Auscultation of cardiac murmurs in adults

INTRODUCTION — Cardiac auscultation is one of the most useful bedside diagnostic tools that a clinician can use to detect alterations in cardiovascular anatomy and physiology. Significant valvular heart disease is often first diagnosed based upon the finding of a murmur. 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].

In clinical practice, echocardiography is the standard for establishing the cause of a murmur. 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.

This topic will review the auscultation of cardiac murmurs in adults, including the maneuvers (eg, respiration, Valsalva maneuver) that can be used to differentiate one murmur from another. These maneuvers, as well as auscultation of other heart sounds, are discussed in detail separately. (See "Physiologic and pharmacologic maneuvers in the differential diagnosis of heart murmurs and sounds" and "Auscultation of heart sounds".)

Cardiac murmurs in infants and children are discussed separately. (See "Approach to the infant or child with a cardiac murmur" and "Common causes of cardiac murmurs in infants and children".)

ORIGIN OF MURMURS — Cardiac murmurs are the direct result of blood flow turbulence. The amount of turbulence and consequently the intensity of a cardiac murmur depend on the size of the orifice or vessel through which the blood flows; the pressure difference or gradient across the narrowing; and the blood flow or volume across the site [4-6]. Murmurs are generally the loudest near the point of origin since sound radiates away from its source, and the intensity diminishes according to the inverse square law (inversely proportional to the square of the distance from the source). Other factors influence this relationship including the transmission characteristics of the tissues (eg, fat and air), the distance from the location of auscultation to the origin of the murmur (eg, truncal obesity, emphysema), and the course of flow.

AUSCULTATORY TOOLS

●Standard stethoscope (acoustic based) – The standard stethoscope includes both a shallow bell for low frequency and a thin, stiff diaphragm for high frequency sounds.

●Electronic stethoscope (sensor based) – Auscultatory devices have been developed that utilize advanced acoustic sensor-based digital signal processing. The clinician has the choice of a bell, a diaphragm, and a wide range of frequencies for better body sound acquisition. It also allows the clinician to record the heart sounds directly onto a computer for further visualization and analysis.

There are no objective data to support the claim that the electronic stethoscope provides superior auscultatory skills over the conventional stethoscope. 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].

PERFORMANCE OF AUSCULTATION — The examination involves systematic listening to all components of the cardiac cycle in all auscultatory areas with both the bell and diaphragm. The timing of murmurs is best assessed by identifying S1 and S2, helped if needed by timing them with the carotid pulse. (See "Auscultation of heart sounds".)

For example, in patients with marked tachycardia, a long diastolic murmur can occasionally be confused with a systolic murmur; timing with the carotid pulse upstroke avoids an incorrect diagnosis. 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.

MURMUR DESCRIPTION — The character of a murmur is described by several features, including intensity (grade), pitch (frequency), configuration, timing, quality, location, and radiation.

Intensity — 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. In general, the intensity declines in the presence of obesity, emphysema, and pericardial effusion. Murmurs are usually louder in thin individuals. The gradation of intensity is purely subjective. However, it allows recognition of changes in the intensity of the murmur, which has diagnostic relevance.

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.

Pitch — The frequency of the murmur determines the pitch, which may be high or low. The quality can be described as harsh, rumbling, scratchy, grunting, blowing, squeaky, vibratory, and musical. Quality and pitch are closely related.

Configuration — The time course of murmur intensity corresponds to the "shape" of a diagram of murmur intensity over time, as in a phonocardiogram. A number of configurations or shapes of murmurs are recognized:

●Crescendo (increasing)

●Decrescendo (diminishing)

●Crescendo-decrescendo (increasing-decreasing or diamond shaped)

●Plateau (unchanged in intensity)

Location and radiation — The location on the patient's chest where the murmur is loudest is typically described as apical, and parasternal or over the base of the heart (aortic and pulmonary areas) [9]. 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.

Classification by timing — The duration of a murmur is assessed by determining the length of systole or diastole that the murmur occupies. The murmur can be long (eg, it occupies most of systole or diastole), or it can be short. The following classification is useful [8]:

●Systolic murmurs – Starts with or after S1 and terminates before or at S2 (figure 2):

•Early systolic – Obscures S1 and extends for a variable length in systole but does not extend up to S2.

•Midsystolic (or systolic ejection) – Begins after S1 and ends before A2 (left sided) or P2 (right sided) (table 2). Both S1 and S2 are audible.

•Holosystolic (or pansystolic) – Starts with S1 and extends up to A2 (left sided) or P2 (right sided), obscuring both S1 and S2.

•Late systolic – Starts after S1 and obscures A2 (left sided) or P2 (right sided).

●Diastolic murmurs – Starts with or after S2 and ends at or before S1:

•Early diastolic – Starts with A2 (left sided) or P2 (right sided) and extends into diastole for a variable duration.

•Middiastolic – Starts after S2 and terminates before S1.

•Late diastolic (or presystolic) – Starts well after S2 and extends up to the mitral component (left sided) or to the tricuspid component (right sided) of S1.

●Continuous murmurs – Begins in systole and continues to diastole without interruption, encompassing S2 (figure 3 and table 3).

SYSTOLIC MURMURS — Classification of systolic murmurs by timing is described above. (See 'Classification by timing' above.)

Early systolic murmurs — Early systolic murmurs may result from mitral regurgitation (MR), tricuspid regurgitation, or ventricular septal defect (VSD).

Mitral regurgitation — Either acute severe or mild chronic MR can be associated with an early systolic murmur. Acute severe MR usually causes a rapid increase in left atrial pressure leading to progressive equalization with left ventricular (LV) pressure. This hemodynamic alteration prevents regurgitant flow during the latter part of systole. Thus, the regurgitant murmur terminates before A2. Since the regurgitant flow is maximal at the beginning of systole and decreases with increasing left atrial pressure, a decrescendo configuration of this early systolic murmur is common [11-13]. Associated clinical findings include pulmonary hypertension, hyperdynamic apical impulse, a late systolic left parasternal impulse, and atrial and ventricular gallops. (See "Acute mitral regurgitation in adults".)

