Mitral Stenosis

Background

Mitral stenosis (MS) is characterized by obstruction to left ventricular inflow at the level of mitral valve due to structural abnormality of the mitral valve apparatus. The most common cause of mitral stenosis is rheumatic fever. The association of atrial septal defect with rheumatic mitral stenosis is called Lutembacher syndrome.

Stenosis of the mitral valve typically occurs decades after the episode of acute rheumatic carditis. Acute insult leads to formation of multiple inflammatory foci (Aschoff bodies, perivascular mononuclear infiltrate) in the endocardium and myocardium. Small vegetations along the border of the valves may also be observed. With time, the valve apparatus becomes thickened, calcified, and contracted, and commissural adhesion occurs, ultimately resulting in stenosis.

Whether the progression of valve damage is due to hemodynamic injury of the already affected valve apparatus or to the chronic inflammatory nature of the rheumatic process is unclear.

Other causes

Other, less common etiologies for mitral stenosis include malignant carcinoid disease, systemic lupus erythematosus, rheumatoid arthritis, mucopolysaccharidoses of the Hunter-Hurler phenotype, Fabry disease, Whipple disease, and methysergide therapy. Congenital mitral stenosis can also occur.

A number of conditions can simulate the physiology of mitral stenosis: severe nonrheumatic mitral annular calcification,^[1] infective endocarditis with large vegetation, left atrial myxoma, ball valve thrombus, and cor triatriatum.

Indeed, a study by Iwataki et al indicated that in patients with degenerative aortic stenosis, calcific extension to the mitral valve, causing mitral annular/leaflet calcification, can result in nonrheumatic mitral stenosis.^[2] Using real-time three-dimensional (3D) transesophageal echocardiography in 101 patients with degenerative aortic stenosis and 26 control subjects, the investigators found an average decrease of 45% in the effective mitral annular area of the patients with degenerative aortic stenosis, as well as a significant reduction in the maximal anterior and posterior leaflet opening angle. Consequently, a significant decrease in the mitral valve area in these patients was found, with an area of less than 1.5 cm² detected in 24 of them (24%).^[2]

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Pathophysiology

The normal mitral valve orifice area is approximately 4-6 cm². As the orifice size decreases, the pressure gradient across the mitral valve increases to maintain adequate flow.

Patients will not experience valve-related symptoms until the valve area is 2-2.5 cm² or less, at which point moderate exercise or tachycardia may result in exertional dyspnea from the increased transmitral gradient and left atrial pressure.

Severe mitral stenosis occurs with a valve area of less than 1 cm². As the valve progressively narrows, the resting diastolic mitral valve gradient, and hence left atrial pressure, increases. This leads to transudation of fluid into the lung interstitium and dyspnea at rest or with minimal exertion. Hemoptysis may occur if the bronchial veins rupture and left atrial dilatation increases the risk for atrial fibrillation and subsequent thromboembolism.

Pulmonary hypertension may develop as a result of (1) retrograde transmission of left atrial pressure, (2) pulmonary arteriolar constriction, (3) interstitial edema, or (4) obliterative changes in the pulmonary vascular bed (intimal hyperplasia and medial hypertrophy). As pulmonary arterial pressure increases, right ventricular dilation and tricuspid regurgitation may develop, leading to elevated jugular venous pressure, liver congestion, ascites, and pedal edema.

Left ventricular end-diastolic pressure and cardiac output are usually normal in the person with isolated mitral stenosis. As the severity of stenosis increases, the cardiac output becomes subnormal at rest and fails to increase during exercise. Approximately one third of patients with rheumatic mitral stenosis have depressed left ventricular systolic function as a result of chronic rheumatic myocarditis. The presence of concomitant mitral regurgitation, systemic hypertension, aortic stenosis, or myocardial infarction can also adversely affect left ventricular function and cardiac output.

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Epidemiology

United States data

The prevalence of rheumatic disease in developed nations is steadily declining with an estimated incidence of 1 in 100,000.

International data

The prevalence of rheumatic disease is higher in developing nations than in the United States.^[3] In India, for example, the prevalence is approximately 100-150 cases per 100,000, and in Africa the prevalence is 35 cases per 100,000. However, rheumatic fever has been decreasing in industrialized countries.^{[4, 5]}

Sex- and age-related demographics

Two thirds of all patients with rheumatic mitral stenosis are female.

The onset of symptoms usually occurs between the third and fourth decade of life.

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Prognosis

In the presurgical era, symptomatic patients with mitral stenosis had a poor outlook with 5-year survival rates of 62% among patients with mitral stenosis in NYHA Class III and only 15% among those in Class IV.

