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Rheumatic mitral stenosis: Clinical manifestations and diagnosis

Rheumatic mitral stenosis: Clinical manifestations and diagnosis
Literature review current through: Jan 2024.
This topic last updated: Dec 06, 2022.

INTRODUCTION — Mitral stenosis (MS) causes obstruction to blood flow from the left atrium to left ventricle. As a result, there is an increase in pressures in the left atrium, pulmonary vasculature, and right side of the heart, while the left ventricle is unaffected in isolated MS. The most common cause of MS is rheumatic heart disease with mitral commissural fusion; thickened mitral valve leaflets with restricted motion at the leaflet tips; and thickening, shortening, fusion, and calcification of the chordae tendineae. Among patients with rheumatic heart disease in resource-limited countries, some present with pure MS, some present with pure mitral regurgitation, and some present with mixed MS and mitral regurgitation. (See "Clinical manifestations and diagnosis of rheumatic heart disease", section on 'Chronic valve disease'.)

Severe mitral annular calcification and congenital MS are less common causes of MS. (See "Pathophysiology and natural history of mitral stenosis".)

This topic will review the clinical features and evaluation of MS due to rheumatic heart disease [1]. Other issues related to rheumatic MS, such as the pathophysiology, natural history, and management (including medical therapy, percutaneous mitral balloon commissurotomy, and mitral valve surgery) are discussed separately. (See "Pathophysiology and natural history of mitral stenosis" and "Rheumatic mitral stenosis: Overview of management" and "Surgical and investigational approaches to management of mitral stenosis" and "Percutaneous mitral balloon commissurotomy in adults".)

CLINICAL MANIFESTATIONS

Symptoms — The duration of the asymptomatic phase of rheumatic MS (or mixed MS and mitral regurgitation) varies widely, with generally more rapid progression in resource-limited countries, and slower progression to symptoms in resource-abundant countries.

MS usually presents with exertional dyspnea and/or decreased exercise tolerance [1]. These symptoms are primarily related to the severity of the valvular stenosis, as it impacts the left atrial pressure, pulmonary pressures, pulmonary vascular resistance, and cardiac output. However, many patients with severe MS do not recognize symptoms because slow progression of disease is accompanied by a gradual reduction in activity and generalized deconditioning. As a result, a careful history regarding exercise tolerance is often required to document a slow decline in functional status. (See 'Staging' below.)

Less common clinical presentations include fatigue, hemoptysis, and chest pain.

Additional clinical manifestations are caused by complications including ascites and lower extremity edema associated with right heart failure (particularly in patients with severe pulmonary arterial hypertension), stroke or other thromboembolic event (particularly in patients with atrial fibrillation [AF]), hoarseness, and, rarely, fever due to infective endocarditis [1]. (See 'Complications' below.)

Dyspnea — The most common and, often, the only symptom of MS is exertional dyspnea, which occurs in up to 70 percent of symptomatic patients [2]. Dyspnea results from elevation in left atrial pressure and pulmonary venous hypertension, which leads to reduced compliance of the lungs, a decrease in vital capacity, and increased work of breathing. Dyspnea also may be related to an inability to increase the cardiac output with increased metabolic demands. As the degree of MS increases, dyspnea occurs with very little effort and orthopnea and fatigue may also occur.

However, for some patients, the initial clinical presentation is acute dyspnea with hypoxic respiratory failure due to pulmonary edema precipitated by AF with rapid ventricular response, intercurrent noncardiac infection, pregnancy, or fluid overload. (See 'Precipitants of symptoms' below and 'Atrial fibrillation' below.)

Fatigue — Fatigue is a less common symptom that may occur as the degree of MS worsens, cardiac output declines, and right heart failure develops (see 'Right heart failure' below). Thus, fatigue may be associated with low forward flow and a low transmitral gradient.

Hemoptysis — The increased pulmonary pressures and vascular congestion can lead to hemoptysis, which may have a variety of clinical manifestations:

Sudden hemorrhage (pulmonary apoplexy) due to the rupture of thin-walled and dilated bronchial veins when there is a sudden increase in left atrial pressure. This complication is rarely life-threatening, despite what appears to be a large amount of bleeding. (See "Evaluation and management of life-threatening hemoptysis".)

Blood-tinged sputum induced by severe coughing associated with paroxysmal nocturnal dyspnea or bronchitis.

Pink frothy sputum resulting from pulmonary edema associated with left heart failure.

