Mitral regurgitation
Mitral regurgitation leads to volume overload of the left ventricle, which must increase in size to achieve a normal stroke output to accommodate the leakage of blood back into the left atrium. Progressive left ventricular dilatation eventually leads to an increase in afterload, contractile impairment, reduction of cardiac output, and heart failure. In acute mitral regurgitation (such as can occur with chordal rupture, ischemia, or endocarditis), left atrial and pulmonary venous and arterial pressures increase quickly, giving rise to dyspnea and, often, acute pulmonary edema. In more chronic forms of mitral regurgitation, an increase in left atrial pressure is often offset by a concomitant increase in atrial compliance; and hence, symptoms appear late in the course of the disease. Left atrial enlargement predisposes the patient to atrial fibrillation and atrial thromboembolism. In long-standing mitral regurgita-tion, pulmonary hypertension can develop, which in turn leads to tricuspid regurgitation and right-sided heart failure.
Diagnosis
Clinical manifestations In most patients, mitral regurgita-tion remains asymptomatic for many years. Dyspnea, fatigue from low cardiac output, and edema occur late in the course of the disease. Mitral regurgitation is recognized clinically by a systolic murmur at the apex, radiating to the axilla and increasing on expiration. In patients with a posteriorly directed jet of mitral re-gurgitation, the murmur is heard well at the back. In more severe cases, the murmur lasts throughout systole, the first and second heart sounds are soft or difficult to hear, and a third heart sound is present. A midsystolic click can be present in myxomatous disease; in less severe cases, this click can precede the murmur. The murmur can also be confined to late systole, with papillary muscle dysfunction. Mitral regurgitant murmurs caused by ischemia can be variable in duration and intensity, depending on the degree of ischemia and the loading conditions.
Imaging studies Doppler echocardiography is the noninva-sive method of choice in confirming the presence of mitral regur-gitation. Echocardiography is used to diagnose the mechanism of the regurgitation (e.g., prolapse or annular dilatation); color-flow mapping is used to provide a semiquantitative assessment of severity based on the size and penetration of the left atrium by the regurgitant jet. Additionally, echocardiography can be used to assess the effects of the regurgitation on left ventricular size and function. Quantitative measurements of regurgitation, such as the regurgitant volume, regurgitant fraction ([regurgitant volume plus stroke volume] divided by regurgitant volume), and re-gurgitant orifice area (the area through which the valve leaks), are now possible with newer Doppler techniques. These techniques are useful in determining the true severity of the lesion and following it over time.22 Left ventricular size and volume, as well as contractile function assessed by the ejection fraction, are used to determine the need for surgical intervention.
However, asymptomatic mitral regurgitation is more difficult to assess and manage than other valvular lesions because in this condition, the true contractile function of the left ventricle is difficult to determine with conventional measures such as the ejection fraction. These measurements of contractility are confounded by the increase in ventricular preload caused by the extra volume of blood in the left atrium and the variable effect on afterload. After-load is increased by left ventricular dilatation, but this effect is offset as the ventricle ejects much of its blood into a relatively low pressure system (the left atrium). The left ventricular ejection fraction can appear falsely elevated in mitral regurgitation and usually falls after surgical correction. An ejection fraction of less than 60% should be considered abnormally low in patients with mitral regurgitation.
Transesophageal echocardiography is very sensitive in the detection of mitral regurgitation and is used mainly in those patients who are difficult to evaluate by the transthoracic approach.23 Contrast ventriculography is used to determine the severity of mitral regurgitation in patients undergoing cardiac catheterization. This procedure involves injecting radiopaque contrast medium into the left ventricle and assessing the extent and duration of opacification of the left atrium. In patients undergoing hemodynamic monitoring, large systolic V waves on the pulmonary arterial wedge tracing raise the suspicion of acute severe mitral regurgitation, as can occur in acute ischemia, but such V waves can occur in the absence of severe regurgitation.
Treatment
Indications for surgery In the management of asymptomatic mitral regurgitation, it should be borne in mind that left ventricular dysfunction is often latent and that, once present, the dysfunction cannot be corrected by operative intervention.24 Therefore, it is important to refer patients for surgery before the onset of true left ventricular dysfunction even in the absence of symptoms.