Data from unoperated patients in the surgical era still report a 5-year survival rate of only 44% in patients with symptomatic mitral stenosis who refused valvotomy.^[6]

Overall clinical outcomes are greatly improved in patients who undergo surgical or percutaneous relief of valve obstruction based on current guidelines. However, longevity is still shortened compared with expected for age, largely because of complications of the disease process.

Morbidity/mortality

Mitral stenosis is a progressive disease consisting of a slow, stable course in the early years followed by an accelerated course later in life. Typically, there is a latent period of 20-40 years from the occurrence of rheumatic fever to the onset of symptoms. Once symptoms develop, it is almost a decade before they become disabling. In some geographic areas, mitral stenosis progresses more rapidly, presumably due to either a more severe rheumatic insult or repeated episodes of rheumatic carditis due to new streptococcal infections, which results in severe symptomatic mitral stenosis in the late teens and early 20s.

In the asymptomatic or minimally symptomatic patient, survival is greater than 80% at 10 years. When limiting symptoms occur, 10-year survival is less than 15% in the patient with untreated mitral stenosis. When severe pulmonary hypertension develops, mean survival is less than 3 years. Most (60%) patients with severe untreated mitral stenosis die of progressive pulmonary or systemic congestion, but others may suffer systemic embolism (20-30%), pulmonary embolism (10%), or infection (1-5%)

Complications

Complications of mitral stenosis include the following:

• Atrial fibrillation
• Systemic embolism due to left atrial thrombus formation mostly secondary to atrial fibrillation: 20% of patients with mitral stenosis and systemic embolism are in sinus rhythm.
• Infective endocarditis: Estimated risk of endocarditis in a patient with mitral stenosis is 0.17 per 1000 patient-years.
• Pulmonary hypertension
• Pulmonary edema
• Complications of balloon valvotomy
• Complications of mitral valve replacement

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Patient Education

All patients should be informed about the following:

• Signs and symptoms of severe mitral stenosis (Patients should be advised to present for reevaluation.)
• Secondary prevention of rheumatic fever
• Infective endocarditis prophylaxis
• Need for chronic evaluation if atrial fibrillation is present
• Evaluation of new-onset palpitations for possible atrial fibrillation if not previously diagnosed

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History

Symptoms of mitral stenosis usually manifest during the third or fourth decade of life and nearly half of the patients do not recall a history of acute rheumatic fever.

Patients are generally asymptomatic at rest during the early stage of the disease. However, factors that increase heart rate such as fever, severe anemia, thyrotoxicosis, exercise, excitement, pregnancy, and atrial fibrillation may result in dyspnea.

Nearly 15% of patients develop embolic episodes that are usually associated with atrial fibrillation. Rarely, embolic episodes may occur even in the patient with sinus rhythm. Systemic embolization may lead to stroke, renal failure, or myocardial infarction.

Hoarseness can develop from compression of the left recurrent laryngeal nerve against the pulmonary artery by the enlarged left atrium. Also, compression of bronchi by the enlarged left atrium can cause persistent cough.

Hemoptysis may occur and is usually not fatal.

Pregnant women with mild mitral stenosis may become symptomatic during their second trimester because of the increase in blood volume and cardiac output.

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Physical

The presence of mitral facies (pinkish-purple patches on the cheeks) indicate chronic severe mitral stenosis leading to reduced cardiac output and vasoconstriction.

Jugular vein distension may be seen. In the patient with sinus rhythm, a prominent a wave reflects increased right atrial pressure from pulmonary hypertension and right ventricular failure. A prominent v wave is seen with tricuspid regurgitation. The apical impulse may be laterally displaced or not palpable, especially in cases of severe mitral stenosis. This can be explained by decreased left ventricular filling. Rarely, a diastolic thrill can be felt at the apex with the patient in the left lateral recumbent position. See the videos below.

View Video

Apical 4-chamber view demonstrating restricted opening of the anterior and posterior mitral valve leaflet with diastolic doming of anterior leaflet with left atrial enlargement.

View Video

Apical 4-chamber view with color Doppler demonstrating aliasing in the atrial side of the mitral valve consistent with increased gradient across the valve. This figure also shows mitral regurgitation and left atrial enlargement.

Often a right ventricular lift is palpable in the left parasternal region in the patient with pulmonary hypertension. A P₂ may be palpable in the 2nd left intercostal space.

The auscultatory findings characteristic of mitral stenosis are a loud first heart sound, an opening snap, and a diastolic rumble.

The first heart sound is accentuated because of a wide closing excursion of the mitral leaflets. The degree of loudness of the first heart sound depends on the pliability of the mitral valve. The intensity of the first heart sound diminishes as the valve becomes more fibrotic, calcified, and thickened.

The second heart sound is normally split, and the pulmonic component is accentuated if pulmonary hypertension is present. The opening snap follows the second heart sound. The sudden tensing of the valve leaflets after they have completed their opening excursion causes an opening snap. In patients with elevated left atrial pressure and hence with severe mitral stenosis, the opening snap occurs closer to the second heart sound.

