Structural Valve Deterioration

Structural valve deterioration is intrinsic, permanent degeneration of a bioprosthetic valve (surgical or transcatheter) that causes stenosis, regurgitation or both. It is the main limit to bioprosthesis durability and the commonest reason for reintervention.

Deterioration is defined by morphological change (leaflet thickening, calcification, tear, flail, or stent or frame fracture) and by haemodynamic change from the early post-implantation baseline.

Haemodynamic deterioration is staged as:

• moderate: increase in mean gradient of 10 mmHg or more to a mean gradient of 20 mmHg or more, or new moderate regurgitation
• severe: increase in mean gradient of 20 mmHg or more to a mean gradient of 30 mmHg or more, or new severe regurgitation

Surgical bioprostheses usually last 10 to 15 years, with failure becoming frequent after 10 years. Durability is shorter in younger patients (deterioration is fastest under age 40 to 50), in the mitral position and with chronic kidney disease. Transcatheter valve durability is less well defined beyond 8 to 10 years.

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

Pathophysiology.

Calcification of the leaflets is driven by lipid and calcium deposition, glutaraldehyde fixed tissue, and inflammation. Collagen fibres degrade from mechanical stress, which causes tears, perforation and cuspal prolapse.

Immune responses to residual xenoantigens and high pressure stress on the leaflets add to damage. Younger patients with higher blood pressure and metabolic activity deteriorate faster.

Deterioration must be distinguished from non-structural failure (thrombosis, pannus, endocarditis, paravalvular leak, mismatch), which has different treatment.

Often asymptomatic and found on routine echocardiography. Symptoms are gradual: exertional dyspnoea, fatigue, angina, syncope, orthopnoea or oedema. A new systolic ejection murmur (aortic stenosis), diastolic murmur (regurgitation or mitral stenosis) or a change in murmur is the usual sign. Acute leaflet tear causes sudden pulmonary oedema.

• Echocardiography at baseline (6 weeks to 3 months after implantation) and then at each review for comparison.
• Aortic bioprosthesis: peak velocity over 3 m/s, mean gradient over 20 mmHg, dimensionless velocity index under 0.30, acceleration time over 100 ms, and new central or transvalvular regurgitation.
• Mitral bioprosthesis: mean gradient over 5 to 10 mmHg at a normal heart rate, pressure half time over 130 ms, and new regurgitation.
• Transoesophageal echocardiography to visualise leaflets and distinguish deterioration from thrombosis, pannus, vegetation and paravalvular leak.
• Cardiac CT with contrast for leaflet thickening, calcification, hypoattenuated leaflet thickening (thrombus) and anatomical planning for valve-in-valve procedures (coronary height, sinus dimensions, and neo left ventricular outflow tract area).
• Blood cultures and inflammatory markers when fever or new regurgitation (exclude endocarditis). Calcium, phosphate, parathyroid hormone, creatinine, glucose and lipids to find correctable drivers.
• Exercise echocardiography when symptoms exceed resting findings in aortic stenosis.

Differential diagnosis.

• Prosthetic valve thrombosis and subclinical leaflet thrombosis.
• Pannus, endocarditis and paravalvular leak.
• Patient prosthesis mismatch and pressure recovery.
• High output states causing high gradients (anaemia, fever, pregnancy, thyrotoxicosis).

Exclude a reversible cause first. Subclinical leaflet thrombosis and valve thrombosis respond to anticoagulation.

• Warfarin to INR 2.0 to 3.0 for 3 months, with repeat imaging at 3 months.
• Or a direct oral anticoagulant such as apixaban 5 mg twice daily in patients without a mechanical valve or severe rheumatic mitral stenosis.

Treat endocarditis with 6 weeks or more of organism directed intravenous antibiotics, with early surgical review.

For methicillin susceptible Staphylococcus aureus: flucloxacillin 2 g intravenously every 4 hours with rifampicin 900 to 1200 mg daily in 2 to 3 doses and gentamicin 3 mg/kg daily for the first 2 weeks.

