Auscultation of cardiac murmurs in adults: General concepts and systolic murmurs

INTRODUCTION — 

Cardiac auscultation is one of the most useful bedside diagnostic tools to detect alterations in cardiovascular anatomy and physiology. Valvular heart disease, congenital heart disease, and other cardiovascular disorders are often first suspected upon auscultation of a murmur.

This topic will review general concepts in auscultation of cardiac murmurs and features of systolic murmurs in adults, with some discussion of maneuvers (eg, respiration, Valsalva maneuver) used to differentiate murmurs with different causes. 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".)

Auscultation of diastolic and continuous murmurs is discussed separately. (See "Auscultation of diastolic and continuous murmurs in adults".)

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".)

DIAGNOSTIC PROCESS

Auscultatory tools — While standard (acoustic-based) stethoscopes continue to be commonly used for cardiac auscultation, digital stethoscopes offer enhanced signal detection, recording, and analysis capabilities, although limited evidence is available on the clinical utility of these enhancements.

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

●Digital (sensor based) stethoscope – ​A digital stethoscope provides the clinician with a choice of a diaphragm and a bell for detection of a wide range of frequencies (including subsonic and audible frequencies) for enhanced signal detection [1]. Digital tools enable direct transfer of acoustic information to computer systems for visualization and analysis. Studies are exploring the diagnostic capabilities of analyzing digital stethoscope data using artificial intelligence methods including deep learning [2,3].

Small studies have yielded differing results when comparing digital versus analog stethoscopes. One study in which 48 medical students were randomly assigned to training with either a digital or analog stethoscope found no difference in the cardiac auscultation skills of the two training groups [4]. However, a study in which a cardiologist and a resident physician examined 30 patients with obesity found that digital stethoscopes provided higher sensitivity with similar specificity compared with analog stethoscopes in detection of valve disease confirmed by echocardiography [5].

Auscultation procedure — Key elements of effective auscultation include [6,7]:

●Examination conditions – Auscultation is optimized by ensuring quiet surroundings and patient comfort.

●Stethoscope use – When using the stethoscope's diaphragm, apply firm pressure; when using the bell, apply light pressure.

●Patient position – A complete cardiac examination includes auscultation (as clinically appropriate) with the patient in supine, left lateral decubitus, sitting and in some cases, standing positions.

●Auscultatory areas – A complete cardiac examination involves systematic listening to all components of the cardiac cycle with both the bell and diaphragm in each of the four auscultatory areas (figure 1) and may extend to more remote areas:

•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.

•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.

•More remote areas – Some examples of murmurs well heard in areas remove from the heart include:

-In patients with peripheral pulmonary stenosis, a systolic murmur can be audible over the anterior aspects of both lungs.

-In patients with severe mitral regurgitation (MR), a systolic murmur can be appreciated on the back below or adjacent to left scapula.

-In patients with an arteriovenous fistula for dialysis, a continuous murmur may be audible over the ipsilateral apical region of lung (just above the clavicle on the anterior chest and just above the scapula on the posterior chest).

●Assessing timing – The timing of murmurs is best assessed by identifying S1 and S2 (movie 1), helped if needed by timing the heart sounds with the carotid pulse (see "Auscultation of heart sounds"). For example, in patients with marked tachycardia, a long diastolic murmur may occasionally be confused with a systolic murmur; timing with the carotid pulse upstroke avoids an incorrect diagnosis.

Accuracy of auscultation — While auscultation of a murmur is a key sign for detection of valve disease, the reported sensitivities and specificities of auscultation for detection of valvular heart disease have varied widely. These results were summarized in a systematic review including 23 studies in which detection of valve disease by physician-performed auscultation was compared with confirmation of significant valvular heart disease (by some form of echocardiography/ultrasound in 18 studies and by aortography/ventriculography in five studies) [8]. Auscultation was performed using analog stethoscopes in all except two studies. The number of participants in each study ranged from 20 to 2977. Significant valvular heart disease was defined as moderate or severe MR or aortic regurgitation, or mild to severe aortic stenosis (AS). Sensitivity of auscultation for significant valvular heart disease ranged from 30 to 100 percent, and specificity ranged from 28 to 100 percent. The likelihood ratio for auscultation changing the probability of valve disease ranged 1.35 to 26.

