Susan A. Mayer
Edward P. Shapiro
The past two decades have seen significant changes in the techniques used for the diagnosis of, and the strategies for intervention in, valvular heart disease. For a detailed review and discussion of controversial aspects, the reader is referred to the American College of Cardiology/American Heart Association Guidelines for the Management of Patients with Valvular Disease, published in its full form (1) or executive summary (2). These valuable aids can be accessed on the Internet at http://www.acc.org and http://www.americanheart.org, respectively.
Heart Sounds
First Heart Sound (S1)
The first heart sound (S1) is a high-frequency sound produced by closure of the atrioventricular (AV) valves, that is, M1 (mitral valve closure) followed closely by T1 (tricuspid valve closure). Mitral valve closure is louder than tricuspid valve closure.
Abnormally wide splitting of the first heart sound is produced by delays in closure of the tricuspid valve (as in patients with right bundle-branch block), ventricular ectopic beats, idioventricular rhythm, or left ventricular (LV) pacing. In mitral stenosis, mitral valve closure may be so delayed that tricuspid valve closure may actually precede mitral valve closure.
Increased intensity of the first heart sound is associated with a rapid increase in ventricular pressure, which occurs when the ventricles are presented with an increased volume (e.g., ventricular septal defect and atrial septal defect) or with a wide-open AV valve at the end of diastole, which occurs when there is shortening of the AV filling time (e.g., atrial tachycardia and conditions associated with a short PR interval) and when AV filling time is prolonged (e.g., mitral stenosis).
Reduced intensity of the first heart sound may indicate an immobile valve (e.g., severe mitral regurgitation or stenosis) or a long PR interval.
Second Heart Sound (S2)
The second heart sound (S2) is produced by closure of the semilunar valves, that is, A2 (aortic valve closure) followed closely by P2(pulmonic valve closure). Normal splitting of the second heart sound occurs at the height of inspiration,
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when the splitting may be as wide as 0.10 seconds, and is caused by the increase in stroke volume in the right heart with the increase in venous return with inspiration. The two components of the second heart sound normally are synchronous and virtually single during expiration.
Abnormally wide splitting of S2 without change in expiration is characteristic of an atrial septal defect or anomalous pulmonary venous return. S2 is widely split but variable in patients with right bundle-branch block or pulmonic stenosis. In the presence of severe aortic stenosis, A2 is delayed beyond P2, resulting in wide splitting during expiration with no splitting during inspiration (reversed or paradoxical splitting). Paradoxical splitting of the second heart sound also occurs in the presence of a left bundle-branch block, severe hypertension, or severe LV failure.
Increased intensities of A2 and P2 are features of aortic and pulmonary hypertension, respectively. Decreased intensities of A2 or P2 are features of an immobile or severely thickened aortic or pulmonic valve.
Gallops
The identification of a gallop sound affords valuable information about diagnosis, prognosis, and treatment. Gallops are diastolic sounds and appear to be related to the two periods of filling of the ventricles: the rapid filling phase (S3, or ventricular diastolic gallop) and the presystolic filling phase related to atrial systole (S4, or atrial gallop).
The atrial gallop sound, or S4, is a low-frequency presystolic sound and is found in patients with primary myocardial disease, coronary artery disease, systemic or pulmonary hypertension, or severe aortic or pulmonic stenosis. The atrial gallop indicates severity of the underlying disorder; as the patient's condition improves, the sound may become fainter or disappear. With ventricular hypertrophy, an S4 is a fixed finding of no prognostic significance. An atrial gallop is commonly heard in people older than 65 years, even in the absence of heart disease or hypertension (see Doppler echocardiography in Clinical Applications of Echocardiography).
The ventricular gallop sound, or S3, is a low-frequency sound (see Chapter 66). It occurs with the same timing as the normal physiologic third sound, approximately 0.14 to 0.16 seconds after the second heart sound. The third sound is a normal finding in children, pregnant women, and young adults up to age 30 years (see Doppler Echocardiography in Clinical Applications of Echocardiography). An S3 gallop otherwise is a feature of severe cardiac decompensation, whatever the underlying cause (e.g., hypertension, coronary artery disease, rheumatic heart disease), and indicates a poor prognosis.
Ejection Sounds (Clicks)
Ejection sounds are produced at the time of ejection of blood from the left ventricle into the aorta or from the right ventricle into the pulmonary artery. The sound may originate in a thickened valve or dilated great vessel. The aortic ejection sound is located in the area of aortic auscultation, namely, from the second right intercostal space in a straight line to the cardiac apex, and occurs 0.05 seconds after M1. It is a high-frequency sound, often called a click. In the presence of systemic hypertension, the aortic ejection sound is an indication of severity. It disappears as hypertension improves. Aortic ejection clicks may also be heard in patients with aortic stenosis, aneurysm of the ascending aorta, and aortic insufficiency.
Pulmonic ejection sounds (or clicks) often are localized to the second left intercostal space and may increase in intensity with expiration. They occur immediately after M1. Pulmonic clicks are a feature of valvular pulmonic stenosis and pulmonary hypertension.
A midsystolic clicking sound, with or without a late systolic murmur, may indicate mitral valve prolapse (see below).
Opening Snaps
An opening snap occurs because of a stenotic, but still mobile, mitral or tricuspid valve. The mitral opening snap is best heard between the pulmonic area and the cardiac apex. It occurs 0.04 to 0.12 seconds after S2 in early diastole. It is heard in patients with a thickened mitral valve. The earlier the snap, the more severe the stenosis. The tricuspid opening snap is best heard at the lower left or right sternal border and occurs immediately after S2 in early diastole.
Murmurs
Evaluation of a heart murmur is one of the most common tasks confronting a practitioner conducting a physical examination. Almost all normal people have a systolic murmur at some time in their lives. On the other hand, a murmur may be a sign of serious underlying cardiac or noncardiac disease. It is important to distinguish innocent murmurs from those that reflect an underlying disorder and to appropriately select the tests that will lead to the precise diagnosis and proper management.
General Characteristics of Murmurs
A murmur is a series of audible vibrations produced by turbulence in the circulation. These vibrations can be characterized by intensity, pitch, shape, quality, and timing in the cardiac cycle; precordial location of maximal intensity; and radiation.
The intensity or loudness of a murmur is, by convention, graded on a scale from 1 to 6. A grade 1 murmur is audible only after concentrated auscultation. A grade 2 murmur is faint but readily audible. A grade 3 murmur is prominent
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but not loud. Grade 4 murmurs are loud and often, but not always, are associated with a palpable thrill. A grade 5 murmur is very loud and can be heard with only the edge of the stethoscope touching the chest wall. A grade 6 murmur is heard with the stethoscope held 1 cm above, but not actually touching, the chest wall.
The pitch of a murmur refers to the frequency of the sound, from high to low. High-frequency murmurs usually reflect high velocity or high pressure.
The shape of a murmur refers to the change in intensity throughout the duration of the sound, for example, crescendo (increasing in intensity), decrescendo (decreasing in intensity), or constant.
The quality of a murmur refers to the nature of the sound: harsh, blowing, musical, cooing, rumbling, and so forth. Although these terms are not precise, they are useful in identifying various benign and significant conditions, as described below.
The timing of a murmur is particularly important in establishing the cause of the sound—first, whether the murmur is systolic, diastolic, or continuous and, second, whether it is heard in early, middle, or late systole or diastole. Murmurs that last throughout systole are calledholosystolic. Late diastolic murmurs are sometimes called presystolic.
The location of a murmur refers to the site on the chest wall where the sound is loudest. The direction of radiation refers to the other sites where the murmur, although less intense, can still be heard; those sites may be outside the chest (e.g., the back or neck). Aortic murmurs may be heard anywhere in a straight line from the second right interspace to the apex. Pulmonic murmurs are heard best at the second left intercostal space; tricuspid murmurs, at the lower left sternal border; and mitral murmurs, at the cardiac apex radiating into the axilla.
There are two kinds of systolic murmurs: ejection and regurgitant. The ejection systolic murmur may be an innocent flow murmur, or it may reflect organic heart disease. The regurgitant murmur may be caused by dilation of the annulus of the valve in an otherwise normal heart, or it may represent organic heart disease.
The ejection murmur is a crescendo–decrescendo (or diamond-shaped) murmur caused by the turbulence of blood flowing through either the aortic or the pulmonic valve. The murmur is most commonly midsystolic and ends before the second or closing sound (S2) of the valve from which the murmur was generated, that is, aortic ejection murmurs end before A2 and pulmonic ejection murmurs end before P2. The loudness of the murmur depends in part on the pressure gradient across the valve and in part on other factors, such as thickness of the chest and the cardiac output. The shape depends on the acceleration and deceleration of blood flow across the valve as systole proceeds. When diastole is prolonged, for example, by a premature ventricular contraction, ejection murmurs become louder because of the passage of a large volume of blood through the valve. In general, the greater the cardiac output, the louder the murmur. Increases in cardiac output caused by hypermetabolic states, such as anemia, fever, or thyrotoxicosis, increase the loudness of the murmur. Decreases in cardiac output, as in congestive heart failure, decrease the loudness of the murmur.
The regurgitant murmur is a murmur produced by backward flow of blood from a high-pressure chamber to a compartment of lower pressure. Intensity may be constant, as in mitral regurgitation, tricuspid regurgitation, or ventricular septal defect, or it may be decrescendo, as in aortic and pulmonary regurgitation.
A number of maneuvers can be performed to alter the intensity of a systolic murmur and to help determine its origin. For example, the strain phase of the Valsalva maneuver reduces intrathoracic venous return and softens the murmur of aortic stenosis while intensifying that of hypertrophic cardiomyopathy (HCM). Squatting, which increases venous return, has the opposite effect. Isometric handgrip, which increases blood pressure and therefore reduces forward flow, softens the murmur of aortic stenosis and intensifies that of mitral regurgitation.
Innocent Murmurs
Innocent murmurs are a series of vibrations that are produced in the absence of significant abnormalities of cardiac anatomy or function (Table 65.1). Innocent murmurs usually can be distinguished from significant murmurs by the absence of other physical, radiologic, or electrocardiographic evidence of disease. Also, innocent murmurs usually are in early systole or midsystole, are grade 1 or 2 in intensity, and vary with respiration and position. Occasionally, echocardiography (see below) is performed to clarify the cause of a murmur, but more elaborate studies, such as stress tests, radionuclide studies, and cardiac catheterization, are used only after a murmur is determined to be not innocent and a more precise diagnosis is necessary.
The most common innocent systolic murmur of childhood and young adulthood that is clearly recognizable as benign based on the characteristics of the murmur alone is the musical or vibratory midsystolic murmur (best heard at the lower left sternal border) caused by the vibration of the leaflets of the pulmonary valve.
The venous hum is a continuous murmur, loudest in the neck, caused by altered flow through the jugular veins. It
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can be eliminated by turning the patient's head, compressing the internal jugular vein on the side where the murmur is heard, or placing the patient in the supine position.
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TABLE 65.1 Benign or Innocent Systolic Murmurs |
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The pulmonic ejection systolic murmur is a systolic crescendo–decrescendo murmur generated by the flow of blood through the pulmonary valve. It is loudest in the left second intercostal space or at the midleft sternal border.
Similarly, the aortic ejection systolic murmur is an early systolic murmur generated by the flow of blood through the aortic valve. It is loudest in the right second intercostal space or at the apex of the heart. This innocent or flow murmur, caused by sclerosis of the aorta or the aortic valve, is the most common benign systolic murmur in middle-aged or elderly patients and may have a cooing quality. An echocardiogram may be necessary to rule out LV hypertrophy and aortic stenosis.
Benign flow murmurs are commonly heard in pregnant women. Because of the normally increased stroke volume at 28 to 30 weeks of gestation, diastolic filling sounds and systolic ejection murmurs of turbulent flow are common. In pregnant women, an S3 may be prominent enough to be confused with the mid-diastolic murmur of mitral stenosis. The S3 of pregnancy may be distinguished from the murmur of mitral stenosis, however, by the absence of an opening snap and by the accompanying hyperdynamic apical movement. An echocardiogram is indicated occasionally in some patients to make a precise diagnosis.
In a pregnant woman it is critical to compare the femoral and brachial pulses and the blood pressures in the presence of a heart murmur because coarctation of the aorta may present with a soft heart murmur and, if left untreated, may rarely result in aortic dissection or rupture.
Clinical Applications of Echocardiography
Echocardiography is a valuable adjunct to the clinical assessment of patients suspected of having cardiovascular disease (3). This technique uses high-frequency pulsed sound waves to record echoes of cardiac structures as they move within a beam of sound directed into the chest.
To record a transthoracic M-mode echocardiogram, an ultrasound transducer is placed at one point on the chest wall and rocked to inscribe an arc that encompasses several areas of the heart sequentially. The transducer serves as a source of the sound beam and as a receiver of the echoes. A transthoracic two-dimensional (2D) echocardiogram is recorded using a pulse transducer that is automatically directed across an arc, providing a simultaneous view of the cardiac structures, which is recorded on videotape. Both modes usually are combined and reported together. These procedures do not cause discomfort, but ideally the patient must be able to lie flat for approximately 30 to 45 minutes for performance of the test.
