Background/Purpose: Libman-Sacks endocarditis (LSE) is an inflammatory phenomenon, typically involving the mitral or aortic valve, that affects some patients with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). These thrombotic vegetations can cause valve failure or become a nidus for bacterial endocarditis. The pathophysiologic mechanisms underlying LSE, including the role played by specific APS-associated autoantibodies (aPL), are poorly understood. Here, we set out to define any unique clinical characteristics of patients with a history of LSE. We also sought preliminary evidence of inflammatory pathways more likely to be activated in these patients.

Methods: We identified cases of LSE from an academic cohort of approximately 300 patients with durably positive aPL testing; roughly 75% of the cohort met criteria for APS. All available TTE and TEE reports were reviewed to identify APS patients with and without valve disease. Those with TTE/TEE evidence of LSE and/or those who had undergone valvular replacement for LSE were selected as cases (n=10). Patients with positive blood cultures or with valve thickening without vegetation were excluded. Age- and sex-matched controls were randomly selected from the cohort of APS patients with normal TTE/TEE results (n=20). Clinical characteristics, including comorbid conditions and standard laboratory results (e.g., platelet count, complement levels), were noted. Plasma levels of selected aPL were measured by ELISA. We also assessed biomarkers tending to track with activation of endothelial cells (E-selectin), platelets (P-selectin), and neutrophils (calprotectin).

Results: In our patient population, the average age was 47.9 years in the case group and 47.8 years in the control group. In both groups, 80% of patients were female, and 20% had SLE. LSE most frequently involved the mitral valve (90%), followed by the aortic valve (10%). Overall, 60% of patients required valve surgery. Patients with LSE were significantly more likely to have a history of hypertension (80% vs. 25%, p=0.007), catastrophic APS (30% vs. 0%, p=0.039), and white matter hyperintensities (70% vs. 25%, p=0.045) than those without; significant differences were not found in the rates of hyperlipidemia (30% vs. 5%), venous thrombosis (60% vs. 50%), or stroke (70% vs. 40%). Patients with LSE tended to have lower platelet counts (mean 225 K/µl vs. 289, p=0.028), as well as lower complement C4 levels (mean 19.6 mg/dl vs. 25.5, p=0.029). LSE patients were more likely to have positive testing for anti-β2GPI IgG and anti-PS/PT IgG; however, these differences were not statistically significant. Though E-selectin and calprotectin levels were not statistically different between the groups, P-selection was increased in the LSE patients (mean 32.2 ng/ml vs. 25.0, p=0.035).

Conclusion: Durably aPL-positive patients with a history of LSE were more likely to have a history of hypertension, catastrophic APS, and white matter hyperintensities, as compared to those without. They also tended to have lower platelet counts and complement C4 levels. Candidate biomarker testing suggests that platelet activation likely deserves further study as a contributor in the pathogenesis of aPL-associated LSE.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/libman-sacks-endocarditis-in-aps-a-case-control-study-of-clinical-and-serologic-features/