Mitral Stenosis Topic Review

Etiology | Pathophysiology | Symptoms | Physical Examination | Diagnosis | Treatment

Introduction

The area of a normal mitral valve is 4 to 6 cm2. This area is sufficient to allow a great deal of blood to flow from the left atrium (LA) to the left ventricle. When any disease process decreases the mitral valve area, mitral stenosis (MS) develops. As mitral stenosis progresses over time, the pressure in the left atrium rises. This pressure is transmitted to the pulmonary veins, the pulmonary vasculature, and eventually to the right side of the heart. This transmitted pressure is responsible for nearly all of the clinical manifestations of mitral stenosis.

mitral_stenosis

Etiology – Mitral Stenosis

The number one cause of mitral stenosis, rheumatic valvular disease accounts for approximately 98% of the condition. Rheumatic valvular disease is more common in females than in males. Up to 50% of the time, a person with newly-diagnosed mitral stenosis will 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.

Many other causes of impaired left ventricular filling exist and can mimic mitral stenosis in both hemodynamics and symptoms. Left atrial myxomas are relatively common and occur as a part of the Carney complex; the slow-growing tumors obstruct the mitral valve, causing mitral stenosis. Pulmonary vein stenosis after attempted radiofrequency ablation of atrial fibrillation can also occur, and this may mimic mitral stenosis; however, newer techniques have reduced this risk.

The anterior leaflet of the mitral valve is the most common site for an infectious vegetation to form in patients with infective endocarditis. If the vegetation grows to a large enough size, as often occurs in fungal endocarditis, obstruction of LV filling may occur and symptoms of mitral stenosis may develop. When the regurgitant jet from severe aortic regurgitation strikes the anterior leaflet of the mitral valve, mitral stenosis hemodynamics can occur, causing the “Austin-Flint” murmur. Other rare causes of true mitral stenosis include congenital mitral stenosis, severe mitral annular calcification and prosthetic valve dysfunction.

A complete list of causes of mitral stenosis, including those 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, an autoimmune attack on the mitral valve produces thickening of the valve leaflets. 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 mitral valve damage due to high pressures and turbulence is unknown; both most likely contribute to the progressive nature of mitral stenosis.

Over time, as mitral stenosis worsens and the mitral valve area decreases, the left atrial pressure increases to try to force more blood into the left ventricle. A pressure gradient develops between the left atrium and the left ventricle to help assist diastole. The elevated left atrial pressures are transmitted to the pulmonary veins and the right side of the heart. On exertion, with increases in cardiac output and the velocity of flow through the mitral valve, the transmitted 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 four times. The resultant large increase in LA pressure is primarily responsible for the exertional symptoms seen in mitral stenosis.

Symptoms – Mitral Stenosis

Mitral stenosis is often asymptomatic early in disease, until the mitral valve area decreases enough to cause a large increase in left atrial pressure. The first symptoms of mitral stenosis occur on exertion when a higher cardiac output is needed, as explained above. This occurs because the mitral valve area is fixed, the cardiac output is unable to increase enough above resting (a low cardiac reserve is present) and high pressures are transmitted to the pulmonary vasculature. This transmission of pressures results in transient pulmonary edema and exertional dyspnea.

Fatigue and inability to exercise are also common complaints. Signs of left heart failure including paroxysmal nocturnal dyspnea and orthopnea can occur. Symptoms of heart failure with concomitant mitral stenosis also occur in disease states that require an increased cardiac output for the same reason such as anemia, sepsis and thyrotoxicosis, as well as during pregnancy.

Most patients with moderate to severe mitral stenosis will have some degree of left atrial enlargement (LAE) due to the chronic increases in left atrial pressures, predisposing them to atrial fibrillation. Because patients with mitral stenosis rely on atrial contraction for about 20% of their cardiac output, and tachycardia decreases diastolic filling time, the onset of atrial fibrillation with a rapid ventricular rate and loss of atrial contraction results in significant symptoms of low cardiac output and heart failure. These include fatigue, dyspnea, lightheadedness 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 stagnation of blood. This may lead to embolic events including stroke, acute myocardial infarction, acute mesenteric ischemia or “blue toe syndrome.”

Hemoptysis may occur due to sudden rupture of a bronchial vein; this phenomenon is termed “pulmonary apoplexy.” Ortner syndrome may occur when a massively enlarged left atrium compresses the left recurrent laryngeal nerve, leading to a hoarse voice. Chest pain from right-sided heart strain may occur due to severe venous pulmonary hypertension. Other signs of right heart failure, such as right upper quadrant pain due to hepatic congestion and peripheral edema, can occur.

Physical Examination – Mitral Stenosis

Mitral stenosis is difficult to appreciate on physical exam. Canadian physician Sir William Osler said: “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 decrescendos (see picture 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 of blood through the mitral valve that occurs during atrial contraction; it makes sense that this aspect of the murmur would be absent if the patient is in atrial fibrillation, as active left atrial contraction would be lost.

