Echocardiographic diagnosis of Libman-Sacks endocarditis in systemic lupus erythematosus: description of two cases

Introduction

Libman-Sacks endocarditis (LSE) is a form of non-infective endocarditis (IE) that results in sterile vegetations on cardiac valves, predominantly affecting the mitral and aortic valves (1). It is most commonly associated with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) (2). The underlying pathogenesis of LSE involves autoimmune responses and inflammatory processes, which lead to the deposition of fibrin, platelets, and immune complexes on the valve surfaces (3,4). The presence of antiphospholipid antibodies significantly increases the risk of developing LSE, particularly in patients with SLE and APS, where endothelial dysfunction and a prothrombotic state contribute to the formation of these vegetations (5).

Globally, the prevalence of LSE parallels that of SLE and APS, with approximately 10% to 15% of SLE patients developing LSE (6). It is also frequently observed in patients with APS, especially among women and younger individuals (7). Despite being relatively rare, LSE can result in severe complications, including valvular dysfunction or systemic embolization, highlighting the importance of early diagnosis and intervention (5,7).

Echocardiography is the primary diagnostic tool for LSE, as it can identify characteristic vegetations on the heart valves (8). Compared to other imaging techniques, echocardiography offers the benefits of being non-invasive, real-time, and widely available. It is particularly effective in differentiating LSE from IE, as LSE vegetations do not cause destructive valvular lesions. Advances in imaging technology, such as three-dimensional echocardiography, have further improved diagnostic accuracy, especially in evaluating the morphology of the vegetations and their impact on valvular function (9,10).

In this article, we report two cases of LSE diagnosed through echocardiography in patients with SLE. These cases underscore the importance of echocardiographic screening for detecting LSE, even in the absence of obvious cardiac symptoms. Furthermore, they highlight the diagnostic and clinical significance of echocardiography in guiding treatment decisions, including immunosuppressive and anticoagulant therapy or surgical intervention when necessary.

Case presentation

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the 45-year-old patient, and from the parents or legal guardians of the 15-year-old patient, for publication of this article and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Case 1

A 15-year-old female was admitted due to “recurrent fever and cough for 10 days”. During the fever, her highest temperature reached 39.0 ℃, accompanied by dizziness, headache, cough, and sputum production. Despite receiving 7 days of anti-infection treatment, her symptoms did not improve significantly, and she developed nausea, vomiting, and loose stools. Continuous blood cultures were negative. Medical history: she had a history of APS for 2 years and deep vein thrombosis (DVT) in the lower limbs for 2 years. She was currently on a daily dose of 3.75 mg warfarin. Her previous treatments included hydroxychloroquine sulfate, prednisone acetate, mycophenolate mofetil capsules, and alfacalcidol, all of which had been self-discontinued during the previous 6 months.

Auxiliary examination: a lower limb ultrasound performed upon admission showed the formation of a thrombus in the left lower limb’s deep veins (Figure 1A), while the left lower limb arteries showed no significant abnormalities. Blood gas analysis revealed: pH 7.49, PCO₂ 25.4 mmHg, PO₂ 136 mmHg, HCO₃⁻ 19.0 mmol/L, standard base excess (SBE) −3.8 mmol/L, and O₂ saturation 99.4%. Laboratory tests: erythrocyte sedimentation rate (ESR) 50 mm/h, antiphospholipid antibody tests [immunoglobulin A (IgA), IgG, IgM]: anti-cardiolipin antibody-IgM 14.40 positive (+), anti-cardiolipin antibody-IgG 31.70 positive (+), lupus anticoagulant: significant. Antinuclear antibodies (ANA) screening: ANA nuclear particle positive 1:100. ANA profile negative, immunoglobulins and complement tests were negative.

Figure 1 Ultrasonographic images of Case 1. (A) Compression ultrasound demonstrates deep-vein thrombosis of the lower limb. (B) Apical four-chamber echocardiographic view reveals mitral regurgitation. (C,D) Two different echocardiographic views demonstrating a well-defined hyperechoic mass attached to the lateral papillary muscle of the left ventricle (blue arrows), showing slight mobility during the cardiac cycle.