The diastolic murmur of mitral stenosis is of low pitch, rumbling in character, and best heard at the apex with the patient in the left lateral position. It commences after the opening snap of the mitral valve, and the duration of the murmur correlates with the severity of the stenosis. The murmur is accentuated by exercise, whereas it decreases with rest and Valsalva maneuver. In patients with sinus rhythm, the murmur increases in intensity during late diastole (so called, presystolic accentuation) due to increased flow across the stenotic mitral valve caused by atrial contraction.

A high-pitched decrescendo diastolic murmur secondary to pulmonary regurgitation (Graham Steell murmur) may be audible at the upper sternal border.

A pansystolic murmur of TR and an S₃ originating from the right ventricle may be audible in the 4th left intercostal space in the patient with right ventricular dilatation.

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Laboratory Studies

Perform routine baseline tests such as complete blood cell (CBC) count, electrolyte status, and renal and liver function tests.

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Imaging Studies

Chest radiographic findings suggestive of mitral stenosis include left atrial enlargement (eg, double shadow in the cardiac silhouette, straightening of left cardiac border due to the large left atrial appendage, and upward displacement of the mainstem bronchi), prominent pulmonary vessels, redistribution of pulmonary vasculature to the upper lobes, mitral valve calcification, and interstitial edema (Kerley A and B lines).

Echocardiography is the most specific and sensitive method of diagnosing and quantifying the severity of mitral stenosis.^{[4, 7]} Using a transthoracic 2-dimensional echocardiogram, Doppler study, and color-flow Doppler imaging, the anatomic abnormalities of the stenotic valve (ie, thickening, mobility, motion, calcification), involvement of the subvalvular apparatus and the characteristic fusion of the commissures can be well defined.^[8]

With echocardiography, the size of the mitral valve orifice can be precisely quantified. Important information about the ventricular and atrial chamber sizes, the presence of a left atrial thrombus, measurement of transvalvular gradient, and pulmonary arterial pressure can also be obtained.

With the use of Doppler echocardiography, sufficient information can be obtained to develop a therapeutic plan, and, consequently, most patients do not require invasive procedures such as cardiac catheterization.

Transesophageal echocardiography (TEE) provides better quality images than transthoracic echocardiography (TTE) and is more accurate in assessing the anatomic features of the valve and the presence of left atrial appendage thrombus. Studies have shown that mitral valve area planimetry is feasible in the majority of patients with rheumatic mitral stenosis using 3-dimensional TEE; also, 3-dimensional TEE allows excellent assessment of commissural fusion^[9] and commissural opening after catheter-balloon commissurotomy.

The mitral valve score appears to be an independent predictor of match and mismatch between opening area and resistance in mild and moderate rheumatic mitral stenosis.^[10]

In study that assessed the feasibility and validity of a novel method to measure mitral valve area (MVA) in 30 patients with severe rheumatic mitral stenosis undergoing percutaneous balloon mitral valvuloplasty, investigators reported that mitral valve navigation software of the Philips Q-Lab 10.2 in a diastolic frame with maximum diastolic opening of the mitral valve was feasible and was more correlated to invasive measurements of MVA (derived by Gorlin formula) than use of 3-D TEE.^[11]

See the image and videos below.

View Image

Transesophageal echocardiogram with continuous wave Doppler interrogation across the mitral valve demonstrating an increased mean gradient of 16 mm Hg....

View Video

Magnified view of the mitral valve in apical 4-chamber view revealing restricted opening of both leaflets.

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Transesophageal echocardiogram in an apical 3-chamber view showing calcification and doming of the anterior mitral leaflet and restricted opening of both leaflets.

View Video

Transesophageal echocardiogram in an apical 3-chamber view with color Doppler interrogation of the mitral valve revealing aliasing, which is consistent with increased gradient across the mitral valve secondary to stenosis. Also shown in this image, a posteriorly directed jet of severe mitral regurgitation.

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Other Tests

In patients with moderate-to-severe mitral stenosis, the ECG can show signs of left atrial enlargement (P wave duration in lead II >0.12 seconds, P wave axis of +45 to -30 marked terminal negative component to the P wave in V₁ [1 mm wide and 1 mm deep]) and, commonly, atrial fibrillation. A mean QRS axis in the frontal plane is greater than 80 and an R-to-S ratio of greater than 1 in lead V₁ indicates the presence of right ventricular hypertrophy. As the severity of the pulmonary hypertension increases, the mean QRS axis in the frontal plane moves toward the right.

