Bioprosthetic Valve Degeneration

Bioprosthetic valve degeneration (structural valve deterioration) is the progressive failure of tissue valves, whether surgical (porcine or bovine pericardial) or transcatheter, through leaflet calcification, fibrosis, stiffening or tear. It produces stenosis, regurgitation or both.

Failure is uncommon in the first 5 years and then rises. Freedom from structural deterioration at 10 years is roughly 90% in patients over 65 years but much lower in patients under 50 years, in those with renal failure and in the mitral position.

Risk factors are young age, chronic kidney disease and dialysis, hyperparathyroidism, hypercalcaemia, hyperphosphataemia, diabetes, metabolic syndrome, hypertension, smoking, patient prosthesis mismatch, mitral position, and pregnancy.

Other causes of valve dysfunction include thrombosis, endocarditis, pannus, paravalvular leak and mismatch, and they are distinct from structural degeneration.

Pathophysiology. Calcium phosphate deposits on non-viable tissue and cellular remnants in glutaraldehyde fixed leaflets, aided by mechanical stress at the commissures and cusps, and perhaps by immune reactions to xenoantigens. Calcification stiffens leaflets and causes stenosis.

Tears, usually at the commissures, cause regurgitation, sometimes acute. High calcium phosphate product accelerates the process.

Staging. Stage 1 is morphological deterioration (thickening, calcification, tear) without haemodynamic change.

Stage 2 is moderate haemodynamic deterioration: mean gradient rise of 10 mm Hg or more to 20 mm Hg or more with a fall in effective orifice area of 0.3 cm2 or more (or 25% or more) and a Doppler velocity index fall of 0.1 or more (or 20% or more), or new intraprosthetic regurgitation of moderate grade.

Stage 3 is severe haemodynamic deterioration: mean gradient rise of 20 mm Hg or more to 30 mm Hg or more with a fall in effective orifice area of 0.6 cm2 or more (or 50% or more), or severe intraprosthetic regurgitation.

• Asymptomatic in early stages, found on routine echocardiography.
• Progressive exertional dyspnoea, fatigue, angina and syncope (aortic), heart failure, palpitations, atrial fibrillation.
• Acute severe regurgitation from a leaflet tear: sudden pulmonary oedema or shock.
• Examination: new or changing systolic ejection murmur (stenosis) or regurgitant murmur, and signs of congestion.

Red flags.

• Acute pulmonary oedema or shock (leaflet tear)
• Syncope or angina
• Fever or new regurgitation (endocarditis)
• Rising gradient on serial echocardiography
• Ejection fraction under 50%, left ventricular dilatation or pulmonary hypertension
• New atrial fibrillation or embolic event

• Echocardiography. Compare with the baseline study at 4 to 12 weeks after implantation.
  • Aortic: peak velocity over 3 m/s (4 m/s or more is severe), mean gradient over 20 mm Hg (35 mm Hg or more is severe), Doppler velocity index under 0.30 (under 0.25 is severe), acceleration time over 100 ms, effective orifice area falling, intraprosthetic regurgitation.
  • Mitral: mean gradient over 5 mm Hg (10 mm Hg or more is severe), pressure half time over 130 ms (200 ms or more is severe), effective orifice area under 1.0 cm2, velocity time integral ratio over 2.5, and regurgitation by vena contracta and pulmonary vein flow.
• Transoesophageal echocardiography and ECG-gated CT. Leaflet thickening, calcification and restricted motion. Hypoattenuating leaflet thickening suggests thrombosis rather than degeneration.
• Stress echocardiography when symptoms are unclear. Natriuretic peptide.
• Laboratory. Calcium, phosphate, parathyroid hormone, creatinine, blood cultures when fever is present.
• Planning for reintervention. Gated CT for coronary heights, valve-to-coronary distance and neo outflow tract, coronary angiography or CT, and measurement of the true internal diameter of the failed valve.

Differential diagnosis.

• Prosthetic valve thrombosis (responds to anticoagulation)
• Infective endocarditis with vegetation or perforation
• Patient prosthesis mismatch (normal leaflets, high gradients from the outset)
• Pannus (rare in bioprostheses)
• Paravalvular leak
• Dynamic left ventricular outflow obstruction
• High flow states (anaemia, sepsis, thyrotoxicosis, pregnancy)
• Pressure recovery effect and measurement error
• Prosthesis malposition or under expansion (transcatheter valves)
• Left ventricular dysfunction from other causes

• No drug prevents or reverses degeneration. Control hypertension, diabetes and lipids, and treat hyperparathyroidism and hyperphosphataemia in kidney disease. Treat heart failure and atrial fibrillation with their usual therapy.
• Anticoagulation after implantation of a bioprosthesis: 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, for 3 months. INR every 2 to 3 days at the start, weekly until stable, then every 4 to 12 weeks. Then aspirin 75 to 100 mg orally once daily long term.
• Congestion: 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). Monitor sodium, potassium and creatinine.
• Indications for reintervention:
  • Severe symptomatic dysfunction (stenosis or regurgitation).
  • Severe dysfunction without symptoms when ejection fraction is under 50%, the ventricle dilates, pulmonary hypertension develops, or exercise testing is abnormal.
  • Acute leaflet tear with severe regurgitation (urgent).
• Options. The heart team chooses by age, surgical risk, anatomy and patient preference.
  • Redo surgical valve replacement, with operative mortality about 2 to 5% for elective aortic cases and higher for mitral and emergency cases.
  • Transcatheter valve-in-valve implantation. In the aortic position, risks are coronary obstruction (about 1 to 3%, higher with stentless or small valve-to-coronary distances), residual high gradients and mismatch in small valves (true internal diameter under 21 mm), and leaflet thrombosis. Fracture of the failed valve ring with a high pressure balloon can increase the orifice. In the mitral position, risks are left ventricular outflow obstruction (neo outflow area under 1.7 cm2 predicts it), embolisation and thrombosis.
  • Balloon valvuloplasty of a degenerated bioprosthesis is not effective.
• Endocarditis prophylaxis before high risk dental procedures: amoxicillin 2 g orally as a single dose 30 to 60 minutes before the procedure. For penicillin allergy, azithromycin 500 mg or doxycycline 100 mg orally as a single dose. Avoid clindamycin.

Special groups.

• Young patients and women planning pregnancy: expect reintervention and choose valves and later procedures with this in mind.
• Dialysis and hyperparathyroidism: degeneration is faster, so surveillance is closer.
• Pregnancy with severe stenosis: high risk. Plan with the heart team and defer intervention when possible.

Monitoring. Baseline echocardiography at 4 to 12 weeks. Annual echocardiography from year 5 after surgery (earlier in young patients and with risk factors), every 6 to 12 months in moderate degeneration, and at once for symptoms or fever. CT when thrombosis is suspected. Natriuretic peptide with symptoms.

Referral and escalation. Refer to a heart team with structural intervention capability. Urgent for acute pulmonary oedema, syncope, severe regurgitation or fever.