Chest pain — Patients with MS rarely present with chest pain. Although the pain often resembles angina and may be due to underlying coronary artery disease or a coronary artery embolism, it is most commonly the result of pulmonary hypertension (PH) and right ventricular hypertrophy, which may be associated with right ventricular endocardial ischemia. Another cause of intermittent chest pain is an atrial tachyarrhythmia with left atrial and pulmonary vascular distension. (See "Pulmonary hypertension due to left heart disease (group 2 pulmonary hypertension) in adults", section on 'Symptoms and signs' and "Outpatient evaluation of the adult with chest pain".)

Precipitants of symptoms — Any situation that increases the cardiac output, which raises transmitral flow or causes tachycardia (which decreases diastolic filling time), can increase the transmitral pressure gradient and precipitate symptoms such as dyspnea or hemoptysis. Activities or conditions that can provoke symptoms include exertion, emotional stress, fever, infection (eg, pneumonia), AF, and pregnancy. However, stroke or other thromboembolic complication may be the first manifestation in previously asymptomatic individuals.

As an example, the increase in heart rate and cardiac output during pregnancy can substantially increase the resting transmitral gradient in pregnant patients with MS, which can lead to symptoms in a previously asymptomatic (and perhaps undiagnosed) patient or an exacerbation of symptoms in an already symptomatic patient [3]. These issues are discussed in detail separately. (See "Pregnancy in women with mitral stenosis".)

Physical examination — Except in patients with severe long-standing disease, the physical findings are subtle and the murmur may be difficult to appreciate.

General examination

When MS is severe, causing PH and diminished cardiac output, cutaneous vasodilation results in pinkish-purple patches on the cheeks (mitral facies).

Lung examination may demonstrate crackles (rales) consistent with pulmonary edema. However, pulmonary congestion is absent in some patients with chronically elevated left atrial pressure, which has been attributed to compensatory lymphatic hyperfunction [4].

Advanced disease may be associated with the signs of right-sided heart failure such as elevated jugular venous pressure, lower extremity edema, and ascites.

Cardiovascular examination

Pulse examination — The arterial pulses are preserved in most patients with MS, reflecting preserved stroke volume. In patients with severe MS with AF, the arterial pulses are reduced in volume due to the decreased stroke volume. (See "Examination of the arterial pulse".)

Findings on jugular venous examination include a prominent "a" wave (atrial contraction or systole) reflecting elevated right atrial pressure in the setting of PH and right ventricular hypertrophy. The "a" wave is absent in patients with AF and only a prominent "v" wave (atrial filling during ventricular systole when the tricuspid valve is closed) is seen. If present, tricuspid regurgitation can lead to a prominent "c-v" wave (reflecting regurgitation of blood into the right atrium) and the neck veins are very pulsatile. (See "Examination of the jugular venous pulse".)

Cardiac examination — Identification of characteristic heart sounds, opening snap, and diastolic murmur may be diagnostic for MS with appropriate patient positioning in a quiet room. The classic findings of MS were originally described in populations in which rheumatic heart disease manifested at an early age, often in underweight individuals. The physical signs may be more difficult to detect in older patients with comorbidities such as obesity and chronic lung disease. The opening snap and murmur may be difficult to appreciate, particularly when MS presents during pregnancy or with rapid AF. In individuals with suspected rheumatic heart disease, the threshold for proceeding with echocardiography should be low.

Palpation — Palpation of the chest wall reveals an apical impulse that is generally normal, although it may be reduced in magnitude. However, if PH is present, there may be a right ventricular heave (parasternal lift) and a palpable S2. The first heart sound (S1) may also be palpable. (See "Examination of the precordial pulsation", section on 'Right ventricular impulse'.)

Heart sounds — The following findings are characteristic for MS, but their absence does not exclude the diagnosis.

S1 – With stenotic but noncalcified mitral leaflets, the leaflets are widely separated at the onset of ventricular contraction due to elevated left atrial pressure, and the first heart sound (S1) is loud, reflecting the increased excursion of the stiff leaflets (movie 1A). As the leaflets become more rigid and calcified with severe obstruction, their motion is limited, and S1 becomes soft. (See "Auscultation of heart sounds", section on 'Intensity of S1'.)

S2 – The second heart sound is initially normal, but, with the development of PH, P2 becomes increased in intensity and may be widely transmitted. As pressure increases further, splitting of S2 is reduced, and, ultimately, S2 becomes a single sound.