In some patients with mitral stenosis, an early systolic murmur is heard and probably represents mild MR. Secondary MR in dilated cardiomyopathy is usually mild and may be early systolic in timing. Mitral annular calcification can be associated with an early systolic murmur and suggests trivial MR. Ineffective reduction of the circumference of the annulus at the beginning of systole, due to calcification, is probably the underlying mechanism for mild MR and the early systolic murmur [12].

Tricuspid regurgitation — Primary tricuspid regurgitation with normal right ventricular systolic pressure, as seen with infective endocarditis in individuals with substance use disorders, may be associated with an early systolic murmur with a decrescendo configuration. The mechanism is similar to that in acute severe MR. The frequency of these murmurs is usually lower than the murmurs associated with an elevated right ventricular systolic pressure, presumably due to a lower rate of regurgitation. In addition to a relatively normal S2, palpating and recording the left parasternal impulse may reveal a systolic inward movement and a diastolic outward movement, reflecting right ventricular volume changes.

Ventricular septal defect — In a large VSD with pulmonary hypertension, the murmur may be early systolic in timing, since the increasing right ventricular pressure during late systole decreases the left-to-right shunt. Findings of pulmonary hypertension are always present. An early systolic murmur may also occur in some patients with a VSD in the absence of pulmonary hypertension or increased pulmonary vascular resistance; these murmurs are more frequently localized and of shorter duration. They tend to occur with VSDs that later close spontaneously [14].

Small muscular VSDs may also cause an early systolic murmur, since the defect closes soon after the onset of systole. Evidence of pulmonary hypertension is absent. (See "Clinical manifestations and diagnosis of ventricular septal defect in adults", section on 'Physical signs'.)

Midsystolic ejection murmurs — The ejection or midsystolic murmur (MSM) is related to flow of blood across the semilunar valves; onset of the MSM coincides with the beginning of ejection and termination occurs with the cessation of forward flow. S1 occurs at the onset of isovolumic systole when ventricular pressure rises; ejection, and thus the MSM, begins at the end of isovolumic systole when the ventricular pressures exceed the semilunar valve opening pressure. The onset of an MSM is separated from S1, and the interval between S1 and the onset of the murmur is proportional to the duration of isovolumic systole (figure 2).

The intensity of the MSM increases (crescendo) during acceleration of blood flow early in systole; intensity declines (decrescendo) with the later deceleration of flow, resulting in a crescendo-decrescendo (diamond-shaped) configuration. Forward flow from the ventricle stops when ventricular pressure falls below the aortic or pulmonary artery pressures, before the closure of the semilunar valves. The murmur terminates with cessation of flow, before A2 or P2, depending upon whether the murmur is left or right sided, respectively. The interval between the termination of the murmur and A2 or P2 is proportional to the aortic or pulmonic hangout time, respectively.

The most common causes of an MSM are benign (innocent) flow murmurs, an increase in flow rate across a normal semilunar valve, and aortic valve sclerosis. These physiologic murmurs need to be distinguished from the abnormal MSM in patients with fixed or dynamic outflow tract obstruction (table 2).

Innocent midsystolic murmurs — A systolic murmur is present in up to 60 percent of patients, with 90 percent being associated with a normal echocardiogram [15]. These innocent or benign "flow" murmurs are typically ejection type and midsystolic in timing (table 2) [16]. The "innocence" of an MSM should not depend upon the duration or intensity of the murmur, but on the absence of other abnormal findings. Even a short grade I/VI ejection MSM may not be innocent if there are coexisting findings such as an abnormal S2.

In young adults, an innocent MSM can be heard that has a blowing quality and is best heard over the pulmonary area. This murmur is thought to originate from vibrations of the pulmonary trunk.

In patients with the straight back syndrome who have a decreased anteroposterior diameter of the chest, a grade I to II (rarely grade III) MSM is heard over the left second interspace [17]. The mechanism of the murmur remains unclear. The murmur is often enhanced by firm application of the stethoscope over the pulmonary area, suggesting that an anatomical distortion of the RV outflow tract and pulmonary valve and artery by the chest deformity plays a role in generating the murmur.

Increased semilunar blood flow — An MSM also occurs in the presence of normal valves when flow across the semilunar valve is significantly increased, as occurs in the following settings (table 2):

●Anemia, pregnancy, and thyrotoxicosis. As an example, a pulmonic MSM is present in over 80 percent of normal pregnant women.

●In patients with pure aortic regurgitation, an ejection MSM may result from markedly increased flow across the aortic valve and should not be considered evidence for aortic stenosis (AS) in the absence of other findings.

●An atrial septal defect with left to right shunting results in an ejection MSM resulting from increased flow across the pulmonic valve accompanied by fixed split S2. This does not indicate associated pulmonic stenosis.

Aortic valve sclerosis — The murmur of aortic sclerosis is also a midsystolic ejection murmur (figure 2). It is not associated with hemodynamic consequences, but it must be considered in the differential diagnosis of AS in older adults. (See "Aortic valve sclerosis and pathogenesis of calcific aortic stenosis".)

The murmur is usually best heard over the right second interspace. In some patients, a musical high-frequency murmur of brief duration can be heard along the lower left sternal border and cardiac apex. In general, the murmur is brief and not very loud. A normal carotid pulse and normal S2 confirm the absence of significant aortic valve obstruction.

The clinical significance of the diagnosis of aortic sclerosis is that it is a risk factor for long-term adverse outcomes due to atherosclerotic heart disease.

Aortic outflow obstruction — An MSM associated with fixed aortic obstruction due to valvular, subvalvular, or supravalvular stenosis or hypertrophic cardiomyopathy (HCM) typically is harsh and medium pitch (table 2). The time the murmur peaks after its onset bears some correlation to the severity of the obstruction. In patients with AS, the longer- and later-peaking murmur is usually associated with hemodynamically significant obstruction; a brief and early peaking murmur indicates less severe AS (figure 2).

However, the intensity of the murmur is variable and may not correlate with the severity of stenosis. A grade 4 or greater murmur is specific but not sensitive for the diagnosis of severe AS, as most patients with severe AS have a grade 3 murmur. The A2 component of S2 is diminished and frequently absent in severe AS. Furthermore, the presence of heart failure and a reduced stroke volume, the duration, configuration, and intensity bear a poor correlation to the degree of obstruction.

An ejection sound at the onset of the murmur suggests congenital AS or a bicuspid valve. The ejection sound is usually absent in severe AS.

