Mechanical Prosthetic Valve Dysfunction

Mechanical prosthetic valve dysfunction is any abnormality of function of a mechanical heart valve. It includes obstruction from thrombus or pannus, regurgitation (paravalvular leak or leaflet entrapment), endocarditis, patient prosthesis mismatch, haemolysis, and rare structural failure. Acute obstruction is a surgical or medical emergency.

Obstructive thrombosis affects about 0.3 to 1.3% of left sided mechanical valves each year, and is far more frequent in the tricuspid position. The main trigger is inadequate anticoagulation. Pannus is a late event, years after implantation, and thrombus and pannus often coexist.

Risk factors for thrombosis are subtherapeutic INR, mitral or tricuspid position, atrial fibrillation, low ejection fraction, pregnancy, hypercoagulable states (including antiphospholipid syndrome), and older, more thrombogenic valve designs.

Mortality of obstructive valve thrombosis is high, particularly when it presents with obstructive shock.

Pathophysiology.

Thrombus forms on the sewing ring, hinges or leaflets when anticoagulation is inadequate. It fixes or restricts a leaflet, causing obstruction or incomplete closure, or it embolises.

Pannus is fibrous tissue that grows inward from the sewing ring. It narrows the orifice or impedes leaflet motion and is chronic and progressive.

Paravalvular leaks arise from suture dehiscence in calcified or friable annular tissue, or from endocarditis. Patient prosthesis mismatch is a valve effective orifice that is too small for body size (indexed effective orifice area under 0.85 cm2/m2 for aortic valves is moderate, and under 0.65 cm2/m2 severe). It causes persistent high gradients from implantation and is not a progressive complication.

Acute obstruction: abrupt breathlessness, pulmonary oedema, hypotension or shock, muffled or absent prosthetic closing clicks and a new murmur. Subacute obstruction: gradually worsening exertional dyspnoea, fatigue, or recurrent embolic events (transient ischaemic attack, stroke, limb ischaemia).

Paravalvular leak: heart failure, a new regurgitant murmur, and symptoms of haemolysis (jaundice, dark urine, anaemia). Endocarditis presents with fever, embolism and new regurgitation.

The anticoagulation history, recent INR values, missed doses, interacting drugs, pregnancy and recent illness are essential parts of the history.

• INR immediately. Full blood count, LDH, creatinine, inflammatory markers, blood cultures (three sets before antibiotics when fever or any suspicion of endocarditis).
• Transthoracic echocardiography with model specific reference values, then transoesophageal echocardiography (two- and three dimensional) for leaflet motion, thrombus, pannus, vegetations and paravalvular leak.
• Obstruction is suggested, for aortic valves, by a peak velocity over 4 m/s, mean gradient over 35 mmHg, dimensionless velocity index under 0.25, and acceleration time over 100 ms. For mitral valves, the markers are peak E velocity over 1.9 m/s, mean gradient over 5 mmHg at a normal heart rate, pressure half time over 130 ms, and a ratio of prosthetic to left ventricular outflow velocity time integral over 2.5. Gradients are also raised by high flow states (anaemia, fever, pregnancy, thyrotoxicosis), so compare with the early post-operative baseline.
• Cine fluoroscopy shows leaflet opening angle (reduced in obstruction) without contrast. Cardiac CT separates thrombus (usually under 90 Hounsfield units) from pannus (usually over 145 Hounsfield units), and sizes the thrombus.
• Thrombus area on transoesophageal echocardiography or CT: under 0.8 cm2 is small and 0.8 cm2 or more is large.
• Right heart catheterisation or invasive gradients are seldom needed.

Differential diagnosis.

• Patient prosthesis mismatch and pressure recovery.
• High output states causing high gradients.
• Prosthetic valve endocarditis, with or without dehiscence.
• Left ventricular dysfunction and pulmonary embolism, and other causes of acute heart failure.

Anticoagulation to prevent dysfunction.

• Warfarin is the only suitable oral anticoagulant for mechanical valves. Direct oral anticoagulants are contraindicated because of excess thrombosis and bleeding.
• INR targets: aortic bileaflet valve without risk factors 2.5 (2.0 to 3.0). Aortic valve with risk factors (atrial fibrillation, previous thromboembolism, left ventricular ejection fraction under 35%, hypercoagulable state), any mitral or tricuspid mechanical valve, and older high thrombogenicity designs: 3.0 (2.5 to 3.5), with higher targets for the most thrombogenic designs set by the surgical team.
• Start warfarin 5 mg orally daily (2 to 3 mg in older adults, liver disease or low weight), check INR every 2 to 3 days until stable, then every 4 weeks (or more often if unstable). Self-testing is encouraged. Maximum dose is set by INR. Review drug and dietary interactions. Warfarin sensitivity rises in heart failure, liver congestion and fever.
• Routine adjunctive aspirin is not advised because of bleeding. Aspirin 75 to 100 mg daily may be added after a thromboembolic event despite INR in range.
• Out-of-range INR: INR 4.5 to 10 without bleeding, omit warfarin one or two doses and restart at a lower dose; INR over 10, or over 5 with bleeding risk, give vitamin K 1 to 2 mg orally. Major bleeding: stop warfarin, give four factor prothrombin complex concentrate 25 units/kg (INR 2 to under 4), 35 units/kg (INR 4 to 6) or 50 units/kg (INR over 6), plus vitamin K 5 mg intravenously slowly (lower doses reduce the risk of valve thrombosis).
• Interruption for procedures: stop warfarin 5 days before; bridge with enoxaparin 1 mg/kg subcutaneously every 12 hours for mitral valves, older valves or high risk features (last dose 24 hours before; halve for creatinine clearance under 30 mL/min to 1 mg/kg once daily) and restart warfarin 12 to 24 hours after the procedure.