MS

The severity of mitral stenosis can be estimated on physical exam by the position 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 later in diastole indicates milder mitral stenosis. This happens because there is a much higher left atrial pressure in severe mitral stenosis, and a transmitral gradient develops immediately after the mitral valve opens. A longer murmur indicates more severe mitral stenosis, as it takes more time for blood to pass through the stenotic mitral valve and for the pressure gradient to dissipate once the mitral valve opens.

Inspection of the jugular venous pulsations may reveal a prominent “A wave,” attributable to vigorous 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 of heart sounds will reveal a loud, accentuated S1 early in mitral stenosis and soft S1 in severe mitral stenosis (see Heart Sounds Topic Review). This occurs because the increased left atrial pressures in early mitral stenosis force the mobile portion of the mitral valve leaflets far apart. At the onset of ventricular systole, they are forced closed from a relatively far distance, resulting in a loud S1. When mitral stenosis becomes more severe and the mitral valve leaflets become significantly more calcified, their mobility declines and they are unable to be separated a great deal, resulting in a soft or even absent S1 heart sound. When pulmonary hypertension develops, the P2 component of the S2 heart sound will be accentuated. 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

Echocardiography is the primary means to both diagnose and evaluate the severity of mitral stenosis. The mitral leaflet tips become calcified and thickened. A characteristic “hockey stick” appearance of the anterior mitral leaflet is seen.

Below is an echocardiographic view of this finding:

The two most important measurements made on echocardiography include the pressure gradient between the left ventricle and left atrium and the mitral valve area.

Because transmitral velocities can be determined, the transmitral pressure gradient can be calculated using the modified Bernoulli equation, as described above. The mitral valve area can be found using the continuity equation, and the pulmonary artery pressure can be calculated to assess the severity of pulmonary hypertension.

Cardiac catheterization can also measure the mitral valve area using the Gorlin equation:

MVA =       MVF       
         37.7 x (MVG)½

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

Mitral valvular flow is proportional to cardiac output. This equation assumes that no mitral regurgitation is present and the mitral valve area remains constant. With this equation, it is clear that if the 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.

Mitral stenosis is categorized as mild, moderate or severe. The parameters associated with the severity are summarized below.


Pressure Gradient (mmHg) Mitral Valve Area (cm2)
Normal 0 > 4.0
Mild 1-5 2.5-4.0
Moderate 6-10 1.0-2.5
Severe > 10 < 1.0

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

The chest radiograph will again 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 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 if 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 be beneficial, at times, especially in patients with predominantly exertional symptoms.

Definitive treatment includes 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 down across the stenotic mitral valve. A balloon is then inflated, fracturing the calcium deposits and relieving the stenosis. Unlike valvuloplasty in the setting of aortic stenosis, PBMV is highly successful with a low rate of restenosis. Complications include residual mitral regurgitation, a persistent atrial septal defect and, rarely, calcium embolization.

PBMV is indicated for patients who are symptomatic with moderate to severe mitral stenosis in the absence of a pre-existing LA thrombus and mitral regurgitation. PBMV is also indicated for patients who are asymptomatic with severe mitral stenosis and a Wilkins (Abascal) echocardiographic score of 8 or less.

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

Closed commissurotomy

This 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

This requires the use of a cardiopulmonary bypass machine, significantly increasing cost and complication rates of the procedure. However, the surgeon is able to debride calcifications on the mitral valve, remove left atrial thrombi if found, and remove the left atrial appendage — a common site for thrombi 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

This is also an option for patients with symptomatic or severe mitral stenosis requiring definitive therapy. This is usually reserved only for patients who are not candidates for PBMV or commissurotomy due to the long-term complications associated with prosthetic valves. Patients with mitral stenosis along with moderate to severe mitral regurgitation can benefit greatly from mitral valve replacement.

The indications for PBMV according to the American College of Cardiology/American Heart Association guidelines depend on the severity of symptoms based on NYHA Functional Class, the presence of pulmonary hypertension and the morphology of the valve, which determines if PMBV is possible. The guidelines have excellent flow sheets to help determine the correct definitive treatment. Contraindications to PMBV include moderate or severe mitral regurgitation, a left atrial appendage thrombus or a Wilkins echocardiographic score of 8 or higher. Open surgical commissureotomy is rarely performed, and mitral valve replacement is the preferred surgical intervention when indicated.

Level of Indication
Indications for PMBV
Indications for mitral valve replacement
Class I
NYHA Functional Class II-IV and moderate to severe MS
NYHA Functional Class III-IV, moderate to severe MS and valve not favorable for PMBV
Class IIA
NYHA Functional Class III-IV, moderate to severe MS, valve not favorable for PMBV, but high-risk surgical candidate
NYHA Functional  Class II, moderate to severe MS, valve not favorable for PMBV and PA pressure > 60
Class IIIB
NYHA Functional Class II-IV, mild MS and PA pressure > 60 upon exercise

References:
1. ACC/AHA Guidelines: Valvular Heart Disease
2. Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine
3. Carabello et al. Mitral Stenosis. Circulation 2005;112:432-437.
4. Hurst’s the Heart, 13th Edition