Auscultation of heart sounds

INTRODUCTION — The cardiovascular physical examination includes auscultation

and palpation of the heart, as well as examination of the arterial and venous pulses.
The purpose of auscultation of the heart is to characterize heart sounds and
murmurs. (See "Examination of the precordial pulsation" and "Examination of the
arterial pulse" and "Examination of the jugular venous pulse".)

CLASSIFICATION OF HEART SOUNDS — Heart sounds are broadly classified into high-
and low-frequency sounds.

High-frequency sounds arise from closing or opening valves, including mitral and
tricuspid valve closing sounds (M1 and T1), non-ejection sounds, opening snaps,
aortic and pulmonary valve closure sounds (A2 and P2), and early valvular ejection
sounds. Prosthetic valve sounds are also high frequency. (See 'First heart sound (S1)'
below and 'Second heart sound (S2)' below and 'Ejection sounds' below and 'Non-
ejection systolic sounds' below and 'Early diastolic high-frequency sounds' below
and 'Prosthetic valve sounds' below.)

Low-frequency sounds include the third heart sound (S3, which may be physiologic
or pathologic), associated with early ventricular filling, and the fourth heart sound
(S4), associated with the atrial contribution to ventricular filling in late diastole. (See
'Third (S3) and fourth (S4) heart sounds' below.)

FIRST HEART SOUND (S1)

Genesis, timing, and location of S1 — The classic hypothesis for the genesis of the
first heart sound (S1), for which there is much support, relates the high-frequency
components of S1 to mitral and tricuspid valve closure. The first component of S1 is
attributed to mitral valve closure (M1) and the second to closure of the tricuspid
valve (T1) [7-10]. More detailed examination of closure sounds also suggest that the
peak tension on the chordae tendineae and leaflets themselves appear to
contribute to the production of M1 and T1 [11,12]. A second hypothesis suggests
that the principal high-frequency elements of S1 are related to movement and
acceleration of blood in early systole, and are influenced by the peak rate of rise of
left ventricular (LV) systolic pressure (dP/dt), which is a measure of contractility and
ejection of blood into the root of the aorta [13].

S1 occurs just before or is coincident with the upstroke of the carotid pulse. M1
precedes the upstroke of the carotid pulse because it occurs before LV ejection
begins. However, the delay between M1 and the upstroke of the carotid pulse
normally is too short to be appreciated at the bedside. T1 normally coincides with
the upstroke of the carotid pulse.
S1 normally is louder than the second heart sound (S2) over the apex and along the
lower left sternal border; intensity is reduced if S1 is softer than S2 over these areas.
S1 intensity is likely to be accentuated if S1 is much louder than S2 over the left or
right second interspace. The M1 sound is much louder than the T1 sound due to
higher pressures in the left side of the heart; thus, M1 radiates to all precordial areas
(loudest at the apex), and T1 is usually only heard at the left lower sternal border.
This makes the M1 sound the main component of S1, and is best heard with the
diaphragm of the stethoscope.

Intensity of S1 — The following factors influence the intensity of S1:

●Mitral valve position at the onset of systole (wide versus partially open).

●Rate of M1 and T1.

●Mobility and structural integrity of the atrioventricular (AV) valves (eg, fibrosis,
commissural fusion of the leaflets, tethering of the posterior mitral leaflet, etc).

●The PR interval, the timing of atrial contraction (a determinant of mitral valve

position) as it relates to the onset of LV contraction.

●Force of ventricular systolic contraction.

Some of these factors, such as the rate of M1 and the strength of ventricular systole,
are interrelated; more than one factor may contribute to altered S1 intensity.

●Increased intensity of S1 – The following factors contribute to the position of mitral

valve (distance to closure) and velocity of closure (table 1):

•Increased transvalvular gradient, especially at end-diastole (mitral or tricuspid

valve obstruction as in mitral stenosis (movie 1), tricuspid stenosis, or atrial myxoma).

•Increased transvalvular flow (left-to-right shunt in patent ductus arteriosus,

ventricular septal defect, and high output state).

•Short diastole (tachycardia).

•Short PR intervals (preexcitation syndrome)

The relative contribution of the distance of travel and the velocity of M1 to increased
S1 intensity is difficult to determine; both factors are likely to play a role. When M1
occurs on the steeper part of the LV pressure development, the intensity of S1
increases; this phenomenon may also contribute to an accentuated S1 observed in
patients with extremely short PR intervals, mitral stenosis, and left atrial myxoma
(figure 1)[14].

Similarly, S1 is normal or even accentuated in patients with mitral valve prolapse with
late systolic regurgitation. Increased intensity of S1 in some patients with mitral valve
prolapse syndrome may be caused by an increased strength of ventricular systole
(hyperkinetic).
The increased intensity of T1 in atrial septal defect and tricuspid valve obstruction
(eg, tricuspid stenosis, right atrial myxoma) can also be explained by the same
phenomenon. The tricuspid valve is held open by increased transvalvular flow and
the transvalvular gradient until final closure with increased velocity occurs with right
ventricular (RV) systole.

●Decreased intensity of S1 – A soft S1 is mostly related to decreased mobility or due

to a semi-closed position of the leaflets prior to systole. Thus, S1 is soft when the mitral
valve is immobile due to calcification and fibrosis, despite a significant transvalvular
gradient. S1 may also be reduced when the leaflets are semi-closed prior to the
onset of systole or when the velocity of closure is reduced, as can occur with LV
dysfunction. These situations are illustrated by the following examples (table 1):

•S1 is very soft or absent when mitral regurgitation (MR) results from fibrosis and
destruction of the valve leaflets (as in patients with rheumatic valve disease), which
prevent effective M1. In contrast, MR due to perforation of the valve leaflets from
bacterial endocarditis may not be associated with a reduced intensity of S1.