The anatomic site where the murmur is best heard corresponds to the site of obstruction, direction, and radiation of the jet in the aortic root. Nevertheless, echocardiography is required for accurate determination of the site and severity of a fixed obstruction (valvular, supravalvular, or subvalvular).

Valvular aortic stenosis — The murmur of AS is usually of maximum intensity over the right second interspace; a thrill may be palpable over the same area. The murmur radiates up into the neck and over both carotid arteries (table 4).

In older patients with calcific trileaflet AS, an MSM with a musical quality is frequently heard over the cardiac apex or along the lower left sternal border, in addition to a harsh murmur over the right second interspace (movie 1 and movie 2). A musical murmur appears to originate from the vibration of the valve and subvalvular structures and can be recorded in the LV cavity (Gallavardin phenomenon); a harsh murmur originates in the aortic root and is related to the high-velocity ejection jet. (See "Clinical manifestations and diagnosis of aortic stenosis in adults".)

A bicuspid aortic valve is another common cause of an MSM, and the murmur may be present before leaflet thickening and calcification result in outflow obstruction (table 2). The murmur is best heard over the right second interspace with little or no radiation (movie 3 and movie 4).

The diagnosis of a nonstenotic bicuspid valve is virtually confirmed if it is accompanied by an aortic ejection sound, a short early diastolic murmur, and normal carotid pulse upstroke and S2. However, these findings are not sensitive for the diagnosis and many patients with a bicuspid valve are first diagnosed when echocardiography is performed for other indications. (See "Clinical manifestations and diagnosis of bicuspid aortic valve in adults".)

Prosthetic aortic valve — A short systolic murmur is often appreciated in patients with normal functioning bioprosthetic and mechanical valves due to size of the prosthesis. The systolic murmur increases in intensity and duration over time commensurate with the inevitable progressive degeneration of the bioprosthetic valve. An absent mechanical aortic valve closing click (S2) and medium to long systolic murmur is characteristic of a thrombosed mechanical aortic valve (in the setting of inadequate anticoagulation).

Supravalvular aortic stenosis — In supravalvular AS, the murmur may be loudest at a slightly higher location than in valvular AS (table 4). In addition, the intensity of the radiated murmur over the right carotid may be greater than over the left carotid artery. (See "Valvar aortic stenosis in children".)

Subvalvular outflow obstruction — In subvalvular LV outflow obstruction, usually due to HCM, the maximum intensity of the murmur is usually located along the lower left sternal border or over the cardiac apex (table 4). It radiates poorly to the base and neck. The site of the LV outflow obstruction cannot be identified with certainty by the location, radiation, and character of the MSM. (See "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation".)

Fixed versus dynamic outflow obstruction — It is usually not difficult to distinguish between fixed valvular AS and dynamic (obstructive HCM) LV outflow obstruction (table 4). With respect to the carotid pulse:

●In fixed valvular AS, the initial upstroke and the peak of the carotid pulse are delayed and the volume may be reduced.

●In obstructive HCM, the initial upstroke of the carotid pulse is usually sharp and the volume is normal.

The change in intensity of the MSM in response to different maneuvers is also useful diagnostically.

●The transition from a squatting position to a standing position increases the intensity of the murmur in HCM. Conversely, this change in position decreases the murmur of valvular AS. This is the most reliable maneuver for evaluation of an MSM.

●The murmur of HCM increases in intensity with the straining phase of a Valsalva maneuver and the carotid pulse decreases or is unchanged. Both the intensity of the murmur and the carotid pulse volume decline with Valsalva in AS.

●Amyl nitrate inhalation increases the intensity of the murmur of HCM, and the carotid pulse volume decreases or remains unchanged. Heart rate increases and arterial blood pressure falls. In AS, both the intensity of the murmur and carotid pulse volume increase with amyl nitrate inhalation. It is generally more difficult to interpret the responses to amyl nitrite than to standing or the Valsalva maneuver in distinguishing HCM from valvular AS.

These features can also be used to distinguish HCM from fixed subvalvular AS (subaortic stenosis), which is seen primarily in children (table 4). (See "Subvalvar aortic stenosis (subaortic stenosis)".)

The murmur of dynamic LV outflow obstruction has been observed transiently in patients who develop acquired LV outflow obstruction during acute myocardial infarction or in patients with apical ballooning syndromes [1]. However, these complications are distinctly rare. (See "Clinical manifestations and diagnosis of stress (takotsubo) cardiomyopathy".)

Pulmonic outflow obstruction — The murmur of valvular pulmonic stenosis is harsh and best heard over the left second interspace. When the murmur is loud, it radiates to the left side of the neck and is frequently accompanied by a palpable thrill. A pulmonic ejection sound at the onset of the murmur may be heard, and S2 is widely split with a decreased intensity of P2. (See "Clinical manifestations and diagnosis of pulmonic stenosis in adults".)

The duration of murmur correlates reasonably well with the severity of stenosis. The duration can be determined by timing the termination of the murmur in relation to A2. A murmur terminating before A2 (relatively short) is usually associated with mild to moderate stenosis. Stenosis is likely to be more severe if the murmur drowns A2 (terminating after A2) [18].

Occasionally, the long, harsh MSM of pulmonic stenosis can be confused with the holosystolic murmur of a VSD. This is more likely to occur with infundibular than valvular stenosis because of the lower location of the murmur. Careful attention to the behavior of S2 helps in the differential diagnosis: S2 is usually normal in VSD, while in pulmonic stenosis, it is widely split and the intensity of P2 is decreased. Amyl nitrite inhalation is sometimes helpful; it usually decreases the intensity of the VSD murmur but not that of the pulmonic stenosis (which may be accentuated).

Dilation of the aortic root or pulmonary artery — Aortic root dilatation or dilatation of the proximal pulmonary artery may be associated with an MSM. The usual findings of idiopathic dilatation of the pulmonary artery are a pulmonary ejection sound, a short MSM, a relatively widely split S2 with normal intensity of P2, and occasionally a short pulmonic regurgitant murmur. There is no hemodynamic abnormality. The auscultatory findings are very similar in pulmonary hypertension, except S2 is narrowly split with P2 markedly accentuated, the pulmonic ejection sound is relatively late, and hemodynamic abnormalities are always evident.