Transthoracic echocardiography (TTE) performed upon admission demonstrated focal thickening of the anterior mitral leaflet, predominantly involving the A1 scallop. During systole, mild prolapse of the affected leaflet toward the left atrium was observed, resulting in incomplete leaflet coaptation and moderate mitral regurgitation on color Doppler imaging (Figure 1B). In addition, a well-circumscribed hyperechoic mass measuring approximately 1.4 cm × 1.2 cm was identified in the left ventricle, attached to the lateral papillary muscle (Figure 1C,1D). The lesion had clear margins, relatively homogeneous internal echogenicity, and slight mobility during the cardiac cycle, without obvious acoustic shadowing. These echocardiographic findings suggested a non-infective thrombotic or vegetative lesion. When interpreted together with the patient’s history of APS, recurrent deep venous thrombosis, and positive antiphospholipid antibodies, and repeatedly negative blood cultures, these findings strongly supported the diagnosis of LSE. Transesophageal echocardiography (TEE) was not performed in this case.

Case 2

A 45-year-old female was admitted with a 5-year history of “chest tightness and shortness of breath after activity, aggravated for 1 month”. Medical history: liver intrahepatic bile duct stones, surgery 10 years ago. Drug allergy history: allergic to penicillin and cephalosporins. Physical examination revealed diastolic murmur at the mitral area and a faint murmur at the aortic valve area.

Laboratory tests: ANA nuclear particle type positive 1:100, ESR normal, immunoglobulin A 5.22 g/L, ANA profile, anti-neutrophil cytoplasmic antibody (ANCA), ds-DNA, and anti-streptolysin O (ASO) were generally normal. Continuous blood cultures were negative. TTE examination demonstrated a thickened fibrous structure extending from the anterior and lateral papillary muscles to the upper interventricular septum, consistent with a left ventricular false tendon. Multiple irregular, oscillating echogenic masses were observed along this structure and on the mitral valve leaflets. The mitral valve leaflets appeared diffusely thickened, with superimposed irregular vegetative lesions predominantly located along the leaflet edges. These lesions exhibited heterogeneous echogenicity and a shaggy, filamentous appearance, resulting in restricted leaflet motion, moderate mitral regurgitation, and mild-to-moderate stenosis. Color Doppler imaging confirmed regurgitant flow across the mitral valve, further supporting significant valvular dysfunction (Figure 2).

Figure 2 Ultrasonographic images of Case 2. (A,B) Two-chamber and apical long-axis views demonstrating a shaggy, filamentous mitral valve (blue arrows) and left ventricular false chordae tendineae (red arrows). (C) Color Doppler showing moderate mitral regurgitation at the valve orifice.

TEE, including intraoperative TEE, was not performed in this case. Ten days after admission, the patient underwent cardiac valve surgery. Intraoperatively, the mitral valve leaflets showed thickening and focal calcification, and the chordae tendineae exhibited fluffy vegetative outgrowths. The mitral valve opening showed moderate stenosis and incomplete closure. The three aortic valve leaflets were thickened with nodular formations, causing severe regurgitation. Pathological examination of the excised aortic valve, mitral valve, and mitral valve outgrowths revealed: (aortic valve) fibrous tissue proliferation with mucinous changes and focal calcification; (mitral valve) fibrous tissue proliferation with mucinous changes; (mitral valve outgrowths) predominantly collagen fibers with some degeneration (Figure 3). After surgery, the patient’s condition stabilized. The diagnosis of LSE was confirmed based on postoperative histopathological findings, which demonstrated fibrous tissue proliferation with myxoid degeneration and focal calcification, without evidence of bacterial infection. These findings, together with repeatedly negative blood cultures and supportive autoimmune-related laboratory results, were consistent with non-bacterial thrombotic endocarditis.

Figure 3 Post-operative pathological specimens of Case 2. (A₁) Gross appearance of the resected aortic valve. (A) Histological section of the aortic valve showing prominent interstitial fibrous tissue hyperplasia with myxoid change and focal calcification (hematoxylin and eosin staining, ×10). (B₁) Gross appearance of the resected mitral valve. (B) Histological section of the mitral valve showing prominent interstitial fibrous tissue hyperplasia with myxoid change (hematoxylin and eosin staining, ×20). (C₁) Gross appearance of the resected mitral valve vegetation. (C) Histological section of the mitral vegetation showing dense collagenous fibers (hematoxylin and eosin staining, ×20).