S3 – A third heart sound of left ventricular origin is not heard in pure MS because of the obstruction to flow across the mitral valve. However, it may be present if there is coexisting aortic or mitral regurgitation or it may be generated from the right ventricle.

S4 – A fourth heart sound may be heard, generally originating from the right ventricle when it is hypertrophied and dilated and the patient is still in sinus rhythm.

Opening snap — In the presence of MS with leaflets with preserved mobility, an opening snap (OS) of the mitral valve is heard (movie 1A-B). The OS is due to the abrupt halt in leaflet motion in early diastole, after rapid initial rapid opening, due to fusion at the leaflet tips. It is best heard at the apex and lower left sternal border. The OS following S2 may be mistaken for a split S2 unless the examiner recognizes that the two components of S2 are followed by the OS during the inspiration and that the OS is best appreciated at the apex, not the base. (See "Auscultation of heart sounds", section on 'Opening snap'.)

As the MS progresses and left atrial pressure increases, the OS occurs earlier after S2 or A2. Thus, more severe MS is generally associated with a shorter A2-OS interval. However, this relationship is complicated by the effects of other conditions including tachycardia, hypertension, mitral regurgitation, and aortic valve disease, as discussed separately. (See "Auscultation of heart sounds", section on 'Mitral valve'.)

The OS is loudest when there is preserved excursion of the mitral leaflets. The OS is absent when the mitral valve leaflet motion is severely limited with calcification [5].

Diastolic murmur — The murmur caused by MS is a low-pitched diastolic rumble that is most prominent at the apex. It is heard best in a quiet room with the patient lying on the left side in held expiration and by using the bell of the stethoscope or the low frequency range of an electronic stethoscope carefully positioned over the apex (movie 1A).

Although the intensity of the diastolic murmur does not correlate with the severity of the stenosis, the duration of the murmur is helpful since it reflects the transvalvular gradient and the duration of blood flow across the valve.

When MS is mild, the gradient is confined to late diastole (during atrial contraction), and, hence, the murmur is heard late in diastole, just before S1.

As the stenosis becomes more severe, there is a gradient at the very onset of the diastolic flow period, immediately following the OS. This early diastolic murmur is decrescendo, becoming softer as the transvalvular gradient decreases. If the patient is still in sinus rhythm, the increase in atrial pressure during atrial contraction results in an increase in the loudness of the murmur, termed "presystolic accentuation" (movie 1A).

With more severe MS, there is a continuous gradient throughout all of the diastolic flow period, from mitral valve opening to mitral valve closure. However, the diastolic murmur may be inaudible or absent when MS is very severe, due to the very slow flow across the mitral valve. (See "Auscultation of cardiac murmurs in adults".)

There are several maneuvers that have been used to evaluate heart sounds in MS. (See "Physiologic and pharmacologic maneuvers in the differential diagnosis of heart murmurs and sounds".)

The diastolic murmur and OS are diminished with inspiration, but augmented with expiration (in contrast to tricuspid stenosis). With inspiration, the A2-OS interval widens and a distinct P2 may be heard.

Increasing venous return (eg, by lying the patient down and lifting the legs) augments the gradient; as a result, the diastolic murmur lengthens while the A2-OS intervals shorten. Similar changes are seen in response to exercise. In contrast, reducing venous return with amyl nitrate, the Valsalva maneuver, or standing after squatting shortens the murmur and lengthens the A2-OS interval.

Other sounds — There are other murmurs or sounds that may be heard in patients with MS, particularly when PH is present.

A pulmonary ejection sound is heard in early systole; the sound diminishes with inspiration when the pulmonary arteries dilate.

With the development of tricuspid regurgitation, there is a holosystolic murmur best heard along the right sternal border that increases with inspiration. (See "Etiology, clinical features, and evaluation of tricuspid regurgitation".)

A faint and brief early diastolic murmur of pulmonic regurgitation (Graham Steell murmur) may be heard at the base. (See "Auscultation of cardiac murmurs in adults", section on 'Pulmonic regurgitation'.)

Murmurs of mitral or aortic regurgitation may also be present if these valve lesions coexist with MS.

COMPLICATIONS

Atrial fibrillation — AF is common in patients with MS due to the elevation of left atrial pressure and left atrial enlargement. The prevalence of AF is higher with more severe disease, increasing age, and the presence of other valvular abnormalities. In a report that included 854 patients with MS, AF was present in 47 percent overall; the rate was higher in those with other valvular abnormalities (such as mitral or tricuspid regurgitation) [6]. The two independent risk factors for AF were left atrial diameter and increasing age. In other studies, the rate of AF among patients with severe MS ranged from 4 to 7 percent with mean patient age under 30 years to as high as 50 to 60 percent when the mean age was 50 to 60 years [7-11].

