The mitral valve is made up of the annulus, the anterior and posterior leaflets, and the chordae, which attach the leaflets to their respective papillary muscles. A normally functioning valve allows blood to flow unimpeded from the left atrium to the left ventricle during diastole and prevents regurgitation during systole. Normal mitral valve function is dependent not only on the integrity of the underlying valvular structure, but on that of the adjacent myocardium as well.

This chapter reviews three types of mitral valve disease: mitral stenosis, mitral regurgitation (including primary nonischemic, ischemic, and functional mitral regurgitation), and mitral valve prolapse. Practice guidelines published jointly by the American College of Cardiology (ACC) and the American Heart Association (AHA) for the management of patients with valvular heart disease are referenced within this chapter.¹

Mitral stenosis is usually caused by rheumatic involvement of the mitral apparatus. Single or recurrent bouts of rheumatic carditis may cause progressive thickening and calcification of the leaflets and chordae. Fusion of the mitral commissures decreases the size of the mitral opening. Although the incidence of rheumatic fever and secondary rheumatic valvular disease has steeply declined during the past 4 decades in the United States, rheumatic heart disease is still a major cause of cardiovascular disease worldwide. Patients often do not recall a history of rheumatic fever, and clinically apparent mitral stenosis frequently does not develop for more than 20 years after such an episode. Less common etiologies of mitral stenosis include infective endocarditis, severe calcification of the mitral annulus, tumors, systemic lupus erythematosus, and carcinoid.

The clinical manifestations of mitral stenosis are caused by the mechanical obstruction that impairs ventricular filling through the narrowed mitral orifice. This obstruction results in the development of a pressure gradient across the valve in diastole and causes an elevation in left atrial and pulmonary venous pressure. The gradient (and left atrial pressure) can be elevated by an increase in cardiac output, a decrease in diastolic filling time (which occurs with faster heart rates), or the development of atrial fibrillation.

The characteristic findings of mitral stenosis on auscultation are an accentuated first heart sound, an opening snap, and a mid-diastolic rumble, which is best heard at the cardiac apex. The first heart sound may be diminished in intensity if the valve is heavily calcified and with limited mobility. In sinus rhythm, there is a further accentuation of the murmur during atrial systole. The timing of the opening snap during diastole may provide evidence of the severity of the stenosis. With increasingly severe stenosis, the opening snap occurs earlier during diastole (closer to S₂) as a result of the higher left atrial pressure and the subsequent more-rapid equalization of LV and atrial pressure. There is accentuation of P₂ when pulmonary hypertension is present.

On chest radiography, the characteristic findings of mitral stenosis are pulmonary congestion, enlargement of the main pulmonary arteries, and enlargement of the left atrium without cardiomegaly (Figure 1).

An electrocardiogram (ECG) might reveal evidence of left atrial enlargement or atrial fibrillation; in advanced disease, the ECG might reflect underlying pulmonary hypertension with right ventricular hypertrophy (Figure 2).

Echocardiography is the most useful noninvasive test for the diagnosis of mitral stenosis. Typical findings on two-dimensional echocardiography include valve thickening and decreased leaflet motion and opening. In addition to measurement of the valve opening, echocardiography demonstrates other prognostically important morphologic features of the valve apparatus, such as calcification and involvement of chordal structures. Doppler investigation of the flow across the mitral valve is used to estimate the transmitral pressure gradient. In patients with mitral stenosis, the mean pressure gradient is at least 5 mm Hg; in severe stenosis, it is greater than 10 mm Hg.

Mitral valve area can also be estimated by measuring the pressure half-time, which is the amount of time it takes for the transmitral pressure to fall to one-half of its initial value. Pulmonary artery pressures are estimated by measuring the velocity of the tricuspid regurgitant jet. Cardiac catheterization is helpful in characterizing the severity of mitral stenosis when the degree of disease as determined by echocardiography does not correlate with the clinical findings or the severity of symptoms.

Medical Therapy
Given the mechanical nature of mitral inflow obstruction in mitral stenosis, medical therapy has no role in altering the natural history or delaying the need for surgery. Medical treatment is directed toward alleviating pulmonary congestion with diuretics, treating atrial fibrillation, and anticoagulating patients who are at increased risk of arterial embolic events.

Atrial fibrillation is especially troublesome in mitral stenosis. It decreases cardiac output and worsens pulmonary congestion, as atrial contribution to ventricular filling is lost, and filling itself is impaired with a rapid heart rate. Beta blockers, calcium channel blockers, or digoxin may be used to control ventricular rate. An attempt to restore sinus rhythm with either direct-current electrical cardioversion or antiarrhythmic drugs should be considered. Given the high rate of peripheral and cerebrovascular embolization observed in patients with mitral stenosis and atrial fibrillation, all patients with a history of atrial fibrillation or arterial embolism should be anticoagulated with warfarin. There are no prospective clinical trials to support the routine use of anticoagulation in patients without such a history. Although echocardiographic predictors of left atrial thrombus formation-including left atrial spontaneous echo contrast ("smoke") and marked left atrial enlargement-have been identified, there is controversy over whether or not these patients should receive long-term anticoagulation.

