APPROACH TO THE PATIENT WITH A HEART MURMUR - Patrick T.

O'Gara, Eugene Braunwald

Auscultation of the heart constitutes the final step in the cardiovascular examination and for many patients with established or suspected cardiac disease represents the defining moment in the doctor-patient relationship. The examiner must bring to this exercise an integrated approach that incorporates pertinent information simultaneously from several sources. The auscultatory findings must be interpreted in the context of the history and general physical examination and must be consonant with the observations made regarding the venous wave forms and major arterial pulses. In this way, abnormalities of the heart sounds, adventitious sounds, and murmurs can be placed in their proper perspective. In many patients, a heart murmur is the only or the most conspicuous finding on physical examination. The recognition of a heart murmur commonly leads to additional testing, such as electrocardiography, chest radiography, and echocardiography, and may result in referral to a cardiologist. The differential diagnosis of a heart murmur should more properly begin with an unbiased and systemic evaluation of its major attributes: timing, duration, intensity, quality, frequency, configuration, location, radiation, and response to maneuvers (Table 227-1). Laboratory testing can be pursued thereafter to clarify any remaining ambiguity and to provide additional anatomic and physiologic information that will impact on patient management. Heart murmurs are defined in terms of their timing within the cardiac cycle. Systolic murmurs begin with or after the first heart sound (S1) and terminate at or before the component (A2 or P2) of the second heart sound (S2) that corresponds to their side of origin (left or right). Diastolic murmurs begin with or after the associated component of S2 and end at or before the subsequent S1.

Continuous murmurs are not confined to either phase of the cardiac cycle but rather begin in systole and proceed through S2 into all or part of diastole.
The appropriate timing of heart murmurs is the first critical step in their identification. The distinction between S1 and S2, and, therefore, systole and diastole, is usually a straightforward process but can be difficult in the setting of a tachyarrhythmia, in which case the heart sounds can be distinguished by simultaneous palpation of the carotid arterial pulse. The upstroke should closely follow S1. The principal causes of heart murmurs are shown in Table 34-1, and the critical importance of the timing of heart murmurs in the differential diagnosis is shown in Fig. 34-1. SYSTOLIC HEART MURMURS Systolic heart murmurs derive from the increased turbulence associated with (1) enhanced or accelerated flow across a normal semilunar valve or into a dilated great vessel, (2) flow across a structurally abnormal semilunar valve or through a narrowed ventricular outflow tract, (3) flow across an incompetent atrioventricular valve, and (4) flow across the interventricular septum. One approach to their differential diagnosis further subdivides these murmurs according to their time of onset and duration within the systolic phase of the cardiac cycle.

EARLY SYSTOLIC MURMURS Early systolic murmurs begin with S1 and extend for a variable period of time, ending well before S2.

