Mitral stenosis

Article written and reviewed by Dr Luca Moretti

Mitral stenosis is a reduction in the diastolic opening area of the valve to the point that it obstructs blood flow from the left atrium to the left ventricle. The narrowing creates a transmitral gradient and increases atrial pressure, which is transmitted to the pulmonary veins and capillaries; over time, congestion, atrial fibrillation, pulmonary hypertension and right-sided heart dysfunction may develop. The left ventricle, by contrast, may remain small and maintain an apparently preserved ejection fraction.

Mitral stenosis is not a single disease, and the etiologic distinction also changes treatment. In the rheumatic form, a cicatricial commissural disease predominates, often associated with chordal abnormalities, whereas in the degenerative form of older adults the narrowing results from extension of annular calcification toward the leaflet bases without the typical commissural fusion. Epidemiology, morphology, measurement methods and procedural options are therefore different, and applying the criteria of the rheumatic form to degenerative calcification leads to errors.

The 2025 ESC/EACTS guidelines define rheumatic stenosis as clinically severe when the mitral valve area is no greater than 1.5 cm². This threshold identifies the group in which narrowing may limit flow and in which intervention is considered, but it does not replace assessment of symptoms, gradient, rhythm, cardiac output, pulmonary pressure and anatomy. A reduced area may be tolerated at rest and become critical under stress.

Worldwide, rheumatic heart disease continues to represent the predominant cause and mainly affects children, adolescents and young adults in settings of poverty and limited access to prevention. Its prevalence has declined in high-income countries, while aging, kidney failure and calcific burden have made degenerative stenosis more apparent. Migration and late diagnosis cause both forms to coexist in the same clinical practice.

Etiology and pathophysiology

Rheumatic heart disease is a late consequence of acute rheumatic fever, an aberrant immune response following group A streptococcal pharyngitis. Molecular mimicry triggers cardiac inflammation; recurrent episodes worsen the damage. Subsequent scarring fuses the commissures, thickens and calcifies the leaflets, shortens the chordae and narrows the orifice into a funnel shape.

In the early stages of rheumatic disease, the leaflets may retain reasonable mobility while fusion primarily involves the commissures. As the disease progresses, calcification and fibrosis increase, the subvalvular apparatus retracts and the chordae may fuse; the anterior leaflet thus develops the typical doming motion because the central portion remains mobile while the margins are tethered. Retraction and failed coaptation explain why a regurgitant component may coexist with stenosis.

The interval between rheumatic fever and symptoms may last decades in settings with a low recurrence rate, but it is shorter when repeated episodes accelerate scarring. Progression is not uniform: pregnancy, infections, anemia, hyperthyroidism or atrial fibrillation do not suddenly narrow the orifice, but increase flow or heart rate and unmask the limitation.

Degenerative stenosis arises from mitral annular calcification, a fibrocalcific process that predominantly involves the posterior annulus and may extend anteriorly and to the leaflet bases. The commissures often remain free; the lumen is reduced by a calcific “tunnel” rather than a commissural diaphragm. Age, chronic kidney disease, calcium-phosphate abnormalities, hypertension, diabetes and aortic calcification are frequent associations.

Other causes are rare. Congenital stenosis includes parachute mitral valve, supravalvular ring, double orifice and papillary muscle abnormalities; it often belongs to the Shone complex. Lupus, rheumatoid arthritis, mucopolysaccharidoses, exceptional left-sided carcinoid syndrome, ergot derivatives and serotonergic drugs may thicken or retract the leaflets. Mediastinal radiotherapy produces fibrosis and calcium, often with multivalvular involvement and involvement of the mitral-aortic continuity.

Iatrogenic stenosis may follow an undersized annuloplasty, edge-to-edge repair with excessive reduction in area, or prosthetic implantation with mismatch. Atrial tumors, large vegetations or thrombi may functionally obstruct the orifice but do not constitute true valvular stenosis. Cor triatriatum creates a gradient above the valve and should be distinguished by imaging.

The relationship between pressure and flow depends both on orifice area and on the time available for filling. For the same area, the gradient increases approximately with the square of flow, and tachycardia increases it further by shortening diastole and concentrating the same volume into a shorter interval. For this reason, exercise, pregnancy, fever and anemia may unmask or accentuate symptoms, whereas low cardiac output may attenuate the gradient even in the presence of severe anatomic stenosis.