Midsystolic versus holosystolic murmurs — It can be difficult to distinguish between a long MSM and a holosystolic regurgitant murmur in certain situations. The MSM transmitted to the cardiac apex in dynamic or fixed LV outflow obstruction may sound similar to the murmur of MR or VSD. It is often difficult to appreciate the onset of the murmur when S1 is soft, which can occur in AS or MR. When A2 is soft, determining the timing of murmur termination may also be difficult. Although the etiology of the murmur will be readily established by echocardiography [10], a number of helpful distinguishing features can be elicited by auscultation (figure 2):

●The murmur is likely to be midsystolic if A2 is clearly audible over the cardiac apex. If A2 is heard over the right and left second interspaces but not over the apex, it is likely that A2 is "drowned" by the holosystolic murmur of MR.

●The intensity of an MSM increases with a longer RR cycle (eg, in patients with atrial fibrillation and varying RR cycles) and with a post-ectopic beat (in patients with premature beats); the intensity of a regurgitant murmur usually remains unchanged in these situations.

●Changes in the intensity of the murmur may occur in response to hand grip; it increases the intensity of an MR murmur (increased afterload effect) and usually decreases the intensity of an AS murmur. However, the physiologic responses to hand grip are complex; in addition to an increase in systemic vascular tone and arterial pressure, a reflex increase in contractility may occur, which may increase, rather than decrease, the intensity of the stenotic murmur.

Holosystolic murmurs — Holosystolic murmurs are usually regurgitant murmurs and occur when blood flows from a chamber in which pressure throughout systole is higher than pressure in the chamber receiving the flow. There are three causes of holosystolic murmurs:

●MR

●Tricuspid regurgitation

●VSD

The timing and duration of holosystolic murmurs are best explained by the hemodynamic changes of MR. In hemodynamically significant MR, regurgitant flow from the left ventricle to the left atrium begins with the onset of isovolumic systole when pressure in the left ventricle just exceeds pressure in the left atrium. This pressure crossover point also marks S1, explaining the onset of the holosystolic murmur with S1. Throughout systole and extending to the early part of the isovolumic relaxation phase, the LV pressure remains higher than the left atrial pressure. Thus, the regurgitant flow continues throughout systole, and even after aortic valve closure, explaining the holosystolic character of the regurgitant murmur. This also explains why A2 is often drowned by the murmur over the cardiac apex.

Mitral regurgitation — The holosystolic murmur of MR is high pitched and best heard with the diaphragm of the stethoscope and the patient in the left lateral decubitus position (movie 5). Radiation depends upon the murmur intensity, which may be variable. The direction of radiation follows the direction of the regurgitant jet into the left atrium.

●When the jet is directed posterolaterally, the apical holosystolic murmur radiates toward the left axilla, inferior angle of the left scapula, and over the thoracic spine [19]. In some patients, a loud murmur may be transmitted up the spine and sometimes to the top of the head.

●The murmur radiates toward the base and root of the neck if the regurgitant stream is directed anteromedially against the interatrial septum near the base of the aorta. Thus, it can be confused with the murmur of AS or obstructive HCM. The character of the carotid pulse and the behavior of S2 provide important clues to the diagnosis.

Associated physical findings may help to characterize the nature and severity of MR, although with significant limitations. A more benign overall examination is suggestive of less severe MR and primary valve disease. Abnormalities (eg, S3, an accentuated P2, or a displaced apical impulse) are less helpful, since they can occur with primary valve disease, secondary MR, or a separate cardiac or pulmonary abnormality. The holosystolic murmur of severe MR is occasionally accompanied by a middiastolic flow murmur due to increased diastolic flow across the mitral valve. (See "Clinical manifestations and diagnosis of chronic mitral regurgitation".)

The value and limitations of associated physical findings in a patient with MR is illustrated by the following:

●The absence of an S3 and cardiac enlargement suggest hemodynamically insignificant chronic MR. In contrast, clinical evidence of pulmonary hypertension (accentuated P2, right ventricular systolic hypertension) and right-sided heart failure are almost always associated with significant MR, provided no other cause of pulmonary hypertension coexists.

●A normal or hyperdynamic LV apical impulse suggests normal LV systolic function, and therefore primary MR. However, a displaced or sustained apical impulse may occur with either primary or secondary MR.

●In patients with either severe primary MR or a dilated cardiomyopathy with secondary (functional) MR, there may be an S3 gallop due to the high antegrade flow across the mitral valve, and findings of pulmonary hypertension and right heart failure. However, in dilated cardiomyopathy, S3 and findings of pulmonary hypertension may be present with mild or insignificant MR.

Thus, physical examination cannot reliably distinguish chronic severe MR due to primary valve disease from secondary MR due to dilated cardiomyopathy. (See "Examination of the precordial pulsation".)

Tricuspid regurgitation — The holosystolic murmur of tricuspid regurgitation is best heard with the diaphragm of the stethoscope along the left lower sternal border [9]. The location of maximum intensity may be shifted toward the cardiac apex when the right ventricle is dilated, and the murmur can be misdiagnosed as MR. Radiation and respiratory changes in the intensity of the murmur are two important distinguishing features.

●With tricuspid regurgitation, the murmur is heard along the left or right sternal border and may radiate to the epigastrium.

●During the inspiratory phase of respiration, the intensity of the murmur of tricuspid regurgitation increases (Carvallo sign, also known as Rivero-Carvallo sign) if severe right ventricular failure is not present. The increase in intensity does not occur immediately with the onset of inspiration, but after one or two cardiac cycles. The mechanism for the increase in intensity appears to be augmented regurgitant flow following the inspiratory increase in right ventricular volume. A right ventricular S3 gallop and a middiastolic flow murmur, which also increase in intensity with inspiration, suggest more severe tricuspid regurgitation.

Murmur intensity does not change in the presence of severe right ventricular failure when right ventricular volume may not change appreciably. With severe right-sided heart failure, the murmur can be absent, or only an early systolic murmur may be recognized. In these circumstances, the bedside diagnosis of tricuspid regurgitation relies upon the presence of other physical findings, such as a prominent v wave in the jugular venous pulse and systolic hepatic pulsation.

