Libman-Sacks endocarditis

Libman-Sacks endocarditis
ICD-10	I39, M32.1
ICD-9	710.0
DiseasesDB	29254
eMedicine	med/1295
MeSH	D008180

Template:Search infobox Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sara Mohsin, M.D.[2]

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

Overview

Libman-Sacks endocarditis is a form of nonbacterial endocarditis that is seen in systemic lupus erythematosus. It is the most common cardiac manifestation of lupus. It can be associated with the development of aortic insufficiency. LSE is a sterile and verrucous vegetation around the heart valves. LSE is usually associated with autoimmune diseases especially SLE and APS. LSE mostly affects mitral and aortic heart valves, which may cause thromboembolic cerebrovascular events, valvular regurgitation, and increased risk of infective endocarditis. Although APS and valvular involvements are not rare, and have mostly low clinical significance, they could cause severe complications. Secondary APS compared to primary APS also have higher rate of cardiac involvement, mostly due to the autoimmune causes related to the SLE. Here, we report three cases of LSE in patients with SLE and secondary APS diagnosed after presenting with neurological manifestations. Libman-Sacks (LS) endocarditis is a form of nonbacterial thrombotic endocarditis (NBTE). It is a term which is used for sterile vegetations on the cardiac valves. These sterile vegetations are often associated with malignancies, systemic lupus erythematosus (SLE), and antiphospholipid antibody syndrome (APS). Other terms used to describe these vegetations include marantic and verrucous endocarditis. The first time this form of endocarditis was described was in 1924 by Emanuel Libman and Benjamin Sacks.[1] Libman-Sacks endocarditis most commonly affects the mitral and aortic valves, but other valves may also be involved.[1] LS endocarditis can be complicated by embolic cerebrovascular disease, peripheral arterial embolism, and by superimposed infective endocarditis. It is also associated with increased mortality.[2] Therefore, early recognition of LS endocarditis and appropriate treatment are of paramount importance in preventing complications.

Historical Perspective

• 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 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
• In 1985, the association between Libman-Sacks endocarditis and antiphospholipid antibody syndrome was noted for the first time.

Pathophysiology

• The vegetations are formed from strands of fibrin, neutrophils, lymphocytes, and histiocytes.
• The mitral valve is typically affected, and the vegetations occur on the ventricular and atrial surface of the valve.
• Libman-Sacks lesions rarely produce significant valve dysfunction and the lesions only rarely embolize.

Pathology

• The pathology is the same as nonbacterial thrombotic endocarditis except focal necrosis (hematoxylin bodies) can be found only 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
• 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 most often found postmortem with rates in autopsy series ranging from 0.9% to 1.6%.

• It has been reported in every age group, most commonly affecting patients between the fourth and eighth decades of life with no sex predilection.
• Patients with advanced malignancy and those with systemic lupus erythematosus are the most common populations affected by NBTE.
• One autopsy series reported that, compared to the general population, patients with underlying malignancy have a higher rate of NBTE (1.25% versus 0.2%).
• When compared to other malignancies, higher rates were reported in those with adenocarcinoma (eg, lung, colon, ovary, biliary and prostate) (2.7% versus 0.47%) with the highest rates observed in patients with mucin-secreting and pancreatic adenocarcinoma (10%).
• In patients with systemic lupus erythematosus, observational studies using transthoracic echocardiography have reported prevalence rates of 6% to 11%, with higher rates (43%) observed when the more sensitive transesophageal echocardiography was performed.

Natural History, Complications and Prognosis

Complications

• Systemic emboli may occur but they are probably not very common.
• The risk is much higher with mitral stenosis and subsequent atrial fibrillation.
• When strokes occur it is difficult to know if they were due to systemic emboli or the underlying pathology of SLE or APS.
• Valvular disease can lead to heart failure.
• Maternal SLE with anti-Ro/SS-A (Sjögren's syndrome antigen A) autoantibodies is associated with congenital heart block in the baby in about 1 or 2%. It is usually complete but can be 1st or 2nd degree.
• The rate of recurrence is around 16%.
• Fluorinated steroids that do not cross the placenta may be beneficial.

