Nonbacterial thrombotic endocarditis of the tricuspid valve with recurrent pulmonary embolism in a patient with pancreatic adenocarcinoma: a case report

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BACKGROUND

Nonbacterial thrombotic endocarditis (NBTE) is a rare disease, diagnosed predominantly post-mortem, the detection rate of which at autopsy varies from 0.9% to 1.6% [1, 2].

In most cases, NBTE is detected in patients with malignant neoplasms and systemic lupus erythematosus, as well as with antiphospholipid syndrome, both primary and in the case of its occurrence in patients with systemic lupus erythematosus. In turn, in malignant tumors, NBTE is predominantly associated with adenocarcinomas (lung, colon, ovary, biliary tract), with the highest frequency noted in patients with mucinous cancer and pancreatic adenocarcinoma [3, 4].

Vegetations in NBTE consist of platelets located between fibrin strands, immune complexes, and mononuclear cells. According to their morphological structure, they correspond to the so-called white thrombus [5]. For large vegetations, the term verrucous endocarditis, or Libman–Sacks endocarditis, is used. In NBTE, vegetations are predominantly localized in the left chambers of the heart: about 2/3 are lesions of the mitral valve and 1/4 are aortic valve lesions, with concurrent involvement of both valves being even rarer [4, 6]. In turn, isolated tricuspid valve involvement in NBTE is rare, and its exact frequency is unknown, as information about it is limited to descriptions of individual clinical cases [7–10].

NBTE is usually asymptomatic. The clinical picture is primarily determined by embolic events, while signs of valvular dysfunction, including manifestations of heart failure, are encountered less frequently. Embolic complications are observed in approximately 50% of patients with NBTE [4].

Since the most frequent localization of sterile vegetations is the valves of the left heart chambers, the most common areas of embolism are the spleen, kidneys, skin, and extremities. They may manifest as pain, hematuria, and digital ischemia. The diagnosis of NBTE is most often preceded by episodes of embolism to the vessels of the central nervous system and coronary arteries [11, 12].

Treatment of NBTE includes the use of low-molecular-weight heparins, intravenous administration of unfractionated heparin, and oral anticoagulants (e.g., dabigatran, apixaban, rivaroxaban, edoxaban). Surgical intervention, that is, removal of vegetations with or without replacement of the affected valve is indicated in cases of recurrent embolism that develops despite ongoing anticoagulant therapy [13, 14].

To date, it is unknown whether therapy aimed at treating malignant neoplasms affects the course of NBTE in cases where oncology is its cause. Nevertheless, it has been established that cancer treatment in such patients must be started as early as possible [15].

In this work, we present a rare case of NBTE with isolated tricuspid valve involvement in a patient with pancreatic adenocarcinoma and recurrent episodes of pulmonary embolism (PE).

CASE DESCRIPTION

Patient Information

A 70-year-old female patient was admitted to the hospital with complaints of general weakness, dyspnea, and palpitations during physical activity over the last month and a half.

At the time of hospitalization, she had persistent signs of respiratory failure in the form of an increased respiratory rate at rest up to 24 breaths per minute and a heart rate of up to 115 bpm; additionally, a decrease in blood saturation to 91% while breathing room air was noted.

Medical History

One month prior to hospitalization, because of these symptoms, the patient sought medical attention at another healthcare facility, where computed tomography pulmonary angiography was performed. The results demonstrated bilateral PE, signs of infarction pneumonia in the lateral and posterior basal segments (R₉ and R₁₀) of the right lung and in the anterior basal segment S₈) of the left lung, as well as a mass in the pancreas and presumably metastatic foci in the liver [during the first computed tomography (CT) scan, the entire peritoneal cavity was not examined]. Additionally, deep vein thrombosis was identified in the patient using sonography and CT, and anticoagulant therapy with apixaban at a dose of 5 mg twice daily was prescribed.

The patient had undergone nephrectomy for right-sided renal cancer 14 years earlier. Subsequently, she felt well. During regular follow-up examinations, there was no evidence of disease progression.

Diagnostic Assessment

According to the repeat CT scan of the chest, and the peritoneal cavity and retroperitoneal space with intravenous contrast enhancement performed in the hospital, the presence of a large tumor of the pancreas body with atrophy of its tail was confirmed, and para-aortic lymphadenopathy and multiple (more than 20) metastases in all segments of the liver were detected (Fig. 1).

 

Fig. 1. Computed tomography results, venous phase: a, axial section, large tumor of the pancreatic body (arrow), multiple liver metastases; b, coronal reformation, solitary right kidney with a small cyst in the lower pole.