As the area decreases, the atrium must generate a higher pressure to maintain filling. Increased pressure causes atrial dilatation, stretch and fibrosis, creating a substrate for atrial fibrillation. Loss of atrial contraction and a rapid rate reduce filling and cardiac output and abruptly increase pulmonary pressure.

Pulmonary venous pressure causes interstitial and alveolar transudation. Initially, arteriolar vasoconstriction protects the capillaries; if persistent, it promotes medial hypertrophy and vascular remodeling with a precapillary component. Pulmonary hypertension may then become disproportionate and regress only partially after correction.

The right ventricle faces increasing afterload, hypertrophies and eventually dilates. Annular dilatation and tethering cause tricuspid regurgitation, which amplifies systemic congestion, liver disease and edema. Left-sided cardiac output decreases because of limited filling; exercise cannot be sustained even if left ventricular systolic function appears normal.

A reduction in left ventricular ejection fraction may result from underfilling, relative afterload, rheumatic myocardial fibrosis, dyssynchrony or associated lesions. It should not automatically be attributed to stenosis. Aortic valve disease, mitral regurgitation, coronary artery disease or cardiomyopathy may alter gradients and symptoms and must be integrated into the assessment.

Clinical presentation and complications

Exertional dyspnea is the most common manifestation. The patient first notices reduced walking capacity, then breathlessness during ordinary activities. As atrial pressure rises, orthopnea, paroxysmal nocturnal dyspnea and pulmonary edema develop. Onset may coincide with pregnancy or rapid atrial fibrillation.

Irregular palpitations suggest paroxysmal or persistent atrial fibrillation. A high rate is poorly tolerated because it shortens diastole; even an apparently brief arrhythmia may cause congestion. Fibrillation promotes stasis in the atrial appendage, spontaneous echo contrast and thrombus, with a risk of cerebral or systemic embolism.

Hemoptysis may result from rupture of dilated bronchial veins, alveolar edema, pulmonary infarction or infection. Massive hemoptysis is now less frequent in healthcare systems with early diagnosis. Cough, hoarseness from recurrent laryngeal nerve compression by an enlarged atrium or pulmonary artery, and dysphagia due to a large atrium are historical manifestations but remain possible.

Chest pain may accompany pulmonary hypertension and right ventricular ischemia or result from concomitant coronary artery disease. Syncope suggests fixed cardiac output, severe pulmonary hypertension or arrhythmia and is an advanced sign. Fatigue and weakness reflect reduced cardiac output, often accentuated by deconditioning and anemia.

When right-sided heart failure predominates, jugular venous distention, edema, ascites, early satiety and hepatic discomfort develop. At this stage, pulmonary congestion may appear less evident because the right ventricle can no longer generate sufficient flow; this does not represent improvement. Cachexia and renal and hepatic dysfunction identify late disease.

On examination, a loud first heart sound reflects still-mobile leaflets that close from a widely open position; it becomes softer with calcification and immobility. The opening snap follows the aortic component of the second heart sound and tends to move closer to it as atrial pressure increases, but it disappears with rigid calcification. These findings do not quantify severity by themselves.

The low-frequency diastolic rumble is maximal at the apex with the bell, in the left lateral decubitus position. Presystolic accentuation requires sinus rhythm and disappears in atrial fibrillation. The duration of the rumble correlates with severity better than its intensity; low cardiac output, obesity or calcific stenosis may make it difficult to hear.

An accentuated pulmonary component of the second heart sound, a right parasternal impulse and a Graham Steell murmur indicate pulmonary hypertension. A parasternal holosystolic murmur that increases with inspiration suggests tricuspid regurgitation. Subtle physical findings do not exclude important obstruction in an older adult with low flow.

Embolism may be the first manifestation. Risk increases with atrial fibrillation, age, a large atrium, spontaneous echo contrast, thrombus and previous embolism, but it is not absent in sinus rhythm. Thrombus may be located in the appendage or extend into the cavity and may affect eligibility for commissurotomy.

Pregnancy increases plasma volume, heart rate and cardiac output from the second trimester, with a further rise during labor and postpartum because of autotransfusion. Previously minimally symptomatic stenosis may cause pulmonary edema and impair fetal growth. Preconception assessment is safer than managing a first episode during advanced pregnancy.

