Diseases of the mitral valve: mitral regurgitation

01Definition and overview

Mitral regurgitation (mitral incompetence) is backward flow of blood from the left ventricle into the left atrium during systole, because the mitral apparatus fails to close. The apparatus has five parts, and disease of any of them can cause a leak: the annulus, the two leaflets, the chordae tendineae, the papillary muscles and the ventricular wall that carries them.

Two divisions matter most for treatment:

Regurgitation is also acute or chronic, and the two behave very differently. Surgeons describe the mechanism by leaflet motion, the Carpentier classification: type I, normal leaflet motion (annular dilatation, perforation); type II, excessive motion (prolapse, flail); type IIIa, motion restricted in systole and diastole (rheumatic); and type IIIb, motion restricted in systole (tethering in an ischaemic or dilated ventricle).

02Etiology and pathophysiology

Causes

• Degenerative disease is the commonest cause in Europe. Barlow disease is myxomatous thickening of large, billowing leaflets in younger patients; fibroelastic deficiency is thin, weak tissue with a single ruptured chord in older patients.
• Mitral valve prolapse is the systolic billowing of one or both leaflets more than 2 mm above the annulus. It affects about 2 to 3 per cent of people, runs in families, and is associated with Marfan syndrome, Ehlers–Danlos syndrome and pseudoxanthoma elasticum. Most cases cause little or no regurgitation.
• Rheumatic disease, the main cause in low-income countries, often with stenosis.
• Infective endocarditis, which perforates leaflets and ruptures chordae.
• Ischaemic heart disease: papillary muscle dysfunction or rupture after myocardial infarction, and tethering of the leaflets by a scarred, remodelled ventricle.
• Cardiomyopathies: dilated (annular dilatation and tethering), and hypertrophic, where the anterior leaflet is drawn into the outflow tract in systole.
• Others: atrial fibrillation with a large atrium, lupus (Libman–Sacks vegetations), annular calcification, congenital clefts, and drugs, including the appetite suppressants fenfluramine and benfluorex and the ergot-derived dopamine agonists cabergoline and pergolide.

Chronic regurgitation

1. 1

   Volume overload

   Part of each stroke goes backwards, so the ventricle must pump more to keep the forward output. It dilates and develops eccentric hypertrophy, and its stroke volume rises.
2. 2

   A compliant atrium

   The left atrium enlarges slowly and accepts the extra volume at a modest pressure, so the lungs are protected for years and the patient feels well.
3. 3

   Hidden dysfunction

   The ventricle ejects partly into the low-pressure atrium, so its afterload is low and its ejection fraction looks normal or high even as the muscle weakens. An ejection fraction of 60 per cent or less already means damage in severe regurgitation.
4. 4

   Decompensation

   The ventricle dilates further, the leak grows ("mitral regurgitation begets mitral regurgitation"), the atrial pressure rises, and atrial fibrillation, pulmonary hypertension and heart failure follow. If surgery waits until this stage, the ventricle may not recover.

Acute regurgitation

A sudden leak, from a ruptured chord, a ruptured papillary muscle or endocarditis, meets a normal-sized, stiff atrium. The atrial pressure rises steeply (a giant v-wave), the lungs flood and the forward output falls. Acute severe mitral regurgitation is an emergency, and the murmur may be soft and short because the atrial and ventricular pressures equalise in late systole.

03Clinical features

Chronic regurgitation is often silent for years, and the heart may be much enlarged before symptoms appear:

• exertional breathlessness and orthopnoea, from pulmonary venous congestion and later from ventricular failure;
• fatigue and lethargy from a low forward output;
• palpitations from atrial fibrillation, which is less dramatic than in mitral stenosis;
• in late disease, right heart failure and cachexia.

Acute regurgitation presents with sudden pulmonary oedema, often with cardiogenic shock.

The signs of chronic regurgitation are:

• an apex beat displaced down and out, diffuse and forceful, with a systolic thrill when severe;
• a soft first heart sound;
• a pansystolic murmur loudest at the apex and radiating to the axilla; a posterior leaflet prolapse sends its jet forwards, so the murmur may be heard at the base;
• a third heart sound from the rapid filling of the ventricle with the returning volume, sometimes followed by a short mid-diastolic flow murmur;
• in prolapse, a mid-systolic click and a late systolic murmur, which come earlier on standing or with a Valsalva manoeuvre;
• later, atrial fibrillation and the signs of pulmonary hypertension and heart failure.

04Diagnosis and management

Tests

• ECG: left atrial enlargement, left ventricular hypertrophy in about half, and atrial fibrillation.
• Chest X-ray: an enlarged left atrium and ventricle; pulmonary oedema in acute regurgitation, often with a normal heart size.
• Transthoracic echocardiography is the key test. It shows the mechanism and grades the leak by several measures together: the width of the jet at its narrowest point (vena contracta), the effective regurgitant orifice area (EROA), the regurgitant volume and fraction, and flow reversal in the pulmonary veins. In primary regurgitation, severe means an EROA of 40 square millimetres or more and a regurgitant volume of 60 mL or more, with a regurgitant fraction of 50 per cent or more and a vena contracta of 7 mm or more; in ventricular secondary regurgitation, European guidance counts an EROA of 30 square millimetres or a volume of 45 mL as already significant, because the orifice is often elliptical and the flow low, while American guidance keeps the same thresholds as for primary regurgitation. It also measures the ventricle (ejection fraction, end-systolic diameter), the atrium and the pulmonary pressure.
• Transoesophageal echocardiography shows the exact lesion, often in 3D, and whether it can be repaired, and is used during surgery and transcatheter repair.
• Cardiac magnetic resonance measures the regurgitant volume and the ventricle when echocardiography is uncertain; exercise testing reveals hidden limitation; natriuretic peptides help with timing; coronary angiography is done before surgery when coronary disease is possible.

