Primary Care Medicine: Office Evaluation and Management of the Adult Patient 6th Edition 2009 Lippincott Williams

s & Wilkins

Chapter 21 Evaluation of the Asymptomatic Systolic Murmur In the outpatient setting, systolic murmurs are often noted incidentally in otherwise asymptomatic patients. Although many asymptomatic murmurs are due to conditions of no prognostic significance, the absence of symptoms does not rule out the presymptomatic phase of potentially serious pathology, such as tight aortic stenosis. The primary physician should be able to conduct an effective clinical assessment in the office that differentiates the harmless murmur from one that requires additional investigation. Early detection of clinically silent but prognostically important disease is critical to optimizing outcomes and to identifying patients who require close follow-up. Routinely ordering a cardiac ultrasound examination on every patient discovered to have a systolic heart murmur is both expensive and unnecessary, but selective use can be very helpful. This chapter focuses on clinical and ultrasound assessment of the asymptomatic patient (see Chapters 20, 24, 25, 33, and 40 for detailed discussions of evaluation and management of symptomatic patients with structural heart disease). Pathophysiology and Clinical Presentation (1,2,3,4,5,6,7,8,9,10,11) Systolic murmurs can be divided into two broad categories: ejection and regurgitant (see also Chapter 33). Ejection murmurs result from turbulent flow of blood across the ventricular outflow tracts during systole. They are characteristically crescendo decrescendo, medium to low pitched, and heard best at the base of the heart, beginning after the first heart sound and ending before the second. Regurgitation murmurs represent backflow of blood due to incompetence of the mitral or tricuspid valve or the ventricular septum. They are typically higher in pitch, heard best at the apex or mid-sternal border, holosystolic or mid-systolic to late systolic in timing, and, like ejection murmurs, crescendo decrescendo in pattern (unless rheumatic in origin, in which case the intensity is constant). Ejection murmurs are common and often occur in the absence of heart disease. However, absence of symptoms does not mean absence of important underlying pathology. Regurgitant murmurs are associated with some abnormality of the mitral or tricuspid valve apparatus, valve ring, or septum, but the underlying lesion is not always of clinical significance. Ejection Murmurs Physiologic Murmurs Physiologic murmurs occur when there is increased ejection velocity across a normal valve creating turbulence. Causes of increased velocity include fever, anemia, pregnancy, hyperthyroidism, exercise, and conditions associated with a large stroke volume (e.g., aortic regurgitation, bradycardia, atrial septal defect [ASD]). Dilation of the aorta, as in hypertension or aging, may also produce a flow murmur by causing turbulent flow in the dilated segment. Innocent Murmurs

Innocent murmurs occur in normal hearts under resting conditions. The origin of such murmurs is a subject of debate, with recent evidence pointing to the aortic root. Because there is no obstruction in the outflow tract, the murmur reflects the normal ejection pattern of blood from the ventricles and is early systolic and crescendo decrescendo. Because chamber pressures are normal, there is normal splitting of heart sounds. Valves are normal; there are no adventitious sounds or other murmurs. Early Aortic and Pulmonic Valve Disease Early aortic and pulmonic valve disease may produce murmurs identical to physiologic ones, except that the former are often accompanied by an early systolic ejection click. In pulmonic stenosis, the murmur increases with inspiration, and the pulmonic component of the second sound is delayed as the disease progresses, widening the splitting of the second heart sound. With increasing stenosis, ejection murmurs usually become louder and more prolonged, with peak intensity occurring later in systole. In hemodynamically significant aortic stenosis, a sustained left ventricular heave develops, the carotid upstroke becomes delayed and lower in amplitude (the parvus et tardus pattern), and the second heart sound becomes softer and single as the aortic closing sound decreases. Calcific Aortic Stenosis Calcific aortic stenosis is the most common cause of aortic stenosis in the elderly. Onset is in the fourth decade if the underlying valve is bicuspid and in the sixth to eighth decades if the valve is an otherwise normal tricuspid one. Most patients present with symptoms of advanced disease (angina, heart failure, syncope) because the condition often goes unrecognized in the asymptomatic phase. Early diagnosis is often made difficult by the speed of disease progression and the deceptively subtle and atypical physical findings in elderly persons with hemodynamically significant disease. Valve calcification can progress rapidly, leading to hemodynamically significant outflow tract obstruction in as little as 1 to 2 years. Unlike other forms of aortic stenosis, the murmur at the base may reappear at the apex as a higher-pitched sound and simulate mitral regurgitation (Gallavardin s phenomenon). In addition, the left ventricular lift associated with hemodynamically significant disease may be less prominent due to myocardial decompensation, and the carotid upstroke may be normal if the carotid artery is stiff due to age. Aortic Sclerosis Aortic sclerosis, also referred to as aortic valve thickening, is a precursor of calcific aortic stenosis, with 1-year risk of P.153