Echocardiography allows visualization of all four cardiac valves, the aortic root, both atria, the right ventricle, the left ventricle including all individual wall segments (Fig. 65.1), and the pericardium. The size and function of these structures are analyzed and patterns of specific diseases may be recognized.
M-mode echocardiography provides a one-dimensional or “ice pick” view of cardiac structures moving over time. It can be used to measure LV wall thickness and chamber size and to detect some valvular conditions. It has largely been supplanted by 2D echocardiography.
Two-dimensional echocardiography is particularly helpful in assessing LV function in patients with ischemic heart disease, in whom regional structure and function are most important. It should be understood that echo assessment of overall or regional LV function usually is semiquantitative. Wall motion usually is categorized as normal or as mildly, moderately, or severely depressed. An ejection fraction, if reported, often represents a visual estimate by the echocardiographer. Small differences reported in serial studies of the same patient, therefore, may not represent an important change unless the studies have been compared side by side by the same observer. LV systolic function can be quantitated by tracing the endocardial border of the left ventricle at end diastole and end systole in one or more tomographic planes. This technique is limited to patients with adequate endocardial border definition. The Food and Drug Administration has approved two intravenous contrast agents, Definity and Optison, which are microbubbles <10 µm in size with a high acoustic impedance and reflect ultrasonic transmissions better than blood (4). After administration of a contrast agent, the left ventricle is opacified with enhanced endocardial border definition, allowing a more accurate measurement of LV ejection fraction (5).
The noninvasive nature of the test, the lack of associated risks, and its ease of performance make 2D echocardiography extremely important in the evaluation of clinical signs and symptoms in patients with chest pain, palpitations, heart failure, cardiac murmurs, cardiomegaly, hypertension, and a systemic embolic event. The 2D echocardiogram can be diagnostic in cases of valvular heart disease, cardiomyopathy, congenital heart disease, aortic disease, intracardiac masses, pericardial effusion, and pericardial disease. Also, various echocardiographic indices of cardiac function and size add prognostic value to patients with cardiovascular disease. For example, assessments of left atrial size, left and right ventricular size and function, and LV diastolic function provide prognostic information on patients with heart failure (6). The 2D echocardiogram is an important screening tool in first-degree relatives (parents, siblings, and children) of patients with genetic cardiovascular diseases, such as bicuspid aortic valve (7), HCM (8), Marfan syndrome, and other related connective tissue disorders (9).
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FIGURE 65.1. The four basic views of the two-dimensional echocardiogram. Tomographic slices obtained from different vantage points and angles reveal valvular structure and all left ventricular walls. Top left: Parasternal long-axis view demonstrating septum and posterior wall. Top right: Parasternal short-axis view displaying a “bread loaf” slice of the left ventricle. Bottom left: Apical four-chamber view revealing septum, apex, and lateral wall. Bottom right: Apical two-chamber view revealing inferior wall, apex, and lateral wall. |
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Doppler echocardiography is an extremely useful tool for the detection and quantification of the severity of valvular heart disease. High-frequency sound is directed at a column of moving red blood cells, and the reflected sound is analyzed for changes in frequency, which indicate the direction and velocity of flow. Flow velocity information is color coded and superimposed on the 2D echocardiographic image, providing visual representation of blood flow through the heart and great vessels.
In valvular stenosis, a high-velocity jet of blood is detected distal to the stenosis; the higher the transvalvular gradient, the higher the velocity of the jet. The pressure gradient across a valve and the area of the aortic (10,11) and mitral (12) valves can be calculated, providing precise quantification of the severity of aortic and mitral stenosis.
Valvular regurgitation can be detected by reverse flow and its severity estimated, usually by visualization of the origin, width, direction, and extent of the regurgitant jet in the receiving chamber by color flow Doppler (13). For example, mitral regurgitation is considered severe on a color Doppler study if a central regurgitant jet occupies >40% of the area of the left atrium during systole (14). The qualitative assessment of mitral regurgitation can be difficult, especially with eccentric regurgitant jets. For the severity of aortic and mitral regurgitation, the American Society of Echocardiography has recommended the quantitative assessment of valvular regurgitation (13), and this has been shown to be a powerful predictor of clinical outcomes in patients with asymptomatic mitral regurgitation (15). A small degree of tricuspid regurgitation usually is seen in normal subjects and does not represent disease. The presence of tricuspid regurgitation allows estimation of right ventricular systolic pressure, which is equal to the pulmonary artery systolic pressure in the absence of pulmonic stenosis. This is useful in the detection and followup of patients with pulmonary hypertension of any cause. Small
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amounts of mitral and pulmonic regurgitation usually are seen in normal people and are not a cause for concern if the echocardiographer comments that the extent is “mild.” Small amounts of aortic regurgitation are frequently seen and are considered normal if their extent is graded as “trivial.”
Doppler echocardiography often is used to detect diastolic dysfunction (16,17), a frequent contributor to the development of congestive heart failure, especially in the elderly (see Chapter 66). The normal diastolic flow pattern consists of two phases: passive filling during early diastole (termed the E wave), which is aided by elastic recoil of the ventricle, and filling during late diastole (termed the A wave) due to atrial contraction. In young normal people, the left ventricle is pliable, and elastic recoil during diastole is vigorous, resulting in brisk early filling and hence a large E wave. Very little filling then remains to be accomplished during late diastole, hence a small A wave occurs. The ratio of early to late filling (E/A ratio) therefore is high, typically approximately 1.5 to 2.0 in normal people in their thirties or forties. However, the left ventricle loses its pliability in patients with LV hypertrophy, other forms of chronic heart disease, and even during the process of normal aging. Early diastolic elastic recoil then becomes ineffective in aiding filling, and the E wave becomes small. To compensate, a substantial proportion of filling must occur during late diastole, and the A wave enlarges. The E/A ratio thus is reduced. When the ratio falls to <1, “grade I diastolic dysfunction” is said to be present. This pattern is also called “abnormal relaxation.” Grade I diastolic dysfunction is a normal finding in people older than 65 years.
However, the E/A ratio is an imperfect index of diastolic function because the velocity of early LV filling depends on several factors in addition to LV relaxation. For instance, a high left atrial pressure, which occurs in congestive heart failure, causes a high AV pressure gradient, which accelerates early filling irrespective of LV stiffness, resulting in a large E wave and a high E/A ratio. This pattern is calledpseudonormalization of the E/A ratio, or “grade II diastolic dysfunction.” Distinguishing pseudonormal from normal may require ancillary Doppler procedures, such as repeating the recording during a Valsalva maneuver, measuring flow through the pulmonary vein, or tissue Doppler imaging of mitral annular motion. However, the presence of grade II diastolic dysfunction should be considered likely in the elderly and in people with LV hypertrophy who are found to have a high E/A ratio, because these individuals are likely to have grade I diastolic dysfunction at baseline. Common causes of grade II diastolic dysfunction include systolic dysfunction, valvular heart disease, fluid overload, and myocardial ischemia. When grade II diastolic dysfunction occurs in the absence of those conditions, “diastolic heart failure” is considered to be present. This latter phenomenon is commonly seen in the elderly in the presence of LV hypertrophy or severe hypertension.
When the E/A ratio is >2.0, “grade III diastolic dysfunction” or a “restrictive pattern” is said to be present. This occurs in restrictive cardiomyopathy and constrictive pericarditis, but also in all conditions that cause grade II diastolic dysfunction, when they are severe.
Several conditions may produce the pattern of grade II or III diastolic dysfunction in the absence of congestive heart failure. For example, in significant mitral regurgitation that is well compensated, the left atrial pressure in early diastole may be elevated because of the large “v” wave, increasing the E/A ratio, but the mean diastolic pressure may not be high enough to cause pulmonary congestion. Also, in patients who have recently converted from atrial fibrillation to sinus rhythm, a transient atrial myopathy is often present, resulting in a small “A” wave and a high E/A ratio (18).
In patients in whom a large E wave is present, an S3 is often audible. These patients include normal people younger than 30 years, elderly patients with congestive heart failure, and patients with constrictive cardiomyopathy, in whom the early diastolic sound is called apericardial knock. In patients in whom a large A wave is present, an S4 is usually audible. These patients include normal elderly people and patients with LV hypertrophy resulting from hypertension or aortic stenosis.
A common limitation of standard transthoracic echocardiography is that ultrasound penetrates lung and bone poorly, and the available acoustic window is limited in many patients, resulting in poor-quality studies. The technique of transesophageal echocardiography (TEE) has extended the diagnostic utility of echocardiography by allowing high-quality studies, with markedly increased resolution, in all patients (19,20). Additional structures can be assessed, including the venae cavae, coronary sinus, pulmonary veins, atrial septum, atrial appendages, pulmonary artery, and ascending and descending aorta. Valve leaflets are seen with great clarity. Resolution is adequate to detect atheromas on the walls of the aorta. The method transforms a noninvasive imaging modality into a semi-invasive one; the procedure is similar to esophagoscopy and is often performed in an endoscopy unit, often on an outpatient basis. The patient is asked to fast for 6 to 8 hours and is treated with a pharyngeal topical anesthetic and intravenous sedation. The patient then is assisted in swallowing a small (i.e., 1-cm diameter) echo transducer mounted on a gastroscopelike tube. Visualization of the cardiac structures from the esophagus and stomach usually is accomplished in approximately 20 minutes. The examination may include the intravenous injection of agitated saline, which creates ultrasonic contrast via tiny bubbles, to assess for right-to-left shunting. Complications of TEE are rare and include inability to intubate the esophagus successfully (1.9%), pulmonary difficulties such as laryngospasm (0.14%), cardiac arrhythmias (0.5%), and bleeding (0.2%) (21,22). Esophageal perforation
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is extremely rare (21). TEE is contraindicated in patients with severe atlantoaxial joint disease with inability to flex the neck, history of radiation to the chest, perforated viscus, and esophageal pathology (e.g., varices, strictures, carcinoma, scleroderma, or diverticula). Respiratory compromise may occur in patients with severe underlying pulmonary disease or obstructive sleep apnea, and an anesthesiologist may need to be consulted for assistance with patient management during the study.
The indications for TEE are evolving. The method allows visualization of almost the entire aorta and is sensitive (97.7%) and specific (76.9%) in the diagnosis of aortic dissection (23). The method is much better than transthoracic echocardiography for visualizing cardiac sources of embolus, such as thrombus in the left atrium or left atrial appendage, sluggish blood flow in the left atrium (spontaneous echo contrast), atrial septal aneurysm, patent foramen ovale, and complex aortic atheromas, sometimes with attached thrombus. Therefore, it often is ordered in patients with cryptogenic strokes (i.e., strokes in patients without evidence of atheroma in the carotid or vertebral systems). Because TEE can detect left atrial thrombi with a high degree of accuracy, TEE can guide treatment of patients with recent-onset atrial fibrillation who are being considered for cardioversion (24). This is the method of choice for assessing the function of prosthetic mitral valves and for visualizing vegetations or intracardiac abscesses caused by endocarditis. TEE is sometimes indicated when transthoracic echo quality is poor and information about cardiac structure or function is deemed crucial.
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TABLE 65.2 Comparison of Valvular Aortic Stenosis and Hypertrophic Cardiomyopathy |
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Selected Disorders Associated with Abnormal Heart Sounds
Aortic Stenosis
Stenosis of the aortic valve obstructs the flow of blood into the aorta and therefore raises the LV pressure above the aortic pressure. The pressure gradient across the valve is related to the severity of the stenosis. The elevated pressure results in a concentric hypertrophy of the left ventricle. Symptoms develop when the left ventricle can no longer compensate for the pressure load; the heart fails and the cardiac output declines.
Aortic stenosis may occur at any one of several levels. The most common obstruction (75% of patients) occurs at the aortic valve, although patients with subvalvular and supravalvular aortic stenosis may have symptoms and signs of severity similar to those of valvular disease. It is particularly important to differentiate fixed aortic outflow obstruction from HCM, in which the obstruction is dynamic in nature (Table 65.2).
Hemodynamically significant stenosis usually is associated with a gradient ≥50 mm Hg (unless cardiac output is reduced, in which case the gradient may be much lower even if there is severe stenosis). The effective aortic valve orifice in patients with severe obstruction usually is <0.4 or 0.5 cm2 per square millimeter of body surface area (compared to 1.6–2.6 cm2 per square millimeter in normal people). Many laboratories report absolute, rather than normalized, valve areas. At some centers, aortic stenosis is considered severe if the valve area is <0.75 cm2. At most centers, aortic valve areas of <1.0 cm2 are considered
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severe, 1.0 to 1.5 cm2 considered moderate, and >1.5 cm2 considered mild.
Causes and Epidemiology
In patients younger than 30 years, aortic stenosis most likely is caused by a congenitally stenotic unicuspid valve. Between the ages of 30 and 65 years, a bicuspid aortic valve, which has become calcified and gradually more rigid over the years, is the most common cause of aortic stenosis. A bicuspid aortic valve is found in 1% to 2% of the population, predominantly in men (25). Rheumatic valvular disease accounts for <25% of cases of isolated aortic stenosis in patients between the ages of 30 and 70 years. With the decline of rheumatic fever and the aging of the population, calcific aortic stenosis of an anatomically normal trileaflet valve has become the most common form of the disease encountered, present in 2% to 4% of adults older than 65 years (26). Evidence suggests that calcific aortic stenosis is a chronic, active inflammatory process associated with atherosclerotic risk factors rather than a degenerative process associated with aging (27). Except in the elderly, in whom the prevalence is the same in both sexes, isolated aortic stenosis is three to four times more common in men.
