Valves Gone Wild in SLE Save

Lupus valvulitis is a rare cardiac manifestation of active systemic lupus erythematosus (SLE) and is defined by inflammation of one or more cardiac valves. It is often associated with Libman-Sacks endocarditis (LSE), which is characterized by the presence of sterile vegetations on the heart valves.

The clinical presentation of valvulitis can vary. Many patients are asymptomatic, but some may develop significant valvular dysfunction such as regurgitation or stenosis, which can result in heart failure necessitating surgical intervention. The diagnosis of SLE valvulitis is primarily made using echocardiography, which can reveal valve thickening, vegetations, and regurgitation. Transesophageal echocardiography (TEE) is more sensitive than transthoracic echocardiography (TTE) for detecting these abnormalities [1, 2].

Lupus valvulitis in the absence of LSE in patients with systemic lupus erythematosus (SLE) is a specific subset of valvular heart disease that is infrequently observed. The prevalence of valvular abnormalities in SLE patients varies, but specific data on lupus valvulitis without Libman-Sacks endocarditis is limited due to its rarity.

To comprehensively review the existing literature on non-Libman-Sacks lupus valvulitis, we conducted a systematic search to identify relevant studies, reviews, and case reports published up to April 2025. The prevalence of systemic lupus erythematosus (SLE) patients with lupus valvulitis, excluding those with bacterial or Libman-Sacks endocarditis, is generally not well reported. Valvular abnormalities are common in SLE patients, with estimates ranging from 44% to 74% depending on the study and the diagnostic method used. [2-4]  Cervera et al reported that 44% of SLE patients had valvular abnormalities [2, 3], while the study by Roldan et al. found that 74% of SLE patients had valvular abnormalities, including leaflet thickening and valve masses, regardless of the presence of antiphospholipid antibodies [2].

Valvular involvement in systemic lupus erythematosus (SLE) is multifactorial, involving both inflammatory and thrombotic mechanisms. The mechanisms leading to valvular involvement in SLE include chronic inflammation and the prothrombotic effects of antiphospholipid antibodies, which contribute to valvular thickening, fibrosis, and thrombus formation, resulting in valvular dysfunction. Antiphospholipid antibodies (aPL) play a significant role in the pathogenesis of valvular heart disease (VHD) in SLE patients, even in the absence of Libman-Sacks endocarditis.

Chronic inflammation in SLE leads to immune complex deposition and complement activation, resulting in endothelial damage and subsequent valvular thickening and fibrosis. This process can cause valvular dysfunction, primarily regurgitation, and less commonly stenosis.

The inflammatory milieu in SLE, characterized by cytokine release and immune cell infiltration, contributes to the structural changes in the heart valves. [2-4] aPL, including lupus anticoagulant and anticardiolipin antibodies, are strongly associated with valvular abnormalities in SLE. These antibodies promote thrombus formation on the valves, leading to nonbacterial vegetations and thickening. The presence of aPL increases the risk of valvular lesions and thromboembolic events. [5, 6] Even in the absence of Libman-Sacks endocarditis, aPL are associated with valvular thickening and dysfunction, particularly affecting the mitral and aortic valves. [6, 7]

Mitral regurgitation, valve thickening, and vegetations are common types of valvular lesions seen in lupus valvulitis in SLE without Libman-Sacks endocarditis. These lesions result from chronic inflammation, immune complex deposition, and the prothrombotic effects of antiphospholipid antibodies.[4] Valvular thickening is a predominant finding in lupus valvulitis. It typically involves the mitral and aortic valves and is characterized by diffuse thickening of the valve leaflets. This thickening is associated with chronic inflammation and immune complex deposition. [4]  Mitral regurgitation is frequently observed in SLE patients. Studies have shown that mild to moderate mitral regurgitation is common, with prevalence rates of 33% and 16%, respectively. The regurgitation is often due to leaflet thickening and fibrosis, which impair the valve's ability to close properly. [3, 8] Vegetations in lupus valvulitis in systemic lupus erythematosus (SLE) patients without Libman-Sacks endocarditis are characterized by several distinct features: composition, size, appearance, location. Vegetations in lupus valvulitis without Libman-Sacks endocarditis are characterized by their fibrin and immune complex composition, small size, typical location on the mitral and aortic valves, and association with antiphospholipid antibodies. [1, 4, 7] The valvular findings of lupus valvulitis differs from Libman Sacks endocarditis in that Libman sacks vegetations are notably sterile, verrucous valvular lesions composed of granular material containing immune complexes, hematoxylin bodies, and platelet thrombi. [1, 9].