Tricuspid regurgitation is most often secondary to pulmonary arterial hypertension. Thus, a prominent left parasternal impulse and narrow splitting of S2 with an accentuated P2 suggest secondary tricuspid regurgitation. Theoretically, severe tricuspid regurgitation may produce reversed splitting of S2 due to shortened right ventricular ejection time; however, this is a rare finding.

Primary tricuspid regurgitation is much less common but can occur following bacterial endocarditis (eg, with intravenous drug abuse) or in patients with Ebstein anomaly, carcinoid heart disease, or prior right ventricular infarction. Primary tricuspid regurgitation has become an increasing problem following placement of endocardial leads. At least moderate tricuspid regurgitation has been reported in approximately 10 percent of patients following lead placement [20]. A hyperdynamic left parasternal impulse and normal or only slightly accentuated P2 suggest primary tricuspid regurgitation, but its diagnosis primarily depends upon the elimination of pulmonary hypertension and left-sided disorders such as mitral and aortic valve disease and cardiomyopathy. In primary tricuspid regurgitation, the murmur may be early systolic rather than holosystolic, and have a decrescendo shape. (See "Etiology, clinical features, and evaluation of tricuspid regurgitation".)

Ventricular septal defect — VSDs cause a holosystolic murmur if pressure in the right ventricle is lower than the left ventricle throughout systole, resulting in a continuous left-to-right shunt [21,22]. This hemodynamic profile is present in small VSDs and is associated with normal pulmonary artery pressure and pulmonary vascular resistance. Thus, S2 is normal and pulmonary hypertension is absent.

The murmur is usually loud and may be accompanied by a thrill. The left-to-right shunt is directed toward the right ventricular cavity. The murmur is maximal over the third and fourth interspaces along the sternal border when the VSD is below the crista supraventricularis. When the defect is above the crista, the shunt is directed toward the pulmonary trunk; the maximal intensity of the murmur may be in the left second interspace in this case, and it can be confused with the murmur of pulmonary valve stenosis [18].

Changes in S2 help in the differential diagnosis. A wide splitting of S2 with reduced intensity of P2 is present in pulmonary stenosis; a normal S2 favors VSD.

The character and timing of the systolic murmur change with large VSDs due to increased right ventricular and pulmonary artery pressure and an elevated pulmonary vascular resistance. Instead of being holosystolic, it becomes early systolic and the peak of the murmur occurs earlier. The physical findings of pulmonary arterial hypertension and right ventricular hypertrophy are present.

When ventricular pressures are equal in Eisenmenger complex, there is no murmur across the VSD; instead, an MSM due to dilatation of the pulmonary trunk appears. S2 is markedly accentuated and single [23].

Hence, a loud holosystolic murmur in a patient with a VSD signifies favorable hemodynamics (eg, relatively normal right-sided pressures). (See "Isolated ventricular septal defects (VSDs) in infants and children: Anatomy, clinical features, and diagnosis" and "Clinical manifestations and diagnosis of ventricular septal defect in adults".)

Late systolic murmurs — A late systolic murmur starts after S1 and, if left-sided, extends to A2, usually in a crescendo manner (figure 3).

Mitral valve prolapse — Mitral valve prolapse is the most common cause of a late systolic murmur. It is best heard with the diaphragm of the stethoscope, over or just medial to the cardiac apex. It is usually preceded by single or multiple clicks [24]. Mitral valve prolapse can occur from disorders of the mitral annulus, redundancy of the leaflets, abnormalities of the chordae, or contraction abnormalities of the LV wall. MR occurs when prolapse is sufficient to cause a lack of apposition of the leaflets. (See "Mitral valve prolapse: Clinical manifestations and diagnosis".)

The most common etiology for mitral valve prolapse is redundancy of valve tissue with respect to the valve ring ("floppy" valve or Barlow's syndrome). This disparity increases with a decreased LV volume, which is associated with an earlier onset of prolapse and, therefore, the late systolic murmur occupies a relatively greater portion of systole. Abrupt standing, sitting, or Valsalva maneuver (phase 2) decreases LV volume and causes an earlier onset of the click and murmur, so the murmur lengthens (table 5 and movie 6 and movie 7). The murmur is also often intensified.

Conversely, squatting or passive elevation of the legs, which increases LV volume, delays the onset of the click and murmur, and the intensity of the murmur may decrease. However, the intensity of the murmur may increase in some cases in response to squatting due to the increase in afterload.

A "whoop" or "honk," which is a high-frequency, musical, loud, and widely transmitted murmur, can appear intermittently in some patients with mitral valve prolapse and may be precipitated by a change of posture.

In general, mitral valve prolapse with a late systolic murmur is associated with mild MR and is not accompanied by an S3 or signs of pulmonary hypertension. LV function is normal.

In patients with pseudohypertrophic muscular dystrophy, mitral valve prolapse and a late systolic murmur are manifestations of cardiac involvement. These may or may not be associated with midsystolic clicks. The electrocardiogram almost always demonstrates a relatively tall R wave in leads V1 and V2, simulating true posterior myocardial infarction. The mechanism of mitral valve prolapse and its electrocardiographic changes is fibrosis of the posterior LV wall.

Tricuspid valve prolapse — Tricuspid valve prolapse is uncommon in the absence of mitral valve prolapse. It causes a late systolic murmur that extends up to P2. It is best heard over the left lower sternal border. Onset of the murmur may be delayed during inspiration due to an increase in right ventricular volume.

Ischemic mitral regurgitation — A late systolic murmur may occur with mild MR due to papillary muscle displacement (previously known as papillary muscle dysfunction) in patients with "ischemic MR" due to acute or chronic myocardial infarction. It can also occur in patients with chronic coronary artery disease during an episode of myocardial ischemia, presumably due to ischemic papillary muscle displacement. In these patients, isometric exercise or maneuvers that increase ventricular volume may precipitate MR and a late systolic murmur because of increased myocardial oxygen requirements, which may induce myocardial ischemia. (See "Role of echocardiography in acute myocardial infarction" and "Chronic secondary mitral regurgitation: General management and prognosis".)

DIASTOLIC MURMURS

Early diastolic murmurs — Early diastolic murmurs, most often due to aortic or pulmonary regurgitation, typically start at the time of semilunar valve closure and their onset coincides with S2. An aortic regurgitation murmur begins with A2; pulmonary regurgitation begins with P2.