Expertise and proficiency in auscultation have been waning in the modern era, which has contributed to greater dependence on resource-intensive imaging techniques, mainly echocardiography [9-12]. (See 'Role of echocardiography' below.)

Role of echocardiography — In clinical practice, echocardiography is the standard method for establishing the cause of cardiac murmurs. An echocardiogram is indicated for the diagnosis and evaluation of patients with known or suspected valve disease, congenital heart disease, and other structural heart disease, as noted in major society guidelines [11-14]. Echocardiography is not indicated for asymptomatic patients with a benign flow murmur.

Echocardiography is indicated in the following settings:

●Patients with cardiac symptoms and a murmur.

●Patients with or without cardiac symptoms and one or more of the following:

•A diastolic murmur.

•A grade 2 or greater systolic murmur.

•A systolic murmur in association with an abnormal examination finding, such as a systolic click or reduced carotid upstroke.

The role of echocardiography in the diagnosis and follow-up of cardiac disease (valve disease, congenital heart disease and other cardiac conditions) is discussed in separate topic reviews on the diagnostic evaluation of each of these conditions.

MURMUR DESCRIPTION — 

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

●Location and radiation – The location on the patient's chest where the murmur is loudest is typically described as apical, upper parasternal (including aortic and pulmonary areas at the base of the heart), or lower parasternal (tricuspid) [15]. The location of parasternal murmurs are further characterized by the intercostal space to the right or left of the sternum [16].

It is also helpful to assess the area over which the murmur is audible (radiation); for example, if the murmur is audible in the axilla, suprasternal notch, or over the inferior aspect of the left scapula.

●Timing – The duration of a murmur is assessed by determining the length of systole or diastole that the murmur occupies [17]. The murmur can be long (eg, it occupies most of systole or diastole), or it can be short.

•Systolic murmurs – Starts with or after S1 and terminates before or at S2:

-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 1). 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 (see "Auscultation of diastolic and continuous murmurs in adults", section on 'Diastolic murmurs'):

-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 2 and table 2). (See "Auscultation of diastolic and continuous murmurs in adults", section on 'Continuous murmurs'.)

●Configuration – The time course of murmur intensity corresponds to the "shape" of a diagrammatic representation 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)

●Intensity – The intensity of a murmur is correlated with the severity of valve lesions in some clinical settings, but this relationship is inconsistent since other factors (such as cardiac output) influence murmur intensity [18].

A murmur's intensity is determined by the following factors:

•Turbulence – Cardiac murmurs arise from turbulent blood flow. The degree of blood flow turbulence is related to the rate of blood flow and the pressure gradient across narrowed cardiac structures, such as a stenotic valve [11,12,19]. The pressure gradient across a stenotic valve is inversely related to the orifice size.

•Transmission – Murmurs are typically most audible near their point of origin, as sound diminishes with distance from its source. This decrease in intensity is influenced by the sound transmission characteristics of tissues (eg, limited transmission through fat or air), the distance from the auscultation site to the murmur's origin, and the direction of blood flow. Thus, murmur intensity is generally greater in individuals with low body weight and lesser in individuals with obesity, emphysema, or pericardial effusion.

Although the grading of murmur intensity is subjective, it provides a means of identifying changes in murmur intensity, which has diagnostic relevance.

Six grades are used to classify the intensity of a systolic murmur:

•Grade I – Very faint; heard only with careful listening and may not be detected in all positions.

•Grade II – Soft murmur that is readily detectable.

•Grade III – Moderately loud without a palpable 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.

The first four grades (I through IV) are commonly used for diastolic murmurs since louder diastolic murmurs are very rare. (See "Auscultation of diastolic and continuous murmurs in adults".)

●Pitch and quality – Pitch and quality are closely related.

•The frequency of the murmur determines the pitch, which may be high, medium, or low.

•The quality of the murmur can be described as harsh, rumbling, scratchy, grunting, blowing, squeaky, vibratory, and musical. Blowing murmurs suggest regurgitant flow, as seen in mitral regurgitation. Harsh murmurs indicate increased turbulent flow across a stenotic valve or ventricular septal defect. Rumbling murmurs are associated with low-pitched diastolic murmurs like mitral stenosis. Musical murmurs have a melodic or vibrating quality, such as Still murmur, an innocent murmur commonly found in children. (See "Approach to the infant or child with a cardiac murmur", section on 'Quality'.)

