on 04-Oct-2023 (Wed)

Auscultation has a reported sensitivity of 70 percent and a specificity of 98 percent for the detection of valvular heart disease [1]. However, the sensitivity and specificity vary substantially with the expertise of the examiner. The expertise and proficiency in auscultation have been waning in the modern era, which has led to a greater dependence on more expensive imaging techniques [2-5].

As noted in major society guidelines, an echocardiogram is indicated for the diagnosis and evaluation of patients with known or suspected valve disease [4,5]. Echocardiography is not needed in asymptomatic patients with a benign flow murmur but is appropriate in patients with cardiac symptoms and any cardiac murmur. It is also indicated in asymptomatic patients with a diastolic murmur, a grade 3 or greater systolic murmur, or a systolic murmur in association with other abnormal exam findings, such as a systolic click or reduced carotid upstroke.

In a study from Norway, cardiac auscultation skills of undergraduate medical students were not impacted by being trained on either an electronic or a conventional stethoscope [7].

When appropriate, patients should routinely be auscultated in the supine (including left lateral decubitus), sitting, and standing positions.

It is helpful to routinely assess at least four surface anatomical areas with the stethoscope ( figure 1) [8]:

● Tricuspid area – The fourth and fifth intercostal spaces along the left sternal edge often extending to the right of the sternum as well as downward to the subxiphoid area.

● Pulmonary area – The second intercostal space along the left sternal border. Murmurs that are best heard in this area may also extend to the left infraclavicular area or lower along the left sternal edge to the third intercostal space.

● Mitral area – At the cardiac apex, which is generally at the fifth intercostal space in the midclavicular line. This area may also extend medially to the left sternal edge and also laterally to the region of the axilla.

● Aortic area – Mainly centered at the second right intercostal space, but may extend to the suprasternal area, neck, and inferiorly to the third left intercostal space

Areas remote from the heart – A systolic murmur can be audible over the anterior aspects of both lungs in patients with peripheral pulmonary stenosis. Systolic murmurs can also be appreciated over the back of the chest below or adjacent to left scapula in patients with severe mitral regurgitation. In addition, a continuous murmur can be audible in the apical region of lung on the side of created arteriovenous fistula in the arm.

The intensity of a murmur is primarily determined by the quantity and velocity of blood flow at the site of its origin, the transmission characteristic of the tissues between the blood flow and stethoscope, the site of auscultation or recording, and the distance of transmission.

Six grades are used to classify the intensity of a systolic murmur (table 1):

● Grade I – Faintest murmur that can be heard.

● Grade II – Soft murmur that is readily detectable.

● Grade III – Louder than grade II but without a palpable precordial thrill.

● Grade IV – Loud murmur associated with a palpable precordial thrill.

● Grade V – Very loud murmur; audible with the stethoscope placed lightly on the chest; occurs with a palpable precordial thrill.

● Grade VI – Loudest murmur; audible with the stethoscope off the chest; occurs with a palpable precordial thrill.

Four grades (I through IV) are commonly used for diastolic murmurs since louder diastolic murmurs are very rare.

Parasternal murmurs are further characterized by the intercostal space and right or left side of the sternum [10]. It is also helpful to assess the area over which the murmur is audible (radiation); for example, document if the murmur is audible in the axilla, suprasternal notch, or over inferior aspect of the left scapula.

In a review of the literature, the presence of an early diastolic murmur was the most useful finding for establishing the presence of aortic regurgitation (positive likelihood ratio 8.8 [ie, the odds of aortic regurgitation are increased 8.8-fold]) and its absence the most useful finding for eliminating the presence of aortic regurgitation (negative likelihood ratio 0.2 to 0.3 [ie, the odds of disease are reduced by a factor of 0.2 to 0.3]) [25]

Among patients with end-stage kidney disease, a transient murmur of aortic regurgitation may be induced by the effects of volume overload; thus, such patients should be reexamined after dialysis, when the excess fluid has been removed [ 25].

The murmur of aortic regurgitation is best heard with the diaphragm of the stethoscope. Low-intensity, high-pitched aortic regurgitation murmurs may not be heard unless firm pressure is applied with the diaphragm of the stethoscope over the left sternal border or over the right second interspace, while the patient sits and leans forward with the breath held in full expiration (movie 8 and movie 9).

The radiation of an aortic regurgitation murmur is toward the cardiac apex and the location of maximum intensity may vary considerably. It can be best heard in some patients over the mid precordium, along the lower left sternal border, or even over the cardiac apex (movie 10). Radiation of the murmur to the right sternal border is more common in aortic regurgitation caused by aortic root or aortic cusp anomalies [26].