 

In addition, the CT results showed multiple thromboemboli in the branches of the pulmonary artery on both sides and foci of infarction pneumonia. When comparing the data from the initial CT and those obtained during hospitalization, a partial regression of thrombotic masses in the segmental branches of the pulmonary arteries was noted, while the dilation of the right heart chambers persisted (Fig. 2).

 

Fig. 2. Computed tomography pulmonary angiography results: a, obtained a week earlier, the arrow indicates complete occlusion of the lower lobe branch of the pulmonary artery; b, obtained during hospitalization, partial restoration of blood flow, enlargement of the right heart chambers.

 

According to echocardiography (TTE), dilation of the right heart chambers with signs of systolic overload, moderate tricuspid regurgitation, and an increase in systolic pulmonary artery pressure to 90 mmHg were revealed.

In the hospital, the patient was prescribed low-molecular-weight heparin therapy in therapeutic doses.

A few days later, due to the need to verify the diagnosis, a biopsy of one of the liver lesions was planned; therefore, anticoagulant therapy was temporarily suspended. However, 16 hours after the last administration of low-molecular-weight heparin, the patient experienced a sharp increase in dyspnea and a drop in saturation to 89% during humidified oxygen inhalation at a rate of 6 L/min.

CT data revealed the appearance of new filling defects in the segmental branches of the right pulmonary artery, right ventricular enlargement, leftward displacement of the interventricular septum, and dilation of the pulmonary artery trunk (Fig. 3, a), indicating pulmonary hypertension in the patient. Additionally, CT results showed small "verrucous" thickenings on the territories of the tricuspid valve leaflets (see Fig. 3, b), which required clarification using echocardiography.

 

Fig. 3. Results of the second computed tomography scan obtained during hospitalization: a, sagittal reformation, increased degree of enlargement of the right heart chambers, leftward displacement of the interventricular septum; b, transverse section, arrows show small thickenings on the tips of the tricuspid valve.

 

Repeated TTE, along with marked enlargement and overload of the right heart chambers, decreased right ventricular contractility, progression of tricuspid regurgitation to a severe degree, and signs of high pulmonary hypertension, revealed verrucous ("warty") thickenings of the tricuspid valve leaflets (Fig. 4) and multiple small formations on its leaflets, appearing as "kissing" vegetations in one of the sections (Fig. 5).

 

Fig. 4. Echocardiography results, parasternal view, right ventricular inflow tract position: verrucous thickenings of the tricuspid valve leaflets (red arrows).

 

Fig. 5. Echocardiography results, parasternal view, modified short-axis view of the aortic valve with a focus on the tricuspid valve: "verrucous" thickenings of the tricuspid valve leaflets (green arrow).

 

Given the absence of fever and other signs of infective endocarditis in the patient, the identified neoplasms were considered sterile vegetations on the tricuspid valve leaflets — a manifestation of NBTE.

Interventions

Anticoagulant therapy with unfractionated heparin was initiated with laboratory hemostasis parameters.

Follow-Up and Outcomes

Within several days, the symptoms of respiratory failure regressed, and a decrease in the need for oxygen support and an increase in the patient's physical activity were noted.

Since the verification of the tumor lesion morphology was paramountly important for the initiation of adequate antitumor therapy, a biopsy of one of the metastatic foci in the liver was planned. However, 6 hours after the discontinuation of intravenous heparin administration, the patient experienced a sharp increase in dyspnea, desaturation, and a decrease in blood pressure, followed by cardiac arrest.

Resuscitation efforts carried out for 30 minutes were unsuccessful. The patient was pronounced dead.

Post-Mortem Diagnosis

Pancreatic malignant neoplasm with liver metastases without histological verification. Non-bacterial endocarditis of the tricuspid valve. Pulmonary embolism of the artery branches, pulmonary infarctions.

Autopsy Results

Autopsy revealed cancer of the body of the pancreas; moderately differentiated ductal adenocarcinoma — with invasion into the posterior wall of the stomach, metastases to the parapancreatic and splenic lymph nodes, and both right and left hepatic lobes. Subacute marantic (polypous) endocarditis of the tricuspid valve with vegetation sizes of 2 × 1 cm and 5 × 1 cm (Fig. 6). PE of the segmental branches of the right and left pulmonary arteries. Hemorrhagic infarction of the superior, anterior, and posterior basal segments (S₆, S₈, S₁₀) of the right lung and the superior lingular, superior, and posterior basal segments (S₄, S₆, S₁₀) of the left lung.