EARLY SYSTOLIC MURMURS — 

Early systolic murmurs may result from atrioventricular (AV) valve regurgitation (mitral regurgitation [MR] or tricuspid regurgitation [TR]), or a ventricular septal defect (VSD).

AV valve regurgitation

●Mitral regurgitation – Either acute severe or mild chronic MR can be associated with an early systolic murmur. ​In patients with acute severe MR, the rapid rise in left atrial pressure during systole leads to early equalization with left ventricular (LV) pressure, resulting in an early systolic, decrescendo murmur that typically ends before the aortic component of the second heart sound (A2). However, some patients with acute MR have midsystolic or holosystolic murmurs (the latter timing similar to some types of chronic MR). (See 'Mitral regurgitation' below and "Acute mitral regurgitation in adults: Clinical presentation and diagnosis", section on 'Murmur'.)

●Tricuspid regurgitation – Severe primary TR with normal right ventricular (RV) systolic pressure may be associated with an early systolic murmur with a decrescendo configuration. The mechanism is similar to that in acute severe MR.

However, secondary TR (which is generally holosystolic) is more common than primary TR. (See 'Tricuspid regurgitation' below and "Tricuspid regurgitation: Etiology, clinical features, and evaluation", section on 'Etiology'.)

Large VSDs and some muscular VSDs — In individuals with a large VSD accompanied by pulmonary hypertension, the murmur may be early systolic. This occurs because rising RV pressure during late systole reduces the left-to-right shunt, shortening the murmur's duration. Signs of RV hypertrophy and pulmonary hypertension are typically present in this setting.

Conversely, some patients with a muscular VSD may exhibit an early systolic murmur (since the defect closes soon after the onset of systole). In these instances, the murmurs are often more localized and of shorter duration and pulmonary hypertension is absent. (See "Clinical manifestations and diagnosis of ventricular septal defect in adults", section on 'Physical signs'.)

VSDs associated with holosystolic murmurs are discussed below. (See 'Small ventricular septal defect' below.)

MIDSYSTOLIC EJECTION MURMURS

Characteristics of SEMs — A midsystolic ejection murmur (also known as systolic ejection murmur or SEM) is typically caused by blood flow across the semilunar valves (aortic or pulmonary); an SEM starts with the beginning of ejection and terminates with the cessation of forward flow. S1 occurs at the onset of isovolumic systole. After isovolumic systole, the onset of an SEM coincides with the beginning of ejection when rising ventricular pressures exceed the semilunar valve opening pressure.

During acceleration of blood flow in early systole there is an increase in intensity (crescendo); 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 is the aortic hangout time and the interval between the termination of the murmur and P2 is the pulmonic hangout time.

Without ventricular outflow obstruction — The most common causes of an SEM are conditions in which there is left or right ventricular outflow obstruction. These benign (innocent) flow murmurs include those caused by increased flow across a normal semilunar valve and the murmur associated with aortic valve sclerosis (table 1).

Innocent systolic ejection murmurs — Innocent, physiologic, functional, or benign "flow" murmurs are typically SEMs (table 1) [20].

Innocent murmurs should be distinguished from SEMs caused by fixed or dynamic outflow tract obstruction (table 1). The "innocence" of an SEM is not based upon the duration or intensity of the murmur, but on the absence of other abnormal findings. Even a short grade I SEM may not be innocent if there are coexisting findings such as an abnormal S2.

Although epidemiologic data are limited, a systolic murmur associated with no cardiovascular disease is relatively common in children and less common in adults (estimated at approximately 10 percent) [21].

Types of innocent murmurs include:

●Vibratory murmur – In young adults, an innocent SEM can be heard that has a musical or vibratory quality and is best heard over the pulmonary area (typically the left sternal border). This murmur is thought to originate from vibrations of the pulmonic valve and/or pulmonary trunk. This murmur is commonly heard in children. (See "Approach to the infant or child with a cardiac murmur", section on 'Left lower sternal border'.)

●Straight back syndrome – In patients with the straight back syndrome (see "Scoliosis in the adult", section on 'Terminology') who have a decreased anteroposterior diameter of the chest, a grade I to II (rarely grade III) high-pitched SEM is heard over the left second interspace [22]. 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 without cardiac disease – Another cause of an SEM in the absence of cardiac disease is increased flow across the semilunar valve with elevated cardiac output. Common high cardiac output states include anemia, pregnancy, and thyrotoxicosis (table 1). As an example, a pulmonic SEM is present in over 80 percent of pregnant patients without heart disease. (See "Maternal adaptations to pregnancy: Cardiovascular and hemodynamic changes", section on 'Physical examination'.)

