Mitral stenosis is a diagnosis that has been declining in frequency due to near eradication of rheumatic fever.  In fact, in 1995, the Centers for Disease for Control declared that rheumatic fever was one of ten diseases that has been removed from the list of nationally nodifiable diseases. It is only about the last 35 years that this picture has changed with improved housing, reduction in family sizes, the widespread of penicillin and amoxicillin to treat strep throat, and tonsillitis. Despite this fact, in the mid-1980s, after more than a decade of the apparent absence of cases of rheumatic fever, numerous outbreaks occurred in a variety of geographic and socioeconomic settings across the United States, this could be because of a rise in homelessness and immunity to penicillin, use of antibiotics unnecessarily / or not completely, may produce a rise in this disease process once again.  In addition, patients who had rheumatic fever 30 to 50 years ago are now presenting with mitral stenosis.  These statements apply to the demographics of mitral stenosis in the United states, but they are not true for other parts of the world, where rheumatic fever is still epidemic.

Etiologies:

     As indicated in the above paragraph, the primary cause of mitral stenosis is acquired through Rheumatic Fever in childhood which can emanate from the group B and A streptococcus (GAS)  infection after a latent period of approximately 3 weeks.  It takes approximately 2 years after an acute onset of rheumatic fever for severe mitral stenosis to develop. The rheumatic process is expressed as an inflammatory reaction that involves multiple organs: primarily the heart, the joints, and the central nervous system usually affecting the tips of the mitral valve leaflets first, later scaring and calcifying the leaflets.  Streptococcal infections, such as scarlet fever or recurrent tonsillitis or pharyngitis (rheumatic equivalents) are considered to be the primary cause of mitral valve stenosis in as many as 24% of the patients with mitral stenosis.

The infection follows the flow through the heart, first the mitral valve then the aortic valve and then the tricuspid and pulmonic valves.

Streptococcus throat infections (preceding rheumatic fever) are characterized by:

    1.  Beefy read throat with exudate

    2.  Tender, anterior cervical lymph nodes

    3.  Fever (as high as 104 degrees by day two lasting from days to weeks)

    4.  Contagious - low incidence of resultant rheumatic fever if penicillin is administered within 10 days.

There is no specific clinical laboratory, or other test that establishes the diagnosis of rheumatic fever.  In 1944, T. Duckett Jones formulated a criteria for the diagnosis of rheumatic fever and these criteria are still valuable.  The most recent guidelines emphasize the diagnosis of initial attacks of rheumatic fever.  Divided clinical and laboratory findings into major and minor manifestations is based on the diagnostic importance of a particular finding.  If supported by evidence of preceding GAS infection, the presence of two major manifestations or one major and two minor manifestations indicates a high probability of rheumatic fever.

Major Clinical Manifestations:

1.  Carditis - affecting the endocardium, myocardium, and pericardium to varying degrees.  Almost always associated with a murmur of valvulitis.   Valvulitis (endocarditis) involving mitral and aortic valves and the chordae of the mitral valve is the most characteristic component of rheumatic carditis. Valvulitis that causes the mitral valve to become narrowed, is the result of thickening, sclerosis, retraction, and distortion of the valve leaflets and chordae tendinea, along with commissural fusion. Mitral insufficiency is the hallmark of rheumatic carditis.  Aortic insufficiency is less common and usually associated with mitral insufficiency.

2.  Arthritis - affecting many areas (polyarthritis) is the most common major manifestation of rheumatic fever.  Usually involves larger joints such as the knees, ankles, elbows, and wrists.  Characteristically there is swelling, redness, heat, severe pain, limitation of motion, and tenderness to touch.  The arthritis of rheumatic fever is benign and does not result in permanent joint deformity. If left untreated cases, usually lasts 2 to three weeks.

3.  Chorea - Sydenham's chorea, St. Vitus' dance or chorea minor occurs in about 20% of patients with rheumatic fever.  The manifestation usually is delayed and appears in 3 months or longer after the onset of rheumatic fever.  Sydenham's chorea is characterized clinically by purposeless and involuntary movements, muscular in coordination and weakness, and emotional lability. All muscles may be involved, but primarily muscles of the face and extremities.