The configuration of the aortic regurgitation murmur is usually decrescendo because the magnitude of regurgitation progressively declines. The murmur is high-frequency and has a "blowing" character. Occasionally the murmur can be musical in quality (diastolic whoop); this has been attributed to a flail everted aortic cusp. The "whoop" can be mid-, late-, or pandiastolic [27].

Bedside evaluation of the severity of aortic regurgitation should be primarily based upon a determination of the hemodynamic consequences.

The duration of the murmur is variable but usually terminates before S1.

The duration of the murmur does not always correlate with the severity of aortic regurgitation, although mild aortic regurgitation is usually associated with a murmur of brief duration. The murmur may also be short with acute severe aortic regurgitation because of a rapid increase in LV diastolic pressure, which equalizes with aortic diastolic pressure soon after the onset of diastole

An Austin Flint murmur is usually associated with significant aortic regurgitation (see 'Austin Flint murmur' below).

A decreased intensity of S2 does not necessarily suggest significant aortic regurgitation; however, reversed splitting of S2, which in the absence of left bundle branch block results from increased LV forward stroke volume, indirectly suggests significant aortic regurgitation.

Changes in the intensity of S1 should be noted, since a reduced intensity is usually associated with an elevated LV end-diastolic pressure, which is more likely to occur in severe aortic regurgitation.

Physical findings of pulmonary venous, arterial hypertension, and right-sided heart failure indicate hemodynamically significant aortic regurgitation. (See "Clinical manifestations and diagnosis of chronic aortic regurgitation in adults".)

A hyperdynamic LV impulse is associated with a relatively normal ejection fraction. On the other hand, a sustained impulse and S3 gallop may indicate a reduced ejection fraction; further evaluation to assess LV function is indicated in this circumstance.

The onset of heart failure can modify many of the physical findings that suggest significant aortic regurgitation. The pulse pressure that was initially high may decrease, and the arterial diastolic pressure that was low may increase. The duration of the regurgitant murmur may decrease as the LV diastolic pressure increases.

The hemodynamic consequences of acute, severe aortic regurgitation differ considerably from those of chronic aortic regurgitation, explaining the differences in physical findings. (See "Acute aortic regurgitation in adults".)

● Sudden severe volume overload in a nondilated LV causes a rapid increase in diastolic pressure and often equalization of LV and aortic root pressures in middiastole. Thus, the regurgitant murmur can be of short duration.

● S1 is soft or absent due to a reduced intensity of the mitral component of S1 and premature closure of the mitral valve [28].

● The P2 of S2 is frequently accentuated due to postcapillary pulmonary hypertension. The A2 component of S2 is often attenuated due to incomplete leaflet coaptation.

Austin Flint murmur — An apical diastolic rumbling murmur has been described in patients with pure aortic regurgitation [38,39]. Several mechanisms have been proposed to explain the genesis of this murmur, including fluttering of the mitral valve from the impingement by the aortic regurgitant jet, relative (functional) mitral stenosis, and regurgitant jets directed against the LV free wall [38-40].

Mitral fluttering is not the mechanism of the Austin Flint murmur, since fluttering occurs in early diastole with the onset of regurgitation, while the rumble occurs in mid or late diastole. A second proposed mechanism was premature partial closing movement of the mitral valve at middiastole due to the regurgitant flow, leading to functional mitral stenosis. However, use of M-mode and two-dimensional echocardiography, color flow Doppler, and cine magnetic resonance imaging has shown that the murmur arises from the regurgitant jets that are directed at the LV free wall, thus excluding functional mitral stenosis as the etiology [40].

If the Austin Flint murmur is not recognized, a mistaken diagnosis of organic mitral stenosis can occur.

The presence of an opening snap suggests organic mitral stenosis. Amyl nitrite inhalation can also be a helpful method of differentiation. An Austin Flint murmur tends to decrease in intensity and duration as the severity of the aortic regurgitation decreases with decreased LV afterload. In contrast, the murmur of mitral stenosis increases in intensity and duration with an increased heart rate and increased antegrade flow across the mitral valve.

The two most common causes of acute AR of a native aortic valve are endocarditis and aortic dissection. This was illustrated in a single center review of 268 adults referred for aortic valve replacement for isolated AR, 18 percent of whom had acute AR [13]. All of the cases were due to active endocarditis (56 percent) or acute aortic dissection (44 percent).