Other causes — The following causes of a SEM without ventricular outflow obstruction do not qualify as innocent since cardiac disease is present.

●Increased semilunar valve flow caused by cardiac disease – Some cardiac conditions cause increased semilunar blood flow, which produces an SEM without semilunar valve stenosis. Since a cardiac condition is present, these are not innocent murmurs. These include:

•Aortic regurgitation – In patients with pure aortic regurgitation, an SEM may result from markedly increased flow across the aortic valve and should not be considered evidence for AS in the absence of other findings. (See "Clinical manifestations and diagnosis of chronic aortic regurgitation in adults", section on 'Cardiac auscultation'.)

•Atrial septal defect – An atrial septal defect with left to right shunting results in increased flow across the pulmonic valve which causes a SEM and fixed split S2. In this setting a SEM is commonly present in the absence of pulmonic stenosis.

●Aortic valve sclerosis – The murmur of aortic sclerosis is also an SEM (figure 3). It is not associated with hemodynamic consequences, but its differential diagnosis includes AS. The clinical significance of aortic sclerosis is that it may progress to AS and it is associated with atherosclerotic cardiovascular risk factors. (See "Aortic valve sclerosis: Pathogenesis, clinical manifestations, diagnosis and management".)

The murmur of aortic sclerosis 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.

●Nonstenotic bicuspid aortic valve – A nonstenotic bicuspid aortic valve produces an ejection click (heard at the apex or base) and may be accompanied by a brief SEM. The diagnosis of a nonstenotic bicuspid valve is virtually confirmed if a brief SEM is accompanied by an aortic ejection click, 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".)

Heart sounds with a stenotic bicuspid aortic valve are discussed below. (See 'Valvular aortic stenosis' below.)

With LVOT obstruction

Characteristics of LVOT obstruction murmurs — The SEM associated with LV outflow tract (LVOT) obstruction due to valvular, subvalvular, or supravalvular AS or hypertrophic cardiomyopathy (HCM) is typically harsh and medium pitch.

Clinical findings (including the anatomic site where the murmur is generally best heard) vary depending upon the level of the obstruction (table 3). However, the site of the LVOT obstruction cannot be identified with certainty by the location, radiation, and character of the SEM. Echocardiography is performed to assess the location, cause, and severity of the obstruction.

Valvular aortic stenosis — For patients with valvular AS or suspected AS, the characteristics of the murmur, associated heart sounds, and pulses are helpful for initial clinical assessment of AS severity, although echocardiographic evaluation is required to stage AS (table 4) [11,12].

●Timing – In patients with AS, a longer- and later-peaking murmur is usually associated with hemodynamically significant obstruction; a brief and early peaking murmur indicates less severe AS (figure 3).

●Intensity – 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.

●Effects of low stroke volume – In the presence of heart failure and/or reduced stroke volume, the duration, configuration, and intensity of the murmur correlate poorly with the degree of obstruction.

●Heart sounds – Associated heart sounds may be helpful in assessing the cause of the murmur.

•Ejection click – Bicuspid valve is suggested by an ejection click at the onset of the murmur. An ejection click is usually absent with a calcified aortic valve and/or severe AS.

•A2 – With severe AS, the A2 component of S2 is diminished and frequently absent.

●Location and quality of the murmur – The location where an AS murmur is best heard and the murmur's quality depend upon the cause of AS. An intense murmur of AS (with calcific trileaflet or bicuspid valve) may be accompanied by a thrill in the region where it is best heard. An AS murmur radiates into the neck and to both carotid arteries.

•Calcific trileaflet AS – With calcific trileaflet AS, an SEM 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 originating in the aortic root related to the high-velocity jet (movie 2 and movie 3). The musical murmur appears to originate from the vibration of the valve and subvalvular structures and can be recorded in the LV cavity (Gallavardin phenomenon). (See "Clinical manifestations and diagnosis of aortic stenosis in adults".)

•Bicuspid aortic valve stenosis – With a stenotic bicuspid aortic valve, the SEM is best heard over the right second interspace (movie 4 and movie 5). As the AS progresses, the SEM becomes harsher and later peaking.