Endocarditis is less common in isolated stenosis than in regurgitant lesions, but it may occur and add regurgitation or embolism. Respiratory infection, anemia, thyroid dysfunction, nonadherence, excessive salt intake or tachyarrhythmia are frequent precipitants of decompensation and should be sought rather than attributing every deterioration to anatomic progression.

Diagnosis and definition of severity

The ECG may show P mitrale, right axis deviation, right ventricular hypertrophy and atrial fibrillation. Chest radiography may show atrial enlargement, vascular redistribution, edema, pulmonary artery prominence and, later, right-sided dilatation; the left ventricle is not typically enlarged in isolated stenosis. None of these tests measures the orifice.

Transthoracic echocardiography is the central examination. In the rheumatic form, it shows commissural fusion, thickening of the leaflet tips, doming of the anterior leaflet, reduced posterior leaflet excursion and subvalvular disease. In the degenerative form, it documents massive annular calcium and basal narrowing without typical fusion. The atrium, pulmonary pressure, right ventricle and other valves complete the staging.

Direct planimetry of the orifice in diastole is the reference method in rheumatic stenosis. The imaging plane must be perpendicular to the funnel and located at the leaflet tips, where the opening is smallest. An oblique or excessively atrial cut overestimates the area; gain and calcium alter the border. 3D imaging facilitates alignment but does not eliminate artifacts.

The mean Doppler gradient is obtained by tracing the diastolic envelope from the apical view. It should be reported together with heart rate, rhythm and flow conditions. A high gradient supports hemodynamic significance, but there is no universal correspondence with area: tachycardia, mitral regurgitation, anemia or pregnancy increase it, whereas low cardiac output reduces it.

Pressure half-time estimates the area as 220 divided by the pressure half-time. The method assumes a relatively stable relationship between gradient decay and area, but it is influenced by atrial and ventricular compliance, aortic regurgitation, end-diastolic pressure and recent interventions. It is unreliable immediately after commissurotomy and often in degenerative stenosis.

The continuity equation and PISA method can provide alternative estimates, but they become problematic with concomitant regurgitant lesions, arrhythmia and complex geometry. In atrial fibrillation, beats with comparable RR intervals and heart rates are averaged. The best diagnosis derives from concordance among morphology, planimetry, gradient and hemodynamic consequences.

In rheumatic stenosis, an area no greater than 1.5 cm² identifies clinically severe disease on which interventional recommendations are based. Values around or below 1.0 cm² describe very severe narrowing, but a purely numerical classification should not ignore flow and symptoms. A mean gradient above 10 mmHg at a normal heart rate is often associated with severity, without constituting an absolute independent threshold.

Pulmonary artery systolic pressure is estimated from the tricuspid jet and right atrial pressure. A value above 50 mmHg at rest is an indicator of high risk of decompensation in recommendations for asymptomatic patients with favorable rheumatic stenosis. An incomplete Doppler signal or severe right-sided dysfunction may underestimate it.

Transesophageal echocardiography is required before commissurotomy to exclude atrial thrombus. It defines the commissures, regurgitation and subvalvular apparatus. A mass in the appendage changes the timing and requires anticoagulation and reassessment.

The Wilkins score assigns a value from 1 to 4 to mobility, thickening, calcification and the subvalvular apparatus; a score no greater than 8 is generally favorable. It does not, however, describe the commissural distribution of calcium, a true determinant of tearing and regurgitation, nor does it adequately capture focal deformities. Modern decision-making adds 3D echocardiography and morphologic judgment.

Features unfavorable for commissurotomy include advanced age, a previous procedure, NYHA class IV, atrial fibrillation, severe pulmonary hypertension, a very small area, concomitant regurgitation, a high score and commissural calcification. Not all are absolute contraindications: they define probability of success and durability and must be weighed against surgical risk.

Exercise echocardiography is particularly useful when symptoms appear disproportionate to resting findings or when a patient reports being asymptomatic despite significant stenosis. The test documents functional capacity, transmitral gradient and pulmonary pressure during a physiologic increase in flow, while cardiopulmonary exercise testing helps distinguish a circulatory limitation from a pulmonary limitation or simple deconditioning. Dobutamine echocardiography, by contrast, is not the usual test in mitral stenosis.