Unfortunately, no load-independent measure of contractile function is readily available. Stress echocardiography is useful in detecting latent left ventricular dysfunction not evident on a resting study. Failure of the left ventricular ejection fraction to increase on exercise or of the left ventricular end-systolic volume to decrease on exercise is predictive of incipient left ventricular dysfunction and should be considered an indication for early surgery.23
Other echocardiographic indices that have been associated with a less favorable surgical outcome include an absolute end-systolic dimension that is greater than 4.5 cm or that is greater than 2.6 cm/m2 when indexed for body surface area; an end-systolic volume of greater than 50 ml/m2; and a resting ejection fraction of less than 60%.23 Surgical referral should be considered if ventricular size and function approach these indices.25 Serial echocardiograph-ic evaluation should be performed at least yearly and should be performed more frequently as ventricular dilatation progresses in patients with severe asymptomatic mitral regurgitation. Studies indicate a better long-term survival rate in patients with severe mitral regurgitation when surgery is performed early.26,27
Symptomatic severe mitral regurgitation is considered an indication for surgical intervention if the valve is primarily involved. Symptomatic patients with ischemic mitral regurgitation often require mitral valve surgery in addition to revascularization. Mitral regurgitation secondary to left ventricular dilatation often improves with afterload reduction, and surgical intervention is not usually indicated.
Patients with moderately severe or severe left ventricular dysfunction (ejection fraction < 35%) and significant mitral regurgita-tion were thought in the past to be poor surgical candidates because of high operative risk. However, recent research has shown that there is acceptable risk associated with operations in these patients. Symptoms usually improve, but a survival benefit associated with surgery in this group has not yet been shown.2829 Patients who are not considered suitable for surgery because of left ventricular dysfunction often benefit from afterload reduction and diuretics.30 However, in patients who have primary asymptomatic mitral regurgitation with preserved left ventricular function, af-terload reduction has not been shown to delay surgery or improve left ventricular function in the few small studies that have addressed this issue; afterload reduction is not currently recommended to treat such patients.31 Afterload reduction is beneficial for stabilizing patients with hemodynamically significant acute mitral regurgitation in preparation for surgery.
Surgical intervention Mitral valve repair is currently the technique of choice in the surgical management of mitral regurgi-tation because the operative mortality is lower, ventricular function is better preserved, and long-term complications such as thromboembolism and infection are lower with repair than with replacement [see Figure 4].32-34 Valve repair is most likely to be feasible in patients with myxomatous disease, especially if such disease involves the posterior leaflet, and is least likely to be successful in patients with rheumatic disease and endocarditis.34,35 Valve repair is accomplished by use of a variety of techniques, depending on the mechanism and etiology of the regurgitation. Such techniques include partial leaflet resection, chordal shortening or transfer, and insertion of an annuloplasty ring to reduce the size of the annulus. Long-term failure of repair occurs at a rate of 1% to 2% a year but is higher in patients with rheumatic disease. If mitral valve repair is not possible, a mitral prosthesis is implanted.35 Chordal and papillary muscle preservation is increasingly being employed when a mitral prosthesis is inserted, because preserving the muscles has been shown to help conserve left ventricular function after surgery.
Figure 4 Transesophageal echocardiogram of a patient with severe myxomatous mitral regurgitation (MR) (a) before and (b) after mitral valve repair.
Mitral valve prolapse
Mitral valve prolapse is a common condition in which the mitral valve leaflets are displaced in systole into the left atrium.3 It is usually caused by myxomatous degeneration of the valve and can occur in some form in up to 3% of the general population; it is more common in women than in men. In the majority of cases, mitral valve prolapse represents a benign abnormality; in a minority, mainly older men, significant mitral regurgitation results from rupture of a chord or from endocarditis and requires surgical intervention. Mitral valve prolapse is associated with low body weight, low blood pressure, and thoracic skeletal abnormalities such as pectus excavatum. Patients with mitral valve prolapse have a slightly increased risk of stroke, myocardial ischemia, and sudden death. Ventricular extrasystoles are common and can be symptomatically troublesome. Other arrhythmias, such as ventricular or supraventricular tachycardia, are reported but are uncommon.
