Mitral Annular Disjunction

Mitral annular disjunction (MAD) is a structural abnormality in which the junction of the left atrial wall and the posterior mitral leaflet is displaced away from the crest of the basal left ventricular myocardium.

The hinge point of the leaflet therefore lies on the atrial side, and the annulus separates from the ventricular wall during systole. It is best shown in end systole in the long axis view and is absent in diastole. Prevalence depends strongly on the imaging method and the definition.

It is found in a large share of patients with bileaflet myxomatous mitral valve prolapse (Barlow disease) and in a minority of people without prolapse, in whom it is usually small and benign. It is also linked with connective tissue disorders.

The clinical concern is the arrhythmic mitral valve syndrome: prolapse with disjunction, frequent or complex ventricular ectopy, and sometimes sustained ventricular tachycardia or sudden cardiac death.

The absolute risk of sudden death is low, but it is higher with syncope, complex ventricular ectopy, inferior T wave inversion, papillary muscle fibrosis, severe regurgitation or a family history of sudden death. Young women are over represented among symptomatic patients.

Pathophysiology. The redundant leaflets and the hypermobile annulus exert systolic traction on the papillary muscles and the basal inferolateral wall. This stretch causes myocardial hypertrophy and focal fibrosis, shown as late gadolinium enhancement.

The fibrosis and mechanical stimulation of the Purkinje network and papillary muscles create triggers and re-entrant circuits. Tissue Doppler of the lateral annulus shows a high velocity systolic spike (the Pickelhaube sign, systolic velocity of 16 cm/s or more) that marks the abnormal annular motion.

Disjunction also distorts annular dynamics and contributes to mitral regurgitation.

• Many patients are asymptomatic, and the finding is incidental.
• Palpitations, presyncope, syncope, atypical chest pain, dyspnoea and fatigue. Cardiac arrest can be the first event.
• Midsystolic click with a late systolic murmur, or a holosystolic murmur when regurgitation is significant. Examination can be normal.
• Resting ECG: T wave inversion or biphasic T waves in the inferior or lateral leads, and frequent ventricular premature beats, often of papillary muscle or fascicular origin with a right bundle branch block pattern.
• Family history of mitral valve prolapse or sudden death in some patients.

Red flags.

• Syncope, resuscitated arrest or sustained ventricular tachycardia
• Non-sustained or polymorphic ventricular tachycardia, or ventricular ectopy burden over 10% on ambulatory ECG
• T wave inversion in the inferior leads
• Late gadolinium enhancement of the papillary muscles or inferobasal wall
• Severe mitral regurgitation, left ventricular dilatation or ejection fraction under 60%
• Pickelhaube sign with a long disjunction
• Family history of sudden death under 40 years
• Young woman with Barlow disease and bileaflet prolapse

• Transthoracic echocardiography. Parasternal and apical long axis views in end systole, measuring the distance from the atrial wall and leaflet junction to the top of the basal ventricular wall. Assess prolapse, leaflet length, regurgitation, ventricular size and function, and tissue Doppler of the lateral annulus. Transoesophageal echocardiography with three dimensional imaging defines it more precisely. No single distance defines risk, but longer and more circumferential disjunction is more often linked with arrhythmia.
• Cardiac MRI. Cine long axis imaging for disjunction length, and late gadolinium enhancement and T1 mapping for fibrosis of the papillary muscles and basal wall.
• ECG and ambulatory ECG for at least 48 hours, repeated yearly or extended when syncope occurs, for ectopy burden, morphology, and non-sustained ventricular tachycardia. Exercise testing for exertional arrhythmia.
• Laboratory: potassium, magnesium, calcium, thyroid function, troponin when symptoms are acute.
• Genetic and connective tissue assessment (aortic root imaging) when features of Marfan syndrome or related disorders, or familial clustering, are present.

Differential diagnosis.

• Mitral annular calcification
• Myxomatous mitral valve prolapse without disjunction
• Pseudo disjunction from imaging in diastole or from the normal posterior wall tilt
• Flail mitral leaflet and other causes of severe mitral regurgitation
• Idiopathic outflow tract or fascicular ectopy
• Arrhythmogenic cardiomyopathy and hypertrophic cardiomyopathy
• Myocarditis
• Long QT syndrome and other channelopathies
• Coronary artery anomalies and ischaemia

There are no randomised data, so management follows arrhythmic risk and the usual indications for mitral regurgitation.

• No symptoms, no high risk features, no significant regurgitation: reassurance and surveillance. Avoid stimulants and QT-prolonging drugs.
• Symptomatic ectopy or palpitations: 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), long term, with heart rate and blood pressure monitoring. Contraindicated in severe asthma, sinus node disease and high grade atrioventricular block without a pacemaker. Evidence of benefit for preventing sudden death is limited.
• Catheter ablation of triggering ventricular premature beats (papillary muscle or Purkinje origin) for a high burden, recurrent sustained tachycardia, or ventricular premature beat induced ventricular dysfunction, in a specialist centre.
• Implantable cardioverter defibrillator: secondary prevention after ventricular fibrillation or sustained ventricular tachycardia without another cause. Primary prevention is considered individually when several high risk features coexist (unexplained syncope, non-sustained ventricular tachycardia, fibrosis, severe regurgitation, ejection fraction under 50%), because the evidence is limited. Programme long detection durations and high rate zones.
• Mitral surgery follows the usual indications for primary mitral regurgitation: symptoms, or severe regurgitation with ejection fraction of 60% or less, end systolic diameter of 40 mm or more, new atrial fibrillation, pulmonary systolic pressure over 50 mm Hg, or left atrial volume index of 60 mL/m2 or more. Repair with annular reconstruction is preferred. Ventricular arrhythmia may persist after surgery, so follow up continues.
• Atrial fibrillation: 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.
• Exercise: competitive sport is restricted with syncope, complex ventricular arrhythmia, ejection fraction under 50%, or severe regurgitation. Others may take part after full assessment and a normal maximal exercise test.

Special groups. Pregnancy is usually tolerated without severe regurgitation or complex arrhythmia. Continue the beta blocker with metoprolol tartrate 25 to 100 mg orally twice daily, maximum 200 mg daily in this setting, and avoid atenolol.

Monitoring. Echocardiography every 1 to 2 years, and every 6 to 12 months with moderate or greater regurgitation. Ambulatory ECG yearly and with new symptoms. Cardiac MRI at baseline, repeated when symptoms or arrhythmia change. Device interrogation every 3 to 6 months.

Referral and escalation. Refer to cardiology for any disjunction with symptoms or ectopy, and to electrophysiology for high risk features. Urgent for syncope, sustained arrhythmia, resuscitated arrest or acute severe regurgitation.