progression reported to be in excess of 15%. It is prevalent in the elderly (found in 40% of persons >75 years of age) and characterized by thickening of the aortic valve leaflets without causing outflow obstruction. Nonetheless, the condition is associated with an increased risk of cardiovascular morbidity and mortality, believed related to its association with atherosclerotic risk factors; however, only concurrent calcification of the mitral valve annulus has proven to be predictive of progression to hemodynamically significant aortic stenosis (perhaps reflective of a generalized process). Hypertrophic Cardiomyopathy (Idiopathic Hypertrophic Subaortic Stenosis) Hypertrophic cardiomyopathy produces an ejection quality murmur by dynamically obstructing the left ventricular outflow tract. Displacement of the mitral valve may also occur dynamically and cause regurgitation. The ejection murmur is affected by the size of the left ventricular cavity and contractility. Maneuvers that decrease cavity size (e.g., Valsalva) increase obstruction and intensify the murmur. When there is marked obstruction, the murmur lasts through

most of systole, and its peak is delayed beyond mid-systole. Some patients are prone to tachyarrhythmias. The electrocardiogram (ECG) shows high voltage. Atrial Septal Defects Atrial septal defects produce physiologic murmurs due to increased right ventricular stroke volume. However, unlike other physiologic murmurs, there is often wide and fixed splitting of the second sound due to left-to-right shunting of blood and a delay in right ventricular ejection. Patients with physiologic or innocent murmurs are generally asymptomatic from a cardiac standpoint and usually have no previous history of heart disease. Patients with mild varieties of aortic or pulmonic stenosis hypertrophic cardiomyopathy or a small ASD may be asymptomatic as well. In patients with aortic stenosis, onset of symptoms (e.g., angina, dyspnea, postural lightheadedness) is usually a late development indicating advanced disease (see Chapter 33). Regurgitant Murmurs Regurgitant murmurs of the arterioventricular valves may be holosystolic or late systolic, depending on the anatomy and function of the compromised valve apparatus. Holosystolic Regurgitant Mitral Murmurs Holosystolic regurgitant mitral murmurs usually occur with conditions that render the mitral valve incompetent throughout systole and include rheumatic mitral valve disease, bacterial endocarditis, severe cases of dilated cardiomyopathy, papillary muscle rupture, and endocardial fibrosis of the valve surface. The latter has been associated with prolonged, high-dose use of the diet-pill combination phentermine/fenfluramine (see Chapter 234). The purported mechanism of valve fibrosis is excessive serotonergic effects on valve endocardial metabolism leading to clinically significant incompetence of mitral, tricuspid, and aortic valves. Tricuspid Regurgitation Tricuspid regurgitation due to valve injury or right ventricular dilation produces a murmur similar in quality and timing to that of mitral regurgitation but is heard best along the left sternal border rather than the apex and characteristically increasing with inspiration. Ventricular Septal Defect Another mechanism of holosystolic murmur is left-to-right shunting, as occurs with ventricular septal defect (VSD). The holosystolic murmur of VSD is heard best at the left sternal border as a consequence of turbulence from the left-to-right shunting of blood. With prolonged shunting and resultant increase in right ventricular pressure, the pressure gradient and degree of shunting may decline and with it the intensity of the murmur. It is differentiated from tricuspid regurgitation by maneuvers that increase afterload (see later discussion). Late-Systolic Regurgitant Murmur Late-systolic regurgitant murmurs result from valve incompetence that develops as systole progresses. Mid- to latesystolic murmurs are characteristic of the mitral regurgitation due to mitral valve prolapse (MVP) and papillary muscle dysfunction associated with ischemic heart disease. Mitral valve prolapse is the most common cause of an asymptomatic mitral regurgitant murmur in the outpatient setting. The condition is characterized by myxomatous degeneration of the valve leaflets and chordae due to abnormal glucosaminoglycan composition, making them weaker and more likely to stretch and prolapse. In the Framingham