Natural History and Symptoms
Patients with aortic stenosis usually are asymptomatic until late in the course of their disease. Mild to moderate obstruction does not greatly compromise LV function, and even patients with severe stenosis may compensate for years before they develop symptoms. Patients with asymptomatic severe aortic stenosis have a 1% per year risk of sudden death (28). In a series of 622 adults with asymptomatic severe aortic stenosis, most patients became symptomatic within 5 years, and aortic valve area and LV hypertrophy predicted the development of symptoms (28). Once a patient develops symptoms, survival declines precipitously. If the lesion is not corrected, the average patient dies in approximately 4 years.
The earliest symptoms are easy fatigability and excessive dyspnea during or after strenuous exercise. Syncope or near-syncope with effort (see Chapter 89), angina (see Chapter 62), and dyspnea on usual exercise (see Chapter 66) are indicative of severe valvular obstruction. Patients with heart failure do not survive as long (2 years) as do patients with syncope (3 years) or angina (5 years) (29). Sudden death occurs in approximately 15% of symptomatic patients.
Physical Findings
Patients with aortic stenosis usually have a loud (grade 3–4) systolic ejection murmur. The maximal intensity of the murmur is located at the second right intercostal space or at the cardiac apex. The murmur often has a musical cooing quality at the apex. There is often a thrill in the suprasternal notch or the second right intercostal space. However, the loudness of the murmur may not correlate with the severity of stenosis. Also, if cardiac output is reduced, as in congestive heart failure, or if the diameter of the chest is increased, the intensity of the murmur may be less than expected. A late peak to the murmur suggests severe obstruction, but this may be difficult to appreciate with a stethoscope, and absence of the late peak does not mean that obstruction is not severe. Augmentation of the murmur when the patient suddenly squats and diminution of the murmur when the patient stands or performs a Valsalva maneuver are characteristic of aortic stenosis.
The systolic murmur, although it may not be loud, is an invariable sign of aortic stenosis. Other cardiac sounds depend on the nature of the stenotic lesion. An early systolic ejection click is commonly heard when the valve is still mobile. The second aortic sound (A2) often is not audible when the valve is so rigid that S2 has only one component (P2). Paradoxical splitting of the second heart sound, in the absence of left bundle-branch block, is a sign of severity. A small pulse pressure (<30 mm Hg) also indicates severe obstruction (in elderly people, the pulse pressure may be normal despite severe stenosis). A slowly rising pulse—best assessed by palpation of a carotid artery—is characteristic. Under age 40 years, an S4 is another sign of severe obstruction; over age 40 years, an S4 is common because of the high prevalence of hypertensive and ischemic heart disease and does not correlate with severity of stenosis.
Based on a review of available evidence of the precision and accuracy of the clinical examination for abnormal systolic murmurs, the likelihood of aortic stenosis is increased by the presence of effort syncope, slowly rising carotid pulse, mid or late systolic peak of murmur, soft or absent S2, apical to carotid delay, or brachioradial delay (30). The regurgitant early diastolic murmur of aortic insufficiency is heard in 30% to 40% of patients with aortic valve stenosis.
Laboratory Evaluation
An electrocardiogram (ECG), a chest x-ray film, and an echocardiogram should be obtained routinely in a patient suspected of having aortic stenosis.
Electrocardiogram
The ECG usually is normal until stenosis becomes severe, at which point LV hypertrophy (Table 65.3 and Fig. 65.2) and nonspecific ST depression and T-wave inversion are common but not invariable. In older patients particularly, an abnormal ECG cannot be relied upon to reflect severity because there are often other reasons why it might be abnormal.
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TABLE 65.3 Principal Electrocardiographic Features of Left Ventricular Hypertrophy |
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FIGURE 65.2. Electrocardiogram of a patient with left ventricular hypertrophy (Table 65.3). |
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Chest X-Ray Film
Calcification of the aortic valve is always present in patients older than 40 years with aortic stenosis, but often fluoroscopy is necessary to reveal it. Poststenotic dilation of the ascending aorta is also commonly seen. The heart size and configuration usually are normal until the disease is far advanced.
Echocardiogram
Echocardiography reveals immobile and usually calcified aortic valve leaflets. An increase in ventricular wall thickness on echocardiography implies severe obstruction if there is no other cause for hypertrophy. The severity of aortic stenosis can be accurately assessed in nearly all patients by Doppler echocardiography by measurement of the maximum aortic jet velocity, calculation of the maximum and mean transaortic pressure gradients, and determination of the aortic valve area by the continuity equation (31). Assessment of the aortic valve area by cardiac catheterization is recommended when the echocardiogram is nondiagnostic or when there is a discrepancy between the clinical picture and the echocardiographic data. The valve area is generally considered a better measure of severity of aortic stenosis than the gradient because the gradient may be deceptively low in the presence of reduced cardiac output caused by LV dysfunction, even with severe stenosis (see below). Doppler echocardiography is
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helpful in distinguishing aortic stenosis from aortic valve sclerosis, in which no significant gradient is present.
Management
Asymptomatic patients with mild or moderate disease should be reassessed every 12 months so that signs of progressive disease can be detected promptly. Reassessment should include interval history, pertinent physical examination, ECG, chest x-ray film, and echocardiogram. Current clinical guidelines recommend a transthoracic echocardiogram annually in severe asymptomatic aortic stenosis, every 2 years in moderate aortic stenosis, and every 5 years in mild aortic stenosis (1). Typically, the rate of progression in the aortic valve area is a decrease of 0.1 cm2 per year (26). The asymptomatic patient with severe aortic stenosis presents a management dilemma. Although sudden death is extremely rare in asymptomatic patients (approximately 1% per year) (28), symptoms may appear suddenly and progress rapidly to sudden death (as early as 3 months after symptoms appear). There is a 67% probability of remaining asymptomatic at 2 years and a 33% probability at 5 years with severe aortic stenosis (28). Although these factors suggest that prophylactic valve replacement might be indicated in asymptomatic patients with severe disease, this must be weighed against the operative mortality (3%–12%), the risk of prosthetic valve complications (1%–2% per year), and the fact that many patients would be operated on needlessly (32). Patients with moderate to severe asymptomatic aortic stenosis, therefore, should be referred to a cardiologist. However, many cardiologists recommend that asymptomatic patients be followed extremely closely without prophylactic surgery. These issues should be discussed with the patient. It is accepted practice to perform aortic valve replacement in asymptomatic patients with severe (and sometimes moderate) aortic stenosis who require open heart procedures, such as coronary artery bypass grafting or surgery involving the aorta, or in women contemplating pregnancy.
Patients should be cautioned to avoid undue exertion because acute heart failure, arrhythmia, and sudden death are more likely under such circumstances. Patients with mild aortic stenosis do not have to restrict their physical activity. On the other hand, patients with moderate aortic stenosis should not participate in competitive sports, and those with severe aortic stenosis should engage in only low-level activities (1). The risk of subacute bacterial endocarditis is increased in patients with aortic stenosis and is unrelated to the severity of the stenosis (the risk is unchanged after aortic valve surgery; see below). Therefore, antibiotic prophylaxis (see Chapter 93) is necessary before dental and surgical procedures. Because aortic stenosis is an inflammatory process similar to that of atherosclerosis, prospective studies are currently in progress to determine if statin therapy can retard the progression of calcific aortic stenosis. In one small, prospective study, patients with calcific aortic stenosis who did not have an indication for statin therapy were randomized to atorvastatin or placebo, with a median followup period of 25 months (33). Despite the intensive lipid-lowering effect, atorvastatin did not delay the progression nor cause regression of the disease process.
Atrial arrhythmias are uncommon; if they occur, they must be treated aggressively (see Chapter 64) because they are more likely to cause angina, heart failure, or syncope than in a patient without aortic stenosis. β-Blockers are best avoided in patients with severe aortic stenosis because the agents may compromise LV function. Heart failure, if it develops, should be treated with diuretics (see Chapter 66), but great care must be taken to avoid volume depletion, which may reduce cardiac output to a point where serious hypoperfusion of vital organs occurs.
Table 65.4 lists the indications for referral of a patient with aortic stenosis to a cardiologist. In general, referral is indicated if the diagnosis is unclear, if the patient is symptomatic, or if an asymptomatic patient has moderate to severe obstruction.
The cardiologist is likely to recommend replacement of the stenotic aortic valve with a prosthesis in all symptomatic patients and in asymptomatic patients with signs of severe obstruction who are found to have LV dysfunction or other high risk features. Coronary angiography is required in most patients prior to valve surgery to assess the patency of the coronary arteries to determine if concomitant coronary artery bypass graft surgery is needed.
Operative mortality is 1% to 9% in patients without LV failure (26) and 10% to 25% in patients with LV failure (34). The patient's postoperative health and long-term survival depend on a number of factors (including age, general health, and LV function), but overall, the 5-year
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survival is approximately 80% to 85% and the 10-year survival is approximately 70% to 75%. Most patients experience a considerable improvement in their sense of well-being and exercise tolerance. Death, if it occurs, usually results from a cardiac complication (heart failure, myocardial infarction, or sudden death). (For further details regarding the long-term course and management of the patient with a prosthetic valve, see below.)
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TABLE 65.4 Indications for Referral of Patients with Aortic Stenosis |
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The proper management of aortic stenosis in the elderly is a common clinical challenge. The prognosis in unoperated patients is very poor. In a study of 50 patients with a mean age of 77 years who were offered surgery but refused, only 57% were alive at 1 year and 25% at 3 years (35). In a study of aortic valve replacement in the elderly (36), a group of 44 octogenarians undergoing aortic valve replacement was compared with a group of 83 younger patients undergoing the procedure. Although the early mortality was higher in the elderly (14% vs. 4%), 2-year survival rates were similar (73% vs. 90%, an insignificant difference), the incidence of valve-related complications was comparable, and the total duration of hospital stay did not differ. Other studies confirm that aortic valve replacement is the most appropriate therapy for symptomatic elderly patients with aortic stenosis. Aortic valve replacement should not be withheld because of age itself, although intercurrent illness, common in the elderly, may complicate decision making.
Percutaneous balloon valvuloplasty is a technique in which one or more balloons are placed across a stenotic aortic valve and are then inflated in an attempt to reduce the severity of stenosis. This method has achieved excellent results in children with congenital aortic stenosis. In adults, it has been applied mainly to elderly patients or to those who are considered to be poor surgical candidates. Although the transaortic gradient usually is reduced and initial clinical improvement is achieved, overall results have not been encouraging because high rates of death (24%) and recurrences of severe symptoms of aortic stenosis (47%) have been reported within 6 months of the procedure (37). Long-term survival after the procedure is dismal and resembles the natural history of untreated aortic stenosis. At present, aortic valvuloplasty for adults has been abandoned at most centers and should be considered only in extraordinary circumstances, for example, for a severely symptomatic and hemodynamically compromised patient who requires urgent management of aortic stenosis as a “bridge” to aortic valve replacement.
Hypertrophic Cardiomyopathy
HCM is a disease of cardiac muscle characterized by severe myocardial hypertrophy in the absence of conditions that cause secondary hypertrophy of the heart muscle, such as hypertension and aortic stenosis. The left ventricle is hypercontractile and, during systole, ejects essentially all of its blood, leaving a “clenched fist” with very high wall stress. HCM has been called by a variety of names, including asymmetrical septal hypertrophy (because of predominant hypertrophy in the septal region) and idiopathic hypertrophic subaortic stenosis (because of the common presence of a dynamic outflow tract gradient) (38). However, some patients with HCM do not have asymmetrical septal hypertrophy and may have either concentric hypertrophy or only apical hypertrophy of the left ventricle. In addition, the majority of patients with HCM do not have a significant resting outflow tract gradient (38). In contrast to the microscopic appearance of secondary LV hypertrophy, in which the fibers are enlarged but are properly oriented, the myofibrils in HCM are characterized by myofibrillary disarray (8).
Causes and Epidemiology
The prevalence of HCM in young adults is thought to be approximately 2 per 1,000 (39) but is higher in the elderly. In fact, HCM is the most common genetic cardiovascular disease. The disease occurs as a familial inherited disease in approximately 60% of cases and as a sporadic disease, without affected first-degree relatives, in the remainder. Men and women are equally likely to be affected. In the familial form, the mode of inheritance is autosomal dominant in approximately 75% of pedigrees. A variety of missense mutations have been identified in patients with HCM, including mutations in the β-myosin heavy chain gene (chromosome 14), the cardiac troponin T gene (chromosome 1), and the α-tropomyosin gene (chromosome 15). All these genes code for sarcomeric proteins. The presence of these mutant components perturbs overall contractile function, and cardiac hypertrophy develops as a compensatory response.
Natural History and Symptoms
As echocardiography has become more widely used for the evaluation of patients with heart murmurs, it has become clear that most patients with HCM are asymptomatic or have only mild symptoms (38). Unless there is a family history of sudden death, the prognosis in this group is excellent. One study of 25 patients showed neither death nor progression of disease over a 4.4-year followup period (40).