•Reduced S1 intensity occurs when the mitral valve remains in the semi-closed
position before the onset of ventricular systole, and the velocity of valve closure is
decreased. S1 is usually soft when the PR interval is prolonged (exceeding 0.2
seconds) since semi-closure of the mitral valve occurs following atrial systole and
before ventricular systole begins. Premature closure of the mitral valve can occur in
patients with severe acute aortic regurgitation due to a rapid rise in LV diastolic
pressure; the mitral valve may be virtually closed at the onset of systole, resulting in
a markedly decreased intensity of or even absent S1 [15]. (See "Acute aortic
regurgitation in adults", section on 'Cardiac auscultation'.)

•S1 is soft in some patients with left bundle branch block without any other obvious
abnormality; the mechanism is unclear. Decreased valve closure velocity due to
myocardial dysfunction is possible.

•Hemodynamically significant aortic stenosis may be associated with a soft S1; this
can occur in the absence of spreading calcification to the mitral valve and in the
presence of a normal PR interval [14]. Semi-closure of the mitral valve due to a
powerful atrial contraction and an abnormally elevated LV diastolic pressure before
the onset of ventricular systole is the most likely explanation.

•S1 is frequently soft in patients with dilated cardiomyopathy, even in the absence
of a prolonged PR interval or bundle branch block. The decreased S1 is almost
invariably associated with a significantly reduced LV ejection fraction (LVEF) and
elevated pulmonary capillary wedge pressure. The mechanism for a soft S1 in these
patients remains unclear; semi-closure of the mitral valve due to an elevated LV
diastolic pressure and decreased velocity of valve closure due to myocardial
dysfunction may contribute.
•Decreased conduction of sounds through the chest wall reduces the intensity of
S1 in patients with chronic obstructive pulmonary disease, obesity, and pericardial
effusion.

●Variation in the intensity of S1 may be evident in the following situations:

•It is a common feature of atrial fibrillation; the mechanism appears to be a variation

in the velocity of valve closure related to changes in the RR cycle length.

•The intensity of S1 varies in the presence of premature beats.

•Changing intensity of S1 occurs in AV dissociation, whether the heart rate is slow or

fast (eg, in complete heart block or ventricular tachycardia). The changing intensity
is due to random variation of the PR interval; the short PR interval is associated with
an increased intensity and the long PR interval with a decreased intensity. The pulse
is regular in AV dissociation; thus, the varying intensity of S1 in a patient with a regular
pulse almost always suggests AV dissociation.

•Auscultatory alternans, in which S1 is soft and loud with alternate beats, is a rare
finding in severe cardiac tamponade; it is almost always associated with electrical
alternans and pulsus paradoxus. Although the pulse is regular, changes in the
intensity of S1 occur regularly with the alternate beats and not randomly as in AV
dissociation.

Splitting of S1 — There are normally two components of S1: The mitral component
precedes the carotid pulse upstroke, and the tricuspid component occurs later. The
interval between M1 and T1 is 0.02 to 0.03 seconds, and can be appreciated with
the diaphragm of the stethoscope along the lower left sternal border [7]. The mitral
component is much louder than the tricuspid component and is normally heard
more widely across the precordium; the tricuspid component is of low intensity and
is best heard over the left third and fourth interspaces close to the sternal border.
Abnormal splitting of S1 can result from conduction disturbances (eg, complete right
bundle branch block), and/or hemodynamiccauses (eg, atrial septal defect with
large left to right shunt).

Wide splitting of S1 is a feature of Ebstein anomaly which is associated with right

bundle branch block [16]. The extra early systolic sound around S1 is also referred to
as the "sail sound." This auscultatory finding in patients with Ebstein anomaly appears
not simply as a closing sound of the tricuspid valve, but as a complex closing sound
that includes a sudden stopping sound after the anterior and/or other tricuspid
leaflets balloon out in systole [17]. (See "Clinical manifestations and diagnosis of
Ebstein anomaly".)

SECOND HEART SOUND (S2)

Genesis, timing, and location — The S2 consists of two components: aortic and
pulmonary valve closure sounds, traditionally designated as A2 and P2, respectively
[7]. Simultaneous M-mode echocardiograms and external phonocardiograms in
healthy subjects showed that the onset of A2 was synchronous with the coaptation
of the aortic valve cusps and a sharp vibration on the aortic wall. The closed valve
oscillated for 30 to 45 ms after the coaptation of the cusps. Magnified
echocardiographic studies of the interventricular septum revealed a consistent,
momentary quiver across the septal myocardium a mean of 4 ms after the onset of
S2 [18]. The same mechanism can be inferred for the P2 component of S2.

The onset of A2 occurs with the dicrotic notch of the aortic root pressure pulse
[19,20]. S2 occurs after the peak of the carotid pulse and coincides with its
downslope.

The two components of S2 are best heard with the diaphragm of the stethoscope
and over the left second interspace, close to the sternal border. A2 is widely
transmitted to the right second interspace, along the left and right sternal border,
and to the cardiac apex. P2 is normally best heard and recorded over the upper
left sternal border and is poorly transmitted. S2 is best heard when patients are semi-
recumbent (30 to 40 degrees upright) with quiet inspiration.

Factors determining the intensity of S2 — The major determinants of A2 intensity (and

therefore the major determinants of S2) include (table 2):

●Aortic pressure, a major determinant of the velocity of valve closure

●Relative proximity of the aorta to the chest wall

●Size of the aortic root

●Mobility and structural integrity of the aortic valve

The intensity of P2 is determined by:

●Pulmonary arterial pressure, particularly the diastolic pressure

●Size of the pulmonary artery

●Mobility and structural integrity of the pulmonary valve

The intensity of P2 is determined by comparing its intensity with A2. An increased P2

intensity is suggested when it is louder over the left second interspace or when there
is transmission to the cardiac apex.

●Increased intensity of A2 often occurs in:

•Systemic hypertension.

•Coarctation of the aorta.

•Ascending aortic aneurysm; a "tambour" quality of A2 is commonly heard (table
2).

•When the aortic root is relatively anterior and closer to the anterior chest wall, as in
tetralogy of Fallot and transposition of the great arteries.