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Procedures

Cardiac catheterization was routine performed in the past. However, the accuracy of echocardiographic findings has resulted in only selective use of catheterization. Cardiac catheterization is now indicated in the following situations:

• When a discrepancy exists between clinical and echocardiographic findings
• The patient with associated severe lung disease and pulmonary hypertension, in whom mitral stenosis has contributed to their symptoms, needs to be ascertained.
• In older patients with severe mitral stenosis, cardiac catheterization is strongly indicated to rule out the presence of concomitant coronary artery disease.
• In patients who developed serious symptoms after mitral commissurotomy.

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Medical Care

The goal of medical treatment for mitral stenosis is to reduce recurrence of rheumatic fever, provide prophylaxis for infective endocarditis, reduce symptoms of pulmonary congestion (eg, orthopnea, paroxysmal nocturnal dyspnea), control the ventricular rate if atrial fibrillation is present, and prevent thromboembolic complications.^[12]

Because rheumatic fever is the primary cause of mitral stenosis, secondary prophylaxis against group A beta-hemolytic streptococci (GAS) is recommended.^[13] Duration of prophylaxis depends on the number of previous attacks, the time elapsed since the last attack, the risk of exposure to GAS infections, the age of the patient, and the presence or absence of cardiac involvement. Penicillin is the agent of choice for secondary prophylaxis, but sulfadiazine or a macrolide or azalide are acceptable alternatives in individuals allergic to penicillin (Tables 1 and 2).

A European study involving 315 patients with rheumatic mitral stenosis showed a significantly slower progression of rheumatic mitral stenosis in patients treated with statins compared with patients not taking statins. These findings could have an important impact in the early medical therapy of patients with rheumatic heart disease.^[14]

Initial symptoms of pulmonary congestion can be safely treated by diuretics. Dietary sodium restriction and nitrates decrease preload and can be of additional benefit. Careful use of beta-blockers in patients with a normal sinus rhythm can prolong the diastolic filling time and thus decrease in left atrial pressure. In general, afterload reduction should be avoided as it can cause hypotension.

In a randomized crossover study, Saggu et al investigated the comparative efficacy of ivabradine and metoprolol on symptoms, hemodynamics, and exercise parameters in 33 patients with mild-to-moderate mitral stenosis (mitral valve area, 1-2 cm) in normal sinus rhythm. They found evidence that metoprolol and ivabradine reduced patients’ symptoms and improved hemodynamics significantly from baseline with a similar efficacy. The investigators concluded that ivabradine can be used safely and effectively in patients with mitral stenosis in normal sinus rhythm who are intolerant to or contraindicated for beta-blocker therapy.^[15]

Atrial fibrillation is common in mitral stenosis and often leads to a rapid ventricular rate with reduced diastolic filling time and increased left atrial pressure. Although patients with mitral stenosis have a reduced average early diastolic strain in the presence of atrial fibrillation compared to normal sinus rhythm, those with mitral stenosis and atrial fibrillation show a loss of atrial late diastolic contraction as well as a reduction in early diastolic shortening of the left atrial myocardium.​^[16]

The ventricular rate of atrial fibrillation can be slowed acutely by the administration of intravenous beta-blocker or calcium channel blocker therapy (diltiazem or verapamil). The rate and/or rhythm can be controlled long-term with oral beta-blockers, calcium channel blockers, amiodarone, or digoxin.

In the patient with mild mitral stenosis and recent-onset (< 6 mo) atrial fibrillation, conversion to sinus rhythm can be accomplished with pharmacologic agents or electrical cardioversion. In this circumstance, anticoagulation therapy should be given for at least 3 weeks prior to cardioversion. Alternatively, a TEE can be performed to exclude the presence of left atrial thrombus, prior to cardioversion. Patients who are successfully converted to sinus rhythm should receive long-term anticoagulation and antiarrhythmic drugs. Warfarin should be used for anticoagulation. The novel anticoagulants dabigatran and rivaroxaban was approved for nonvalvular atrial fibrillation; these drugs have not been evaluated in patients with heart valve disease.^[17]

Surgical correction of the mitral stenosis is indicated if embolization is recurrent, despite adequate anticoagulation therapy.

In a retrospective study (2001-2015) of 318 patients with late onset of atrial fibrillation following mitral valve repair for type II dysfunction, significant risk factors for late atrial fibrillation were small ring annuloplasty, left atrial diameter, and pressure half-time.^[18]  In addition, affected patients developed recurrent myocardial infarction more often than those without late-onset atrial fibrillation.

Table 1. Duration of Secondary Rheumatic Fever Prophylaxis

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Table 2. Secondary Prevention of Rheumatic Fever (Prevention of Recurrent Attacks)

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Diet and activity

The patient should start a low-salt diet if pulmonary vascular congestion is present.

In most patients with mitral stenosis, recommendations for exercise are symptom limited. Patients should be encouraged to pursue a low-level aerobic exercise program for maintenance of cardiovascular fitness.