As discussed below, AF is one of the conditions that can precipitate or exacerbate symptoms such as dyspnea or hemoptysis. AF can lead to clinical decompensation via two mechanisms: the loss of atrial contraction, which plays an important role in the generation of adequate left atrial pressure to maintain blood flow across the stenotic valve; and the rapid ventricular response, which diminishes the time available for filling of the left ventricle [12]. (See "Hemodynamic consequences of atrial fibrillation and cardioversion to sinus rhythm".)

AF is suggested by an irregularly irregular pulse on physical examination and confirmed by electrocardiogram (ECG). (See "The electrocardiogram in atrial fibrillation" and "Atrial fibrillation: Overview and management of new-onset atrial fibrillation".)

Thromboembolism — Thromboembolic risk in patients with rheumatic MS is primarily related to the presence of AF and blood stasis in the left atrium. Thromboembolism is the first presentation of MS in some patients. While the most common site for clinically evident embolism is the cerebral circulation, any organ may be involved, especially spleen, kidneys, and the coronary circulation, resulting in a myocardial infarction. Though most emboli in patients with MS arise from the left atrium, emboli can also arise from the right atrium when there is pulmonary hypertension (PH) and right ventricular and atrial dilation. Emboli from this site lead to pulmonary embolism and infarction.

The risk of thromboembolism is higher in older patients (with a longer duration of disease), more severe MS, and heart failure, and is further increased with associated atherosclerotic risk factors including hypertension and diabetes [13,14].

Without anticoagulation – The risk of stroke in unanticoagulated patients with MS has been estimated as approximately 5 to 6 per 100 patient-years [13,14]. Prior to the widespread use of anticoagulant therapy and surgical treatment in patients with MS, as many as 30 percent of patients with MS experienced an embolic event during the course of the disease [2,15-19].

With anticoagulation – In later prospective studies in anticoagulated patients, the risk of stroke or systemic embolism ranged from 0.4 to 4 per 100 patient-years. As an example, in a prospective study of 511 consecutive patients in Brazil (85 percent female) with rheumatic heart disease (80 percent mitral valve) followed for a median 3.9 years, all patients with AF at baseline or a prior stroke (18 percent) were on warfarin anticoagulation [13,14]. Despite this therapy, a new ischemic stroke occurred in 5.2 percent, corresponding to an incidence of 1.47 per 100 patient-years. Taking into consideration death as a competing risk, predictors of incident stroke were age, AF, and prior stroke.

Pulmonary hypertension — Patients with MS commonly develop PH (defined as mean pulmonary artery pressure [mPAP] >20 mmHg).

In patients with MS, pulmonary artery pressure elevation is associated with more severe MS (smaller mitral valve area and higher mitral valve gradient) [20] and lower atrioventricular compliance [21]. PH caused by MS is a type of PH due to left heart disease (PH-LHD; group 2 PH), which is most commonly postcapillary PH but, in a minority of patients, is combined pre-and postcapillary PH. (See "Pulmonary hypertension due to left heart disease (group 2 pulmonary hypertension) in adults".)

Postcapillary PH – Among patients with MS with PH, most have postcapillary PH due to chronically elevated pulmonary venous pressure (figure 1) [22]. The postcapillary PH phenotype is characterized by an mPAP >20 mmHg, pulmonary artery wedge pressure of >15 mmHg, a diastolic pressure gradient (diastolic pulmonary artery pressure – pulmonary artery wedge pressure) of <7 mmHg, and a pulmonary vascular resistance ≤3 Wood units [23]. Another metric is the transpulmonary gradient (TPG = mPAP – pulmonary capillary wedge pressure) which is normal (≤12 to 15 mmHg) in patients with postcapillary PH.

Combined pre- and postcapillary PH – A minority of patients with MS and PH develop combined pre- and postcapillary PH. Precapillary PH is caused by vasoconstriction [24] and pathologic remodeling of the pulmonary vasculature [25] and may be, in part, mediated by the potent vasoconstrictor endothelin-1 (ET-1) (figure 1). The combined pre- and postcapillary phenotype is characterized by an mPAP >20 mmHg, pulmonary artery wedge pressure of >15 mmHg, a diastolic pressure gradient (diastolic pulmonary artery pressure – pulmonary artery wedge pressure) of ≥7 mmHg, and a pulmonary vascular resistance ≥3 Wood units [23]. The TPG is elevated (>15 mmHg) is elevated in patients with combined pre-and postcapillary PH.