Aortic regurgitation — Discovery of a diastolic murmur is essential for the diagnosis of aortic regurgitation. 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].

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. If the aortic pressure remains higher than LV pressure throughout diastole, a pandiastolic murmur may be present, even when the severity of aortic regurgitation is only moderate. Bedside evaluation of the severity of aortic regurgitation should be primarily based upon a determination of the hemodynamic consequences. (See "Examination of the arterial pulse".)

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".)

Assessment of LV function is important, particularly with respect to the timing of surgery. 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.

Pulmonic regurgitation — A small amount of pulmonic regurgitation is normal and occasionally can be heard in thin subjects.

Pathologic pulmonic regurgitation is most frequently a result of pulmonic hypertension (Graham-Steell murmur) or residual after tetralogy of Fallot repair in adults [29]. The murmur of pulmonic regurgitation associated with pulmonary hypertension is high-pitched and "blowing." It begins with an accentuated P2 of S2 and can be of variable duration. It may occupy all of diastole if there is a pandiastolic gradient between the pulmonary artery and the right ventricular diastolic pressure. The murmur has a decrescendo configuration like that of aortic regurgitation; differentiation is difficult if not impossible by auscultation alone. The murmur may increase in intensity during inspiration and can be more localized. It is best heard over the left second and third interspaces.

In contrast, the murmur of residual pulmonic regurgitation after Tetralogy of Fallot repair typically is low pitched and soft because pulmonary pressures are normal, so there is only a small diastolic pressure difference between the pulmonary artery and right ventricle. A to-and-fro murmur over the left second intercostal space may be noted or there may be no audible murmur with severe pulmonic regurgitation.

Pulmonic regurgitation can occur in the absence of pulmonary hypertension, as in patients with idiopathic dilatation of the pulmonary artery, after pulmonic valvulotomy, with right-sided endocarditis, and with congenital absence of the pulmonic valve. In these conditions, the pulmonary artery diastolic pressure is normal or low and there is a lower rate of regurgitant flow; the regurgitant murmur is of low to medium pitch.

In congenital absence of the pulmonic valve, P2 is absent and there is a silent interval between A2 and the onset of the regurgitant murmur. A loud to-and-fro murmur may be heard in these patients.

Left anterior descending artery stenosis — Left anterior descending coronary artery stenosis very rarely causes a diastolic murmur similar to aortic regurgitation (Dock murmur) [30]. The murmur is not widespread like that of aortic regurgitation and usually is best heard over the left second or third interspace, a little lateral to the left sternal border. The murmur may be long or short. It is caused by turbulent flow across the coronary artery stenosis and usually indicates moderately severe stenosis. Coronary artery bypass surgery or percutaneous coronary intervention abolishes the murmur.

Middiastolic murmurs — Middiastolic murmurs result from turbulent flow across the atrioventricular valves during the rapid filling phase because of mitral or tricuspid valve stenosis and an abnormal pattern of flow across these valves.

Mitral stenosis — The middiastolic murmur of mitral stenosis has a rumbling character and is best heard with the bell of the stethoscope over the LV impulse with the patient in the left lateral decubitus position (movie 11 and movie 12). The murmur originates in the LV cavity, explaining its location of maximum intensity.

The murmur is present both in sinus rhythm and in atrial fibrillation. It characteristically starts with an opening snap. Its duration, which correlates with the duration of the diastolic pressure gradient across the mitral valve, is a reasonably good guide to assess the severity of mitral stenosis [31]. In patients with sinus rhythm, there is frequently a presystolic accentuation of the diastolic murmur. The longer the duration of the murmur, the more severe is the mitral stenosis, provided the diastolic interval is not too short (absence of tachycardia). If the murmur extends up to S1 during a longer diastolic interval, it can be assumed that the pressure gradient is still present at end-diastole, which implies severe mitral stenosis.

The murmur of mitral stenosis may be of very brief duration or even absent (so-called silent mitral stenosis), even in the presence of severe mitral stenosis, when the flow across the mitral valve is markedly reduced. This may occur in the setting of right-sided heart failure and pulmonary hypertension. Conversely, with enhanced flow across the valve, as in the high-output state of pregnancy, the intensity and duration of the murmur increase even with less severe stenosis. In these circumstances, one cannot rely on the duration of the murmur to assess the severity of mitral stenosis; other ancillary investigations, particularly echocardiographic studies, are necessary. (See "Rheumatic mitral stenosis: Clinical manifestations and diagnosis".)

Prosthetic mitral valve — A diastolic murmur is usually not appreciated in patients with normal functioning bioprosthetic and mechanical mitral valves. A diastolic murmur may become evident over time due the progressive degeneration of the bioprosthetic valve. An absent mechanical mitral valve closing click (S1) and medium to long diastolic murmur is characteristic of a thrombosed mechanical mitral valve (in the setting of inadequate anticoagulation).

Tricuspid stenosis — Tricuspid stenosis may be associated with a middiastolic rumble that is best heard along the left sternal border. The most characteristic feature is the increase in intensity of the murmur with inspiration (Carvallo sign or Rivero-Carvallo sign) [32]. The middiastolic rumble may be associated with a tricuspid opening snap and wide splitting of S1 due to delayed closure of the tricuspid valve. Most patients with tricuspid stenosis are in atrial fibrillation and the murmur is middiastolic when the transvalvular pressure gradient is maximum. In sinus rhythm, the murmur may occur only in late diastole, resulting from an increased flow due to right atrial systole.

Tricuspid stenosis most frequently occurs in association with mitral stenosis. Isolated tricuspid stenosis is uncommon; when suspected, carcinoid heart disease and right atrial myxoma should be investigated as possible etiologies.

Atrial myxoma — Atrial myxoma may cause obstruction of the atrioventricular valves and a middiastolic murmur. In left atrial myxoma, the auscultatory findings can be similar to those of mitral stenosis. The murmur is frequently presystolic and crescendo in configuration; it appears to occur with the onset of ventricular systole when the tumor is moved toward the left atrium through the mitral orifice, and when the flow across the valve is still continuing.

It is difficult to distinguish between a left atrial myxoma and mitral stenosis at the bedside. However, the character and intensity of the murmur due to an atrial myxoma may change with alterations of position [33]. Sinus rhythm, changing intensity and character of the murmur, and a "tumor plop" sound favor the diagnosis of left atrial myxoma. Nevertheless, echocardiographic evaluation is necessary and is always recommended in a patient with suspected mitral stenosis.