Prognosis

• All the SLE patients have a shorter life span.
• The major cause of mortality in SLE patients is occurrence of cardiovascular events 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

History and symptoms

• Most patients with Libman-Sacks endocarditis are asymptomatic.
• If valves are severely affected there may be features of the valve disease.
• Mitral valve disease is more common than aortic valve disease.
• Regurgitation is more frequent than stenosis and involvement of the tricuspid or pulmonary valves is unusual.
• Systemic embolism may occur with effects depending upon the destination of the emboli but brain and kidney are likely victims.
• Emboli can cause blockage of the peripheral circulation.
• The vegetations of Libman-Sacks endocarditis are sterile but secondary infective endocarditis can occur.
• There may or may not be typical features of SLE with the characteristic butterfly rash, fever and arthritis or features of APS, including recurrent miscarriage.

Physical Examination

• A patient of Libman-Sacks endocarditis can present with any of the following signs and symptoms:
  • Left ventricular hypertrophy causing displacement of the apex beat
  • Congestive heart failure physical exam findings
  • IE findings
  • Mitral valve disease findings
  • Aortic valve disease findings

Laboratory findings

• Blood culture is important to exclude infective endocarditis (IE), which may coexist.
• Investigations for SLE, including antiphospholipid antibodies and other autoantibodies. False-positive serology in the form of VDRL is common in SLE and anticardiolipin antibodies increase the risk of cardiac abnormalities.
• FBC may show raised neutrophils and some anaemia.

Imaging findings

Echocardiography

• Echocardiography should be employed, although not all lesions will be detected.
• Results with transoesophageal echo are superior but it is an invasive procedure.

Chest X-Ray

• CXR may show cardiomegaly and pulmonary congestion if the disease is severe.
• Calcification of lesions is uncommon.

Other Diagnostic studies

Cardiac Catheterization

• If valvular disease seems severe then cardiac catheterization may be required with a view to valve replacement.

Treatment

• There is no specific treatment for Libman-Sacks endocarditis.
• Steroids and immunosuppressive agents are useful in the treatment of the underlying disease but there is some controversy about their role in the pathogenesis of vegetations:
  • Compared with reports of postmortems on patients before the advent of steroids, those that have been treated have smaller and fewer lesions, mostly on one valve and usually confined to the left side.
  • Hypertension was 5 times as common and congestive heart failure was 8 times as common as in the days before corticosteroids. The steroids may be directly responsible for hypertension and heart failure. This paper was from 1975 and it is possible that better control of hypertension and heart failure may offset these problems today.
  • Expert opinion seems to conclude that steroids are detrimental to Libman-Sacks endocarditis although some praise them. The situation is far from certain.
• Advice for procedures creating a risk of infective endocarditis can be found in the separate record Prevention of Endocarditis.
• If there are systemic emboli then anticoagulation with warfarin is beneficial but the possible role of aspirin has not been adequately investigated. If there is evidence of 1 cerebrovascular event, anticoagulation is advised.
• In serious valve disease it may be necessary to replace valves. Mechanical valves may be more susceptible to thromboemboli but it is uncertain if bioprosthetic valves are at risk of the disease. The operative mortality of mitral valve replacement in this condition may be as high as 25%.

