Congenital Mitral Stenosis

The mitral valve is the inlet valve to the left ventricle (LV). The normal mitral valve is a complex apparatus composed of an annulus and two leaflets that are attached by chordae tendineae to two papillary muscles. The papillary muscles arise from the walls of the LV and secure the chordae and mitral leaflets, preventing prolapse of the valve during ventricular systole.

Proper function of the mitral valve requires an intact mitral valve apparatus and satisfactory LV function. Mitral stenosis (MS) results from any pathologic process that narrows the effective mitral valve orifice at the supravalvular, valvular, or subvalvular levels. MS can be congenital or acquired.

Congenital MS is a rare entity which takes several forms. These forms include hypoplasia of the mitral valve annulus, mitral valve commissural fusion, double orifice mitral valve, shortened or thickened chordae tendineae, and parachute mitral valve in which all chordae attach to a single papillary muscle.[1] The most common associated malformations are coarctation of the aorta, aortic valve stenosis, and subvalvular aortic stenosis. The association of multiple levels of left-sided inflow and outflow tract obstruction is termed the Shone complex.[2]

Severe hypoplasia, or atresia, of the mitral valve results in a hypoplastic LV cavity size that is not capable of sustaining the systemic cardiac output. This situation is considered part of the spectrum of the hypoplastic left heart syndrome and is not considered further in this article. This article deals with MS that, although occasionally severe, allows enough blood flow into the LV to sustain the systemic cardiac output.

Mitral stenosis (MS) obstructs blood flow into the left ventricle (LV), elevating left atrial pressure in proportion to severity of the stenosis. This, in turn, restricts pulmonary venous return to the left atrium, elevating pulmonary vascular and, consequently, right heart pressures. Elevated hydrostatic pressure in the pulmonary capillaries forces fluid into the alveoli and interstitial space, producing pulmonary congestion. Congested bronchial veins may encroach on small bronchioles, with subsequent increase in airway resistance.

As a compensatory mechanism, pulmonary vasoconstriction occurs. The right ventricle (RV) pressure increases, resulting in RV hypertrophy. Elevated pulmonary pressure can progress to fixed pulmonary arterial hypertension from medial hypertrophy and intimal thickening of the pulmonary arterioles. The RV eventually fails, and pulmonary blood flow decreases, decreasing systemic blood flow. RV failure results in systemic venous congestion with development of hepatomegaly, ascites, and pedal edema. If the reduction in cardiac output is critical, end organ failure with renal and/or hepatic insufficiency, shock, and metabolic acidosis can occur.

Hemodynamic changes in severe congenital MS are illustrated in the image below.

Atrioventricular (AV) valve morphogenesis is a complex process comprised of cell migration, proliferation, apoptosis, and remodeling, all geared towards forming an annulus, AV valve leaflets, and a subvalvar support apparatus comprised of tendinous cords and papillary muscles.

As we know it today, the mitral and tricuspid valves develop at 21 days gestation in the human embryo when endocardial cells migrate into the developing cushion. This is known as the endothelial to mesenchymal transformation (EMT). As these mesenchymal cells proliferate, the endocardial cushions expand and valve primordia appear. The AV canal is then divided into left and right AV valve orifices. The cushions also become populated by epicardial cells as well as cells derived from the second heart field.[3]  Individual valve leaflets can be observed as early as week 5 and 6 of fetal development. These valve primordia continue to remodel well into postnatal life, where they become a laminar structure of elastin, collagen, and proteoglycans.

Several genes, including transforming growth factor (TGF)-β, Sox9, and erbB3, are known to contribute to these processes through signaling and downstream activation dependent on the nuclear factor of activated T-cells transcription factors.[3] Therefore, absence of any of such genes will result in AV valve malformations. That genes are responsible for valvar malformation is clear in the fact that the prevalence of MS in offspring of family members with left ventricular outflow tract obstruction is increased, especially if the mother is affected.

In addition, formation of the mitral valve requires proper division of the AV canal as well as commitment of the aortic valve to the left ventricle, which results in fibrous continuity between the anterior (aortic) mitral valve leaflet and the non-coronary and left coronary leaflets of the aortic valve.[4]

United States data

Congenital mitral stenosis (MS) is rare, occurring in 0.5% of patients with congenital heart disease (CHD).

