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]
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.
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.
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
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
-
Mitral Stenosis. M-mode across the mitral valve showing a flat E-F slope resulting from elevated left atrial pressure throughout diastole due to a significant gradient across the mitral valve. Increased thickness and calcification of anterior leaflet of the mitral valve and decreased opening of the anterior and posterior leaflets in diastole are also shown.
-
Mitral Stenosis. Parasternal long-axis view demonstrating calcification and doming in diastole of the anterior valve leaflet and mild restriction in the opening of posterior mitral valve leaflet.
-
Mitral Stenosis. 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.
-
Mitral Stenosis. Transesophageal echocardiogram with continuous wave Doppler interrogation across the mitral valve demonstrating an increased mean gradient of 16 mm Hg consistent with severe mitral stenosis.
-
Mitral Stenosis. 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.
-
Mitral Stenosis. Magnified view of the mitral valve in apical 4-chamber view revealing restricted opening of both leaflets.
-
Mitral Stenosis. Transesophageal echocardiogram in an apical 3-chamber view showing calcification and doming of the anterior mitral leaflet and restricted opening of both leaflets.
-
Mitral Stenosis. 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.
Tables
- Table 1. Duration of Secondary Rheumatic Fever Prophylaxis
- Table 2. Secondary Prevention of Rheumatic Fever (Prevention of Recurrent Attacks)
- Table 3. Primary Prevention of Rheumatic Fever (Treatment of Streptococcal Tonsillopharyngitis*)
- Table 4. Recommendations for Mitral Stenosis (MS) Intervention
Category |
Duration After Last Attack |
Rating* |
|
Rheumatic fever with carditis and residual heart disease (persistent valvular disease† ) |
10 y or until age 40 y (whichever is longer); sometimes lifelong prophylaxis |
IC |
|
Rheumatic fever with carditis but no residual heart disease (no valvular disease† ) |
10 y or until age 21 y (whichever is longer) |
IC |
|
Rheumatic fever without carditis |
5 y or until age 21 y (whichever is longer) |
IC |
|
*Rating indicates classification of recommendation and level of evidence (eg, IC indicates Class I, level of Evidence C). †Clinical or echocardiographic evidence. |
|||
Agent |
Dose |
Mode |
Rating* |
Benzathine penicillin G |
Children 27 kg (60 lb): 600,000 U Patients >27 kg: 1,200,000 every 4 wk† |
Intramuscular |
IA |
Penicillin V |
250 mg bid |
Oral |
IB |
Sulfadiazine |
Children 27 kg: 0.5 g qd Patients >27 kg: 1 g qd |
Oral |
IB |
Macrolide or azalide (for individuals allergic to penicillin and sulfadiazine) |
Variable |
Oral |
IC |
*Rating indicates classification of recommendation and level of evidence (eg, IA indicates Class I, level of Evidence A). †In high-risk situations, administration every 3 weeks is justified and recommended. |
|||
Agent |
Dose |
Mode |
Duration |
Rating † |
Penicillins |
||||
Penicillin V (phenoxymethyl penicillin) |
Children 27 kg (60 lb): 250 mg bid or tid Patients >27 kg: 500 mg bid or tid |
Oral |
10 d |
IB |
Amoxicillin |
50 mg/kg qd (maximum 1 g) |
Oral |
10 d |
IB |
Benzathine penicillin G |
Children 27 kg (60 lb): 600,000 U Patients >27 kg: 1,200,000 U |
Intramuscular |
Once |
IB |
For individuals allergic to penicillin |
||||
Narrow-spectrum cephalosporin (cephalexin, cefadroxil) |
Variable |
Oral |
10 d |
IB |
Clindamycin |
20 mg/kg/d divided in 3 doses (maximum 1.8 g/d) |
Oral |
10 d |
IIaB |
Azithromycin |
12 mg/kg qd (maximum 500 mg) |
Oral |
5 d |
IIaB |
Clarithromycin |
15 mg/kg/d divided bid (maximum 250 mg bid) |
Oral |
10 d |
IIaB |
*Sulfonamides, trimethoprim, tetracyclines, and fluoroquinolones are not acceptable. †Rating indicates classification of recommendation and level of evidence (eg, IB indicates Class I, level of Evidence B) |
||||
Recommendation |
AHA/ACC (2014) [12] |
|
Concomitant mitral valve surgery for patients with severe MS (stage C or D) undergoing other cardiac surgery |
Class I |
|
Percutaneous mitral balloon commissurotomy (PMBC) for asymptomatic patients with very severe MS (stage C) and favorable valve morphology in the absence of left atrial (LA) thrombus or moderate-to-severe mitral regurgitation (MR) |
Class IIa: Reasonable |
|
PMBC for asymptomatic patients without unfavorable clinical characteristics when the risk of thromboembolism or hemodynamic decompensation is high |
Class IIa: Reasonable |
|
Mitral valve surgery for severely symptomatic patients (NYHA class III/IV) with severe MS (stage D), provided there are other operative indications |
Class IIa: Reasonable |
|
PMBC for asymptomatic patients with severe MS (stage C) and favorable valve morphology who have new onset of atrial fibrillation (AF) in the absence of an LA thrombus or moderate-to-severe MR |
Class IIb: Consider |
|
PMBC for symptomatic patients with a mitral valve area (MVA) above1.5 cm² if there is evidence of hemodynamically significant MS during exercise |
Class IIb: Consider |
|
PMBC for severely symptomatic patients (NYHA class III/IV) with severe MS (stage D) who have suboptimal valve anatomy and are not candidates or are at high risk for surgery |
Class IIb: Consider |
Class IIa: Reasonable |
Concomitant mitral valve surgery for patients with moderate MS undergoing cardiac surgery for other causes |
Class IIb: Consider |
|
Mitral valve surgery and excision of the LA appendage for patients with severe MS (stages C and D) who have had recurrent embolic events while receiving anticoagulation |
Class IIb: Consider |
