American College of Cardiology

BONOW ET AL., ACC/AHA TASK FORCE REPORT
JACC Vol. 32, No. 5, November 1998:1486-1588

ACC/AHA Guidelines for the Management of Patients With Valvular Heart Disease

II. General Principles

A. Evaluation of the Patient With a Cardiac Murmur

1. Introduction. Cardiac auscultation remains the most widely used method of screening for heart disease. The production of murmurs is due to 3 main factors: (1) high blood flow rate through normal or abnormal orifices; (2) forward flow through a narrowed or irregular orifice into a dilated vessel or chamber; or (3) backward or regurgitant flow through an incompetent valve, septal defect, or patent ductus arteriosus. Often, several of these factors are operative (5-7).

A heart murmur may have no pathological significance or may be an important clue to the presence of valvular, congenital, or other structural abnormalities of the heart (8). Most systolic heart murmurs do not signify cardiac disease, and many are related to physiological increases in blood flow velocity (9). In other instances, a heart murmur may be an important clue to the diagnosis of undetected cardiac disease (eg, valvular aortic stenosis) that may be important even when asymptomatic or that may define the reason for cardiac symptoms. In these situations, various noninvasive or invasive cardiac tests may be necessary to establish a firm diagnosis and form the basis for rational treatment of an underlying disorder. Two-dimensional (2-D) and Doppler echocardiography is particularly useful in this regard, as discussed in the ACC/AHA Guidelines for the Clinical Application of Echocardiography (2). Diastolic murmurs virtually always represent pathological conditions and require further cardiac evaluation, as do most continuous murmurs. Continuous "innocent" murmurs include venous hums and mammary soufflés.

The traditional auscultation method of assessing cardiac murmurs has been based on their timing in the cardiac cycle, configuration, location and radiation, pitch, intensity (grades 1 through 6), and duration (5-9). The configuration of a murmur may be crescendo, decrescendo, crescendo-decrescendo (diamond-shaped), or plateau. The precise times of onset and cessation of a murmur associated with cardiac pathology depend on the point in the cardiac cycle at which an adequate pressure difference between 2 chambers appears and disappears (5-9). A classification of cardiac murmurs is listed in Table 1.

2. Classification of Murmurs. Holosystolic (pansystolic) murmurs are generated when there is flow between chambers that have widely different pressures throughout systole, such as the left ventricle and either the left atrium or right ventricle. With an abnormal regurgitant orifice, the pressure gradient and regurgitant jet begin early in contraction and last until relaxation is almost complete.

Midsystolic (systolic ejection) murmurs, often crescendo-decrescendo in configuration, occur when blood is ejected across the aortic or pulmonic outflow tracts. The murmurs start shortly after S₁, when the ventricular pressure rises sufficiently to open the semilunar valve. As ejection increases, the murmur is augmented, and as ejection declines, it diminishes.

In the presence of normal semilunar valves, this murmur may be caused by an increased flow rate such as that which occurs with elevated cardiac output (eg, pregnancy, thyrotoxicosis, anemia, arteriovenous fistula), ejection of blood into a dilated vessel beyond the valve, or increased transmission of sound through a thin chest wall. Most benign innocent murmurs occurring in children and young adults are midsystolic and originate either from the aortic or pulmonic outflow tracts. Valvular or subvalvular obstruction (stenosis) of either ventricle may also cause a midsystolic murmur, the intensity depending in part on the velocity of blood flow across the narrowed area. Midsystolic murmurs also occur in certain patients with mitral regurgitation (MR) or, less frequently, tricuspid regurgitation (TR) resulting from papillary muscle dysfunction. Echocardiography is often necessary to separate a prominent and exaggerated (Grade 3 or greater) benign midsystolic murmur from one due to valvular aortic stenosis (AS).

Early systolic murmurs are less common; they begin with the first sound and end in midsystole. An early systolic murmur is often due to TR occurring in the absence of pulmonary hypertension and in other patients with acute MR. In large ventricular septal defects with pulmonary hypertension and small muscular ventricular septal defects, the shunting at the end of systole may be insignificant, with the murmur limited to early and midsystole.

Late systolic murmurs are soft or moderately loud, high-pitched murmurs at the left ventricular (LV) apex that start well after ejection and end before or at S₂. They are often due to ischemia or infarction of the mitral papillary muscles or to their dysfunction due to LV dilatation. Late systolic murmurs in patients with midsystolic clicks result from late systolic regurgitation due to prolapse of the mitral leaflet(s) into the left atrium. Such late systolic murmurs can also occur in the absence of clicks.