Race-, sex-, and age-related demographics

No racial or sex predilection is known in congenital MS.

Congenital MS is usually detected in infancy if MS and/or associated heart lesions are severe enough to produce physical findings or to provoke overt symptoms.

Untreated newborns with severe mitral stenosis (MS) have a grim prognosis. Surgical intervention is ideally avoided for as long as possible. Mechanical mitral valve replacement in a small infant or child is a high-risk procedure and carries a guarded prognosis.

Because MS can be associated with other cardiac lesions such as atrial septal defects, ventricular septal defects, left ventricular outflow tract obstruction, and coarctation of the aorta, operative results and long-term outcomes are widely variable and highly dependent on the abnormalities that are present.

Mitral valve replacement entails a less than 5% mortality risk in young, healthy patients without other significant cardiac abnormalities.

Morbidity/mortality

In the fetus, mitral valve obstruction does not interfere with normal growth and development, even if the mitral valve is atretic. This is because the amount of pulmonary venous return to the left atrium is small and the fetal bronchial collateral circulation is adequate to relieve the obstructive effects. In this case, the RV supplies all of the systemic blood flow via the ductus arteriosus, and the patient presents with hypoplastic left heart syndrome.

Less severe forms of MS permit normal fetal circulatory pathways to continue with normal development of the LV and ascending aorta. After birth, if congenital MS is left untreated, morbidity and mortality are high, with mean survival estimated at 3 years. Associated cardiac lesions such as coarctation of the aorta and aortic valve stenosis such as in the Shone complex increase morbidity and mortality.

Complications

If MS is left untreated, the following complications may arise:

• Pulmonary edema

• Right heart failure with progression to congestive heart failure

• Renal insufficiency (due to congestive heart failure)

• Progression to pulmonary hypertension

• Atrial arrhythmias: Atrial arrhythmias such as fibrillation or flutter occur more frequently in patients with chronic left atrial enlargement. Initiation and perpetuation of these arrhythmias has been attributed to a vertical line of conduction delay that runs between the pulmonary veins.

• Thrombus formation in the dilated left atrium (due to stasis of blood)

• Embolization of a left atrial thrombus, stroke

• Dysphagia from compression of the esophagus by an enlarged left atrium

Complications of medical treatment include the following:

• Diuretics may provoke dehydration (decreased preload) with subsequent compromise in cardiac output that may precipitate prerenal renal failure.

• Warfarin may cause bleeding, such as intracranial hemorrhage and gastrointestinal (GI) bleeding.

Complications of surgery include the following:

• Patients with associated congenital cardiac anomalies have a higher risk of early death after mitral valve surgery.

• The risks of mitral valve replacement include those associated with anticoagulation, valve thrombosis, valve dehiscence, infective endocarditis, valve malfunction, and embolic events.

• Iatrogenic mitral valve insufficiency may occur as a result of surgery (or balloon dilatation, when performed) of the stenotic mitral valve. This can be corrected immediately as repairs are assessed by intraoperative transesophageal echocardiography.

• Mitral commissurotomy may cause significant postoperative mitral regurgitation, which may necessitate subsequent mitral valve replacement.

• Patients with associated left ventricular outflow tract obstruction who require subaortic membrane resection may develop complete atrioventricular block and require a permanent pacemaker.

Complications of percutaneous balloon valvuloplasty include the following:

• Safety depends on the mitral valve morphology and on the operator's experience. Very few forms of congenital MS are amenable to balloon valvotomy. Percutaneous balloon valvotomy should not be performed in patients with pre-existing moderate-to-severe mitral valve regurgitation.

• The most frequent complication after percutaneous balloon valvuloplasty is mitral regurgitation.

Counsel the patient and families regarding the appearance and worsening of symptoms of mitral stenosis.

Prior to any invasive or surgical procedure, advise the patient regarding subacute bacterial endocarditis (SBE) prophylaxis.

Monitor prothrombin time (PT) and international normalized ratio (INR) if the patient is on anticoagulation medication.

Advise pregnant mothers to avoid taking warfarin due to teratogenicity, avoid strenuous activity and excessive salt intake, and have their blood pressure frequently monitored.