In chronic AR, the volume overload of the left ventricle (LV) results in a gradual increase in LV size that provides a normal forward cardiac output despite the regurgitant valve flow; LV diastolic pressures remain normal. By contrast, with acute AR, the regurgitant volume fills a small ventricle that has not had time to dilate, resulting in an acute increase in LV diastolic pressure and a fall in forward cardiac output [14,15].

Acute AR results in the following pathophysiologic events:

● The LV cannot acutely increase total stroke volume, resulting in a decline in forward stroke volume and cardiac output. The decline in forward stroke volume may be exacerbated by a shortening of diastolic filling time due to the combination of early closure of the mitral valve (due to high diastolic pressures) and tachycardia (related to a decrease in forward flow and cardiac output). The net effect is often profound hypotension and cardiogenic shock.

● With severe AR, LV diastolic pressure rises sharply, with equalization of end-diastolic aortic and LV pressures. The elevated LV diastolic pressure leads to elevated left atrial and pulmonary venous pressures, which can lead to pulmonary edema.

Severe acute AR commonly presents with sudden cardiovascular collapse and pulmonary edema.

Aortic dissection should always be suspected in patients with AR and chest or back pain.

Manifestations of cardiogenic shock usually dominate in patients with severe acute AR. These include profound hypotension, pallor, diaphoresis, occasional cyanosis and other signs of peripheral vasoconstriction, as well as signs of pulmonary edema. The pulse pressure is normal or may be reduced, but the arterial pulsation is usually low amplitude and rapid. The cardiac apex is generally not displaced and is not hyperdynamic.

If aortic dissection is the cause, an inequality of pulses and blood pressure between the left and right arms may be observed. However, this finding may not be appreciated in the setting of profound hypotension.

The peripheral manifestations of chronic AR, associated with an increased pulse pressure, such as Traube's sign, Duroziez's murmur, and water hammer (Corrigan) pulses, are less apparent or may be entirely absent with acute AR. This difference from chronic AR is due to the fact that left ventricular (LV) stroke volume is not increased, and as a result the wide pulse pressure of chronic AR is not seen.

Acute AR alters the quality of most of the heart sounds

● The early closure of the mitral valve generally produces a soft or absent S1, which can occasionally be heard in mid-diastole.

● The aortic component of S2 is often soft, while P2 is usually increased, reflecting pulmonary hypertension.

● An S3 is often heard, but an S4 is absent.

By contrast to the high pitched holodiastolic decrescendo murmur of chronic AR, the murmur with acute AR is a low pitched early diastolic murmur beginning after S2 (movie 1 and movie 2). The murmur, however, may not be audible or recognized as regurgitation, especially if there is only a small diastolic gradient between the aorta and LV and the location of the murmur is variable, so it may be helpful to check multiple locations (eg, left sternal border, right sternal border, and back).

A systolic murmur resulting from the increased volume of blood crossing the aortic valve may be heard, but is usually not loud. The combination of a soft systolic and a low-pitched diastolic murmur often produces a "to-and-fro" murmur at the cardiac base in acute AR.

At least trace AR by color Doppler echocardiography is common, even in healthy subjects. A study from the Framingham Heart Study found that, in a population-based cohort, AR of at least trace severity on color Doppler echocardiography was present in 13 percent of men and 8.5 percent of women [1].

The prevalence of AR varied with age and disease severity [1]. More than trace AR was unusual before age 50 and then increased progressively.

● For mild AR, the prevalence was 3.7, 12.1, and 12.2 percent in men at ages 50 to 59, 60 to 69, and 70 to 83, respectively. The comparable values in women were 1.9, 6.0, and 14.6 percent.

● For moderate to severe AR, the prevalence was 0.5, 0.6, and 2.2 percent in men at ages 50 to 59, 60 to 69, and 70 to 83, respectively. The comparable values in women were 0.2, 0.8, and 2.3 percent.

All forms of AR produce a similar hemodynamic abnormality. The inability of the aortic valve leaflets to remain closed or coapted during diastole results in a portion of the left ventricular (LV) stroke volume leaking back from the aorta into the LV. The added volume of regurgitant blood produces an increase in LV end-diastolic volume and an elevation in wall stress. The ventricle responds and adapts with compensatory eccentric hypertrophy (figure 1A-B).

CAUSES — Chronic AR is caused by disease of the valve leaflets or enlargement of the aortic root. In the developing world, the most common cause of AR is rheumatic heart disease. However, in developed countries, AR is most often due to aortic root dilation, congenital bicuspid aortic valve, and calcific valve disease (table 1) [2].

The combination of LV eccentric hypertrophy with chamber enlargement raises the total stroke volume. The net effect is that forward stroke volume and systemic blood flow are initially maintained despite the regurgitant lesion. Although LV volume is increased, end-diastolic pressure remains normal due to an increase in ventricular compliance. Thus, the heart initially adapts well to chronic AR, functioning as a compliant high-output pump.