The most common symptom of patients with HCM is dyspnea, but patients also often complain of angina (with or without evidence of occlusive coronary artery disease) and syncope or near-syncope. These symptoms are much more likely to be induced by exertion than to occur spontaneously. Once marked symptoms develop, some patients become rapidly worse, with progressive heart failure, angina, or arrhythmias.
The overall mortality for patients with HCM is <1% per year (8). However, a subset of patients are at high risk for sudden death, primarily from ventricular arrhythmias.
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The incidence of sudden death is approximately 3% to 4% per year in symptomatic patients with HCM, but some families have a particularly high incidence, depending on the specific mutation in the pedigree. For example, survival is poor in cardiac troponin T mutations but near normal in α-tropomyosin mutations (41). Some of the major clinical risk factors that are strong predictors of sudden death include a history of cardiac arrest, spontaneous sustained ventricular tachycardia, and a first-degree relative with a history of sudden death. Some of the minor clinical risk factors for sudden death are unexplained syncope, nonsustained ventricular tachycardia, LV wall thickness >30 mm, abnormal blood pressure response with exercise, LV outflow obstruction, and the presence of microvascular obstruction on a nuclear or magnetic resonance imaging study (38).
Physical Findings
Table 65.2 lists the clinical and laboratory features that distinguish aortic stenosis from HCM. The characteristic signs of the disease are a sustained LV apical impulse, a loud S4, and a harsh systolic ejection murmur, loudest at the left lower border of the sternum and often accompanied by a thrill. The location of the murmur helps to distinguish the condition from valvular aortic stenosis. Other distinguishing features are as follows: the second heart sound (A2) usually is audible, a diastolic murmur is rare, the pulse pressure is normal, ejection sounds are uncommon, and, most important, the upstroke of the carotid pulse is brisk. In addition, the murmur of HCM is augmented when the patient stands or during the strain phase of a Valsalva maneuver and is diminished when the patient squats—the opposite of the findings in patients with aortic stenosis. The murmur often diminishes rapidly during the release phase of the Valsalva maneuver.
Laboratory Evaluation
An ECG, chest x-ray film, and echocardiogram should be obtained routinely in patients suspected of having HCM. Genetic testing to identify a specific mutation is available at specialized medical centers, although the clinical value of this screening is uncertain.
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FIGURE 65.3. Chest x-ray film of a patient with atrial septal defect. |
Electrocardiogram
The ECG is abnormal in most patients and is always abnormal in patients with obstruction. Typically, there is evidence of LV hypertrophy (Fig. 65.2 and Table 65.3), and there is nonspecific ST depression and T-wave inversion. Q waves are often seen in the inferior and lateral leads, reflecting septal hypertrophy.
Chest X-Ray Film
The left ventricle is sometimes enlarged, but unpredictably so. In contrast to aortic valvular stenosis, the aortic valve is not calcified and the ascending aorta is not dilated.
Echocardiogram
Echocardiography is diagnostic; it usually demonstrates a thickened ventricular septum, hypertrophied out of proportion to the posterior wall of the left ventricle, although concentric or apical hypertrophy is sometimes present. Cavity obliteration, or near cavity obliteration, usually occurs during systole. The mitral valve apparatus moves anteriorly during systole (systolic anterior motion), and may contribute to obstruction of the outflow tract and to mitral regurgitation.
Management
The goal of therapy is to relieve symptoms by reducing the hypercontractile state of the left ventricle and the dynamic LV outflow tract obstruction. Currently, this is best accomplished using the calcium channel blocker verapamil (240 mg daily of long-acting formulation, maximum 480 mg daily) (38) unless the patient has signs or symptoms of heart failure or marked LV outflow tract obstruction. Alternatively, a β-blocker may be prescribed (e.g., metoprolol, 25 mg twice daily, with a maximum total dose of 600 mg daily, or an equivalent sustained-release preparation). Angina, especially, is often relieved by treatment, but dyspnea also may be decreased as a result of a slower heart rate and increased LV filling time. Although it is not clear that the risk of sudden death is reduced by therapy, most patients are symptomatically improved or at least stabilized by treatment. Disopyramide (initial dose of 100 mg of sustained-release formulation twice daily, maximum total dose 600 mg daily) (38), a type IA antiarrhythmic agent (see Chapter 64) with negative inotropic properties, has also been used successfully in patients with HCM and does not appear to be proarrhythmic in this patient population (42). However, long-term studies are necessary to assess for the efficacy and side effects of this therapy.
Drugs that increase ventricular contractility or decrease ventricular volume (digitalis, vasodilators, β-adrenergic stimulants, and diuretics) are best avoided, if possible. Patients, even if asymptomatic, should avoid undue exertion (e.g., running) and participation in competitive sports (43).
Patients with HCM have an increased risk for endocarditis and therefore should receive antibiotic prophylaxis before dental and surgical procedures (see Chapter 93).
Many patients with HCM eventually become refractory to beta blockers or verapamil or develop intolerable side effects from those medications. Two other therapies are also sometimes used in patients with HCM, especially when medications are ineffective or are poorly tolerated. First, dual-chamber cardiac pacing, even in the absence of bradyarrhythmias, may reduce the symptoms of angina,
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dyspnea, and presyncope over 6 to 12 weeks. Some (44,45), but not all (46,47), studies have shown that objective measures of disease, such as exercise treadmill time and outflow tract gradient, also improve with this therapy. Second, studies suggest that alcohol, injected during cardiac catheterization to produce septal ablation, is a helpful procedure in some patients. The alcohol is injected into a septal perforator branch of the left anterior descending coronary artery supplying the proximal septum and results in a controlled and localized myocardial infarction with thinning of the septum and reduction of the LV outflow tract gradient (48). Because of the controlled myocardial infarction and resultant scarring, there may be a potential risk for ventricular arrhythmias and sudden death.
An alternative to alcohol-induced septal ablation in patients who are severely symptomatic and refractory to medical therapy is surgical removal of a portion of the hypertrophied septum (septal myectomy). Improved surgical techniques have reduced the perioperative mortality of this procedure to 1% to 2% (49). However, the elderly are at higher risk for complications. Symptoms of heart failure are relieved through reduction of the LV outflow tract gradient, and long-term mortality is similar to that of the general population (50,51). However, this surgery is not widely available and is performed mainly at tertiary referral centers. Patients with HCM who show progression of symptoms or intolerance of medical treatment should be referred to a cardiologist and, if appropriate, to a cardiac surgeon for consideration of these alternative treatments.
For primary or secondary prevention of sudden cardiac death, an implantable cardiac defibrillator should be placed in patients who have major predictors of sudden cardiac death, such as history of cardiac arrest, sudden death in first-degree relatives with HCM, and sustained ventricular arrhythmias. Patients with three or more minor risk factors for sudden death, as discussed above, also should be considered for an implantable defibrillator. Once the diagnosis of HCM is made, patients should be risk stratified with an exercise treadmill test and a 48-hour Holter monitor.
Screening of first-degree relatives by echocardiography may detect other family members with the syndrome. Because there is a bimodal distribution of the disease process, an echocardiogram should be done approximately every 5 years to assess for the echocardiographic features of HCM. Referral to a center that can perform genetic testing to identify the specific mutation and offer genetic counseling also can be considered.
Atrial Septal Defect
Atrial septal defect of the ostium secundum type (in the midportion of the septum, known as the fossa ovalis) is one of the most common congenital cardiac diseases diagnosed in adults. It causes, until late in the course (see below), a left-to-right atrial shunt with volume overload of the right ventricle and overperfusion of the lungs. Ostium primum atrial septal defect, which occurs as part of the spectrum of endocardial cushion defects, is a less common form of this condition. It is often associated with trisomy 21 (Down syndrome).
Causes and Epidemiology
The defect is more common in females; the reported female/male ratio ranges from 1.5 to 3.5:1. Occasionally the defect is associated with other cardiac abnormalities, including mitral valve prolapse, pulmonic stenosis, and HCM.
Natural History and Symptoms
Patients with atrial septal defect usually are asymptomatic until their third or fourth decade. Thereafter, symptoms almost always develop (usually dyspnea on exertion, fatigue, and palpitations), the result of heart failure and supraventricular arrhythmias. Less commonly, symptoms of pulmonary embolism (see Chapter 59) or paradoxical embolism (e.g., a stroke) occur. Almost all patients are symptomatic by age 60 years. In fact, three fourths of untreated patients are dead by age 50 years and 90% by age 60 years. Increased pulmonary blood flow eventually produces pulmonary vascular disease and, consequently, pulmonary hypertension in approximately 15% of patients (52). When this happens, the left-to-right shunt first decreases and then reverses; at that point, cyanosis develops. Fortunately, this rarely occurs (52). Coexistent atherosclerotic or hypertensive cardiovascular disease may complicate the course of older patients with atrial septal defect and may make diagnosis and treatment more difficult.
Physical Findings
Atrial septal defect usually causes a wide fixed splitting of the second heart sound due to late closure of the pulmonic valve as a result of increased flow into the right atrium and right ventricle. A soft blowing systolic pulmonic ejection murmur and a low to medium frequency middiastolic flow murmur across the tricuspid valve are common. The precordium may be hyperdynamic with a palpable S3. If pulmonary hypertension has developed (see below), clubbing and cyanosis may be observed, and P2 is accentuated. Signs of right ventricular failure (edema, distended neck veins, hepatomegaly) are common late in the disease.
Laboratory Evaluation
An ECG, chest x-ray film, and echocardiogram should be obtained routinely in a patient suspected of having an atrial septal defect.
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Electrocardiogram
The ECG displays an incomplete right bundle-branch block or rSR′ in lead V1 90% to 95% of the time. If the defect is of the secundum type, a vertical frontal plane axis or right-axis deviation usually is present. The presence of frank right ventricular hypertrophy suggests the development of pulmonary hypertension. Ostium primum atrial septal defect is distinguished by the presence of left-axis deviation. Atrial fibrillation occurs commonly in symptomatic patients; atrial flutter and paroxysmal atrial tachycardia occur less often.
Chest X-Ray Film
The chest x-ray film in this disease is almost always abnormal and shows increased pulmonary vascularity with a prominent main pulmonary artery and increased heart size (Fig. 65.3). The right pulmonary artery usually is more prominent than the left because of differential flow.
Echocardiogram
The echocardiogram demonstrates right ventricular enlargement and paradoxical motion of the ventricular septum with respect to the posterior wall of the left ventricle. These findings are also seen with other lesions that cause volume overload of the right ventricle, such as tricuspid and pulmonic regurgitation, and partial anomalous pulmonary venous return. Flow across the atrial septum often can be visualized by color Doppler echocardiography. Contrast echocardiography, in which agitated saline is injected intravenously and is visualized echocardiographically as bubbles, usually can detect the presence of some right-to-left shunting across the atrial septum, even if the direction of the shunt is predominantly from left to right.
Management
Patients suspected of having an atrial septal defect should be referred to a cardiologist for definitive diagnosis. The cardiologist usually performs TEE and, if the patient is older than 40 years, cardiac catheterization (see Chapter 62 for a description of the patient experience). All patients, even if they are asymptomatic, should undergo repair of their defect if pulmonary blood flow is more than 1.5 times systemic blood flow. The operative mortality is <2%, although some degree of persistent right ventricular or LV dysfunction is common in adults. If severe pulmonary hypertension has developed (pulmonary pressure equal to or greater than the systemic pressure), corrective surgery is generally contraindicated, but patients with lesser degrees of pulmonary hypertension may still benefit from repair of the defect. Survival after corrective surgery is influenced by the age of the patient and the degree of persistent cardiac dysfunction. Patients with otherwise normal hearts have normal survival rates after successful repair of the atrial defect and usually can resume normal activity. An alternative to surgical repair of a secundum atrial septal defect is transcatheter closure with intracardiac or transesophageal echocardiographic guidance. Percutaneous closure using this technique has been successful in >98% of reported cases, with relatively few complications (53,54). After successful transcatheter closure of large atrial septal defects, right atrial area and right ventricular volume are significantly reduced at 6-month followup (55). Percutaneous device closure is now generally preferred over surgical closure if the defect is appropriate for this approach. However, patients who have a large secundum atrial septal defect or a defect with an inadequate tissue rim for deployment of the closure device or patients with atrial septal defects other than the secundum type do not have suitable anatomy for the percutaneous approach and require surgical closure. Unless an associated valvular abnormality is present, endocarditis prophylaxis is not recommended for patients with an atrial septal defect (see Chapter 93).
Mitral Regurgitation
Mitral regurgitation may develop because of an abnormality of any part of the mitral valve apparatus: valve leaflets, chordae tendineae, papillary muscles, or annulus (56). Such abnormalities may result in either acute or chronic signs and symptoms, depending on the nature of the lesion.
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An incompetent mitral valve allows regurgitation into the left atrium of blood from the left ventricle. The reduced load on the ventricle reduces the tension in the ventricular muscle and allows it to use more energy in contraction. Therefore, in patients with chronic mitral regurgitation, cardiac output remains normal for years until, because of age or intercurrent disease, the ventricle can no longer compensate and heart failure ensues. In patients with acute mitral regurgitation, ventricular compensation is inadequate and heart failure develops abruptly.