For patient education resources, see the Heart Health Center, as well as Mitral Valve Prolapse.

Congenital mitral stenosis (MS) in infancy

Patients with severe MS may present with respiratory distress from pulmonary edema shortly after birth if a significant atrial septal communication is not present. The presence of an atrial septal defect decompresses the left atrium, resulting in a clinical picture of pulmonary overcirculation and decreased systemic cardiac output.

Patients with mild-to-moderate MS present after the neonatal period with signs of low cardiac output and RV failure such as pulmonary infections, failure to gain weight, exhaustion and diaphoresis with feeding, tachypnea, and chronic cough.

Congenital MS in older children

Children with MS may present with the insidious onset of exercise limitation and other clinical signs.

Pulmonary congestion evidenced by increasing severity of dyspnea (depending on degree of MS) that may range from dyspnea during exercise to paroxysmal nocturnal dyspnea, orthopnea, or even frank pulmonary edema. Dyspnea may be precipitated or worsened by an increase in blood flow across the stenotic mitral valve (eg, pregnancy, exercise) or by a reduction in diastolic filling time achieved by increasing the heart rate (eg, emotional stress, fever, respiratory infection, atrial fibrillation with rapid ventricular rate).

Signs of right heart failure, including peripheral edema and fatigue, may be present.

Patients with MS, including those previously without symptoms may develop atrial fibrillation, although this is an uncommon event in childhood. It results from chronic distension of the left atrium. Atrial fibrillation may cause the following:

• Loss of the atrial kick to LV filling reduces systemic output; this may precipitate or exacerbate congestive heart failure.

• Thromboembolic events (seeding of systemic emboli) occur in 10-20% of patients with MS. Many of these emboli lodge in the brain, causing a stroke.

• Infective endocarditis (a rare event) should be suspected when embolization occurs during sinus rhythm.

Hemoptysis may be caused by rupture of dilated bronchial veins. Pink frothy sputum may be a manifestation of frank pulmonary edema. Both are associated with end-stage severe MS but rarely occur in pediatric patients.

Chest pain occurs in approximately 15% of patients with MS.

Dysphagia can be produced by compression of the esophagus as a result of a dilated left atrium. It rarely occurs in children.

Hoarseness can occur if the dilated left atrium impinges on the recurrent laryngeal nerve. It is a rare manifestation of severe MS.

Physical examination findings vary according to the severity of mitral stenosis (MS).

Mild-to-moderate MS

Features of mild-to-moderate MS include the following:

• Normal peripheral pulses and good perfusion

• Loud S1 caused by abrupt closure of the stenotic mitral valve

• Increased intensity of the pulmonic component of the second heart sound in proportion to elevation of pulmonary arterial pressure

• A long low-frequency diastolic murmur beginning shortly after S2 best heard at the apex, with late diastolic accentuation (as long as sinus rhythm is present) (Intensity and length of the murmur are in proportion to severity of the obstruction.)

• Possible demonstration of S4 at the apex in older children

Severe MS

Features of severe MS include the following:

• Diminished peripheral perfusion and pulses

• Palpation of an RV impulse (enlarged RV) when pulmonary hypertension is present

• Soft S1 in the presence of heart failure and diminished left ventricular filling

• Accentuation of the pulmonic component of S2 with minimal respiratory splitting of S2

• Holodiastolic murmur with presystolic accentuation best heard at apex (The diastolic murmur may diminish secondary to low cardiac output from heart failure.)

• With severe pulmonary hypertension, possible occurrence of a high-frequency early diastolic murmur of pulmonic valve regurgitation in the pulmonic listening area

• RV S3 or S4

Echocardiography is the most important diagnostic tool to evaluate patients with mitral stenosis (MS). This noninvasive imaging modality provides excellent anatomic and hemodynamic assessment of MS.

Echocardiography provides the following:

• Direct anatomic data, such as visualization of valve leaflet morphology and motility as well as measurement of valve orifice dimensions

• Evaluation of left atrial size and detection of left atrial thrombi

• Indirect physiologic data (ie, estimation of pressure gradients across the mitral valve and right ventricular systolic pressure), which may be measured using Doppler echocardiography

Transesophageal echocardiography

Transesophageal echocardiography is used when transthoracic echocardiographic pictures are inadequate. It may also be used to guide intervention and assess results in the operating room and cardiac catheterization laboratory.

