BySteven Lome, MD

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Mitral Stenosis Topic Review

BySteven Lome, MD

Etiology
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Pathophysiology
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Symptoms
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Physical Examination
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Diagnosis
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Treatment

Introduction

The mitral valve, so named because of its similarity to a bishop’s miter, has five important structural elements: 1) the mitral annulus, 2) the mitral valve leaflets, 3) the commissures, 4) chordae tendineae and 5) papillary muscles.

The typical normal adult mitral valve area is between 4 and 5 cm². (Hurst’s The Heart;Chapter 50, 12a.) This area allows the normal stroke volume to flow from the left atrium (LA) to the left ventricle without any significant pressure gradient. When any disease process decreases the mitral valve area, mitral stenosis (MS) develops. As mitral stenosis progresses, increased left atrial pressure is required to maintain stroke volume. This pressure increase is generated primarily by the right heart and results in increased pulmonary arterial and venous pressures that are responsible for nearly all of the clinical manifestations of mitral stenosis.

Etiology – Mitral Stenosis

By far the most common cause of mitral stenosis, rheumatic valvular disease accounts for approximately 98% of mitral stenosis cases. Rheumatic valvular disease is more common in females than in males. Up to 50% of the time, patients with newly diagnosed mitral stenosis do not report a history of rheumatic fever as a child. The incidence of mitral stenosis has drastically decreased in the United States since the advent of antibiotics, which resulted in the aggressive treatment of Streptococcus pyogenes pharyngitis — the primary cause of rheumatic heart disease.

Other causes of impaired left ventricular filling can mimic mitral stenosis in both hemodynamics and symptoms. Left atrial myxomas are relatively common and may occur as a part of a rare autosomal dominant syndrome with pigmented skin and mucosal lesions and cardiac and other myxomas, and multiple endocrine tumors (the Carney complex). (Correa R, et al. Eur J Endocrinol. 2015;1a.) Atrial myxomas are slow-growing tumors that may obstruct mitral valve inflow, causing functional mitral stenosis. Cor triatriatum sinister, a congenital cardiac abnormality, may also obstruct LV inflow. (Ather B, et al. Cor Triatriatum. 2021;2a.)

Rarely, pulmonary vein stenosis developing following attempted atrial fibrillation ablation may mimic mitral stenosis, presenting with dyspnea, cough, fatigue and decreased exercise tolerance.

The anterior leaflet of the mitral valve is the most common site of infectious vegetations in patients with infective endocarditis. Very large vegetations, as in fungal endocarditis, may obstruct LV inflow and cause symptoms of mitral stenosis.

A regurgitant jet from severe aortic regurgitation may impinge on the anterior leaflet of the mitral valve, causing LV inflow obstruction and the “Austin Flint” murmur.

Other rare causes of true mitral stenosis include congenital mitral stenosis, severe mitral annular calcification and prosthetic valve dysfunction.

A list of known causes of LV inflow obstruction, including conditions that mimic mitral stenosis, is below.

Acquired

Rheumatic valve disease
Left atrial myxoma
Left atrial thrombus
Large mitral valve vegetation
Pulmonary vein stenosis (post atrial fibrillation ablation)
Prosthetic valve dysfunction
Severe mitral annular calcification
Inflammatory disorders (systemic lupus erythematosus, rheumatoid arthritis)

Congenital

Congenital mitral stenosis
Cor triatriatum
Congenital pulmonary vein stenosis
Congenital subvalvular ring

The remainder of this review focuses on mitral stenosis due to rheumatic valvular disease.

Pathophysiology – Mitral Stenosis

In rheumatic heart disease, autoimmune inflammation involving the mitral valve produces thickening of the valve leaflets and commissural fusion. The mitral valve is often described as having a “fish-mouth” appearance. Whether the worsening of mitral stenosis over time is secondary to a smoldering rheumatic process or simply progressive mitral valve damage due to high pressures and turbulence is unknown; both most likely contribute to the slowly progressive process of mitral stenosis.

Over time, as mitral stenosis worsens and the mitral valve area decreases, right heart pressures increase to maintain cardiac output across the stenotic valve with a pressure gradient between the left atrium and the left ventricle. On exertion, with increases in cardiac output and increased flow through the mitral valve, the pressure gradient becomes exponentially larger, and pulmonary edema can occur.

This is explained by the modified Bernoulli equation:

Pressure gradient = 4V²

Thus, if the velocity (V) of flow is doubled, the transmitral pressure gradient increases by a factor of four. The resultant large increase in pulmonary and LA pressures is responsible for the exertional symptoms seen in mitral stenosis.