Prosthetic aortic valve — A short SEM is often appreciated in patients with normal functioning bioprosthetic and mechanical aortic valves related to the limited effective orifice area of the prosthesis.

●Bioprosthetic valve obstruction – As a bioprosthetic aortic valve progressively degenerates (or is thrombosed) with increasing transvalvular gradient, the SEM increases in intensity and duration over time. (See "Bioprosthetic valve thrombosis, thromboembolism, and obstruction: Clinical manifestations and diagnosis", section on 'Symptoms and signs'.)

●Mechanical valve obstruction – An absent mechanical aortic valve closing click (S2) and medium to long systolic murmur is characteristic of an obstructed mechanical aortic valve due to thrombus and/or pannus. (See "Mechanical prosthetic valve thrombosis or obstruction: Clinical manifestations and diagnosis", section on 'Clinical manifestations'.)

Supravalvular aortic stenosis — Supravalvular AS presents predominantly in children. In supravalvular AS, the murmur may be loudest at a slightly higher parasternal location (at the right first intercostal space) than in valvular AS (at the right second intercostal space) (table 3). In addition, the intensity of the radiated murmur over the right carotid may be greater than over the left carotid artery. (See "Supravalvar aortic stenosis".)

Subvalvular outflow obstruction — Subvalvular LV outflow obstruction in adults is mostly commonly caused by HCM but can also be due to a congenital subaortic membrane. In dynamic LV outflow obstruction, the maximum intensity of the murmur is usually located along the left lower sternal border, base of the heart, or over the cardiac apex (table 3). The murmur may radiate to the axilla but does not generally radiate to the neck. (See "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation".)

Individuals with HCM with LVOT obstruction may also have a systolic murmur caused by associated mitral regurgitation (MR) due to systolic anterior motion of the mitral valve or other causes of MR. (See "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation", section on 'Systolic murmurs' and 'Systolic anterior motion of the mitral valve' below.)

Fixed versus dynamic outflow obstruction — It is usually not difficult to distinguish between fixed valvular AS and dynamic LV outflow obstruction (table 3). With respect to the carotid pulse:

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

●With dynamic LV outflow obstruction, the initial upstroke of the carotid pulse is usually sharp and the volume is normal. The most recognized cause of dynamic LVOT obstruction is obstructive HCM. Dynamic LVOT obstruction may also occur in stress cardiomyopathy and with non-HCM related LV hypertrophy. (See "Acute mitral regurgitation in adults: Clinical presentation and diagnosis", section on 'Nonischemic causes'.)

The change in intensity of an SEM 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 with LVOT obstruction. Conversely, this change in position decreases the murmur of valvular AS. This is the most reliable maneuver for distinguishing these causes of SEM.

●The murmur of HCM increases in intensity with the straining phase of a Valsalva maneuver and the carotid pulse decreases or is unchanged (table 3). Both the intensity of the murmur and the carotid pulse volume decline with Valsalva with valvular AS or fixed subvalvular AS (subaortic stenosis), which is seen primarily in children. (See "Subvalvar aortic stenosis (subaortic stenosis)".)

With RV outflow tract obstruction

Pulmonic valve stenosis — 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) [23].

Occasionally, the long, harsh SEM 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.

Subvalvular pulmonic stenosis — Isolated primary subvalvular pulmonic stenosis is rare. RV outflow tract obstruction is one of the features of tetralogy of Fallot and causes a harsh SEM best heard along the left mid to upper sternal border with posterior radiation. (See "Tetralogy of Fallot (TOF): Pathophysiology, clinical features, and diagnosis", section on 'Murmur'.)

Supravalvular pulmonic stenosis — Supravalvular pulmonic stenosis causes a harsh SEM over the left upper sternal border. (See "Clinical manifestations and diagnosis of pulmonic stenosis in adults", section on 'Supravalvular pulmonic stenosis'.)

Dilation of the aortic root or pulmonary artery — Dilation of the aortic root or proximal main pulmonary artery may be associated with an SEM due to altered blood flow dynamics within the dilated vessel [7]. When these great arteries dilate, the normal laminar (smooth) flow of blood can become disrupted, resulting in turbulent flow.

●Aortic root dilation – Aortic root dilation with an associated SEM occurs most commonly in patients with systemic hypertension.

