Introduction
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. Other less common etiologies include congenital mitral stenosis, malignant carcinoid disease, systemic lupus erythematosus, rheumatoid arthritis, mucopolysaccharidoses of the Hunter-Hurler phenotype, Fabry disease, Whipple disease, and methysergide therapy. The association of atrial septal defect with rheumatic mitral stenosis is called Lutembacher syndrome.
A number of conditions can simulate the physiology of mitral stenosis: severe nonrheumatic mitral annular calcification, infective endocarditis with large vegetation, left atrial myxoma, ball valve thrombus, or cor triatriatum.
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.
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.
Frequency
United States
The prevalence of rheumatic disease in developed nations is steadily declining with an estimated incidence of 1 in 100,000.
International
The prevalence of rheumatic disease is higher in developing nations than in the United States.1 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.
Mortality/Morbidity
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%).
Sex
Two thirds of all patients with rheumatic mitral stenosis are female.
Age
The onset of symptoms usually occurs between the third and fourth decade of life.
Clinical
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.
Physical
* 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.
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.
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Apical 4-chamber view demonstrating restricted op...
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.
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.
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Apical 4-chamber view with color Doppler demonstr...
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 P 2 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.
o 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.
o 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.
o 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 S 3 originating from the right ventricle may be audible in the 4th left intercostal space in the patient with right ventricular dilatation.Differential Diagnoses
Cor Triatriatum
Other Problems to Be Considered
* Left atrial myxoma
* Ball valve thrombus
* Endocarditis
* Massive mitral annular calcification
Workup
Laboratory Studies
Perform routine baseline tests such as CBC count, electrolyte status, and renal and liver function tests.
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. 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.2
* 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.
See the image and videos below.
Transesophageal echocardiogram with continuous wa...
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.
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Transesophageal echocardiogram with continuous wa...
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.
Magnified view of the mitral valve in apical 4-chamber view revealing restricted opening of both leaflets.
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Magnified view of the mitral valve in apical 4-ch...
Magnified view of the mitral valve in apical 4-chamber view revealing restricted opening of both leaflets.
Transesophageal echocardiogram in an apical 3-chamber view showing calcification and doming of the anterior mitral leaflet and restricted opening of both leaflets.
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Transesophageal echocardiogram in an apical 3-cha...
Transesophageal echocardiogram in an apical 3-chamber view showing calcification and doming of the anterior mitral leaflet and restricted opening of both leaflets.
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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Transesophageal echocardiogram in an apical 3-cha...
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.
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.
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 valvotomy.Treatment
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.
* Because rheumatic fever is the primary cause of mitral stenosis, secondary prophylaxis against group A beta-hemolytic streptococci (GAS) is recommended.3 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 recent study done in Europe on 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.4
* The current American Heart Association (AHA) recommendations5 no longer suggest infective endocarditis prophylaxis for patients with rheumatic heart disease. 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, such as those with prosthetic valves or prosthetic material used in valve repair, the current AHA recommendations should be followed. 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.
* 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.
* 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. The ventricular rate 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.
* Surgical correction of the mitral stenosis is indicated if embolization is recurrent, despite adequate anticoagulation therapy.
Table 1. Duration of Secondary Rheumatic Fever Prophylaxis
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Table
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
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.
Table 2. Secondary Prevention of Rheumatic Fever (Prevention of Recurrent Attacks)
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Table
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
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.
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 open or closed technique; the latter technique is rarely used, except in developing countries, and has largely been replaced by the percutaneous balloon valvotomy.2
Asymptomatic patients with moderate or severe mitral stenosis (mitral valve area <1.5 cm2) and a suitable valve should be considered for percutaneous balloon valvuloplasty 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.6
Symptomatic patients with moderate or severe mitral stenosis (mitral valve area <1.5 cm2) and suitable valve are also candidates for percutaneous balloon valvuloplasty.
If percutaneous balloon valvuloplasty is not an option, patients should be referred for surgical repair or mitral valve replacement.
* Percutaneous balloon valvuloplasty
o Percutaneous balloon valvuloplasty 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 valvotomy to clearly define the valve anatomy and exclude the presence of a left atrial thrombus.
o 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.
o With percutaneous balloon valvuloplasty, 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.
o Improvement in symptoms is noted immediately following the procedure. If symptoms do not improve, the valvuloplasty was either ineffective or resulted in mitral regurgitation.
o The short- and long-term prognoses are favorable compared with surgical valvotomy.
o Balloon valvuloplasty offers certain advantages over surgical valvotomy, including avoidance of a thoracotomy and general anesthesia and their attendant complications.
o The major contraindications to balloon valvuloplasty 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).
o Complications of a balloon mitral valvuloplasty include embolization, mitral regurgitation, ventricular rupture, residual atrial septal defect, stroke, and death.
* Surgical valvotomy/valve replacement7
o Open surgical commissurotomy allows direct visualization of the mitral valve.
o 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.
o 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.
o 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.
o 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.
