Chapter 20. Mitral Regurgitation

• Dyspnea or orthopnea.
• Characteristic apical systolic murmur.
• Color-flow Doppler echocardiographic evidence of systolic regurgitation into the left atrium.

The mitral apparatus consists of the left ventricular walls that support the papillary muscles, the chordae tendineae, mitral leaflets, annulus, and adjacent left atrial walls. Because defects in any of these components can lead to systolic regurgitation, the list of diseases that can cause mitral regurgitation includes many types of heart disease. Anything that causes left ventricular dilatation may disrupt the alignment of the papillary muscles, impairing their function and dilating the annulus, resulting in mitral regurgitation. Myocardial infarction involving the papillary muscles or the left ventricular walls that support them can impair the function of the mitral apparatus. Mitral chordae can rupture, especially in patients with hypertension or mitral valve prolapse. The most common diseases affecting the mitral leaflets are rheumatic heart disease and the myxomatous changes of mitral valve prolapse. In addition, infective endocarditis can destroy the mitral leaflets, and mitral annular calcification can impair the normal systolic contraction of the annulus, leading to mitral regurgitation. Finally, left atrial dilatation from any cause can disrupt annular function and cause mitral regurgitation. Some patients have combinations of these defects, making mitral regurgitation both more likely and more severe.

For clinical purposes, mitral regurgitation can be divided into two broad categories: organic and functional. The former refers to diseases that involve the valve leaflets and their immediate supporting apparatus, ie, chordae and annulus. The latter refers to diseases that affect the left ventricle and atrium, leaving the valve apparatus intact (Table 20–1). Most clinical studies involve patients with organic mitral regurgitation, so, unless otherwise specified, the following discussion focuses on organic mitral regurgitation.

Mitral valve prolapse is unique among the many causes of chronic organic mitral regurgitation in many ways. An increase in the middle connective tissue layer of the mitral valve causes an increase in leaflet size and elongated chordae. The resultant systolic prolapse of the valve into the left atrium may or may not be accompanied by regurgitation. In some patients, regurgitation depends on left ventricular volume. Large volumes tend to reduce prolapse and hence regurgitation; small volumes have the opposite effect.

Consequently, the presence or absence of regurgitation and its severity and timing in systole (the ventricle becomes progressively smaller during systole) are determined by a complex interplay of left ventricular volume, pressure, and contractile state. Patients with mitral valve prolapse are also unique because the condition can be hereditary connective tissue disease (eg, Marfan syndrome) or acquired (inflammation of the valve). Some patients exhibit abnormalities of connective tissue in other organs (eg, thoracic skeleton) and have demonstrable abnormalities in the autonomic nervous system. Thus, the clinical presentation of mitral valve prolapse varies from one that is similar to other forms of mitral regurgitation to a unique presentation that is dominated by extracardiac manifestations.

In chronic mitral regurgitation, the more common of the two general clinical presentations, the mitral regurgitation progressively worsens as the underlying heart disease worsens. In this situation, the heart has time to adapt to the mitral leak. The increased pressure in the left atrium during systole causes left atrial dilatation. If this is not adequate to decompress the left atrial pressure, the pulmonary arterial tone increases to protect the pulmonary capillaries from increased hydrostatic pressure, resulting in pulmonary hypertension. Because the regurgitated blood returns to the left ventricle in diastole, along with the normal atrial stroke volume, the volume load on the left ventricle results in left ventricular dilatation and eccentric hypertrophy.

Initially, the loading conditions in mitral regurgitation enhance left ventricular performance because preload is increased and afterload is normal. Preload is increased by the augmentation of left ventricular diastolic volume, which increases left ventricular systolic function via the Frank-Starling mechanism. Afterload, or the left ventricular wall tension after the aortic valve opens in systole, is not increased, despite increased left ventricular volume, because much of the increased volume is regurgitated into the left atrium in early systole before the aortic valve opens and because the continued regurgitation during systole reduces forward stroke volume and blood pressure. As the severity of mitral regurgitation increases over time, the ability of the dilated left ventricle to augment systolic function reaches its limits, left ventricular systolic function falls, and heart failure ensues.