●Increased intensity of P2 often occurs in:

•Pulmonary arterial hypertension of any etiology (most common, even with

pulmonary regurgitation) [21].

•Idiopathic pulmonary artery dilation.

•Atrial septal defect (ASD); P2 is increased considerably and frequently greater than
A2 over the left second interspace.

A2 is soft in patients with mitral regurgitation (MR), and P2 may appear to be

increased. In these circumstances, one cannot rely on the relative intensity of P2 for
the diagnosis of pulmonary hypertension (PH).

●Decreased intensity of A2 occurs in:

•Conditions that affect the mobility and integrity of the aortic valve

•Severe aortic regurgitation (AR) or stenosis

•Hypotension

●Decreased intensity of P2 occurs in:

•Conditions that affect the mobility and integrity of the pulmonary valve.

•Pulmonary stenosis and regurgitation.

•Significant RV outflow obstruction associated with a soft and delayed P2. The low
pulmonary artery pressures also play a role in attenuating P2.

Splitting of S2 — Under normal physiologic conditions, the A2 and P2 components of

S2 vary with inspiration. A2 and P2 are usually fused during the expiratory phase of
continuous respiration, but during the inspiratory phase, separation of A2 and P2
occurs; the degree of splitting varies from 0.02 to 0.06 seconds (movie 2) [22]. The
underlying mechanism for the normal splitting of S2 during inspiration relates to
longer RV ejection during inspiration compared with the LV, which is correlated with
increased right-sided and decreased left-sided filling. The width and order of splitting
of S2 are altered in a variety of clinical settings.

●Wide splitting of S2 occurs in the following conditions:

•Electromechanical delay of the RV (table 2 and figure 2):

-Right bundle branch block (RBBB) (movie 3), artificial pacing from the LV, and Wolff-
Parkinson-White (WPW) syndrome with LV preexcitation.

-Premature beats and an idioventricular rhythm of LV origin (QRS complex of RBBB

morphology) are also associated with wide splitting.

•Hemodynamic causes:

-Increased resistance to RV ejection and prolongation of RV ejection time are other

important causes of wide expiratory splitting of S2 as seen in pulmonary valve,
infundibular, supravalvular, or pulmonary branch stenosis, and pulmonary arterial
hypertension.

In patients with pulmonary valve and infundibular stenosis, wide splitting of S2 is

associated with reduced intensity of P2, while P2 is accentuated in PH and
pulmonary branch stenosis.

In pulmonary valve stenosis, the degree of expiratory splitting of S2 (the A2-P2

interval) is directly related to the severity of stenosis and RV systolic hypertension [23].
Further splitting of S2 during inspiration usually occurs in these conditions, but wide
splitting of S1 is not observed.

-Isolated reduction of the LV ejection time may also cause wide splitting of S2, due
to the early occurrence of A2. Examples of this hemodynamic abnormality include
severe MR when forward stroke volume decreases with increases in regurgitant
volume [24]. In constrictive pericarditis, differential filling of the ventricles occurs
during inspiration, resulting in a lower LV stroke volume [25].

●Wide and fixed splitting of S2 – Fixed splitting of S2 has been defined as ≤20 ms of
variation in the A2-P2 interval between the inspiratory and expiratory phases of
respiration [26]. However, such limitation in variation of splitting may be difficult to
discern clinically, so wide and variable splitting may be difficult to distinguish from
wide and fixed splitting.

One common cause of wide and fixed splitting of S2 is a large interatrial

communication (ASD, common atrium) and left-to-right or bidirectional shunt;
abnormally wide splitting of S2 occurs, and respiratory variations of the A2-P2
intervals are minimal or absent (movie 4). (See "Clinical manifestations and diagnosis
of atrial septal defects in adults", section on 'Heart sounds'.)

The mechanism of wide expiratory splitting of S2 in ASD appears to result from two
physiological mechanisms. First, P2 is delayed due to a marked increase in RV stroke
volume (left-to-right shunt), which prolongs right-sided ejection. Second, when the
right and left atria become a near common chamber, differential filling that
normally occurs between the RV and LV during inspiration no longer exists (table 2)
[26,27].
The other cause of fixed splitting of S2 is RV failure, when the RV is unable to vary its
stroke volume during inspiration, and inspiratory prolongation of its ejection time and
delay of P2 does not occur. Therefore, any condition that induces severe RV failure,
such as RV outflow obstruction, PH, and primary RV dysfunction, can be associated
with fixed splitting (table 2).

●Reversed (paradoxical) splitting of S2 – Paradoxical splitting occurs when A2 follows

P2 during the expiratory phase of respiration. The splitting of S2 is then maximal during
expiration, and the splitting is less or S2 becomes single during inspiration with the
normal inspiratory delay of P2 [7,28].

Reversed splitting of S2 may result from either conduction disturbances or

hemodynamic causes (table 2).

•Electromechanical delay Left bundle branch block, artificial RV pacing,

preexcitation of the RV (WPW syndrome), and premature beats of RV origin are
examples of conduction disturbances associated with delayed activation of the LV,
and consequently delayed completion of LV ejection causes a delayed A2 and
reversed splitting of S2.

•Hemodynamic factors:

-A markedly prolonged LV ejection time may delay A2 sufficiently to cause reversed

splitting of S2. With fixed LV outflow tract obstruction, as in patients with aortic valve
stenosis, LV ejection time is lengthened, and reversed splitting of S2 usually indicates
hemodynamically significant outflow obstruction (movie 5). However, P2 may be
inaudible due to the long ejection systolic murmur of aortic stenosis, making it
difficult to recognize the reversed splitting.

-A prolonged LV ejection time and reversed splitting of S2 can occur with

myocardial dysfunction, as in myocardial ischemia, or in patients with long-standing
severe AR [29]. However, reversed splitting is rarely observed with severe heart failure
(HF) because of the concomitant decrease in stroke volume, which is an important
determinant of LV ejection time.