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Surgical Care

Surgical therapy for mitral stenosis consists of mitral valvotomy (which can be either surgical or percutaneous) or mitral valve replacement. The surgical mitral valvotomy approach can be through an closed or open technique; the latter technique is rarely used, except in developing countries, and has largely been replaced by the percutaneous balloon commissurotomy.^[8]

Asymptomatic patients with moderate or severe mitral stenosis (mitral valve area < 1.5 cm²) and a suitable valve should be considered for percutaneous balloon commissurotomy if the pulmonary arterial systolic pressure is ≥50 mm Hg at rest or ≥60 mm Hg with exercise, or pulmonary capillary wedge pressure is ≥25 mm Hg with exercise.^[19]

Symptomatic patients with moderate or severe mitral stenosis (mitral valve area < 1.5 cm²) and suitable valve are also candidates for percutaneous balloon commissurotomy.

If percutaneous balloon commissurotomy is not an option, patients should be referred for surgical repair or mitral valve replacement.

Some patients may have recurrent moderate mitral regurgitation after repair; there appears to be an increased likelihood of having a recurrent mitral regurgitation of 2+ or higher within 1 year after the repair in patients who required a subsequent mitral valve reoperation.^[20]

Percutaneous balloon valvuloplasty/percutaneous mitral commissurotomy (PMC)

PMC is the procedure of choice for patients with uncomplicated mitral stenosis. Patients with pliable, mobile, relatively thin, minimally calcified mitral leaflets with minimal or no subvalvular stenosis are good candidates for this procedure. A TEE should be performed prior to commissurotomy to clearly define the valve anatomy and exclude the presence of a left atrial thrombus.

The echocardiographic scoring system (Wilkins score) has been used as a valuable tool for patient selection. Leaflet mobility, valvular thickening, valvular calcification, and subvalvular disease are each given a score of 0-4, with higher scores indicating more severe involvement. A total score of less than 8 results in good short- and long-term outcome with balloon valvuloplasty.

With PMC, a catheter is directed into the left atrium after transseptal puncture, and a balloon is directed across the valve and inflated in the orifice. This results in separation of the mitral leaflets. The valve size can be increased up to 2-2.5 cm².

Improvement in symptoms is noted immediately following the procedure. If symptoms do not improve, the commissurotomy was either ineffective or resulted in mitral regurgitation.

In a prospective study of 56 patients with critical mitral stenosis in normal sinus rhythm and 37 healthy controls that used transthoracic echocardiography to measure aortic stiffness before percutaneous mitral balloon valvuloplasty (PMBV), 24-48 hours postprocedure, and 1 year postprocedure, investigators found that mitral valve stenosis was associated with impaired aortic stiffness.^[21]  Following PMBV, aortic stiffness decreased during the acute and intermediate periods.

The short- and long-term prognoses are favorable compared with surgical valvotomy.

PMC offers certain advantages over surgical valvotomy, including avoidance of a thoracotomy and general anesthesia and their attendant complications.

The major contraindications to balloon commissurotomy are the presence of thrombus in the left atrium or its appendage, moderate-to-severe mitral regurgitation, and an unfavorable valve morphology (ie, high Wilkins echo score).

Complications of a PMC include embolization, mitral regurgitation, ventricular rupture, residual atrial septal defect, stroke, and death.

Surgical valvotomy/valve replacement

Open surgical commissurotomy allows direct visualization of the mitral valve.

Using current techniques, even severe regurgitant or stenotic valves can often be repaired, with good long-term results. Valves that are not suitable for repair can be replaced using either bioprosthetic or metallic prosthetic valves.

With bioprosthetic valves, the patient does not require anticoagulation, as long as he or she remains in sinus rhythm; however, 20-40% of these valves fail within 10 years, secondary to structural deterioration.

Mechanical valves are placed in young patients who do not have any contraindications for anticoagulation, and these valves are associated with good long-term durability.

Patients who have chronic atrial fibrillation and who undergo mitral valve surgery can have simultaneous Cox Maze procedure or pulmonary vein ablation, which helps to maintain sinus rhythm in up to 80% of the cases during the postoperative period.