Diagnosis
Mitral valve prolapse has been associated with multiple nonspecific symptoms, such as atypical chest pain, presyncope, anxiety, and panic attacks. These symptoms are more commonly reported by women than men. A causal relation between these symptoms and mitral valve prolapse has not been established.
A midsystolic click at the mitral area during cardiac auscultation is often the finding that first brings mitral valve prolapse to the attention of the examiner. The click has been attributed to tensing of the redundant valvular tissue with cardiac contraction. A late systolic murmur can follow the click. Maneuvers that reduce intracardiac volume, such as having the patient stand or perform the Valsalva maneuver, cause the click to occur earlier in systole and cause an increase in the duration of the murmur. The typical auscultatory findings and their response to these maneuvers are sufficient to make a diagnosis of mitral valve prolapse.
Two-dimensional echocardiography is the method of choice to confirm the diagnosis. Apparent systolic displacement beyond the annular plane is possible with both M-mode and two-dimensional approaches because the annulus is nonplanar and saddle-shaped. The possibility of a false positive diagnosis can be minimized by seeking systolic displacement of the leaflets in a parasternal long-axis view. Myxomatous mitral valve leaflets frequently are thicker, are more redundant, and have longer chordae than normal as seen on echocardiography. Doppler echocardiography is used to detect and quantify associated regurgitation.
Treatment
Asymptomatic mitral valve prolapse requires no specific treatment. Periodic examination is indicated to detect any progression in the severity of mitral regurgitation. Prophylaxis for endocarditis is indicated if both a click and a murmur are present but is not indicated in the absence of mitral regurgitation.37 Symptomatic ventricular ectopy often responds to beta blockade. Many patients with atypical chest pain and other nonspecific symptoms improve when they are reassured of the relatively benign nature of the condition. Empirical treatment with small doses of beta blockers can also provide symptomatic relief. Mitral regurgita-tion should be treated as described earlier.
Aortic stenosis
The normal aortic valve is 3 to 4 cm2 in area when fully open. Aortic stenosis is considered severe when the valve area is 1 cm2 or less and is considered critical when the area is less than 0.75 cm2. Aortic stenosis causes concentric left ventricular hypertrophy as a compensatory mechanism that maintains cardiac output at rest despite the increased pressure gradient across the valve. Eventually, this compensatory mechanism is overcome, causing the left ventricle to fail and dilate and the resting cardiac output to decline.
Diagnosis
Clinical manifestations There is a variable relation between the severity of stenosis and symptoms. Many patients with critical aortic stenosis are asymptomatic, whereas patients in states of volume overload, such as pregnancy, may have symptoms with stenosis of lesser severity. Dyspnea is often the presenting feature; it reflects increased left atrial pressure and pulmonary venous hypertension from the increased left ventricular pressure in systole and the diastolic ventricular dysfunction imposed by left ventricular hypertrophy. Angina is common even in the absence of significant obstruction in the epicardial coronary blood vessels because of impaired supply of blood to the subendocardium in the hypertrophied left ventricle. Exertional syncope also occurs with stenosis and can result from the inability to increase cardiac output sufficiently to supply both skeletal muscle and the cerebral vasculature, resulting in impaired cerebral blood supply, or from abnormal baroreceptor reflexes. Serious arrhythmia can also cause syncope and, in severe aortic stenosis, even sudden death. Fatigue is common because of low cardiac output.
In severe aortic stenosis, the carotid pulse typically is reduced in intensity and has a slow delayed upstroke. Aortic stenosis gives rise to a systolic murmur that is heard over the aortic area and that can radiate to the carotid arteries and to the apex. In severe stenosis, the murmur peaks later in systole and can be associated with a thrill. A fourth heart sound is usually present. In mobile congenitally abnormal valves, an ejection click can precede the murmur. Severe calcific aortic stenosis is often associated with a diminished intensity of the aortic component of the second heart sound. Although the physical findings are important in alerting the clinician to the presence of aortic valve disease, the degree of hemodynamic severity is more reliably determined with Doppler echocardiography.