In degenerative stenosis, planimetry is difficult because the orifice is nonplanar and shadowed by calcium; pressure half-time is particularly unreliable. The mean gradient corrected for heart rate and cardiac output, area by continuity when applicable, 3D morphology, CT and consequences must converge. A high gradient may reflect high flow and reduced atrioventricular compliance.

CT is particularly useful when stenosis is associated with calcification because it defines its extent and distribution, annular dimensions, the mitral-aortic angle and the predicted neo-left ventricular outflow tract, and it is essential when planning transcatheter replacement in MAC. Magnetic resonance imaging can quantify chamber size and associated disease but is not the primary method for measuring valve area. Catheterization, with simultaneous atrial and ventricular measurements, is reserved for the rare discrepancies unresolved by imaging, while recognizing that wedge pressure does not always correspond perfectly to atrial pressure.

Treatment

Primary prevention of rheumatic fever requires appropriate diagnosis and treatment of streptococcal pharyngitis in the settings in which this is indicated; secondary prevention with penicillin reduces recurrences in patients with documented rheumatic fever. Duration and regimen depend on age, carditis, residual disease and exposure. These measures do not reopen an already stenotic valve, but they limit further damage.

Diuretics reduce venous pressure and congestion. Beta-blockers or drugs that slow atrioventricular conduction prolong diastole and improve symptoms in tachycardia or atrial fibrillation; they should be adjusted to blood pressure and function. Digoxin is useful mainly for rate control in atrial fibrillation with heart failure, not in sinus rhythm as therapy for the obstruction.

Anticoagulation with a vitamin K antagonist is indicated in rheumatic stenosis with atrial fibrillation, atrial thrombus or previous embolism. It may be considered in sinus rhythm with dense spontaneous echo contrast or a markedly enlarged atrium according to risk. The INVICTUS trial showed worse outcomes with rivaroxaban than with vitamin K antagonist therapy in patients with rheumatic heart disease and atrial fibrillation.

Cardioversion may be considered after correction of the obstruction or in selected scenarios, with anticoagulation and thrombus assessment. In a markedly dilated atrium and untreated stenosis, maintenance of sinus rhythm is unlikely. Heart rate should be controlled before attributing dyspnea to new anatomic progression.

Percutaneous mitral commissurotomy with a balloon works by separating fused commissures. In the 2025 ESC/EACTS guidelines, it is recommended in symptomatic patients with clinically severe rheumatic stenosis and no unfavorable characteristics, and is recommended in symptomatic patients with a contraindication to or high risk from surgery when technically feasible. It does not implant a prosthesis and preserves the apparatus.

The procedure may also be considered as initial treatment when anatomy is suboptimal if the symptomatic patient has no unfavorable clinical characteristics. The optimal result combines an increase in area, reduction in gradient, commissural opening and absence of significant regurgitation. Simply pressing a balloon against a calcific valve without fusion does not reproduce this mechanism.

The main contraindications to percutaneous commissurotomy are:

• Left atrial thrombus, especially in the appendage or adherent to the puncture septum.
• Mitral regurgitation greater than mild.
• Severe calcification or bicommissural calcification and absence of commissural fusion.
• Associated disease requiring surgery, such as severe aortic valve disease or coronary artery disease requiring bypass surgery.

Commissurotomy may be complicated by severe regurgitation from tearing, tamponade due to transseptal puncture, embolism, perforation, a persistent interatrial defect and the need for emergency surgery. Moderate or severe postprocedural regurgitation worsens prognosis. Operator experience and commissural assessment are decisive.

Surgery is recommended in symptomatic patients with clinically severe stenosis who are not suitable for the percutaneous procedure. Surgical commissurotomy is possible when tissue is repairable, but replacement is frequent in advanced calcific or subvalvular forms. Chordal preservation, tricuspid treatment and possible atrial fibrillation ablation are planned together.

In an asymptomatic patient with favorable anatomy, commissurotomy may be considered in the presence of high thromboembolic risk - previous embolism, dense spontaneous echo contrast, new or paroxysmal atrial fibrillation - or a high risk of decompensation, such as systolic pulmonary pressure above 50 mmHg at rest, major noncardiac surgery or desire for pregnancy. The objective is to prevent a predictable event, not to treat an isolated number.