The increased stroke volume results in an increase in systolic pressure. Regurgitation into the LV leads to a rapid fall in arterial pressure with quick collapse of the arteries and a low diastolic pressure that may approach LV diastolic pressure in severe disease. The resulting wide pulse pressure leads to a number of characteristic physical findings. (See 'Arterial pulse and related findings' below.)

Symptoms that develop in some patients with severe AR (stage D) include exertional dyspnea, angina, and other symptoms of heart failure (table 2).

Exertional dyspnea develops in some patients with severe AR, particularly (but not exclusively) in patients who have developed LV systolic dysfunction. More severe heart failure symptoms such as orthopnea, paroxysmal nocturnal dyspnea, and pulmonary edema may develop without appropriate treatment.

Exertional angina develops in some patients with severe AR. Angina can occur even in the absence of underlying coronary artery disease, though the coronary arteries are typically large. With severe AR, angina is caused by reduced coronary flow reserve as epicardial coronary flow shifts from predominantly diastolic to predominantly systolic. Angina can also occur at night when the heart rate slows, arterial diastolic pressure falls, and regurgitant volume increases, thus reducing coronary diastolic perfusion pressure. Some patients with severe AR also develop nocturnal abdominal discomfort due to splanchnic ischemia.

Some patients with severe AR may complain of symptoms related to the increased LV size and stroke volume. Such symptoms differ from those that generally lead to consideration of aortic valve replacement (eg, dyspnea, angina). These include a sense of pounding, an uncomfortable awareness of the heartbeat, and atypical chest pains. These symptoms are especially pronounced when lying down or lying on the left side which brings the LV apex closer to the chest wall, augmenting the sensation of cardiac activity.

Examination of the peripheral pulses, precordial inspection and palpation, and auscultation of the heart are all helpful in patients with AR. The physical examination in patients with chronic severe AR is often dramatic and frequently establishes the diagnosis, though findings are frequently more subtle in patients with milder disease.

Corrigan pulse – A "water hammer" or "collapsing" pulse is characterized by a rapidly rising and falling arterial pulse with a wide pulse pressure. This finding is best appreciated by palpation of the radial or brachial arteries (exaggerated by raising the arm) or the carotid pulses.

de Musset sign – A head bob occurring with each heartbeat.

Mayne sign – More than a 15 mmHg decrease in diastolic blood pressure with arm elevation from the value obtained with the arm in the standard position.

Hill sign – Popliteal cuff systolic pressure exceeding brachial cuff pressure by more than 20 mmHg with patient in the recumbent position.

Duroziez sign – A systolic and diastolic bruit heard when the femoral artery is partially compressed.

Although all of these clinical signs have been described as ancillary findings useful in the diagnosis of AR, there are few published studies that have assessed the predictive value of any of these findings [3].

Among the four signs with sufficient literature for review (Corrigan pulse, Duroziez sign, Hill sign, and Austin Flint murmur [discussed below]), information on specificity was strongest for the Hill sign (specificity 71 to 100 percent overall) and the Hill sign is more frequent with more severe AR (sensitivity 75 to 100 percent among patients with moderate to severe or severe AR).

Precordial examination — On precordial inspection and palpation, the combination of LV enlargement and forceful systolic function results in the apical impulse being displaced laterally and inferiorly and being diffuse and hyperdynamic. A prominent pulsation (and occasionally a thrill) may be felt at the sternal notch due to concurrent dilation of the ascending aorta.

Chronic AR is associated with a distinctive early diastolic murmur as well as less specific sounds (such as a mid-systolic ejection murmur) that may be heard in addition to or instead of the characteristic murmur.

The heart sounds typically have the following characteristics (see "Auscultation of cardiac murmurs in adults", section on 'Aortic regurgitation' and "Auscultation of heart sounds"):

● S1 may be soft, often reflecting a long PR interval

● S2 is variable; it may be soft, absent, or single

● A2 is often soft or absent while P2 may be normal, but obscured by the diastolic murmur

● A systolic ejection sound may be due to abrupt aortic distension caused by the large stroke volume

● A third heart sound (S3 gallop) is heard when LV function is severely depressed

A diastolic murmur is a key sign favoring the diagnosis of AR, though absence of a diastolic murmur does not exclude the diagnosis. In a review of the literature, the presence of an early diastolic murmur, as heard by a cardiologist, was the most useful finding for establishing the presence of AR (positive likelihood ratio 8.8 [ie, the odds of AR are increased 8.8-fold]) and its absence the most useful finding for reducing the likelihood of AR (negative likelihood ratio 0.2 to 0.3) [4]. However, the reported frequency of a diastolic murmur among patients with chronic AR has varied widely (14 to 73 percent) [5,6].