Study, the prevalence was initially reported to be as high as 17% among young women and 4% among young men. Use of more-stringent echocardiographic criteria and avoidance of selection bias has refined and reduced the estimated prevalence to 2.4%, with little difference between young men and young women. MVP, with its late-systolic murmur, is often preceded by a click as the redundant mitral valve leaflets prolapse into the atrium during late systole. Most patients with MVP have no other signs or symptoms of heart disease, although an important minority experience atypical chest pain, dysrhythmias, or dyspnea. In a few instances, particularly in older men, hemodynamically significant mitral regurgitation occurs. Asthenic builds in both men and women have been associated with MVP, as has small breast size in women. Nonspecific T-wave changes, particularly inferior lead T-wave inversion, have been described. Diagnosis is confirmed by finding definite prolapse of mitral valve leaflets in the parasternal long-axis view on two-dimensional (Bmode) ultrasound study. Differential Diagnosis (12) The differential diagnosis can be listed according to the underlying pathophysiology. Thus, systolic ejection murmurs can be classified as innocent, physiologic, aortic, and pulmonic. Regurgitant murmurs may be caused by incompetence of the mitral or tricuspid valves or by a VSD (Table 21.1). Of note, some patients have more than one cause present; in a study of patients coming to ultrasound, 28% had evidence of combined heart disease. Workup (3,6,7,8,12,13,14,15,16,17,18,19,20,21,22,23) Differentiating Systolic Regurgitant Murmurs from Ejection Murmurs In many instances, the distinction can be made early in the evaluation by physical examination. Doing so helps to narrow the P.154

differential diagnosis (Table 21.1) and focus the workup. The murmur s timing, quality, and location are among the most important differentiating features. As noted earlier, ejection-quality murmurs are typically harsh, best heard with the bell, usually loudest at the base, and radiate into the neck and down to the apex. In elderly patients with calcific aortic stenosis, the murmur may be higher pitched and maximal at the apex, mimicking mitral regurgitation. The systolic regurgitant murmurs of mitral and tricuspid regurgitation are characteristically high pitched, well localized to the apex or left sternal border (unless very loud), and pansystolic or late systolic (and sometimes preceded by a click). All ejection murmurs and most regurgitant murmurs (except for those of rheumatic origin) have a crescendo decrescendo pattern, making this feature of little use in differentiation. Similarly, finding of electrocardiographic evidence of hypertrophy does not rule out a regurgitant etiology because some degree of eccentric hypertrophy often develops in compensated mitral regurgitation. Table 1 Differential Diagnosis of Systolic Ejection Murmur Innocent Murmurs Physiologic Murmurs Exercise or emotion Fever Anemia

Hyperthyroidism Conditions with large stroke volumes: atrial septal defect, aortic regurgitation, bradycardia Pregnancy Aortic Murmurs Aortic stenosis Hypertrophic cardiomyopathy Sub- and supravalvular fixed stenoses Pulmonic Murmurs Pulmonic stenosis Mitral Regurgitation Murmurs Rheumatic mitral insufficiency Mitral valve prolapse syndrome Congenital mitral valve disease Rupture of chordae tendineae Papillary muscle dysfunction Left atrial myxoma Dilated mitral valve ring Tricuspid Regurgitation Murmurs Rheumatic tricuspid insufficiency Dilated tricuspid valve ring Ventricular Septal Defect A few additional murmur characteristics and responses to maneuvers can be helpful diagnostically. Ejection murmurs change in intensity with heart rate and length of the cardiac cycle, becoming softer with increases in rate and louder as rate decreases. Regurgitant murmurs change little if at all with heart rate. Handgrip and other maneuvers that increase systolic pressure (e.g., transient arterial occlusion by inflation of blood pressure cuffs applied to both arms) markedly augment the intensity of the regurgitant murmurs of mitral regurgitation and VSD. Right-sided heart murmurs can be differentiated from left-sided ones by the augmentation in intensity that occurs with quiet inspiration. Cardiac ultrasound examination is sometimes necessary for differentiating regurgitant disease from causes of an ejection murmur, especially in the context of concurrent left ventricular dysfunction, involvement of multiple valves, or cardiomyopathy. The test, particularly when performed in conjunction with a Doppler study, is also an important adjunct for assessment of disease severity; it should be considered when there is clinical suspicion of a hemodynamically significant lesion (see later discussion).