The clinical manifestations of lupus valvulitis without Libman-Sacks endocarditis include mitral regurgitation, valve thickening, and vegetations, which can lead to symptoms such as dyspnea, fatigue, palpitations, heart failure, and embolic events. These manifestations are often detected through echocardiographic evaluation,[1] the cornerstone diagnostic tool for detecting valvular abnormalities in SLE patients. Transthoracic echocardiography (TTE) is commonly used for initial evaluation, while transesophageal echocardiography (TEE) provides more detailed images and is particularly useful for identifying subtle lesions such as valve thickening, vegetations, and regurgitation. The American Society of Echocardiography recommends echocardiography for evaluating cardiac sources of embolism, which includes valvular lesions in SLE. [1]

Laboratory tests to detect the presence of antiphospholipid antibodies (aPL), such as lupus anticoagulant, anticardiolipin antibodies, and anti-β2-glycoprotein I antibodies, are essential. These antibodies are associated with an increased risk of valvular lesions and thromboembolic events. Active disease assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) can also correlate with valvular abnormalities. [10, 11]

Cardiovascular Magnetic Resonance (CMR) can be used as an adjunct to echocardiography for detailed assessment of myocardial inflammation, fibrosis, and valvular abnormalities. It is particularly useful in cases where echocardiographic findings are inconclusive or when there is a need to evaluate the extent of myocardial involvement. [12] A valvular biopsy might be considered in very specific and rare circumstances where there is a need to differentiate between lupus valvulitis and other potential causes of valvular disease, such as infective endocarditis or malignancy, especially when non-invasive methods are inconclusive. However, this is not a routine practice due to the invasive nature of the procedure and the risks involved.

The treatment options for lupus valvulitis in SLE without Libman-Sacks endocarditis include both medical management and surgical interventions. The use of glucocorticoids (GCs) and other immunosuppressive agents can help control the underlying inflammation in SLE. The Latin American Group for the Study of Lupus (GLADEL) and the Pan-American League of Associations of Rheumatology (PANLAR) recommend the use of low to moderate doses of glucocorticoids for managing cardiac manifestations in SLE. [13] Hydroxychloroquine is recommended for all SLE patients to prevent flare-ups, organ damage, and thrombosis, and to increase long-term survival. [14]

In the presence of antiphospholipid antibodies (aPL), anticoagulation therapy is recommended to prevent thromboembolic complications. This is particularly important as aPL increases the risk of valvular disease and thrombotic events. [10] Surgical interventions are reserved for severe cases and should be managed by a multidisciplinary team. Surgical intervention may be considered in cases of severe valvular dysfunction that is refractory to medical management. However, surgery in SLE patients carries increased risks, including infection, thromboembolic and bleeding complications, and cardiovascular events due to premature atherosclerosis. Therefore, it is recommended that surgical decisions be made by a multidisciplinary team including a rheumatologist, cardiologist, and cardiothoracic surgeon. [10]

Valvular abnormalities are common in SLE, affecting 44–74% of patients depending on diagnostic methods  [2-4], but data specifically on lupus valvulitis excluding Libman-Sacks endocarditis are limited. This subset likely represents a distinct entity driven by chronic inflammation and antiphospholipid antibodies (aPL)[2-7] . Typical findings include mitral regurgitation, valve thickening, and small nonbacterial vegetations, primarily affecting the mitral and aortic valves [3, 4, 8]. These result from immune complex deposition, fibrosis, and aPL-related thrombosis [4-7]. Diagnosis relies on echocardiography, particularly TEE, with CMR as an adjunct in selected cases [1, 12]. aPL testing and SLE disease activity scores (e.g., SLEDAI) support risk assessment [10, 11].

Treatment involves glucocorticoids, hydroxychloroquine, and anticoagulation for aPL-positive patients [10, 13, 14]., with surgery reserved for severe, refractory cases [10].

This review is limited by the lack of studies focused solely on lupus valvulitis without Libman-Sacks endocarditis. Inconsistent diagnostic criteria and heterogeneous study populations further limit the generalizability of findings, underscoring the need for targeted prospective research.

Conclusion

Lupus valvulitis without Libman-Sacks endocarditis is an underrecognized yet clinically significant form of valvular involvement in SLE. It is associated with chronic inflammation and antiphospholipid antibodies, leading to valve thickening, regurgitation, and vegetations. Diagnosis relies on echocardiography and serological testing. Medical management is typically effective, with surgery reserved for advanced cases. More focused research is needed to better understand this distinct SLE complication.

Reference list

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