Mitral stenosis

Mitral Stenosis

I. What every physician needs to know.

Mitral stenosis (MS) results from thickening and immobility of the mitral valve leaflets. This condition results in an obstruction in blood flow from the left atrium to the left ventricle. If left untreated, the stenosis gradually worsens and can cause fluid overload, pulmonary hypertension and right-sided heart failure.

MS is most frequently caused by rheumatic fever, although only about half the patients remember having rheumatic fever. In developed countries, other causes of mitral stenosis include degenerative changes such as mitral annular calcification with calcium deposition in the valve leaflets, congenital abnormalities, carcinoid heart disease, and systemic lupus erythematosus. Rheumatic heart disease is believed to be caused by an inflammatory process in the valves initiated by cross-reactivity between streptococcal antigen and the valve tissue. The valve itself is not infected in rheumatic heart disease. A recurrence of rheumatic fever increases the chances of developing rheumatic heart disease.

In developed countries, the rate of progression of MS is very slow. The interval between rheumatic fever and onset of symptoms can be 20-40 years, with symptoms developing between the 3rd and 5th decades of life. Progression from mild symptoms to severe disability can be up to 10 years.

In developing countries, where patients can be repeatedly exposed to group A streptococcus, patients can develop symptoms in their 20s and have a more rapid progression of disease.

Historically, MS was the first disease to be diagnosed by echocardiography and the first valve lesion to be treated with surgery.

II. Diagnostic Confirmation: Are you sure your patient has Mitral Stenosis?

The diagnosis of MS is made with cardiac imaging, typically a transthoracic echocardiography (TTE). Both the mitral valve area and the gradient are measured with a TTE to classify MS into mild, moderate and severe based on ACC/AHA guidelines.

The normal mitral valve area is 4-6cm^2 and the mean transmitral gradient is 0 mmHg.
Mild MS is classified by a valve area >1.5cm^2 and a mean gradient <5mmHg.
Moderate MS has a valve area 1-1.5cm^2 and a mean gradient 5-10mmHg.
Severe MS has a valve area <1.0cm^2 and a mean gradient >10mmHg.

Symptoms typically begin in moderate MS, and worsen when the disease is severe.

A. History Part I: Pattern Recognition:

Symptoms of MS are related to the severity of the stenosis as reflected by the left atrial pressure, pulmonary pressures and the cardiac output.

The most common (and sometimes only) symptom of MS is dyspnea. Chronic elevations in left atrial pressure and pulmonary venous pressure result in significant dyspnea and often frank pulmonary edema. Pulmonary arterioles develop reactive changes over time which can lead to pulmonary hypertension and eventually right-sided heart failure.

Exercise often brings about dyspnea in patient with MS, and therefore many of these patients reduce their activity level to avoid symptoms. Patients with MS decompensate with tachycardia or high flow due to a decrease in diastolic filling time and an increase in the pressure gradient across the valve. Patients with severe MS can be asymptomatic if their heart rate consistently remains low. A stenotic mitral valve remains as a fixed orifice despite changes in flow and pressure with exercise or dobutamine.

Atrial contraction helps maintain flow across the stenotic mitral valve. Conditions associated with a loss in atrial contraction, such as atrial fibrillation, is an important precipitating factor in dyspnea. Chronic or paroxysmal atrial fibrillation occurs in roughly 45% of patients with MS.

Hemoptysis can occur due to increased pulmonary pressures and vascular congestion. Hemoptysis can present as a sudden hemorrhage (due to rupture of a thin walled vein), blood tinged sputum after coughing (due to bronchitis) or pink frothy sputum (from pulmonary edema).

Embolic events can occur, most commonly to the cerebral vasculature. Predictors of embolization in patients with MS are increased size of the left atria and its appendage, and presence of atrial fibrillation. In fact, over 80% of patients with an embolic event are in atrial fibrillation.

Rarer symptoms include chest pain (mostly commonly due to pulmonary hypertension), fatigue, hoarse voice from left atrial enlargement compressing the laryngeal nerve, and signs of right heart failure (e.g., lower extremity edema, ascites and hepatomegaly).