Obstructive thrombosis, left sided.

• Critically ill (obstructive shock, severe heart failure) with large thrombus: emergency surgical valve replacement when available and the risk is acceptable. If surgery is unavailable or the risk is prohibitive, give fibrinolysis.
• Not critically ill, small thrombus (under 0.8 cm2): intravenous unfractionated heparin (aPTT 1.5 to 2.5 times control) and optimised warfarin, reassessed by echocardiography within 48 to 72 hours. If no response, give fibrinolysis or operate.
• Not critically ill, large thrombus (0.8 cm2 or more) or failed heparin: surgery when the risk is low. Fibrinolysis when the risk of surgery is high.
• Fibrinolysis options: alteplase 10 mg intravenous bolus, then 90 mg over 90 minutes, with unfractionated heparin; or low dose slow infusion (alteplase 25 mg over 6 hours without bolus, then heparin, repeated on subsequent days as set by the centre's regimen), which has fewer complications; or streptokinase 1.5 million units over 60 minutes without heparin. Stop once leaflet motion and gradients normalise. Contraindications are previous intracranial haemorrhage, ischaemic stroke within 6 months, intracranial neoplasm, active bleeding, recent major trauma or surgery, and large left atrial or ventricular thrombus. Stroke or systemic embolism complicates roughly 10% of fibrinolytic treatments and major bleeding about 5%.
• After treatment: warfarin to a higher INR range for 3 months, then the usual target.

Obstructive thrombosis, right sided. Fibrinolysis is the first choice (alteplase 25 mg over 6 hours without a bolus with heparin, repeated on subsequent days, or alteplase 10 mg bolus then 90 mg over 90 minutes with unfractionated heparin), because tricuspid thrombosis is often catastrophic with surgery. Surgery is for failure or contraindication.

Pannus. Obstruction from pannus needs valve re-replacement, since anticoagulation or fibrinolysis does not remove it. Maintain anticoagulation.

Paravalvular leak. Treat heart failure (diuretics) and anaemia. Close the leak by transcatheter closure with a vascular plug or septal occluder in suitable anatomy, or by redo surgery, for symptomatic heart failure or for haemolysis needing transfusion. Exclude endocarditis first.

Leaflet entrapment, strut or leaflet fracture, or dehiscence with rocking valve. Urgent surgery.

Endocarditis. Treat with the antibiotic regimens and surgical indications of prosthetic valve endocarditis, with daily ECG for PR interval and early surgical review.

Heart failure. Furosemide 40 to 80 mg intravenously for pulmonary oedema; avoid vasodilators in obstruction. Treat atrial fibrillation with rate control (metoprolol succinate 25 to 200 mg orally daily).

Monitoring. Echocardiography with gradients at baseline (6 weeks to 3 months after implantation, as the comparator for later studies), then yearly and with any change. INR every 4 weeks when stable. Full blood count, LDH and creatinine yearly, or sooner if haemolysis is suspected.

Referral and escalation. Refer every patient with suspected obstruction, new regurgitation or embolism immediately to a cardiac centre with surgical capability. Treat acute obstruction with shock as an emergency requiring intensive care and surgery.

Special groups.

• Pregnancy: highest risk group. Options are warfarin throughout (lowest valve risk, dose 5 mg daily or under to reduce embryopathy risk), changing to low molecular weight heparin from week 36 or planned delivery; or low molecular weight heparin throughout, enoxaparin 1 mg/kg subcutaneously every 12 hours with anti-Xa peak (4 to 6 hours after the dose) of 0.8 to 1.2 units/mL and checks every 1 to 2 weeks. Dose adjustment is needed as weight and renal clearance change. Valve thrombosis is more frequent with heparin. Direct oral anticoagulants are contraindicated. Care in a specialist cardio obstetric centre.
• Children: weight based warfarin with age specific INR targets.
• Kidney impairment: enoxaparin accumulates, so adjust and check anti-Xa; prefer unfractionated heparin when creatinine clearance is under 30 mL/min.
• Region specific: limited access to INR testing is a major cause of valve thrombosis, so point-of-care testing and a bioprosthesis may be preferred when reliable monitoring is not available.