Imaging studies The presence of left ventricular hypertrophy on electrocardiography provides useful supporting evidence for significant aortic stenosis. Doppler echocardiography is used to determine the mechanism and the hemodynamic severity of the stenosis as well as the effects on left ventricular size and function. In aortic stenosis, the opening of the aortic valve is reduced, as seen on the echocardiogram. Continuous wave Doppler echocardiogra-phy is used to measure the peak velocity across the valve and thus the aortic pressure gradient; the mean pressure gradient across the valve is often 50 mm Hg or more in patients with severe aortic stenosis. However, the pressure gradient is determined not only by the degree of stenosis but also by flow through the valve and can be relatively low despite severe aortic stenosis if cardiac output is reduced. In most instances, therefore, the valve area as well as the pressure gradient should be calculated. The valve area is estimated readily from the flow through the valve and the pressure gradient across the valve. With cardiac catheterization, the pressure difference across the aortic valve between the left ventricle and the aorta is measured directly. Valve area can be calculated from the cardiac output and the pressure gradient. Because Doppler echo-cardiography and invasive measurements of aortic valve severity have been shown to agree when both are performed expertly, cardiac catheterization is now used less often as the primary diagnostic tool in assessing aortic stenosis [see Figure 5 ]. Cardiac catheteri-zation is used to confirm the echocardiographic findings in patients being considered for surgery or when there is significant discrepancy between the clinical findings and echocardiography: findings.
Treatment
Indications for surgery Aortic stenosis is a progressive disease, and patients with the disease can remain asymptomatic for many years. The rate of progression varies greatly but increases with age, associated coronary artery disease, and the severity of the stenosis.38 Progression to symptoms or intervention is likely within 2 years in older patients with severe asymptomatic aortic stenosis.37 Once symptoms become manifest, the survival rate without surgical treatment is reduced; mean survival is 5 years in patients with angina, 3 years in patients with syncope, and 2 years or less in patients with heart failure.38 Operative mortality increases with severe symptoms, advanced age, and the presence of left ventricular dysfunction. The onset of symptoms, therefore, is the major indication for surgical intervention. Left ventricular dysfunction attributable to aortic stenosis is another indication for intervention because it demonstrates failure of compensatory mechanisms and incipient symptoms. Sudden death can occur with aortic stenosis, but this is rare in the absence of symptoms. Patients should be instructed to report the onset of any symptoms and should undergo regular follow-up evaluations with physical examination and Doppler echocardiography. Doppler examination should be performed at least yearly and should be performed more frequently in patients with severe stenosis and in older patients. Surgical relief of aortic stenosis usually leads to relief of symptoms and improvement in left ventricular function when such function was abnormal preoperatively.
Aortic valve surgery in the very elderly is associated with an increased mortality but provides excellent palliation of symptoms; surgery should be considered for such patients provided they are otherwise viable candidates.39 Patients with severe left ventricular dysfunction resulting from aortic stenosis should also be considered for surgery, because significant improvement in ventricular function and symptoms often results, and without surgery the survival rate in these patients is poor.
Figure 5 Simultaneous left ventricular (broken blue line) and aortic (solid blue line) pressure tracings and continuous wave Doppler tracing in a patient with severe aortic stenosis. The pressure gradient (P-P, or 30 mm Hg) is the area between the aortic and LV tracings. Maximal pressure gradient (Max) by cardiac catheterization (60 mm Hg) is similar to that measured by Doppler echocardiography (64 mm Hg).
Surgical intervention Surgical intervention for patients with aortic stenosis usually involves insertion of a prosthesis or a human valve. In congenital aortic stenosis, valve repair or commis-surotomy can be feasible, although significant aortic regurgita-tion can result. Balloon valvuloplasty has proved disappointing in the long-term treatment of adult calcific aortic stenosis. Valve area typically increases from 0.5 cm2 to 0.8 cm2 and is associated with improvement of symptoms in the majority of cases.18 However, stenosis recurs in as many as 50% of patients within 6 months, and fewer than 25% survive more than 3 years.40 Balloon valvuloplasty is now indicated in the palliative treatment of adult patients with aortic stenosis who are not surgical candidates because of significant comorbidity; it is also used to stabilize critically ill patients for whom surgery is planned at a later stage. Balloon dilatation is effective in young patients with congenital aortic stenosis and is an alternative to surgery in symptomatic aortic stenosis during pregnancy.