Symptoms – Mitral Stenosis

Early mitral stenosis is often asymptomatic, until the mitral valve area decreases enough to require large increases in pulmonary and left atrial pressure to maintain cardiac output with activity.

Advanced symptoms include fatigue, exercise intolerance, and, with the onset of right heart failure, paroxysmal nocturnal dyspnea and orthopnea. Symptoms of mitral stenosis are exacerbated by concomitant conditions that increase cardiac output, such as anemia, thyrotoxicosis and pregnancy.

Patients with moderate to severe mitral stenosis will have some degree of left atrial enlargement (LAE) due to the chronically increased left atrial pressures; this increases the likelihood of atrial fibrillation. With mitral stenosis, atrial contraction contributes about 20% of LV filling, and tachycardia decreases diastolic filling time. Therefore, the onset of atrial fibrillation with a rapid ventricular rate and loss of atrial contraction may result in significant reduction of cardiac output with fatigue, dyspnea, dizziness, and even syncope.

In the absence of atrial fibrillation, patients with mitral stenosis still have an increased risk for thrombus formation in their left atrial appendage due to stasis. This may lead to thromboembolic events including stroke, coronary embolism with myocardial infarction, acute mesenteric ischemia or acute digital ischemia (“blue toe syndrome”).

Less common today are symptoms of advanced valve disease. Hemoptysis may occur due to sudden rupture of a bronchial vein; this phenomenon is termed “pulmonary apoplexy.” Ortner’s syndrome may occur when a greatly enlarged left atrium compresses the left recurrent laryngeal nerve, leading to hoarseness. Chest pain from right ventricular ischemia may occur with severe pulmonary hypertension. Other signs of right heart failure, such as right upper quadrant pain due to hepatic congestion and peripheral edema, can also occur.

Physical Examination – Mitral Stenosis

Mitral stenosis is difficult to appreciate on physical examination. The 19th/early 20th century Canadian physician Sir William Osler told his students: “Mitral stenosis may be concealed under a quarter of a dollar. It is the most difficult of heart diseases to diagnose.”

The murmur of mitral stenosis is diastolic, low frequency, and referred to as a “rumble.” The first part of the mitral stenosis murmur reflects the pressure gradient between the left atrium and the left ventricle. It begins after S2 with the opening snap, then decrescendoes (see image below), ending in mid-diastole. The second part of the murmur occurs just before S1 in a crescendo fashion. This part of the murmur is due to the increased flow through the mitral valve during atrial contraction; this aspect of the murmur would be absent if the patient were in atrial fibrillation, as active left atrial contraction would be lost.

The severity of mitral stenosis can be estimated on physical examination by the timing of the opening snap in diastole and the length of the first part of the murmur. An opening snap that almost immediately follows S2 indicates severe mitral stenosis, whereas an opening snap that occurs somewhat later indicates milder mitral stenosis. This reflects a much higher left atrial pressure in severe mitral stenosis, with a transmitral gradient immediately after the mitral valve opens. A longer murmur indicates more severe mitral stenosis, as the pressure gradient persists throughout diastole.

Inspection of the jugular venous pulsations may reveal a prominent “A wave” attributable to vigorous right atrial contraction, or a prominent V wave due to tricuspid regurgitation that develops from pulmonary hypertension. The presence of “mitral facies” refers to a pinkish-purple discoloration of the cheeks produced by a chronic low cardiac output state combined with systemic vasoconstriction; this sign is rare and non-specific.

There may be a palpable S1 over the apex, and this finding is pathognomonic for mitral stenosis. A diastolic thrill may rarely be appreciated at the apex with the patient in the left lateral decubitus position.

Auscultation will reveal a loud, accentuated S1 in early mitral stenosis and a softer S1 in advanced mitral stenosis (see Heart Sounds Topic Review). The S1 sound is typically loud because the transmitral pressure gradient causes the mitral valve to remain fully open throughout diastole, closing only at the onset of systole. In far advanced mitral stenosis, the stenotic valve has extremely limited mobility, resulting in decreased intensity of S1. (Hurst’s The Heart;Chapter 50, 14a.) Accentuation of the P2 component of the S2 heart sound suggests pulmonary hypertension. A left ventricular S3 is almost always absent in pure mitral stenosis, as left ventricular early diastolic filling is impaired. The significantly increased opening pressure causes an opening snap to occur when the mitral valve leaflets suddenly tense and dome into the left ventricle. This high frequency sound is best heard at the apex.