Dynamic 3-dimensional transthoracic or transesophageal echocardiography

These techniques can provide good insight into valvular motion and help preoperative planning in situations in which valve reconstruction is considered.[5] However, the accuracy of these techniques is currently limited by the quality of the original 2-dimensional echo cross-sectional images, which can be adversely affected by patient motion, breathing, and cardiac arrhythmia such as atrial fibrillation.

A 2-dimensional echocardiogram of a boy with congenital MS is depicted below.

A 2-dimensional echocardiogram of a patient requiring mitral valve replacement is depicted below.

Chest radiography

Chest radiographic findings may include may the following:

• Left atrial dilation

• Posteroanterior (PA) dilation secondary to high pulmonary vascular pressure and resistance

• Pulmonary venous congestion

• Right ventricular enlargement

Computed tomography

Computed tomography may be an adjunct to echocardiography for preprocedural or preoperative planning when mechanical mitral valve malfunction is suspected.

Magnetic resonance imaging

Magnetic resonance imaging is used infrequently. It may be an adjunct to echocardiography when masses or lesions are suspected.

Laboratory studies

Measure electrolyte balance and renal function if congestive heart failure is suspected.

Electrocardiography

Electrocardiography (ECG) findings may be normal in patients with mild MS. Hemodynamically significant stenosis results in ECG findings of left atrial or biatrial enlargement and right ventricular enlargement in proportion to severity of the obstruction.

Cardiac catheterization

Cardiac catheterization may be used to obtain direct intracardiac pressure measurements, the mitral valve gradient, pulmonary vascular resistance, and systemic cardiac output.

The mitral valve effective orifice can be calculated using the Gorlin formula.

The diagnosis and hemodynamic assessment of most patients with MS is performed noninvasively with echocardiography. However, cardiac catheterization is used only when echocardiography does not provide complete information or if the patient undergoes mitral balloon valvuloplasty.

Asymptomatic patients with mild mitral stenosis (MS) require no significant therapy. They should undergo yearly follow-up care with physical examination, chest radiography, and ECG with echocardiography as indicated by this assessment. These patients may remain stable for decades before MS progresses and the patient requires surgical intervention. Note the following:

• More significant stenosis producing mild symptoms can be managed with diuretics alone. Direct careful attention to proper diet and to early intervention for pulmonary disease.

• For the patient with congestive heart failure, loop diuretics plus potassium-sparing diuretics are essential. Digoxin may improve right ventricular function in the setting of pulmonary hypertension.

• Address cardiac rhythm abnormalities with appropriate medications.

• Patients with chronic uncontrolled atrial tachyarrhythmias should be on anticoagulant therapy.

Critically ill patients or patients unable to take oral medication may receive intravenous medications. Admission to the ICU and endotracheal intubation may be required because of ineffective breathing caused by pulmonary edema.

Closely monitor the patient's anticoagulation therapy to prevent thrombus formation and to decrease the risk of embolization in case of a mechanical mitral valve. Embolization is to the systemic circulation; these emboli originate in the left atrium and are able to reach the brain.

Consultations

Consultation with a cardiologist is indicated, and with a cardiothoracic surgeon if the cardiologist determines that MS is worse than mild.

Transfer

Transfer the patient to an intensive care unit when general status is unstable because of low cardiac output or pulmonary edema.

Diet and activity

Restrict salt and avoid excessive fluids. Proper nutrition is paramount to maintain adequate cardiopulmonary health. Caloric supplementation may be necessary in the symptomatic infant.

Patients should avoid strenuous exercise, because an increased heart rate decreases diastolic filling time. If atrial flutter and atrial fibrillation are present and atrial kick is lost, a further decrease in LV stroke volume occurs. This may result in syncope from decreased cerebral perfusion.