Balloon-expandable valve implantation

Early results of direct transatrial implantation of a balloon-expandable valve in the mitral position in 6 patients with symptomatic severe mitral annular calcification considered to be high-risk surgical candidates indicates that although this approach appears to be feasible, the technique requires further refinement due to significant morbidity and mortality.^[22]  Although no left ventricular outflow tract obstruction was noted, 3 patients had severe mitral valve periprosthetic regurgitation and 1 had moderate to severe mitral valve periprosthetic regurgitation, and in-hospital death occurred in 3 other patients (noncardiac cause, 1 patient; cardiogenic shock, 2 patients).^[22]

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Consultations

Key members of a multidisciplinary team for structural heart valve disease management include primary cardiologists, interventional cardiologists, cardiac surgeons, noninvasive and heart failure cardiologists, echocardiographers and cardiac imaging specialists, cardiac anesthesiologists, nurse practitioners, physician assistants, research coordinators, administrators, dietary and rehabilitation specialists, and social workers. Each component will need to develop and implement specific protocols depending on the individual patient and specific technical procedure.^[23]

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Prevention

Primary prevention of acute rheumatic fever is summarized in Table 3 below.^[13]

For secondary prevention of rheumatic fever and for infective endocarditis prophylaxis, see Medical Care.

Table 3. Primary Prevention of Rheumatic Fever (Treatment of Streptococcal Tonsillopharyngitis*)

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Long-Term Monitoring

Serial follow-up testing of a patient with mitral stenosis should be based on whether the results of a test will dictate either a change in therapy or a recommendation for a procedure.

All patients should be informed that any change in symptoms warrants re-evaluation.

In the asymptomatic patient, yearly re-evaluation is recommended; history, physical examination, chest radiograph, and electrocardiogram (ECG) should be obtained.

An echocardiogram is not recommended yearly unless there is a change in clinical status or the patient has severe mitral stenosis.

Ambulatory ECG monitoring (Holter or event recorder) to detect paroxysmal atrial fibrillation is indicated in patients with palpitations.

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Guidelines Summary

In 2014, the American Heart Association/American College of Cardiology(AHA/ACC) released a revision to its 2008 guidelines for management of patients with valvular heart disease (VHD).^[12]  They published a focused update to these guidelines in 2017.^[24]  Similarly, in 2017, the European Society of Cardiology/European Association for Cardio-Thoracic Surgery (ESC/EACTS) issued a revision of its 2012 guidelines, which were an update of their 2007 guidelines.^{[5, 25]}

The 2014 AHA/ACC guidelines classify progression of mitral stenosis (MS) into 4 stages (A to D) as follows^[12] :

• Stage A: At risk of MS 
• Stage B: Asymptomatic with progressive MS (mild to moderate) 
• Stage C: Asymptomatic with severe MS
• Stage D: Symptomatic with severe MS 

The AHA/ACC and ESC/EACTS guidelines require intervention decisions for severe VHD to be based on an individual risk-benefit analysis.^{[5, 12, 24, 25]}  Improved prognosis should outweigh the risk of intervention and potential late consequences, particularly complications related to prosthetic valves.^{[5, 24, 25]}

Recognizing the known limitations of the EuroSCORE (European System for Cardiac Operative Risk Evaluation) and the STS (Society of Thoracic Surgeons) score, the AHA/ACC guidelines suggest using STS plus three additional indicators: frailty (using accepted indices), major organ system compromise not to be improved postoperatively, and procedure-specific impediment when assessing risk.^[12]

Diagnosis

The 2014 AHA/ACC guidelines include the following class I recommendations for diagnostic testing and the initial diagnosis of MS^[12] :

• Transthoracic echocardiography (TTE) for the initial evaluation of patients with signs or symptoms of MS to establish the diagnosis, determine the hemodynamic severity (mean pressure gradient, mitral valve area, pulmonary artery pressure), assess concomitant valvular lesions, and demonstrate valve morphology (to determine suitability for mitral commissurotomy). (Level of evidence: B)
• TEE in patients under consideration for percutaneous mitral balloon commissurotomy (PMBC) to assess the presence or absence of left atrial (LA) thrombus and to further evaluate the severity of mitral regurgitation (MR). (Level of evidence: B)
• Exercise testing with Doppler or invasive hemodynamic assessment to evaluate the response of the mean mitral gradient and pulmonary artery pressure when there is a discrepancy between resting Doppler echocardiographic findings and clinical symptoms or signs. (Level of Evidence: C)

The ESC/EACTS guidelines recommend transesophageal echocardiography (TEE) be considered to exclude LA thrombus before percutaneous mitral commissurotomy or after an embolic episode when TTE is of suboptimal quality.^[25] Intervention is indicated in symptomatic patients with severe valve disease and/or ventricular dysfunction unless patient is unsuitable for surgery.^{[5, 25]} These guidelines also indicate stress testing in asymptomatic patients or symptoms that are equivocal or discordant with the severity of their MS.^{[5, 25]}

Medical management

The 2014 AHA/ACC guidelines class I recommendations indicate anticoagulation (a vitamin K antagonist, as opposed to direct oral anticoagulants^[24] ) in patients with MS and the following conditions (level of evidence: B)^[12] :

• Atrial fibrillation (AF) (paroxysmal, persistent, or permanent)
• A prior embolic event
• An LA thrombus