Assessment of Ejection Murmurs Separating Harmless Causes from More Serious Pathology Attention to timing, quality, intensity, and location is helpful. Innocent and physiologic murmurs are usually mid-range in frequency, less than 3/6 in intensity, peak in early to mid-systole, stop long before S2, and are heard best at the base, although they can radiate to neck and apex. Valsalva and standing decrease their intensity. The second sound is normally split and of normal intensity; there are no clicks, heaves, S3, S4, or other murmurs. The ECG and chest radiograph are normal. Signs of anemia, fever, hyperthyroidism, and anxiety should be sought. The murmurs resulting from ASD and hemodynamically insignificant aortic and pulmonic stenoses may resemble physiologic murmurs. However, in most cases of ASD there is widened and fixed splitting of S2, and in more than 90% of cases there is a conduction defect of the right-bundle-branch type, producing a QRS and lead V1 with an RSR prime configuration. A normal ECG and normal splitting of S2 indicate that an ASD is unlikely. When one is in doubt, an echocardiogram can be used to look for abnormal septal motion and right ventricular enlargement; a normal study rules out the diagnosis. Mild aortic stenosis in the young patient may be impossible to distinguish from a physiologic murmur; the presence of an ejection click is an important clue to the former. Clinical assessment is usually sufficient to distinguish the functional or innocent murmur from that due to underlying pathology. Sensitivity of the physical examination appears to equal that of ultrasound is this respect, making ultrasound confirmation unnecessary when clinical certainty is high. Estimating the Severity of Aortic Stenosis As aortic stenosis progresses and becomes more hemodynamically significant, the murmur typically gets louder and peaks later in systole, the second heart sound decreases in intensity as the aortic closure sound fades, a left ventricular lift develops, a thrill may be palpable, and the carotid upstroke becomes delayed and diminished in intensity. Evidence of left ventricular hypertrophy may appear on ECG (e.g., increased voltage, strain pattern), although the test is not a sensitive indicator. A high index of suspicion is necessary both for the detection of calcific aortic stenosis in the elderly and the estimation of its severity. One needs to remember to listen at the apex and at the base and not to be lulled into a false sense of security by the softness of the murmur, the absence of a vigorous left ventricular heave, or the normality of the carotid upstroke. Its presentation as a medium- to high-pitched musical murmur, heard best at the apex, may lead to confusion with mitral regurgitation. Helping to differentiate it from mitral regurgitation is the decrease in the murmur s intensity with increase in heart rate; in mitral regurgitation, there is no change in the murmur with heart rate. Clinical detection of hemodynamically P.155

significant disease can be particularly difficult in the context of declining left ventricular function, which may blunt many of the characteristic physical findings of severe stenosis. However, such patients usually have dyspnea or other symptoms (see Chapter 33), which should help raise the index of suspicion. Cardiac ultrasound is indicated when physical examination raises the question of important outflow-tract obstruction the fact that the patient is asymptomatic does not rule out hemodynamically significant disease. Confirmation of suspected valvular and subvalvular obstruction to left ventricular outflow and accurate estimation of its severity can be accurately accomplished echocardiographically, especially when performed in conjunction with a continuous-wave