Medical treatment (does not slow structural deterioration).

• Control blood pressure (target under 130/80 mmHg) with an ACE inhibitor or ARB (ramipril 2.5 to 10 mg daily, or losartan 50 to 100 mg daily).
• Treat heart failure with diuretics (furosemide 20 to 80 mg orally daily) and the usual heart failure drugs when left ventricular function is reduced.
• Correct hypercalcaemia, hyperparathyroidism and hyperphosphataemia in chronic kidney disease. Statins do not prevent deterioration.
• Atrial fibrillation: apixaban 5 mg twice daily (2.5 mg twice daily if two of age 80 or over, weight 60 kg or under, creatinine 133 micromol/L or over), or rivaroxaban 20 mg once daily with food (15 mg when creatinine clearance is 15 to 49 mL/min).
• Use warfarin (INR 2.0 to 3.0) in the first 3 months after surgical implantation or when mitral stenosis is severe.
• Baseline antithrombotic therapy: aspirin 75 to 100 mg daily lifelong after a bioprosthesis; warfarin to INR 2.0 to 3.0 for 3 to 6 months after a surgical mitral or tricuspid bioprosthesis.
• Aspirin 75 to 100 mg daily after transcatheter aortic valve implantation (no additional antiplatelet drug when oral anticoagulation is needed).

Indications for reintervention (heart team decision):

• Symptomatic severe stenosis or severe regurgitation.
• Asymptomatic severe deterioration with left ventricular dysfunction (ejection fraction under 50%), left ventricular dilatation or pulmonary hypertension, when the risk is acceptable.
• Rapidly progressive deterioration, or acute leaflet tear with heart failure (urgent).

Options.

• Redo surgical valve replacement, preferred in younger patients, with endocarditis, with structural issues of the frame, or when valve-in-valve is anatomically unsuitable.
• Transcatheter valve-in-valve implantation in patients at high or intermediate surgical risk, using either balloon expandable or self-expanding valves.
• For aortic valve-in-valve: CT assessment of the virtual valve-to-coronary distance (under 4 mm indicates a high risk of coronary obstruction) and of sinus dimensions, with leaflet modification or coronary protection when needed.
• Bioprosthetic valve fracture can reduce residual gradients in small valves (mismatch risk).
• For mitral valve-in-valve: transseptal approach, assess risk of left ventricular outflow tract obstruction (predicted neo outflow area under 1.7 cm2 is high risk), with alcohol septal ablation or leaflet laceration in selected patients.
• Post-procedure anticoagulation: warfarin to INR 2.0 to 3.0 for 3 to 6 months after mitral valve-in-valve, then lifelong aspirin 75 to 100 mg daily; aspirin 75 to 100 mg daily after aortic valve-in-valve (anticoagulation when an indication exists).
• Antibiotic prophylaxis for dental procedures involving gingival manipulation is advised in all patients with a prosthetic valve: amoxicillin 2 g orally 30 to 60 minutes before the procedure; azithromycin 500 mg or doxycycline 100 mg with penicillin allergy.

Monitoring. Clinical review and echocardiography at 6 weeks to 3 months after implantation, then yearly from 5 years (earlier in young patients, mitral position, dialysis and pregnancy), and every 6 months once deterioration is established. NT-proBNP with symptoms, and cardiac CT when valve-in-valve is being planned.

Referral and escalation. Refer to a valve heart team when gradients rise, regurgitation appears or symptoms develop. Urgent referral for acute leaflet tear, pulmonary oedema, syncope or suspected endocarditis.

Special groups.

• Pregnancy and young women: bioprostheses deteriorate faster in pregnancy, and the choice of valve (mechanical versus biological) must be discussed before surgery; planning of reintervention before conception for severe deterioration.
• Chronic kidney disease and dialysis: faster calcification; plan early; avoid contrast injury with CT and use minimal volumes.
• Older adults: valve-in-valve is favoured; assess frailty.
• Children and young adults: reintervention is anticipated, and a lifetime valve strategy is made at the first operation.