The prevalence of PH in patients with MS is not well defined since differing definitions of PH have been used in various studies. In a series of 317 patients with MS undergoing percutaneous mitral balloon commissurotomy, most (73 percent) had PH (defined as mPAP >25 mmHg) and a minority of patients (19 percent) also had an elevated TPG (>15 mmHg) consistent with combined pre- and postcapillary PH [26]. (See "Pulmonary hypertension due to left heart disease (group 2 pulmonary hypertension) in adults", section on 'Diagnostic criteria'.)

Right heart failure — Chronic PH increases right ventricular afterload which can lead to right ventricular enlargement, right ventricular dysfunction, secondary tricuspid regurgitation, and signs of right-sided heart failure. (See "Pathophysiology and natural history of mitral stenosis", section on 'Pulmonary hypertension'.)

Signs of right-sided heart failure include (see "Right heart failure: Clinical manifestations and diagnosis"):

Increased jugular venous pressure. (See "Examination of the jugular venous pulse".)

Lower extremity edema, which may progress to involve the upper thighs, sacral area, and abdominal wall; ascites and pleural effusions can also occur.

Hepatomegaly in which the liver may be pulsatile if tricuspid regurgitation is present.

Infective endocarditis — Since the rheumatic mitral valve is deformed with disturbed blood flow patterns, there is a risk of infective endocarditis. In an international cohort of 3343 children and adults with rheumatic MS in low-income, lower-middle-income and upper-middle-income countries, the frequency of infective endocarditis ranged from 2.3 to 5.7 percent [11]. Clinical manifestations of infective endocarditis, including fever and embolism, are discussed separately. (See "Clinical manifestations and evaluation of adults with suspected left-sided native valve endocarditis".)

Hoarseness — If the left atrium becomes very large, there may be compression of the recurrent laryngeal nerve, leading to hoarseness (Ortner syndrome or cardiovocal syndrome) or coughing. (See "Hoarseness in adults".)

INITIAL TEST FINDINGS

Electrocardiogram — An ECG is commonly obtained in patients with MS. The most important finding on ECG in patients with MS is the presence of AF. Other findings on the surface ECG are nonspecific and are not recommended as part of the diagnostic evaluation. The finding of left atrial hypertrophy in a young patient without another obvious cause should prompt a search for MS. Findings on ECG include:

The QRS amplitude and morphology are normal unless there is mitral regurgitation or coexistent aortic valve disease.

Left atrial hypertrophy and enlargement results in a P wave that becomes broader (duration in lead II >0.12 s), is of increased amplitude, and is notched (due to the delay in left atrial activation). This is termed "P-mitrale." The left atrial changes also produce a prominent negative terminal portion of the P wave in lead V1.

The P-wave changes are not seen in patients with AF. The fibrillatory waves are coarse, generally >0.1 mV in amplitude, reflecting left atrial hypertrophy.

Additional changes occur with the development of pulmonary hypertension (PH) and right ventricular hypertrophy. The frontal axis shifts to the right (S>R in lead I and aVL) and a tall R wave develops in V1 and V2 (R>S or R/S ratio >1).

Chest radiograph — A chest radiograph is recommended for evaluation of heart failure symptoms in patients with MS, but a routine periodic chest radiograph is not recommended. However, an initial diagnosis of MS may be suggested by abnormal findings on a chest radiograph requested for other indications. The chest radiograph in mild MS may be normal, although there is often evidence of some enlargement of the left atrium and appendage. Left atrial enlargement may produce the following findings: a "double density" (double right heart border caused by the right side of the left atrium extending behind the right cardiac shadow), straightened left heart border (image 1), elevated left bronchus (image 2), and, on the lateral projection, posterior displacement of the left atrium, impinging on the esophagus (image 3).

The size of the left atrium reflects the duration of severe MS. Younger patients with severe MS may have only mild left atrial enlargement, while marked enlargement is typical in older patients. Left atrial size may be greater in patients with combined MS and regurgitation.

Other findings that may be seen include:

Calcification of the mitral annulus may be observed on an overpenetrated film in older adult patients with calcified rheumatic mitral disease (image 4).

Enlargement of the main pulmonary artery may be caused by PH, while the aorta and left ventricle are often small (image 5).