●Proximal pulmonary artery dilation – Pulmonary artery dilation occurs most commonly in the setting of pulmonary hypertension.

•With pulmonary hypertension

-General features – In this setting, the pulmonary ejection sound is relatively late, there is a short SEM, S2 is narrowly split (if RV function is preserved) with P2 markedly accentuated. A holosystolic murmur of tricuspid regurgitation and an early diastolic murmur of pulmonic regurgitation may be present. (See 'Tricuspid regurgitation' below and "Auscultation of diastolic and continuous murmurs in adults", section on 'Pulmonic regurgitation'.)

-Eisenmenger syndrome – Eisenmenger syndrome is the most advanced form of congenital shunt-related irreversible pulmonary arterial hypertension. It is comprised of the triad of a large intracardiac or extracardiac congenital shunt (ventricular, atrial, or great artery) that was initially systemic-to-pulmonary, severe pulmonary arterial hypertension with shunt reversal or bidirectional shunting, and hypoxemia with cyanosis. (See "Pulmonary hypertension with congenital heart disease: Clinical manifestations and diagnosis", section on 'Definitions'.)

With Eisenmenger syndrome, there is no murmur across the defect, but an SEM due to dilation of the pulmonary trunk may be heard. S2 is commonly markedly accentuated and single. (See "Pulmonary hypertension with congenital heart disease: Clinical manifestations and diagnosis", section on 'Symptoms and signs'.)

•Without pulmonary hypertension – The usual findings of idiopathic dilatation of the pulmonary artery (without pulmonary hypertension) are a pulmonary ejection sound, a short SEM, a relatively widely split S2 with normal intensity of P2, and occasionally a short pulmonic regurgitant 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 conditions that are commonly associated with holosystolic murmurs: mitral regurgitation (MR), tricuspid regurgitation (TR), and ventricular septal defects (VSDs).

The timing and duration of holosystolic murmurs are best explained by the hemodynamic changes of MR. In hemodynamically significant MR, regurgitant flow from the LV to the left atrium begins with the onset of isovolumic systole when pressure in the LV 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 apical holosystolic murmur of chronic MR (and some acute MR) is high pitched and best heard with the diaphragm of the stethoscope and the patient in the left lateral decubitus position (movie 6). 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 [24]. In some patients, a loud murmur may be transmitted up the spine and sometimes to the top of the head.

●When the jet is directed anteromedially against the interatrial septum near the base of the aorta, the murmur radiates toward the base and root of the neck. 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.

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", section on 'Physical examination'.)

Associated physical findings may help to characterize the nature and severity of MR, although with significant limitations, as illustrated by the following observations (see "Clinical manifestations and diagnosis of chronic mitral regurgitation"):

●A more benign overall examination (eg, absence of S3 and cardiac enlargement) is suggestive of primary valve disease and hemodynamically insignificant chronic MR.

●Presence of concurrent abnormal cardiac findings (eg, S3, accentuated P2, or a displaced apical impulse) are less specific, since they can occur with primary MR, secondary MR, or a separate cardiac or pulmonary abnormality.

•Among patients with MR without other causes of pulmonary hypertension, clinical evidence of pulmonary hypertension (accentuated P2, RV systolic hypertension) and right-sided heart failure suggests significant MR.

•On the other hand, among patients with a concurrent cause of pulmonary hypertension, an S3 and findings of pulmonary hypertension occur in patients with or without significant MR.

Tricuspid regurgitation — The holosystolic murmur of TR is best heard with the diaphragm of the stethoscope along the left or right mid or lower sternal border or at the subxiphoid area [15].

With inspiration, there is an increase in venous return to the RV, so the murmur of mild or moderate TR may become louder and longer (ie, holosystolic). However, respiratory variation in the murmur may not occur in patients with severe TR or marked RV dilation and systolic dysfunction.

With severe right-sided heart failure, a TR murmur may be absent or only early systolic (rather than holosystolic). When the TR murmur is difficult to appreciate, the bedside diagnosis of TR relies upon the presence of other physical findings, such as a prominent v wave in the jugular venous pulse and systolic hepatic pulsation. (See "Tricuspid regurgitation: Etiology, clinical features, and evaluation", section on 'Physical examination'.)

Characteristic findings depend upon the cause of TR:

●Secondary TR – TR 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 TR. Theoretically, severe TR may produce reversed splitting of S2 due to shortened RV ejection time; however, this is a rare finding.