Consultations
A cardiology and/or cardiothoracic surgery consult may be necessary.
Diet
The patient should start a low-salt diet if pulmonary vascular congestion is present.
Activity
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.
Medication
The goals of pharmacotherapy are to reduce morbidity and to prevent complications.
Antiarrhythmics
These agents alter the electrophysiologic mechanisms responsible for arrhythmia.
Digoxin (Lanoxicaps, Lanoxin)
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.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
0.125-0.375 mg PO qd
Pediatric
Not established
* Dosing
* Interactions
* Contraindications
* Precautions
IV calcium may produce arrhythmias in digitalized patients
Medications that may increase levels include alprazolam, benzodiazepines, bepridil, captopril, cyclosporine, propafenone, propantheline, quinidine, diltiazem, aminoglycosides, oral amiodarone, anticholinergics, diphenoxylate, erythromycin, felodipine, flecainide, hydroxychloroquine, itraconazole, nifedipine, omeprazole, quinine, ibuprofen, indomethacin, esmolol, tetracycline, tolbutamide, and verapamil
Medications that may decrease serum levels include aminoglutethimide, antihistamines, cholestyramine, neomycin, penicillamine, aminoglycosides, oral colestipol, hydantoins, hypoglycemic agents, antineoplastic treatment combinations (including carmustine, bleomycin, methotrexate, cytarabine, doxorubicin, cyclophosphamide, vincristine, and procarbazine), aluminum or magnesium antacids, rifampin, sucralfate, sulfasalazine, barbiturates, kaolin/pectin, and aminosalicylic acid
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; beriberi heart disease, hypertrophic obstructive cardiomyopathy, constrictive pericarditis, and carotid sinus syndrome
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Hypokalemia may reduce positive inotropic effect; hypercalcemia predisposes patient to digitalis toxicity; hypocalcemia can make digoxin ineffective until serum calcium levels are normal; magnesium replacement therapy must be instituted in patients with hypomagnesemia to prevent digitalis toxicity; patients with incomplete AV block may progress to complete block when treated with digoxin; exercise caution in hypothyroidism, hypoxia, and acute myocarditis; adjust dose in renal impairment; highly toxic (overdoses can be fatal)
Amiodarone (Cordarone, Pacerone)
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.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
Loading dose: 800-1600 mg/d PO in 1-2 doses for 1-3 wk; decrease to 600-800 mg/d in 1-2 doses for 1 mo
Maintenance dose: 400 mg/d PO
Alternatively: 150 mg (10 mL) IV over first 10 min, followed by 360 mg (200 mL) over next 6 h, then 540 mg over next 18 h
Pediatric
Not established
* Dosing
* Interactions
* Contraindications
* Precautions
Increases effect and blood levels of theophylline, quinidine, procainamide, phenytoin, methotrexate, flecainide, digoxin, cyclosporine, beta-blockers, and anticoagulants; cardiotoxicity is increased by ritonavir, sparfloxacin, and disopyramide; coadministration with calcium channel blockers may cause additive effect and further decrease myocardial contractility; cimetidine may increase levels; protease inhibitors (eg, indinavir, ritonavir, amprenavir, nelfinavir) inhibit metabolism, resulting in increased serum levels, and may prolong QT interval
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; complete AV block; intraventricular conduction defects; patients taking ritonavir or sparfloxacin
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in thyroid or liver disease
Calcium channel blockers
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.
Diltiazem (Cardizem CD, Dilacor, Tiazac, Cardizem LA)
During depolarization, inhibits calcium ions from entering slow channels and voltage-sensitive areas of vascular smooth muscle and myocardium.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
Cardizem SR: 60-120 mg PO bid
Cardizem CD: 180-240 mg PO qd in hypertension
Pediatric
Not established
* Dosing
* Interactions
* Contraindications
* Precautions
May increase carbamazepine, digoxin, cyclosporine, and theophylline levels; when administered with amiodarone, may cause bradycardia and a decrease in cardiac output; when given with beta-blockers, may increase cardiac depression; cimetidine may increase levels
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; severe CHF; sick sinus syndrome; second- or third-degree AV block; hypotension (<90 mm Hg systolic)
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in impaired renal or hepatic function; may increase LFT levels, and hepatic injury may occur
Anticoagulants
These agents prevent recurrent or ongoing thromboembolic occlusion of the vertebrobasilar circulation.
