Essentials of Diagnosis

• Variable causes determine clinical presentation.
• May be asymptomatic for many years (or for life) or may cause left-sided heart failure.
• Pansystolic murmur at the apex, radiating into the axilla; associated with S₃.
• ECG shows left atrial abnormality or atrial fibrillation and left ventricular hypertrophy; x-ray shows left atrial and ventricular enlargement. Echo-Doppler confirms diagnosis and estimates severity.

General Considerations
Mitral regurgitation may result from many processes. Rheumatic disease is associated with a thickened valve with reduced mobility and often a mixed picture of stenosis and regurgitation. In developed countries, more common causes of mitral regurgitation include myxomatous degeneration (eg, mitral valve prolapse with or without connective tissue diseases such as Marfan’s syndrome), infective endocarditis, and subvalvular dysfunction (due to papillary muscle dysfunction or ruptured chordae tendineae).

Cardiac tumors, chiefly left atrial myxoma, are a rare cause of mitral regurgitation.

Clinical Findings

A. Symptoms and Signs
During left ventricular systole, the mitral leaflets do not close normally, and blood is ejected into the left atrium as well as through the aortic valve. The net effect is an increased volume load on the left ventricle, and the presentation depends on the rapidity with which the lesion develops. In acute regurgitation, left atrial pressure rises abruptly, leading to pulmonary edema if severe. When it is chronic, the left atrium enlarges progressively, but the pressure in pulmonary veins and capillaries rises only transiently during exertion. Exertional dyspnea and fatigue progress gradually over many years.

Mitral regurgitation leads to left atrial enlargement and may cause subsequent atrial fibrillation. Systemic embolization is relatively unusual compared with other conditions causing atrial fibrillation. Mitral regurgitation may predispose to infective endocarditis.

Clinically, mitral regurgitation is characterized by a pansystolic murmur maximal at the apex, radiating to the axilla and occasionally to the base; a hyperdynamic left ventricular impulse and a brisk carotid upstroke; and a prominent third heart sound. Left atrial enlargement is usually considerable in chronic mitral regurgitation; the degree of left ventricular enlargement usually reflects the severity of regurgitation. Calcification of the mitral valve is less common than in pure mitral stenosis. Hemodynamically, left ventricular volume overload may ultimately lead to left ventricular failure and reduced cardiac output, but for many years the left ventricular end-diastolic pressure and the cardiac output may be normal at rest, even with considerable increase in left ventricular volume.

Nonrheumatic mitral regurgitation may develop abruptly, such as with papillary muscle dysfunction following myocardial infarction, valve perforation in infective endocarditis, or ruptured chordae tendineae in mitral valve prolapse. In acute mitral regurgitation, patients are in sinus rhythm rather than atrial fibrillation and have little or no enlargement of the left atrium, no calcification of the mitral valve, no associated mitral stenosis, and in many cases little left ventricular dilation.

Myxomatous mitral valve (“floppy” or “billowing” mitral valve, or mitral valve prolapse) is usually asymptomatic but may be associated with nonspecific chest pain, dyspnea, fatigue, or palpitations. Most patients are female, many are thin, and some have minor chest wall deformities. There are characteristic midsystolic clicks, which may be multiple, often but not always followed by a late systolic murmur. These findings are accentuated in the standing position. The diagnosis is primarily clinical but can be confirmed echocardiographically. Its significance is in dispute because of the frequency with which it is diagnosed in healthy young women (up to 10%), but in occasional patients this lesion is not benign. Patients who have only a midsystolic click usually have no sequelae, but patients with a late or pansystolic murmur may develop significant mitral regurgitation, often due to rupture of chordae tendineae. The need for valve replacement is commonest in men and increases with aging, so that approximately 2% of patients with clinically significant regurgitation over age 60 will require surgery. Infective endocarditis may occur, chiefly in patients with murmurs; such patients should have antibiotic prophylaxis prior to dental work and surgical procedures. ß-Adrenergic blocking agents are often effective for supraventricular arrhythmias. Sudden death is rare in mitral prolapse, but when symptomatic ventricular tachycardia is present, aggressive management with an implantable cardioverter-defibrillator is usually indicated. An association between mitral prolapse and embolic cerebrovascular events has also been reported but not confirmed in subsequent studies. Echocardiographic evidence of marked thickening or redundancy of the valve is associated with a higher incidence of most complications.

Papillary muscle dysfunction or infarction following acute myocardial infarction is less common. When mitral regurgitation is due to papillary dysfunction, it may subside as the infarction heals or left ventricular dilation diminishes. If severe regurgitation persists, these patients have a poor prognosis with or without surgery. Transient-but sometimes severe-mitral regurgitation may occur during episodes of myocardial ischemia. Patients with dilated cardiomyopathies of any origin may have secondary mitral regurgitation due to papillary muscle dysfunction or dilation of the mitral annulus. In these, mitral valve replacement has been considered contraindicated because of the poor risk:benefit ratio and deterioration of left ventricular function postoperatively. However, several groups have reported good results with mitral valve repair in patients with left ventricular ejection fractions greater than 30% and secondary mitral insufficiency.

B. Diagnostic Studies
Echocardiography is useful in demonstrating the underlying pathologic process (rheumatic, prolapse, flail leaflet), and Doppler techniques provide qualitative and semiquantitative estimates of the severity of mitral regurgitation. It should be noted that Doppler also detects clinically insignificant regurgitation in many normal individuals, and this finding must be interpreted in the context of the clinical presentation. The accompanying information concerning left ventricular size and function, left atrial size, pulmonary artery pressure, and right ventricular function can be invaluable in planning treatment as well as in recognizing associated lesions. Transesophageal echocardiography may reveal the cause of regurgitation and identify candidates for valvular repair. Nuclear medicine techniques as well as MRI permit measurement of left ventricular function and estimation of the severity of regurgitation.

Cardiac catheterization provides accurate assessment of regurgitation and, additionally, of left ventricular function and pulmonary artery pressure. Coronary angiography is often indicated to determine the presence of coronary artery disease prior to valve surgery.

Treatment & Prognosis
Acute mitral regurgitation due to endocarditis, myocardial infarction, and ruptured chordae tendineae often requires emergency surgery. Some patients can be stabilized with vasodilators or intra-aortic balloon counterpulsation, which reduces the amount of regurgitant flow by lowering systemic vascular resistance. Patients with chronic lesions may remain asymptomatic for many years. Operation is usually necessary when patients develop symptoms. However, because progressive and irreversible deterioration of left ventricular function may occur prior to the onset of symptoms, early operation is indicated even in asymptomatic patients with a declining ejection fraction (< 55-60%) or marked left ventricular dilation (end-systolic dimension > 4.5-5 cm on echocardiography).

There has been growing success with valve repair in nonrheumatic lesions, which avoids the complications of prosthetic valves described earlier. In addition, left ventricular function is better preserved when the subvalvular structures can be maintained intact by valve repair. Selected patients with poor left ventricular function and severe mitral regurgitation may benefit from this intervention. Mitral valve surgery is increasingly being performed using the appreciably less invasive thoracoscopic approach.

Preferences:
Freed LA et al: Mitral valve prolapse in the general population: the benign nature of echocardiographic features in the Framingham Heart Study. J Am Coll Cardiol 2002;40: 1298.
Otto CM: Clinical practice. Evaluation and management of chronic mitral regurgitation. N Engl J Med 2001;345:740.
Otto CM: Timing of surgery in mitral regurgitation. Heart 2003;89:100.
Thomas JD: Doppler echocardiographic assessment of valvar regurgitation. Heart 2002;88:651.