 

Fig. 6. Autopsy data: verrucous endocarditis, large vegetations on all leaflets of the tricuspid valve.

 

DISCUSSION

This case presents a verified case of NBTE with a rare variant of isolated tricuspid valve involvement presenting with recurrent PE in a cancer patient. The complexity of this case was due to recurrent PE occurring with any attempt at even short-term discontinuation of anticoagulant therapy. In turn, its discontinuation is a prerequisite for the safe performance of a biopsy and subsequent histological verification of the pancreatic mass, without which it is impossible to prescribe adequate antitumor therapy. The situation was also complicated by a history of kidney cancer, which made it impossible to certainly identify the pancreatic tumor as the cause of the metastatic organ involvement.

The case demonstrates certain challenges in the management and treatment of the patient, which at the time of hospitalization did not have a clear solution. The question remains open whether it is permissible to refrain from performing a biopsy of the neoplasm and initiate empirical antitumor therapy in accordance with pancreatic cancer treatment guidelines. Another question is whether antithrombotic therapy can be intensified in cases where standard regimens are associated with recurrent embolic events.

The description of this case confirms the possibility of NBTE developing as a manifestation of an oncological disease. Similar observations are presented in literature [3, 4], but they are rare, which emphasizes their clinical significance.

CONCLUSION

In patients with oncological diseases accompanied by embolic events, both systemic and pulmonary, as well as in the presence of deep vein thrombosis of the lower extremities, TTE should be performed to thoroughly assess the left and right heart valves for possible vegetations. Given the limited amount of available data on the management of such patients, the therapeutic approach requires individualization and nonstandard clinical decisions by the treating physician.

ADDITIONAL INFORMATION

Author contributions: K.S. Dalgatova: echocardiography, diagnosing, data curation, writing — original draft; M.K. Alaniya: supervision (Oncology), writing — review & editing; S.A. Fedorov: investigation, writing — review & editing; A.D. Erlikh: supervision (Cardiology), writing — review & editing; O.P. Bliznyukov: investigation; V.E. Sinitsyn: writing — review & editing, formal analysis, visualization. All the authors approved the version of the manuscript to be published and agreed to be accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Ethics approval: Not applicable.

Consent for publication: No informed consent was obtained from the patient’s family members for publication of information on her health status during hospitalization. Reason: the patient was lost to follow-up (contact information of the patient’s family members was unavailable). All data presented are anonymized, and no photographs are published.

Funding sources: No funding.

Disclosure of interests: The authors have no relationships, activities, or interests for the last three years related to for-profit or not-for-profit third parties whose interests may be affected by the content of the article.

Statement of originality: No previously published material (text, images, or data) was used in this study or article.

Data availability statement: The editorial policy regarding data sharing does not apply to this work.

Generative AI: No generative artificial intelligence technologies were used to prepare this article.

Provenance and peer-review: This article was submitted unsolicited and reviewed following the standard procedure. The peer-review process involved three external reviewers.

About the authors

Kira S. Dalgatova

Olymp Clinic Mars

Email: kira_1975@mail.ru
ORCID iD: 0009-0007-3327-009X
Russian Federation, Moscow

Mariya K. Alaniya

Ilinskiy Hospital

Email: malaniya17@gmail.com
ORCID iD: 0009-0009-6948-8183
Russian Federation, Moscow

Sergey A. Fedorov

Ilinskiy Hospital

Email: serhiofedorucci@gmail.com
ORCID iD: 0000-0001-8214-9826
SPIN-code: 9234-2015

MD, Cand. Sci. (Medicine)

Russian Federation, Moscow

Alexey D. Erlikh

Ilinskiy Hospital

Email: alexeyerlikh@gmail.com
ORCID iD: 0000-0003-0607-2673
SPIN-code: 4697-0822

MD, Dr. Sci. (Medicine)

Russian Federation, Moscow

Oleg P. Bliznyukov

Russian Scientific Center of Roentgenology and Radiology

Email: opblisnukov@mail.ru
ORCID iD: 0000-0003-2401-5007
SPIN-code: 6182-0840

MD, Dr. Sci. (Medicine)

Russian Federation, Moscow

Valentin E. Sinitsyn

Lomonosov Moscow State University; Research and Practical Clinical Center for Diagnostics and Telemedicine Technologies

Author for correspondence.
Email: vsini@mail.ru
ORCID iD: 0000-0002-5649-2193
SPIN-code: 8449-6590

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Moscow; Moscow

References

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