Discussion

LSE is a well-recognized cardiac manifestation of SLE and APS, characterized by sterile verrucous vegetations and valvular thickening. Echocardiography remains the cornerstone of diagnosis, with typical findings including irregular, sessile, echogenic masses of varying size that are firmly attached to the valve surface and lack independent motion (11). These vegetations most commonly involve the left-sided valves, particularly the mitral valve, often along the line of closure, producing characteristic appearances such as the so-called “kissing lesions” involving both mitral leaflets (2). The prevalence of LSE in patients with SLE varies depending on the imaging modality and population studied. Echocardiographic studies have reported valvular vegetations in approximately 11% of SLE patients, with earlier studies suggesting even higher rates ranging from 53% to 74%, and the mitral valve involved in up to 63% of cases (12). These findings suggest a relatively high prevalence of subclinical valvular involvement in SLE, further emphasizing the importance of transthoracic echocardiographic screening in this population.

Despite these established features, most previously reported cases describe LSE vegetations as predominantly involving valvular leaflets, particularly along the line of closure. However, the clinical presentation of LSE remains heterogeneous and diagnostically challenging, particularly in distinguishing it from IE or intracardiac masses. In this context, our cases illustrate two distinct but complementary clinical scenarios that expand the recognized spectrum of LSE. Case 1 demonstrates the occurrence of LSE in a patient with previously diagnosed but clinically quiescent SLE, emphasizing that disease activity may not reliably predict cardiac involvement and that diagnosis can be challenging in the absence of overt systemic manifestations. In contrast, Case 2 highlights LSE as the initial and revealing manifestation of previously undiagnosed SLE, with definitive confirmation by postoperative histopathology. Importantly, both cases exhibited highly atypical echocardiographic findings, with vegetations located outside the valvular leaflets—specifically on the lateral papillary muscle in Case 1 and on left ventricular false chordae in Case 2. This is in contrast to the classical description of LSE vegetations arising on valve leaflets or along the line of closure (12). These unusual non-valvular locations differ from the classical echocardiographic description of LSE and represent a novel imaging presentation, thereby expanding the currently recognized morphological spectrum of the disease. Taken together, these cases not only underscore the educational value of recognizing diverse presentations of LSE but also highlight the novel contributions of this report, including atypical non-valvular vegetation locations, complementary clinical scenarios (clinically quiescent SLE and initial manifestation of SLE), and their implications for improving echocardiographic diagnosis and differential diagnosis.

One of the major clinical challenges is differentiating LSE from IE, as both conditions can present with valvular vegetations. Unlike IE, vegetations in LSE rarely cause valve destruction or abscess formation, a feature that is particularly evident on echocardiography. Therefore, recognizing these echocardiographic characteristics such as irregular shape, heterogeneous internal echoes, broad-based attachment, associated valvular thickening, and the relative absence of destructive changes is essential for the early diagnosis and management of patients with SLE (13-15). In our cases, the echocardiographic findings, including mitral valve thickening, irregular echogenic lesions, and valvular regurgitation, were highly suggestive of LSE when interpreted in conjunction with the clinical and laboratory context.

From an immunological perspective, the autoimmune dysfunction inherent in SLE results in the production of various autoantibodies, including ANA and antiphospholipid antibodies, both of which contribute to the deposition of immune complexes on the heart valves. This cascade of immune activity not only leads to valve damage but also creates a hypercoagulable environment that facilitates thrombus formation. The presence of these immune complexes on the valve surfaces triggers further inflammatory responses, resulting in a cycle of immune-mediated damage that supports the growth of sterile vegetations (5).

Clinically, LSE often presents with heart murmurs due to mitral or aortic regurgitation, and in more severe cases, systemic embolic events such as strokes may occur (5,11). However, it is worth noting that LSE is often asymptomatic in its early stages, especially in patients with SLE, and may go undetected without routine echocardiographic screening (12). In addition to valve dysfunction, patients may also experience signs of systemic inflammation, such as fatigue, fever, and other manifestations of lupus, although the typical symptoms of IE, such as fever and leukocytosis, are usually absent. This makes the clinical presentation of LSE distinct, and it is crucial to consider the underlying autoimmune conditions, such as SLE and APS, when diagnosing LSE. The risk of embolic events is particularly high in patients with APS, where the prothrombotic state is further aggravated (2). Valvular dysfunction, including regurgitation or stenosis, is another common complication. Over time, this can lead to heart failure if left untreated. Therefore, early detection of LSE through echocardiography is crucial to prevent such complications and initiate appropriate treatment (4).