Acute regurgitation

The patient needs oxygen, diuretics and vasodilators (nitrates or nitroprusside) to reduce afterload and push blood forwards, inotropes and an intra-aortic balloon pump or other mechanical support for shock, and urgent surgery, or transcatheter edge-to-edge repair in selected patients at high surgical risk. Papillary muscle rupture and endocarditis usually need valve replacement, while a ruptured chord can often be repaired. Papillary muscle rupture after infarction carries a very high mortality without treatment.

Chronic primary regurgitation

Mild and moderate regurgitation are followed with echocardiography, yearly to every two years for moderate disease. Drugs do not delay the need for surgery when the blood pressure and the ventricle are normal. For severe regurgitation:

• Surgery is indicated when symptoms appear, and in asymptomatic patients when the ventricle shows dysfunction: an ejection fraction of 60 per cent or less, or an end-systolic diameter of 40 mm or more (20 mm per square metre of body surface).
• In asymptomatic patients with a good ventricle, surgery is considered for atrial fibrillation caused by the leak or a resting pulmonary artery systolic pressure above 50 mmHg, and repair is considered for a left atrium of 60 mL per square metre or more (or 55 mm or more) when a durable repair is likely in an expert centre. European guidance recommends repair in low-risk patients when at least three of four are present: atrial fibrillation, a pulmonary pressure above 50 mmHg, that degree of atrial dilatation, and at least moderate tricuspid regurgitation. American guidance goes further and supports early repair in any asymptomatic severe case when a durable repair is more than 95 per cent likely and the operative risk is under 1 per cent.
• Mitral valve repair is preferred to replacement whenever it is feasible: it preserves the chordae and the ventricle, avoids the long-term problems of a prosthesis and gives better survival. Degenerative posterior leaflet disease can be repaired in almost all cases in experienced centres. A repair uses leaflet resection or artificial chords and a ring to reshape the annulus.
• Transcatheter edge-to-edge repair (TEER) clips the two leaflets together at the site of the leak, through a catheter from the femoral vein. It is the option for symptomatic patients who are at high surgical risk or frail and have suitable anatomy.
• Atrial fibrillation is treated with rate control and anticoagulation, and a direct oral anticoagulant is preferred to warfarin, unlike in rheumatic mitral stenosis. At surgery the left atrial appendage is closed and ablation is considered.

Secondary regurgitation

• The ventricle is treated first: the full heart failure treatment, cardiac resynchronisation when it is indicated, and revascularisation where ischaemia is the cause. The regurgitation is reassessed afterwards, when the patient is euvolaemic.
• Transcatheter edge-to-edge repair reduces heart failure admissions and improves quality of life in patients who still have symptoms and significant regurgitation despite this, with an ejection fraction of about 20 to 50 per cent, an end-systolic diameter of 70 mm or less, a pulmonary pressure of 70 mmHg or less, no severe right ventricular failure, and a recent admission or high natriuretic peptides. The two main trials disagreed: one showed fewer admissions and deaths, the other no benefit. The likely reasons are the patients chosen (regurgitation out of proportion to the size of the ventricle in the positive trial), how far heart failure drugs had been optimised, and differences in technique. Taken together, the trials show fewer admissions and better quality of life, but no clear effect on survival.
• Surgery for secondary regurgitation is usually done alongside coronary bypass or another operation.
• Atrial secondary regurgitation improves with rhythm control of atrial fibrillation and treatment of heart failure; in symptomatic severe cases surgery with ablation and closure of the left atrial appendage is considered, or edge-to-edge repair if surgery is not possible.

Routine antibiotic prophylaxis for dental work is not given for native mitral regurgitation; it is for patients with a prosthetic valve or a valve repaired with a ring or other prosthetic material (and is considered after edge-to-edge repair), a previous endocarditis or some congenital heart disease.

05Epidemiology

Mitral regurgitation is the commonest valve lesion in the community. In an American population study, moderate or severe regurgitation was found in about 1.7 per cent of adults, rising to almost 1 in 10 of those over 75. In Europe it is the second commonest valve disease leading to intervention, after aortic stenosis. Primary regurgitation accounts for just over half of the patients who need treatment, and degenerative disease is its main cause in high-income countries, rheumatic disease in low-income ones.

Secondary regurgitation is common in heart failure: significant regurgitation is found in about a quarter of patients with a reduced ejection fraction. Atrial regurgitation is growing with the number of older people with atrial fibrillation.

06Prognosis

Mild and moderate primary regurgitation are compatible with a normal life, and most prolapse is benign. Severe primary regurgitation is not: in asymptomatic patients with an effective regurgitant orifice of 40 square millimetres or more, only about 58 per cent were alive at 5 years in one large series, and a flail leaflet carries a mortality of several per cent a year. Symptoms, atrial fibrillation, pulmonary hypertension, a falling ejection fraction and a dilating ventricle all predict a worse outcome.

Repair before the ventricle fails restores a near-normal life expectancy, while surgery after dysfunction has set in leaves a damaged ventricle and a worse survival. Repairs are durable in most patients; replacement brings anticoagulation or the wear of a tissue valve. Secondary regurgitation doubles the risk of death in heart failure, and its outlook is mainly that of the ventricle. All patients with significant regurgitation need regular clinical and echocardiographic review, every 6 months in asymptomatic severe disease.