Their causes are relatively few in number. Acute severe mitral regurgitation into a normal-sized, relatively noncompliant left atrium results in an early and attenuated systolic murmur that is decrescendo in configuration and usually best heard at or just medial to the apical impulse (Chap. 237). These characteristics reflect the rapid rise in left atrial pressure caused by the sudden volume load into a nondilated chamber and contrast sharply with the auscultatory features of chronic mitral regurgitation. Clinical settings in which this occurs include: (1) papillary muscle rupture complicating acute myocardial infarction, (2) infective endocarditis, (3) rupture of chordae tendineae, and (4) blunt chest wall trauma. Acute mitral regurgitation from papillary muscle rupture usually accompanies an inferior, posterior, or lateral infarction. The murmur is associated with a precordial thrill in approximately one-half of cases and is to be distinguished from that associated with postinfarction ventricular septal rupture. The latter is more commonly (90 percent) accompanied by a thrill at the left sternal edge, is holosystolic, and complicates anterior infarctions as often as inferior-posterior events. The recognition of either of these mechanical defects mandates aggressive medical stabilization and emergent surgical intervention (Chap. 243). The other potential causes of acute severe mitral regurgitation may be distinguished on the basis of associated findings. Spontaneous chordal rupture usually occurs on a substrate of myxomatous degeneration, such as that underlying most forms of mitral valve prolapse (Chap. 237). This lesion may be part of a more generalized process, as can occur with the Marfan or Ehlers-Danlos syndromes, or it may be an isolated phenomenon. Infectious endocarditis is associated with fever, peripheral embolic lesions, and positive blood cultures and most commonly occurs on a previously abnormal valvular apparatus (Chap. 126). Trauma is usually self-evident but may be disarmingly trivial (Chap. 241). It can result in papillary muscle contusion and rupture, chordal interruption, or leaflet avulsion or perforation. Echocardiography should be performed in all cases of suspected acute severe mitral regurgitation to define the responsible mechanism, estimate the severity, and provide a preliminary assessment as to the feasibility of surgical repair (versus replacement). Other causes of early systolic murmurs include congenital, small muscular ventricular septal defect. The duration of the murmur is attenuated by the closure of the defect during systolic contraction. The murmur is localized to the left sternal edge and is commonly of grade IV/VI or V/VI intensity. Signs of pulmonary hypertension or left ventricular volume overload are absent. Tricuspid regurgitation with normal pulmonary artery pressures, such as that caused by infectious endocarditis in intravenous drug users, may produce an early systolic murmur. The murmur is soft, best heard at the lower left sternal edge, and may accentuate with inspiration (Carvallo's sign). Regurgitant c waves may be visible in the jugular venous pulse. v MIDSYSTOLIC MURMURS

Midsystolic murmurs begin at a short interval following S1, end before S2, and are usually crescendo-

decrescendo in configuration (Fig. 34-1C). Semilunar valve stenosis is the classic prototype. With aortic valve stenosis the murmur is usually loudest in the second right intercostal space (aortic area) and radiates along the carotid arteries (Chap. 237). The intensity of the murmur varies directly with the cardiac output; aortic valve stenosis with severe heart failure may produce a misleadingly soft systolic murmur. With a normal cardiac output, a systolic thrill is usually indicative of severe stenosis with a peak gradient in excess of 50 to 60 mmHg. An accompanying early systolic ejection click may be audible in younger patients with a bicuspid valve; its presence localizes the obstruction to the valvular (as opposed to the sub- or supravalvular) level. The midsystolic murmur of aortic stenosis may be well transmitted to the apex, especially in older patients, where it becomes less harsh and slightly higher pitched (Gallavardin effect). The murmur of aortic stenosis should increase following a postpremature beat, whereas a mitral regurgitant murmur would not be expected to change in intensity. Sclerosis of the aortic valve produces a murmur of similar location, radiation, and configuration, albeit without the usual signs of hemodynamic significance. The carotid upstroke is well preserved, the murmur peaks in midsystole and is not accompanied by a thrill, and only a modest gradient is estimated by Doppler echocardiography. Noncritical sclerodegenerative thickening of the aortic valve leaflets is perhaps the most common cause of a midystolic murmur in an older adult. The similar midsystolic murmur of pulmonic valve stenosis, usually introduced by an ejection click, is best appreciated in the second and third left intercostal spaces (pulmonic area). The murmur lengthens and the intensity of P2 diminishes with increasing degrees of stenosis. A midsystolic murmur in the aortic position of no functional significance can also be detected in hyperdynamic states (fever, thyrotoxicosis, pregnancy, anemia) and in the presence of isolated aortic regurgitation with the augmented flow into a dilated proximal aorta. Crescendo-decrescendo midsystolic murmurs of grade II/VI or III/VI intensity heard in the pulmonic area may be innocent (Still's murmur), if unaccompanied by any other signs of cardiac disease in children or young adults, or they may reflect enhanced flow into a normal pulmonary artery in hyperkinetic states or augmented flow into a dilated pulmonary artery. The latter may occur with an atrial septal defect, in which case splitting of S2 should be abnormal (fixed). The midsystolic murmur of hypertrophic cardiomyopathy (Chap. 239) is usually loudest between the left sternal edge and apex, of grade II/VI to III/VI intensity, and crescendo-decrescendo in configuration. In contrast to aortic valve stenosis, the murmur does not radiate into the neck and the carotid upstrokes are brisk and full and may even be bifid. The intensity of the murmur associated with hypertrophic cardiomyopathy increases following maneuvers that decrease left ventricular volume (strain phase of the Valsalva maneuver, standing, amyl nitrite) or increase myocardial contractility (inotropic therapy). Conversely, the intensity of the systolic murmur decreases with maneuvers that increase ventricular volume (squatting, passive leg raising), impair contractility (betaadrenoreceptor blockade), or raise preload and systemic afterload (squatting). Among these several maneuvers, auscultation in the standing and squatting positions, if possible, is perhaps the most sensitive technique to elicit a dynamic change in the intensity of the murmur associated with hypertrophic obstructive cardiomyopathy. 3