Right atrial myxoma is far less common than left atrial myxoma. Auscultatory findings may be similar to those of tricuspid stenosis. (See "Cardiac tumors".)

Increased flow across the atrioventricular valve — An early diastolic rumbling murmur can be appreciated at the apex in the presence of complete heart block when atrial contraction coincides with rapid early diastolic filling. Middiastolic murmurs may occur in the presence of normal atrioventricular valves when the flow across the valve is markedly increased in middiastole (flow murmurs). In pure severe mitral regurgitation (MR), a larger volume of blood (due to the regurgitant volume) moves from the left atrium to the left ventricle during diastole; the etiology is a partial closing movement of the mitral valve, which occurs after it opens widely at the beginning of diastole. The rapid flow to the left ventricle continues, and thus "functional mitral stenosis" occurs, explaining the middiastolic rumble. In some patients, a middiastolic pressure gradient has been demonstrated [34-36].

With a left-to-right shunt across a ventricular septal defect or patent ductus arteriosus, antegrade blood flow across the mitral valve increases during diastole, which may be associated with a middiastolic murmur. The mechanism may be similar to that seen in MR. When the etiology is an atrial septal defect or anomalous pulmonary venous drainage, a tricuspid flow murmur can also be heard along the lower left sternal border; this is due to a partial closing movement of the tricuspid valve after its full opening in early diastole and functional tricuspid stenosis at middiastole [37]. The intensity of the tricuspid flow murmur tends to increase during inspiration.

Carey-Coombs murmur — In acute rheumatic fever, a middiastolic murmur over the LV impulse, a Carey-Coombs murmur, has been attributed to acute mitral valvulitis. However, first-degree atrioventricular block (prolonged PR interval) is common in rheumatic carditis and an increased flow due to earlier atrial systole coinciding with the rapid filling phase may contribute to a Carey-Coombs murmur.

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.

Left-to-right shunts — Flow murmurs due to a large left-to-right shunt are usually middiastolic in timing. Occasionally, they can extend to late diastole.

Late diastolic murmurs — Presystolic murmurs occur in late diastole and extend up to S1. They usually have a crescendo configuration. The murmurs result from increased flow across the mitral or tricuspid valve and are most frequently observed in the presence of normal sinus rhythm. However, crescendo presystolic murmurs can occur in the presence of atrial fibrillation in the absence of atrial systole; mitral valve closure, resulting in a reduction of an effective mitral orifice, begins before the onset of isovolumic systole and S1 and during this period antegrade flow across the mitral valve continues [41].

Mitral stenosis — Atrial contraction increases the pressure gradient and flow at end-diastole when mitral stenosis is present, generating the presystolic murmur. When a middiastolic rumble accompanies a presystolic murmur, the intensity of the middiastolic murmur frequently decreases before the onset of the presystolic murmur. The presence of only a presystolic murmur associated with increased intensity of S1 suggests mild mitral stenosis.

Tricuspid stenosis — In tricuspid stenosis with sinus rhythm, the murmur is usually presystolic because the transvalvular gradient is maximum during this period [32]. The intensity of the presystolic murmur of tricuspid stenosis also increases during inspiration, which is associated with an increased venous return to the right atrium. Increased right atrial volume is associated with more forceful right atrial contraction and, therefore, an increased pressure gradient during this interval and accentuation of the murmur.

Myxoma — Presystolic murmurs may occur with left or right atrial myxomas. This is due to obstruction of the atrioventricular valves.

Complete heart block — In complete atrioventricular block with a slow idioventricular rhythm, a short late diastolic murmur can occasionally be heard and recorded (Rytand murmur). The precise mechanism of Rytand murmur has not been elucidated; diastolic MR has been postulated [42,43]. Diastolic MR appears to depend upon the timing of the P wave and atrial systole relative to ventricular diastole. (See "Third-degree (complete) atrioventricular block".)

CONTINUOUS MURMURS — Continuous murmurs are defined as murmurs that begin in systole and extend up to diastole without interruption. They do not necessarily need to occupy the total duration of systole and diastole. Continuous murmurs result from blood flow from a higher pressure chamber or vessel to a lower system associated with a persistent pressure gradient between these areas during systole and diastole. These murmurs may occur due to aortopulmonary connections, arteriovenous communication, and disturbances in the flow patterns in the arteries or veins (figure 3 and table 3) [44-47].

Patent ductus arteriosus — Patent ductus arteriosus is a relatively common cause of a continuous murmur in adults. Aortic pressure is higher than pulmonary artery pressure during both systole and diastole; blood flow from the high pressure descending thoracic aorta to the low pressure pulmonary artery causes the continuous murmur (Gibson murmur or machinery murmur).

The maximum intensity of the murmur usually occurs at S2. The duration of the murmur depends upon the pressure difference between aorta and pulmonary artery. With pulmonary hypertension, pulmonary artery diastolic pressure increases; when it approaches systemic level, the diastolic portion of the continuous murmur becomes shorter and ultimately absent [48]. With more severe pulmonary hypertension, pulmonary artery systolic pressure can equalize with aortic systolic pressure and the systolic component of the murmur may also be absent (silent ductus). Differential cyanosis due to the reversal of the shunt and signs of pulmonary hypertension with or without evidence of right-sided heart failure are the only physical findings that are recognizable at the bedside in these circumstances.

Aortopulmonary window — Continuous murmurs may be present with an aortopulmonary window. However, because of the large size of the communication, pulmonary vascular resistance and pulmonary artery diastolic pressure tend to be higher, which is associated with a shorter duration of the diastolic component of the continuous murmur.

Shunts — A left-to-right shunt through a small atrial septal defect in the presence of mitral valve obstruction, known as Lutembacher syndrome, may occasionally cause a continuous murmur [49]. Total anomalous pulmonary venous drainage, a small atrial septal defect without mitral valve obstruction, and mitral stenosis with a persistent left superior vena cava are very rare causes of continuous murmurs.

Arteriovenous fistulas — Congenital or acquired arteriovenous fistulas also cause continuous murmurs.