Surgery is considered when the peak instantaneous transmitral gradient is >10 mmHg by Doppler echocardiography. However, if MS is associated with other cardiac lesions such as atrial septal defect (which will decrease the transmitral gradient due to left to right shunting of blood), hemodynamic measurement of pulmonary artery pressures are required to aid in the decision making process.[6]

Worth mentioning is that unlike what occurs in acquired MS, commissural fusion of the mitral leaflets is not a predominant mechanism for stenosis in patients with congenital MS (see Background). Therefore, balloon dilation of congenital MS, although performed in some centers, is not always successful. Younger patients and those who develop significant mitral regurgitation after balloon-dilation have a worse outcome.[7] However, because the 5-year survival is still relatively poor in those with severe congenital MS, regardless of treatment modality, the optimal therapeutic strategy remains unclear. Surgical options depend on specific mitral valve pathology.[8]

Mitral valve repair

Commissurotomy consists of an incision of fused mitral valve commissures and shaving of thickened mitral valve leaflets. Open surgical commissurotomy is preferable.

Divide fused chordae tendineae and papillary muscles to relieve subvalvular stenosis.

Resect any supravalvular tissue contributing to the MS.

Mitral valve replacement with mechanical valve or bioprosthesis

Note the following:

• This is reserved for patients with severe MS in whom mitral valve repair is not possible. In older children for whom warfarin (Coumadin) therapy may be contraindicated, mitral valve replacement can be performed using a bioprosthesis, although the durability of tissue valves is less than mechanical protheses.

• The risk of warfarin therapy should be weighed against the disadvantage of progressive bioprosthetic valve deterioration resulting in the certain need for reoperation.

• Mitral valve replacement is best avoided in infants and small children because of frequent size mismatch between the smallest mechanical valves and the hypoplastic mitral valve annulus. In addition, somatic growth in children leads to the need for subsequent mitral prosthesis replacements.

• Warfarin therapy is also more difficult to administer and to monitor in children. A less-than-perfect mitral valve repair is frequently preferable to mitral valve replacement in this group of patients.

• Complications after mitral valve replacement include the risks of anticoagulation, valve thrombosis, valve dehiscence, infective endocarditis, valve malfunction, and embolic events.

• However, in complex anatomy, replacement is the only solution to achieve an acceptable result. The Ross II operation, which uses a pulmonary autograft, is a difficult technique that may be useful in the youngest patient group when prosthetic devices cannot be used. This technique is still under clinical evaluation.

Correction of associated lesions

Pediatric patients must sometimes undergo correction of associated LV obstructive lesions such as subaortic stenosis, aortic valve stenosis, coarctation of the aorta, and hypoplastic aortic arch.[9]

Antibiotics for endocarditis prophylaxis are required for patients with certain cardiac conditions, such as mitral stenosis, before performing procedures that may cause bacteremia. For more information, see Antibiotic Prophylactic Regimens for Endocarditis.

Note the following:

• Avoid excessive salt intake, which increases fluid retention and may worsen symptoms.

• Avoid excessive heat, excessive use of diuretics, and dehydration, which may decrease LV output by reducing preload.

• Patients taking anticoagulants should avoid contact sports because of risks of cerebral, splenic, renal, or other internal organ bleeding. Pregnant women should avoid warfarin because of its teratogenic effects and risk of miscarriage.

Long-term monitoring of patients with mitral stenosis may include the following:

• Regular visits to the pediatrician and/or generalist to monitor general health status, depending on the severity of the mitral stenosis (MS)

• Regular visits to the pediatric cardiologist to monitor hemodynamic status, antiarrhythmic drug levels, and anticoagulation

• Serial echocardiography to monitor anatomic and hemodynamic progression of the MS; the frequency varies according to the patient's general health status and according to the cardiologist's criteria.

• Stress Doppler hemodynamics using a supine bicycle or treadmill: Hemodynamics may be measured using transthoracic echocardiographic Doppler. This noninvasive test has replaced the traditional exercise stress test in the catheterization laboratory.

Valvular Heart Disease Clinical Practice Guidelines (ACC/AHA, 2021)

The American College of Cardiology (ACC) and American Heart Association (AHA) released their updated recommendations on managing valvular heart disease in December 2020.[10, 11] Key messages are outlined below.