Heart rate control may provide benefit in individuals with MS and AF and fast ventricular response (class IIa; level of evidence: C); it may also be considered in those with MS and normal sinus rhythm with exercise-associated symptoms (class IIb; level of evidence: B).^[12]

The 2012 and 2017 ESC/EACTS guidelines recommend anticoagulation in patients with MS and permanent or paroxysmal AF, using a target international normalize ratio in the upper half of the range 2-3.^{[5, 25]}  As with the AHA/ACC guidelines, a vitamin K antagonist is recommended rather than other anticoagulants. For those with MS and sinus rhythm, anticoagulation is indicated in those with a previous embolism or in the presence of an LA thrombus (class I; level of evidence C), as well as in those whose TEE reveal dense spontaneous echo contrast or an enlarged LA (class IIa; level of evidence C). The guidelines do not consider aspirin and other antiplatelet agents as valid alternatives.^{[5, 25]}

Interventions

Both the 2014 AHA/ACC, 2012 ESC/EACTS, and 2017 ESC/EACTS guidelines, recommend PMBC for all patients with Stage D disease (symptomatic with severe MS; mitral valve area ≤1.5 cm²), no contraindications, and favorable valve morphology (class I; level of evidence A).^{[5, 12, 25]}  Surgical intervention is recommended in patients with severe MS (Stage D) and New York Heart Association (NYHA) class III-IV symptoms who are not at high risk for surgery and who are not candidates for or have had failure of a previous PMBC (class I; level of evidence B).^{[12, 25]}

Contraindications to PMBC include a mitral valve area over 1.5 cm², presence of an LA thrombus, more than mild MR, severe or bicommissural calcification, absence of commissural fusion, severe concomitant aortic valve disease or severe combined tricuspid stenosis and regurgitation, and concomitant coronary artery disease requiring bypass surgery.^{[5, 25]}

A comparison of the additional recommendations for surgical intervention and PMBC for mitral stenosis is provided in Table 4 below.

Table 4. Recommendations for Mitral Stenosis (MS) Intervention

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Infective Endocarditis

Both the AHA and ESC released updated guidelines for the management of infective endocarditis (IE) in 2015,^{[26, 27]}  and these were reaffirmed in their 2017 guidelines. Major recommendations for the management of IE are summarized below^[26] :

Class I recommendations

• The Modified Duke Criteria should be used in evaluating a patient with suspected IE.^[12] (Level of evidence: B)
• At least 3 sets of blood cultures from different venipuncture sites should be obtained, with the first and last samples drawn at least 1 hour apart. (Level of evidence: A)
• Appropriate antibiotic therapy should be initiated and continued after blood cultures are obtained with guidance from antibiotic sensitivity data and infectious disease consultants.(Level of evidence: B)
• TTE should be performed in all cases of suspected IE. (Level of evidence: B)
• TEE should be performed if the initial TTE images are negative or inadequate in patients for whom there is an ongoing suspicion for IE or when there is concern for intracardiac complications in patients with an initial positive TTE. (Level of evidence: B)
• If there is a high suspicion of IE despite an initial negative TEE, then a repeat TEE in 3 to 5 days or sooner if clinical findings change. (Level of evidence: B)
• Repeat TEE should be performed after an initially positive TEE if clinical features suggest a new development of intracardiac complications. (Level of evidence: B)
• Patients with IE should first be evaluated and stabilized in the hospital before being considered for outpatient therapy, and they should be at low risk for IE complications (eg, heart failure, systemic emboli). (Level of evidence for both: C)

Surgery should be performed before completion of a full therapeutic course of antibiotics in patients with the following (all level of evidence: B)^[26] : 

• IE and valve dehiscence, intracardiac fistula, or severe prosthetic dysfunction resulting in symptoms of heart failure
• IE caused by fungi or highly resistant organisms (eg, vancomycin-resistant Enterococcus, multidrug-resistant gram-negative bacilli)
• IE complicated by heart block, annular or aortic abscess, or destructive penetrating lesions
• Persistent bacteremia lasting longer than 5 to 7 days after administration of appropriate antimicrobial therapy and exclusion of other potential sites of infection

Months to years after completion of medical therapy for IE, patients should have ongoing observation for and education about recurrent infection and delayed onset of worsening valve dysfunction (level of evidence: C).^[26]

Class III recommendations

Patients should not receive antibiotics before blood cultures are obtained for unexplained fever (level of evidence: C).^[26]

Antimicrobial therapy should not be initiated for the treatment of undefined febrile illnesses unless the patient’s condition (eg, sepsis) warrants it (level of evidence: C).^[26]

Prophylaxis against infective endocarditis (IE) 

American Heart Association (AHA) guidelines do not recommend infective endocarditis prophylaxis for most patients with rheumatic heart disease.^{[12, 26]}  However, the maintenance of optimal oral health care remains an important component of an overall healthcare program. For the relatively few patients with rheumatic heart disease in whom infective endocarditis prophylaxis remains recommended (eg, those with prosthetic valves or prosthetic material used in valve repair, previous infective endocarditis, unrepaired cyanotic or repaired congenital heart disease, or cardiac transplant recipients with valve regurgitation from a structurally abnormal valve), the current AHA recommendations should be followed before dental procedures that involve manipulation of gingival tissue, manipulation of the periapical region of teeth, or perforation of the oral mucosa (class IIa; level of evidence: C-LD^[24] ).^{[12, 26]}

These recommendations advise the use of an agent other than a penicillin to prevent infective endocarditis in those receiving penicillin prophylaxis for rheumatic fever because oral alpha-hemolytic streptococci are likely to have developed resistance to penicillin.^[26]

The indication for antibiotic prophylaxis for endocarditis was significantly reduced in the 2012 ESC/EACTS guidelines, although they recommended considering antibiotic prophylaxis for high-risk procedures in high-risk patients and were otherwise in agreement with the AHA guidelines.^[25] These were reaffirmed in the 2017 updated ESC/EACTS guidelines.^[5]

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Medication Summary

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

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Digoxin (Lanoxicaps, Lanoxin)

• Dosing, Interactions, etc.

Clinical Context:  Cardiac glycoside with direct inotropic effects and indirect effects on the cardiovascular system. Acts directly on cardiac muscle, increasing myocardial systolic contractions. Indirect actions result in increased carotid sinus nerve activity and enhanced sympathetic withdrawal for any given increase in mean arterial pressure.

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Amiodarone (Cordarone, Pacerone)

• Dosing, Interactions, etc.

Clinical Context:  May inhibit AV conduction and sinus node function. Prolongs action potential and refractory period in myocardium and inhibits adrenergic stimulation. Prior to administration, control ventricular rate and CHF (if present) with digoxin or calcium channel blockers.

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Class Summary

These agents alter the electrophysiologic mechanisms responsible for arrhythmia.

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Diltiazem (Cardizem CD, Dilacor, Tiazac, Cardizem LA)

• Dosing, Interactions, etc.

Clinical Context:  During depolarization, inhibits calcium ions from entering slow channels and voltage-sensitive areas of vascular smooth muscle and myocardium.

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Class Summary

In specialized conducting and automatic cells in the heart, calcium is involved in the generation of the action potential. Calcium channel blockers inhibit movement of calcium ions across the cell membrane, depressing both impulse formation (automaticity) and conduction velocity.

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Warfarin (Coumadin)

• Dosing, Interactions, etc.

Clinical Context:  Interferes with hepatic synthesis of vitamin K–dependent coagulation factors. Used for prophylaxis and treatment of venous thrombosis, pulmonary embolism, and thromboembolic disorders. Tailor dose to maintain an INR of 2-3.

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Heparin

• Dosing, Interactions, etc.

Clinical Context:  Augments activity of antithrombin III and prevents conversion of fibrinogen to fibrin. Does not actively lyse but is able to inhibit further thrombogenesis. Prevents reaccumulation of clot after spontaneous fibrinolysis.

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Class Summary

These agents prevent recurrent or ongoing thromboembolic occlusion of the vertebrobasilar circulation.

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Metoprolol (Lopressor, Toprol XL)

• Dosing, Interactions, etc.

Clinical Context:  Selective beta1-adrenergic receptor blocker that decreases automaticity of contractions. During IV administration, carefully monitor blood pressure, heart rate, and ECG.

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Class Summary

These agents inhibit chronotropic, inotropic, and vasodilatory responses to beta-adrenergic stimulation.

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Penicillin G benzathine (Bicillin L-A, Permapen)

• Dosing, Interactions, etc.

Clinical Context:  Interferes with synthesis of cell wall mucopeptides during active multiplication, which results in bactericidal activity. Used to treat syphilis and for prophylaxis of recurrent streptococcal infections.

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Class Summary

Must cover all likely pathogens in the context of this clinical setting. Use as prophylaxis against streptococcal infections.

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Furosemide (Lasix)

• Dosing, Interactions, etc.

Clinical Context:  Increases excretion of water by interfering with chloride-binding cotransport system, which, in turn, inhibits sodium and chloride reabsorption in ascending loop of Henle and distal renal tubule. Dose must be individualized to patient. Depending on response, administer at increments of 20-40 mg, no sooner than 6-8 h after previous dose, until desired diuresis occurs. When treating infants, titrate with increments of 1 mg/kg/dose until a satisfactory effect is achieved.

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Class Summary

Diuretics are used for treatment of pulmonary congestion. Treatment may improve symptoms of venous congestion through elimination of retained fluid and preload reduction.

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