LATE SYSTOLIC MURMURS A late systolic murmur begins well after the onset of ejection and is usually best heard at the left ventricular apex or between the apex and the left sternal edge. When introduced by a nonejection click, it is usually indicative of systolic prolapse of the mitral valve leaflet(s) into the left atrium. The click and murmur move closer to S1 following maneuvers that decrease left ventricular volume (standing, Valsalva) and move oppositely upon increases in volume (leg raising, squatting). The intensity of the murmur augments with increases in systemic afterload (squatting, pressor agents) and decrease with vasodilation (amyl nitrite). Isometric exercise, which also delays the onset of the murmur, accentuates the intensity. HOLOSYSTOLIC MURMURS These murmurs, also termed pansystolic murmurs, begin with S1 and continue through systole to S2

(Fig. 34-1C). They are, with rare exception, indicative of atrioventricular valve regurgitation or of a ventricular septal defect; the differential diagnosis is shown in Fig. 34-2. The murmur of mitral regurgitation is loudest at the left ventricular apex. Its radiation reflects the direction of the regurgitant jet. With a flail posterior mitral leaflet due to ruptured chordae tendineae, for example, the jet is directed anterosuperiorly, and the murmur radiates prominently to the base of the heart where it might be confused with aortic valve stenosis unless the carotid upstrokes are carefully examined. Conversely, a flail anterior leaflet is associated with a posteriorly directed jet, which radiates into the axilla and the back. It may even strike the spine and be transmitted to the base of the neck. Severe mitral regurgitation is usually associated with a systolic thrill, a soft S3, and a short diastolic rumbling murmur best appreciated in the left lateral decubitus position. The holosystolic murmur of tricuspid regurgitation is generally softer (grades I to III/VI) than that of mitral regurgitation, is loudest at the left lower sternal edge, and increases in intensity upon inspiration. Associated signs include prominent "c " waves in the jugular venous pulse, systolic v hepatic pulsations, and peripheral edema. Among the several causes of tricuspid regurgitation, annular dilatation from right ventricular enlargement in the setting of pulmonary artery hypertension is the most common. Ventricular septal defect (Chap. 235) also produces a holosystolic murmur, the intensity of which varies inversely with the anatomic size of the defect. It is usually accompanied by a palpable thrill along the mid-left sternal border. The murmur of a ventricular septal defect is louder than that due to tricuspid regurgitation and does not share the latter's inspiratory increase in intensity or associated peripheral signs. DIASTOLIC HEART MURMURS Like systolic murmurs, diastolic murmurs also can be subcategorized according to their time of onset. EARLY DIASTOLIC MURMURS (Fig. 34-1E)