Warfarin (Coumadin)
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.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
5-15 mg/d PO qd for 2-5 d; adjust dose according to desired INR
Pediatric
Not established
* Dosing
* Interactions
* Contraindications
* Precautions
Drugs that may decrease anticoagulant effects include griseofulvin, carbamazepine, glutethimide, estrogens, nafcillin, phenytoin, rifampin, barbiturates, cholestyramine, colestipol, vitamin K, spironolactone, oral contraceptives, and sucralfate
Medications that may increase anticoagulant effects include oral antibiotics, capecitabine, phenylbutazone, salicylates, sulfonamides, chloral hydrate, clofibrate, diazoxide, anabolic steroids, ketoconazole, ethacrynic acid, miconazole, nalidixic acid, sulfonylureas, allopurinol, chloramphenicol, cimetidine, disulfiram, metronidazole, phenylbutazone, phenytoin, propoxyphene, sulfonamides, gemfibrozil, acetaminophen, and sulindac
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; severe liver or kidney disease; open wounds or GI ulcers
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Do not switch brands after achieving therapeutic response; caution in active tuberculosis or diabetes; patients with protein C or S deficiency are at risk of developing skin necrosis
Heparin
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.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
Initial dose: 40-170 U/kg IV
Maintenance infusion: 18 U/kg/h IV
Alternatively: 50 U/kg/h IV initially, followed by continuous infusion of 15-25 U/kg/h; increase dose by 5 U/kg/h q4h prn using aPTT results
Pediatric
Not established
* Dosing
* Interactions
* Contraindications
* Precautions
Digoxin, nicotine, tetracycline, and antihistamines may decrease effects; NSAIDs, aspirin, dextran, dipyridamole, and hydroxychloroquine may increase heparin toxicity
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; subacute bacterial endocarditis; active bleeding; history of heparin-induced thrombocytopenia
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
In neonates, preservative-free heparin is recommended to avoid possible toxicity (gasping syndrome) from benzyl alcohol, which is used as a preservative; caution in severe hypotension and shock; monitor for bleeding in peptic ulcer disease, menstruation, increased capillary permeability, and when giving IM injections
Beta-adrenergic blockers
These agents inhibit chronotropic, inotropic, and vasodilatory responses to beta-adrenergic stimulation.
Metoprolol (Lopressor, Toprol XL)
Selective beta1-adrenergic receptor blocker that decreases automaticity of contractions. During IV administration, carefully monitor blood pressure, heart rate, and ECG.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
100 mg/d PO qd or divided bid/tid initially; increase at 1-wk intervals prn, not to exceed total of 450 mg/d
Pediatric
Not established
* Dosing
* Interactions
* Contraindications
* Precautions
Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels, possibly resulting in decreased pharmacologic effects; toxicity may increase with coadministration of sparfloxacin, phenothiazines, astemizole, calcium channel blockers, quinidine, flecainide, and contraceptives; may increase toxicity of digoxin, flecainide, clonidine, epinephrine, nifedipine, prazosin, verapamil, and lidocaine
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; uncompensated congestive heart failure; bradycardia, asthma; cardiogenic shock; AV conduction abnormalities
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Pregnancy category D in second or third trimester; beta-adrenergic blockade may reduce signs and symptoms of acute hypoglycemia and may decrease clinical signs of hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; monitor patient closely and withdraw drug slowly; during IV administration, carefully monitor blood pressure, heart rate, and ECG
Antibiotics
Must cover all likely pathogens in the context of this clinical setting. Use as prophylaxis against streptococcal infections.
Penicillin G benzathine (Bicillin L-A, Permapen)
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.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
2 million U IM qmo
Pediatric
Not established
* Dosing
* Interactions
* Contraindications
* Precautions
Probenecid can increase effectiveness by decreasing clearance; coadministration with tetracyclines can decrease effectiveness
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in impaired renal function
Diuretics
Diuretics are used for treatment of pulmonary congestion. Treatment may improve symptoms of venous congestion through elimination of retained fluid and preload reduction.
Furosemide (Lasix)
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.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
20-80 mg/d PO/IV/IM; titrate up to 600 mg/d for severe edematous states
Pediatric
Not established.Follow-up
Further Outpatient Care
* 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 echocardiogram (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.
Deterrence/Prevention
* Primary prevention of acute rheumatic fever3 (see Table 3 below).
* Secondary prevention of rheumatic fever (see Medical Care).
* Infective endocarditis prophylaxis (see Medical Care).
Table 3. Primary Prevention of Rheumatic Fever (Treatment of Streptococcal Tonsillopharyngitis*)
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Table
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
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)
Complications
* 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
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.8
* 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.
Patient Education
All patients should be informed about the following:
* Signs and symptoms of severe mitral stenosis (Patients should be advised to present for re-evaluation.)
* 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
Miscellaneous
Special Concerns
* Pregnant women with mild-to-moderate mitral stenosis can almost always be managed with judicious use of diuretics and beta blockade.
* Pregnant women with severe mitral stenosis who are symptomatic before conception will not predictably tolerate the hemodynamic burden of pregnancy and should be considered for percutaneous balloon mitral valvotomy before conception provided the valve is anatomically suitable.
* Patients with severe mitral stenosis who develop NYHA functional class III–IV symptoms during pregnancy should undergo percutaneous balloon valvotomy.