●Primary TR – Primary TR is much less common than secondary TR. Causes include bacterial endocarditis (particularly when a complication of injection drug use), Ebstein anomaly, carcinoid heart disease, and damage to the tricuspid valve apparatus caused by endocardial pacemaker leads. A hyperdynamic left parasternal impulse and normal or only slightly accentuated P2 suggest primary TR, but diagnosis of primary TR is based primarily upon excluding pulmonary hypertension and left-sided disorders such as mitral and aortic valve disease and cardiomyopathy. In primary TR, the murmur may be early systolic rather than holosystolic, and have a decrescendo shape. (See "Tricuspid regurgitation: Etiology, clinical features, and evaluation".)

Location and respiratory changes in the intensity of the murmur are two features that may help distinguish TR from MR:

●Location – With TR, the murmur is generally heard along the left or right sternal border and may radiate to the epigastrium. However, the location of maximum intensity may be shifted toward the cardiac apex when the RV is dilated, so a murmur of TR may misdiagnosed as an apical MR murmur. (See 'Mitral regurgitation' above.)

●Respiratory changes – During the inspiratory phase of respiration, the intensity of the murmur of TR increases (Carvallo sign, also known as Rivero-Carvallo sign) if severe RV 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 RV volume. An RV S3 gallop and a middiastolic flow murmur, which also increase in intensity with inspiration, suggest more severe TR.

Small ventricular septal defect — With small VSDs with normal pulmonary artery pressure and pulmonary vascular resistance, RV pressure is lower than LV pressure throughout systole, resulting in a continuous left-to-right shunt (toward the RV cavity), which causes a holosystolic murmur [25,26]. The murmur is usually loud and may be accompanies by a thrill. In this setting, S2 is generally normal. Thus, a loud holosystolic murmur in a patient with a VSD is a sign of favorable hemodynamics (eg, relatively normal right-sided pressures). (See "Clinical manifestations and diagnosis of ventricular septal defect in adults", section on 'Physical signs'.)

●Below the crista supraventricularis – When the VSD is below the crista, the murmur is maximal over the third and fourth interspaces along the left sternal border, but radiates over the entire precordium [7].

●Above 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 [23]. 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 a VSD.

In contrast, a large VSD causes an early systolic murmur, as described above. (See 'Large VSDs and some muscular VSDs' above.)

MIDSYSTOLIC VERSUS HOLOSYSTOLIC MURMURS — 

It can be difficult to distinguish between a long midsystolic ejection murmur (SEM) and a holosystolic regurgitant murmur in certain situations. The SEM transmitted to the cardiac apex in dynamic or fixed LV outflow obstruction may sound similar to the murmur of mitral regurgitation (MR) or ventricular septal defect. 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 [16], a number of helpful distinguishing features can be elicited by auscultation (figure 3):

●Audible A2 at the apex – 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.

●Variation in murmur intensity with cardiac cycle length – The intensity of an SEM increases with a longer RR cycle (eg, in patients with atrial fibrillation and varying RR cycles) and with a postectopic beat (in patients with premature beats); the intensity of a regurgitant murmur usually remains unchanged in these situations.

●Response to handgrip – 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.

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 can occur from disorders of the mitral annulus, redundancy of the leaflets, abnormalities of the chordae, or contraction abnormalities of the LV wall. Mitral regurgitation (MR) occurs when prolapse is sufficient to cause a lack of apposition of the leaflets. The most common etiology for mitral valve prolapse is redundancy of valve tissue with respect to the valve ring ("floppy" valve or Barlow syndrome). (See "Mitral valve prolapse: Clinical manifestations and diagnosis".)

Mitral valve prolapse is the most common cause of MR associated with 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 [27]. In general, mitral valve prolapse with a late systolic murmur is associated with mild MR with normal LV function and no pulmonary hypertension. 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.

●Effect of decreased LV volume - MV leaflet prolapse increases and leaflet coaptation worsens with a decreased LV volume, so the late systolic murmur starts earlier. 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 and is also often intensified (table 5 and movie 7 and movie 8).

●Effect of increased LV volume - 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.

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.

