Mitral Valve Stenosis: Etiology, Pathogenesis, Symptoms, Diagnosis, and Treatment

Mitral stenosis is a pathologic narrowing of the mitral valve orifice that impairs diastolic filling of the left ventricle and increases pressure in the left atrium and pulmonary circulation.

In countries with advanced healthcare systems, mitral stenosis is rare and is seen predominantly in patients with a history of rheumatic fever. In developing regions, however, it remains an important cause of valvular heart disease. Women are affected more often than men. Symptoms usually become apparent many years later, often over a period of 10–30 years.

Etiology

• Rheumatic heart disease is the leading cause of mitral stenosis, accounting for about 90% of cases. In countries with advanced healthcare systems, the incidence of rheumatic mitral stenosis has declined.

• Degenerative mitral stenosis is associated with calcification of the mitral annulus. It is the second most common cause of mitral stenosis. The condition is seen predominantly in older patients.

• Radiation-induced valvular heart disease develops 10–20 years after mediastinal irradiation and is caused by fibrosis and thickening of valvular structures.

• Congenital forms of mitral stenosis are rare and usually present in childhood.

• Infiltrative and systemic disorders, including Fabry disease, mucopolysaccharidoses, carcinoid heart disease, endomyocardial fibrosis, and systemic lupus erythematosus, are extremely rare causes.

True mitral stenosis should be distinguished from nonvalvular obstruction of mitral inflow, which may occur in left atrial myxoma, thrombosis, large infective vegetations, or degeneration of a mitral bioprosthesis.

Pathogenesis

Valvular and Anatomic Changes

• In rheumatic heart disease, chronic immune-mediated inflammation leads to leaflet fibrosis, commissural fusion, and thickening and shortening of the chordae. This produces central narrowing of the mitral orifice, with doming of the leaflets. Over time, turbulent flow promotes progressive calcification and valvular rigidity, thereby reinforcing the stenosis.

• In degenerative calcification of the mitral annulus, fibrocalcific change extends from the annulus to the base of the leaflets, restricting leaflet mobility without the typical commissural fusion.

Hemodynamic Changes

1. Narrowing of the mitral orifice increases the diastolic pressure gradient between the left atrium and the left ventricle.
2. Chronic pressure overload raises left atrial pressure. As the valve area decreases, left ventricular filling becomes progressively limited and cardiac output falls.
3. Prolonged pressure overload causes left atrial dilatation, hypertrophy, and fibrosis. This promotes atrial fibrillation and creates conditions favorable for left atrial thrombus formation.
4. Elevated left atrial pressure is transmitted to the pulmonary veins and capillaries, causing post-capillary pulmonary hypertension and pulmonary vascular remodeling.
5. As the disease progresses, right ventricular overload develops, followed by right-sided heart failure and functional tricuspid regurgitation.

Clinical manifestations

• A prolonged asymptomatic phase;

• Dyspnea on exertion and, later, at rest. As the disease progresses, orthopnea and paroxysmal nocturnal dyspnea may occur;

• Reduced exercise tolerance and fatigue, related to limited cardiac output and impaired diastolic filling of the left ventricle;
• Atrial fibrillation, which may be the first clinical sign of the disease. It often causes abrupt hemodynamic deterioration because of tachycardia and loss of the atrial contribution to ventricular filling;

• Hemoptysis, resulting from pulmonary hypertension and rupture of bronchial veins;
• Systemic embolic events, related to the high risk of thrombus formation in the left atrium;
• Signs of right-sided heart failure, including lower-extremity edema and ascites;
• Hoarseness (Ortner’s syndrome), caused by compression of the recurrent laryngeal nerve by an enlarged left atrium.

Diagnosis

There are no specific laboratory markers for mitral stenosis. BNP or NT-proBNP may be used to assess the severity of heart failure.