Valvular heart disease (VHD) stages (stages A-D) in patients should be classified based on symptoms, valve anatomy, severity of valve dysfunction, and response of the ventricle and pulmonary circulation.

When evaluating patients with VHD, findings from the history and physical examination (PE) should be correlated with those from noninvasive testing (ie, electrocardiography [ECG], chest x-ray, transthoracic echocardiography [TTE]). If conflict exists between results on the PE and that of initial noninvasive studies, consider obtaining further noninvasive (computed tomography [CT], cardiac magnetic resonance imaging [CMRI], stress testing) or invasive (transesophageal echocardiography [TEE], cardiac catherization) studies to decide the optimal treatment strategy.

In the setting of VHD and atrial fibrillation (AF) (except for patients with rheumatic mitral stenosis [MS] or a mechanical prosthesis), the decision to use oral anticoagulation with either a vitamin K antagonist (VKA) or a non-VKA anticoagulant to prevent thromboembolic events should be a shared decision-making process based on the CHA2DS2-VASc score (congestive heart failure [CHF], hypertension, age ≥75 years, diabetes mellitus, previous stroke/transient ischemic attack/thromboembolic event, vascular disease, age 65-74 years, sex). Oral anticoagulation with a VKA should be given to those with rheumatic MS or a mechanical prosthesis and AF.

All those with severe VHD under consideration for valve intervention should be evaluated by a multidisciplinary team, either with a referral or in consultation with a primary or comprehensive valve center.

Bioprosthetic valve dysfunction may occur because of either degeneration of the valve leaflets or valve thrombosis. Catheter-based treatment for prosthetic valve dysfunction is reasonable in selected patients for bioprosthetic leaflet degeneration or paravalvular leak in the absence of active infection.

Go to 2021 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy: Developed by the Task Force on cardiac pacing and cardiac resynchronization therapy of the European Society of Cardiology (ESC) with the special contribution of the European Heart Rhythm Association (EHRA) for full details.

Management of Valvular Heart Disease (VHD) Clinical Practice Guidelines (ESC/EACTS, 2021)

Mitral Valve Disease

Percutaneous mitral commissurotomy (PMC) is recommended for symptomatic patients with moderate-to-severe mitral stenosis who have no unfavorable characteristics for PMC and for any symptomatic patients who have a contraindication or a high risk for surgery. Symptomatic patients unsuitable for PMC should undergo mitral valve surgery if doing so is not deemed futile.

Go to 2021 ESC/EACTS Guidelines for the management of valvular heart disease for full details.

For more information, please go to Mitral Stenosis and Mitral Regurgitation.

For more Clinical Practice Guidelines, please go to Guidelines.

Medical therapy is used to avoid or decrease pulmonary congestion as well as to treat atrial tachyarrhythmias. These require medical therapy to prevent thromboembolic complications.

Class Summary

By promoting renal excretion of water and electrolytes, loop diuretics decrease pulmonary congestion. Pulmonary congestion results from back-flow to the lungs caused by obstruction across a narrowed mitral valve orifice.

Furosemide (Lasix)

Furosemide acts by inhibiting absorption of the electrolytes sodium and chloride in the proximal and distal tubules and in the loop of Henle, thereby promoting excretion of salt (sodium chloride) and water. It acts as a diuretic and as an antihypertensive.

Class Summary

Potassium-sparing diuretics are used to prevent potassium depletion induced by the more potent loop-diuretics (such as furosemide).

Spironolactone (Aldactone)

Spironolactone retains potassium by competing with aldosterone for the receptor sites in the distal convoluted renal tubules. This increases sodium and water excretion while retaining potassium and hydrogen ions.

Class Summary

Anticoagulants are used in general for the prophylaxis and treatment of venous thrombosis, pulmonary embolism, and thromboembolic disorders. In the case of MS, they are used to prevent clot formation secondary to blood stasis in an enlarged, many times fibrillating, left atrium and in case of a prosthetic (mechanical) mitral valve.

Warfarin (Coumadin)

Warfarin inhibits vitamin K–dependent clotting factors II, VII, IX, and X and the anticoagulant proteins C and S. Its anticoagulation effect occurs 24 h after administration, but the peak effect may occur 72-96 h later. Antidotes are vitamin K and FFP.