The distinction between hypertrophic cardiomyopathy (HCM) and MR or ventricular

septal defect (VSD), conditions in which the character and locations of the systolic
murmur may appear similar on auscultation, is facilitated by recognizing the
character of S2 splitting. Reversed splitting suggests HCM, while physiologic splitting
favors MR or VSD.

Single S2 — A single S2 may result from the absence of either of the two components
of S2 or from the fusion of A2 and P2 without inspiratory splitting (table 2).
●Absence of A2 is occasionally observed in severe calcific aortic stenosis with an
immobile aortic valve. A2 may be absent in some patients with severe AR due to
destruction of the valve leaflets. (See "Clinical manifestations and diagnosis of aortic
stenosis in adults", section on 'Cardiac auscultation' and "Clinical manifestations and
diagnosis of chronic aortic regurgitation in adults", section on 'Cardiac
auscultation'.)

●P2 is absent with congenital absence of the pulmonary valve, pulmonary atresia,
or truncus arteriosus. In severe pulmonary valve stenosis or in tetralogy of Fallot, P2
may be markedly attenuated and escape recognition by auscultation. (See
"Clinical manifestations and diagnosis of pulmonic stenosis in adults", section on
'Clinical manifestations' and "Pathophysiology, clinical features, and diagnosis of
tetralogy of Fallot", section on 'Cardiac auscultation'.)

●A2 is delayed and may be fused with P2 with aortic stenosis (movie 6). Fusion of A2
and P2 without inspiratory splitting occurs in Eisenmenger syndrome with VSD and in
patients with a single ventricle. (See "Clinical manifestations and diagnosis of aortic
stenosis in adults", section on 'Cardiac auscultation' and "Evaluation and prognosis
of Eisenmenger syndrome", section on 'Physical examination'.)

However, a truly single S2 is rare. An apparently single S2 usually results from the
inability to hear or record P2 due to emphysema, obesity, or pericardial effusion.

THIRD (S3) AND FOURTH (S4) HEART SOUNDS

Genesis, timing, and location of S3 and S4 — S3 and S4 are low-frequency diastolic

sounds that appear to originate in the ventricles. The precise mechanism of the
genesis of S3 and S4 has not been identified with certainty [30]. It is generally agreed
that both sounds, occasionally termed "ventricular filling sounds," are associated
with ventricular filling and an increase in ventricular dimensions. They are heard
during the rapid filling and atrial filling phases of ventricular diastole, respectively.

●S3 occurs as the rapid filling phase of diastole is completed [31]. It appears to be
related to a sudden limitation of the movement during ventricular filling along its
long axis [32], and it coincides with the y descent of the atrial pressure pulse,
occurring usually 0.14 to 0.16 seconds after the second heart sound (S2).

●S4 occurs during the atrial filling phase after the P wave on the electrocardiogram
(ECG) and coincides with atrial systole and a waves of the atrial pressure pulse, and
with the apical impulse.

S3 and S4 are best heard with the bell of the stethoscope. Auscultation over the
cardiac apex in the left lateral decubitus position is preferable for identification of
LV S3 and S4. RV S3 and S4 are best heard along the lower left sternal border;
occasionally, right-sided filling sounds are also heard over the lower right sternal
border and over the epigastrium. The intensity of S3 and S4 of RV origin usually
increases during inspiration, while that of LV origin remains unchanged. S3 is closer
to S2, and S4 occurs prior to the first heart sound (S1).

An abnormal S3 or S4 tends to be louder and of higher pitch (sharper) and is

frequently referred to as a "gallop." S3 is the ventricular gallop, and S4 is the atrial
gallop. S3 and S4 can be fused during tachycardia to produce a loud diastolic filling
sound, termed a "summation gallop" [33]. At the bedside, carotid massage can
cause separation of S3 and S4 as the heart rate slows. S3 and S4 may occasionally
be intensified or precipitated by exercise or by sustained hand grip. Gallops can
sometimes be seen and palpated. (See "Examination of the precordial pulsation".)

It is often difficult to distinguish between gallop sounds of RV and LV origin at the

bedside when they are present in the same patient. However, if one follows the
"inching" method of auscultation (eg, auscultation starting over the cardiac apex
and then gradually moving the stethoscope inch by inch to the left lower sternal
border), the decreasing intensity of gallops of LV origin and the increasing intensity
of gallops of RV origin can be appreciated. Furthermore, the intensity of the right-
sided gallop sound increases during inspiration.

LV gallops

Clinical significance of S3 — Although an S3 can be heard in healthy young children

and adults (movie 7), it is usually abnormal in patients over the age of 40 years,
suggesting an enlarged ventricular chamber.

An S3 gallop is an important and common early finding of HF associated with dilated

cardiomyopathy and may also be heard in patients with diastolic HF (although less
frequently than with systolic HF), aortic valve disease, and coronary artery disease
(CAD) (movie 8) [34]. In such patients, an S3 gallop is usually associated with left
atrial pressures exceeding 20 mmHg, increased LV end-diastolic pressures (>15
mmHg), and elevated serum brain natriuretic peptide (BNP) concentrations [35-37].
(See "Evaluation of the patient with suspected heart failure", section on 'Heart
sounds'.)

An S3 gallop is almost always present in patients with hemodynamically significant

chronic mitral regurgitation (MR); the absence of S3 is an important finding to
exclude severe chronic MR. An S3 gallop in patients with chronic aortic regurgitation
(AR) is frequently associated with a decreased LVEF and increased diastolic volume;
its recognition should prompt further evaluation [38].

The diagnostic test characteristics of the S3 and S4 for detection of LV dysfunction

were evaluated in a phonocardiographic study of patients who were undergoing
cardiac catheterization [37]. These sounds were not very sensitive (40 to 50 percent)
for the detection of an elevated LV end-diastolic pressure or a reduced LVEF;
however, the S3 was highly specific (90 percent) for these parameters and for an
elevated serum BNP concentration. An additional problem is appreciable
interobserver variability in the ability to detect an S3 on cardiac auscultation that
cannot be solely explained by the experience of the observer [39,40].