Chronic Mitral Regurgitation
Causes and Epidemiology
Chronic mitral regurgitation in adults may occur in association with a variety of disorders. Mitral valve prolapse appears to be the most common cause of mitral regurgitation today, although the spectrum of this condition is changing as rheumatic heart disease becomes less frequent (rheumatic heart disease is now the cause of only 5%–15% of cases). Other causes of chronic mitral regurgitation include papillary muscle necrosis or dysfunction (the result of ischemic heart disease), an inherited (e.g., Marfan syndrome, see below) or an acquired disorder of connective tissue, idiopathic calcification of the valve (primarily a disorder of the elderly), endocarditis, congenital maldevelopment of the mitral apparatus, or as a consequence of LV remodeling with tethering of the mitral valve leaflets in patients with LV dysfunction (57).
Natural History and Symptoms
The left ventricle characteristically adapts to the increased preload of mitral regurgitation by adding new sarcomeres in series, which returns preload toward normal. The chamber becomes larger and more compliant and fully compensates for the volume overload by increasing the end-diastolic volume and stroke volume. Therefore, patients may remain asymptomatic for many years, even for their entire lives, if the regurgitation is not severe (58). Characteristically, symptoms, when they do develop, appear gradually over years as LV dysfunction slowly develops and the ability to compensate for the loss of more than half of the stroke volume back into the left atrium is lost. Dyspnea and fatigue are the usual symptoms of LV failure. Supraventricular arrhythmias, especially atrial fibrillation, are likely to develop if left atrial enlargement becomes marked, compromising somewhat the ability of the heart to compensate. Acute pulmonary edema occasionally occurs but is uncommon. Sometimes severe pulmonary hypertension develops without much enlargement of the left atrium. Early surgical correction of the lesion in patients with pulmonary hypertension and signs of right ventricular hypertrophy is important.
Patients with symptomatic mitral regurgitation often have adverse health consequences related to their valvular disease. In a series of patients with symptomatic mitral regurgitation, 80% treated medically survived 5 years and 60% survived 10 years (59). Moderately to severely symptomatic patients do less well. In one study, 46% of patients with chronic rheumatic mitral regurgitation survived 5 years (60). Data suggest that even patients with asymptomatic, but severe, mitral regurgitation have adverse health consequences related to their valve disease (61). In asymptomatic patients with severe mitral regurgitation, the 5-year rate of death from any cause was 22%, and there was a 33% incidence of adverse cardiovascular events (death, heart failure, and new-onset atrial fibrillation) (61). Cardiac surgery, especially if mitral valve repair is feasible, is associated with a reduction in the development of heart failure and death. Thus, referral to a cardiologist for discussion of surgical mitral valve repair should be considered for patients with severe mitral regurgitation regardless of the presence of symptoms.
Physical Findings
A high-pitched holosystolic murmur, loudest at the apex, is characteristic of chronic mitral regurgitation (patients with mild regurgitation may have only a late systolic murmur). The holosystolic murmur is constant in intensity and radiates always to the axilla and sometimes to the back and the base of the heart. It is best heard when the patient is in the left lateral decubitus position. The murmur is diminished when the patient stands or performs a Valsalva maneuver and is intensified when the patient squats. Mitral valve prolapse is an exception to this general statement about mitral regurgitation. The onset of the click and murmur in patients with mitral valve prolapse occurs earlier in systole during the strain phase of the Valsalva maneuver or upon standing. Squatting delays the onset of the click and murmur in mitral valve prolapse.
If mitral regurgitation is severe, the precordium usually is hyperdynamic and there is an S3 gallop. S1 is soft. If pulmonary hypertension has developed, an S4 gallop, a loud P2, and a right ventricular heave may be appreciated. Signs of right ventricular failure—edema, hepatomegaly, distended neck veins, hepatojugular reflux—may be seen late in the course of this disease.
Laboratory Evaluation
An ECG, chest x-ray, and echocardiogram should be obtained routinely if a patient is suspected of having mitral regurgitation.
Electrocardiogram.
The ECG shows evidence of left atrial enlargement (Fig. 65.4 and Table 65.5) and, if present, of atrial fibrillation. The pattern of LV hypertrophy (Fig. 65.2 and Table 65.3) is often seen as well, primarily in patients with severe disease. A pattern of right ventricular hypertrophy (Table 65.6), indicating pulmonary hypertension, is less common and, when seen, is cause for great concern.
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FIGURE 65.4. Electrocardiogram of a patient with left atrial enlargement (Table 65.5). |
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Chest X-Ray Film.
LV and left atrial enlargement are common. On a posteroanterior film, elevation of the left bronchus and prominence of the left atrial appendage are the earliest signs of left atrial enlargement. A double density is seen posteriorly when the left atrium is grossly enlarged (Fig. 65.5).
Echocardiogram.
Echocardiography demonstrates left atrial and LV enlargement and hyperdynamic motion of the left ventricle, especially the septum. Two-dimensional echocardiography usually can define the etiology of the valvular disease (i.e., rheumatic, prolapsing, ischemic). Color Doppler echocardiography (see above) is sensitive in detecting mitral regurgitation and can estimate its severity. Occasionally, patients may require TEE for assessment of the mechanism and severity of mitral regurgitation.
Management
Patients who have mild disease (graded by clinical examination and Doppler echocardiography) can be managed medically (see below). Antibiotic prophylaxis against bacterial endocarditis should be administered before all dental and surgical procedures (see Chapter 93). If atrial fibrillation is present, restoration of sinus rhythm may be considered, particularly if the patient is symptomatic. (Chapter 64 gives a detailed discussion of the treatment of atrial fibrillation.) However, the development of atrial fibrillation may represent a marker of severe or progressive disease (management discussed below). Likewise, new-onset heart failure may signal either worsening of mitral regurgitation or the development of secondary LV dysfunction and may constitute an indication for surgical intervention.
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TABLE 65.5 Principal Electrocardiographic Features of Left Atrial Enlargement |
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The management of moderate and severe mitral regurgitation depends on the severity of symptoms and on LV function. In patients who are symptomatic with fatigue, congestive heart failure, or arrhythmias, mitral valve replacement or repair may be indicated, and referral to a cardiologist should be made (Table 65.7). Cardiac
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catheterization and angiography (see Chapter 62) likely will be performed to confirm the severity of the lesion and to determine the patency of the coronary arteries. At this point, a decision is made about the value of operative repair of the lesion. Unless the patient has severe noncardiac disease, replacement or repair of the defective valve is very likely to be recommended.
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TABLE 65.6 Electrocardiographic Criteria of Right Ventricular Hypertrophy in Adults without Conduction Defects Known Not to Have Infarction |
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FIGURE 65.5. Chest x-ray film of a patient with left atrial enlargement. Note the straight left heart border and calcification of the left atrial wall. |
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Surgical reconstruction of the diseased mitral valve has been shown to be an excellent alternative to mitral valve replacement, particularly for valves that are leaking because of myxomatous degeneration (see Mitral Valve Prolapse). Repair most likely is feasible if the etiology of the mitral regurgitation is a flail posterior leaflet. The mitral valve should be repaired whenever possible, but this may not be feasible if the valve has been severely damaged by endocarditis or rheumatic fever. Repaired valves usually maintain their competency and seem not to be as susceptible to infectious endocarditis, and the patient does not require chronic anticoagulation unless another indication is present (1). Valve repair results in better operative mortality, long-term survival, and postoperative ejection fraction than does valve replacement (62,63). Mitral valve repair in severe LV dysfunction is not associated with a reduced mortality rate (64,65), but most patients have improvement of heart failure symptoms, LV systolic function, and LV size (66). The operative mortality is largely dependent on preoperative ejection fraction but averages approximately 2% to 5%.
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TABLE 65.7 Indications for Referral of Patients with Mitral Regurgitation |
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The decision about whether to recommend valve repair or replacement depends on the availability of a surgeon who is skilled at this procedure and usually is made in consultation with the cardiologist and the cardiac surgeon. A novel approach for mitral valve repair via a percutaneous route is in early clinical trials and may become available to patients in the future.
Because mitral regurgitation often is well tolerated for years or even decades, many patients are asymptomatic. However, the long-standing chronic volume overload often results in gradual deterioration in LV function, which greatly increases the risk and reduces the benefit of mitral valve repair or replacement when it eventually becomes necessary. Progressive LV dysfunction may be difficult to detect by the usual means of assessment of wall motion (echocardiography and gated blood pool scanning) because regurgitation into the low-pressure left atrium reduces the afterload of the left ventricle during ejection and results in exaggerated wall motion and falsely optimistic estimates of contractility. Many patients develop irreversible LV dysfunction before they note symptoms, even if the ejection fraction has remained within normal limits. In patients with severe mitral regurgitation caused by flail leaflet, this insidious ventricular dysfunction results in a high annual mortality rate (4.1%) even if symptoms are minimal or absent. Early surgery is associated with an improved prognosis (67). In this group, at the end of a followup period of 10 years, 90% of patients have either undergone surgical treatment or died (67). A flail mitral valve leaflet is also associated with an increased risk for sudden cardiac death estimated at 1.8% per year, even in asymptomatic patients (68). As discussed above, patients with asymptomatic, severe mitral regurgitation have a lower survival rate than the general population (61). In the past, surgery has been advised for patients with LV ejection fractions near the low end of normal (55%–60%) or below or with an LV end-systolic dimension ≥4.5 cm (69). The adverse outcomes associated with severe mitral regurgitation and the successes with mitral valve repair (that obviate the need for a prosthetic valve) suggest that patients should be considered for surgery earlier than previously
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recommended. Therefore, the diagnosis of moderate or severe mitral regurgitation is an indication for referral of the patient to a cardiologist.
Patients with moderate mitral regurgitation should undergo echocardiography annually to assess for worsening mitral regurgitation or the development of LV dysfunction. If there is clinical evidence of worsening mitral regurgitation, an echocardiogram should be requested sooner. Patients with severe mitral regurgitation should undergo echocardiography every 6 to 12 months to exclude asymptomatic LV dysfunction or LV chamber enlargement. Annual echocardiograms are not required in patients with mild mitral regurgitation and can be obtained approximately every 5 years, unless symptoms develop.
Afterload reduction achieved by an arteriolar vasodilator may be particularly useful in this condition; by lowering peripheral resistance, ejection of blood into the aorta, rather than back into the left atrium, is favored. Intravenous vasodilator therapy can result in dramatic hemodynamic improvement in hospitalized patients with congestive heart failure caused by mitral regurgitation. However, the efficacy of vasodilator therapy in asymptomatic patients with preserved LV function has not been studied in multicenter randomized trials. If a beneficial hemodynamic effect could be sustained, it might be possible to delay the development of LV dysfunction or symptoms and postpone the need for surgery. On the other hand, use of vasodilators and β-blocker therapy in patients with congestive heart failure caused by mitral regurgitation is well established.
The health and survival of patients who have undergone successful valve replacement depend on a number of factors (also see below). Advanced age and the preoperative presence of concomitant mitral stenosis, reduced LV function (ejection fraction <50%), and severe symptoms (New York Heart Association class III or IV; see Chapter 66) are adverse factors that reduce long-term postoperative survival (69). In general, patients with mitral regurgitation on the basis of ischemic heart disease do less well than patients with rheumatic heart disease. Nevertheless, even patients with one or more adverse risk factors live longer, on average, with a prosthetic valve than they would without one, and most patients are able to be more active than they were before surgery. The overall 10-year survival for patients who have undergone successful mitral surgery is approximately 70%. Postoperatively, anticoagulation with warfarin is used routinely to prevent thromboembolic complications in patients with mechanical prosthetic valves (see Chapter 57).
Acute Mitral Regurgitation
Causes and Epidemiology
Acute mitral incompetence is most often caused by rupture of the chordae tendineae, the cords that connect the valve cusps to the papillary muscles of the left ventricle. Most often the cause of the rupture is myxomatous degeneration of the valve (see Mitral Valve Prolapse), although occasionally acute mitral regurgitation is caused by papillary muscle rupture or dysfunction (complications of myocardial infarction) or by perforation of a mitral cusp as the result of bacterial endocarditis. The disorder is primarily encountered in middle-aged and elderly patients.
Natural History and Symptoms
Because the left atrium is suddenly presented with a volume load to which it cannot rapidly accommodate, acute pulmonary edema is much more common in patients with acute, compared with chronic, mitral regurgitation.
Physical Findings
A harsh holosystolic murmur of constant intensity, loudest at the apex, is characteristic. If a posterior cord has ruptured, the murmur may radiate to the base of the heart and may mimic the murmur of aortic stenosis. Sometimes an early systolic, midsystolic, or even a crescendo–decrescendo murmur is heard. An S3 gallop is almost always heard, and an S4 gallop is common. Unlike the situation in patients with chronic mitral regurgitation, S1 is normal or even loud. Signs of left-sided heart failure (rales) and right-sided failure (edema, distended neck veins) are common.
Chest X-Ray Film.
The chest x-ray film shows marked pulmonary congestion. The left atrium and left ventricle are minimally enlarged.
Echocardiogram.