During pregnancy, cautious use of diuretics and rate control are first-line measures; anticoagulation and medications require specialist maternal-fetal management. If severe symptoms or pulmonary pressure persist despite therapy and the anatomy is favorable, commissurotomy may be performed at an expert center while minimizing radiation, preferably after the 20th week of pregnancy. Preconception correction remains preferable.

Degenerative stenosis due to MAC does not respond to balloon commissurotomy because there are no fused commissures to open. Surgery carries a risk of atrioventricular disruption, circumflex injury, leak and anchoring difficulties; strategies involving calcium resection or respect depend on experience. The benefit must outweigh an often high risk and symptoms with multiple causes.

Valve-in-MAC transcatheter replacement uses dedicated prostheses or, in selected settings, devices originally designed for the aortic position. Embolization, leak, mortality and, above all, left ventricular outflow tract obstruction remain major problems. CT with neo-LVOT simulation, possible pre-emptive laceration of the anterior leaflet or septal modification belong to highly specialized programs.

Follow-up of asymptomatic severe stenosis is clinical and echocardiographic at least annually, with closer follow-up if there are symptoms, pulmonary pressure changes or other changes. After commissurotomy, residual area, gradient and regurgitation are established and restenosis is monitored. The benefit lasts longer with younger age, favorable anatomy, a good initial result and absence of rheumatic recurrence.

Prognosis and management of complications

The natural history is variable but changes markedly after the onset of symptoms, atrial fibrillation and pulmonary hypertension. A long period of compensation may be followed by rapid deterioration when hemodynamic reserve is exhausted. Correction before severe pulmonary vascular disease and right-sided dysfunction offers the best likelihood of recovery.

Atrial fibrillation worsens functional capacity and increases embolic risk. Adequate rate control may produce striking improvement, but it does not remove the obstruction. Subtherapeutic anticoagulation, interruptions or interactions expose the patient to stroke; structured INR management is part of valve therapy.

An atrial thrombus requires anticoagulation and follow-up imaging. Resolution may permit a percutaneous procedure if anatomy and regurgitation remain favorable; a persistent organized thrombus may require surgery. The appendage remains an embolic source even after correction if fibrillation and atrial myopathy persist.

Passive pulmonary hypertension tends to decrease when atrial pressure normalizes; the remodeled vascular component may persist. Late elevated pressures, tricuspid regurgitation and right-sided dysfunction limit recovery and increase procedural risk. Drugs specific for pulmonary arterial hypertension are not automatically indicated in postcapillary hypertension due to stenosis.

Acute pulmonary edema requires oxygenation, ventilation if needed, diuresis, rate control and treatment of the precipitating factor. Vasodilators are limited by blood pressure and the fixed mechanism. In refractory cases, urgent or expedited correction of the obstruction should be assessed, after excluding thrombus and significant regurgitation if balloon treatment is being considered.

Restenosis after commissurotomy results from refusion, calcific progression and subvalvular disease. A repeat procedure is possible if the commissures are fused again and there is no unfavorable regurgitation or calcium; otherwise, surgery is considered. The decision is not based on the time interval alone.

After replacement, thrombosis, degeneration, endocarditis, leak and mismatch may recreate a gradient. A high gradient does not prove prosthetic obstruction: heart rate, flow, size and baseline values are essential. Echocardiography, transesophageal echocardiography, dynamic CT and fluoroscopy distinguish the mechanisms.

In the degenerative form, mortality and symptoms are influenced by age, kidney disease, aortic disease, coronary artery disease, preserved ejection fraction with ventricular stiffness and frailty. Even a technically successful procedure may fail to normalize atrial pressure if the ventricle is noncompliant. Selection must therefore demonstrate that the obstruction truly contributes to the clinical picture.

A favorable prognosis does not simply coincide with a larger area. A complete result includes low mortality, absence of significant regurgitation, functional improvement, reduction in pulmonary pressure, prevention of embolism and durability. Assessment over time makes it possible to distinguish procedural success from clinical recovery.

Mitral stenosis remains a treatable disease when recognized at the appropriate time. In the rheumatic form, a well-selected percutaneous procedure can provide years of benefit with low invasiveness; in the calcific form, options are more complex and judgment must be rigorously individualized. In both, the most harmful error is to ignore rhythm, flow and cardiopulmonary consequences while focusing on a single value.