The presence of an S3 gallop also has prognostic significance, being associated with
a higher risk of progression to symptomatic HF in those with asymptomatic LV
dysfunction, and a higher risk of hospitalization for HF or death from pump failure in
patients with overt HF [41,42]. One limitation to these observations is the operator
dependence for the detection of this physical finding.

An S3 often occurs in high-output states such as thyrotoxicosis or pregnancy. It can

also be appreciated in athletes with slow heart rates and increased filling volumes
[43]. In these settings, it does not necessarily indicate LV dysfunction [44].

Clinical significance of S4 — An audible S4 is generally abnormal in young adults

and children. Effective atrial contraction and ventricular filling are both required for
production of atrial gallop sounds. Thus, this sound is usually absent in atrial fibrillation
and in significant AV valve stenosis.

S4 can be heard in many healthy older adults without any other cardiac
abnormality, due to decreased ventricular compliance with age. An S4 is always
abnormal when it is palpable, regardless of patient age.

S4 may become audible in otherwise healthy subjects with a prolonged PR interval

due to the separation of S4 from S1. In patients with complete AV block, S4 is heard
at a faster rate than S1 and S2 and may not indicate any hemodynamic
abnormality.

An abnormal S4 is most frequently observed in patients with decreased LV

distensibility (movie 9) [45]. Thus, S4 is common in hypertensive heart disease, aortic
stenosis, and HCM. LV hypertrophy, which is present in all these conditions,
contributes to decreased LV distensibility.

In aortic stenosis, the presence of an S4 has been reported to indicate

hemodynamically significant LV outflow obstruction, with a peak transvalvular
gradient ≥70 mmHg and an elevated LV end-diastolic pressure [46]. However, in
patients over 40 years of age, S4 can occur due to myocardial disease in the
absence of significant aortic stenosis. Thus, in elderly patients, the presence of an S4
cannot be used to assess the severity of aortic stenosis. Associated CAD may also
cause an S4 in patients with mild to moderate aortic stenosis.

An S4 is heard in the vast majority of patients during the acute phase of myocardial
infarction (MI) [47]. Although pulmonary venous pressure may also be elevated,
there is a poor correlation between the presence and absence of an S4 and
hemodynamic abnormalities. Thus, S4 is a poor guide to assess the severity of LV
dysfunction in patients with acute MI.

Audible and/or palpable atrial gallops are a frequent finding in chronic LV aneurysm
and are usually found with LV dyskinesia associated with elevated end-diastolic
pressures. In patients with chronic CAD, the transient appearance of an S4,
particularly during chest pain, is a strong indication of transient myocardial ischemia.

A loud S4 that is also usually palpable is a frequent finding in patients with acute and
severe MR or AR. It is almost always associated with an increased LV end-diastolic
pressure (>15 mmHg) [48]. The predictive value is increased in the presence of both
S3 and S4 gallops [35]. (See "Examination of the precordial pulsation".)

Right ventricular gallops — An S3 gallop of RV origin frequently occurs in patients

with significant tricuspid regurgitation, whether it is primary or secondary to
pulmonary hypertension and RV failure. An S3 gallop is also heard in RV failure in the
absence of tricuspid regurgitation.

An S4 of RV origin is most commonly heard in patients with RV outflow obstruction

(pulmonary valve stenosis) and pulmonary arterial hypertension [49]. It likely denotes
decreased RV distensibility due to hypertrophy.

Differential diagnosis — An S3 and S4 may be confused with a split S2 and split S1,
respectively. When split, the two parts of S1 or S2 typically have a similar pitch, while
S3 and S4 are lower pitched sounds than S2 and S1.

This difference in pitch can be brought out by listening with the bell and the
diaphragm of the stethoscope. The lower-pitched S3 and S4 will be more
pronounced when listening gently with the bell, while the higher-pitched split S1 and
S2 will be more pronounced when listening with the diaphragm or when applying
the bell more firmly to the skin. (See 'Stethoscopes' above.)

Auscultation to distinguish S3 and S4 from a splitting of S2 and S1 is best performed

in the 45-degree left lateral decubitus position (ie, with the chest rotated toward the
examination table). The location of the sound is useful in distinguishing an S4 from a
split S1. The LV S4 is usually localized over the cardiac apex, and becomes softer as
the bell of the stethoscope is moved gradually to the left sternal border.

PERICARDIAL KNOCK — Ventricular filling is confined to early diastole in constrictive

pericarditis and terminates with a sharp S3; this is termed a "pericardial knock." Its
timing is earlier than a normal S3 and typically occurs 0.10 to 0.12 seconds after an
S2. It is a common finding in constrictive pericarditis and can occur with or without
pericardial calcification [50]. It is occasionally heard only during inspiration and
along the lower right sternal border, suggesting an early manifestation of RV
constriction. (See "Constrictive pericarditis".)

EJECTION SOUNDS — An ejection sound is a high-frequency "clicky," early systolic

sound. When aortic or pulmonary ejection sounds occur in the presence of normal
semilunar valves, the origin may be the proximal aortic or pulmonary artery
segments. Thus, the term "vascular ejection sound" has been suggested. These
sounds generally tend to occur later and are not associated with "doming" of the
semilunar valves, which is characteristic of a valvular ejection sound. The
mechanism of the vascular ejection sound remains unclear.
Aortic ejection sound — The aortic ejection sound is usually recorded 0.12 to 0.14
seconds after the Q wave on the ECG. It is best heard with the diaphragm of the
stethoscope and is widely transmitted, heard at the cardiac apex and also over the
right second interspace. Its intensity does not vary with respiration. Aortic ejection
sounds occur in association with a deformed but mobile aortic valve and with aortic
root dilation. Thus, it is present in aortic valve stenosis, bicuspid aortic valve, aortic
regurgitation, and with aneurysm of the ascending aorta. An aortic ejection sound
is also heard in some patients with systemic hypertension, probably due to
associated aortic root dilation.