Early diastolic murmurs result from semilunar valve incompetence and begin at the valve closure sound (A2 or P2), which reflects their side of origin. They are generally high pitched and decrescendo in configuration, especially in states of chronic regurgitation, wherein their duration is a crude index of the severity of the lesion. The murmur of aortic regurgitation is generally, but not always, best heard in the second intercostal space at the left sternal edge. There is a tendency for the murmur associated with primary valvular pathology (e.g., rheumatic deformity, congenital bicuspid valve, endocarditis) to radiate more prominently along the left sternal border and to be well transmitted to the apex, while the murmur associated with primary aortic root pathology (e.g., annuloaortic ectasia, aortic dissection) radiates more often along the right sternal edge. It is occasionally necessary to examine the patient sitting forward in full expiration to appreciate the murmur, a maneuver that brings the aortic root closer to the anterior chest wall. Severe aortic regurgitation may be accompanied by a lower-pitched mid- to late-diastolic murmur at the apex (Austin Flint murmur), which is generally thought to reflect turbulence at the mitral inflow area from the mixing of the regurgitant (aortic) and forward (mitral) streams, and should be distinguished from mitral stenosis (see above). In the absence of significant heart failure, chronic severe aortic regurgitation is accompanied by several peripheral signs of significant diastolic runoff, including a wide systemic pulse pressure and water-hammer carotid upstrokes (Corrigan's pulse). The murmur associated with acute aortic regurgitation is notably shorter in duration, lower pitched, and can be difficult to appreciate in the presence of tachycardia. Peripheral signs of significant diastolic runoff may be absent. These attributes reflect the abrupt rise in diastolic pressure within the noncompliant left ventricle, with a correspondingly rapid decline in the aortic diastolic-left ventricular pressure gradient. The murmur of pulmonic valve regurgitation (Graham Steell murmur) begins with a loud (palpable) pulmonic closure sound (P2) and is best heard in the pulmonic area with radiation along the left sternal border. Typically, it is high pitched, with a decrescendo quality, and is indicative of significant pulmonary artery hypertension with a diastolic pulmonary artery-right ventricular pressure gradient. Its increase in intensity upon inspiration is one means by which to distinguish it from aortic regurgitation. Signs of right ventricular pressure and volume overload are also usually present. With significant mitral stenosis, an early decrescendo diastolic murmur along the left sternal border is not uncommon and is almost always due to aortic rather than pulmonic regurgitation, despite the coexistence of pulmonary artery hypertension. Pulmonic valve regurgitation in the absence of pulmonary artery hypertension can occur on a congenital basis and rarely with infectious endocarditis. In these instances, the early diastolic murmur is softer and lower pitched than the classic Graham Steell murmur. It begins at or even after P2, which should be easily separable from A2 and thus produce appreciation of an early diastolic pause. MIDDIASTOLIC MURMURS Middiastolic murmurs usually result from obstruction and/or augmented flow across the antrioventricular valves. The classic example is that of mitral stenosis due to rheumatic deformity

(Fig. 34-1F). In the absence of extensive calcification, the first heart sound (S1) is loud and the murmur begins after the opening snap; the time interval between S2 and the opening snap is inversely related to the left atrial-left ventricular pressure gradient. The murmur is low pitched and best heard with the bell of the stethoscope over the apex, particularly in the left lateral decubitus position. While its intensity does not reflect the severity of the obstruction accurately, the duration of the murmur does provide some indication as to the magnitude of the obstruction. A longer murmur denotes persistence of a left atrioventricular pressure gradient over a greater proportion of the diastolic time interval. Presystolic accentuation of the murmur (Fig. 34-1A) is frequently appreciated in the presence of sinus rhythm and reflects a further increase in transmitral flow consequent to mechanical atrial systole. The murmur associated with tricuspid stenosis shares many of these features, but it is best heard at the lower left sternal border and, like most right-sided events, increases in intensity upon inspiration. The observant examiner may discern a prolonged y descent in the jugular venous pulse. Signs of right heart failure may predominate. There are several other causes of mid-diastolic murmurs that are important to distinguish from mitral stenosis. Left atrial myxomas (Chap. 241) may masquerade as mitral stenosis, but the diastolic murmur is not accompanied by an opening snap or pre-systolic accentuation. Augmented flow across the mitral valve in diastole, such as occurs with severe mitral regurgitation or with large left to right intra-cardiac or great vessel shunts may produce a short, low pitched mid-diastolic apical murmur. The murmur usually follows a soft S3 that is lower pitched and later in timing than the opening snap (Fig. 34-1G). Severe tricuspid regurgitation can also result in enhanced diastolic tricuspid flow and produce a right-sided filling complex similar to that which accompanies severe mitral regurgitation. The Austin Flint murmur of severe aortic regurgitation has been previously described and occurs in the presence of severe aortic regurgitation. CONTINUOUS MURMURS Continuous murmurs begin in systole, peak near S2, and continue into all or part of diastole (Fig. 34-