Pulmonary vascular congestion causes redistribution or "cephalization" of pulmonary blood flow to the upper lobes, dilated pulmonary vessels, Kerley B lines at the bases, and interlobar effusions (Kerley C lines) (image 6). In more severe cases, Kerley A lines (straight dense lines running toward the hilum) may be seen.

DIAGNOSIS AND EVALUATION

Approach to diagnosis — The diagnosis of rheumatic MS is suspected in a patient with demographics consistent with risk of rheumatic heart disease and symptoms and signs suggestive of MS.

Since symptoms may be slowly progressive, a careful history is required to determine if dyspnea or exercise intolerance is present. Although the physical examination can be diagnostic, findings are often subtle. Thus, resting transthoracic echocardiography is used to confirm the diagnosis. If there is a discrepancy between resting echocardiography and clinical symptoms or signs, exercise hemodynamic testing is suggested to evaluate changes in mean mitral gradient and pulmonary artery pressure. Cardiac catheterization is not generally required for diagnosis of MS but is indicated if echocardiography is nondiagnostic or conflicts with clinical findings.

Echocardiography — A transthoracic echocardiogram is indicated in patients with signs or symptoms of MS to establish the diagnosis, quantify the hemodynamic severity (table 1), determine the etiology, and assess concomitant valve disease. (See "Echocardiographic evaluation of the mitral valve" and "Percutaneous mitral balloon commissurotomy in adults".)

Use of echocardiography to monitor patients with MS and for screening patients who appear to be candidates for percutaneous mitral balloon commissurotomy (PMBC) is discussed separately. Transesophageal echocardiography is required to exclude left atrial thrombus. (See "Rheumatic mitral stenosis: Overview of management", section on 'Monitoring' and "Echocardiographic evaluation of the mitral valve", section on 'Mitral stenosis' and "Percutaneous mitral balloon commissurotomy in adults", section on 'Evaluation of candidates for PMBC'.)

Echocardiographic findings include:

Rheumatic changes of the mitral valve are pathognomonic, with commissural fusion resulting in a pattern of diastolic "doming" with the leaflet tips pointing towards each other in middiastole. In addition, commissural shortening, fusion, and thickening are present. In contrast, with calcific mitral valve disease, the leaflet tips separate normally, although the base of the leaflets may be thickened and fibrotic, along with calcification of the mitral annulus (movie 2A-F). (See "Echocardiographic evaluation of the mitral valve", section on 'Mitral stenosis' and "Clinical manifestations and diagnosis of mitral annular calcification".)

The mitral valve orifice area can be measured at the mitral leaflet tips in patients with rheumatic MS using two-dimensional (2D) or, preferably, three-dimensional (3D) echocardiography. (See "Echocardiographic evaluation of the mitral valve", section on 'Mitral stenosis'.)

Standard 2D Doppler echocardiography is appropriate for diagnosis of rheumatic MS, but 3D echocardiography provides a more reproducible and accurate cross-sectional view of the mitral orifice at the leaflet tips, to which planimetry can be applied to accurately determine the valve area (image 7) [27,28]. (See "Three-dimensional echocardiography", section on 'Mitral valve'.)

Left atrial size, and left and right ventricular size and systolic function, can be assessed. Left ventricular systolic function is unaffected by MS, but chamber size is small due to reduced diastolic filling across the stenotic mitral valve. However, MS often coexists with mitral regurgitation and occasionally with aortic valve dysfunction, which may cause left ventricular dilation or dysfunction [29].

Doppler echocardiography provides accurate hemodynamics measurements, including mean transvalvular gradient and the pressure half-time valve area (movie 3 and waveform 1). For rheumatic MS, the estimated mitral valve area is calculated from the pressure half-time:

Mitral valve area  =  220  /  pressure half-time

Mean transmitral gradient can be calculated from the diastolic velocity curve. However, guidelines do not recommend using mean gradient to define MS severity because mean gradient is highly dependent on loading conditions, stroke volume, and heart rate. Any condition that elevates left atrial pressure results in an increased transmitral gradient, even without a change in valve area. More importantly, the mean diastolic gradient depends on the duration of the diastolic filling interval. At a higher heart rate, diastole is shorter, resulting in a higher mean gradient compared with a slower heart rate (longer diastole) for the same stenosis severity.

Two-dimensional Doppler echocardiography is also used to evaluate coexisting mitral regurgitation and aortic valve disease. Pulmonary pressures are calculated from the velocity of the tricuspid regurgitation jet and right atrial pressure, which is estimated from the size and respiratory variation in the inferior vena cava. (See "Echocardiographic assessment of the right heart", section on 'Hemodynamics'.)

Additional testing — Exercise testing and/or cardiac catheterization is performed in selected patients with MS with indications for these tests.

Exercise testing — Hemodynamic exercise testing is helpful in selected patients with symptoms on exertion (dyspnea) with resting hemodynamics consistent with nonsevere ("progressive") MS (eg, resting mitral valve area is >1.5 cm2); these patients often have elevations in pulmonary artery wedge pressure (>25 mmHg) on exercise testing during cardiac catheterization or mean mitral valve gradient (>15 mmHg) on exercise echocardiography (or cardiac catheterization). These hemodynamic thresholds are used to identify patients likely to benefit from intervention with PMBC (recommendations discussed separately) [30,31]. (See "Rheumatic mitral stenosis: Overview of management", section on 'Our approach'.)

Dobutamine stress testing is less useful in evaluation of patients with MS but can also document the increase in transmitral gradient with an increase in heart rate. (See "Echocardiographic evaluation of the mitral valve", section on 'Stress echocardiography' and "Overview of stress echocardiography", section on 'Indications'.)

Cardiac catheterization — The widespread availability of echocardiography has led to a limited role for cardiac catheterization in the diagnosis of MS [31]. However, invasive pressure measurements are warranted if noninvasive tests are inconclusive, there is a discrepancy between clinical findings and noninvasive tests, or severe pulmonary arterial hypertension is out of proportion to the severity of MS as determined by noninvasive tests [31]. (See "Hemodynamics of valvular disorders as measured by cardiac catheterization", section on 'Mitral stenosis' and "Pulmonary hypertension due to left heart disease (group 2 pulmonary hypertension) in adults".)

In addition, invasive measurements are used, along with echocardiography, to monitor hemodynamics during a PMBC procedure (waveform 2 and figure 2). (See "Percutaneous mitral balloon commissurotomy in adults".)

DIFFERENTIAL DIAGNOSIS — Conditions that can present with symptoms and signs similar to those with rheumatic MS include the following obstructive cardiac lesions:

Other causes of MS:

Severe mitral annular calcification is a cause of functional MS due to a reduction in the annular size and fibrocalcific changes of the mitral leaflets. (See "Clinical manifestations and diagnosis of mitral annular calcification".)

Congenital MS is a rare presentation of MS with multiple morphologies including parachute mitral valve. (See "Pathophysiology and natural history of mitral stenosis", section on 'Congenital MS'.)

Infective endocarditis is a very rare cause of nonrheumatic MS in a patient with a previously normal valve [32,33].

Other causes of left atrial or left ventricular inflow obstruction:

Left atrial myxoma is a benign cardiac neoplasm that occurs most frequently in the left atrium and can present with symptoms caused by obstruction, evidence of systemic embolization, and/or constitutional symptoms such as fever and weight loss. The physical signs of left atrial myxoma may mimic those of rheumatic MS. Myxoma is generally identified by echocardiography. (See "Cardiac tumors", section on 'Myxomas'.)

Cor triatriatum (division of the left or right atrium by a membrane that may cause obstruction to flow) is diagnosed by echocardiography. (See "Echocardiographic evaluation of the atria and appendages".)

Iatrogenic causes – Additional causes of obstruction to left ventricular inflow can occur after mitral valve intervention (such as transcatheter mitral valve repair or after mitral valve replacement):

Functional MS can occur after a transcatheter mitral valve edge-to-edge clip procedure. The reduction in mitral regurgitant severity may be accompanied by a decrease in functional diastolic mitral orifice area and an increase in the diastolic mean gradient. (See "Transcatheter edge-to-edge mitral repair".)

Prosthetic mitral valve obstruction (by acute or chronic thrombus, pannus ingrowth, or leaflet calcification) is suspected by history (history of prosthetic valve implantation with change in prosthetic sounds, dyspnea, or heart failure) and diagnosed by echocardiography.

STAGING — Based on integration of information about valve anatomy, valve hemodynamics, secondary hemodynamic effects, and patient symptoms, MS severity is graded as follows (table 1) [31]:

Stage A includes asymptomatic patients at risk for MS. Features include mild mitral valve diastolic doming and normal transmitral flow velocities.

Stage B includes asymptomatic patients with progressive MS. Rheumatic mitral valve changes include commissural fusion and diastolic doming. Transmitral flow velocities are increased, but the mitral valve area is >1.5 cm2 and diastolic pressure half-time is <150 ms. Mild to moderate left atrial enlargement is present, and pulmonary artery pressures are normal at rest.

Stage C includes asymptomatic patients with severe MS, defined as a mitral valve area ≤1.5 cm2 and diastolic pressure half-time ≥150 ms. Rheumatic mitral valve changes are present, along with severe left atrial enlargement and pulmonary artery systolic pressure >30 mmHg.

Stage D includes patients with symptomatic severe MS, defined as a mitral valve area ≤1.5 cm2 and diastolic pressure half-time ≥150 ms. Rheumatic mitral valve changes are present, along with severe left atrial enlargement and pulmonary artery systolic pressure >30 mmHg.

The normal mitral valve orifice has a cross-sectional area of approximately 4.0 cm2. When the orifice is reduced to 2.0 cm2, the pressure gradient across the valve begins to increase. Many patients develop symptoms when the mitral valve area is reduced to 1.5 cm2 and nearly all patients becoming symptomatic when valve area is reduced to 1.0 cm2 or less. However, as noted above, many patients with severe MS do not recognize symptoms because slow progression of disease is matched by a gradual reduction in activity. (See 'Symptoms' above.)

In patients with severe MS (mitral valve area ≤1.5 cm2), the transmitral mean pressure gradient is usually >5 to 10 mmHg at normal heart rates, but this varies with changes in heart rate and forward flow, so the mean mitral gradient is not used to define severe MS [31].

Once the valve area is reduced to 2.0 cm2, the average rate of hemodynamic progression is a decrease in valve area of approximately 0.1 to 0.3 cm2/year, but the rate is highly variable [1,34,35]. (See "Pathophysiology and natural history of mitral stenosis", section on 'Rate of progression'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cardiac valve disease".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topic (see "Patient education: Mitral stenosis in adults (The Basics)")

SUMMARY AND RECOMMENDATIONS

Clinical presentation – The duration of the asymptomatic phase of rheumatic mitral stenosis (MS) varies widely, with generally more rapid progression to symptoms developing in children and young adults in resource-limited countries and slower progression to symptoms developing in older adults in resource-abundant countries. Rheumatic MS most commonly presents with exertional dyspnea and/or decreased exercise tolerance. Less common clinical presentations include hemoptysis, chest pain, fatigue, ascites and lower extremity edema, and stroke or other thromboembolic event. (See "Pathophysiology and natural history of mitral stenosis", section on 'Natural history' and 'Symptoms' above.)

Precipitants of symptoms – In patients with MS, any situation that increases the cardiac output or causes tachycardia can markedly increase the transmitral pressure gradient and precipitate symptoms such as dyspnea or hemoptysis. Activities or conditions that can provoke symptoms include exertion, emotional stress, fever, infection, atrial fibrillation (AF), and pregnancy. (See 'Precipitants of symptoms' above.)

Auscultation – Identification of characteristic heart sounds, opening snap, and diastolic murmur may be diagnostic for MS with appropriate patient positioning in a quiet room (movie 1A-B). However, the opening snap and murmur may be difficult to appreciate, particularly with higher heart rates. (See 'Cardiac examination' above.)

Complications – Complications of MS include AF, thromboembolism, pulmonary hypertension (PH), right heart failure, infective endocarditis, and hoarseness. (See 'Complications' above.)

Diagnosis and evaluation – The diagnosis of rheumatic MS is suspected in a patient with demographics consistent with risk of rheumatic heart disease with symptoms and signs suggestive of MS. Transthoracic echocardiography is used to confirm the diagnosis and is integrated with symptoms to determine the stage of disease (table 1). (See 'Diagnosis and evaluation' above.)

Role of additional testing – If there is a discrepancy between resting echocardiography and clinical symptoms or signs, hemodynamic exercise testing is suggested to evaluate changes in mean mitral gradient (generally by exercise stress echocardiograph) or pulmonary artery wedge pressure (by exercise testing during cardiac catheterization). Cardiac catheterization is rarely needed for diagnosis of MS and is most commonly performed as part a therapeutic interventional procedure. (See 'Approach to diagnosis' above and "Percutaneous mitral balloon commissurotomy in adults".)

Differential diagnosis – The differential diagnosis of rheumatic MS includes conditions that present with similar symptoms and signs, including obstructive cardiac lesions such as functional MS after transcatheter mitral valve repair, calcific MS, left atrial myxoma, and cor triatriatum. (See 'Differential diagnosis' above.)

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References

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