Aortic ejection sounds are heard frequently in patients with mild to moderate aortic
valve stenosis; they may be absent in severe calcific aortic stenosis, presumably due
to the loss of valve mobility [51]. Since ejection sounds are usually absent in
subvalvular and supravalvular aortic stenosis, the presence of an ejection sound
helps to identify the site of obstruction at the level of the aortic valve. An ejection
sound also does not favor the diagnosis of HCM.

Identification of the aortic ejection sound is the most important and consistent
bedside clue for the diagnosis of an uncomplicated bicuspid aortic valve [52]. In
patients with coarctation of the aorta, an aortic ejection sound usually signifies the
presence of an associated bicuspid aortic valve.

Pulmonary ejection sound — A pulmonary ejection sound occurs earlier than an

aortic ejection sound and is recorded 0.09 to 0.11 seconds after the Q wave on the
ECG, beginning at the time of maximal opening of the pulmonary valve. It is also a
"clicky" sound of high frequency and is best heard with the diaphragm of the
stethoscope. In contrast to the aortic ejection sound, it is not widely transmitted and
is usually best heard at the left second interspace and along the left sternal border;
it is not usually heard over the cardiac apex or right second interspace.

The most helpful distinguishing feature of a pulmonary ejection sound is its

decreased intensity, or even its disappearance during the inspiratory phase of
respiration. During expiration, the valve opens rapidly from its fully closed position;
sudden "halting" of this rapid opening movement is associated with a maximal
intensity of the ejection sound. With inspiration, the increased venous return to the
RV augments the effect of right atrial systole and causes partial opening of the
pulmonary valve prior to ventricular systole. The lack of a sharp opening movement
of the pulmonary valve explains the decreased intensity of the pulmonary ejection
sound during inspiration.

The tricuspid closure sound should not be confused with the pulmonary ejection
sound. The intensity of tricuspid closure sound tends to increase rather than
decrease during inspiration.

Pulmonary ejection sounds tend to be present in clinical conditions associated with

a deformed pulmonary valve and pulmonary artery dilation, including pulmonary
valve stenosis, idiopathic dilation of the pulmonary artery, and chronic pulmonary
arterial hypertension of any etiology [53-56]. The interval between the S1 and the
pulmonary ejection sound is directly related to the RV isovolumic contraction time,
which usually is prolonged in PH, explaining a relatively late occurrence of the
ejection sound in these patients. With increasing severity of pulmonary valve
stenosis, the isovolumic systolic interval shortens, and the pulmonary ejection sound
therefore tends to occur soon after the S1. In patients with very severe pulmonary
valve stenosis, the ejection sound can fuse with the S1 and may not be recognized.

NON-EJECTION SYSTOLIC SOUNDS — The non-ejection systolic sounds are also high-
frequency sounds that occur much later after the first heart sound (S1) and are best
heard with the diaphragm of the stethoscope. These sounds are not widely
transmitted and not usually heard over the right or left second interspace.

Midsystolic click — Prolapse of the mitral valve is the most common cause for a non-
ejection midsystolic click; the timing coincides with maximal prolapse of the mitral
valve into the left atrium. It may or may not be associated with a late systolic murmur
(movie 10 and movie 11) [57-60]. (See "Definition and diagnosis of mitral valve
prolapse".)

When the click occurs early in systole, it can be confused with the ejection sound or
the second component of a widely split S1. A number of bedside maneuvers can
be performed to confirm the presence of a midsystolic click. These maneuvers are
based upon the fact that the systolic dimension or volume at which mitral valve
prolapse and the click occur tend to remain fixed in the same patient [61]. Thus,
whenever the "click" volume or dimension is reached following the onset of
ventricular ejection (corresponding roughly to the S1), a midsystolic click occurs. The
S1-click interval, then, can vary according to the preejection (end-diastolic)
ventricular volume and the rate of ejection.

●The S1-click interval will increase, producing a late mid-systolic click whenever
there is an increase in end-diastolic volume (eg, supine position, squatting, hand
grip) (movie 11).

●The S1-click interval usually shortens, and the click tends to occur earlier when there
is a reduction in end-diastolic volume (eg, standing, phase 2 Valsalva maneuver,
amyl nitrite) or when there is an increased rate of ejection, as occurs after an
ectopic beat as a result of post-ectopic potentiation (movie 10).

It is important to identify the other cardiovascular anomalies that may accompany

mitral valve prolapse, including Marfan syndrome, atrial septal defect (secundum
or primum), musculoskeletal abnormalities, systemic lupus erythematosus, and HCM.
When there is no associated anomaly, isolated mitral valve prolapse is identified
[57]. (See "Definition and diagnosis of mitral valve prolapse", section on 'Clinical
manifestations'.)

Tricuspid valve prolapse also produces high-frequency midsystolic, "clicky" sounds;

these are best heard with the diaphragm of the stethoscope over the lower left
sternal border and occasionally over the lower right sternal border. The interval
between S1 and the tricuspid valve click tends to increase following inspiration and
after raising the legs and other maneuvers that increase RV volume. Isolated
tricuspid valve prolapse occurs only rarely, and in most instances it accompanies
mitral valve prolapse. Tricuspid valve prolapse, however, may occur in the absence
of mitral valve prolapse in patients with Ebstein anomaly.

Precordial honk — The systolic "whoop" or "precordial honk" are short musical systolic
murmurs often preceded by a click and occurring in mid or late systole. These
sounds can be transient, occur only in certain positions, or may be precipitated by
exercise. Mitral valve prolapse is the cause for the "whoop" or "honk" in most cases
[62,63].

Pseudo-ejection sound — A nonejection sound has been observed in some patients

with HCM associated with systolic anterior motion of the anterior mitral leaflet. This
sound has been termed a "pseudo-ejection sound" [64]. Unlike the ejection click of
aortic stenosis, this sound begins considerably after the upstroke of the carotid pulse.
The precise mechanism of the pseudo-ejection sound in HCM remains unclear. It
may either result from contact of the anterior leaflet with the septum or from the
deceleration of blood flow in the LV outflow tract.

EARLY DIASTOLIC HIGH-FREQUENCY SOUNDS — The most common causes for sounds
occurring in diastole include the opening snap of the mitral or tricuspid valve or a
tumor plop associated with an atrial myxoma (table 3).

Opening snap — The opening snap is a high-frequency, early diastolic sound

associated with mitral or tricuspid valve opening (movie 1). This opening of the AV
valves, which is normally silent, becomes audible in the presence of pathologic
conditions.

The opening snap results from rapid opening of the mitral valve to its maximal open
position; thus, mobility of the valve contributes to its genesis. It is absent when the
mitral valve is heavily calcified and immobile. However, the opening snap is heard
in the vast majority of patients with mitral stenosis, and along with an accentuated
first heart sound (S1), frequently provides the first clue to the diagnosis.

Mitral valve — Mitral stenosis is the most frequent and important cause of an opening
snap. It can occur rarely in patients with pure mitral regurgitation (MR) [48,65].

The opening snap is best heard with the diaphragm of the stethoscope, medial to
the cardiac apex. It is usually widely transmitted and can be easily heard over the
left second interspace and along the left sternal border. The opening snap
coincides with the full opening of the mitral valve and occurs 0.04 to 0.12 seconds
after the second heart sound (S2) (movie 1) [66].
The opening snap can easily be confused with a split S2 since it is frequently
transmitted to the left second interspace. However, careful auscultation over the
left second interspace in the supine position and during both phases of respiration
reveals three high-frequency sounds in close proximity to each other during
inspiration; the initial two are the two components of S2, and the third is the opening
snap. The recognition of these three sounds during inspiration helps to differentiate
mitral stenosis, as seen in mitral valve obstruction, from atrial septal defect (ASD),
which may also be associated with a mid-diastolic rumble. In ASD, only the two
components of the S2 are heard during expiration and inspiration.

The severity of mitral stenosis can be assessed at the bedside by noting the interval
between the aortic component of S2 and the opening snap. The S2-opening snap
interval is related to the difference in pressures at the time of aortic valve closure
and the opening of the mitral valve, which occurs during the isovolumic relaxation
phase when the LV pressure falls below the left atrial pressure. When mitral stenosis
is severe, left atrial pressure is higher, and the pressure crossover point between the
LV and left atrium is closer to S2, which reduces the S2-opening snap interval. At the
bedside, the shorter S2-opening snap interval sounds like a widely split S2. However,
the S2-opening snap interval is not only related to the height of the left atrial
pressure, but also to aortic valve closing pressure. Thus, with a higher aortic valve
closing pressure (systemic hypertension) and earlier closure of the aortic valve, the
S2-opening snap interval may be longer with the same degree of elevation of left
atrial pressure. Similarly, when the aortic valve closing pressure is lower (aortic
regurgitation and aortic stenosis), aortic valve closure is later, and the S2-opening
snap interval becomes shorter with the same degree of mitral stenosis. The S2-
opening snap interval also becomes shorter when mitral stenosis is associated with
MR with a large V wave. Furthermore, tachycardia decreases the S2-opening snap
interval as the left atrial pressure increases with increasing heart rate in mitral stenosis.
Thus, assessment of the severity of mitral stenosis by estimating the S2-opening snap
interval alone should be done with caution in the presence of tachycardia,
hypertension, MR, and aortic valve disease. (See "Clinical manifestations and
diagnosis of rheumatic mitral stenosis".)

Tricuspid valve — Tricuspid valve stenosis may be associated with a tricuspid valve
opening snap that is not widely transmitted and is heard best over the lower left
sternal border. The tricuspid opening snap can also be heard in some patients with
an ASD and a large left-to-right shunt [26].

Tumor plop — Early diastolic sounds (tumor "plop") are occasionally heard in atrial
myxoma. These sounds appear to occur when tumors move into the ventricle and
come to a sudden halt [67]. (See "Cardiac tumors".)

Vegetation plop — Vegetation plop is an early diastolic sound that is occasionally

heard in bacterial endocarditis. It appears that this sound is produced when a large
vegetation attached to the mitral valve leaflet enters the LV during early diastole
[68].

Other causes — A high-frequency, diastolic sound can be heard in other conditions

and should be differentiated from the opening snap or tumor plop.

●In some patients with mitral valve prolapse, a high-frequency sound is heard in
early diastole that appears to be related to the rapid inward movement of the
prolapsed mitral valve toward the LV cavity before the opening of the mitral valve
[69]. This early diastolic sound should not be confused with an opening snap due to
mitral stenosis.

●In some patients with HCM who have a small LV cavity size, early diastolic high-
frequency sounds are heard coinciding with the time of contact of the anterior
leaflet of the mitral valve to the interventricular septum [70].

●High-frequency early diastolic sounds, similar to the opening snap, can be heard
in some patients with severe MR due to ruptured chordae.

PROSTHETIC VALVE SOUNDS — The various types of prosthetic and tissue valves that
are in use for valve replacement may produce both opening and closing sounds.
The relative intensity of the opening and closing sounds vary according to the type
and design of the prosthetic valve used (table 4). The artificial valve sounds are of
high frequency, are much louder than normal valve sounds, and are of a "clicky"
character. The opening or closing sound may consist of multiple clicks, which do not
necessarily indicate valve malfunction.

●The closing sound is generally louder than the opening sound with a disk valve

●Both the opening and closing sounds are loud with the ball-and-cage type of valve

●The closing sounds of the porcine valve are much louder than the opening sounds

Valve malfunction — Changes in the normal sounds produced by the prosthetic

valve may indicate valve malfunction. However, malfunction of an artificial valve
can exist despite a normal intensity or character of the opening or closing sounds.
Doppler echocardiography and cardiac catheterization are usually necessary to
establish this diagnosis. (See "Diagnosis of mechanical prosthetic valve thrombosis
or obstruction" and "Overview of the management of patients with prosthetic heart
valves".)

