Libman-Sacks Endocarditis

Libman-Sacks endocarditis is a sterile, verrucous valve lesion that occurs in systemic lupus erythematosus and in antiphospholipid syndrome. It consists of fibrin, platelets, immune complexes and inflammatory cells.

Transoesophageal echocardiography finds valve lesions in about 10 to 40% of patients with lupus, and clinically important valve disease in a smaller share, about 3 to 5%. Prevalence is higher with antiphospholipid antibodies, longer disease and active disease.

Lesions occur on the atrial surface of the mitral valve (near the leaflet base), the ventricular surface of the aortic valve and on either surface in other places. Healing causes thickening, calcification and regurgitation. Stenosis is rare.

The lesions raise the risk of stroke and embolism, and are a site for infective endocarditis.

Pathophysiology. Immune complex deposition and antiphospholipid antibody mediated endothelial activation lead to fibrin and platelet deposition on valve surfaces. Steroid therapy may promote fibrosis and scarring.

• Usually asymptomatic. A regurgitant murmur (mitral or aortic) may be found.
• Embolic events: stroke, transient ischaemic attack, peripheral emboli, and retinal artery occlusion.
• Heart failure from severe regurgitation, which is uncommon.
• Features of lupus (rash, arthritis, serositis, nephritis, cytopenias) or antiphospholipid syndrome (thrombosis, pregnancy loss, livedo).
• Fever, new murmur and embolic stigmata suggest superimposed infection.

Red flags.

• Stroke or other embolism in a patient with lupus or antiphospholipid antibodies
• Fever or positive blood cultures (superimposed infective endocarditis)
• Heart failure or severe regurgitation
• Vegetation over 10 mm or enlarging on repeat imaging
• Triple positive antiphospholipid antibodies

• Echocardiography. Transthoracic first, then transoesophageal. Irregular sessile vegetations of 1 to 10 mm (usually 1 to 4 mm) on the leaflet base and atrial or ventricular surface, valve thickening, regurgitation, and rarely stenosis.
• Blood cultures. Three sets before antibiotics to exclude infective endocarditis.
• Lupus and antiphospholipid testing. Antinuclear antibody, anti-double-stranded DNA, complement (C3, C4), full blood count, creatinine and urinalysis. Lupus anticoagulant, anticardiolipin and anti-beta-2 glycoprotein I antibodies, repeated at 12 weeks.
• Brain MRI after any neurological event. Cardiac MRI or CT when echocardiographic windows are poor.
• Inflammatory markers: ESR and CRP (CRP is usually modest in lupus, so a high CRP raises the question of infection).

Differential diagnosis.

• Infective endocarditis
• Nonbacterial thrombotic endocarditis in malignancy
• Rheumatic valve disease
• Papillary fibroelastoma, Lambl excrescences and myxoma
• Degenerative valve calcification and prolapse
• Valvulitis of rheumatoid disease and other autoimmune conditions
• Thrombus on a prosthetic valve

Treat the lupus.

• Hydroxychloroquine 200 to 400 mg orally once daily, maximum 5 mg/kg actual body weight daily. Reduce at creatinine clearance under 30 mL/min. Retinal screening at baseline and yearly from 5 years (earlier with kidney disease or high dose). Monitor QTc when given with other QT-prolonging drugs.
• Prednisolone 0.5 to 1 mg/kg orally once daily (maximum 60 mg) for active disease, tapered to 5 mg daily or less. Add calcium, vitamin D and gastric protection, and monitor glucose and blood pressure.
• Steroid sparing drugs for active disease: azathioprine 1 mg/kg orally once daily, increased to a maximum of 2 mg/kg daily (check TPMT or NUDT15 first, full blood count weekly for 4 weeks then monthly, reduce to a quarter of the dose with allopurinol), or mycophenolate mofetil 1 g orally twice daily (maximum 3 g daily, contraindicated in pregnancy, full blood count monthly).

Antithrombotic therapy.

• Embolic event, antiphospholipid syndrome or a mobile vegetation: unfractionated heparin 80 units/kg intravenous bolus, then 18 units/kg/h (anti-Xa 0.3 to 0.7 IU/mL or aPTT ratio 1.5 to 2.5, platelets on days 5 to 14), then warfarin 5 mg orally once daily at the start (2 to 3 mg in older adults, liver impairment or interacting drugs), adjusted to an INR of 2.0 to 3.0, no fixed maximum, with INR every 2 to 3 days at the start, weekly until stable, then every 4 to 12 weeks. Higher intensity (INR 3.0 to 4.0) is used in some practice for recurrent arterial events, with limited evidence. Direct oral anticoagulants are avoided, particularly in triple positive disease.
• Antiphospholipid antibodies without events: aspirin 75 to 100 mg orally once daily (usual maximum 325 mg daily) in high risk profiles, with pantoprazole 40 mg for gastric protection when needed.

Valve surgery. Indicated for severe symptomatic regurgitation or stenosis, heart failure, recurrent embolism despite adequate anticoagulation, large or growing vegetations, and infective endocarditis with complications. Valve repair is preferred.

Mechanical valves need warfarin to an INR of 3.0 (2.5 to 3.5) and carry a high thrombosis risk in antiphospholipid syndrome.

Hydrocortisone 100 mg intravenously at induction, then 50 mg every 6 hours for 24 hours, in patients taking over 5 mg prednisolone daily or recently on steroids. Active lupus raises operative risk.

Heart failure and regurgitation. Furosemide 40 mg orally once daily in the morning, increased to 80 to 120 mg daily as needed (higher doses in renal impairment under specialist care), with sodium, potassium and creatinine monitoring. Ramipril 2.5 mg orally once daily, increased every 2 to 4 weeks to 10 mg once daily (maximum 10 mg daily, 5 mg daily at creatinine clearance under 30 mL/min), with potassium and creatinine 1 to 2 weeks after each change, contraindicated in pregnancy.

Endocarditis prophylaxis. Not indicated for native valve lesions alone. Advised with a prosthetic valve or previous endocarditis before high risk dental procedures: amoxicillin 2 g orally as a single dose 30 to 60 minutes before. For penicillin allergy, azithromycin 500 mg or doxycycline 100 mg orally as a single dose.

Superimposed infection. Treat with prolonged intravenous antibiotics chosen by culture and early surgery for heart failure, abscess or uncontrolled infection.

Special groups.

• Pregnancy: continue hydroxychloroquine, prednisolone and azathioprine. Use aspirin 75 to 150 mg from 12 weeks and enoxaparin 1 mg/kg subcutaneously every 12 hours with a peak anti-Xa of 0.8 to 1.2 IU/mL 4 to 6 hours after the dose for antiphospholipid syndrome with thrombosis (1 mg/kg once daily at creatinine clearance under 30 mL/min). Avoid warfarin in weeks 6 to 12, and avoid mycophenolate and methotrexate.
• Kidney impairment: limit hydroxychloroquine to 5 mg/kg actual body weight daily and reduce it at creatinine clearance under 30 mL/min, give enoxaparin 1 mg/kg subcutaneously once daily at creatinine clearance under 30 mL/min, and avoid direct oral anticoagulants in antiphospholipid syndrome.

Monitoring. Echocardiography every 6 to 12 months, and at once with fever, embolism or new symptoms. Lupus activity markers and creatinine every 3 months. INR as indicated. Retinal screening yearly after 5 years of hydroxychloroquine.

Referral and escalation. Refer to cardiology and rheumatology. Urgent for stroke, fever with bacteraemia, or heart failure.