• Transthoracic echocardiography (TTE) is the key diagnostic method for mitral stenosis.
  • Morphologic assessment: leaflet thickening and partial fusion; shortening and fibrosis of the chordal apparatus; restricted leaflet mobility; doming of the anterior leaflet in diastole; left atrial size; presence of thrombus in the left atrium; and the condition of the right-sided chambers.
  • Classification by effective orifice area: ≤ 1.0 cm² indicates very severe stenosis with particularly high risk; ≤ 1.5 cm² indicates severe stenosis; > 1.5 cm² suggests a hemodynamically less significant lesion.
  • Mean transmitral gradient: severe stenosis is generally associated with a mean gradient greater than 10 mm Hg. p.
  • Doppler assessment: used to measure transmitral flow velocity and calculate peak and mean gradients. It also helps estimate systolic pulmonary artery pressure from the tricuspid regurgitation jet and identify associated mitral regurgitation.
• Stress echocardiography (exercise or dobutamine) is performed when there is a discrepancy between symptom severity and resting TTE findings. The study assesses the increase in transmitral gradient and pulmonary hypertension.
• Transesophageal echocardiography (TEE)
  • TEE provides detailed assessment of leaflet and commissural morphology.
  • It is performed before balloon mitral commissurotomy to exclude thrombus in the left atrium and left atrial appendage and to further assess the degree of mitral regurgitation.
  • Spontaneous echo contrast in the left atrium is a marker of marked blood stasis and high thromboembolic risk. It is often associated with a small mitral valve area and a high gradient.
• CT angiography is useful for assessing thoracic anatomy, the aorta, and the vessels of the lower extremities, and for choosing the optimal surgical access when mitral valve surgery is planned.
• Cardiac catheterization is rarely required and is reserved for cases in which noninvasive findings are inconclusive.

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Treatment

Medical therapy

Medical therapy does not eliminate the obstruction. It is used to control symptoms, stabilize hemodynamics, manage complications, and prepare the patient for intervention when needed.

• Diuretics
  • Loop diuretics such as furosemide reduce pulmonary congestion and relieve dyspnea.
  • They are effective in pulmonary hypertension and right ventricular failure.
  • Excessive diuresis may reduce cardiac output and worsen fatigue.

• Heart rate control
  • Beta-blockers are first-line agents. They prolong diastole and reduce the transmitral gradient.
  • Nondihydropyridine calcium channel blockers (verapamil, diltiazem) are alternatives when beta-blockers are contraindicated.
  • Ivabradine may be considered in patients with sinus rhythm who cannot tolerate beta-blockers. It lowers heart rate without a negative inotropic effect.

• Digoxin may be considered in patients with atrial fibrillation, uncontrolled ventricular rate, or concomitant systolic dysfunction.

• Atrial fibrillation
  • Loss of atrial contraction and tachycardia in mitral stenosis may rapidly lead to pulmonary edema.
  • Electrical cardioversion is required in hemodynamically unstable patients.

• Anticoagulation
  • Anticoagulation is indicated in patients with mitral stenosis and atrial fibrillation, as well as in those with thrombus in the left atrium and/or left atrial appendage or a history of embolism, regardless of rhythm.
  • Because the evidence base for direct oral anticoagulants in this setting remains limited, the treatment of choice remains a vitamin K antagonist (warfarin) with a target INR of 2.0–3.0.

Endovascular Treatment (Percutaneous Balloon Mitral Commissurotomy)

Percutaneous balloon mitral commissurotomy (PBMC) is the treatment of choice in patients with rheumatic mitral stenosis and favorable valve anatomy.

• Indications
  • Symptomatic severe mitral stenosis, most often of rheumatic origin;
  • Asymptomatic severe stenosis in the presence of pulmonary hypertension (> 50 mm Hg) or atrial fibrillation;
  • No indication for open surgery;
  • Suitable anatomy, including mobile leaflets, minimal calcification, limited subvalvular involvement, and an overall favorable morphologic profile.

• Contraindications
  • Thrombus in the left atrium or left atrial appendage;
  • Moderate or severe mitral regurgitation;
  • Marked calcification;
  • Previous unsuccessful PBMC.

• Technique
  • A balloon catheter is advanced through the interatrial septum into the left atrium and inflated across the mitral orifice, splitting the fused commissures.

Surgical Therapy

• Surgical commissurotomy and valve-preserving repair
  • Indicated in patients with anatomy unfavorable for PBMC, left atrial thrombus, or combined valvular disease;
  • The procedure includes commissurotomy, repair of the subvalvular apparatus, and annuloplasty when needed.

• Mitral valve replacement
  • Indicated in severe valvular deformity, marked calcification, mixed valvular disease, or recurrent stenosis after repeat interventions;
  • In addition to median sternotomy, mitral valve surgery may be performed via a right mini-thoracotomy with peripheral cardiopulmonary bypass in selected patients with suitable anatomy and adequate peripheral vascular access.

• Mechanical prosthetic valves are recommended for younger and middle-aged patients (up to 60 years of age) with expected long-term survival. They require lifelong vitamin K antagonist therapy and are less desirable in women planning pregnancy.

• Bioprosthetic valves are recommended in older patients (65 years of age and older) and in women of reproductive age. Their durability is limited by structural degeneration and the potential need for repeat intervention.