Doppler study. For aortic stenosis, reasonably accurate estimates can often be obtained of valve area and pressure gradient across the valve. Severe stenosis is defined as a mean gradient in excess of 40 mm Hg with a calculated valve area less than 0.75 cm2. A valve area in the range of 0.76 to 1.1 cm2 and a gradient in the range of 15 to 39 mm Hg define moderate disease. Overestimates of severity can occur in the setting of low flow. The degree of valve calcification noted on echocardiography corresponds to the severity of stenosis. Ultrasound performed in the setting of aortic stenosis can provide additional information that may be useful, including estimation of ejection fraction and detection of hemodynamically significant aortic regurgitation. Diastolic regurgitant murmurs are often missed in the setting of prominent systolic murmurs, with even experienced examiners demonstrating no more than 40% sensitivity for clinical recognition of hemodynamically significant aortic insufficiency. Recognition of Idiopathic Hypertrophic Subaortic Stenosis Several maneuvers help to differentiate the systolic ejection murmur associated with this type of cardiomyopathy from other ejection murmurs. Most distinctive are the murmur s responses to squatting, passive leg elevation, and Valsalva, maneuvers that affect left ventricular chamber size through their effects on venous return. A lessening of venous return decreases chamber size and increases obstruction to outflow by the hypertrophic heart muscle. This is why Valsalva (bearing down against a closed glottis) results in an increase in the intensity of the murmur. With passive leg elevation and with change from standing to squatting, the murmur of hypertrophic disease characteristically decreases as venous return rises. Although sometimes the murmur may not change substantially with increasing venous return, any clear-cut increase in the murmur under such circumstances rules out hypertrophic cardiomyopathy. The murmur peaks around mid-systole, which helps to distinguish it from those innocent murmurs that peak earlier. Other features of the murmur include maximal intensity along the left sternal border and a brisk carotid upstroke that is sometimes bisferiens (bifid) in quality. Cardiac ultrasound is indicated when the diagnosis is suspected on clinical grounds. Moreover, the study may reveal mitral regurgitation, which is sometimes present in the setting of this hypertrophic cardiomyopathy. Recognition of Pulmonic Stenosis Hemodynamically significant pulmonic stenosis is suggested by a prolonged and loud murmur (greater than 3/6) that characteristically increases with inspiration, wide splitting or absence of the pulmonic component of the second heart sound, an ejection click that decreases with inspiration, a right ventricular lift, evidence of pulmonary artery dilation on chest film, and prominent R wave in V1 indicative of right ventricular hypertrophy. A normal ECG and an early systolic murmur rule out significant pulmonic stenosis. Mild hemodynamically insignificant pulmonic stenosis may be indistinguishable from an innocent murmur, but usually no therapy is indicated, and therefore misdiagnosis is of little consequence. Summary The key components of the initial evaluation of the systolic ejection murmur in the asymptomatic patient include attention to carotid upstroke; left and right ventricular impulses; second heart sound; clicks; the quality, timing, intensity, and location of the murmur; and the effects of provocative maneuvers that affect venous return, heart rate, and systemic resistance. ECG and chest radiograph may be helpful. Cardiac ultrasound examination in conjunction with Doppler study is indicated if there is clinical suspicion of hemodynamically significant disease or the diagnosis remains in doubt and there are adverse consequences to not identifying the lesion. Of note, aortic regurgitation is often missed clinically in the setting of aortic stenosis. Assessment of Regurgitant Systolic Murmurs

The timing and location of the regurgitant murmur are among the most helpful features diagnostically. The response to a number of simple bedside maneuvers can also provide useful information. Holosystolic Murmurs A holosystolic murmur suggests rheumatic or cardiomyopathic mitral insufficiency, tricuspid insufficiency, or a VSD. The murmur of classic mitral insufficiency is best heard at the apex and radiates laterally into the axilla; it varies little with cycle length or with respiration but increases markedly with handgrip and other maneuvers that transiently increase systemic resistance (e.g., bilateral blood pressure cuff inflation). With chronic increase in volume load, there is likely to be palpable enlargement of the left ventricle. Because multivalve involvement is the rule and heart failure may occur, a careful listening for other murmurs and a check for signs of heart failure (e.g., rales, third heart sound) are in order. However, a third heart sound is quite common in mitral regurgitation and not as predictive of systolic dysfunction as it is in other forms of heart disease. Differentiating Tricuspid from Mitral Insufficiency One notes the effect of respiration on the murmur. The systolic regurgitant murmur of tricuspid insufficiency increases with quiet inspiration and sustained abdominal pressure (applied to the right upper quadrant to compress the liver). Moreover, it is usually loudest at the lower left sternal border, but when the right ventricle is very large, it may be heard at the apex. It does not radiate well to the axilla. Intensity is strongly influenced by respiration, increasing at the beginning of inspiration and fading during early expiration. The presence of hepatojugular reflux is very suggestive and should be checked. Identifying Ventricular Septal Defect The holosystolic murmur of VSD can be heard best at the sternal border and does not radiate to the axilla. Intensity does not vary with respiration, but, like mitral regurgitation, it is increased with Valsalva, handgrip, and blood pressure cuff application. The murmur often has some mid-systolic accentuation and may be confused P.156