Because the most common cause of mitral stenosis is rheumatic carditis, secondary prophylaxis for rheumatic fever is recommended for all patients who do not have another obvious etiology for their valvular disease. Benzathine penicillin G is the agent of choice; intramuscular administration is preferred over oral dosing because its compliance rates are higher.² Patients with a history of rheumatic heart disease should be maintained on antibiotic prophylaxis for at least 5 years after their most recent attack of rheumatic fever. Patients who are at increased risk for exposure to group A streptococci, (eg, childcare workers) are candidates for longer periods of antibiotic prophylaxis. Whether or not long-term prophylaxis is required for all patients is controversial.

Patients with mitral stenosis should receive antibiotic prophylaxis for endocarditis before they undergo dental or other invasive procedure as outlined by published guidelines.³

Surgery
Three surgical options are available for patients with mitral stenosis: percutaneous mitral balloon valvotomy, open mitral commissurotomy, and mitral valve replacement.

Percutaneous mitral balloon valvotomy is a catheter-based technique in which a balloon is inflated across a stenotic valve to increase the valve area. This procedure should be considered for (1) symptomatic patients with moderate or severe stenosis (valve area: < 1.5 cm²) who have a favorable valve structure and (2) asymptomatic patients with pulmonary hypertension and valve area < 1.5 cm² provided that their valve structure is suitable. Echocardiography is used to determine whether the valve is heavily calcified or has significant involvement of the subvalvular apparatus, factors, which would be unfavorable to percutaneous valvotomy. Valvotomy should not be performed in patients who have left atrial thrombus or in patients with more than 2+ (moderate) mitral regurgitation because the degree of mitral regurgitation usually increases following this procedure. Following valvotomy, the size of the mitral valve area typically is doubled, and hemodynamic as well as clinical improvements are seen immediately (Figure 3).⁴ Studies have shown that in selected patients—particularly young patients with pliable valves—valvotomy yields excellent results at 3 to 7 years, and that its success rates are comparable to those of open mitral commissurotomy.^4,5

Open mitral commissurotomy involves the use of cardiopulmonary bypass and the surgical repair of a diseased mitral valve by direct visualization. In the presence of a left atrial thrombus or significant mitral regurgitation, open mitral commissurotomy can be considered if the valve anatomy is suitable. Commissurotomy also might be indicated for patients who have other concomitant valvular disease or coronary artery disease that requires surgery.

Mitral valve replacement is required for patients with calcified valves that cannot be treated by valvotomy or commissurotomy, or those with significant mitral regurgitation. Both mechanical and biologic prostheses are used for mitral valve replacement; the choice of valve often depends on factors such as age, need for concomitant anticoagulation, and LV size.

Mitral regurgitation is leakage of blood from the left ventricle into the left atrium during systole. Mitral regurgitation imposes an extra load on the heart because the left ventricle pumps more blood per beat in order to maintain its normal output. It occurs from a variety of mechanisms that are related to structural or functional abnormalities of the mitral apparatus, the adjacent myocardium, or both.

Mitral valve regurgitation occurs in about 2% of the population with a similar prevalence in males and females.

The most common etiologies of mitral regurgitation in the United States are myxomatous degeneration, chordal rupture, rheumatic heart disease, infective endocarditis, coronary artery disease, and cardiomyopathy. Myxomatous disease is the most common cause of nonischemic mitral regurgitation in the US (Figure 4).

Patients with chronic severe mitral regurgitation may remain asymptomatic for years because the regurgitant volume load is well tolerated as a result of compensatory ventricular dilatation. When symptoms do develop, the most common are dyspnea on exertion, fatigue, orthopnea, paroxysmal nocturnal dyspnea, and palpitations due to atrial fibrillation. Acute severe mitral regurgitation, as occurs with chordal rupture, is nearly always symptomatic because the sudden regurgitant volume load in the nondilated left ventricle leads to pulmonary venous hypertension and congestion. Acute papillary muscle rupture may occur as a complication of acute myocardial infarction, and is often characterized by acute pulmonary edema and cardiogenic shock.

The characteristic finding in a patient with mitral regurgitation is a blowing holosystolic murmur that is heard best at the cardiac apex. In cases of anterior leaflet prolapse, the murmur radiates posteriorly to the axilla and back; in posterior leaflet prolapse, the murmur radiates to the base of the heart. When ventricular enlargement is present, the apical impulse may be diffuse and laterally displaced, and a third heart sound may be heard.

The management of primary nonischemic mitral regurgitation, in which the valve structure is abnormal such as myxomatous valve disease, differs from that of ischemic and functional mitral regurgitation.

Primary Nonischemic Mitral Regurgitation
Data are conflicting with regard to the hemodynamic benefits of the long-term administration of angiotensin-converting enzyme (ACE) inhibitors for patients with chronic primary mitral regurgitation. In patients with primary abnormalities of valve structure, no studies have shown that the use of ACE inhibitors alters the natural course of the disease, alleviates symptoms, or delays the need for surgery. Therefore, there is no evidence to support the routine use of vasodilators in asymptomatic patients with chronic severe regurgitation. Vasodilators might have a role in patients with symptomatic congestive heart failure and reduced LV systolic function who are not amenable to surgical therapy⁶ and in patients who have coexisting systemic hypertension. In addition, because they reduce LV size, vasodilators might be useful when mitral regurgitation is secondary to LV dysfunction. Patients with acute severe mitral regurgitation might respond to the administration of intravenous vasodilators (eg, sodium nitroprusside). They might also benefit from intra-aortic balloon counterpulsation as a means of medical stabilization prior to mitral valve repair or replacement, which is often required on an urgent basis.

Antibiotic prophylaxis for endocarditis is recommended for patients who undergo dental or other invasive procedures as outlined by published guidelines.²

Patients with moderate or severe mitral regurgitation should be evaluated clinically every 6 to 12 months; this evaluation should include an echocardiogram to determine the severity of mitral regurgitation and left ventricular size and function.

Surgery is indicated for symptomatic patients with severe mitral regurgitation. The two available options are mitral valve repair (Figure 5) and mitral valve replacement.

Repair offers several advantages over replacement, including a lower risk of subsequent infective endocarditis, no need for long-term anticoagulation, and better LV performance. On the other hand, repair is technically more difficult than replacement, and operative success is dependent on the specific valve lesion and the skill of the cardiac surgeon.

Surgery should also be considered for asymptomatic patients with severe mitral regurgitation and impaired LV function or LV chamber enlargement. Moreover, mitral valve repair may be considered in certain patients with asymptomatic severe mitral regurgitation and normal LV size and function in centers where this procedure can be performed with a high degree of success and low operative risk.

Ischemic Mitral Regurgitation
Chronic mitral regurgitation frequently is the result of scarring of the papillary muscles due to ischemia or infarction, but more often is the result of infarction of the left ventricular wall where the papillary muscle is attached. Chronic ischemic mitral regurgitation usually is treated medically, but surgery is indicated when it is severe or when it is necessary to treat underlying coronary artery disease surgically; in these situations, mitral valve repair is preferred over replacement. Medical treatment is based on achieving afterload reduction with an ACE inhibitor or other vasodilator in order to reduce LV size and thereby produce a concomitant reduction in both mitral annular size and the degree of mitral regurgitation. In addition, anti-ischemic agents such as nitrates and beta blockers are used in situations when mitral regurgitation is worsened by acute ischemia.

Functional Mitral Regurgitation
Mitral regurgitation may occur with ischemic or nonischemic dilated cardiomyopathy due to changes in ventricular shape and failure of mitral leaflet coaptation. Patients with cardiomyopathy and mitral regurgitation have a worse prognosis than those without mitral regurgitation.⁷ Medical treatment should be directed to the underlying cardiomyopathy with the use of an ACE inhibitor, a beta blocker, digoxin, and a diuretic. ACE inhibitors and beta blockers have also been shown to reduce the degree of mitral regurgitation. Surgical repair of severe mitral regurgitation may be considered for patients with dilated cardiomyopathy who have symptomatic heart failure despite medical therapy, although a survival benefit to this approach has not been demonstrated. Biventricular pacing has also been shown to decrease the degree of MR in dilated cardiomyopathy.

Rare but serious complications have been associated with MVP, including infective endocarditis, cerebrovascular events, progressive severe mitral regurgitation, and sudden death. The risk of developing fatal and nonfatal complications has been found to be highest in men, in those older than 45 years of age, in probands of relatives with familial MVP, and in patients who have a holosystolic murmur or left-sided chamber enlargement.¹¹ Although most patients with MVP do not develop severe mitral regurgitation, MVP is a common underlying cause of progressive, mitral regurgitation, often necessitating mitral valve repair or replacement.

The classic findings of MVP on physical examination are a mid-systolic click with a late-systolic murmur that are heard best at the cardiac apex. The mechanism responsible for the audible click is the tensing of the mitral apparatus during leaflet prolapse in mid-systole. The click often is followed by a systolic murmur of varying duration. Dynamic maneuvers that diminish preload (eg, standing and the Valsalva maneuver) or decrease afterload (eg, administration of amyl nitrate) tend to move the click and murmur to an earlier point in systole. In contrast, the click and murmur occur later in systole during those maneuvers that increase ventricular filling (eg, squatting) or increase afterload (eg, isometric handgrip exercise).

Two-dimensional echocardiography is the most important test for diagnosing MVP. The diagnosis is made when there is displacement of one or both mitral leaflets into the left atrium by 2 mm or more during late systole or by 3 mm or more if the prolapse is holosystolic (Figure 6). Because the mitral annulus is known to have a saddle shape, a normal mitral valve can appear to prolapse in certain echocardiographic views, most notably in the apical two- and four-chamber views. Therefore, the diagnosis of MVP should be based on either a long-axis parasternal or apical view. In patients with MVP, echocardiography is also useful in determining the presence and severity of mitral regurgitation, assessing left atrial and ventricular chamber size, LV function, and leaflet thickening and redundancy. Unless severe mitral regurgitation is present, findings on chest radiography and ECG typically are unremarkable (Figure 6).

MVP patients without mitral regurgitation should be evaluated every 3 years. Echocardiography should be performed if cardiovascular symptoms develop or if the physical examination suggests that mitral regurgitation has developed. Patients with mild-to-moderate mitral regurgitation should be monitored annually with echocardiography. Patients with severe mitral regurgitation should be monitored every 6 to 12 months with a stress echocardiogram—more often if their clinical condition warrants it.

Surgery
In MVP patients with severe mitral regurgitation, the indications for mitral valve surgery are similar to those for patients with other causes of severe regurgitation. When surgery is required, mitral valve repair is usually feasible. Repair is characterized by low mortality and long-lasting durability; the 10-year reoperation-free survival rate ranges between 93% and 96% (Figure 7).¹²

1. Bonow RO, Carabello B, de Leon AC Jr, et al. Guidelines for the management of patients with valvular heart disease: executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Patients with Valvular Heart Disease). Circulation. 1998;98:1949-84.
   
   
2. Dajani A, Taubert K, Ferrieri P, Peter G, Shulman S. Treatment of acute streptococcal pharyngitis and prevention of rheumatic fever: a statement for health professionals: Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young, the American Heart Association. Pediatrics. 1995;96:758-764.
   
   
3. Dajani AS, Taubert KA, Wilson W, et al. Prevention of bacterial endocarditis. Recommendations by the American Heart Association. JAMA. 1997;277:1794-801.
   
   
4. Reyes VP, Raju BS, Wynne J, et al. Percutaneous balloon valvuloplasty compared with open surgical commissurotomy for mitral stenosis. N Engl J Med. 1994;331:961-967.
   
   
5. Ben Farhat M, Ayari M, Maatouk F, et al. Percutaneous balloon versus surgical closed and open mitral commissurotomy: seven-year follow-up results of a randomized trial. Circulation. 1998;97:245-250.
   
   
6. Greenberg BH, DeMots H, Murphy E, Rahimtoola SH. Arterial dilators in mitral regurgitation: effects on rest and exercise hemodynamics and long-term clinical follow-up. Circulation. 1982;65:181-187.
   
   
7. Blondheim DS, Jacobs LE, Kotler MN, Costacurta GA, Parry WR. Dilated cardiomyopathy with mitral regurgitation: decreased survival despite a low frequency of left ventricular thrombus. Am Heart J. 1991;122:763-771.
   
   
8. Freed LA, Levy D, Levine RA, et al. Prevalence and clinical outcome of mitral-valve prolapse. N Engl J Med. 1999;341:1-7.
   
   
9. Nishimura RA, McGoon MD, Shub C, Miller FA Jr, Ilstrup DM, Tajik AJ. Echocardiographically documented mitral-valve prolapse. Long-term follow-up of 237 patients. N Engl J Med. 1985;313:1305-1309.
   
   
10. Devereux RB, Brown WT, Kramer-Fox R, Sachs I. Inheritance of mitral valve prolapse: effect of age and sex on gene expression. Ann Intern Med. 1982;97:826-832.
    
    
11. Zuppiroli A, Rinaldi M, Kramer-Fox R, Favilli S, Roman MJ, Devereux RB. Natural history of mitral valve prolapse. Am J Cardiol. 1995;75:1028-1032.
    
    
12. Gillinov AM, Cosgrove DM, Blackstone EH, et al. Durability of mitral valve repair for degenerative disease. J Thorac Cardiovasc Surg. 1998;116:734-743.

This information is provided for general medical education purposes only and is not meant to substitute for the independent medical judgment of a physician relative to diagnostic and treatment options of a specific patient's medical condition.

In no event will The Cleveland Clinic Foundation be liable for any decision made or action taken in reliance upon the information provided through this web site.