Early immediate diastolic murmurs begin with or shortly after S₂, when the associated ventricular pressure drops sufficiently below that in the aorta or pulmonary artery. High-pitched murmurs of aortic regurgitation (AR) or pulmonic regurgitation due to pulmonary hypertension are generally decrescendo, consistent with the rapid decline in volume or rate of regurgitation during diastole. The diastolic murmur of pulmonic regurgitation without pulmonary hypertension is low to medium pitch, and the onset of this murmur is slightly delayed because regurgitant flow is minimal at pulmonic valve closure, when the reverse pressure gradient responsible for the regurgitation is minimal.

Middiastolic murmurs usually originate from the mitral and tricuspid valves, occur early during ventricular filling, and are due to a relative disproportion between valve orifice size and diastolic blood flow volume. Although they are usually due to mitral or tricuspid stenosis, middiastolic murmurs may also be due to increased diastolic blood flow across the mitral or tricuspid valve when such valves are severely regurgitant, across the normal mitral valve in patients with ventricular septal defect or patent ductus arteriosus, and across the normal tricuspid valve in patients with atrial septal defect. In severe, long-term AR, a low-pitched diastolic murmur (Austin-Flint murmur) is often present at the LV apex; it may be either middiastolic or presystolic.

Presystolic murmurs begin during the period of ventricular filling that follows atrial contraction and therefore occur in sinus rhythm. They are usually due to mitral or tricuspid stenosis. A right or left atrial myxoma may cause either middiastolic or presystolic murmurs similar to tricuspid or mitral stenosis (MS).

Continuous murmurs arise from high- to low-pressure shunts that persist through the end of systole and the beginning of diastole. Thus, they begin in systole, peak near S₂, and continue into all or part of diastole. There are many causes of continuous murmurs, but they are uncommon in patients with valvular heart disease (5-9).

a. Dynamic Cardiac Auscultation. Attentive cardiac auscultation during dynamic changes in cardiac hemodynamics often enables the careful observer to deduce the correct origin and significance of a cardiac murmur (10-13). Changes in the intensity of heart murmurs during various maneuvers are indicated in Table 2.

b. Other Physical Findings. The presence of other physical findings, either cardiac or noncardiac, may provide important clues to the significance of a cardiac murmur and the need for further testing (Figure 1). For example, a right heart murmur in early to midsystole at the lower left sternal border likely represents TR without pulmonary hypertension in an intravenous drug user who presents with fever, petechiae, Osler's node, and Janeway lesion.

Associated cardiac findings frequently provide important information about cardiac murmurs. Fixed splitting of the second heart sound during inspiration and expiration in a patient with a grade 2/6 midsystolic murmur in the pulmonic area and left sternal border should suggest the possibility of an atrial septal defect. A soft or absent A₂ or reversed splitting of S₂ may denote severe AS. An early aortic systolic ejection sound heard during inspiration and expiration suggests a bicuspid aortic valve, whereas an ejection sound heard only in the pulmonic area and left sternal border during expiration usually denotes pulmonic valve stenosis. LV dilatation on precordial palpation and bibasilar pulmonary rales favor the diagnosis of MR in a patient with a grade 2/6 holosystolic murmur at the cardiac apex. A slow-rising, diminished arterial pulse suggests severe AS in a patient with a grade 2/6 midsystolic murmur at the upper intercostal spaces. The typical pulsus parvus and tardus may be absent in the elderly, even with severe AS secondary to the effects of aging on the vasculature. Pulsus parvus may also occur with severely low output from any cause. Factors that aid in the diagnosis of LV outflow tract obstruction are listed in Table 3.

c. Associated Symptoms. An important consideration in a patient with a cardiac murmur is the presence or absence of symptoms (14) (Figure 1). For example, symptoms of syncope, angina pectoris, or congestive heart failure in a patient with a midsystolic murmur will usually result in a more aggressive approach than in patients with a similar midsystolic murmur who have none of these symptoms. 2-D and Doppler echocardiography to rule in or out the presence of significant AS will likely be obtained. A history of thromboembolism or possible infective endocarditis will also usually result in a more extensive workup. In patients with cardiac murmurs and clinical findings suggestive of endocarditis, 2-D and Doppler echocardiography is usually indicated (2).