with an ejection murmur. Like mitral regurgitation, intensity of the murmur increases markedly with handgrip and other maneuvers that increase systemic resistance. Late-Systolic Murmurs MVP is characterized by a mid- to late-systolic murmur preceded by a mid-systolic click. Some forms of papillary muscle dysfunction will also result in a mitral regurgitant murmur of similar timing, usually in the setting of anteroseptal ischemia. Suspicion of MVP is reinforced by hearing a mid-systolic click, which tends to move toward the first heart sound with standing (a maneuver that reduces left ventricular volume and softens the murmur). The MVP murmur may occur in the absence of a click. The intensity of the suspected MVP murmur should be noted. The louder the murmur, the more hemodynamically significant is the regurgitation and the greater are the risks of endocarditis and other cardiovascular complications. Handgrip or Valsalva maneuver may increase the intensity of the murmur. Increasing duration of the murmur is a sign of worsening prolapse. Development of a holosystolic murmur without a systolic click in a person with known MVP is associated with an increased risk of an adverse event. Testing for Mitral Valve Prolapse

An echocardiogram can confirm MVP when uncertainty persists. Minor degrees of valve prolapse are normal. One should insist that ultrasound criteria are met before giving the patient a diagnosis of MVP. The major criterion is systolic displacement of one or both valve leaflets into the left atrium beyond the plane of the mitral annulus in the parasternal long-axis view on two-dimensional (B-mode) ultrasound study. Valve thickening and redundancy are other features, but a nonclassic form of MVP has been described in which there is no thickening, little risk for endocarditis, and little hemodynamically significant regurgitation. Ultrasound can differentiate the two and thus may help with cardiac risk stratification, although a very small risk of embolic stroke is similar in both forms. Indiscriminate use of echocardiography is to be avoided. Searching for silent MVP in the patient with vague chest pains and an entirely normal cardiac examination is of no value. Use of ultrasound in suspected MVP can facilitate diagnosis, but the contribution to outcome remains to be demonstrated. In most instances, the change in management engendered involves initiation of endocarditis prophylaxis (see Chapter 16). However, Doppler echocardiographic studies suggest that audible, and especially loud, systolic regurgitant murmurs are very likely to represent hemodynamically significant disease. An ultrasound examination is indicated when such a murmur is encountered. Patient Education and Indications for Referral Patient Education When the murmur is determined to be innocent or hemodynamically insignificant after careful evaluation, it is essential to provide detailed explanation as part of the delivery of meaningful reassurance. Marked concern and even distrust may be precipitated by a perfunctory explanation that it s harmless and nothing serious, especially if detailed auscultation continues to be conducted on subsequent visits. Concern about a murmur that is left incompletely explained can lead to unnecessary self-restriction of activity. Reassurance should include a discussion of the cause of the murmur, its significance, and prognosis. Informing the patient of other possible causes considered and ruled out is particularly helpful to the well-educated or medically curious patient and can obviate the demand for unnecessary testing or referral. The patient with a harmless murmur should be specifically told that there is no need to restrict activity or undergo further evaluation at the present time. Aortic Stenosis Asymptomatic persons found to have aortic stenosis (especially the elderly) should be informed of the importance of regular follow-up examinations and taught to watch for the symptoms of hemodynamically significant disease (i.e., postural lightheadedness, angina, exertional dyspnea), with instructions given to report them immediately should they occur (also see Chapter 33). Mitral Valve Prolapse Counseling is particularly important for the patient with insignificant MVP. Patients should be informed that MVP is a heterogeneous condition, and that most of them at no increased risk for cardiac complications. Those with readily audible MVP regurgitant murmurs should be advised about the need for endocarditis prophylaxis (see Chapter 16). Indications for Referral The person with hemodynamically significant aortic stenosis (valve area <0.9 cm2) needs close follow-up, annual echocardiography, and consideration of cardiac consultation if stenosis continues to progress, even in the absence of symptoms. Onset of symptoms makes the referral urgent (see Chapter 33). Worsening exertional dyspnea in the patient with rheumatic, ischemic, or cardiomyopathic mitral regurgitation is also an indication for prompt cardiac consultation because it suggests that the left ventricle is decompensating (see Chapter 33). Annual echocardiography has been recommended for asymptomatic persons with hemodynamically significant mitral regurgitation, with referral indicated