Chamber enlargement usually is not seen, but increased systolic motion of the valve is common. If the chordae have ruptured, the flailing chordae or marked prolapse of the leaflets into the left atrium may be visualized by 2D echocardiography. Doppler echocardiography allows detection of the lesion, but Doppler criteria for estimating the severity of acute mitral regurgitation are not yet established.
Management
Patients suspected of having acute mitral regurgitation should be hospitalized immediately for diagnosis, treatment of acute heart failure, and consideration for early operative repair.
Mitral Valve Prolapse
Causes and Epidemiology
Systolic prolapse of a leaflet of the mitral valve into the left atrium has proved to be a common phenomenon. In the past, the prevalence of mitral valve prolapse was believed
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to be 5% to 15% of the population. The echocardiographic criteria for the diagnosis of mitral valve prolapse have been refined throughout the years as knowledge has been acquired about how the saddle shape of the mitral annulus influences the diagnosis (70). When strict criteria for mitral valve prolapse were applied to the Framingham Heart Study population, only 2.4% of the patients had the condition (71). Women were slightly more likely to be affected than men in the Framingham Heart Study population (71), although reported sex ratios vary considerably. The exact nature of this abnormality is not entirely clear, but the condition appears to be inherited (autosomal dominant) in some cases, with reduced penetrance in men and children. Most cases are sporadic. Histologic study of prolapsing valves removed at operation shows myxomatous degeneration, a proliferation of the spongiosa layer of mucopolysaccharides into the fibrosa layer and structural alterations of collagen, resulting in weakness in the supporting structure of the valve (72). This abnormality is also seen in a number of known disorders of connective tissue, including Marfan syndrome and Ehlers-Danlos syndrome. However, echocardiographic prolapse has also been reported in patients with ischemic heart disease, HCM, and atrial septal defect. These cases may represent secondary prolapse in which the valve is normal, but changes in ventricular geometry cause prolapsing of the leaflets. In these secondary cases, the click and associated symptoms (see below) usually are not present.
Natural History and Symptoms
Most patients are asymptomatic, and the condition is identified during a routine physical examination. Less often, patients complain of palpitations, chest pain, or dyspnea. The palpitations reflect arrhythmias (see below) or, more commonly, just an awareness of sinus tachycardia. The chest pain often is vague and prolonged and, rather than constituting a true part of the mitral valve prolapse syndrome, its reported association with the condition may represent ascertainment bias (73). That is, patients with nonspecific complaints may be found to have mitral valve prolapse coincidentally and an incorrect association is then made (74). Similarly, dyspnea in the absence of significant mitral regurgitation may be unrelated to the syndrome (75).
The syndrome is benign in most patients. However, significant mitral regurgitation occurs in approximately 15% of patients (76), and patients may complain of dyspnea caused by LV failure. Approximately 3% to 4% of patients require mitral valve surgery during a followup period of approximately 8 years (76).
Some studies have suggested that patients with mitral valve prolapse are at risk for embolic strokes (77), but others have ascribed this association to ascertainment bias (75). The risk of infective endocarditis in patients with mitral valve prolapse is approximately five times that of the general population, and it is the most common condition predisposing patients to infective endocarditis. This risk is highest in patients with mitral regurgitation or thickened mitral leaflets.
Sudden death, the most feared complication of mitral valve prolapse, is extremely rare (78). The risk is higher in patients who have a family history of sudden death or who have a prolonged QT interval on ECG (see below), a flail mitral valve leaflet (68), or LV dysfunction. Sudden death is presumed to be secondary to ventricular arrhythmias. In a small series of seven patients with mitral valve prolapse and malignant ventricular arrhythmias, the patients presented with syncope, out-of-hospital cardiac arrest, palpitations, and near-syncope despite normal LV function and no significant mitral regurgitation (79).
The hemodynamic and infectious complications appear to be more common in men than in women and in patients who have mitral regurgitation at the time of presentation (80). The echocardiographic findings of thickening and redundancy of the mitral leaflet also identify patients with mitral valve prolapse who are at higher risk (81). Patients with the classic form of mitral valve prolapse have mitral leaflet thickening of at least 5 mm, and complications such as infective endocarditis, moderate to severe mitral regurgitation, and mitral valve surgery are more prevalent in this group than in patients with the nonclassic form (leaflet thickening <5 mm) (81).
Physical Findings
The characteristic finding in patients with mitral prolapse is a midsystolic click, best heard at the lower left sternal border, caused by sudden tensing of the prolapsed valve. It occurs later than the systolic ejection sound commonly heard in association with systemic hypertension (see above). Very often the click is followed immediately by a crescendo late systolic murmur that continues until A2.
The physical findings may vary from time to time in any given patient and may vary with the position of the patient. Standing generally augments the click and makes it occur earlier in systole because afterload is reduced and the ventricle becomes smaller with respect to the mitral valve, increasing the prolapse. Squatting and isometric handgrip increase afterload and have the opposite effect. In those instances in which chronic mitral regurgitation has developed, the typical physical findings—including the holosystolic murmur—of this condition will be encountered (see above).
The mitral valve prolapse syndrome is commonly associated with skeletal abnormalities, such as scoliosis and pectus excavatum, suggesting that valve prolapse may be only one component of a generalized disease of connective tissue.
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Laboratory Findings
Electrocardiogram
The ECG usually is normal, especially in asymptomatic patients. Symptomatic patients may show nonspecific ST-T wave changes, usually in the inferior leads, and sometimes prolongation of the QT interval. A variety of arrhythmias may occur in patients with mitral valve prolapse. The most common are premature ventricular contractions and paroxysmal supraventricular tachycardia.
Echocardiogram
The echocardiogram usually is diagnostic in this condition. It shows late systolic or holosystolic prolapse of one or both leaflets of the mitral valve of at least 2 mm from the annular plane into the left atrium in the parasternal long-axis or apical long-axis view. Sometimes, however, the echocardiogram shows no abnormalities despite the typical cardiac findings. These patients probably have minor degrees of prolapse. Mitral regurgitation, if present, can be detected by Doppler echocardiography (see above).
Management
Asymptomatic patients require no treatment but should be reassessed by interval history, physical examination, and echocardiogram every few years. Care should be taken to ensure that the diagnosis does not produce unwarranted anxiety. Patients who have a systolic murmur or echocardiographic evidence of thickening or redundancy of the mitral leaflet should receive antibiotic prophylaxis before dental or surgical procedures (see Chapter 93). Other patients probably do not require prophylaxis.
Patients with palpitations should have an ambulatory electrocardiographic monitor or event recorder to determine the nature and severity of their arrhythmia, and therapy should be prescribed based upon the type of arrhythmia present (see Chapter 64). A β-blocking agent is often the drug of choice for the treatment of these patients and for those with mitral prolapse who complain of chest pain or who have persistent palpitations caused by sinus tachycardia (e.g., long-acting propranolol, usual dosage 40– 120 mg/day, or atenolol 25–50 mg/day). The drug's mechanism of action in relieving pain is unknown but may be explained by the fact that many untreated patients have increased blood levels of norepinephrine and increased sympathetic tone.
Patients with symptomatic mitral regurgitation should be treated as described above. Referral to a cardiologist is recommended at any time for patients become symptomatic from arrhythmia (other than sinus tachycardia) or develop chronic mitral regurgitation or thromboembolism.
Mitral Stenosis
Stenosis of the mitral valve obstructs the flow of blood out of the left atrium, therefore raising the left atrial pressure above the LV diastolic pressure. The pressure gradient across the valve and the area of the valve orifice are measures of the severity of stenosis. Because of the increase in left atrial pressure, there is an increase in pressure in the pulmonary blood vessels and a tendency to develop atrial fibrillation. Pulmonary congestion and atrial fibrillation account for most of the symptoms of the disease.
Causes and Epidemiology
By far the most common cause of mitral stenosis in adults is rheumatic fever (although a history of rheumatic fever can be elicited in only 50% of patients with pure mitral stenosis). Pure mitral stenosis occurs in 25% of all patients with rheumatic heart disease, and 40% of patients have combined mitral stenosis and regurgitation (82). The remainder of patients with rheumatic heart disease have associated mitral regurgitation, aortic valve disease, and, uncommonly, tricuspid valve disease. Two thirds of patients with rheumatic mitral stenosis are women.
Natural History and Symptoms
On average, there is a latent period of at least 20 years between an attack of acute rheumatic fever and the development of symptomatic mitral stenosis (83). Thus, symptoms usually do not develop before the fourth decade. The severity of symptoms is quite variable. In fact, some people are never symptomatic, some are mildly symptomatic indefinitely, and some develop progressively severe cardiopulmonary decompensation. Of the patients with progressive disease, an estimated average of 7 years elapses between the onset of symptoms and the development of total disability (class IV cardiac status; see Chapter 66).
Pulmonary congestion causes many of the symptoms of mitral stenosis: dyspnea, orthopnea, and paroxysmal nocturnal dyspnea. If left atrial pressure rises acutely because of a sudden stress, frank pulmonary edema may occur. Hemoptysis caused by rupture of small bronchial veins or by pulmonary edema is not unusual.
As the disease progresses, pulmonary hypertension develops and is followed by symptoms of right heart failure: edema, distended neck veins, a tender liver, and ascites. At this point, the flow of blood into the left heart is limited, and the pulmonary arterioles hypertrophy, diminishing the risk of pulmonary edema. Low cardiac output is responsible for the fatigue that is a common complaint of patients at this stage.
Atrial fibrillation (see Chapter 64) complicates the course of 40% to 50% of patients with mitral stenosis (84,85). The 20% reduction in blood flow across the mitral
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valve by the subsequent loss of left atrial contraction may intensify symptoms of heart failure and fatigue.
At some time in their course, 20% of patients with mitral stenosis experience symptomatic thromboembolism (86), most often to the brain. Eighty percent of these patients have known atrial fibrillation (i.e., atrial fibrillation may be intermittent in some other individuals, so the condition may not be diagnosed).
Physical Findings
A mid-diastolic rumbling murmur with presystolic accentuation is characteristic of mitral stenosis. It is best heard at, and is often limited to, the cardiac apex. To hear it, it may be necessary to turn the patient to the left lateral position and to have the patient expire fully. Sometimes, the patient must be exercised before the murmur is audible. The murmur is best heard with the bell of the stethoscope pressed lightly against the chest. A loud first heart sound and opening snap (see above) usually accompany the murmur when the valve is mobile. Late in the course, signs of pulmonary hypertension (loud P2 and a right ventricular heave) and right heart failure may be found.
Laboratory Findings
Electrocardiogram
The ECG shows left atrial enlargement (Fig. 65.4 and Table 65.5) in 90% of patients who are in sinus rhythm. With the development of pulmonary hypertension, signs of right ventricular hypertrophy appear (Table 65.6).
Chest X-Ray Film
Left atrial enlargement (see above and Fig. 65.5) is seen in almost all patients with symptomatic mitral stenosis, but left atrial size does not correlate with the severity of stenosis. Late in the course, right ventricular and right atrial hypertrophy are seen as well. Symptomatic patients are likely to show radiologic signs of pulmonary congestion, the severity of which determines the findings (see Chapter 66). Calcification of the mitral valve is not unusual in patients with long-standing mitral stenosis, but it is better visualized by fluoroscopy or echocardiography than by a plain x-ray film.
Echocardiogram
Mitral stenosis can be easily diagnosed by echocardiography. Mitral valve thickening can be seen; there is reduced excursion of the anterior leaflet of the valve with doming during diastole so that the valve leaflet resembles a hockey stick (so-called “hockey stick deformity”) and abnormal anterior motion of the posterior leaflet during diastole (it normally moves posteriorly). The severity of the stenosis can be accurately assessed by 2D and Doppler echocardiography (see above). An echocardiographic scoring system has been useful in the selection of patients for percutaneous balloon dilation of the mitral valve (87), a procedure discussed below. This scoring system considers the echocardiographic characteristics of the valve and subvalvular apparatus. The echocardiogram is important in the assessment of mitral regurgitation and of the tricuspid transvalvular gradient for estimation of the pulmonary artery pressure. In selected patients, such as those awaiting balloon mitral valvuloplasty or direct-current cardioversion, a transesophageal echocardiogram is important for excluding left atrial or left atrial appendage thrombus.
Management
Asymptomatic patients in normal sinus rhythm require no treatment except prophylaxis for bacterial endocarditis when they undergo dental or surgical procedures (see Chapter 93). Patients with a history of rheumatic fever with carditis or residual heart disease with valvular abnormalities should receive prophylaxis for β-hemolytic streptococcal infection for at least 10 years or until they reach age 40 years, whichever is longer (1). On occasion, prophylaxis is lifelong in those with relatively high exposure to streptococcal infections, such as day care workers and teachers. For patients without residual heart disease, prophylaxis is recommended for 10 years or well into adulthood, whichever is longer. For those with rheumatic fever without carditis, prophylaxis is given for 5 years or until age 21 years, whichever is longer. When prophylaxis is necessary, one of the easiest regimens is one to two million units of benzathine penicillin G intramuscularly once per month. Alternatively, penicillin V (250 mg) can be taken orally twice daily.