Conversely, many asymptomatic children and young adults with grade 2/6 midsystolic murmurs and no other cardiac physical findings need no further cardiac workup after the initial history and physical examination (Figure 1). A particularly important group is the large number of asymptomatic elderly patients, many with systemic hypertension, who have midsystolic murmurs related to sclerotic aortic valve leaflets; flow into tortuous, noncompliant great vessels; or a combination of these. Such murmurs must be distinguished from those caused by mild to severe valvular AS, which is prevalent in this age group. The absence of LV hypertrophy on electrocardiography is reassuring, and this test is considerably less costly than routine echocardiography.

d. Electrocardiography and Chest Roentgenography. Although echocardiography usually provides more specific and often quantitative information about the significance of a heart murmur and may be the only test needed, the electrocardiogram (ECG) and chest x-ray are readily available and may have been obtained already. The absence of ventricular hypertrophy, atrial abnormality, arrhythmias, conduction abnormalities, prior myocardial infarction, and evidence of active ischemia on the ECG provides useful negative information at a relatively low cost. Abnormal findings on the ECG, such as ventricular hypertrophy or a prior infarction, should lead to a more extensive evaluation including 2-D and Doppler echocardiography (Figure 1).

Posteroanterior and lateral chest roentgenograms often yield qualitative information on cardiac chamber size, pulmonary blood flow, pulmonary venous pressures, pulmonary vascular redistribution, and cardiac calcification in patients with cardiac murmurs. When abnormal findings are present on chest x-ray, 2-D and Doppler echocardiography should be performed (Figure 1). A normal chest x-ray and ECG are likely in patients with insignificant midsystolic cardiac murmurs, particularly in younger age groups and when the murmur is less than grade 3 in intensity (15-17). Many asymptomatic patients need neither an ECG nor a chest x-ray when a careful cardiac examination indicates an insignificant vibratory midsystolic heart murmur and no other abnormal findings.

e. Echocardiography. Echocardiography is an important noninvasive method for assessing the significance of cardiac murmurs by imaging cardiac structure and function and the direction and velocity of blood flow through cardiac valves and chambers. 2-D echocardiography may indicate abnormal valvular motion and morphology but usually does not indicate the severity of valvular stenosis or regurgitation except in MS. With Doppler echocardiography, a change or shift in ultrasound frequency indicates the direction and velocity of flow in relation to transducers. The direction of flow is displayed as a spectral velocity profile of blood flowing toward or away from the transducer. The velocity reflects the pressure gradient across stenotic and regurgitant valves. The presence of an abnormal regurgitant jet on color flow imaging detects valvular regurgitation and provides semiquantitative information about its severity.

Although 2-D echocardiography and color flow Doppler imaging can provide important information on patients with cardiac murmurs, these tests are not necessary for all patients with cardiac murmurs and usually add little but expense in the evaluation of asymptomatic patients with short grade 1 to 2 midsystolic murmurs and otherwise normal physical findings. Alternatively, if the diagnosis is still questionable after transthoracic echocardiography, transesophageal echocardiography or cardiac catheterization may be appropriate.

It is important to consider that many recent studies indicate that Doppler ultrasound devices are very sensitive and may detect valvular regurgitation through the tricuspid and pulmonic valves in a large percentage of young, healthy subjects and through left-sided valves (particularly the mitral) in a variable but lower percentage (18-22).

General recommendations for performing 2-D and Doppler echocardiography in asymptomatic and symptomatic patients with heart murmurs follow. Of course, individual exceptions to these indications may exist.

Recommendations for Echocardiography in Asymptomatic Patients With Cardiac Murmurs

Recommendations for Echocardiography in Symptomatic Patients With Cardiac Murmurs

f. Cardiac Catheterization. Cardiac catheterization can provide important information about the presence and severity of valvular obstruction, valvular regurgitation, and intracardiac shunting. It is not necessary in most patients with cardiac murmurs and normal or diagnostic echocardiograms but provides additional information on some patients in whom there is a discrepancy between echocardiographic and clinical findings. Indications for cardiac catheterization for hemodynamic assessment of specific valve lesions are given in sections III.A. through III.F. of these guidelines. Specific indications for coronary arteriography to assess the presence of coronary disease are given in section VIII.

3. Approach to the Patient. The evaluation of the patient with a heart murmur may vary greatly, depending on many of the considerations discussed above (17,23). These include the intensity of the cardiac murmur, its timing in the cardiac cycle, its location and radiation, and its response to various physiological maneuvers (Table 2). Also of importance is the presence or absence of cardiac and noncardiac symptoms and whether other cardiac or noncardiac physical findings suggest that the cardiac murmur is clinically significant (Figure 1).

Patients with definite diastolic heart murmurs or continuous murmurs not due to a cervical venous hum or a mammary soufflé during pregnancy are candidates for 2-D and Doppler echocardiography. If the results of echocardiography indicate significant heart disease, further evaluation may be indicated. An echocardiographic examination is also recommended for most patients with apical or left sternal edge holosystolic or late systolic murmurs, for patients with midsystolic murmurs of grade 3 or greater intensity, and for patients with softer systolic murmurs in whom dynamic cardiac auscultation suggests a definite cardiac diagnosis (eg, hypertrophic cardiomyopathy).

More specifically, further evaluation including echocardiography is recommended for patients in whom the intensity of a systolic murmur increases during the Valsalva maneuver, becomes louder when the patient assumes the upright position, and decreases in intensity when the patient squats. These responses suggest the diagnosis of either hypertrophic cardiomyopathy or mitral valve prolapse (MVP). Additionally, further assessment is indicated when a systolic murmur increases in intensity during transient arterial occlusion, becomes louder during sustained handgrip exercise, or does not increase in intensity either in the cardiac cycle following a premature ventricular contraction or after a long R-R interval in patients with atrial fibrillation. The diagnosis of MR or ventricular septal defect is likely.

In many patients with grade 1 to 2 midsystolic murmurs, an extensive workup is not necessary. This is particularly true for children and young adults who are asymptomatic, have an otherwise normal cardiac examination, and have no other physical findings associated with cardiac disease.

However, echocardiography is indicated in certain patients with grade 1 to 2 midsystolic murmurs, including patients with symptoms or signs consistent with infective endocarditis or thromboembolism and those with symptoms or signs consistent with congestive heart failure, myocardial ischemia, or syncope. Echocardiography also usually provides an accurate diagnosis in patients with other abnormal physical findings on cardiac palpation or auscultation, the latter including widely split second heart sounds, systolic ejection sounds, and specific changes in intensity of the systolic murmur during certain physiological maneuvers as described in Table 2.

Although 2-D and Doppler echocardiography is an important test for those with a moderate to high likelihood of a clinically important cardiac murmur, it must be reemphasized that trivial, minimal, or physiological valvular regurgitation, especially affecting the mitral, tricuspid, or pulmonic valves, is detected by color flow imaging techniques in many otherwise normal patients and includes many patients who have no heart murmur at all (18-22). This must be considered when the results of echocardiography are used to guide decisions concerning asymptomatic patients in whom echocardiography was used to assess the clinical significance of an isolated murmur.

Very few data address the cost-effectiveness of various approaches to the patient undergoing medical evaluation of a cardiac murmur. Optimal auscultation by well-trained examiners who can recognize an insignificant midsystolic murmur with confidence (by dynamic cardiac auscultation as indicated) results in less frequent use of expensive additional testing to define murmurs that do not indicate cardiac pathology.

Many murmurs in asymptomatic adults are innocent and have no functional significance. Such murmurs have the following characteristics: (1) grade 1 to 2 intensity at the left sternal border; (2) a systolic ejection pattern; (3) normal intensity and splitting of the second heart sound; (4) no other abnormal sounds or murmurs; and (5) no evidence of ventricular hypertrophy or dilatation and the absence of increased murmur intensity with the Valsalva maneuver (10). Such murmurs are especially common in high-output states such as pregnancy (24,25). When the characteristic features of individual murmurs are considered together with information obtained from the history and physical examination, the correct diagnosis can usually be established (17). In patients with ambiguous clinical findings, the echocardiogram can often provide a definite diagnosis, rendering a chest x-ray and/or ECG unnecessary.

In the evaluation of heart murmurs, the purposes of echocardiography are to (1) define the primary lesion in terms of etiology and severity; (2) define hemodynamics; (3) define coexisting abnormalities; (4) detect secondary lesions; (5) evaluate cardiac chamber size and function; (6) establish a reference point for future comparisons; and (7) reevaluate the patient after an intervention.

As valuable as echocardiography may be, the basic cardiovascular physical examination is still the most appropriate method of screening for cardiac disease and will establish many clinical diagnoses. Echocardiography should not replace the cardiovascular examination but can be useful in determining the etiology and severity of lesions, particularly in elderly patients.

B. Endocarditis and Rheumatic Fever Prophylaxis

1. Endocarditis Prophylaxis. Endocarditis is a serious illness associated with significant mortality. Its prevention by appropriate administration of antibiotics before procedures expected to produce bacteremia merits serious consideration. Experimental studies suggest that endothelial damage leads to platelet and fibrin deposition and thus a nonbacterial thrombotic endocardial lesion. In the presence of bacteremia, the organisms adhere to these lesions and multiply within the platelet-fibrin complex, leading to an infective vegetation (26,27). Valvular and congenital abnormalities, especially those that result in abnormal high-velocity jet streams, can damage the endothelial lining and predispose to platelet aggregation and fibrin deposition at those sites, which are thus at higher risk for bacterial colonization.