Death is mainly due to heart failure or systemic embolization.

B. History Part 2: Prevalence:

MS is most frequently caused by rheumatic fever. The prevalence and incidence of rheumatic fever has decreased dramatically in Western countries during the last 50 years. Published reports estimate the incidence of rheumatic fever between 3 to 14 cases per 100,000 hospitalized children. The mean age of onset of rheumatic fever is 10 years old. As the incidence of rheumatic fever has fallen, so too has the incidence of MS. In 1960, MS accounted for 43% of all valve disease at European centers, compared with just under 10% in 1985.

In contrast, developing countries encounter higher rates of rheumatic fever. The mean incidence of rheumatic fever is 19 per 100,000 total population. Accordingly, in developing countries, rheumatic heart disease is a leading cause of cardiovascular death in patients younger than 60.

C. History Part 3: Competing diagnoses that can mimic Mitral Stenosis.

A left atrial myxoma or ball-valve thrombus that obstructs left ventricular inflow can be mistaken as mitral stenosis. These diastolic murmurs can be distinguished from MS because there is no opening snap or presystolic crescendo to the S1.

Diastolic apical murmurs can be heard in the absence of stenosis in the setting of excessive flow through a normal mitral valve. Conditions causing flow murmurs include anemia, thyrotoxicosis, severe mitral regurgitation or a large left-to-right shunt as in a ventricular septal defect. Flow murmurs differ from the murmur of MS because flow murmurs usually starts with an S3, they are short, and have no presystolic crescendo to the S1.

In addition, the Austin Flint murmur is an apical diastolic murmur that imitates the murmurs of MS but is due to an aortic regurgitation stream that prevents the mitral valve from opening fully. It can be distinguished from MS because there is no opening snap and no presystolic crescendo to the S1.

D. Physical Examination Findings.

Though the physical exam findings are often subtle, they can be diagnostic of MS.

Most physical exam findings are found on the cardiac exam.

The arterial pulses are diminished due to a low stroke volume.

Jugular exam may reveal a prominent “a” wave from pulmonary hypertension and an elevated right atrial pressure, and a prominent “c-v” wave from tricuspid regurgitation.

The apical impulse may be reduced in intensity from decreased left ventricular filling. A right ventricular heave, if present, reflects underlying pulmonary hypertension.

The first heart sound may be loud at first (due to widely separated leaflets from increased left atrial pressure) but becomes softer as the valve becomes more rigid.

The second heart may be normal, but becomes louder as pulmonary hypertension progresses.

An opening snap of the mitral valve occurs in early diastole at the apex. This snap is from an abrupt halt in the leaflet opening after an initial rapid opening.

The murmur of MS is a low-pitched diastolic rumble most prominent at the apex. Due to a relatively low gradient across the mitral valve, the MS murmur is faint and difficult to hear. It is best appreciated using the bell of the stethoscope with the patient in the left lateral decubitus position, listening over the site where you palpated the apical impulse. The shape of the murmur is a decrescendo rumble that ends with a late crescendo to the first heart sound. This sound may be likened to the growl (rumble) and bark (late crescendo) of a dog. The intensity of the murmur does not correlate with the severity of the valvular disease.

Signs of right heart failure may also be found. These include lower extremity edema, hepatomegaly, and ascites. A tricuspid regurgitation murmur from pulmonary hypertension is a holosystolic murmur along the left sternal border that increases in intensity with inspiration.

E. What diagnostic tests should be performed?

Two commonly obtained tests can help assess the duration of severe mitral stenosis. Severe MS of a long duration often leads to left atrial enlargement and pulmonary hypertension, which can be picked-up on EKG and chest x-ray.

EKG: left atrial enlargement alters the p wave, making it broad (lead II duration >0.12sec), notched and increased in amplitude. Atrial fibrillation is also frequently seen. Pulmonary hypertension and associated right ventricular hypertrophy can be seen as a rightward axis (S>R in lead I and aVL) and a tall R wave in V1 and V2 (R/S ratio >1).