Patients who develop atrial fibrillation should be anticoagulated with warfarin to achieve a target international normalized ratio (INR) of 2.0 to 3.0. Anticoagulation should be continued long term because of the high risk for stroke and venous thrombosis. Patients usually are symptomatic from the atrial fibrillation, and ventricular rate control should be achieved with a β-blocking agent or calcium channel blocker (verapamil or diltiazem). Electrical cardioversion may be necessary and can be performed by a cardiologist if the patient has been adequately anticoagulated for at least 3 weeks; otherwise, a TEE-guided cardioversion is necessary.
Mildly symptomatic patients should be treated with diuretics and sodium restriction (see Chapter 66 for a detailed discussion of the treatment of heart failure). Because it does not affect the hemodynamic abnormality, digitalis is not useful in this situation unless rapid atrial fibrillation or flutter develops. Although the use of β-blockers has been advocated in patients with mitral stenosis in normal sinus rhythm (to reduce heart rate and prolong the diastolic
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filling period), randomized studies have not demonstrated a clinical benefit (88).
In addition to patients with atrial fibrillation, warfarin anticoagulants should be administered to patients who have a history of a prior embolic event such as venous thromboembolism or pulmonary embolism because of the high risk for recurrent thromboembolism in this patient population (see Chapter 57). The American College of Chest Physicians recommends that patients with severe mitral stenosis and a dilated left atrium (>55 mm by echocardiography) be considered for long-term anticoagulation therapy (89).
The poor prognosis of symptomatic medically treated patients with severe or progressive disease (see Natural History and Symptoms) dictates that such patients be offered a mechanical procedure to improve transmitral flow, either percutaneous balloon valvuloplasty or valve surgery. Percutaneous valvuloplasty can be achieved using a balloon catheter passed through the venous system and then across the atrial septum to the mitral valve. This procedure is generally effective in patients who have low LV end-diastolic pressures, who do not have New York Heart Association class IV symptoms, and in whom the echocardiogram shows good mitral valve mobility and minimal valvular or subvalvular thickening and calcification. It is contraindicated in patients who have moderate to severe mitral regurgitation or a left atrial thrombus by TEE (1). Valvuloplasty should be considered in asymptomatic patients with moderate or severe mitral stenosis who are planning pregnancy, because symptoms are likely to develop late in pregnancy, and pulmonary edema may complicate labor or delivery. Patients with mitral stenosis and moderate to severe tricuspid regurgitation should be referred for surgery because both the mitral and tricuspid valves can be operated on during the same operation. In a prospective randomized trial comparing percutaneous valvuloplasty with open surgical commissurotomy in suitable patients, mitral valve orifice size and functional class after the procedure were better in the percutaneous group than in the surgical group (90). Of the patients who underwent percutaneous valvuloplasty, 72% were asymptomatic after 3 years, compared with 57% of the surgically treated patients. The better hemodynamic results, lower costs, and elimination of the need for thoracotomy suggest that balloon valvuloplasty should be considered for all suitable patients. The procedure is well tolerated and effective, even in elderly frail patients. From the patient's perspective, the procedure is similar to cardiac catheterization. An overnight hospitalization is required for observation after the procedure. In patients with a history of atrial fibrillation, warfarin typically is resumed the day after the procedure and continued long term. In other patients, anticoagulation with warfarin usually is recommended for 4 weeks following balloon valvuloplasty despite the absence of a left atrial thrombus or a history of atrial fibrillation.
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TABLE 65.8 Indications for Referral of Patients with Mitral Stenosis |
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In patients requiring mechanical relief of mitral valve obstruction who are not suitable for percutaneous valvuloplasty, the preferred surgical procedure depends on the valve anatomy at the time of operation. If possible, a mitral commissurotomy is performed. The operative mortality of this procedure is low (1%–3%), and the results are excellent for a number of years. However, after commissurotomy, 10% of patients require reoperation within 5 years because of restenosis or because of the development of symptomatic mitral regurgitation or symptomatic aortic stenosis (91,92). If a prosthetic valve is implanted, the operative mortality is 3% to 10%. The course of patients who survive surgery depends on a number of factors (see below) but certainly is better than that of symptomatic patients treated medically.Table 65.8 lists the reasons to refer patients with mitral stenosis to a cardiologist.
Aortic Regurgitation
An incompetent aortic valve allows regurgitation into the left ventricle of blood ejected into the aorta. To compensate for the increased volume load, the left ventricle dilates and hypertrophies, so the effective stroke volume may be normal for a long time. Eventually, however, the left ventricle cannot maintain the workload, and clinical signs and symptoms of heart failure ensue.
Causes and Epidemiology
Aortic regurgitation may be caused by disease of the aortic valve cusps and/or dilation of the aortic root. Rheumatic fever now accounts for <15% of cases of chronic aortic regurgitation in developed countries (93), many fewer than it did 20 to 30 years ago. In developing countries, rheumatic heart disease is still the most common cause of aortic regurgitation. Another cause of chronic aortic regurgitation is a congenitally bicuspid aortic valve. Although aortic stenosis is more common than is aortic regurgitation
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in patients with a bicuspid aortic valve, aortic regurgitation may occur in isolation or in combination with aortic stenosis, and the majority of patients will require valve surgery during their lifetime (94). Calcific degeneration of the aortic valve is associated with aortic regurgitation, often mild in severity. Less common primary diseases of the aortic valve causing chronic aortic regurgitation include anorectic drugs, systemic lupus erythematosus, and rheumatoid arthritis. Structural degeneration of bioprosthetic aortic valves is becoming an increasingly common cause of chronic aortic regurgitation. Acute valvular incompetence is most often caused by infective endocarditis and, occasionally, by trauma to the aortic valve.
The most common cause of aortic regurgitation requiring aortic valve replacement today is aortic root disease (95). Marked aortic root dilation may be seen in patients with bicuspid aortic valve; connective tissue disorders such as Marfan syndrome, Ehlers-Danlos syndrome, and osteogenesis imperfecta; calcific degeneration of the aortic valve; and in patients with poorly controlled systemic hypertension. When the aortic root is dilated failure of coaptation of the aortic cusps leads to aortic regurgitation. In other diseases, the aortic wall becomes thickened and dilated, such as in ankylosing spondylitis, syphilitic aortitis, and reactive arthritis. Acute aortic regurgitation caused by dilation of the aortic root is most commonly caused by aortic dissection, usually associated with medial necrosis of the aorta. Dissection is associated with systemic hypertension in approximately two thirds of cases (96); occasionally a primary disorder of connective tissue, such as Marfan syndrome, can be incriminated. Aortic regurgitation in general is more common in men than women, but specific exceptions exist (e.g., rheumatoid arthritis).
Natural History and Symptoms
In chronic aortic regurgitation, volume overload usually is tolerated for years or decades because of adaptive dilation and hypertrophy that maintains cardiac performance in or near the normal range. Patients may remain asymptomatic for up to 20 years or have only mild dyspnea on exertion. However, the chronically overloaded heart eventually develops irreversible structural and functional damage, often during the asymptomatic period (97). When symptoms do develop (progressively more severe dyspnea, orthopnea, paroxysmal nocturnal dyspnea, and, less often, angina), they reflect an ominous deterioration in the condition.
Patients with acute aortic regurgitation develop fulminant pulmonary edema because of the inability of the left ventricle to compensate for the sudden volume load and for the abrupt rise in LV end-diastolic pressure. Marked dyspnea and weakness may be experienced virtually overnight and, in most cases, within 2 or 3 months. Other symptoms depend on the underlying cause, for example, fever if the cause is infective endocarditis or severe pain in the chest if the cause is aortic dissection.
Physical Findings
Patients with chronic aortic regurgitation have a characteristic high-frequency early diastolic decrescendo murmur, best heard at the aortic area and at the left sternal border. The duration (but not the intensity) of the murmur correlates with the severity of the lesion, so the murmur is holodiastolic in patients with severe chronic aortic regurgitation. Often an accompanying harsh systolic ejection murmur is heard at the base of the heart. Severe aortic regurgitation may also cause a loud apical diastolic murmur (Austin Flint murmur), simulating the murmur of mitral stenosis. Unlike the situation in true mitral stenosis, however, S1 in patients with aortic regurgitation is sometimes soft, the result of premature closure of the mitral valve, and there is no opening snap. If aortic regurgitation is moderate or severe, the pulse pressure is ordinarily wide, reflecting peripheral vasodilation. The combination of increased systolic pressure and reduced diastolic pressure (sometimes as low as 30 mm Hg) produces characteristic changes in the peripheral pulse (e.g., the so-called “water-hammer pulse” and pistol-shot sounds heard over the femoral artery) and a typical head bobbing with each heartbeat.
Patients with acute aortic regurgitation often show signs of left- and right-sided heart failure. The regurgitant diastolic murmur is lower pitched and shorter than it is in patients with chronic aortic regurgitation. S1 often is absent and S3, uncommon with chronic regurgitation, usually is present. The pulse pressure often is normal, the result of intense peripheral vasoconstriction.
Laboratory Findings
Electrocardiogram
The ECG reflects the severity and duration of aortic regurgitation. Patients with chronic disease show the ECG pattern of LV hypertrophy (Fig. 65.2 and Table 65.3), whereas patients with acute disease do not (although they commonly do show nonspecific ST-T wave changes).
Chest X-Ray Film
The size of the heart in patients with aortic regurgitation depends on the duration and severity of the disease. Patients with chronic severe disease have very large left ventricles, but patients with acute regurgitation may have no cardiac enlargement at all.
Echocardiogram
Echocardiography with Doppler is useful in confirming the diagnosis and assessing LV function and the degree of
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hypertrophy. Premature mitral valve closure is helpful in confirming very severe aortic regurgitation. The severity of aortic regurgitation also can be estimated by Doppler echocardiography using a number of described criteria (13).
Management
Asymptomatic patients with mild aortic regurgitation do not require treatment but should be assessed once or twice per year by interval history, physical examination, and chest x-ray film. Yearly ECGs and echocardiograms also should be obtained. Prophylaxis against bacterial endocarditis is indicated when patients are to undergo dental or certain endoscopic or surgical procedures (see Chapter 93).
Vasodilating drugs acutely reduce the regurgitant volume and have long been known to be useful in improving hemodynamics in the short term. Randomized clinical trials demonstrate that long-term treatment with hydralazine (98), nifedipine (99), or enalapril (100) reduces end-diastolic and end-systolic volumes and increases ejection fraction in asymptomatic or minimally symptomatic patients with moderate or severe aortic regurgitation. A reduction in the extent of hypertrophy also can be demonstrated. Angiotensin-converting enzymes seem to be the most potent in this regard (100), probably because suppression of the renin–angiotensin system inhibits the development of detrimental hypertrophy. These data suggest that vasodilator therapy has the potential to delay the need for valve replacement and should be prescribed in patients with moderate or severe aortic regurgitation, even if they are asymptomatic. Patients with moderate to severe aortic regurgitation also should be assessed once or twice per year by interval history, physical examination, and chest x-ray film. Yearly ECGs and echocardiograms also should be obtained. If evidence of worsening LV dilation, hypertrophy, or LV function is detected, valve repair or replacement should be considered. As noted above for asymptomatic patients with mild aortic regurgitation, prophylaxis against bacterial endocarditis is indicated for dental or certain endoscopic or surgical procedures.
Table 65.9 lists the reasons to refer patients with aortic regurgitation to a cardiologist. In general, referral is indicated in patients with chronic disease to consider whether to recommend aortic valve replacement for symptomatic patients and for asymptomatic patients with physical findings of severe disease (widened pulse pressure, holodiastolic murmur, increasing LV enlargement, decreasing ejection fraction) (101). All patients with suspected acute aortic regurgitation should be seen by a cardiologist as soon as possible. The cardiologist may perform cardiac catheterization (see Chapter 62) to assess the severity of the lesion, the presence of other valvular disease or coronary artery disease, and the function of the left ventricle. Patients with marked LV dilation and ejection fractions <50% are at high risk for requiring aortic valve replacement for symptoms of deteriorating LV function within 3 years (97).
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TABLE 65.9 Indications for Referral of Patients with Aortic Regurgitation |
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When patients with chronic aortic regurgitation develop symptoms of congestive heart failure, 50% are dead within 2 years (102). Thus, valve replacement is warranted in all symptomatic patients, preferably before severe LV dysfunction develops. The operative mortality is 3% to 10%. However, of the patients who survive surgery, 77% live at least 10 years (103), and their quality of life usually is significantly improved (see below). Symptoms of congestive heart failure are responsive to diuretics and vasodilators.
The Patient with a Prosthetic Valve
Although patients usually demonstrate clear improvement in symptoms and prognosis after valve replacement, they should not be considered cured. Despite refinements in design, no valve currently available is free of potential serious complications, which, because they may occur many years after surgery, dictate careful long-term followup of all patients who have prosthetic valves.
Many varieties of mechanical valves and tissue (bioprosthetic) valves have been developed. Types of mechanical valves include the caged-ball valve (Starr-Edwards), the single tilting-disk valve (Medtronic-Hall, Omnicarbon, Bjork-Shiley), and bileaflet tilting-disk valve (St. Jude Medical, Carbomedics). The St. Jude bileaflet valve is the most commonly implanted mechanical valve today. The most common tissue valves are the Hancock and Carpentier-Edwards valves, which are constructed of porcine aortic valve leaflets that have been fixed in glutaraldehyde, and various valves constructed from bovine pericardium. Occasionally, homografts (preserved human valve from cadaveric donors) are implanted in the aortic position. Mechanical prosthetic valves are extremely durable, lasting at
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least 20 to 30 years, but require long-term anticoagulation with warfarin, which is associated with a higher incidence of bleeding complications (104,105). Bioprosthetic valves, on the other hand, have a 15% to 40% risk of structural degeneration at 10 to 15 years, which usually requires valve replacement (104,105).