Acute mitral regurgitation presents differently because there is insufficient time for these compensatory mechanisms to develop. Sudden rupture of the chordae tendineae, for example, may result in severe acute mitral regurgitation, which markedly increases left atrial pressure. Because the left atrium has no time to dilate, the pulmonary capillary pressure rises markedly, and pulmonary edema usually ensues. The left ventricle also does not dilate adequately to handle the tremendous volume load, and forward failure occurs because of an impaired left ventricular stroke volume. Acute mitral regurgitation (caused by the abrupt failure of a component of the mitral apparatus) can precipitate or aggravate symptoms in a patient with chronic mitral regurgitation.

Symptoms & Signs

Chronic Mitral Regurgitation

The medical history of patients with chronic mitral regurgitation may suggest its cause. Look for a possible history of acute rheumatic fever, coronary artery disease, or a cardiomyopathy. The most common symptom in patients with chronic mitral regurgitation is progressive dyspnea, beginning with dyspnea on exertion and progressing to paroxysmal nocturnal dyspnea and finally orthopnea. Patients may also complain of fatigue and other symptoms associated with congestive heart failure, such as edema. Chronic mitral regurgitation can lead to atrial fibrillation, and palpitations or other symptoms related to this rhythm disturbance may present in patients. Some patients with mitral valve prolapse may have atypical chest pain or inappropriate sympathetic nervous system activation (eg, inappropriate tachycardia, orthostatic hypotension).

Acute Mitral Regurgitation

The patient with acute mitral regurgitation is usually markedly symptomatic, with severe orthopnea or frank pulmonary edema. Although sudden pulmonary edema in itself may suggest the diagnosis, other features of the history may point to the cause of mitral apparatus failure, such as a history of acute myocardial infarction, uncontrolled hypertension, or symptoms of infective endocarditis.

Physical Examination

Chronic Mitral Regurgitation

In chronic mitral regurgitation, the heart rate may be increased because of atrial fibrillation or heart failure. The carotid pulse is usually brief and of low amplitude, and blood pressure examination shows a narrow pulse pressure. These findings reflect the reduced forward stroke volume. In the presence of heart failure, the respiratory rate may be increased and rales, pleural effusion, edema, increased jugular venous pressure, or ascites may be present. Left ventricular enlargement may result in an enlarged apical impulse. The first and second heart sounds are usually normal, but the pulmonic component of the second heart sound may be increased if pulmonary hypertension is evident. A third heart sound is common because of the left ventricular volume overload, but it does not necessarily indicate heart failure. A fourth heart sound is unusual unless associated coronary artery disease or hypertension is present. The characteristic murmur of chronic mitral regurgitation is usually holosystolic and heard best at the apex, with radiation to the axilla. Occasionally, in patients with posterior leaflet defects, the direction of the regurgitant jet may be anterior, and the murmur is heard in the aortic area. With anterior leaflet defects, the direction of the mitral jet may be posterior and transmitted to the back, where it can be heard up and down the spine. Some reports even note hearing this murmur with the stethoscope on the top of the head. In patients with mitral valve prolapse, the murmur can be crescendo and late systolic. This type of murmur, in fact, almost always represents mitral regurgitation. Often, the late systolic crescendo murmur of mitral valve prolapse is preceded by a midsystolic click from the sudden tensing of the prolapsing leaflets when the end of chordal tethering is reached. Some patients may manifest only a midsystolic click. Occasionally, mitral murmurs will be honking or musical in quality, presumably from a prolapsing leaflet that vibrates in the regurgitant stream. Some patients occasionally have other murmur configurations, whereas others with echocardiographically documented mitral regurgitation have no audible murmur, especially if the regurgitation is mild.

