Mitral Annular Calcification

Mitral annular calcification (MAC) is chronic degenerative calcification of the fibrous mitral annulus, usually the posterior annulus, which may extend into the leaflet bases, the subvalvular apparatus and the adjacent conduction tissue.

It is found in about 8 to 10% of adults overall and in a third or more of people over 80 years, and in a high share of patients on dialysis.

Risk factors are age, female sex, hypertension, diabetes, chronic kidney disease, hyperparathyroidism, hypercalcaemia, hyperphosphataemia, aortic stenosis, hypertrophic cardiomyopathy, mitral valve prolapse (especially Barlow disease), Marfan syndrome, previous chest radiotherapy, dyslipidaemia, smoking and atherosclerosis.

MAC is associated with atrial fibrillation, ischaemic stroke, coronary events, aortic stenosis, atrioventricular and bundle branch block, endocarditis, and mitral regurgitation or stenosis. A rare variant, caseous calcification of the mitral annulus, has a liquefied core and can mimic a tumour or abscess.

Pathophysiology. The process resembles atherosclerosis, with lipid deposition, inflammation and active osteogenic change in the annulus under mechanical stress, accelerated by a raised calcium phosphate product in kidney disease. Calcium stiffens the annulus and removes its sphincter action, causing regurgitation.

Extension onto the leaflet bases restricts opening and causes stenosis, because the commissures are spared. Calcium and thrombus can embolise. Extension toward the His bundle causes conduction disease.

• Frequently asymptomatic and found incidentally on echocardiography, CT, or chest X-ray.
• Dyspnoea, fatigue and heart failure from mitral regurgitation or stenosis.
• Palpitations from atrial fibrillation. Syncope or presyncope from atrioventricular block.
• Embolic stroke or transient ischaemic attack.
• Fever and embolic signs when endocarditis complicates MAC.
• Examination: a soft apical systolic murmur (regurgitation), a low pitched diastolic rumble (stenosis), and an irregular pulse in atrial fibrillation.

Red flags.

• Embolic stroke or transient ischaemic attack
• Syncope, high grade atrioventricular block or new bundle branch block
• Fever with a new murmur
• Severe mitral regurgitation or a mean gradient of 5 mm Hg or more with symptoms
• Pulmonary hypertension
• A mass like calcified lesion (caseous MAC) or rapid progression
• Planned mitral valve surgery or intervention in severe MAC

• Transthoracic echocardiography. A bright, shelf like echo dense band at the posterior annulus, extending into the leaflet base. Grade by thickness: under 5 mm mild, 5 to 10 mm moderate, over 10 mm severe. Assess mitral regurgitation, and mitral stenosis by mean gradient (for MAC, 5 mm Hg or more at a heart rate of 60 to 80/min is clinically significant), planimetry and the continuity equation. Pressure half time is unreliable in MAC.
• Transoesophageal echocardiography. Leaflet involvement, thrombus, vegetations, and caseous change.
• Cardiac CT. Extent of calcification (circumference of 270 degrees or more is extensive), annular dimensions and neo outflow tract area when valve implantation is considered. Caseous MAC has a low attenuation core with a calcified rim.
• Cardiac MRI. Caseous necrosis shows a hypointense core with a rim of enhancement.
• ECG and ambulatory ECG for atrioventricular block and atrial fibrillation.
• Laboratory. Calcium, phosphate, parathyroid hormone, 25-hydroxyvitamin D, creatinine and eGFR, lipids, HbA1c. Blood cultures with fever.

Differential diagnosis.

• Mitral annular disjunction
• Rheumatic mitral stenosis (commissural fusion, doming of the anterior leaflet)
• Myxomatous mitral valve prolapse
• Endocarditis with annular abscess
• Left atrial or ventricular thrombus
• Mitral valve tumour (myxoma, papillary fibroelastoma)
• Caseous MAC versus abscess or tumour
• Calcified mitral prosthesis
• Papillary muscle calcification

• Risk factor control. Treat hypertension and diabetes, and give a statin for atherosclerotic risk (atorvastatin 20 to 80 mg orally once daily, with liver enzymes at baseline and 3 months, reduced dose with interacting drugs, avoided in pregnancy). Statins have not been shown to slow MAC. Refer patients with kidney disease to nephrology for control of phosphate, calcium and parathyroid hormone.
• Atrial fibrillation: anticoagulation directed by stroke risk. Apixaban 5 mg orally twice daily, reduced to 2.5 mg twice daily when at least two of age 80 years or over, weight 60 kg or under and serum creatinine 133 micromol/L or over are present. Also 2.5 mg twice daily at creatinine clearance 15 to 29 mL/min, and avoided under 15 mL/min. Maximum 10 mg daily. Long term. Use warfarin to an INR of 2.0 to 3.0 when MAC causes significant mitral stenosis (mean gradient 5 mm Hg or more), because direct oral anticoagulant data are lacking.
• Embolic stroke or transient ischaemic attack without atrial fibrillation: aspirin 75 to 100 mg orally once daily (usual maximum 325 mg daily), a high intensity statin, and blood pressure control. Anticoagulation for thrombus on the annulus.
• Heart failure and mitral 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. Control blood pressure to reduce afterload.
• Mitral stenosis from MAC with symptoms or atrial fibrillation: rate control to lengthen diastole with bisoprolol 2.5 mg orally once daily, increased to 5 to 10 mg once daily, maximum 20 mg daily (do not exceed 10 mg daily at creatinine clearance under 20 mL/min or in severe liver impairment).
• Conduction disease: permanent pacing for symptomatic or high grade atrioventricular block.
• Intervention is for severe symptomatic mitral regurgitation or stenosis, after a heart team assessment.
  • Surgery on a heavily calcified annulus carries a high risk of atrioventricular groove rupture, left ventricular injury and embolisation. Techniques include annular decalcification with reconstruction and intra-annular prosthesis placement.
  • Transcatheter valve implantation within the calcified annulus (transseptal or transapical) is used in selected inoperable patients at centres with expertise. Risks are left ventricular outflow tract obstruction (about 10% or more), valve embolisation or malposition, residual leak, and substantial early mortality. CT planning of the neo outflow area is essential (a neo outflow area under 1.7 cm2 predicts obstruction).
• Caseous MAC: observe asymptomatic lesions with imaging. Surgery for embolism, compression or rapid growth. Antibiotics are not needed unless infection is shown.
• Endocarditis (MAC raises the risk): blood cultures and a full antibiotic course directed by organism, with early surgery for abscess or heart failure.

Special groups. Dialysis patients develop MAC faster and have higher complication rates, so manage mineral and bone disorder with nephrology and review echocardiography every 6 to 12 months.

Monitoring. Echocardiography every 1 to 2 years for MAC with regurgitation or stenosis, and annually for severe disease. ECG yearly, with ambulatory ECG for syncope or palpitations. INR as directed on warfarin. Calcium, phosphate and parathyroid hormone every 3 to 6 months in kidney disease. CT before any mitral intervention.

Referral and escalation. Refer to cardiology for MAC with valve dysfunction, embolism or conduction disease, and to a heart team for any intervention. Urgent for embolism, syncope, high grade block, endocarditis or heart failure.