if there is progressive enlargement of the left ventricle or a fall in ejection fraction below 60%. Referral is also needed for the patient with tricuspid regurgitation and worsening hepatojugular reflux and other signs of right-sided failure. Patients with particularly loud murmurs of MVP suggestive of hemodynamically significant disease should be referred for cardiac consultation after undergoing ultrasound examination for confirmation. Most such patients can be reassured that they are at no increased risk and that progression to more serious disease is very rare. Prompt referral is indicated for the rare MVP patient with complex ventricular irritability, prolonged QT intervals, a family history of sudden death, or a transient ischemic event. Recommendations Begin by determining whether the systolic murmur is regurgitant or ejection in quality by attention to the murmur s location, quality, and timing. Differentiate right-sided from left-sided pathology by observing response of the murmur to inspiration. If the murmur is ejection in quality, distinguish between innocent/physiologic murmurs and those due to structural heart disease. P.157

For left-sided ejection murmurs, distinguish between aortic stenosis and hypertrophic cardiomyopathy. If aortic stenosis is suspected, estimate clinical severity by physical examination and obtain Doppler cardiac ultrasound in those persons with physical findings suggestive of hemodynamically significant disease. Follow patients with calcific aortic stenosis closely, and repeat ultrasound examination periodically. If there is evidence of hypertrophic cardiomyopathy (idiopathic hypertrophic subaortic stenosis) by physical examination, order Doppler cardiac ultrasound to confirm. For holosystolic murmurs, differentiate by physical examination between arteriovenous valve regurgitation and VSD; if arteriovenous valve regurgitation is suspected, determine whether the murmur is mitral or pulmonic. Obtain Doppler ultrasound if there is clinical evidence of hemodynamically significant regurgitation. For late-systolic murmurs, differentiate between MVP and valve regurgitation due to papillary muscle dysfunction. If hemodynamically significant MVP is suspected, obtain Doppler ultrasound to confirm. Refer for cardiac consultation any patient found to have severe aortic stenosis or any other hemodynamically significant lesion with poor prognosis (e.g., hypertrophic cardiomyopathy, mitral regurgitation with falling ejection fraction). Provide detailed reassurance to patients with harmless lesions to minimize demand for unnecessary testing, and make clear to patients with hemodynamically significant disease the need for close follow-up. A.H.G. Annotated Bibliography 1. Barber JE, Kasper FK, Ratliff NB, et al. Mechanical properties of myxomatous mitral valves. J Thorac Cardiovasc Surg 2001;122:955. (Abnormal glycosaminoglycan composition is responsible for abnormal mechanical properties.)