Because murmur configuration and radiation vary in mitral regurgitation, dynamic auscultation is of a great deal of value at the bedside for differentiating this murmur from other heart murmurs. Handgrip exercise is the favored bedside maneuver because it frequently increases the intensity of a mitral regurgitation murmur. In patients with poor grip strength, transient arterial occlusion with two blood pressure cuffs, one on each arm, is useful for producing the same effect (Table 20–2, and Chapter 5). The murmur of mitral valve prolapse behaves like that of mitral regurgitation from any cause, but it has a few unique features. Any maneuver that increases left ventricular volume will (as noted earlier) decrease the amount of mitral valve prolapse and decrease the amount of mitral regurgitation, thereby lessening the intensity of the murmur. Thus, rapid squatting will diminish the murmur of mitral valve prolapse and move the timing of the click-murmur complex later in systole (Figure 20–1). Conversely, maneuvers that decrease left ventricular volume increase the intensity and duration of the murmur of mitral valve prolapse. Thus, standing rapidly from a squatting position will make the murmur louder and move the click-murmur complex toward early systole. Extreme left ventricular volume increases can eliminate the click-murmur and mitral regurgitation, and extreme decrease can result in a pansystolic murmur without a click. Consequently, the auscultatory findings in mitral valve prolapse vary greatly, which can make accurate clinical diagnosis difficult.

Acute Mitral Regurgitation

In acute mitral regurgitation, the physical findings are different. The marked increase in left atrial pressure, caused by regurgitation into a noncompliant left atrium, may raise left atrial pressure in late systole to the point that there is no longer any gradient for regurgitant flow. The murmur thus becomes an early systolic murmur rather than the holosystolic murmur characteristic of patients with chronic mitral regurgitation. In fact, when the acute mitral regurgitation is very severe, the murmur may not be audible. In mild-to-moderate acute mitral regurgitation, the murmur responds like the murmur of chronic mitral regurgitation with dynamic auscultation. More severe acute regurgitation is associated with high catecholamine tone and a lack of responsiveness to bedside maneuvers. Other characteristic features of acute mitral regurgitation include a fourth heart sound caused by vigorous atrial contraction following exaggerated expansion during ventricular systole (atrial diastole). In the presence of pulmonary hypertension, the pulmonary second sound increases, and murmurs of pulmonic and tricuspid regurgitation may be present. As mentioned earlier, acute mitral regurgitation invariably results in pulmonary edema. Consequently, the patient will have an increased respiratory rate, diffuse rales, evidence of plural effusion, increased heart rate, a narrow pulse pressure with low systolic blood pressure, and signs of acute right-heart failure, such as increased jugular venous pressure.

Mixed Valvular Disease

Patients with rheumatic valvular disease often have mixed mitral disease, which is defined as at least 2+ (on a scale of 1–4; see following section on Echocardiography) mitral regurgitation, with a mean mitral valve diastolic gradient of more than 10 mm Hg. The clinical course of mixed mitral valve disease is similar to that of mitral regurgitation, and such patients should be treated similarly. Aortic regurgitation frequently occurs with mitral regurgitation, either because of left ventricular dilatation or because the same disease process affects the aortic valve (eg, Marfan syndrome). This places an additional volume load on the left ventricle and usually accelerates the patient's clinical deterioration.

When aortic stenosis and mitral regurgitation occur together, it is sometimes difficult to ascertain whether the same disease process (eg, rheumatic disease) involved both valves or whether the pressure load of significant aortic stenosis altered left ventricular geometry, performance, or both, resulting in functional mitral regurgitation. Diagnostic imaging studies usually resolve this issue and help direct therapy.

Diagnostic Studies

Electrocardiography

Patients with chronic mitral regurgitation may have evidence of left ventricular hypertrophy, left atrial abnormality, and sometimes, right ventricular enlargement. Patients with coronary artery disease might have evidence of myocardial infarction or ischemia. Electrocardiographic (ECG) exercise testing is usually done only to confirm the patient's physical limitations, because ECG changes in the face of a left ventricular volume load are not likely to be accurate for the diagnosis of coronary artery disease. Ambulatory ECG monitoring is occasionally done in patients with palpitations to document atrial fibrillation or other intermittent rhythm disorders.

Chest Radiography

In cases of chronic mitral regurgitation, an enlarged left ventricle and left atrium would be expected. In severe regurgitation, right-heart enlargement and pulmonary hypertension may be evident. Patients in heart failure will show pulmonary congestion and pleural effusions. In acute mitral regurgitation, there are often signs of pulmonary congestion without enlargement of the heart.

