and TEE