Mitral Valve Endocarditis

Mitral valve endocarditis is infection of a native or prosthetic mitral valve. It destroys leaflets and chordae, causes acute or progressive mitral regurgitation, and carries the highest embolic risk of any valve site.

Infective endocarditis affects about 3 to 10 people in every 100,000 each year. The mitral valve is involved in roughly 35 to 45% of left sided native cases, often together with the aortic valve. In hospital mortality is about 15 to 25%, and higher with prosthetic valves, Staphylococcus aureus, heart failure and perivalvular abscess.

Predisposing conditions are mitral valve prolapse with regurgitation, degenerative disease and mitral annular calcification, rheumatic heart disease, prosthetic valves and repair rings, previous endocarditis, congenital disease, injection drug use, indwelling lines, haemodialysis and poor dentition.

Organisms are Staphylococcus aureus (the commonest), viridans streptococci, Streptococcus gallolyticus, enterococci, coagulase negative staphylococci (early prosthetic), HACEK organisms and culture negative causes (Coxiella burnetii, Bartonella, Brucella). Brucella and Q fever are regionally important.

Pathophysiology.

Turbulent flow injures the atrial surface of the leaflets, where vegetations form along the line of closure. An aortic regurgitant jet can seed the anterior mitral leaflet and cause a secondary kissing lesion.

Infection perforates leaflets and ruptures chordae, giving a flail segment and acute severe regurgitation. A normal sized, non-compliant left atrium transmits the volume load directly to the pulmonary veins, so pulmonary oedema develops quickly.

Extension into the annulus forms abscess, pseudoaneurysm or fistula. Mitral annular calcification favours caseous necrosis and abscess in older adults.

Embolic risk is highest with mobile vegetations of 10 mm or more on the anterior leaflet. Stroke complicates 15 to 30% of cases, and the risk falls steeply within 1 to 2 weeks of effective therapy.

Immune complex phenomena (glomerulonephritis, Osler nodes, Roth spots) appear with longer illness.

Fever (often absent in older adults), malaise, weight loss, night sweats and breathlessness. A new or changing apical holosystolic murmur radiating to the axilla may be soft or absent when regurgitation is acute and severe. Pulmonary oedema, hypotension and a third heart sound indicate acute severe regurgitation.

Embolic events include stroke, splenic and renal infarcts, limb ischaemia and mycotic aneurysm. Peripheral signs are splinter haemorrhages, Janeway lesions, Osler nodes, Roth spots, petechiae and splenomegaly.

Prosthetic mitral endocarditis presents early (under 12 months) or late, and may show valve dehiscence with a new paravalvular leak, obstruction or conduction block.

• Blood cultures: at least 3 sets from separate venepunctures, at least 1 hour apart, taken before antibiotics, with 8 to 10 mL in each aerobic and anaerobic bottle. Repeat every 48 to 72 hours once treatment starts until negative.
• Culture negative disease: serology for Coxiella burnetii (phase I IgG titre of 1:800 or more), Bartonella, Brucella and Legionella; PCR and 16S sequencing of valve tissue; early microbiology advice.
• Echocardiography: transthoracic first, then transoesophageal in all suspected cases and in every prosthetic valve. Look for vegetation (size and mobility), leaflet perforation, chordal rupture, flail segment, annular abscess, pseudoaneurysm of the mitral aortic intervalvular fibrosa, fistula, prosthetic dehiscence, and quantify regurgitation. Repeat in 5 to 7 days if negative and suspicion remains.
• Cardiac CT angiography for abscess and pseudoaneurysm. Fluorodeoxyglucose PET-CT for prosthetic valves with doubtful echocardiography. Brain MRI or CT and body imaging for emboli (these can change the surgical decision).
• Daily ECG for PR interval; inflammatory markers, creatinine, urine dipstick, full blood count, liver tests.
• Modified Duke criteria: definite is 2 major, or 1 major and 3 minor, or 5 minor criteria. Major: typical organisms in 2 separate blood cultures or persistent bacteraemia, and endocardial involvement (vegetation, abscess, new dehiscence or new regurgitation). Minor: predisposition, fever of 38.0 degrees Celsius or more, vascular phenomena, immunological phenomena, and microbiological evidence not meeting a major criterion.

Differential diagnosis.