4.  Eythema Marginatum - This distinctive rash is a rare manifestation of rheumatic fever occurring in less than 5% of patients.  It is a rash with pale centers and rounded margins.  Lesions vary greatly in size and occur mainly on the trunk and proximal extremities, not on the face.

5. Subcutaneous Nodules - These are firm, painless, freely movable nodules that measure 0.5 to 2 cm.

Minor Manifestations:

1. Fever - Fever is a nonspecific finding in patients with acute rheumatic fever.  The diagnostic value is limited because fever is encountered commonly in a variety of other diseases.  It mostly is used to support the diagnosis of rheumatic fever when only  a single major manifestation is present.

2. Group A streptococcus (GAS)  infection - It is important to establish an antecedent streptococcal infection in the form of demonstrating a GAS in the tonsillopharynx or an elevated or rising streptococcal antibody titer. Evidence of an antecedent streptococcal infection is required for the confirmation of the initial diagnosis of acute rheumatic fever.

Other etiologies of mitral stenosis that are more rare are calcified mitral annulus which is a functional mitral stenosis in terms of a narrowed calcified annulus, congenital partial or total anomalies ranging from leaflets, ring or commissure stenosis to stenosis involving chorde, or papillary muscle or hypoplastic mitral valves, and an area that needs to be mentioned is prosthetic valve dysfunction.

Some conditions that may mimic mitral stenosis consists of:

1.  left atrial tumor

2.  left atrial ball valve thrombus

3.  Infective endocarditis

4.  Pulmonary vein compression

5.  Cor Triatriautum

6.  Mitral annular calcification

Pathophysiology

Since carditis is the primary major manifestation of rheumatic fever, and the valves are affected, the process commonly begins with commissural fusion resulting in a narrowed valve.  Typically, the leaflets are thickened and have blunted and rolled edges.  The chordae are foreshortened and often matted together so that normal spaces between the chordae are obliterated.  The entire valve apparatus becomes altered into a funnel-like sleeve; when severe, the mitral valve takes on a "fish mouth" appearance and loses the ability to open during diastole.  Dense calcification is a frequent late accompaniment. Left atrial size in mitral stenosis is variable and depends on the severity and duration of the disease.  Atrial musculature is often replaced by fibrosis, but whether this indicates severe rheumatic myocarditis or merely late secondary changes is uncertain. 

rheumatic mitral valve                                                                                normal valve appearance

Pure mitral stenosis occurs in 25% of patients, whereas 40% have combined mitral stenosis and mitral regurgitation. 

In normal adults the cross-sectional area of the mitral valve orifice is 4 to 6 cm².  When the orifice is reduced to approximately 2 cm², which is considered to represent mild mitral stenosis, blood can flow from the left atrium to the left ventricle only if propelled by a small, although abnormal, pressure gradient.  When the valve opening is reduced to less than 1 cm², which is considered to represent critical mitral stenosis, a left atrioventricular pressure gradient of approximately 20 mm Hg (and therefore, in the presence of a normal left ventricular diastolic pressure, a mean left atrial pressure of approximately 25 mm Hg) is required to maintain normal cardiac output at rest.

Signs and Symptoms

The principle symptom of mitral stenosis is dyspnea, 80% of patients will have shortness of breath. This is due to the elevated left atrial pressure.  First bouts of dyspnea in patients with mitral stenosis are usually precipitated by exercise, emotional stress, sexual intercourse, infection, or atrial fibrillation, all of which increase the rate of blood flow across the mitral orifice and result in further elevation of left atrial pressure.  The mechanism in which dyspnea occurs is because of the rise in left atrial pressure due to the overload of the left atirum (left atrial dilatation is a protective mechanism  to protect the lung beds resulting from increase pressure) , the left atrium emptying time increases resistance to the filling of the left atrium from the pulmonary veins.  This resistance increases the stiffness and reduces the compliance in the lungs.  The heart rate will increase which will further increase pulmonary congestion and result in pulmonary edema, (more liquid than air exchange because the lymphatic system cannot keep up with drainage).  Eventually the pressure will increase in the pulmonary vasculature and right ventricle.  The right heart has to work harder to pump blood to the lungs and may result in pulmonary hypertension and the right heart may eventually fail over time. 