Differential Diagnosis

Libman-Sacks endocarditis should be differentiated from other diseases presenting with fever, chest pain and anorexia. The differentials include the following:

• Thrombotic nonbacterial endocarditis/Marantic endocarditis
• Vasculitis
• Temporal arteritis
• Myocardial abscess
• Connective tissue disease
• Fever of unknown origin (FUO)
• Intra-abdominal infections
• Septic pulmonary infarction

Diseases	Diagnostic tests			Physical Examination			Symptoms							Past medical history	Other Findings
	CT scan and MRI	EKG	Chest X-ray	Tachypnea	Tachycardia	Fever	Chest Pain	Hemoptysis	Dyspnea on Exertion	Wheezing	Chest Tenderness	Nasalopharyngeal Ulceration	Carotid Bruit
Pulmonary embolism	On CT angiography: Intra-luminal filling defect On MRI: Narrowing of involved vessel No contrast seen distal to obstruction Polo-mint sign (partial filling defect surrounded by contrast)	S1Q3T3 pattern representing acute right heart strain	Fleischner sign (enlarged pulmonary artery), Hampton hump, Westermark's sign	✔	✔	✔ (Low grade)	✔	✔ (In case of massive PE)	✔	-	-	-	-	Hypercoagulating conditions (Factor V Leiden, thrombophilia, deep vein thrombosis, immobilization, malignancy, pregnancy)	May be associated with metabolic alkalosis and syncope
Infective Endocarditis		Goldberg's criteria may aid in diagnosis of left ventricular dysfunction: (High specificity) SV1 or SV2 + RV5 or RV6 ≥3.5 mV Total QRS amplitude in each of the limb leads ≤0.8 mV R/S ratio <1 in lead V4		✔	✔	✔	-	-	✔	-	-	-	-	Previous myocardial infarction Hypertension (systemic and pulmonary) Cardiac arrythmias Viral infections (myocarditis) Congenital heart defects	Right heart failure associated with: Hepatomegaly Positive hepato-jugular reflex Increased jugular venous pressure Peripheral edema Left heart failure associated with: Pulmonary edema Eventual right heart failure
Non-Bacterial Thrombotic Endocarditis		ST elevation PR depression		✔	✔	✔ (Low grade)	✔ (Relieved by sitting up and leaning forward)	-	✔	-	-	-	-	Infections: Viral (Coxsackie virus, Herpes virus, Mumps virus, HIV) Bacteria (Mycobacterium tuberculosis-common in developing countries) Fungal (Histoplasmosis) Idiopathic in a large number of cases Autoimmune Uremia Malignancy Previous myocardial infarction	May be clinically classified into: Acute (< 6 weeks) Sub-acute (6 weeks - 6 months) Chronic (> 6 months)
Libman Sack Endocarditis		Prolonged PR interval Transient T wave inversions		✔	✔	✔	✔	-	✔	✔	-	-	-	Ill-contact Travelling Smoking Diabetic Recent hospitalization Chronic obstructive pulmonary disease	Requires sputum stain and culture for diagnosis Empiric management usually started before culture results
Vasculitis	On CT scan: (Takayasu arteritis) Vessel wall thickening Luminal narrowing of pulmonary artery Masses or nodules (ANCA-associated granulomatous vasculitis) On MRI: Homogeneous, circumferential vessel wall swelling	Right or left bundle-branch block (Churg-Strauss syndrome) Atrial fibrillation (Churg-Strauss syndrome) Non-specific ST segment and T wave changes	Nodules Cavitation	✔	✔	✔	✔	✔	✔	-	✔	✔	✔	Takayasu arteritis usually found in persons aged 4-60 years with a mean of 30 Giant-cell arteritis usually occurrs in persons aged > 60 years Churg-Strauss syndrome may present with asthma, sinusitis, transient pulmonary infiltrates and neuropathy alongwith cardiac involvement Granulomatous vasculitides may present with nephritis and upper airway (nasopharyngeal) destruction
Fever of unknown origin (FUO)		Multifocal atrial tachycardia (atleast 3 distinct P wave morphologies)		✔	✔	-	-	-	✔	✔	-	-	-	Smoking Alpha-1 antitrypsin deficiency Increased sputum production (chronic bronchitis) Cough	Alpha 1 antitrypsin deficiency may be associated with hepatomegaly

References

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