Echocardiography

The color-flow Doppler identification of a systolic regurgitant jet across the mitral valve into the left atrium is diagnostic of mitral regurgitation. There are several ways of estimating the severity of mitral regurgitation by analyzing the characteristics of the regurgitant jet on color-flow Doppler. The first method is the depth of penetration of the jet into the left atrium. A penetration of 1 cm or less is considered mild; 2–3 cm, moderate; and 4 cm or more, severe. If the jet is very narrow, the actual volume of regurgitant flow may not be as great as occurs with a more voluminous flow disturbance that penetrates to the same depth. Some investigators have therefore suggested also taking the area of the jet into consideration. One problem with this assessment system, however, is that if the jet impinges on a wall of the left atrium, it appears to penetrate less and be of a smaller area than if it is free in the atrial cavity. There is thus a tendency to underestimate the severity of mitral regurgitation when the jet hits the atrial wall. In addition, a regurgitant jet of any size occurring in a large left atrium will not appear as impressive as the same size jet in a small left atrium. The size of the leak in the mitral valve can be determined by evaluating the jet in a cross-sectional plane at the level of the mitral valve. This method gives an estimate of the size of the hole through which the jet is originating. These qualitative criteria for mitral regurgitation severity can be highly subjective.

For these reasons, there has been interest in more quantitative methods for estimating the severity of mitral regurgitation. The proximal isovelocity surface area observed where flow acceleration and convergence occur on the left ventricular side of the mitral leaflets allows the estimates of regurgitant volume and effective regurgitant orifice area. Fluid dynamics theory states that flow through an isovelocity surface is equal to the velocity times the surface area, which yields instantaneous regurgitant flow. This technique uses the color-flow Doppler color change interfaces observed with accelerating velocity through the orifice to estimate isovelocity surface area. Pulsed Doppler echocardiography can be used to quantitate regurgitant volume. The principle used is that of flow continuity. Systolic flow out the left ventricular outflow tract represents the forward stroke volume. This can be determined by multiplying the outflow tract area (measured on the two-dimensional echocardiographic image) times the outflow tract systolic velocity–time integral. Flow across the mitral valve in diastole represents the total stroke volume (forward plus regurgitant flow) and can be determined by multiplying mitral annulus area times the diastolic velocity–time integral. Regurgitant volume is the difference between total and forward stroke volume. Typically, the regurgitant volume is reported as the regurgitant fraction, which is the regurgitant stroke volume divided by the total stroke volume. Unfortunately, the calculation of regurgitant stroke volume has many possible sources of error, the largest of which is measuring the flow areas—mitral annular and outflow tract. Thus, individuals without valvular regurgitation can have regurgitant fractions of up to 20%. Also, the calculation of regurgitant flow is time-consuming and requires considerable skill. Effective regurgitant orifice area can be estimated as the ratio of regurgitant volume to the regurgitant jet velocity–time integral by pulsed Doppler.

Assessment of pulmonary venous flow velocity by pulsed Doppler echocardiography can also be of value in estimating the severity of mitral regurgitation. Normal pulmonary venous flow velocity is biphasic, with a predominant systolic forward velocity and a lesser diastolic forward velocity in older adults. Systolic forward velocity is reduced in patients with mitral regurgitation, and often the diastolic velocity predominates. In severe mitral regurgitation, the systolic flow in the pulmonary vein signal may reverse. Systolic flow reversal is highly specific for severe regurgitation, but sensitivity is low. Unfortunately, pulmonary venous flow velocity patterns vary considerably in patients with mitral regurgitation, and the predictive value for regurgitation severity is low. In many laboratories, all these factors are integrated to produce a composite estimate of the severity of regurgitation, usually on a scale of 1 to 4, with 4 being severe mitral regurgitation. Table 20–3 exhibits the criteria for grading the severity of mitral regurgitation.

Echocardiography can be used to evaluate the anatomy of the mitral apparatus to determine where the defect lies and what its cause may be. For example, patients with rheumatic mitral valve disease have thickening of the mitral leaflets, especially at the tips, with rolled edges and regurgitation along the commissural fissure lines. Patients with mitral valve prolapse have voluminous mitral leaflets that prolapse into the left atrium in the latter part of systole. Patients with coronary artery disease have wall motion abnormalities near the papillary muscle attachments. Ruptured and flail chordae tendineae are readily detected by echocardiography, as is mitral annular calcification.