• Non-infective endocarditis (Libman-Sacks, marantic) and antiphospholipid syndrome.
• Papillary fibroelastoma, atrial myxoma and degenerative chordal rupture.
• Rheumatic carditis and acute ischaemic mitral regurgitation.
• Sepsis from another source with incidental valve disease, lymphoma and tuberculosis.

Organisation. Treat in a unit with an endocarditis team (cardiology, infectious diseases, cardiac surgery, microbiology, and neurology when emboli are present). Take cultures before antibiotics. In stable subacute disease, wait 24 to 48 hours for cultures. Start empirical therapy at once when unwell.

Empirical therapy (after cultures).

• Native valve, community onset: ampicillin 2 g intravenously every 4 hours, flucloxacillin 2 g intravenously every 4 hours, and gentamicin 3 mg/kg intravenously once daily. With severe penicillin allergy or MRSA risk: vancomycin 25 mg/kg loading dose, then 30 to 60 mg/kg daily in 2 to 3 doses (trough 15 to 20 mg/L), with gentamicin 3 mg/kg once daily.
• Early prosthetic valve (under 12 months) or health care related: vancomycin 25 mg/kg intravenous loading dose, then 30 to 60 mg/kg daily in 2 to 3 doses (trough 15 to 20 mg/L), gentamicin 3 mg/kg once daily, and rifampicin 900 to 1200 mg daily in 2 to 3 doses, starting rifampicin 3 to 5 days later once bacteraemia is controlled. Late prosthetic valve (12 months or more): ampicillin 2 g and flucloxacillin 2 g intravenously every 4 hours with gentamicin 3 mg/kg intravenously once daily.

Directed therapy (duration counted from the first negative blood culture, or from surgery if valve cultures are positive):

• Penicillin susceptible streptococci (MIC 0.125 mg/L or under): benzylpenicillin 12 to 18 million units daily in 4 to 6 doses, or amoxicillin 100 to 200 mg/kg daily in 4 to 6 doses, or ceftriaxone 2 g once daily, for 4 weeks (6 weeks for prosthetic valves). Uncomplicated native disease may be treated for 2 weeks with gentamicin 3 mg/kg once daily. Allergy: vancomycin 25 mg/kg intravenous loading dose, then 30 to 60 mg/kg daily in 2 to 3 doses (trough 15 to 20 mg/L), for the same duration.
• Relatively resistant streptococci (MIC over 0.125 to 2 mg/L): the same beta lactam for 4 weeks (6 weeks prosthetic) with gentamicin 3 mg/kg once daily for 2 weeks.
• Methicillin susceptible Staphylococcus aureus, native valve: flucloxacillin 2 g intravenously every 4 hours (12 g daily), or cefazolin 2 g every 8 hours, for 6 weeks in left sided disease. Prosthetic valve: flucloxacillin plus rifampicin 900 to 1200 mg daily in 2 to 3 doses for 6 weeks or more, with gentamicin 3 mg/kg once daily for the first 2 weeks.
• MRSA: vancomycin 25 mg/kg intravenous loading dose, then 30 to 60 mg/kg daily in 2 to 3 doses (trough 15 to 20 mg/L), or daptomycin 10 mg/kg intravenously once daily (every 48 hours when creatinine clearance is under 30 mL/min), for 6 weeks; add rifampicin and gentamicin for prosthetic valves.
• Enterococcus faecalis: ampicillin 2 g intravenously every 4 hours plus ceftriaxone 2 g every 12 hours for 6 weeks (avoids aminoglycoside nephrotoxicity). Alternative: ampicillin for 6 weeks with gentamicin 3 mg/kg daily in 2 to 3 doses for the first 2 weeks only, after high level resistance testing.
• HACEK organisms: ceftriaxone 2 g once daily for 4 weeks (6 weeks prosthetic).
• Coxiella burnetii: doxycycline 200 mg daily with hydroxychloroquine 200 mg three times daily (plasma level about 1 mg/L) for at least 18 months for native and 24 months for prosthetic valves.
• Bartonella: ceftriaxone 2 g daily or ampicillin 12 g daily for 6 weeks, with gentamicin 3 mg/kg once daily for 3 weeks.
• Brucella: doxycycline 200 mg daily, rifampicin 300 to 600 mg daily and co-trimoxazole 960 mg twice daily for at least 3 to 6 months, with surgery for valve destruction.
• Fungal: surgery plus liposomal amphotericin B 3 to 5 mg/kg daily with or without flucytosine 25 mg/kg four times daily, then long term azole suppression.
• Drug monitoring: gentamicin trough under 1 mg/L and creatinine two to three times weekly; vancomycin trough; creatine kinase weekly on daptomycin; full blood count weekly on prolonged beta lactam therapy; liver tests on rifampicin, with attention to interactions with warfarin, direct oral anticoagulants, hormonal contraceptives and antiretrovirals. Adjust beta lactam, vancomycin, gentamicin and daptomycin doses to creatinine clearance with pharmacy support.
• Partial oral switch after at least 10 days of intravenous therapy in a stable patient without abscess is an option in specialist hands.