●The closing sound is usually louder than the opening sound, regardless of the type
of prosthetic valve used. A decreased intensity of the closing sound should raise the
possibility of malfunction of the artificial valve.

●The absence of an opening click has been found in dehiscence of a mitral valve
prosthesis [71].
●Obstruction of a prosthetic valve in the mitral position may be associated with a
markedly decreased S2-opening sound interval. A marked variation in the S2-mitral
prosthesis opening sound may indicate malfunction of a mechanical mitral
prosthesis. The variation in this interval usually does not exceed 25 ms with a normally
functioning prosthesis [72].

Ball variance — "Ball variance" is a term used to describe certain physical changes
in a ball-and-cage valve and is associated with changes in the intensity of opening
and closing sounds [73]. Ball variance is related to a specific model of the caged
ball type of prosthetic valve, which is rarely used at the present time.

PERICARDIAL FRICTION RUB AND OTHER ADVENTITIOUS SOUNDS — A pericardial rub

is generated by the friction of two inflamed layers of the pericardium and occurs
during the maximal movement of the heart within its pericardial sac. Thus, the rub
can be heard during atrial systole, ventricular systole, and the rapid-filling phase of
the ventricle (three-component rub) (movie 12). However, the rub may be present
only during one (one component) or two phases (two components) of the cardiac
cycle. In myopericarditis following transmural MI, a one-component rub, usually
during ventricular systole, is more frequent than two- or three-component rubs.

Pericardial rubs are of scratching or grating quality and appear superficial. They are
best heard with the diaphragm of the stethoscope. The intensity frequently increases
after application of firm pressure with the diaphragm, during held inspiration, and
with the patient leaning forward. The rub may be localized or widespread, but
usually is heard over the left sternal border. (See "Acute pericarditis: Clinical
presentation and diagnostic evaluation".)

Pericardial rubs should be distinguished from the other superficial "scratchy" sounds.

●In patients with thyrotoxicosis, a to-and-fro, high-pitched sound may be heard over
the left second interspace, known as a Means-Lerman scratch; it may simulate a
pericardial friction rub. (See "Overview of the clinical manifestations of
hyperthyroidism in adults".)

●Acute mediastinal emphysema, usually a benign, relatively common complication

of open heart surgery, may be associated with a "crunching" noise over the
precordium that is coincident with ventricular systole (mediastinal crunch).

●In patients with Ebstein anomaly, the sail sound may be of a scratchy quality and
simulate a pericardial friction rub.

●The movement of the balloon flotation catheter or the transvenous pacing

catheter across the tricuspid valve can cause an early systolic superficial scratchy
sound that may also simulate a soft, one-component friction rub. These sounds
frequently disappear with the alteration of patient position.
●A pleuropericardial rub results from the friction between the inflamed pleura and
the parietal pericardium; it can be heard only during the inspiratory phase of
respiration.

●Twitching of the intercostal muscles or of the diaphragm during artificial pacing

may cause a superficial, scratchy, and high-frequency sound unrelated to the
cardiac cycle. This sound is called "pacemaker heart sound." The twitching of the
intercostal muscles results from stimulation of the adjacent intercostal nerves by the
pacemaker stimulus [74].

●Inadvertent entry of air into the RV cavity via the systemic venous system may
occur during placement of catheters or pacemakers in the right side of the heart or
as a complication of needle aspiration biopsy of the lungs. The movement of air in
the right ventricular cavity with systole and diastole may produce a peculiar
"slushing" or crunching sound ("mill wheel" murmur) over the entire precordium,
which can occasionally resemble pericardial friction rub [75].

●Swallowing sounds – These sounds are produced during swallowing and can be
confused with heart sounds. It is postulated that these sounds are produced by
vibrations of the vocal cords during swallowing [76].

SUMMARY AND RECOMMENDATIONS

●Heart sounds are broadly classified into high- and low-frequency sounds. (See
'Classification of heart sounds' above.)

•High-frequency sounds arise from closing or opening valves including mitral and
tricuspid valve closing sounds (M1 and T1), and aortic and pulmonary valve closure
sounds (A2 and P2).

•Low-frequency sounds include the third heart sound (S3, which may be physiologic
or pathologic), associated with early ventricular filling and the fourth heart sound
(S4), associated with the atrial contribution to ventricular filling in late diastole. (See
'Classification of heart sounds' above.)

●The intensity of the first heart sound (S1) can be helpful in assessing left ventricular
(LV) function and hemodynamics. (See 'Intensity of S1' above.)

•A loud S1 in the absence of a short PR interval indicates increased peak rate of rise
of LV systolic pressure (dP/dt), as seen in patients with increased transatrioventricular
valve gradients (mitral or tricuspid stenosis).

•A soft S1 in the absence of a prolonged PR interval usually indicates increased LV

end-diastolic pressure (LVEDP) and decreased peak dP/dt or reduced mobility of
the atrioventricular valves (calcified mitral stenosis).

●Fixed wide splitting of the second heart sound (S2) is highly suggestive of an atrial
septal defect. (See 'Splitting of S2' above.)
●Paradoxical splitting of S2 in the absence of left bundle branch block suggests LV
outflow obstruction or impaired contractile function. (See 'Splitting of S2' above.)

●An S3 gallop in adults in the absence of mitral regurgitation usually indicates

elevated LVEDP and increased brain natriuretic peptide levels. (See 'Clinical
significance of S3' above and "Evaluation of the patient with suspected heart
failure", section on 'Heart sounds'.)

●An abnormal S4 is most frequently observed in patients with decreased LV

distensibility (eg, acute myocardial ischemia, LV hypertrophy). (See 'Clinical
significance of S4' above.)

●Other early diastolic high-frequency sounds include an opening snap of the mitral
or tricuspid valve (appreciated in mitral or tricuspid stenosis) or a tumor plop
associated with an atrial myxoma. (See 'Early diastolic high-frequency sounds'
above.)

●A pericardial rub is characteristically a scratching or grating sound that may have

one, two, or three components. (See 'Pericardial friction rub and other adventitious
sounds' above.)