These cases highlight the critical role of echocardiography in the early detection of LSE. Echocardiography, being a non-invasive and real-time imaging technique, clearly demonstrates the characteristics of LSE vegetations and provides crucial diagnostic evidence. Research indicates that echocardiography is particularly valuable for early detection of cardiac complications in SLE patients, especially for asymptomatic individuals, underscoring its role in screening. Given that the prevalence of LSE in SLE patients is approximately 10–15% and it can lead to severe complications, routine echocardiographic screening should be promoted in the management of SLE patients.

TEE, owing to its superior spatial resolution compared with TTE, is more sensitive for detecting small vegetations, subtle valvular thickening, and mild regurgitation. In clinical practice, TTE is generally used as the first-line imaging modality due to its non-invasive nature and wide availability. However, TEE should be considered as an adjunct when TTE findings are inconclusive or nondiagnostic, and may also be used as an initial diagnostic tool in patients with SLE who present with suspected cardioembolic events, given its higher sensitivity for detecting small or atypically located vegetations. In the present study, TEE was not performed in either case, which represents a limitation. Although TTE provided important diagnostic information, the absence of TEE may have reduced sensitivity for detecting smaller or additional lesions. Future studies incorporating TEE may further improve diagnostic accuracy and characterization of atypical LSE presentations. In addition to conventional two-dimensional imaging, three-dimensional transesophageal echocardiography (3D TEE) has further improved the evaluation of LSE. Compared with TTE and 2D TEE, 3D TEE provides more accurate visualization of the size, morphology, and spatial relationships of vegetations, as well as their precise attachment sites. This is particularly valuable in cases with atypical or non-valvular lesion locations, such as those observed in our patients. However, TEE and 3D TEE are semi-invasive procedures and may be limited by availability, operator expertise, and patient tolerance. Therefore, the choice of imaging modality should be individualized based on clinical context and diagnostic needs.

Looking ahead, advancements in imaging technologies and further research into the pathological mechanisms of LSE hold promise for breakthroughs in its diagnosis and treatment. In addition to echocardiography, other imaging modalities may provide complementary information in selected cases. Cardiac magnetic resonance (CMR) imaging can offer detailed tissue characterization and may help differentiate thrombotic from inflammatory or neoplastic lesions. Cardiac computed tomography (CT) may assist in evaluating valvular morphology and calcification. However, in the present cases, additional imaging was not performed, as the diagnosis was supported by characteristic echocardiographic findings in combination with clinical and laboratory data. This represents a limitation, as multimodality imaging may further improve diagnostic accuracy in atypical presentations. The development of advanced imaging techniques, including echocardiography and cardiac magnetic resonance imaging (MRI), may further improve the comprehensive evaluation of LSE. However, echocardiography—particularly TEE—remains the primary modality for evaluating valvular vegetations due to its superior spatial resolution and real-time assessment of valve morphology and function. CMR serves as a complementary technique, is mainly useful for tissue characterization and for assessing myocardial or pericardial involvement in SLE, rather than for the primary evaluation of valvular vegetations. Additionally, the discovery of new biomarkers, such as specific autoantibodies or inflammatory markers, may aid in the early identification of LSE. Regarding treatment, ongoing research into immunomodulatory therapies and anticoagulation strategies for LSE aims to reduce vegetation formation and prevent embolic events (16). Future large-scale prospective studies exploring the optimal timing and frequency of echocardiographic screening in SLE patients will contribute to the optimization of clinical management (17,18). Through multidisciplinary collaboration and ongoing research, the diagnosis and treatment of LSE will continue to improve, safeguarding the cardiac health of patients with SLE (19).

Conclusions

LSE should be considered in patients with suspected or confirmed SLE, even in the absence of active disease. Our cases highlight the heterogeneous clinical spectrum of LSE, ranging from occurrence in quiescent SLE to its role as an initial manifestation of previously undiagnosed disease. Importantly, we demonstrate that LSE vegetations may arise in atypical, non-valvular locations, such as papillary muscles and left ventricular false chordae, expanding the currently recognized morphological spectrum. These findings underscore the critical role of TTE in the early recognition of LSE and in prompting further systemic evaluation. Increased awareness of such atypical presentations may improve diagnostic accuracy and facilitate timely management.

Acknowledgments

None.

Footnote

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1-2771/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the 45-year-old patient, and from the parents or legal guardians of the 15-year-old patient, for publication of this article and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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