The patient will be fatigued and may complain of chest pain due to pulmonary hypertension and palpitation due to atrial fibrillation.

The patient may be horse because of a large LA pressing on the left laryngeal nerve, enlarged tracheobronchial lymphnodes, and dilated pulmonary artery this is called Ortner's syndrome.

The tendency for embolization correlates inversely with cardiac output ( the lower the CO the greater the tendency) and directly wit h the patients age and the size of the left atrial appendage, 80% of the patients with mitral stenosis in whom systemic emboli develop are in atrial fibrillation.

Atrial fibrillation almost always develops with the passage of time.  The left atrium becomes distended, irritated, static blood occurs and this is what causes an onset of atrial fibrillation.  This static blood can develop into a clot formation and embolize.  The left atrial appendage is usually the site for clot formation. Atrial fibrillation per se causes diffuse atrophy of atrial muscle, further atrial enlargement.

Hemoptysis is the second common presenting symptom of mitral stenosis. This develops due to pulmonary hemorrhage from a sudden rise in the left atrial pressure and rupture of the bronchi and notation of blood in the sputum.

Pulmonary hypertension in patients with mitral stenosis results from (1) passive backward transition of the elevated left atrial pressure; (2) pulmonary arteriolar constriction, which presumably is triggered by the left atrial and pulmonary venous hypertension; (3) organic obliterative changes in the pulmonary vascular bed, which may be considered to be a complication of longstanding and severe mitral stenosis.  In time, severe pulmonary hypertension results in right sided failure, with dilatation of the right ventricle and its annulus, and secondary tricuspid and sometimes pulmonic regurgitation.

Physical Examination

Two-thirds of mitral stenosis patients are female.  Patients with severe mitral stenosis, a low cardiac output, pulmonary hypertension and systemic vasoconstriction may exhibit "mitral facies".  This consists of a patchy, pinkish-purple appearance of the cheeks resulting from dilated venules.  Such subjects often manifest peripheral cyanosis as well.  Patients with with advanced mitral valve disease and right ventricular failure typically are thin and often have a cyanosis and peripheral edema.

The arterial pulse is usually normal, but in patients in whom the stroke volume is reduced, it may be small in volume.  In patients in sinus rhythm, the jugular venous pulse usually exhibits a prominent  A wave is often seen.  In patients with atrial fibrillation, the A wave and X descent disappear and there is only one crest (V wave) in the jugular venous pulse.

Heart Sounds:

                                                                                         Intercardiac pressure and sound relationship in mitral stenosis

First heart sound:

A loud S₁ is heard when the mitral valve is thickened and stenosed, but still pliable and flexible and is not heavily calcified.  The mitral valve leaflets remain maximally open until ventricular systole begins, at which point the valve closes quickly and creates a loud sound, in part related to decreased compliance of the leaflets themselves.  Conversely, if the valve is particularly thick and calcified, there may be relatively little movement of the valve leaflets with opening or closing; hence, S₁ (and the opening snap OS) may be soft.  The loud S₁ of mitral stenosis often is palpable.

Second heart sound:

The pulmonic component (P₂) of the second heart sound is often increased in amplitude due to pulmonary hypertension.

Opening Snap:

The OS is one of the classic findings in cardiac physical diagnosis.  A loud OS indicates the diagnosis of mitral stenosis.  The OS is the sound produced precisely when the stenotic mitral valve leaflets maximally open; as a loud S₁ in mitral stenosis requires the valve to be flexible and mobile, so does the prominent OS.  The OS is due to sudden tensing of the valve leaflets just after the valve cusps heave completed their opening excursion.  Neither a loud S₁ nor an OS will be present with advanced deformity of the valve involving severe thickening and calcification but the degree of severity can not be qualified.

The OS occurs earlier or closer to S₃ (third heart sound).  The unusual combination of an OS and an S₃ should make one think of combined mitral stenosis and mitral regurgitation.

Diastolic Murmur:

The most notable finding on examination of patients with mitral stenosis, in addition to the OS, is a diastolic rumbling murmur best heard at the cardiac apex with the bell of the stethoscope. The duration of the murmur is a guide to the severity of the mitral narrowing.

Laboratory Examination:

Electrocardiography - The ECG is a relatively insensitive technique for the detection of mild mitral stenosis, but does show characteristic changes in moderate or severe obstruction.  Left atrial enlargement (P-wave changes sometimes they appear broad and bifid).  When atrial fibrillation is present, the fibrillatory waves are usually course.  Right axis deviation can indicate pulmonary hypertension and with severe mitral stenosis there may be right ventricular hypertrophy.  Left ventricular hypertrophy suggests aortic valve disease.

Chest X-ray - left atrial enlargement with normal left ventricular size can be seen on the left anterior oblique view.   Occasionally, calcification of the mitral valve is evident on the lateral view and can appear "c" or "j" shaped). Radiological changes in the lung fields are useful in estimating the height of pulmonary venous pressure and thereby the severity of mitral stenosis.  Interstitial edema, and indication of severe obstruction is manifested as Kerley B lines (dense, short, horizontal lines most commonly seen in the costophrenic angles).  This finding is present in 30% of patients with resting pulmonary artery wedge pressure below 20 mmHg and in 70% with PCWP of > 20 mmHg.  Severe, longstanding mitral obstruction often results in Kerley A lines (straight, dense lines up to 4 cm in length running toward the hilum).

Typically, left atrial enlargement as well as a prominent left atrial appendage is also seen.  is almost always evident on the lateral and left anterior oblique views especially after the administration of barium into the esophagus.  If pulmonary venous pressure is elevated (as is usual), the upper zone vessels are dilated.  A higher pressure in the pulmonary veins produces septal lines and pleural effusions.  With chronic disease the valve frequently becomes calcified.  In patients with mixed stenosis and regurgitation the left atrium may become very large and calcified. Long -standing pulmonary venous hypertension gives rise to pulmonary arterial hypertension and this is reflected in enlargement of the pulmonary artery, right ventricle and right atrium.

Cardiac Catheterization:

Catheterization is rarely necessary in the era of echocardiography, either to make the diagnosis or to assess the severity of mitral stenosis.  The two circumstances in which catheterization is indicated are the presence of a discrepancy between a patient's symptoms suggesting severe mitral stenosis and an non-invasive estimation (findings from echocardiography)  of mild to moderate mitral stenosis or when other problems such as concomitant coronary artery disease which is important for planning surgery must be known. 

A simultaneous left ventricular and pulmonary capillary wedge pressure can demonstrate a mitral valve gradient throughout diastole.

In mitral stenosis and sinus rhythm, the left atrial pressure pulse generally exhibits a prominent atrial contraction in the form of an elevated A wave and a gradual pressure decline after mitral valve opening (Y descent).  The mean left atrial pressure is elevated about 12 mmHg, > 20mmHg is considered severe.  In patients with severe mitral stenosis, and or those in whom the pulmonary vasculature resistance is significantly increased, pulmonary arterial pressure is elevated when the patient is at rest.  The left atrial size and thickening of the mitral valve can be assessed through angiography, and may outline a thrombi. Cardiac output can be determined by the Fick or dilution method and simultaneous registration of the LV-LA or (LV-PCW) pressures.

Treatment:

Patients with rheumatic heart disease should receive prophylaxis antibiotic therapy t prevent recurrence of rheumatic fever and against infective endocrditis.

Catheter balloon valvuloplasty can be performed or if necessary a commissurotomy or even mitral valve replacement.

             Hemodynamic tracings in a patient with mitral stenosis before (A) and after (B) mitral valvuloplasty.