Libman-Sacks Endocarditis

Background

Libman-Sacks endocarditis (otherwise known as verrucous, marantic, or nonbacterial thrombotic endocarditis) is the most characteristic cardiac manifestation of the autoimmune disease systemic lupus erythematosus. Libman and Sacks first published a description of the atypical, sterile, verrucous vegetations of this form of endocarditis in 1924.[1] The condition most commonly involves the mitral and aortic valves, but all 4 cardiac valves and the endocardial surfaces can be involved.[2]

Postmortem studies describe mulberrylike clusters of verrucae on the ventricular surface of the posterior mitral leaflet, often with adherence of the mitral leaflet and chordae to the mural endocardium. The lesions typically consist of accumulations of immune complexes and mononuclear cells. The condition is not always recognized on echocardiographic images. With the introduction of steroid therapy for systemic lupus erythematosus, improved longevity of patients appears to have changed the spectrum of valvular disease.

Valvular abnormalities occur as masses (classic Libman-Sacks vegetations; see the image below), diffuse leaflet thickening, valvular regurgitation, and, infrequently, stenosis. Valvular regurgitation is noted most commonly in patients with leaflet thickening, which is thought to represent the chronic healed phase of disease. The left-sided valves are involved most often.

Transesophageal image of a mitral valve with masses characteristic of Libman-Sacks endocarditis.

Lesions similar to those described by Libman and Sacks also occur in association with primary or secondary antiphospholipid syndrome. However, the role of antiphospholipid antibodies in the pathogenesis of Libman-Sacks endocarditis is disputed. Malignancy and hypercoagulable states are also associated with the formation of verrucous endocarditis.

Lesions are usually clinically silent, without significant valvular dysfunction. When such dysfunction does occur, however, it can result in cardiac failure. Embolic phenomena and secondary infective endocarditis, although uncommon, can also complicate valvular abnormalities and can cause neurologic and systemic complications. The risk of systemic emboli is increased substantially in the presence of mitral stenosis, atrial fibrillation, or both.

Valvular regurgitation and, rarely, stenosis may result in heart failure and arrhythmias, such as atrial fibrillation.

NextEtiologyAntiphospholipid antibodies

The pathogenesis of Libman-Sacks endocarditis is unknown. However, antiphospholipid antibodies are frequently associated with valvular abnormalities. These autoimmune antibodies are directed against negatively charged phospholipids present in endothelial cell membranes.

Although immunohistologic studies suggest a pathogenetic role for antiphospholipid antibodies, a similar prevalence and severity of valvular disease have been described in lupus patients without these antibodies; their presence does not seem to be required.

Impairment of antithrombotic mechanisms

Impaired antithrombotic mechanisms present in patients with antiphospholipid syndrome, malignancy, and hypercoagulable states may play a role in the pathogenesis of thrombosis and valvular lesions. Areas of endothelial damage caused by turbulence and the jet effect on the left side of the heart are potential sites of platelet and fibrin deposition.

Steroid therapy

Steroid therapy is implicated in the modification of the nature of valvular abnormalities and in the dysfunction observed in patients with systemic lupus erythematosus.

With the introduction of steroid therapy, valvular thickening and regurgitation appear to occur more commonly, with histologically active lesions identified less frequently. However, data are circumstantial and may reflect improved longevity of patients. Firm conclusions cannot be made.

PreviousNextEpidemiology

Valvular abnormalities are commonly detected in patients with lupus. The characteristic Libman-Sacks vegetations are reported postmortem in approximately 50% of fatal lupus cases. Current echocardiographic studies reveal valvular abnormalities in 28-74% of patients, with valvular masses in 4-43% of patients with systemic lupus erythematosus. Higher rates are generally detected with transesophageal imaging and in subjects with antiphospholipid antibodies (41% with masses), although this observation is not universal.

One cohort study reported that Libman-Sacks endocarditis was found in 11% of patients with lupus.[3] Pure mitral regurgitation was the most common valvular abnormality, followed by aortic regurgitation, combined mitral stenosis and regurgitation, and combined aortic stenosis and regurgitation. At baseline, Libman-Sacks endocarditis was significantly associated with underlying lupus disease activity. During the follow-up echocardiograph, patients with previous valvular lesions had worsened valve function, and more patients developed new valvular lesions.

Coexistent leaflet thickening is noted in 71% of patients with valvular masses. Echocardiography detects valvular thickening in 19-52% of patients with systemic lupus erythematosus.

In older patients, who have a longer mean duration of systemic lupus erythematosus and have received a larger cumulative dose of steroids, valves that appear to be thickened and rigid occur more commonly than verrucous vegetations.

The prevalence of regurgitation in patients with thickened valve leaflets has been reported to be as high as 73%.

The prevalence of valvular abnormalities detected during echocardiography in patients with primary antiphospholipid syndrome has been reported at 30-32%. Abnormal echocardiographic findings are most common in individuals with peripheral arterial thromboses, having been noted in up to 64% of patients. Leaflet thickening is the most frequent abnormality, having been noted in 10-24% of patients. Vegetationlike masses occur in 6-10% of patients.

Sex- and race-related demographics

Systemic lupus erythematosus and primary antiphospholipid syndrome occur 5-9 times more often in women; therefore, patients with cardiac valvular lesions are generally young women. In the United States, statistics show systemic lupus erythematosus to be more prevalent in black and Hispanic women.

PreviousNextPrognosis

Longitudinal data of valvular abnormalities are limited. Two series reported no progression of mild or moderate regurgitation to severe regurgitation over a 2- to 3-year period and reported only isolated cases of mildly progressive stenosis.

Prognosis is probably dependent on the underlying disease activity of systemic lupus erythematosus and associated renal and myocardial dysfunction.

Morbidity and mortality

Mortality is undefined. Patients with systemic lupus erythematosus have an increased mortality rate compared with the general population. Cardiovascular mortality is ranked third in these patients but includes a wide spectrum of pathology.

The combined rate of heart failure, valve replacement, thromboembolism, and secondary infective endocarditis has been reported to be as high as 22% in lupus patients with valvular disease, compared with 8% of patients without valvular disease. Most patients do not have clinically significant valvular dysfunction.

Regurgitation is noted on echocardiographic images in 25-61% of patients with lupus and in 10-24% of patients with primary antiphospholipid syndrome. The prevalence of moderate or severe regurgitation has been reported in 0-12% (severe in 3%, moderate in 9%) of patients with antiphospholipid syndrome and in 4-26% of patients with lupus. The reported need for valve replacement varies from 1-8% of cases.

The occurrence of clinically significant embolic phenomena is thought to be low. Although stroke rates are higher in patients with lupus and antiphospholipid syndrome, multifactorial etiologies for neurologic events are often present, making the specific contribution of valvular abnormalities difficult to determine.

The likely prevalence of secondary infective endocarditis is low, but it has not been widely reported. Potential contributing factors to infective endocarditis are systemic lupus erythematosus, medications prescribed for lupus, and underlying valvular abnormalities.

PreviousNextPatient Education

Give patients on anticoagulation written information regarding potential drug interactions, dietary advice, the need for regular monitoring of the international normalized ratio, and the warning symptoms of hemorrhage. Referral to an anticoagulation clinic may be appropriate.

Educate patients about the need for antibiotic prophylaxis in case of lacerations or in instances of dental work or other procedures.

Information regarding systemic lupus erythematosus is available through the following Web sites:

Arthritis FoundationLupus Foundation of AmericaNational Institutes of Health

For patient education information, see Lupus (Systemic Lupus Erythematosus).

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