2. Brenner SJ, Duffy CI, Thomas JD. Progression of aortic stenosis in 394 patients. J Am Coll Cardiol 1995;25:305. (A serial Doppler ultrasound study with a 3-year mean duration of follow-up; documents the speed with which progression can occur in elderly patients.) 3. Carabello BA, Crawford FA. Valvular heart disease. N Engl J Med 1997;337:32. (Excellent review, which emphasizes pathophysiology and timely detection of a clinically important disease.) 4. Connolly HM, Crary JL, McGoon MD, et al. Valvular heart disease associated with fenfluramine phentermine. N Engl J Med 1997;337:581. (Major report on valvular damage associated with the use of this once-popular diet-pill combination.) 5. Cosmi JE, Kort S, Tunick PA, et al. The risk of development of aortic stenosis in patients with benign aortic valve thickening. Arch Intern Med 2002;1162:2345. (Retrospective study; the risk of progression exceeds 15% over 1 year; examines predictors of progression.) 6. Devereaux RB, Kramer-Fox R, Kligfield P. Mitral valve prolapse: causes, clinical manifestations, and management. Ann Intern Med 1989;111:305. (Comprehensive review; 172 references.) 7. Finegam RE, Gianelly RD, Harrison DC. Aortic stenosis in the elderly: relevance of age to diagnosis and treatment. N Engl J Med 1969;281:1261. (An important classic paper; physical findings such as carotid upstroke and quality and location of the murmur may be misleading in assessing aortic stenosis in the elderly.) 8. Freed LA, Levy D, Levine RA, et al. Prevalence and clinical outcome of mitral valve prolapse. N Engl J Med. 1999;341:1. (A reconsideration of epidemiologic data based on echocardiographic criteria.) 9. Lombard TJ, Selzer A. Valvular aortic stenosis. Ann Intern Med 1987;106:292. (Clinical presentations of 397 patients, with emphasis on disease in the elderly.) 10. Otto CM, Lind BK, Kitzman DW, et al. Association of aortic valve sclerosis with cardiovascular mortality and morbidity in the elderly. N Engl J Med. 1999;341:142. (Evidence for increased risk of adverse cardiovascular events.) 11. Stein PD, Sabbah H. Aortic origin of innocent murmur. Am J Cardiol 1977;39:665. (Presents extensive data for an aortic origin.) 12. Attenhofer-Jost CH, Turina J, Mayer K, et al. Echocardiography in the evaluation of systolic murmurs of unknown cause. Am J Med 2000;108:614. (Cohort study comparing the diagnostic accuracy of physical examination with echocardiography; a physical exam is excellent for distinguishing functional from hemodynamically significant disease but less sensitive in a number of other situations.) 13. Carabello BA. Aortic stenosis. N Engl J Med 2001;346:677. (Practical review for the clinician, with emphasis on decision making; 32 references.) 14. Etchells E, Bell C, Robb K. Does this patient have an abnormal systolic murmur? JAMA 1997;277:564. (A comprehensive literature review of the evidence for the accuracy and precision of clinical findings in the diagnosis of systolic murmurs.) 15. Etchells E, Glenns V, Shadowitz S, et al. A bedside clinical prediction rule for detecting moderate or severe aortic stenosis. J Gen Intern Med 1998;13:699. (A cross-sectional study confirming the efficacy of physical examination in identifying and ruling out hemodynamically significant aortic stenosis.)

16. Folland ED, Kriegel BJ, Henderson WG, et al. Implications of third heart sounds in patients with valvular heart disease. N Engl J Med 1992;327:458. (Indicative of failure in aortic stenosis but not necessarily in mitral regurgitation.) 17. Heckerling PS, Wiener SL, Moses VK, et al. Accuracy of precordial percussion in detecting cardiomegaly. Am J Med 1991;91:328. (Not often performed but found to be surprisingly useful.) 18. Lembo NJ, Dell Italia LJ, Crawford MH, et al. Bedside diagnosis of systolic murmurs. N Engl J Med 1988;318:1572. (One of the few studies providing sensitivity and specificity data on diagnostic maneuvers.) 19. Maisel AS, Atwood JE, Goldberger AL. Hepatojugular reflux: useful in the bedside diagnosis of tricuspid regurgitation. Ann Intern Med 1984;101:781. (Specificity 100%, sensitivity 66% in detecting tricuspid regurgitation; increase in murmur intensity with deep inspiration was as specific and more sensitive.) 20. Maron BJ, Bonow RO, Cannon RO 3rd, et al. Hypertrophic cardiomyopathy: interrelations of clinical manifestations, pathophysiology, and therapy. Parts 1 and 2. N Engl J Med 1987;316:844. (Best discussion of correlations between pathophysiology and clinical findings.) 21. Nishimura RA, McGoon MD, Shub C, et al. Echocardiographically documented mitral valve prolapse: long-term follow-up of 237 patients. N Engl J Med 1985;313:1305. (Identifies a low-risk subgroup.) 22. Shaver JA. Cardiac auscultation: a cost-effective diagnostic skill. Curr Probl Cardiol 1995;20:447. (Evidence for the utility of a careful clinical examination.) 23. Tribouilloy CM, Enriquez-Sarano M, Mohty D, et al. Pathophysiologic determinants of third heart sounds: a prospective clinical and Doppler echocardiographic study. Am J Med 2001;111:96. (Prospective cohort study; S3 is indicative of serious underlying hemodynamic and valvular dysfunction.)