Potential Complications
Valve replacement exchanges the complications associated with native valve disease with those from prosthetic valves. Overall, the incidence of complications from prosthetic valves is approximately 3% per year (104, 105, 106) and includes such serious problems as thromboembolism, valve thrombosis, bleeding, infection, and structural failure. Thromboembolic phenomena are perhaps the most common life-threatening complications of prosthetic valves and may present as sudden stroke, myocardial infarction, or peripheral arterial occlusion. Alternatively, thrombus may accumulate around the valve ring and prevent proper valve motion, resulting in gradual or sudden obstruction of flow and the development of dyspnea and severe congestive heart failure. Thromboembolic events are more common with prosthetic valves in the mitral than in the aortic position. Despite treatment with full anticoagulation, the incidence of thromboembolic complications with most mechanical valves is approximately 1% to 2% per year (107).
An uncommon finding with prosthetic valves is perivalvular regurgitation. It may be visualized during the intraoperative transesophageal echocardiography after valve implantation. However, the development of new, significant perivalvular regurgitation is suggestive of endocarditis, and blood cultures should be obtained to exclude the possibility of infection (108). In addition to blood cultures, a complete blood count and serum lactate dehydrogenase level should be checked to exclude a hemolytic anemia from infection or actual dehiscence of the prosthetic valve. In cases of severe anemia, significant regurgitation and/or congestive heart failure due to a perivalvular leak, repair or replacement of the valve must be considered.
Prosthetic valve endocarditis develops in 2% to 3% of patients and may present as a febrile illness, a new murmur of valvular regurgitation or stenosis, hemodynamic deterioration, or embolization. Because the infection involves a foreign body, the prognosis for recovery with standard antibiotic therapy is worse than for patients with native valve endocarditis. Recurrence after one trial of medical therapy, abscess formation, or involvement of the sewing ring of the valve or perivalvular tissue is generally an indication for valve replacement. Prognosis is worse for patients in whom infections develop within 60 days of surgery (in which contamination may have occurred at operation) than in those in whom fever develops later, when transient bacteremia may be the source of infection. Despite appropriate antibiotic treatment, prosthetic valve endocarditis has a mortality rate of 50% to 80% (109).
Late valvular degeneration is a significant problem after tissue valve implantation. Histologic studies reveal fibrin deposition, tears in the leaflets, and calcification that commonly result in some degree of valvular stenosis or regurgitation 5 to 15 years after operation. In some cases in which clinical deterioration occurs, reoperation is required. In a multicenter trial (104), the 11-year probability of reoperation for structural failure of bioprosthetic valves was 15% for those in the aortic position and 36% for those in the mitral position. The process of structural degeneration is greatly accelerated in children but also occurs commonly in young adults (age <35 years).
Bleeding complications are more common with the mechanical valves, which always require full anticoagulation. In the same multicenter trial (104), the 11-year probability of bleeding complications was 42% with mechanical valves and 26% with bioprosthetic valves. However, these figures may not reflect the current risk of bleeding because in the 1970s, when most patients were recruited into that study, the recommended degree of anticoagulation was greater than what is generally recommended today. Because the normal prothrombin time varies from laboratory to laboratory, the standard is expressed as the INR (see Chapter 57). The target INR differs depending on the type of prosthetic valve, the position of the valve (i.e., mitral or aortic), and risk factors for thromboembolic events (see below).
Physical and Laboratory Findings
The normal ausculatory findings of a prosthetic valve depend on the type and location of the valve (106). A caged-ball aortic prosthesis produces a loud opening click after the first heart sound, an early-to-mid peaking systolic ejection murmur, followed by a less prominent closing click. The caged-ball mitral prosthesis produces a loud opening click after the second heart sound followed by a softer closing click. On the other hand, the single tilting-disk valve in the aortic position has a softer opening click after the first heart sound, followed by an early-to-mid peaking systolic ejection murmur at the base and then a loud closing click. A soft diastolic murmur is occasionally heard. With an aortic bileaflet tilting-disk valve, the first heart sound is followed by a softer opening click, followed by an early-to-mid peaking systolic ejection murmur heard best at the base and radiating to the carotids, and then a loud closing click. The mitral bileaflet tilting disk has ausculatory findings similar to that of the mitral single tilting-disk valve. A bioprosthetic valve has heart sounds similar to that of a native valve.
It is important to document the baseline physical examination repeatedly so that the significance of any changes that occur in association with new symptoms can be assessed. The most reliable sign of prosthetic valve dysfunction
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is the loss or muffling of the opening and closing clicks. New regurgitant murmurs may occur, and congestive heart failure may ensue.
Prosthetic valve dysfunction can be assessed by several imaging modalities. The 2D echocardiogram may show abnormal, delayed, or intermittent leaflet motion. Doppler echocardiography (see above) is particularly helpful in accurately detecting and quantifying new valve gradients and regurgitation. Tissue valves often are well visualized and can be assessed by echocardiography. However, mechanical valves are not well seen by transthoracic echocardiography, and TEE usually is required to assess valve anatomy if there is clinical suspicion or Doppler evidence of impaired prosthetic valve function. Fluoroscopy usually is helpful if restriction of mechanical leaflet motion is being investigated.
Management
Management of the patient with a prosthetic valve should begin before the valve is implanted; the selection of the proper type of valve for the individual patient is crucial. A mechanical valve is generally preferred if anticoagulation is necessary for the treatment of another condition (e.g., atrial fibrillation). A tissue valve is most appropriate for the patient who likely will not be noncompliant with anticoagulation or who is at high risk for bleeding complications. These individuals include alcoholics; patients with psychiatric problems, unexplained syncope, or previous gastrointestinal bleeds; patients whose occupations put them at high risk of injury; and certain elderly patients (especially frail elderly and/or those individuals with a high risk of falling). Women of child-bearing age who desire future pregnancies should receive pulmonary autografts (the Ross procedure, used if aortic valve disease is the reason for surgery) or tissue valves (see below), but in the latter case they should be made aware that valve replacement may need to be repeated in 8 to 10 years. Young men or women who do not anticipate pregnancy and who will tolerate anticoagulation are better off with the more durable mechanical valves so that reoperation is not necessary. These decisions usually are made by the cardiac surgeon after the options are discussed with the patient, but it is important that the practitioner communicate his or her opinions to the surgeon well in advance.
All patients with mechanical valves in the aortic or mitral position must be fully anticoagulated with warfarin indefinitely (see Chapter 57). For aortic prostheses, the INR should be maintained between 2.0 and 3.0 (target INR 2.5) for bileaflet valves (i.e., St. Jude valves) and tilting-disk valves (i.e., Medtronic Hall valves). If there is a history of a previous thromboembolism, atrial fibrillation, significant LV dysfunction, or hypercoagulable state, the INR should be maintained between 2.5 to 3.5 for patients with a prosthetic aortic valve and for all patients with a prosthetic mitral valve (1,110). An alternative recommendation for patients at higher risk for bleeding complications is a target INR of 2.5 (range 2.0–3.0) in combination with aspirin 80 to 100 mg/day. For patients with a caged-ball (Starr-Edwards) valve or for patients considered at high risk for systemic embolism (e.g., patients with atrial thrombi), a target INR of 3.0 (range 2.5–3.5) is recommended in combination with aspirin 80 to 100 mg/day (89). The incidence of thromboembolism is 9% annually without anticoagulation and 1% to 2% with warfarin. If an elective surgical procedure is planned, modification of warfarin therapy should be individualized. In most patients, warfarin may be safely discontinued 3 days before surgery and resumed afterward (see details in Chapter 93). However, temporary substitution of intravenous heparin should be considered if there has been a recent thromboembolus, if the patient has a Bjork-Shiley valve, or if one (for mitral valves) or three (for aortic valves) of the following risk factors are present: atrial fibrillation, LV dysfunction, previous thromboembolism, hypercoagulable condition, and mechanical prosthesis (107). Antiplatelet agents (see Chapter 57) are not adequate to prevent thromboembolic complications, which occur at an annual rate of 7.5% with aspirin treatment (107). The low-molecular-weight heparins have not been adequately studied for this purpose; numerous cases of both successes and failures with this approach have been reported in the medical literature. The routine addition of low-dose (80–100 mg) aspirin to warfarin has been advocated for patients with the following risk factors for thromboembolism: prior embolization, vascular disease, or hypercoagulable state. This maneuver reduces the risk of thromboembolism but increases the incidence of bleeding complications.
Patients with tissue valves in the aortic position should be anticoagulated for 3 months after operation only so that endothelialization of the valve may occur. Warfarin then should be discontinued unless risk factors for thromboembolism are present. In that case, warfarin should be continued with a target INR of 2 to 3. Controversy exists over whether tissue valves in the mitral position require long-term anticoagulation. Most cardiologists discontinue warfarin after 3 months and then use aspirin only, unless risk factors for thromboembolism were present. In that case, warfarin should be continued with a target INR of 2.5 to 3.5. Strict antibiotic prophylaxis against endocarditis is indicated. Tables 93.11 and 93.12 lists regimens recommended by the American Heart Association before and after various procedures.
Prosthetic valve dysfunction is an indication for referral to a cardiologist, who usually will recommend a transthoracic echocardiogram and possibly a TEE. After valve replacement, patients should be seen on an annual basis by a cardiologist to assess prosthetic valve function.Table 65.10 lists reasons to refer a patient with a prosthetic valve to a cardiologist.
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TABLE 65.10 Indications for Referral of Patients with Prosthetic Valves |
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Pregnancy in a Patient with a Prosthetic Valve
Pregnancy poses a serious problem in patients with mechanical prosthetic valves. Ingestion of warfarin during pregnancy results in a definite increase in the incidence of fetal death and birth defects (see Chapter 57). The spontaneous abortion rate in pregnant women who take warfarin is approximately 30% (111), probably because warfarin crosses the placenta and predisposes the fetus to intrauterine hemorrhage. Between 8% and 16% of liveborn infants have various birth defects, most commonly nasal hypoplasia with stippled epiphysis (a specific warfarin embryopathy), as well as optic atrophy, microcephaly, and mental retardation.
On the other hand, the risk of thromboembolism is greater during pregnancy, and discontinuation of anticoagulation greatly increases the danger of systemic embolism. In one study, systemic embolism was seen in 31% of such patients despite antiplatelet therapy (112). Most of the patients had Starr-Edwards valves.
There is no consensus regarding the management of early pregnancy when a mechanical prosthetic valve is in place. Some authors recommend substituting full-dose heparin, which does not cross the placenta, for warfarin during the first trimester of pregnancy (111). However, such therapy typically requires prolonged hospitalization, and the incidence of fetal death appears to be high with this regimen as well (see Chapter 57). Adjusted-dose unfractionated subcutaneous heparin has been administered during pregnancy but has been associated with a higher risk for thromboembolism and maternal death. Activated partial thromboplastin time or anti-factor Xa levels must be followed closely with unfractionated heparin to prevent thromboembolic events. The safety and efficacy of low-molecular-weight heparin in this situation has not been well established. If low-molecular-weight heparin is used, patients should be weighed frequently during pregnancy (i.e., every 2 weeks) and the dose of heparin adjusted appropriately, following anti-Xa levels throughout pregnancy (see Chapter 57). Heparin should be discontinued 24 hours prior to anticipated delivery. The proper management of anticoagulation at the end of pregnancy is more clearly defined. If warfarin has been given, it should be replaced by unfractionated heparin 2 weeks before delivery is expected. Heparin then can be stopped at the onset of labor to prevent peripartum hemorrhage and resumed 4 to 6 hours after delivery, providing there are no contraindications. Aspirin is not effective in preventing thromboembolism in these patients.
Most clinicians strongly counsel patients with mechanical prosthetic valves to avoid pregnancy. Pregnancy for the patient with a tissue (bioprosthetic) valve is much safer because anticoagulation with warfarin and heparin can be avoided. Patients with prosthetic valves should be well aware of the risks if pregnancy is contemplated. Pregnancy or the desire to become pregnant is an indication for referral to both a cardiologist and an obstetrician specializing in high-risk patients.
The best approach to these problems is to avoid valve replacement in women in whom future pregnancy is likely. If possible, mitral stenosis should be managed medically, with percutaneous valvuloplasty, or with surgical commissurotomy and mitral regurgitation with medical therapy or valve repair. If valve replacement is necessary in such a patient, the surgeon should be strongly urged to use a bioprosthesis rather than a mechanical valve, and the patient should be aware that eventual reoperation will be necessary. For the aortic valve, the pulmonary autograft (Ross procedure) provides good long-term results without the need for anticoagulation. In this procedure, the pulmonary valve is autotransplanted into the aortic position and is replaced with a cadaveric homograft.
Specific References*
For annotated General References and resources related to this chapter, visit http://www.hopkinsbayview.org/PAMreferences.
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