Diagnosis – Mitral Stenosis

Transthoracic echocardiography (TEE) is the primary approach to both diagnosis and pathophysiologic evaluation of mitral stenosis. (Otto CM, et al. Circulation. 2020;42b(e113).) The mitral leaflet tips become calcified and thickened with a characteristic “hockey stick” appearance of the anterior mitral leaflet.

The two most important measurements made on echocardiography are the pressure half-time and the mitral valve area.

Because transmitral flow velocities can be directly measured with Doppler techniques, the transmitral pressure gradient can be calculated using the modified Bernoulli equation, as described above. The pressure half-time, defined as the interval in ms between maximal transmitral pressure gradient and the time at which the gradient has decreased to half the maximal value, can then be derived. (Baumgartner H, et al. J Am Soc Echocardiogr. 2009;12a.) The mitral valve area can be calculated using the continuity equation, and the pulmonary artery pressure can be estimated to assess the severity of pulmonary hypertension.

The 2020 ACC/AHA Guidelines categorize MS into four distinct stages (Stage A through D) on the basis of valve anatomy, valve hemodynamics, hemodynamic consequences of valve obstruction and the presence or absence of symptoms. (Otto CM, et al. Circulation. 2020;42b(e113).)

Stage A disease (at risk of MS) is characterized by mild valve doming in diastole with otherwise normal valve hemodynamics and an absence of symptoms. (Otto CM, et al. Circulation. 2020;42a(table 16, e113).)

Stage B (progressive) mitral stenosis is typified by rheumatic changes in the mitral valve, including fusion of the commissures, as well as valve doming in diastole. Hemodynamic characteristics of Stage B disease include higher transmitral flow velocities, a mitral valve area above 1.5 cm²and a diastolic pressure half-time below 150 ms. This may result in mild or moderate enlargement of the left atrium, but pulmonary pressure is normal at rest, and no symptoms are present. (Otto CM, et al. Circulation. 2020;42a(table 16, e113).)

Stage C disease (asymptomatic severe MS) shows the same rheumatic changes in the mitral valve as Stage B disease, but with greater hemodynamic dysfunction: the mitral valve area is 1.5 cm² or smaller, and the diastolic pressure half-time is 150 ms or longer. This results in severe left atrial enlargement and an elevated pulmonary artery systolic pressure (above 50 mm Hg). Like in Stage A and B disease, no symptoms are present. (Otto CM, et al. Circulation. 2020;42a(table 16, e113).)

Stage D (symptomatic severe) mitral stenosis is distinguished from the Stage C disease by the presence of symptoms: decreased exercise tolerance and exertional dyspnea. It is otherwise characterized by the same anatomic and severe hemodynamic features as Stage C mitral stenosis. (Otto CM, et al. Circulation. 2020;42a(table 16, e113).)

In cases where echocardiography is inconclusive or equivocal (and only then), (Baumgartner H, et al. J Am Soc Echocardiogr. 2009;12a) cardiac catheterization can be used measure the mitral valve area using the Gorlin equation for mitral valve area:

MVA = MVF
37.7 x (MVG)½

MVA = mitral valve area
MVF = mitral valve flow
MVG = mean mitral valvular gradient

Without intracardiac shunting and without aortic or mitral valve regurgitation, mitral valvular flow is identical to cardiac output. The Gorlin equation assumes that no shunt or left-sided valvular regurgitation is present and the mitral valve area remains constant. Then if mitral valve area remains constant and the cardiac output increases, the mitral valve gradient will increase exponentially — as previously described using the modified Bernoulli equation.

The ECG in mitral stenosis is often normal early in the disease. The most common finding is left atrial enlargement (P mitrale), but this finding is lost if the patient develops atrial fibrillation. Right heart strain may produce findings of right axis deviation and right ventricular hypertrophy on ECG. In isolated mitral stenosis, left ventricular hypertrophy is absent.

The chest radiograph will show left atrial enlargement. This finding is often referred to as a “double density.” Elevation of the left mainstem bronchus and a prominent pulmonary artery may also be seen. Both ECG and chest radiograph, however, are non-specific for mitral stenosis.

Treatment – Mitral Stenosis

The initial treatment of mitral stenosis relies on the prevention or early recognition of rheumatic heart disease. Prophylactic penicillin treatment for patients known to have rheumatic heart disease successfully reduces exacerbations and will limit the damage done to the mitral valve. Anticoagulation is of great importance to prevent the formation of a left atrial thrombus and embolic events. Even in the absence of atrial fibrillation, patients with certain risk factors including hypertension or hypercoagulable states should be anticoagulated. Antibiotic prophylaxis before dental procedures and certain surgeries is no longer recommended to prevent bacterial endocarditis unless a prosthetic valve is present.