Chest x-ray: left atrial enlargement causes the left heart border to straighten and the left mainstem bronchus to elevate. Significant pulmonary hypertension leads to an enlargement of the pulmonary arteries at the hilum.

The most important diagnostic test in patients with mitral stenosis is echocardiography.

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Laboratory studies do not help to establish a diagnosis of MS.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Echocardiography is used to diagnose and judge the severity of MS, as well as exclude diseases that mimic MS.

Typically, the evaluation begins with a transthoracic echocardiography (TTE). As previously mentioned, both the mitral valve area and the gradient are measured with a TTE and classify MS into mild, moderate and severe based on ACC/AHA guidelines.

The normal mitral valve area is 4-6cm^2 and the mean transmitral gradient is 0 mmHg.
Mild MS is classified by a valve area >1.5cm^2 and a mean gradient <5mmHg.
Moderate MS has a valve area 1-1.5cm^2 and a mean gradient 5-10mmHg.
Severe MS has a valve area <1.0cm^2 and a mean gradient >10mmHg.
Symptoms typically begin in moderate MS, and worsen when the disease is severe.

In addition to establishing severity of disease, changes to the mitral valve on TTE can help determine which patients will require valvotomy. These changes include: the degree of fibrosis/thickening, the amount of leaflet calcification, restriction in leaflet motion/rigidity and the degree of commissural fusion.

Changes to the mitral valve apparatus diagnostic of rheumatic heart disease are fusion of the leaflet commissures and a thickening and shortening of the chordae tendineae.

Transesophageal echocardiography (TEE) is typically required before valvuloplasty to provide a more detailed image of the anatomy and exclude the possibility of a clot in the left atrium or left-atrial appendage.

Exercise echocardiography is occasionally needed to assess disease severity in borderline symptomatic patients or to provoke symptoms in inactive patients. Additionally, if a patient’s symptoms seem more severe than expected based on a resting TTE, then stress echo can diagnose exertional pulmonary hypertension. Pulmonary systolic pressures >60 mmHg with exertion is an indication for interventional treatment of MS.

Cardiac catheterization provides a direct measurement of intracardiac pressures and a precise gradient across the mitral valve. Due to its invasive nature, the role for cardiac catheterization to evaluate MS is limited to certain instances. Cardiac catheterization may be warranted if: noninvasive tests are inconclusive; if there is a discrepancy between clinical symptoms and echocardiography findings; if there is a discrepancy between the mitral valve area and mean gradient on echocardiography, or if the degree of pulmonary arterial hypertension is out of proportion to the severity of MS.

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.

Due to high cost and lack of clear diagnostic benefit over echocardiography, cardiac MRI is not recommended as part of the evaluation of MS.

III. Default Management.

In general, patients with MS who are asymptomatic are managed with outpatient follow-up. Patients with MS who are symptomatic may require hospitalization for expedited symptom control. Typically, diuretics are given to relieve pulmonary congestion while rate controlling agents can lower the transmitral pressure gradient.

Second, as MS is a mechanical disorder, symptomatic patients generally require an intervention to relieve the stenosis through surgery or percutaneous mitral balloon valvotomy (PMBV).

A. Immediate management.

Symptomatic patients with MS should receive gentle diuresis to reduce the pulmonary congestion and edema.

Loop diuretics are typically the diuretic of choice. Typical initial doses of intravenous loop diuretics are – 40 mg furosemide, 1 mg bumetanide or 10 mg torsemide. Patients on chronic diuretic therapy typically require higher doses of therapy in the acute setting. Throughout the hospitalization, diuretic dosing should be individualized according to the patient’s clinical response.

Patients with MS who are symptomatic at rest or with minimal exertion may benefit from beta-blockers, regardless if the patient is in atrial fibrillation or sinus rhythm. Beta-blockers decrease heart rate and cardiac output, which in turn lowers the transmitral gradient and pulmonary capillary wedge pressure. The lower the heat rate, the more time for diastolic filling across the mitral valve and the lower the pressure gradient across the valve. However, before initiating beta-blockers in these patients, make sure the patient’s symptoms are not due to severe left ventricular systolic dysfunction, which can be worsened by beta-blocker therapy in the acute phase of decompensated heart failure.