The echocardiogram is also useful for assessing the compensatory changes in the cardiovascular system resulting from mitral regurgitation. The degree of left ventricular and left atrial enlargement is related to the severity of the mitral regurgitation and its chronicity. Left ventricular systolic performance is an important determinant of prognosis in mitral regurgitation (see Prognosis). Doppler estimation of pulmonary artery pressures from pulmonic or tricuspid regurgitant jets is valuable for estimating the effect of mitral regurgitation on the pulmonary circulation. An assessment of right-heart chamber sizes and function is additional useful information. Echocardiography can be deployed during bicycle exercise to assess exercise-induced changes in mitral regurgitation severity and pulmonary artery systolic pressure (PASP). Increases in either suggest a worse prognosis. Exercise echocardiography is especially useful for detecting physical limitations in asymptomatic patients with severe mitral regurgitation. Color-flow Doppler echocardiography can detect trivial or mild mitral regurgitation in up to half of otherwise healthy adults. The incidence increases with age and with the rigor with which the operator interrogates the valve. In the absence of anatomic abnormalities, small degrees of regurgitation are probably benign effects of aging. In most cases, mild mitral regurgitation found by echocardiography is not associated with a murmur on physical examination.

Transesophageal echocardiography (TEE) can provide the anatomic details of leaflet anatomy needed to plan surgical repair. The probe is rotated progressively to identify the scallops of the two mitral valve leaflets in midesophageal long axis views. The rotation of the color-flow jet helps confirm the incompetent scallops. In addition, annular size can be determined and the subvalvular apparatus interrogated. TEE during surgery can be of value to the surgeon. Also, three-dimensional echocardiography is useful for identifying the culprit scallops especially with TEE.

Cardiac Catheterization

Cardiac catheterization is rarely needed to diagnose mitral regurgitation, nor is it usually needed to assess the severity of the regurgitation, left ventricular size and function, or any resultant pulmonary hypertension. Coronary angiography is useful, however, for establishing artery disease as the likely cause of mitral regurgitation as well as the risk from surgical correction of mitral regurgitation from any cause.

Hemodynamic evaluation at the time of cardiac catheterization in patients with moderate-to-severe mitral regurgitation will show an increase in pulmonary artery pressures, increases in the pulmonary capillary wedge pressure (PCWP), and possibly a reduction in forward cardiac output. The PCWP tracing often displays a large v wave, which is more than 50% greater than the height of the a wave. Although much has been made of the diagnostic value of large v waves in the PCWP tracing (especially in the intensive care unit setting), it must be remembered that any cause of left atrial pressure elevation will elevate the height of the v wave. It is only when the v wave is elevated out of proportion to the a wave that the diagnosis of mitral regurgitation is likely (> 150% of the a wave).

Left ventricular angiography is graded with a 1–4+ system, where 1+ is mild and 4+ is severe, indicating regurgitation of the angiographic dye into the pulmonary veins (see Table 20–3). This assessment method correlates well with the color-flow Doppler system. In addition, left ventricular angiography is useful for estimating left ventricular volume and ejection fraction. Cardiac catheterization can exclude the presence of other diseases, such as ventricular septal defect (VSD), hypertrophic obstructive cardiomyopathy (HOCM), and aortic stenosis, that might be confused with mitral regurgitation. Certain aspects of the patient's hemodynamics, such as the presence of pulmonary hypertension, are of prognostic value in mitral regurgitation.

Because the symptoms seen in chronic mitral regurgitation are not specific for this condition, the physical examination is crucial for the differential diagnosis. The murmur of tricuspid regurgitation, for example, can occasionally be heard at the apex, especially if the right ventricle is enlarged and displaced leftward. Differentiating features include the increase in the intensity of the murmur with inspiration, the large v waves in the jugular pulse, a right ventricular lift, and a pulsatile liver. It should be noted that tricuspid regurgitation can result from pulmonary hypertension caused by mitral regurgitation, so some patients have both murmurs. In this situation, the murmur of tricuspid regurgitation is best assessed at the left or right sternal border, and that of mitral regurgitation at the apex. It may be difficult, however, to distinguish between the two murmurs in patients where both are moderately severe.