Preload reduction with diuretics and salt restriction can relieve symptoms of mitral stenosis if pulmonary hypertension is present. Many patients experience symptoms only when the heart rate is elevated, as tachycardia decreases diastolic filling time significantly. Therefore, the use of beta-blockers can occasionally be beneficial, especially in patients with predominantly exertional symptoms.

The definitive treatments for mitral stenosis include percutaneous balloon mitral valvotomy (PBMV). In this procedure, a catheter is inserted through the femoral vein into the right heart, then across the interatrial septum into the left atrium, and finally across the stenotic mitral valve. A balloon is then inflated, fracturing the calcium deposits and relieving the stenosis. Unlike valvuloplasty for aortic stenosis, PBMV is highly successful when the valve anatomy is favorable with a low rate of restenosis. Complications include residual mitral regurgitation, a persistent atrial septal defect and, rarely, calcium embolization.

According to the 2020 ACC/AHA Guidelines, PBMV, performed at a comprehensive valve center (CVC), is indicated (recommendation class 1) for:

Patients with Stage D mitral stenosis with amenable valve morphology, no thrombus in the left atrium, and mild (below angiographic grade 2+) or no mitral regurgitation (Otto CM, et al. Circulation. 2020;46a(figure 7, e117).)

PBMV, performed at a CVC, is reasonable (recommendation class 2a) for:

Patients with Stage C mitral stenosis with amenable valve morphology, no thrombus in the left atrium, and mild (below angiographic grade 2+) or no mitral regurgitation (Otto CM, et al. Circulation. 2020;46a(figure 7, e117).)

PBMV, performed at a CVC, may be considered (recommendation class 2b) for:

Patients with Stage D mitral stenosis who either have a thrombus in the left atrium or concurrent mitral regurgitation (angiographic grade 2+ or higher), who exhibit severe symptoms (NYHA Functional Class III-IV) and are not candidates for surgery (Otto CM, et al. Circulation. 2020;46a(figure 7, e117).)
Patients with Stage C mitral stenosis with amenable valve morphology, no thrombus in the left atrium, mild (below angiographic grade 2+) or no mitral regurgitation and new onset of atrial fibrillation (Otto CM, et al. Circulation. 2020;46a(figure 7, e117).)
Patients with progressive MS (mitral valve area greater above 1.5cm²) who show exertional symptoms (NYHA Functional Class II-IV) and present with evidence of hemodynamically significant MS after exercise testing, if valve anatomy is permissive, there is no clot in the left atrium, and mild (below angiographic grade 2+) or no mitral regurgitation (Otto CM, et al. Circulation. 2020;46a(figure 7, e117).)

Surgical approaches to manage mitral stenosis include closed commissurotomy, open commissurotomy and mitral valve replacement.

Closed commissurotomy

Closed commissurotomy is similar to PBMV in that the mitral valve is not directly visualized, and a balloon is used to dilate the stenotic mitral valve. The criteria used for PBMV are the same used to assess which patients may benefit from closed commissurotomy.

Open commissurotomy

Open commissurotomy requires the use of cardiopulmonary bypass, significantly increasing cost and complication rates of the procedure. However, if necessary, the surgeon can debride calcifications on the mitral valve, remove any left atrial thrombi and remove the left atrial appendage — a common site for thrombus formation. Open commissurotomy is the treatment of choice in patients with known left atrial thrombi or mitral stenosis with concurrent severe mitral valve calcifications.

Mitral valve replacement

Mitral valve replacement (MVR) is another option for patients with symptomatic or severe mitral stenosis requiring definitive therapy. However, MVR is usually reserved only for patients who are not candidates for PBMV or commissurotomy due to the long-term complications associated with prosthetic valves. MVR may be the best option for patients with severe valvular thickening and subvalvular fibrosis with leaflet tethering. (Otto CM, et al. Circulation. 2020;46c(e117).) There are a number of transcatheter MVR systems in development, but as of August 2021, none had received FDA approval. (Hensey M, et al. JACC Cardiovasc Interv. 2021;4.)

Mitral valve surgery (commissurotomy preferred) is indicated for:

Patients with Stage D mitral stenosis who either have a thrombus in the left atrium or concurrent mitral regurgitation (angiographic grade 2+ or higher), who exhibit severe symptoms (NYHA Functional Class III-IV) and are suitable candidates for surgery (Otto CM, et al. Circulation. 2020;46a(figure 7, e117).)