Patient with MS and current atrial fibrillation should be treated according to general treatment guidelines of atrial fibrillation. Controlling the ventricular rate is especially important for patients with MS. Typically, beta-blockers or calcium-channel blockers are used for rate control. Hemodynamically unstable patients may require urgent cardioversion. In stable patients, cardioversion into sinus rhythm is reserved only for a few instances. Symptomatic patients with a contraindication to long-term anticoagulation, and patients with a previous thromboembolism despite adequate anticoagulation can be targeted for cardioversion from atrial fibrillation to sinus rhythm. In general, however, it becomes increasingly difficult to maintain a patient in sinus rhythm as the severity of MS increases.

Every effort should be given to anticoagulate patients with MS who have atrial fibrillation (paroxysmal or persistent), a current left atrial thrombus or who have had a prior embolic event. The stroke risk for patients with MS and chronic atrial fibrillation may be as high as 7-15% per year. If there is a possibility of an inpatient invasive procedure, long acting anticoagulants such as coumadin should not be given. Coumadin, with an INR range 2.0-3.0, can be started once it is clear no invasive procedure is required during the hospitalization.

The role of digoxin in patients with MS and symptomatic left ventricular systolic dysfunction is unchanged from typical management of patients with systolic heart failure. Digoxin is not warranted in patients with MS in sinus rhythm and preserved left ventricular systolic function.

B. Physical Examination Tips to Guide Management.

Patients with MS and pulmonary edema may present with crackles on lung exam. After diuresis, these crackles should disappear as the pulmonary edema resolves if the underlying lung function is normal.

Likewise, patients with MS and pulmonary hypertension may present with signs of right-heart failure such as lower extremity edema. After diuresis, the lower extremity edema should improve.

C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.

Symptomatic patients who are being treated with loop diuretics should have their serum potassium and creatinine monitored daily.

Diuretic therapy may result in hypokalemia, which should be aggressively repleted.

Over-diuresis may result in acute kidney injury and resultant decrease in the glomerular filtration rate.

The level of anticoagulation should be closely monitored while the patient is hospitalized. If the patient is on coumadin, obtain a daily INR. Intravenous heparin should have PTT levels checked according to hospital protocol.

Obtaining serial B-type natriuretic peptide (BNP) levels to assess response to diuretic therapy is not indicated.

D. Long-term management.

Initial medical management is used to relieve symptoms, but long-term management generally requires an intervention to relieve the mitral valve obstruction.

An intervention is typically required in patients with moderate or severe MS and either:

Symptoms of heart failure
Asymptomatic with significant pulmonary hypertension (pulmonary artery systolic pressure >50 mmHg at rest or >60 mmHg with exercise)

The choice of intervention is either percutaneous mitral balloon valvotomy (PMBV) or surgery – closed valvotomy, open valvotomy with possible mitral valve repair, or mitral valve replacement.

Choice of intervention

PMBV is the mainstay of treatment for mitral stenosis. The technique is as effective as open valvotomy with reduced morbidity and cost in most patients.

A dilating device is inserted on the venous side through the atrial septum, and is passed across the mitral valve. Inflation and rapid deflation of the balloon splits the commissures and may provide clinically significant improvement. The technique is stopped when an adequate valve area is achieved or there is a significant increase in MR severity. Generally, the technique immediately doubles the mitral valve area and halves the gradient.

Afterwards, most patients remain in asymptomatic or with NYHA II symptoms. About 75% are alive after 7-10 years after intervention and 60% are free of symptoms for long periods of follow-up. Success rates range from more than 95% in ideal patients from highly selected centers, to about 80-85% in usual centers, to less than 50-60% in patients with suboptimal anatomy.

Late deterioration is due to either re-stenosis that is often a function of suboptimal patient anatomy before intervention, or sometimes unrelated cardiac conditions in elderly patients. Re-stenosis can often be treated with repeat PMBV, though results are poorer than those after first intervention.

Mitral valve surgery has similar results to PMBV, but due to increased cost and morbidity, surgery is typically reserved for patients not suitable for PMBV.

Patient selection

PMBV is the treatment of choice in patients with MS who require mitral valve intervention with the following clinical features:

Appropriate valvular anatomy on echocardiography
Absence of LA thrombus
Absence of moderate to severe mitral regurgitation

A surgical repair or replacement is the treatment of choice for patients requiring mitral valve intervention that have one of the following features:

Moderate to severe mitral regurgitation
Left atrial thrombus
Valve anatomy not suitable for PMBV (too thick, rigid and calcified)

In other instances, surgery is generally preferred over PMBV in patients with either:

Congenital MS (anatomy usually too complex for PMBV)
Both severe MS and severe TR

Surgical options are listed below:

Closed valvotomy

– Performed on a beating heart from a left thoracotomy incision, a dilator is introduced across the mitral valve without direct visualization of the mitral valve. Reserved for developing countries due to worse outcomes compared to PMBV or other surgical approaches.

Open valvotomy with possible mitral valve repair

– Performed while the patient is on a cardiac bypass machine via a median sternotomy, this approach allows for direct visualization of the valve. After commissurotomy, the mitral valve can be repaired by removing calcium deposits and splitting papillary muscles. An annuloplasty ring is placed if there is significant mitral regurgitation. Any left atrial thrombus is removed.

Mitral valve replacement

– If the valvular anatomy is not suitable to PMBV or open valvotomy, then mitral valve replacement can significantly improve the natural history of MS. However, its perioperative mortality and morbidity risk is higher than any other mitral valve intervention. The perioperative mortality rate ranges from under 5% for young healthy patients, to 10-20% in older patients with comorbidities to 25% with NYHA IV symptoms. The annual risk of complications (valve thrombosis, systemic embolization, endocarditis) is estimated at ~5%. Generally, mechanical valve is placed in patients younger than 65, while a bioprosthetic valve is favored for patients older than 65.

Clinically stable asymptomatic patients should be evaluated with a TTE every 3-5 years for mild MS, every 1-2 years with moderate MS and annually with severe MS, as recommended by the ACC/AHA. The natural history of MS demonstrates a decline in mean mitral valve area of about 0.1cm^2 per year.

Though one retrospective study suggests statin therapy may slow progression of rheumatic MS, its routine use cannot be recommended without further study.

E. Common Pitfalls and Side-Effects of Management.

As mentioned, diuretic therapy may result in hypokalemia, which should be aggressively repleted.

Over-diuresis may result in acute kidney injury and a resultant decrease in the glomerular filtration rate.

IV. Management with Co-Morbidities.

Hemodynamic changes involved in normal pregnancy can be poorly tolerated in women with MS. Cardiac output and maternal blood volume can increase up to 50% over baseline values, reaching a peak around 24 weeks of gestation.

Pregnant patients with MS who were previously asymptomatic can develop symptoms as the pregnancy progresses due to an increase in the transmitral gradient from increasing cardiac output and heart rate. As a result, MS is often diagnosed during pregnancy.

In general, pregnant women with significant dyspnea should be evaluated with a TTE to evaluate for MS even in patients without an audible diastolic murmur.

Pregnant women with pulmonary edema from MS should be managed with diuretics and beta-blockers as previously mentioned. Whenever possible, the treating physician should avoid hypovolemia – uterine blood flow impairment and placental hypoperfusion can occur as a result of hypovolemia.

Angiotensin converting enzyme inhibitors, typically given to patients with systolic heart failure, are contraindicated during pregnancy.

If medical management is not sufficient to relieve symptoms, percutaneous mitral balloon valvotomy (PMBV) is the preferred treatment to correct the stenosis.

At the time of labor, women with severe MS or symptoms of heart failure should have their hemodynamics closely monitored with a Swan-Ganz pulmonary artery catheter. Fluid management should be directed to the target pulmonary capillary wedge pressure: approximately 14 mmHg. The catheter should be continued in the immediate postpartum period to evaluate for large intravascular volume shifts.

A. Renal Insufficiency.

Patients with renal insufficiency may require a higher initial dose of loop diuretics due to the decreased glomerular filtration rate.