●Coronary arteriovenous fistulas may produce a continuous murmur; the location, duration, and character of the murmur depend upon the anatomical type of fistulas. As an example, the right coronary and right atrial, or coronary sinus, communication produces continuous murmurs that are usually located along the parasternal areas. The murmur of a circumflex coronary artery and coronary sinus communication are usually located in the left axilla. The configuration of the murmur and the intensity of the systolic and diastolic components are variable. Marked systolic compression of the abnormal vessels reduces the systolic flow; thus, the systolic component of the murmur may be very soft. On the other hand, an increased systolic gradient may result from the partial compression of the intramural communication, which will tend to increase the intensity of the systolic portion of the murmur.

Fistulous connection between an internal mammary graft and the pulmonary vasculature or left anterior descending vein are rare causes of continuous murmurs [50].

●A communication between the sinus of Valsalva and the right atrium or right ventricle produces continuous murmurs that may appear as to-and-fro murmurs due to the increased intensity of both the systolic and diastolic components and a softer intensity around S2.

●Systemic and pulmonary arteriovenous fistulas are also associated with continuous murmurs. Although a systemic arteriovenous communication usually produces a loud murmur, the murmur of pulmonary arteriovenous fistulas is softer and may be primarily systolic. The major pressure gradient occurs in systole, and the diastolic gradient is usually very small. Pulmonary arteriovenous fistulas usually involve the lower left or right middle lobe; the location of the murmurs corresponds to these areas. (See "Pulmonary arteriovenous malformations: Epidemiology, etiology, and pathology in adults".)

Coarctation of the aorta — In coarctation of the aorta, a continuous murmur can be heard in the back overlying the area of constriction. Continuous murmurs may originate in large tortuous collateral arteries in coarctation of the aorta, which are also heard in the back over the interscapular regions. Sometimes, large, tortuous intercostal vessels are visible when the shoulders are rotated medially and forward to separate the scapulas (Suzman sign) [51]. (See "Clinical manifestations and diagnosis of coarctation of the aorta".)

Other — Constriction in the systemic or pulmonary arteries can be associated with continuous murmurs due to a persistent pressure gradient across the narrowed segment of the vessel.

Pulmonary artery branch stenosis and a partial occlusion of the pulmonary artery due to pulmonary embolism may also cause continuous murmurs.

Rapid flow through tortuous collateral vessels, as in coarctation of the aorta, may cause a continuous murmur. Bronchial arterial collateral vessels develop in certain types of cyanotic congenital heart disease (tricuspid atresia, pulmonary atresia with ventricular septal defect) and loud continuous murmurs may be heard along the parasternal area.

A large dialysis fistula can be associated with a continuous murmur that can radiate to the infraclavicular area.

The "mammary souffle" associated with pregnancy may be systolic or continuous. These innocent murmurs are usually of higher frequency (high pitched) and louder in systole.

A venous hum, which results from altered flow in the veins, can also cause an innocent continuous murmur. The venous hum is heard with the patient in the sitting position (usually in the supraclavicular fossa) and frequently disappears when the patient moves to the supine position. The hum tends to be louder in diastole and can be completely abolished by compression of the ipsilateral internal jugular vein. A loud, left-sided venous hum transmitted below the clavicle should not be mistaken for the murmur of patent ductus arteriosus. Venous hum is not heard in the supine position, and pressure on the internal jugular vein abolishes the venous hum. In contrast, the murmur of patent ductus arteriosus persists in the supine position and despite pressure on the internal jugular vein.

A pericardial friction rub may be confused with a continuous murmur. It is heard best at the left lower sternal border, and sounds more scratchy and swishing than continuous.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cardiac valve disease".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Heart murmurs (The Basics)")

SUMMARY

●Murmur characteristics – A murmur is characterized by its intensity (grade), timing, configuration (time course), frequency (pitch), and location. (See 'Murmur description' above.)

●Systolic murmurs

•Midsystolic murmur – The most common causes of a midsystolic murmur (MSM) are benign (innocent) flow murmurs, an increase in flow rate across a normal semilunar valve, and aortic valve sclerosis. These physiologic murmurs need to be distinguished from the abnormal MSM in patients with fixed or dynamic outflow tract obstruction (table 2). (See 'Midsystolic ejection murmurs' above.)

Aortic valve stenosis causes an abnormal MSM that typically is loudest over the right second intercostal space and radiates to the carotids. An MSM associated with a single S2 suggests severe aortic stenosis. Fixed aortic valve obstruction is distinguished from dynamic subaortic outflow tract obstruction by changes in the murmur with maneuvers (table 2). (See 'Midsystolic ejection murmurs' above.)

•Holosystolic murmur – A holosystolic murmur is caused by mitral regurgitation (MR), tricuspid regurgitation, or a small ventricular septal defect (except for some small muscular ventricular septal defects). (See 'Holosystolic murmurs' above.)

•Early systolic murmur – An early systolic murmur is caused by acute severe or mild chronic MR, primary tricuspid regurgitation with normal right ventricular pressures, a large ventricular septal defect, or a small muscular ventricular septal defect. (See 'Early systolic murmurs' above.)

•Late systolic murmur is most commonly caused by mitral valve prolapse, which may be accompanied by a late systolic murmur of tricuspid valve prolapse. The murmur of ischemic MR (caused by infarction or ischemia) is frequently late systolic. (See 'Late systolic murmurs' above.)

●Diastolic murmur

•An early diastolic murmur is usually due to aortic or pulmonic regurgitation. (See 'Early diastolic murmurs' above.)

•Mitral stenosis causes a middiastolic murmur, a late diastolic murmur, or both. (See 'Mitral stenosis' above and 'Mitral stenosis' above.)

•Tricuspid stenosis with sinus rhythm causes a late diastolic murmur while tricuspid stenosis with atrial fibrillation causes a middiastolic murmur. (See 'Tricuspid stenosis' above and 'Tricuspid stenosis' above.)

•A myxoma causes a mid- or late-diastolic murmur. (See 'Atrial myxoma' above and 'Myxoma' above.)

●Continuous murmur – Causes of a continuous murmur include patent ductus arteriosus, aortopulmonary window, some shunts, arteriovenous fistulas, and coarctation of the aorta. (See 'Continuous murmurs' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledge Catherine M Otto, MD, who contributed to earlier versions of this topic review.