The murmur of aortic stenosis is often confused with mitral regurgitation, especially when the mitral regurgitant murmur is atypical or radiates to the aortic area. The murmur of aortic stenosis is usually lower in pitch than that of mitral regurgitation; it radiates to the neck and is often accompanied by an S4 sound. In aortic stenosis, the left ventricular apical impulse amplitude often increases but is less likely to be laterally displaced, as is found in patients with mitral regurgitation. On dynamic auscultation, there is no change in the murmur of aortic stenosis with handgrip exercise, as is the case with mitral regurgitation, but the murmur of aortic stenosis does increase in the beat following a premature ventricular contraction, whereas that of mitral regurgitation does not.

A VSD, especially a muscular defect low in the septum, may mimic the murmur of mitral regurgitation. Because dynamic auscultation will not distinguish between these two left ventricular regurgitant murmurs, other signs must be used. The patient with VSD usually has a large right ventricle, and a vibration (thrill) over the anterior chest may be palpable. The murmur of HOCM can also be confused with mitral regurgitation. The major differential features are that the murmur of HOCM increases with the Valsalva maneuver, whereas the murmur of mitral regurgitation decreases; the murmur of HOCM decreases with handgrip, and the murmur of mitral regurgitation increases. In addition, the patient with HOCM usually has a prominent fourth heart sound. However, because many patients with HOCM also have mitral regurgitation, the ability to distinguish it from mitral regurgitation is difficult in some patients.

The murmur of mitral valve prolapse can be difficult to distinguish from the murmur of HOCM because both murmurs change in intensity and in a similar direction with the stand and squat and Valsalva maneuvers.

In this situation, other features of each disease, such as the midsystolic click with mitral valve prolapse and the left ventricular hypertrophy evident on palpation of the chest, or the fourth heart sound in the patient with HOCM, are useful for differentiating the two conditions by physical examination. The major differential diagnosis of acute mitral regurgitation is acute VSD because both may occur in the setting of acute myocardial infarction. A palpable vibration is more common with VSD, but perhaps the best differentiation is that the patient with acute VSD has much less dyspnea than does the patient with acute mitral regurgitation. The response to dynamic auscultation is the same in these two conditions.

Pharmacologic Therapy

Vasodilators

Vasodilators are useful in acute mitral regurgitation to decrease aortic pressure and impedance, favoring forward over regurgitant flow during systole. This decreases left ventricular size and left ventricular and atrial pressures, improves forward cardiac output, and decreases the amount of regurgitation. Studies of acute regurgitation with vasodilators, such as hydralazine, nifedipine, and nitroprusside, have demonstrated this effect in the hemodynamics laboratory and, thus, their usefulness for managing acute mitral regurgitation. Studies on the pharmacologic treatment of patients with chronic mitral regurgitation are scant, and the available data are not particularly encouraging. Because afterload is not increased in patients with well-compensated chronic mitral regurgitation, lowering it further may not improve forward flow and would more likely reduce it. Many patients experience vasodilator side effects, and if forward cardiac output is not improved, the patient's overall hemodynamic status is actually worsened. Thus, until further data are obtained, there is no evidence to support vasodilator therapy for asymptomatic patients with chronic mitral regurgitation. In mildly symptomatic patients who presumably have left ventricular dilation and dysfunction, but who want to avoid surgery, vasodilators could be tried. Markedly symptomatic patients, however, are better treated surgically. Patients with systemic hypertension and those with functional mitral regurgitation due to systolic dysfunction should be treated with vasodilators.

Digoxin

Digoxin is useful in atrial fibrillation for controlling the heart rate. Whether it is of any value for improving forward output with mitral regurgitation in patients with normal sinus rhythm is unknown. If there are other indications for using the drug, however, it is not known to be harmful to the overall hemodynamic status of patients with mitral regurgitation.

