Libman-Sacks endocarditis
Synonyms and keywords:: Nonbacterial thrombotic endocarditis (NBTE), Marantic endocarditis, Verrucous endocarditis

# Overview
Libman-Sacks endocarditis (LSE) is a form of nonbacterial thrombotic endocarditis (NBTE) that is considered to be the most common cardiac manifestation seen in patients with systemic lupus erythematosus. LSE is a term used for sterile and verrucous vegetations around the heart valves mostly affecting the mitral and aortic heart valves but other valves may also be involved. Valvular involvement in LSE may lead to valvular regurgitation, aortic insufficiency, thromboembolic cerebrovascular events, and increased risk of infective endocarditis. It is also usually associated with the other autoimmune diseases such as antiphospholipid syndrome (APS) and some malignancies. Secondary APS has a higher rate of cardiac involvement as compared to primary APS, mostly due to the autoimmune causes related to the SLE. LSE can be complicated by embolic cerebrovascular disease, superimposed infective endocarditis, and peripheral arterial embolism. It is also associated with increased mortality, hence, early recognition of LSE and appropriate treatment are of significant importance in preventing any further complications.

# Historical Perspective
- In 1888, Zeigler was the first one to describe NBTE, and called it "thromboendocarditis" at that time.
- In 1924, the two American physicians Emanuel Libman, and Benjamin Sacks, working at Mount Sinai Hospital, New York, described the Libman-Sacks endocarditis for the first time, hence, it's named after them. They first presented the complete clinical picture of it with or without skin lesions and described it as unusual non-bacterial endocarditis with verrucous vegetations adherent to the endocardium.
- In 1936, Gross and Friedberg finally coined the term "nonbacterial thrombotic endocarditis" (NBTE) for marantic/verrucous endocarditis.
- In 1983, Graham Hughes described the antiphospholipid antibody syndrome for the first time while working as a rheumatologist at St Thomas Hospital. He named it anticardiolipin syndrome (also known as Hughes syndrome named after him) and described it has the following three characteristics:
Venous and/or arterial thrombosis
Recurrent pregnancy loss
Presence of antiphospholipid antibodies
- Venous and/or arterial thrombosis
- Recurrent pregnancy loss
- Presence of antiphospholipid antibodies
- In 1985, the association between Libman-Sacks endocarditis and antiphospholipid antibody syndrome was noted for the first time.
- In 1989, four groups highlighted a probable role of antiphospholipid antibodies in the pathogenesis of valvular heart disease in SLE patients.

# Pathophysiology

## Pathology
- The pathology of Libman-Sacks endocarditis is the same as nonbacterial thrombotic endocarditis except that focal necrosis (seen in the form of hematoxylin bodies) is only found in Libman-Sacks endocarditis.
- Just like NBTE, Libman-Sacks endocarditis develops due to the endothelial damage and subsequent exposure of the sub-endothelial connective tissue to the circulating platelets.
- The factors involved in the pathogenesis can be divided into the ones initiating the Libman-Sacks endocarditis and the subsequent development of vegetations.
- The vegetations in Libman-Sacks endocarditis are formed from the strands consisting of the following four components:
Fibrin
Neutrophils
Lymphocytes
Histiocytes
- Fibrin
- Neutrophils
- Lymphocytes
- Histiocytes
- Most commonly affected valve is the mitral valve with the vegetations involving the ventricular and atrial surface of the valve.
- The lesions of Libman-Sacks endocarditis rarely lead to any significant valvular dysfunction and they only rarely embolize.

## Gross pathology
- Vegetations in Libman-Sacks endocarditis have the following typical features:
Small
Friable
White or tan masses
< 1 cm in diameter
Irregular
Broad based
Usually involve the lines along the valve closure on leaflets (which may be normal or previously damaged)
Vary from tiny lesions to large, exuberant masses
- Small
- Friable
- White or tan masses
- < 1 cm in diameter
- Irregular
- Broad based
- Usually involve the lines along the valve closure on leaflets (which may be normal or previously damaged)
- Vary from tiny lesions to large, exuberant masses

## Microscopic Pathology
- Vegetations in Libman-Sacks endocarditis consist of degenerating platelets interwoven with the fibrin strands and form a bland, featureless eosinophilic mass except for a few trapped leukocytes.
- Following three stages have been described in the evolution of vegetations in Libman-Sacks endocarditis:

# Epidemiology and Demographics
- Approximately 1 out of 10 SLE patients have vegetations associated with Libman-Sacks endocarditis. Presence of these vegetations is indicative of the association with the following:
Lupus duration
Disease activity
Anticardiolipin antibodies
APS manifestations
- Lupus duration
- Disease activity
- Anticardiolipin antibodies
- APS manifestations
- There's a variable incidence of positive findings on transthoracic echocardiography.
- Higher incidence of detection of positive findings is shown with transesophageal echocardiography and especially with higher frequency with positive antiphospholipid antibodies.
- Thickening of the leaflets is more common as compared to finding vegetations.
- Positive findings on echocardiography are found in approximately one-third of the patients with antiphospholipid antibody syndrome.
- These positive findings are five to nine times more frequently found in women than men.
- Libman-sacks endocarditis typically occurs in young women, however, children can be rarely involved.
- Nonbacterial thrombotic endocarditis (NBTE) is a rare condition which is most often found during 0.9% to 1.6% of the postmortem studies.
- NBTE affects every age group but most commonly involves patients between the fourth and eighth decades of life with no sex predilection.
- NBTE most commonly affects patients with systemic lupus erythematosus and advanced malignancy.
- According to one autopsy study, patients with underlying malignancy have a higher rate (1.25%) of NBTE as compared to general population (0.2%).
- NBTE is found at higher rates in patients with adenocarcinoma (e.g., lung, colon, ovary, biliary and prostate) (2.7%) as compared to other malignancies (0.47%), with the highest rates observed in patients with mucin-secreting and pancreatic adenocarcinoma (10%).
- Observational studies in patients with systemic lupus erythematosus have reported 6% to 11% prevalence rates with transthoracic echocardiography, with higher rates (43%) observed with more sensitive transesophageal echocardiography.

# Risk Factors
- Following table shows important risk factors for the development of Libman-Sacks endocarditis:

# Natural History, Complications and Prognosis

## Complications
- Systemic emboli may occur in Libman-Sacks endocarditis but not very commonly with the risk being much higher with mitral stenosis and subsequent atrial fibrillation.
- It is difficult to predict the underlying etiology in case of a stroke occurrence in LSE, whether it is due to systemic emboli or the underlying pathology of SLE or APS.
- Valvular disease in LSE can lead to the heart failure.
- Double-valve Libman-Sacks endocarditis involving both mitral and aortic valves can lead to ventricular fibrillation and cardiac arrest.
- There's 1% to 2% chance of congenital heart block (usually complete,or 1st or 2nd degree) in a baby of mother with SLE associated with anti-Ro/SS-A (Sjogren's syndrome antigen A) autoantibodies with a 16% recurrence rate. Fluorinated steroids that do not cross the placenta may be beneficial in preventing the congenital heart block.

## Prognosis
- All of the SLE patients have got a shorter life span.
- The occurrence of cardiovascular events is the major cause of mortality in SLE patients as SLE is a risk factor for premature & accelerated coronary atherosclerosis and CAD (coronary artery disease) due to the following associated factors:
Hypertension
Hyperlipidemia
Chronic inflammation
Chronic glucocorticoids use
- Hypertension
- Hyperlipidemia
- Chronic inflammation
- Chronic glucocorticoids use

# Diagnosis
- Diagnosis of Libman-Sacks endocarditis requires a high degree of clinical suspicion especially in patients who don't improve clinically after being treated for infective endocarditis.
- Mckay and Wahler proposed the following triad for the diagnosis of NBTE:

# History and Symptoms
- Mostly patients with Libman-Sacks endocarditis are asymptomatic.
- There may be the features of valvular disease if valves are severely affected with the mitral valve disease being more common than the aortic valve disease.
- Valvular regurgitation is more frequent than the valvular stenosis.
- Unusually, the tricuspid or pulmonary valves are involved.
- Systemic embolism may also occur with the effects depending upon the destination of the emboli with the brain and kidneys being more likely involved.
- Emboli can also lead to the blockage of peripheral circulation.
- The vegetations in Libman-Sacks endocarditis are mostly sterile but secondary infective endocarditis can also occur.
- There may or may not be the typical SLE features with the characteristic butterfly rash, fever, and arthritis or the APS features, including recurrent miscarriages.

# Physical Examination
- A patient of Libman-Sacks endocarditis can present with any of the signs and symptoms shown in the following table:

# Laboratory Findings

# Imaging Findings

# Other Diagnostic Studies

## Cardiac Catheterization
- In case of severe valvular disease, cardiac catheterization may be required with a view to valve replacement.

# Treatment
- There is no specific treatment for Libman-Sacks endocarditis.
- Treatment of LSE is quite difficult with the main focus being on the correction of the underlying cause.

# Differentiating Libman-Sacks Endocarditis from other Diseases
Libman-Sacks endocarditis should be differentiated from other diseases presenting with fever, chest pain and anorexia. The differentials include the following:
- Nonbacterial thrombotic endocarditis (Marantic endocarditis)
- Vasculitis
- Temporal arteritis
- Myocardial abscess
- Connective tissue disease
- Fever of unknown origin (FUO)
- Intra-abdominal infections
- Septic pulmonary infarction