Systolic anterior motion of the mitral valve — Systolic anterior motion (SAM) of the mitral valve causes impaired leaflet coaptation with MR associated with a late systolic apical murmur. SAM occurs in patients with HCM with LVOT obstruction, some patients with stress (takotsubo) cardiomyopathy, and in other patients without HCM, particularly in the perioperative setting. (See "Acute mitral regurgitation in adults: Clinical presentation and diagnosis", section on 'Nonischemic causes'.)

Secondary MR — Secondary MR (also known as functional MR) is MR caused by LV disease (dilation, altered geometry, and/or segmental or global dysfunction) and/or dilation of the left atrium and mitral annulus, generally with structurally normal or minimally thickened mitral valve leaflets and chordae [11,12,28]. Secondary MR-associated LV dysfunction may be caused by acute or chronic coronary artery disease (known as "ischemic" MR) or cardiomyopathy (nonischemic). (See "Clinical manifestations and diagnosis of chronic mitral regurgitation", section on 'Etiology'.)

The murmur of secondary MR can be holosystolic (see 'Mitral regurgitation' above) or late systolic. A late systolic murmur may occur with MR due to papillary muscle displacement (previously known as papillary muscle dysfunction) in patients with "ischemic MR" due to acute or chronic myocardial infarction. Secondary MR in patients with chronic coronary artery disease may worsen with exertion, even in the absence of symptoms and signs of myocardial ischemia, presumably due to papillary muscle displacement or altered angulation in response to increased hemodynamic demands. In these patients, isometric exercise or maneuvers that increase ventricular volume may worsen MR and increase the intensity of the systolic murmur. (See "Clinical manifestations and diagnosis of chronic mitral regurgitation", section on 'Stress testing'.)

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 RV volume.

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 AND RECOMMENDATIONS

●Auscultatory tools – Cardiac auscultation is performed with a standard (acoustic-based) stethoscope or a digital (sensor-based) stethoscope. Digital stethoscopes offers enhanced technical capabilities but limited evidence is available on the clinical utility of these enhancements. (See 'Auscultatory tools' above.)

●Auscultation procedure and accuracy – Key elements of effective auscultation include a quiet setting, proper stethoscope use and patient positioning, systematic listening in each of the four auscultatory areas (figure 1) and more remote areas, and careful timing of murmurs. (See 'Auscultation procedure' above.)

The reported accuracy of auscultation for detection of valvular heart disease has varied widely. (See 'Accuracy of auscultation' above.)

●Role of echocardiography – Echocardiography is the standard method for establishing the cause of cardiac murmurs. Echocardiography is not indicated for asymptomatic patients with a benign flow murmur.

Echocardiography is indicated for patients with cardiac symptoms and a cardiac murmur as well as patients (with or without cardiac symptoms) with a diastolic murmur, a grade 2 or greater systolic murmur, or a systolic murmur in association with an abnormal examination finding, such as a systolic click or reduced carotid upstroke. (See 'Role of echocardiography' above.)

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

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

●Midsystolic murmurs – The most common causes of a midsystolic ejection murmur (SEM) are benign (innocent) flow murmurs including an increase in flow rate across a normal semilunar valve or the murmur associated with aortic valve sclerosis (see 'Without ventricular outflow obstruction' above) (table 1). These physiologic murmurs need to be distinguished from the abnormal SEM in patients with fixed or dynamic outflow tract obstruction.

The SEM associated with left ventricular outflow tract (LVOT) obstruction is typically harsh and medium pitch. Clinical findings vary depending upon the level of the obstruction (table 3). Aortic valve stenosis (AS) causes an abnormal SEM that typically is loudest over the right second intercostal space and radiates to the carotids. An SEM associated with a single S2 suggests severe AS. Fixed aortic valve obstruction is distinguished from dynamic subaortic outflow tract obstruction by changes in the murmur with maneuvers. (See 'With LVOT obstruction' above.)

Murmurs of RV outflow tract obstruction are typically heard along the left upper sternal border. (See 'With RV outflow tract obstruction' above.)

●Holosystolic murmurs – A holosystolic murmur is caused by MR, TR, or a small VSD (except for some small muscular VSDs). (See 'Holosystolic murmurs' above.)

●Late systolic murmurs – These are most commonly caused by primary MR associated with mitral valve prolapse (best heard near the cardiac apex). The murmur of secondary MR can be holosystolic or late systolic. (See 'Late systolic murmurs' above.)

ACKNOWLEDGMENT — 

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