Left Ventricle Libman-Sacks Endocarditis Secondary to Systemic Lupus Erythematosus and Antiphospholipid Syndrome: A Case Report

Introduction

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by immune dysregulation and chronic inflammation [1]. Approximately 5–10% of patients with SLE develop cardiac complications, including myocarditis, diffuse myocardial fibrosis, intracardiac thrombi, and ventricular dysfunction [2]. These complex clinical manifestations are driven by autoantibodies, complement activation, and immune-mediated thrombosis [3].

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by thrombocytopenia, thrombosis, and recurrent miscarriages [4]. Its population prevalence is approximately 2%, and around 40% of patients with SLE have concurrent APS [5]. Libman-Sacks endocarditis (LSE) is a non-infectious endocarditis secondary to SLE and APS, with a prevalence of approximately 0.9–1.6% [6]. A typical feature of LSE is the presence of sterile verrucous vegetations on the aortic or mitral valve, with rare involvement of the endocardium beyond the valves [7]. Transthoracic echocardiography (TTE) and serum antibody markers are key to its diagnosis. The clinical manifestations and prognosis of LSE are closely associated with the activity of the underlying primary disease and antibody levels [8]. Long-term anticoagulant therapy is fundamental for preventing embolic events [9]. This report presents a case of a 19-year-old woman with a 2-year history of concurrent SLE and APS who developed LSE.

Case Report

A 19-year-old female patient was diagnosed with SLE and APS at another hospital 2 years ago, based on left popliteal and external iliac vein thrombosis, facial and acral rashes, and twice-positive results for anti-β2-glycoprotein I (anti-β2GPI) antibody, anticardiolipin antibody, antinuclear antibody (ANA), and anti-double-stranded DNA (anti-dsDNA) antibody [10,11]. Over the preceding 4 months, she had experienced occasional chest tightness, dizziness, and chest pain. Physical examination revealed stable vital signs, no abnormalities on cardiopulmonary assessment, and scattered erythematous rashes on her face, hands, and feet (Figure 1).

Transthoracic echocardiography (TTE) demonstrated an inactive, 27×20 mm hypoechoic mass on the left ventricle (LV) inferior wall, with indistinct endocardial borders. The mass showed complete absence of contrast agent perfusion on myocardial contrast echocardiography, and no enhancement on cardiac magnetic resonance (CMR) first-pass perfusion and delayed enhancement sequences, suggesting it was a thrombus. The adjacent LV inferior wall exhibited hypokinesis (3–4 mm) with reduced myocardial contrast perfusion compared with the neighboring myocardium, and a decreased left-ventricular ejection fraction (LVEF: 51%). CMR demonstrated thinning of the adjacent myocardium (3.2 mm) and transmural late gadolinium enhancement (LGE), with no evidence of edema, was consistent with myocardial injury and fibrosis [12] (Figure 2). Multisystem computed tomography (CT) confirmed a mixed-density intracavitary mass within the LV and excluded pulmonary embolism, metastatic disease, and atherosclerotic stenosis.

Laboratory investigations revealed hematological and immunological abnormalities (Table 1). Markedly positive for ANA (1: 10 000), positive for anti-dsDNA antibody (49 IU/mL), and positive for anti-Smith (anti-Sm) antibodies (15 AU/ml), the patient’s results were consistent with the diagnostic criteria for SLE. Reduced complement levels (C3: 42.1 mg/dL, C4: 3 mg/dL) indicated active disease activity. Significantly elevated anti-cardiolipin antibody IgG (193 IU/mL) and anti-β2GPI antibodies (300 RU/mL) met the diagnostic criteria for APS. Abnormalities in erythrocyte sedimentation rate (ESR: 96 mm/h), platelet count (89×109/L), and hemoglobin level indicated multisystem involvement. Additionally, electrocardiogram findings and serological viral neutralizing antibody tests were unremarkable. The patient had no febrile episodes or viral infections in the preceding 6 months. Along with 2 consecutive negative blood cultures, acute viral myocarditis and infective endocarditis were deemed less likely. Given only mildly elevated cardiac injury biomarkers (NT-proBNP), the final diagnosis was SLE with concurrent APS and associated LSE.

Management included methylprednisolone, intravenous immunoglobulin, cyclophosphamide, hydroxychloroquine, and warfarin. The patient’s symptoms significantly improved after 11 days of hospitalization, with the LVEF increasing from 51% to 58%. Relevant immune and inflammatory parameters demonstrated significant changes (Table 1). Post-discharge therapy included belimumab, warfarin, and hydroxychloroquine. At the 6-month follow-up, the patient remained clinically stable. Repeat TTE revealed no significant change in the size of the thrombus, which exhibited heterogeneous moderate echogenicity consistent with fibrosis. M-mode echocardiography showed adjacent myocardial wall motion of 4–5 mm, indicating partial recovery. Immune and inflammatory markers normalized. Long-term therapy included belimumab and warfarin.

Discussion

This case underscores that SLE with concurrent APS can manifest as non-valvular LSE, highlighting the complex intrinsic association between SLE/APS and LSE, the value of comprehensive cardiac imaging (TTE, CMR, CT) combined with immunological assessments, and the significance of timely immunosuppressive and anticoagulant therapy guided thereby [13]. Most reported LSE cases involve the aortic and mitral valves, leading to the formation of valvular vegetations that cause valvular regurgitation and secondary cardiac symptoms [14]. However, after searching through LSE cases over the past 5 years, lesions located in the non-valvular endocardium, as observed in this case, did not appear to have been previously reported.

Current understanding posits that systemic immune-mediated diseases involve the heart primarily through tissue damage, immune complex deposition, complement cascade activation, and subsequent endothelial cell activation [15]. The mechanisms underlying LSE formation may be associated with: 1) immune-mediated endothelial injury and microthrombus formation; 2) deposition of immunoglobulins and complement components; 3) hypercoagulability driven by disease activity of SLE and APS [16]. Positive lupus antibodies, anticardiolipin antibodies, and anti-β2GPI antibodies are closely associated with LSE activity and thrombus formation [5]. In patients with myocardial injury, the positivity rate of anti-Ro-52 antibody reaches 69%, and this antibody can predict myocardial fibrosis and necrosis – a finding consistent with the data in our case (anti-Ro-52 antibody: 96 RU/mL) [17].

Multimodality imaging exhibits substantial clinical value in similar cases. TTE, with its high temporal resolution and repeatability, serves as the first-line modality for early detection of space-occupying lesions and assessment of cardiac function; however, its sensitivity for detecting LSE is only 11% [18]. CMR, given its correlation with histopathology, is highly suitable for evaluating complex LSE. Through T1, T2, and LGE analyses, it can accurately identify endocardial and myocardial inflammatory reactions, thrombi, and lupus-induced pericardial diseases [19].

The patient exhibited no arrhythmias, cardiac conduction blocks, or heart failure; consequently, pharmacological therapy alone was administered. According to guidelines [5], hydroxychloroquine is recommended for all lupus patients due to its anti-inflammatory and thromboprophylactic effects. However, given its rare association with restrictive cardiomyopathy, hydroxychloroquine was administered only during hospitalization [20]. There is currently no consensus on the efficacy of glucocorticoids or cytotoxic agents specifically for LSE. Nevertheless, immunosuppressive therapy remains the standard of care in complex cases to mitigate systemic inflammation [21]. Immune modulators (eg, methotrexate) facilitate corticosteroid tapering and discontinuation. For refractory active lupus myocarditis or LSE, the addition of belimumab – an anti-B-cell activating factor monoclonal antibody that inhibits B-cell maturation and survival – should be considered [22].

Chronic immune dysregulation in SLE promotes endothelial activation and platelet aggregation, creating a prothrombotic environment [9]. Concurrent antiphospholipid antibodies impair fibrinolysis and enhance thrombus stability. Given the high risk of embolism in patients with LSE – particularly cerebrovascular embolism, which is associated with poor prognosis – early anticoagulant therapy should be administered to all patients with SLE and secondary APS [23]. Guidelines recommend long-term warfarin therapy with a target international normalized ratio (INR) of 2.0–3.0 [24]. Studies have shown that despite appropriate anticoagulant therapy, valvular involvement, and LSE can still occur in patients with APS and SLE [14]. In view of the stable intracardiac thrombus after treatment in this case, we continue to administer long-term anticoagulant therapy with regular follow-up examinations.

Several limitations merit consideration in the diagnosis and management of this case. Firstly, comprehensive pre-admission medical records were unavailable. Secondly, pathological analysis was not performed for this rare presentation. Furthermore, standardized treatment guidelines for LSE remain lacking. Although biologic agents represent an exploratory therapeutic approach, they showed promising efficacy in this case.

Conclusions

Non-valvular left-ventricular LSE is a rare complication of SLE and APS. This case highlights the intricate association between LSE and SLE/APS, the critical role of multimodal imaging combined with serological testing in diagnosis, and the complexities in its management. Future research should prioritize longitudinal follow-up and mechanistic studies to clarify pathophysiological pathways and optimize clinical management.