Acute severe regurgitation with pulmonary oedema (before surgery). Sit upright, give oxygen to keep SpO2 over 94%, furosemide 40 to 80 mg intravenously, and glyceryl trinitrate 10 to 20 microgram/min intravenously, increased every 5 to 10 minutes to a maximum of 200 microgram/min while systolic blood pressure stays over 100 mmHg. Use noradrenaline 0.05 to 0.5 microgram/kg/min for hypotension. Avoid beta blockers. Do not delay surgery for stabilisation.

Surgery (during the same admission):

• Emergency (within 24 hours): refractory pulmonary oedema or cardiogenic shock from severe regurgitation or obstruction, or a fistula.
• Urgent (within 3 to 5 days): heart failure from severe regurgitation, abscess or pseudoaneurysm, persistent fever or positive cultures after 7 to 10 days of appropriate antibiotics, fungal or multiresistant organisms, and early prosthetic valve endocarditis.
• Embolism prevention: vegetation of 10 mm or more with a recent embolic event despite treatment, vegetation of 10 mm or more with severe valve disease and low operative risk, or an isolated vegetation over 30 mm.
• Repair (leaflet resection, patch, neochordae or ring) is preferred over replacement whenever the leaflets can be saved, because it avoids prosthetic material in an infected field. Replacement with chordal preservation is used when destruction is extensive.
• Timing after stroke: after an ischaemic stroke without haemorrhage and without coma, proceed without delay. After intracranial haemorrhage, delay surgery for 4 weeks or more when feasible.

Complications.

• Embolic stroke: alteplase is avoided because of haemorrhage risk; consider mechanical thrombectomy.
• Anticoagulation: do not start for embolism prevention in native valve disease. Continue for mechanical valves unless there is intracranial haemorrhage, then switch to unfractionated heparin by aPTT and discuss timing.
• Mycotic aneurysm: vascular imaging and neurosurgical or endovascular treatment before valve surgery.

Prevention of recurrence. Dental review and oral hygiene. Prophylaxis for dental procedures involving gingival manipulation in patients with prosthetic valves, previous endocarditis or unrepaired cyanotic congenital disease: amoxicillin 2 g orally as a single dose 30 to 60 minutes before the procedure; with penicillin allergy, azithromycin 500 mg or doxycycline 100 mg. Patients on regular benzathine benzylpenicillin should receive a different class for dental prophylaxis. Treat injection drug use with addiction services.

Monitoring. Temperature, C-reactive protein and creatinine at least twice weekly; blood cultures at 48 to 72 hours until negative; daily ECG for PR interval; echocardiography at completion of treatment and at 1, 3, 6 and 12 months. Outpatient parenteral therapy only after the first 2 weeks, once complications are controlled.

Referral and escalation. All patients need the endocarditis team. Urgent surgical review for heart failure, abscess, a vegetation of 10 mm or more, embolism or persistent bacteraemia. Immediate intensive care for shock, acute pulmonary oedema or a new neurological deficit.

Special groups.

• Pregnancy: use penicillins and cephalosporins; avoid aminoglycosides, tetracyclines and fluoroquinolones where possible; surgery on bypass carries high foetal loss and needs a specialist obstetric centre.
• Injection drug use: surgery when indicated, together with addiction treatment and an adherence plan.
• Older adults and kidney impairment: prefer the dual beta lactam regimen for enterococci, avoid aminoglycosides where possible, and dose by creatinine clearance.
• Region specific: rheumatic heart disease, brucellosis and Q fever account for a large share of culture negative cases, and limited access to cardiac surgery should prompt early transfer.