Oral Anticoagulation

Oral anticoagulation is indicated for patients in atrial fibrillation and those with concomitant mitral stenosis. Whether patients with moderate-to-severe mitral regurgitation, with large left ventricles and large left atria, who are in normal sinus rhythm and have normal left ventricular function would benefit from anticoagulants is controversial. Eccentric regurgitant jets may produce areas of stasis in the left atrium, according to color-flow Doppler studies. Furthermore, patients with moderate-to-severe mitral regurgitation are always at risk for developing atrial fibrillation. Although an argument can be made for long-term anticoagulation in such patients, no clinical trials support this approach.

Antibiotic Prophylaxis

Only patients with prosthetic heart valves now require antibiotics to prevent the development of bacterial endocarditis. Patients in whom rheumatic heart disease is the likely cause of mitral regurgitation should also have rheumatic fever antibiotic prophylaxis.

Surgical Treatment

Patients with acute, severe, or decompensated chronic severe mitral regurgitation will need urgent surgical therapy—if it is appropriate to their general medical condition. Such patients can usually be stabilized with intravenous vasodilators, such as hydralazine or nitroprusside, and other therapies for heart failure, such as diuretics. If there is no response to pharmacologic therapy, an intra-aortic balloon pump is indicated. This mechanical approach will reduce arterial and left ventricular pressure in systole, favoring forward flow rather than regurgitant and increased diastolic aortic pressure, and may improve left ventricular contractility. Most patients will stabilize on this therapy, allowing for an appropriate evaluation (eg, coronary angiography), thereby maximizing the benefits of surgery.

Patients with either acute or chronic moderately severe mitral regurgitation will eventually need surgical therapy. The issue is the appropriate timing of surgery. If the physician waits until the symptoms are marked because of left heart failure with depressed left ventricular systolic function and severe pulmonary hypertension, not much symptomatic improvement is achieved after surgery, and left ventricular function remains depressed. On the other hand, if surgery is performed earlier, the patient may become relatively asymptomatic, with normal left ventricular function. Considerable effort has been directed at determining prognostic indicators for avoiding a poor response to surgical therapy. Prospective studies have shown that the following are all markers of a poor prognosis following surgery: an ejection fraction of 60% or less, an end-systolic volume index of 50 mL/m2 or more, an end-systolic dimension on echocardiography of 40 mm or more, significant pulmonary hypertension (PASP > 50 mm Hg or peak exercise PASP > 60 mm Hg), and atrial fibrillation. Although it seems logical that surgery should therefore be performed before these indicators are obtained in a patient, even one who is asymptomatic, this decision analysis has never been tested in clinical trials (Table 20–4).

In patients with aortic and mitral regurgitation, if the mitral valve is not obviously diseased and the mitral regurgitation is mild to moderate (1–2+), replacing the aortic valve will often diminish left ventricular size enough to reduce or eliminate the mitral regurgitation. Sometimes a mitral annular ring will be required to reduce mitral annular size. In cases where the mitral valve leaflets and chordae are diseased or the regurgitation is severe, valve repair or replacement will be necessary—at the cost of a higher likelihood of operative mortality or postoperative morbidity. Severe aortic stenosis is often accompanied by mild-to-moderate mitral regurgitation. In this situation, the reduction in left ventricular pressure produced by aortic valve replacement usually reduces the mitral regurgitation, and further mitral surgery can be avoided.

The pulmonary hypertension that often accompanies mitral regurgitation may lead to tricuspid and pulmonic regurgitation. The latter usually resolves when the pulmonary pressure is reduced by mitral valve surgery, and pulmonary valve replacement is rarely necessary. Tricuspid regurgitation, if mild-to-moderate and associated with moderately severe pulmonary hypertension, will usually resolve after successful mitral surgery. If the tricuspid regurgitation is moderately severe, but the leaflets are not diseased, a tricuspid ring may be effective; if tricuspid valve disease is present, repair or replacement will be necessary. One clinical indicator for the need for tricuspid valve repair or replacement is a mean right atrial pressure of more than 15 mm Hg; however, the decision for this is often made during surgery, after the mitral procedure has been completed.