Several issues must be considered in generating recommendations for endocarditis prophylaxis (28). Evidence supporting prophylaxis consists of the following:

1. Clinical experience documents endocarditis following bacteremia.
2. Bacteremia by organisms known to produce endocarditis follows various procedures such as dental procedures, endoscopy, cystoscopy, etc.
3. Antibiotics to which known offending organisms are sensitive are available.
4. In laboratory animal models of endocarditis, antibiotic prophylaxis has been shown to be effective.
5. Small clinical studies in humans appear to show benefit from prophylaxis against endocarditis (29,30).

The following evidence raises questions about the value of prophylaxis:

1. Lack of any sufficiently large, controlled clinical trials to support the application of the results of laboratory animal studies to humans.
2. Clinical reports of failure of antibiotic prophylaxis against endocarditis (28,31) or studies that appear to show that prophylaxis is not protective (32).
3. The evidence that dental and other procedures cause endocarditis is circumstantial. With the incidence of bacteremia (positive blood culture) varying from 8% (urethral catheterization) to as high as 88% (periodontal surgery) (33), the actual incidence of endocarditis is low (10 to 60 cases/1 million persons per year) (28).
4. In specific circumstances, such as prophylaxis for all cases of MVP, the risk of death from penicillin prophylaxis is estimated to be greater than the risk for infective endocarditis (34,35).

In view of these issues, it has been suggested that the risk of endocarditis in patients with preexisting cardiac disorders be classified as relatively high, moderate, and low or negligible, as determined by the cardiac disorder. Guidelines for the prevention of endocarditis have been issued by the American Heart Association (36), and the recommendations made here are based on those guidelines.

Various dental and/or surgical procedures are associated with varying degrees and frequencies of bacteremia. The frequency of bacteremia is highest with dental and oral procedures, intermediate with procedures involving the genitourinary tract, and lowest with gastrointestinal diagnostic procedures (28). Recommendations for endocarditis prophylaxis, as determined by dental, surgical, and other procedures, are listed in Tables 4, 5, 6, 7.

The procedure--thus the portal of entry--is a determinant of the type of organism involved in the resulting bacteremia. This is usually the determinant of the antibiotic chosen for prophylaxis. Because streptococci are normal inhabitants of the oral cavity, the antibiotic prophylaxis regimen for dental and oral procedures is directed against these organisms. For genitourinary and lower gastrointestinal procedures, the antibiotic prophylactic regimen is designed to cover enterococci and other gram-negative organisms.

Recommendations for Endocarditis Prophylaxis

2. Rheumatic Fever Prophylaxis. a. General Considerations. Rheumatic fever is an important cause of valvular heart disease. In the United States (and Western Europe), cases of acute rheumatic fever have been uncommon since the 1970s. However, starting in 1987, an increase in cases has been observed (38,39). With the enhanced understanding of the causative organism, group A streptococcus, their rheumatogenicity is attributed to the prevalence of M protein serotypes in the offending organism. This has resulted in the development of kits that allow rapid detection of group A streptococci with specificity >95% and more rapid identification of their presence in upper respiratory infection. Because the test has a low sensitivity, the negative test requires a throat culture confirmation (39). Prompt recognition and treatment represent primary rheumatic fever prevention. For patients who have had a previous episode of rheumatic fever, continuous antistreptococcal prophylaxis results in secondary prevention.

b. Primary Prevention. Rheumatic fever prevention treatment guidelines have been established by the American Heart Association (40) (Table 8).

c. Secondary Prevention. Patients who have had an episode of rheumatic fever are at high risk of developing recurrent episodes of acute rheumatic fever. Patients who develop carditis are especially prone to similar episodes with subsequent attacks. Secondary prevention of rheumatic fever recurrence is thus of great importance. Continuous antimicrobial prophylaxis has been shown to be effective. Anyone who has had rheumatic fever with or without carditis (including MS) should have prophylaxis for recurrent rheumatic fever. The AHA guidelines for secondary prevention are shown in Table 9. The AHA guidelines for duration of secondary prevention are shown in Table 10.

© 1998 American College of Cardiology and American Heart Association, Inc. Published by Elsevier Science Inc.