Diseases of the mitral valve: mitral stenosis

01Definition and overview

Mitral stenosis is narrowing of the mitral valve orifice, which obstructs the flow of blood from the left atrium into the left ventricle in diastole. The left ventricle itself is usually normal, and often small; the burden falls on the left atrium, the pulmonary circulation and the right heart.

Severity is graded by the valve area and, with care, by the pressure gradient across the valve:

These are the classic echocardiographic grades. Current guidelines use a single threshold instead: European guidance calls a valve of 1.5 square centimetres or less, with symptoms or a high risk, clinically severe, because that is where intervention is considered, and American guidance calls it severe (with a pressure half-time of 150 ms or more). The mean gradient depends on the heart rate and the flow, so it overstates the stenosis in tachycardia, anaemia or pregnancy and understates it when the output is low.

02Etiology and pathophysiology

Causes

• Rheumatic heart disease is by far the commonest cause. Repeated inflammation fuses the commissures, thickens the leaflets and fuses and shortens the chordae, so the valve opens as a narrow "fish-mouth". The anterior leaflet bows into the ventricle in diastole (doming), and stenosis takes decades to develop after the first attack in high-income countries, but where rheumatic fever is common it can be severe by the age of 10 to 20, after repeated attacks.
• Mitral annular calcification: degenerative calcium in the annulus that spreads into the base of the leaflets, in older people and in chronic kidney disease. The commissures are not fused, so a balloon cannot open it.
• Rare causes: congenital stenosis (a parachute mitral valve, with one papillary muscle), radiation, carcinoid disease (usually right-sided, and on the left only with a lung primary or a shunt), lupus and some drugs. Lutembacher syndrome is mitral stenosis with an atrial septal defect.
• A left atrial myxoma or a large thrombus can obstruct the valve and mimic stenosis.

What the obstruction does

1. 1

   A pressure gradient

   Blood can only cross the narrowed valve if the left atrial pressure rises above the ventricular one. The flow depends on the gradient and on the time available, which is diastole.
2. 2

   Left atrium

   The atrium hypertrophies and then dilates. Its pressure is passed back to the pulmonary veins and capillaries, causing congestion, interstitial oedema and, when it exceeds about 25 mmHg, alveolar oedema.
3. 3

   Pulmonary hypertension

   At first the pulmonary pressure rises passively. Later the arterioles constrict and remodel (reactive pulmonary hypertension), which protects the lungs from oedema but loads the right ventricle.
4. 4

   Right heart

   The right ventricle hypertrophies, then dilates and fails, with functional tricuspid regurgitation, a raised venous pressure, hepatomegaly and oedema.

Atrial fibrillation is common, because the atrium is large and scarred. It removes the atrial contraction and, if the rate is fast, shortens diastole, so the left atrial pressure jumps and the patient can go into pulmonary oedema within hours. Anything that raises the flow or the heart rate does the same: exercise, fever, anaemia, thyrotoxicosis and, above all, pregnancy. Blood stagnates in the large atrium and its appendage, so thrombus and systemic emboli are common, most of all with atrial fibrillation.

03Clinical features

Symptoms usually appear when the area falls below about 2 square centimetres, decades after rheumatic fever in Europe:

• exertional breathlessness, then orthopnoea and paroxysmal nocturnal dyspnoea, and fatigue from a low output;
• palpitations from atrial fibrillation, which often marks the first decompensation;
• haemoptysis: pink frothy sputum in pulmonary oedema, blood-streaked sputum in bronchitis, or a sudden large bleed from ruptured bronchial veins (pulmonary apoplexy); pulmonary infarction also causes it;
• systemic emboli, most often a stroke, sometimes the first sign of the disease, and also emboli to the gut, kidneys and limbs;
• hoarseness from compression of the left recurrent laryngeal nerve by the large left atrium and pulmonary artery (Ortner syndrome), and, rarely, dysphagia;
• in late disease, the symptoms of right heart failure.

The signs:

• malar flush, a dusky pink discoloration of the cheeks in severe disease with pulmonary hypertension, and peripheral cyanosis;
• a small-volume pulse, often irregularly irregular;
• a raised jugular venous pressure with a prominent a-wave in sinus rhythm when there is pulmonary hypertension, and a large v-wave with tricuspid regurgitation;
• a tapping apex beat (a palpable first sound), not displaced, and a left parasternal heave from the right ventricle;
• a loud first heart sound while the leaflets are pliable, which fades as they calcify, and a loud pulmonary component of the second sound with pulmonary hypertension;
• an opening snap just after the second sound, followed by a low-pitched, rumbling mid-diastolic murmur at the apex, heard with the bell, the patient turned onto the left side and breathing out. In sinus rhythm it grows louder just before the first sound (presystolic accentuation);
• sometimes the early diastolic murmur of pulmonary regurgitation from pulmonary hypertension (Graham Steell murmur).

The more severe the stenosis, the shorter the gap between the second sound and the opening snap and the longer the murmur. The murmur can be very soft when the output is low.