The onset of heart failure symptoms should prompt consideration of surgical treatment. Symptoms such as dyspnea, fatigue, and edema develop in some patients before the echocardiographic signs of severe mitral regurgitation develop. The importance of other symptoms, such as a history of arrhythmias or recurrent systemic emboli, is less certain. If the hemodynamic indicators are absent, other therapies for these conditions should be attempted first, before surgery.

Other factors to be taken into account when deciding when to perform surgery are the type of operation—valve repair or replacement—and the type of prosthetic valve, should one be needed. It is now possible in many patients with mitral regurgitation to repair rather than replace the mitral valve. Patients with mitral valve prolapse, ruptured chordae tendineae, or a ruptured papillary muscle are especially likely to respond to reparative surgery, whereas patients with markedly deformed valves and fused chordae from rheumatic heart disease or patients with infective endocarditis are less likely to be helped by mitral valve repair and often require valve replacement. Repair is preferable, especially for the patient with normal sinus rhythm because there is no need for long-term anticoagulation therapy following surgery. In addition, mitral valve repair is generally associated with better preservation of left ventricular systolic function following surgery and is therefore highly advantageous for patients with a low left ventricular ejection fraction and a repairable mitral valve. Thus, if it is likely that mitral valve repair can be done, there is less reluctance about operating in asymptomatic patients that otherwise meet criteria for surgery.

If valve replacement is necessary, ventricular function can be preserved by leaving the chordae intact; chordal tethering of the papillary muscles is presumed to improve left ventricular performance. With valve replacement, the choice between a mechanical and a bioprosthetic valve may influence the timing of surgery.

In general, mechanical prosthetic valves are preferred because of their better long-term reliability. Bioprosthetic valves can be chosen when valve longevity is not an issue or when patients want to try to avoid anticoagulation therapy. The latter would apply mainly to young women with normal sinus rhythm who want to become pregnant. They will be much easier to treat without anticoagulation therapy—a feasible goal with a bioprosthetic valve. These patients must realize, however, that this valve will need to be replaced in approximately 10–15 years, as a result of deterioration. This should give these patients time for several pregnancies, if they so desire.

Generally, patients with a mechanical valve and no contraindications to anticoagulation therapy should be treated with such agents. The incidence of systemic emboli is higher with mitral than with aortic prosthetic valves. Without anticoagulation, there is a 1–3% per year chance of systemic emboli with a bioprosthetic valve in the mitral position, so aspirin therapy is recommended for patients with bioprosthetic valves. The use of warfarin for 3 months after bioprosthetic mitral valve replacement is sometimes done until the endothelium grows over the sewing ring, reducing the risk of thrombus development. Patients with other risks for thrombus formation, such as atrial fibrillation, should also receive warfarin.

Percutaneous approaches to mitral valve repair and replacement are developing rapidly. One approach is to put a clip at the tip of the mitral leaflets creating a double orifice valve similar to the surgical Alfieri technique. Initial studies suggest that it may be ideal for patients with severe functional mitral regurgitation due to dilated cardiomyopathy, where surgical risk is high. Another is to deliver an annuloplasty ring percutaneously, reducing the annulus size. Finally, stent-mounted tissue valves can be deployed in the mitral area. At this time, these devices have not been released for routine use in the United States, but they hold great promise for the future.

Patients with chronic mitral regurgitation have an average survival curve similar to that of patients with chronic aortic regurgitation and chronic mitral stenosis. The cause of the chronic mitral regurgitation in individual patients influences the prognosis. In general, patients with coronary artery disease as the cause have a poor prognosis, those with the myxomatous changes of mitral valve prolapse have the best prognosis, and those with rheumatic heart disease have an intermediate prognosis. The onset of infective endocarditis can markedly alter the prognosis. In addition, any sudden deterioration of mitral valve function that leads to acute worsening of the mitral regurgitation lessens the prognosis.

The prognosis in acute mitral regurgitation, when it is associated with acute pulmonary edema and severe symptoms, is guarded; it also depends on the cause. For example, patients with acute severe mitral regurgitation from acute myocardial infarction have a much worse prognosis than do otherwise healthy individuals who rupture a chorda. In general, most patients with acute mitral regurgitation require immediate surgical attention, and their prognosis is not as good as that for patients with chronic mitral regurgitation.