1H). Accordingly, they reflect the persistence of flow between two chambers during both phases of the cardiac cycle. The differential diagnosis of continuous murmurs is shown in Table 34-1. Two innocent variants are the cervical venous hum and the mammary souffle. The former is audible in healthy children and young adults in the right supraclavicular fossa and can be abolished by compression over the internal jugular vein. Its diastolic component may be louder than its systolic counterpart. A mammary souffle represents augmented arterial flow through engorged breasts and becomes audible during the late third trimester of pregnancy or in the early postpartum period. Firm pressure with the diaphragm of the stethoscope can eliminate the diastolic portion of the murmur. The murmur dissipates with time after delivery. The classic continuous murmur is that due to a patent ductus arteriosus. It is best heard at or just above and to the left of the pulmonic area and may be audible in the back. Over time, a large uncorrected shunt may lead to elevation of the pulmonary vascular resistance, with resultant pulmonary artery hypertension and diminution or elimination of the diastolic component. A continuous

murmur can also signify a ruptured congenital sinus of Valsalva aneurysm, which occurs either spontaneously or as a complication of infective endocarditis. Here, a high-pressure fistula is created between the aorta and a cardiac chamber, usually the right atrium or ventricle. The murmur is loudest along the right or left sternal border and is frequently accompanied by a thrill. Notably, the diastolic component is louder than the systolic component. It can be difficult to distinguish continuous murmurs from the temporally separate systolic and diastolic murmurs of mixed aortic valve disease or isolated severe aortic regurgitation. The emphasis is on the envelopment of S2 by continuous murmurs and a gap between the to-and-fro murmurs of aortic valve disease. A variety of other lesions can result in continuous murmurs. A coronary arteriovenous fistula sometimes produces a faint, continuous murmur with a louder diastolic component at the left sternal border or left ventricular apex. Severe atherosclerotic disease of a major systemic artery may produce a continuous bruit, the presence of which signifies very high grade obstruction. Patients with peripheral pulmonary (branch) stenosis or with pulmonary atresia with extensive bronchial collaterals may also have continuous murmurs best heard in the back or along the lateral thoracic cage. Similar findings are present in patients with severe aortic coarctation, a lesion that should be identifiable on the basis of weak and delayed lower extremity pulses and upper extremity hypertension. The continuous murmurs emanate from the enlarged collateral (intercostal) arteries.

Approach to the Patient

In many patients the cause of a heart murmur can be readily elucidated from careful assessment of the murmur itself, as described in this chapter, when considered in the light of the history, general physical examination, and other features of the cardiac examination, as described in Chap. 227. When the diagnosis is in doubt, or when additional pathoanatomic and physiologic data are necessary in assessing the patient and planning treatment, a transthoracic echocardiogram with Droppler interrogation is of great value in identifying not only the etiology of the murmur but also the severity of the responsible lesion. The majority of heart murmurs are midsystolic and soft (Grades I to II/VI). When such a murmur occurs in a child or young adult without , . , ( III/VI), especially those that are holosystolic, as well as in most patients with diastolic or continuous murmurs.