04Diagnosis and management

Tests

• ECG: a broad, notched P wave of left atrial enlargement (P mitrale) in sinus rhythm, often atrial fibrillation, and right axis deviation with right ventricular hypertrophy in pulmonary hypertension.
• Chest X-ray: an enlarged left atrium, with a straight left heart border, a double right heart border and a widened carina; upper lobe venous diversion, Kerley B lines and oedema; sometimes a calcified valve.
• Transthoracic echocardiography is the key test. It measures the valve area by planimetry and by the pressure half-time, the mean gradient, the pulmonary artery pressure and the size of the atrium, and shows the cause and the shape of the valve. The Wilkins score grades leaflet mobility, thickening, calcification and the subvalvular apparatus from 1 to 4 each; a total of 8 or less, with fused commissures and no more than mild regurgitation, predicts a good result from a balloon.
• Transoesophageal echocardiography looks for thrombus in the left atrium and its appendage before any balloon procedure, and after an embolism, and helps when the transthoracic images are poor.
• Exercise echocardiography when the symptoms and the severity at rest do not match: a steep rise in the gradient or the pulmonary pressure on exercise favours intervention.
• Catheterisation is now needed only when the echocardiographic findings are inconclusive, and coronary angiography before surgery in older patients.

Medical treatment

• Diuretics relieve congestion.
• Rate control lengthens diastole: a beta-blocker or a rate-limiting calcium channel blocker, with digoxin in atrial fibrillation. Cardioversion can be tried, but atrial fibrillation tends to return while the valve stays tight.
• Anticoagulation with a vitamin K antagonist (warfarin, target INR 2 to 3) is given for atrial fibrillation of any pattern, a previous embolism or a thrombus in the left atrium, and is considered in sinus rhythm when the atrium is very large or full of dense spontaneous contrast. In rheumatic mitral stenosis with a valve area of 2 square centimetres or less the direct oral anticoagulants are not used: in a large trial in rheumatic atrial fibrillation, rivaroxaban led to more deaths and vascular events than a vitamin K antagonist. Their place in calcific mitral stenosis is less clear.
• Rheumatic disease needs secondary prophylaxis against further attacks of rheumatic fever, with penicillin, as set out in the rheumatic fever topic. Routine antibiotic cover for dental work is no longer given for native valve disease.

Opening the valve

Intervention is for symptomatic patients with clinically severe stenosis (an area of 1.5 square centimetres or less). A balloon can still be considered above 1.5 when the symptoms have no other cause and the valve is favourable:

• Percutaneous mitral commissurotomy (balloon valvotomy) is the first choice when the anatomy is favourable. A catheter is passed from the femoral vein across the atrial septum, and a balloon (often the Inoue balloon) is inflated in the valve to split the fused commissures. A successful result roughly doubles the area. Its risks are severe mitral regurgitation, embolism, tamponade and a small atrial septal defect.
• It is also considered in asymptomatic patients with a suitable valve who are at high risk of embolism (a previous embolism, new or paroxysmal atrial fibrillation, dense spontaneous contrast) or of decompensation (a pulmonary artery systolic pressure above 50 mmHg at rest, a planned pregnancy or major surgery).
• It is not done when there is thrombus in the left atrium, more than mild mitral regurgitation, severe or bicommissural calcification, no commissural fusion, or severe aortic or tricuspid disease or coronary disease that needs surgery anyway.
• Surgery is for the rest: open commissurotomy under bypass in a pliable valve, or mitral valve replacement when the valve is calcified or regurgitant. Closed commissurotomy, done without bypass, with the surgeon's finger in the left atrial appendage guiding a dilator passed through the apex of the left ventricle, is now rare outside low-income countries.
• Annular calcification is hard to treat: the calcium makes surgery difficult, and transcatheter valves are being used in selected patients.

In pregnancy, symptoms are treated with a beta-blocker and diuretics, and a balloon commissurotomy is done after the 20th week if they persist. Moderate or severe mitral stenosis is a reason to treat the valve before a planned pregnancy.

05Epidemiology

Rheumatic heart disease affected an estimated 33 million people in 2015 and 40 million in 2019, almost all in low- and middle-income countries, and causes about 300 000 deaths a year. Mitral stenosis is its typical lesion, and it is two to three times as common in women as in men. In sub-Saharan Africa, South Asia and the Pacific it presents in adolescents and young adults, often severe and fast-moving.

In Western Europe rheumatic fever has become rare, so rheumatic mitral stenosis is now seen mainly in older people and in migrants from high-prevalence countries. Degenerative calcific mitral stenosis, from annular calcification in the elderly and in kidney failure, makes up a growing share.

06Prognosis

Mitral stenosis progresses slowly over years, but once symptoms limit daily life the outlook without intervention is poor: in older series only about a third of patients with limiting symptoms were alive at 10 years, and almost none of those breathless at rest, while patients without symptoms did much better. Death came from pulmonary oedema, right heart failure and embolism. Atrial fibrillation and pulmonary hypertension mark a worse course.

After a successful balloon commissurotomy in a favourable valve, most patients are free of symptoms for a decade or more. Restenosis develops slowly and can be treated by a second balloon procedure or by surgery. A replaced valve brings the burdens of a prosthesis: lifelong anticoagulation for a mechanical valve, and wear of a bioprosthesis. Patients need follow-up with echocardiography, every year when the area is 1.5 square centimetres or less, every 2 to 3 years when the stenosis is milder, and regularly after an intervention, because restenosis can be silent. They should report breathlessness or palpitations early.