The diastolic murmur of AR begins immediately after A2 (movie 1A-C). It is high pitched, often blowing in quality, and may be sustained in intensity or decrescendo. It may be soft and barely audible, often appreciated only when the patient is sitting up, leaning forward, and holding his or her breath in end-expiration.

The intensity of the diastolic murmur does not correlate well with the severity of AR. The timing and duration of the murmur may be helpful in assessing the severity of AR. However, the physical findings are not sufficiently reliable and echocardiography is typically used to assess severity.

● In mild AR, the murmur occurs only in early diastole and is blowing.

● As the regurgitation becomes more severe, the murmur extends through more of diastole, may become holodiastolic, and is often rougher in quality. Patients with a longer diastolic murmur, a displaced LV impulse, a wide pulse pressure, and the peripheral findings of a wide pulse pressure cited in the previous section are considered to have severe AR.

● In very severe regurgitation with ventricular decompensation, the murmur may become soft or even absent. This change in character reflects the near equalization of aortic diastolic and LV diastolic pressures, which diminish regurgitant flow. A similar situation can occur when AR is acute and the LV diastolic pressure is very high.

The intensity of the murmur can also be affected by certain maneuvers. As examples, the murmur increases with squatting and decreases with the Valsalva maneuver

The site at which the murmur is best heard varies with the cause. The murmur is heard best along the left sternal border, at the third and fourth intercostal space, when AR is due to valvular disease. In contrast, abnormalities of the aortic root produce murmurs that are best heard at the right sternal border and apex.

A mid-systolic murmur is heard in many patients with AR [5,7]. A study found that a systolic murmur was more frequently heard than a diastolic murmur by noncardiologists in patients with trace to moderate AR [5]. The systolic murmur typically resembles the ejection type of murmur heard in aortic stenosis, ie, a crescendo-decrescendo harsh murmur beginning after S1. This murmur is caused by a large ejection volume and thus does not necessarily reflect concurrent aortic stenosis.

A second type of diastolic murmur (the Austin Flint murmur) may also be appreciated. This murmur is a low-pitched, mid to late diastolic rumble, heard at the apex. The murmur has been attributed to the effects of competing antegrade turbulent diastolic blood flow from the left atrium and the retrograde regurgitant flow from the aorta. The sensitivity and specificity of the Austin Flint murmur is uncertain. A review found a higher sensitivity (57 to 100 percent) among patients with severe AR compared with patients with mild to moderate disease (0 to 50 percent) [3].

The heart size on a chest radiograph may vary by about one centimeter from end diastole to end systole. Therefore, an apparent increase in heart size on serial examinations does not necessarily indicate progressive LV chamber enlargement.

Chronic AR should be suspected in patients with physical examination findings consistent with AR. This includes patients with typical exam findings (eg, early diastolic murmur) as well as those with less specific findings (eg, a systolic ejection murmur or wide pulse pressure). Symptoms such as dyspnea are present only late in the disease. In addition, AR should be suspected in patients with dilated aortic sinuses or ascending aorta and in patients with bicuspid aortic valve [8], even if no murmur is apparent.

As an example, the exaggerated or bounding pulses are not specific for AR and can be seen in any condition associated with a marked increase in stroke volume and a hyperdynamic circulation. Included in this group are sympathetic hyperactivity, anemia, fever, pregnancy, thyrotoxicosis, large arteriovenous fistula, patent ductus arteriosus, and severe bradycardia. Severe mitral regurgitation also can cause rapid rising arterial pulses, but the pulse pressure is not increased.

The characteristic early diastolic murmur of AR may not be distinguishable from the murmur of pulmonic regurgitation. Rarely, left anterior descending coronary artery stenosis can produce a murmur similar to the murmur of AR. Among patients with end-stage kidney disease, a transient murmur of AR may be induced by the effects of volume overload; the murmur disappears after dialysis, when the excess fluid has been removed [4].

The mid-diastolic Austin Flint murmur of AR may be confused with that of mitral stenosis. Distinguishing features from mitral stenosis include the absence of both a loud S1 and an opening snap of the mitral valve.

Chronic AR is staged according to valve anatomy, valve hemodynamics, hemodynamic consequences, and symptoms, as indicated in the 2020 American Heart Association/American College of Cardiology valve guidelines (table 2) [8]: