American Heart

Association~0
Fighting Heart Disease
and Stroke

Auscultation of the Heart

Examination of the Heart
Part 4
Examination of the Heart Part 4
Auscultation of the Heart

Prepared on behalf of the

Council on Clinical Cardiology
of the American Heart Association

James A. Shaver, MD
Professor of Medicine
Director, Division of Cardiology
University of Pittsburgh
Pittsburgh, Pennsylvania

James J. Leonard, MD
Professor of Medicine
Chairman, Department of Medicine
Uniformed Services University of Medicine
Pittsburgh, Pennsylvania

Donald F. Leon, MD
Professor of Medicine
Georgetown University
Medical Director, Georgetown University Hospital
Washington, DC
 Contents

2 The Stethoscope
Examination of the Heart 3 Examination of the Patient
A Series of Booklets
5 Heart Sounds
5 The First Heart Sound
Part 1
The Clinical History 6 Splitting
Mark E. Silverman, MD 7 Intensity
9 Systolic Ejection Sounds
Part 2
12 Nonejection Systolic Sounds
Inspection and Palpation of
Venous and Arterial Pulses 14 The Second Heart Sound
Michael H. Crawford, MD 14 Hemodynamic Correlates
16 Normal Physiologic Splitting
Part 3
18 Abnormal Splitting
Examination of the Precordium:
Inspection and Palpation 19 Wide Physiologic Splitting
Robert C. Schlant, MD, and J. Willis Hurst, MD 21 Reversed Splitting
22 Narrow Physiologic Splitting
Part 4
24 Single Second Heart Sound
Auscultation of the Heart
James A. Shaver, MD, James J. Leonard, MD, 24 Opening Snaps
and Donald E Leon, MD 26 Third and Fourth Heart Sounds
28 The Third Heart Sound
Part 5
The Electrocardiogram 28 Physiologic Third Heart Sound
Masood Akhtar, MD 28 Pathologic Third Heart Sound
30 Pericardial Knock
Available from your local American Heart Association The Fourth Heart Sound
30
32 Extracardiac Sounds
32 Pericardial Friction Rubs
33 Mediastinal Crunch: Hamman’s Sign
33 Pacemaker Sounds

@1972, 1978, 1990 American Heart Association

34 Heart Murmurs
35 Systolic Murmurs
36 Systolic Ejection Murmurs
47 Pansystolic Regurgitant Murmurs
49 Variations of the Pansystolic Regurgitant Murmur
53 Murmurs of Hypertrophic Obstructive Cardiomyopathy Proper medical evaluation of a patient is based on the patient’s history
54 Diastolic Murmurs and physical examination, supporting laboratory procedures, and special
54 Diastolic Filling Murmurs (Rumbles) diagnostic studies. Cardiac examination, in turn, consists of inspection,
54 Mitral Stenosis palpation, percussion, and auscultation, which includes examination of the
peripheral pulses, such as the carotid and jugular, and examination of the
56 Tricuspid Stenosis heart itself. For simplicity and convenience, various aspects of the cardiac
56 Diastolic Rumbles Due to High Flow Across the examination have been treated separately in this publication. It should be
Atrioventricular Valve remembered that auscultation of the heart is only one component of the
57 Austin Flint Murmur cardiac physical examination.
57 Diastolic Regurgitant Murmurs Recent advances in cardiac auscultation became possible with better
understanding of the relation between intracardiac pressure, flow, and
60 Continuous Murmurs valve motion and the resultant sound phenomena. Analysis of heart
60 Continuous Murmurs Due to Rapid Blood Flow sounds and murmurs by phonocardiography, combined with information
61 Continuous Murmurs Due to High-Pressure Shunts obtained from cardiac catheterization, angiocardiography, echocardiography,
62 Continuous Murmurs Secondary to a Localized Arterial and heart surgery, has made auscultation of the heart a precise discipline
Obstruction based on physiologic principles. These accurate methods of cardiac
investigation have not made the stethoscope obsolete; on the contrary,
63 References they have given cardiac auscultation a more important role in cardiac
diagnosis than it played in the past.
The Stethoscope
The physician must choose a stethoscope that fits the ears comfortably,
has a short segment of flexible tubing, and is equipped with a diaphragm
and a bell.
Selection of the proper earpieces for comfort and the best sound trans-
mission is based on highly individual preferences and is best evaluated by
trial and error. A snug but comfortable fit depends not only on the size of
the earpieces but also the angle at which they enter the canal; therefore,
angulation of the rigid metal tubing must suit the individual. The rubber
tubing should be as short as is practical; experience indicates that
approximately 1 foot of tubing is best. Rappaport and Spraguel have
shown that thick-walled tubing about 1/8" in diameter is the best for
transmitting sounds and murmurs.
The stethoscope should be equipped with a diaphragm and a bell. The
diaphragm brings out high frequencies and attenuates lows; thus, it should
be fairly rigid. When used to accentuate high-pitched sounds, the
diaphragm should be pressed firmly against the skin; this will make high-
frequency murmurs (such as the faint diastolic blowing murmur of
semilunar valve incompetency) audible at the base, when they would
otherwise be missed.
The bell accentuates lower frequency sounds and filters out high-
pitched sounds. It should be placed lightly on the skin, with just enough
pressure to seal the edge. Most low-frequency sounds are diastolic filling
sounds or murmurs; the examiner should listen for them with the patient
lying down, since orthostatic pooling will cause these sounds and
murmurs to diminish in intensity or disappear. The bell can also be used
as a filter system: With very light pressure, low-pitched sounds can be
accentuated. With firm pressure of the bell against the skin, the skin itself
becomes a relatively tight diaphragm. The rumbling, low-pitched murmurs
and filling sounds are pressed out, and attention can be directed to the
high-frequency components. Although this maneuver can be very helpful,
the stethoscope should nevertheless be equipped with a valve system that
makes switching from the diaphragm to the bell easy and efficient.
2 3
Examination of the Patient
The examination should take place in a quiet, well-lit, and comfortably
heated room. The patient should be properly gowned, with adequate
exposure to the waist. The examining table should be large enough to
allow the patient to lie flat, sit up, or roll to one side with ease.
In auscultation, the physician listens specifically and selectively for heart
sounds and murmurs. As so well described by Levine and Harvey,2 the
physician should adopt a systematic way of listening: Starting at the apex,
moving to the lower left sternal border, and "inching" along the sternal
border to the base of the heart, specifically the aortic and pulmonic areas
(second right and second left intercostal spaces, respectively). The patient
should lie flat, and each area should be surveyed with both chest pieces.
In each area examined, the physician listens specifically for the first heart
sound ($1) and notes its intensity, constancy, possible reduplication, or
respiratory variation. He or she then selectively listens to the second heart
sound ($2), noting the same characteristics. Then the physician seeks and
listens to extra sounds, first in systole, then in diastole, and mentally notes
their time of appearance, pitch, and other characteristics that identify them
as gallop sounds, ejection sounds, or valve opening sounds.
The physician next listens for the presence of murmurs, first in systole,
then diastole. After this general survey, the physician listens selectively for
certain sounds and murmurs. While listening carefully with the bell applied
lightly to the skin at the apex, the physician asks the patient to roll onto
the left side and selectively "tunes in" to diastole and the low-frequency
range, searching for the presence or absence of a diastolic filling sound or
murmur of the mitral valve.
Next, the patient is asked to sit up, or preferably, to sit on the side of the
examining table. With the patient leaning slightly forward, the aortic and
pulmonic areas are examined, with the diaphragm firmly pressed against
the chest wall, first during quiet respiration and then with the breath held
in deep expiration. The examiner is again listening selectively, this time to
the high-frequency range to elicit a faint blowing diastolic murmur of
semilunar valve regurgitation or, if the clinical situation warrants, the
presence of a pericardial friction rub. These types of sounds and murmurs
are discovered only when they are sought carefully; otherwise, the
examiner habitually listens only to medium- and high-pitched sounds and
murmurs that are loud and obvious to the ear.
 Auscultation of the heart should be considered a dynamic exercise. In Heart Sounds
addition to having the patient roll onto the left side, he or she should also
be examined during the Valsalva maneuver and after its release and while
standing and squatting. This sort of examination permits observation of the
effects of changes in central blood volume on acoustic events and, in
many instances, may yield diagnostic information.

There are two types of heart sounds: High-frequency transients

associated with the abrupt terminal checking of closing or opening valves
and low-frequency sounds related to early and late diastolic ventricular
filling events. Mitral and tricuspid valve closing sounds (M1 and T1),
nonejection sounds, and opening snaps are related to closing and
opening of the atrioventricular valves. Aortic and pulmonary valve closure
sounds (A2 and P2) and early valvular ejection sounds are related to
closing and opening of semilunar valves. Low-frequency sounds include
the physiologic and pathologic third heart sound ($3) associated with early
ventricular filling events, and presystolic, atrial, or fourth heart sounds ($4)
associated with late diastolic events resulting from the atrial contribution to
ventricular filling.

The First Heart Sound

S~, as recorded by high-resolution phonocardiography, consists of four
sequential components: 1) small low-frequency vibrations, usually
inaudible, which coincide with the beginning of left ventricular contraction
and are considered muscular in origin; 2) a large high-frequency vibration,
usually audible, related to mitral valve closure; 3) a second high-frequency
component related to tricuspid valve closure, which closely follows the
previous vibrations; and 4) small low-frequency vibrations that coincide
with acceleration of blood into the great vessels. The two major
components audible at the bedside are the louder M~, heard best at the
apex, followed by T1, heard best at the left sternal border. They are
separated by only 20-30 msec and are usually heard only as a single
sound in the normal subject.
Although there has been controversy about the genesis of these two
major components for years, several recent hemodynamic and
phonoechocardiographic studies support the original observations of
Dock3 and Leatham4 regarding the role of the atrioventricular valves in
generating both M1 and T~. These studies show that M1 and T1 coincide
with echocardiographic closure of the mitral and tricuspid leaflets,
respectively.5-7 The sounds produced are not due to the mere clapping
together of the delicate leaflets but rather the sudden deceleration of
blood, setting the entire cardiohemic system into vibration when the elastic
4 5
limits of the closed, tensed valves are met.8 Elegant hemodynamic studies
have further shown that neither M1 nor T1 coincide with atrioventricular
pressure crossover, but follow it by 20-40 msec.5,9 This is because forward
flow across the mitral and tricuspid valves continues for a short time after
pressure crossover due to inertia of the anterograde-flowing blood
column.10 These data confirm the prime role of the atrioventricular valves
in the genesis of the major audible components of $1.
Splitting
Onset of left ventricular contraction slightly precedes the same event on
the right side. As a result of this asynchrony, it is possible at times to hear
splitting of $1. Since the sound of tricuspid closure is faint, it is usually
drowned by the louder mitral closure sound that occurs earlier or almost
simultaneously. Therefore, it is often impossible to hear splitting clinically
unless other intervening factors alter the intensity or sequence of
atrioventricular valve closure.
When splitting of $1 is audible at the apex, it is usually caused by a
combination of mitral valve closure with a preceding atrial sound or
subsequent ejection sound. Although tricuspid closure becomes louder as
a result of pulmonary hypertension, the sound is nevertheless still difficult
to distinguish from mitral valve closure unless some alteration in the
closure sequence separates the two. In right bundle branch block, the
onset of right ventricular systole is frequently delayed, and T1 may be
heard sufficiently late to be easily recognized as a sound separated from
MI. The two components are more readily heard if right bundle branch
block is present in pulmonary hypertension, with a resultant loud tricuspid
closure sound. Wide splitting of $1 is also present in left ventricular
pacing, ectopic beats, and idioventricular rhythms originating from the left
ventricle.11 In all these situations, T1 is widely separated from M1 due to
delayed onset of right ventricular contraction. Similarly, pacing from the
right ventricle and ectopic beats and idioventricular rhythms originating
from the right ventricle will produce reverse splitting of $1 (T1 and M1) due
to delayed onset of left ventricular contraction.
In left bundle branch block, M1 is frequently delayed, resulting in
reversal of the $1 sequence.12-~4 However, this sound often cannot be
heard at the bedside because intensity of M1 is also markedly attenuated.
What has frequently been assumed to be splitting of $1 in left bundle
branch block is often a combination of an $4 preceding the atrioventricular
valve closure sound. This is particularly true in severe left ventricular
dysfunction or when left bundle branch block is a complication of
hypertensive cardiovascular disease. Reversed splitting of $1 may also be
present in hemodynamically significant obstruction of the mitral valve, as
mitral valve closure is delayed due to increased left atrial pressure, which
must be overcome by rising left ventricular pressure before closure can
6 7
occur.15 As a result of this delay, T1 may become unmasked, occurring
before MI. Such a tricuspid closure is occasionally audible because its
intensity is augmented by the concomitant pulmonary hypertension;
nevertheless, it is often lost in the presystolic mitral rumble. Reversed
splitting of $1 may be difficult if not impossible to hear at bedside and is
usually documented by phonocardiography.
Intensity
Intensity of S~ depends primarily on three factors: 1) position of the
atrioventricular valve at the onset of ventricular systole16-18; 2) structure of
the leaflets themselves (normal or thickened)19; and 3) rate of pressure rise
and tension development in the ventricle (Figure 1).16,17,20,21 Atrial systole
results in opening of the atrioventricular valves. If ventricular systole begins
when the valves are still wide open, $1 is loud. This situation is present
with short PR intervals from 0.11 to 0.13 second. After atrial systole, if the
ventricular contraction does not intervene, the atrioventricular valves begin
to float back together and may reclose if atrioventricular conduction is
prolonged and ventricular contraction is sufficiently delayed. At this point
(PR, 0.20-0.26 second), a faint $1 occurs. Sounds of intermediate intensity
may occur between these extremes. With complete heart block and a
constantly changing PR interval, $1 varies from beat to beat. In the
presence of bradycardia, a changing $1 permits diagnosis of complete
heart block.
To relate the intensity of $1 to the PR interval and, in turn, equate it to
the probable position of the atrioventricular valve is not entirely accurate.
With a forceful atrial contraction into a noncompliant ventricle, end-diastolic
ventricular pressure exceeds left atrial pressure, which is falling due to
active atrial relaxation. As a result, the valve begins to close. In this
situation, even though the PR interval is normal or short, the valve may be
partially closed at onset of ventricular contraction, resulting in a soft $1.
Such a situation exists in hypertension, in which a faint $1 often occurs in
the face of a normal PR interval in which a hemodynamic situation is the
equivalent of a long atrioventricular conduction time.22
The atrioventricular valves are also wide open during the early rapid
ventricular filling phase of diastole. Ventricular contractions occurring at
this time in the cardiac cycle will result in a loud $1. In atrial fibrillation or
with ventricular extra systoles, conditions in which atrial systole is not
operative, $1 may be very loud if the early or extra beat occurs 0.12-0.20
second after the preceding S2.23,24
Leaflet thickening and scarring due to rheumatic heart disease may
create a louder than normal sound during opening and closing as long as
the valve has mobility. However, complete immobilization (as in severe
calcific fixation of the mitral valve) results in marked attenuation of M~.19
 left ventricle at the end of diastole is considerably lower than the elevated
left atrial pressure; with onset of left ventricular contraction, ventricular
The First Heart Sound pressure may rise 10-25 mm Hg before it exceeds left atrial pressure, at
$1 $2 which time the mitral valve closes. The rate of pressure rise in the
ventricle at this time is far greater than that at the beginning of systole.
Base The presystolic gradient between the left atrium and the left ventricle also
keeps the mitral valve leaflets wide open. Both of these factors result in
a. Normal
high-velocity closure of the mitral valve with a large excursion, and a loud
$2
M1 is generated when the elastic limits of the stenotic valve are met. A
similar mechanism is responsible for the booming $1, with after-vibrations
Apex
observed in left atrial myxoma.3~ S~ intensity is usually decreased and
frequently delayed in patients with left bundle branch block, due primarily
S2 to a delay in onset of left ventricular contraction, associated left ventricular
1 Short PR interval dysfunction, or a combination of the tw0.12-14,17,32
b. Loud First Sound
I 2 Mitral stenosis
3 Left atrial myxoma
4 Exercise, tachycardia
One of the important auscultatory findings in acute aortic regurgitation is
attenuation or absence of M1.17,20,33,34 Severe regurgitation into a left
ventricle that has not had time to adapt to acute volume overload causes a
Anemia, hyperthyroidism
$2 1 Long P-R interval
marked increase in left ventricular end-diastolic pressure, resulting in
S1
2 Severe hypertension
preclosure of the normal mitral valve in mid-diastole. With onset of left
c. Faint First Sound 3 Left bundle branch block ventricuiar systole, minimal valve excursion occurs, causing a marked
4 Acute aortic regurgitation reduction in intensity of
5 Severe LV dysfunction

Figure 1. a. Second heart sound ($2) is characteristically louder than first heart sound ($1)
at base. Although S1 is usually more prominent than S2 at apex, this relation is less
constant and less reliable for timing purposes, b. Loud $1 is heard in presence of short PR
interval, mitral stenosis, left atrial myxoma, exercise, tachycardia, anemia, hyperthyroidism,
and hyperkinetic states in general, c. Faint S~ usually occurs in long PR interval and is
frequent in severe hypertension. It is also commonly seen in patients with left bundle
branch block, severe left ventricular (LV) dysfunction, and acute aortic regurgitation.
The status of ventricular contractility is also an independent factor
affecting intensity of $1. In normal subjects, exercise and catecholamine
infusions increase $1, while administration of I~-blockers decreases $1.17,25
In both situations, the rate of pressure development in the left ventricle is
the prime factor altering intensity. Increased rate of pressure development
is also present in high-output states such as anemia, arteriovenous
fistulas, pregnancy, anxiety, and fever, and results in a loud $1. A decrease
in intensity of $1 associated with a decrease in the rate of left ventricular
pressure development is found in myxedema, severe left ventricular
dysfunction, and acute myocardial infarction.26,27
A loud M1 is the hallmark of hemodynamically significant mitral
stenosis.17,28-30 A loud M1 is associated with a loud opening snap, and the
intensity of both M1 and the opening snap correlate best with valve
mobility. In significant obstruction of the mitral valve, the pressure in the
Systolic Ejection Sounds
Systolic ejection sounds occur simultaneously or shortly after onset of
left or right ventricular systolic ejection. These sounds have been classified
as valvular, originating from deformed aortic and pulmonic valves, or as
vascular or root events associated with the forceful ejection of blood into
the great vessels.
The aortic valvular ejection sound is found in nonstenotic congenital
bicuspid valves and in the entire spectrum of mild-to-severe stenosis of the
aortic valve. This sound introduces the typical ejection murmur of aortic
stenosis, is widely transmitted, does not vary with respiration, and is often
heard best at the apex (Figure 2). It occurs when the deformed aortic
valve reaches its maximal level of ascent into the aorta just before onset of
flow.35,36 At that moment in early systole when the rapidly ascending
deformed valve reaches its elastic limit, it decelerates the oncoming
column of blood abruptly, setting the entire cardiohemic system into
vibration. Low-frequency components of these vibrations produce the
anacrotic notch on the aortic pressure rise, and higher-frequency
components produce the valvular ejection sound.37,38 Inherent in this
mechanism of sound production is the mobility of the deformed valve.

8 9

Early Valvular Systolic
Ejection Sounds
Expiration Inspiration
S1 S2 Sl S2
ValvularSound Ejection
(Apex and Base)
Ej
Valvular Ejection
Sound
Ej
(Base Only)
Ej
Figure 2. Aortic valvular ejection sounds are heard at apex and at base and usually have
little respiratory variation. They are found in nonstenotic congenital bicuspid valves and in
entire spectrum of mild-to=severe valvular aortic stenosis. Intensity of valvular ejection sound
correlates directly with valve’s mobility and becomes faint or disappears with calcific fixation
of aortic valve. Intensity of aortic valve closure sound parallels intensity of aortic valvular
ejection sound. There is little correlation between intensity and severity of obstruction as
long as stenotic valve is mobile. Pulmonary valvular ejection sounds are usually heard best
at base, with little radiation to apex. In contrast to valvular aortic ejection sounds, there is
marked attenuation or disappearance of pulmonary valvular ejection sound during
inspiration. Such sounds are particularly well heard in mild-to-moderate pulmonic stenosis.
$1, first heart sound; S2, second heart sound; Ej, ejection sound.
With severe calcific fixation of the valve, no excursion is possible; sudden
tensing of the valve leaflets or abrupt deceleration of the column of blood
does not occur, and the valvular ejection sound is absent. Therefore,
intensity of the valvular ejection sound correlates directly with the valve’s
mobility; however, there is no correlation between intensity and severity of
the obstruction.
A pulmonary valvular ejection sound is a feature of mild-to-moderate
pulmonary stenosis and occurs simultaneously with the maximal excursion
of the deformed valve when its elastic limit is met.39,40 However, in contrast
to the aortic valvular ejection sound, the pulmonic sound decreases in
intensity or disappears with inspiration in mild-to-moderate stenosis (Figure
2).39,41,42 In mild valvular pulmonic stenosis, respiratory variation may be
absent. In severe pulmonic stenosis, the ejection sound fuses with $1 but
retains its respiratory variation. Under these conditions, an $1 that varies
10 11
with resp~iration is evidence that the sound is due to a combination of both
the $1 and an early pulmonic ejection sound. Occasionally, in severe
pulmonic stenosis, the ejection sound may occur in presystole due to a
vigorous atrial contraction that is capable of completely opening the
pulmonary valve in late diastole.43,~4
An ejection sound that originates from the aortic root is common in
children with cyanotic tetralogy of Fallot. At times, however, a pulmonary
valvular ejection sound is also heard in tetralogy of Fallot, indicating the
presence of valvular in addition to infundibular obstruction.45
Aortic ejection sounds originating from the aortic root are common in
systemic hypertension in the setting of a tortuous sclerotic aortic root, a
tight noncompliant arterial tree, and forceful left ventricular ejection. They
are also commonly heard in aneurysms of the ascending aorta and
nonvalvular aortic regurgitation secondary to abnormalities of the aortic
root. This sound is most likely the result of sudden tensing of the dilating
aortic root at onset of forceful ventricular ejection.37,38 In contrast to the
ejection sound of the stenotic aortic valve, these root sounds tend to be
poorly transmitted from the aortic area and are not well-heard at the apex.
At times it may be difficult, if not impossible, to differentiate this sound
from the tricuspid component of a widely split S~. However, the T~ is best
heard at the fourth parasternal area and often increases with inspiration.
The bedside decision as to whether this is. T~ or a root ejection sound is
often dictated by the clinical situation. In either condition, it should be
emphasized that the benign $1 root ejection sound or the M~-T1 sequence
is frequently misinterpreted as the pathologic $4-$1 sequence. Factors that
favor the S~-S1 complex are an associated palpable presystolic apical
impulse, optimal audibility of the $4 with the stethoscope bell applied
lightly to the apex, and changes in the intensity of $4 with maneuvers that
vary venous return.
Vascular or root ejection sounds may also come from the pulmonary
artery; the common denominator is dilation of the pulmonary artery.39,46
This dilation can be idiopathic or secondary to severe pulmonary
hypertension. Although these sounds have been reported to be louder
during expiration, there is no general consensus on this point. Unlike
splitting of S~, which is heard best at the mitral or tricuspid area, these
sounds are louder at the second and third left intercostal spaces.
Nonejection Systolic Sounds
Formerly, midsystolic and late systolic nonejection sounds were labeled Supine
as extracardiac sounds. It was believed that most of these sounds
originated from pericardial or pleural adhesions, based on the observation
that patients with these sounds frequently had a history of pneumonia,
pleuritis, bronchitis, or asthma, and that these sounds were usually heard S2
in the absence of serious cardiovascular conditions. However, it is now C
clear that the most frequent cause of systolic nonejection sounds is
prolapse of the mitral or tricuspid valve, often associated with a systolic
regurgitant murmur. These sounds are also commonly called systolic
clicks. Their valvular origin has been confirmed by angiographic,47,48
intracardiac phonocardiographic,49,50 and echocardiographic studies.51,52
As originally proposed by Reid,53 systolic clicks are caused by tensing of
the atrioventricular valves during systole. Like other high-frequency cardiac
sounds, systolic clicks are produced by vibrations of the entire cardiohemic Standing
system when the elastic limit of the prolapsed valve is suddenly reached.
The presence of a nonejection click on physical examination is sufficient
for diagnosis of mitral valve prolapse. The sound has a sharp, high-
$2
frequency clicking quality and, although often confined to the apex, can
be transmitted widely on the precordium. It may be an isolated finding
occurring most often in midsystole to late systole, or there may be multiple
clicks, presumably as a result of different areas of the large redundant
scalloped mitral leaflets that prolapse at different times. Numerous
echocardiographic studies have shown the presence of the characteristic
midsystolic to late systolic prolapse, as well as the holosystolic prolapse in
patients with these clicks. Variability of the auscultatory findings from
examination to examination is typical of mitral valve prolapse. The timing
of the click or clicks and the late systolic murmur vary considerably with Squatting
changes in posture (Figure 3).54 In the upright posture, the heart becomes
smaller due to decreased venous return, and the click moves earlier in
systole. Squatting, which causes an immediate increase in venous return $2
and afterload, increases left ventricular volume, resulting in later prolapse
and movement of the click toward $2. At bedside, these simple maneuvers
are helpful in distinguishing nonejection sounds from early ejection
sounds, a split $2, or an $3.
Phonoechocardiographic correlations during inhalation of amyl nitrite
have confirmed the cause-and-effect relation between the prolapse and
timing of the click.55 It has also been shown that echocardiographically
determined left ventricular diameter is relatively constant at the time of the
Figure 3. Midsystolic nonejection sound (C) occurs in mitral valve prolapse and is followed
click in the supine and upright positions and during amyl nitrite inhalation, by late systolic murmur that crescendos to second heart sound ($2). Standing decreases
indicating that a critical size was necessary for prolapse to occur.56 The venous return, heart becomes smaller, C moves closer to first heart sound ($1), and mitral
consistent relation of left ventricular size to timing of the click confirms the regurgitant murmur has earlier onset. With prompt squatting, venous return increases,
belief that the cause of mitral valve prolapse is valvuloventricular heart becomes larger, C moves toward S2, and duration of murmur shortens.

12 13
disproportion or a valve too large for the ventricle.57 In general, sitting or
standing, the strain of the Valsalva maneuver, and use of amyl nitrite
decrease left ventricular volume and cause the click to move closer to $1.
Normal Pressure-Sound Relationships
Vasopressor infusion, squatting, and lying down increase left ventricular of the Second Heart Sound
volume and move the click toward $2. Increased contractility or velocity of
shortening also affect the click timing since the critical size of the ventricle
81 A2 P2
will be reached earlier in systole.
Although the most common cause of nonejection clicks is prolapse of
the atrioventricular valves, systolic nonejection sounds have been reported
in patients with left-sided pneumothorax, adhesive pericarditis, atrial
myxomas, left ventricular aneurysm or aneurysm of the membranous mmHg
ventricular septum associated with a ventricular septal defect, and -100-
incompetent heterograft valves.58-61 Usually, these conditions are easily
recognized in the clinical setting and the absence of typical changes in
the timing of the click associated with physiologic and pharmacologic
maneuvers.

The Second Heart Sound

-0-
Hernodynamic Correlates
-25-
To appreciate the significance of the normal and abnormal S2,
knowledge of its relation to hemodynamic events of the cardiac cycle is
essential.62 In Figure 4, the two components of $2 are displayed
simultaneously with the cardiac cycle, as recorded by high-fidelity catheter-
tipped micromanometers. A2 and P2 coincide with incisura of the aortic
and pulmonary artery traces, respectively, and terminate the left and right
ventricular ejection periods. Right ventricular ejection begins before left
ventricular ejection, has a longer duration, and ends after left ventricular
ejection, resulting in P2 normally occurring after A2. Right and left
ventricular systole are nearly equal in duration, and the pulmonary artery
incisura is delayed relative to the aortic incisura primarily due to a larger Figure 4. Cardiac cycle recorded by high-fidelity, catheter-tipped micromanometers. Aortic
interval separating the pulmonary artery incisura from right ventricular valve (A2) and pulmonic valve (P2) closure sounds coincide with incisura of respective
pressure, compared with the same left-sided event. This interval is called arterial traces. Although duration of left and right ventricular (LV and RV) mechanical systole
the "hangout" interval, a descriptive term coined over 15 years ago.63 Its is nearly equal, RV systolic ejection period terminates after LV ejection because of
duration is thought to reflect impedance of the vascular bed in which increased right-sided hangout interval. As a result, P~ is later than A~. S1, first heart sound;
blood is received.63,~4 Normally, it is less than 15 msec in the systemic AO, aorta; PA, pulmonary artery.
circulation and only slightly prolongs left ventricular ejection time. However,
in the low-resistance-high-capacitance pulmonary bed, this interval is
normally much greater than on the left, varying between 43 and 86 msec,
thus contributing significantly to duration of right ventricular ejection.
14 15
Awareness of this interval is essential for an understanding of normal
physiologic splitting and abnormal splitting seen in many conditions where
significant alterations in pulmonary vascular impedance have occurred. Normal PhysiologicSplitting
The first high-frequency component of A2 and P2 coincides with closure
of the aortic and pulmonary valve leaflets.S5 As with sounds originating A2
from the atrioventricular valves, these sounds are not due to the clapping
together of the valve leaflets but are produced by sudden deceleration of J It
$1 $2
retrograde flow of the blood column in the aorta and pulmonary artery $2
when the elastic limits of the tensed valve leaflets are met. This abrupt
deceleration of flow sets the entire cardiohemic system into vibration; lower
Audible Expiratory Splitting
frequencies are being recorded as the incisura of the pressure tracings, Expiration Inspiration
while higher frequency components constitute valve closure sounds.8,63,66
The amplitude of A2 and P2 is directly proportional to the rate of change of A2 P2 A2 P2
Wide physiologic
the diastolic pressure gradient that develops across the valves; that is, the
driving force accelerating the blood mass retrogradely into the base of the
splitting
I II
great vessels.67,66 This pressure gradient is a result of the level of diastolic $1 $2
pressure in the great vessel and the rate of pressure decline in the
ventricle, and is consistent with the well-known clinical observation of
increased intensity of A2 and P2 in systemic and pulmonary hypertension.
Reversed splitting
Normal Physiologic Splitting
$1 $2 $1 $2
Normally during expiration, A2 and P2 are separated by less than 30
msec and are heard by the clinician as a single sound (Figure 5).69 During
inspiration, both components become distinctly audible as the splitting
interval widens, primarily due to a delayed P2, although an earlier A2 A2 P2
contributes to a lesser degree.4,70-74 Traditionally, the explanation for
normal splitting was that the delayed P2 during inspiration was secondary
to increased venous return, prolonging duration of right ventricular
Narrow physiologic
splitting (,I,P2) I il 1
$1 $2 Sl S2

ejection, while a concomitant decrease in venous return to the left heart

shortens left ventricular ejection.75-77 A more recent study shows that
delayed P2 and early A2 associated with inspiration are due to a complex
interplay of dynamic changes in pulmonary vascular impedance and
changes in systemic and pulmonary venous returnF4 The net effect of
these changes is prolonged right ventricular ejection and a concomitant
decrease in left ventricular ejection, which results in widening of the
splitting interval during inspiration.
On auscultation, splitting is best heard at the left second intercostal
space; the normal P2 is softer than A2 and rarely audible at the apex.F3
When P2 is heard at the apex, either significant pulmonary hypertension is
present or the apex is occupied by the right ventricle, a situation
commonly seen in normotensive atrial septal defect. Occasionally, in a
patient with mitral regurgitation and a giant left atrium, only slight
pulmonary hypertension is present, but the pulmonary closure sound may
be quite loud. This happens because the left atrium is displacing the heart
16
Figure 5. Top panel: Normal physiologic splitting. During expiration, aortic valve closure
sound (A2) and pulmonary valve closure sound (P2) are separated by less than 30 msec
and are heard as one sound. During inspiration, splitting interval widens, and A~ and P~ are
clearly separated into two distinctly audible sounds. Bottom panel: Audible expiratory
splitting. In contrast to normal physiologic splitting, two distinct sounds are easily heard
during expiration. Wide physiologic splitting is due to delay in P2. Reversed splitting is due
to delayed A2, resulting in paradoxical movement; that is, with inspiration, P~ moves toward
A2 and splitting interval narrows. Narrow physiologic splitting is seen in pulmonary
hypertension, and both A2 and P~ are heard during expiration at a narrow splitting interval
due to increased intensity and high-frequency composition of P=. $1, first heart sound; S~,
second heart sound.
17

so that the pulmonary artery moves anteriorly and closer to the sternum.
In patients with pectus excavatum, a loud pulmonary closure is often
heard because of the proximity of the pulmonary outflow tract. The
absolute value of inspiratory splitting varies with age and depth of
respiration. In younger subjects, maximal splitting during inspiration
averages 40-50 msec; with age, this value decreases such that a single
$2 during both phases of respiration may be normal in subjects over 40
years 01d.72,78,79
Abnormal Splitting
All conditions in which abnormal splitting exists can be identified at the
bedside by the presence of audible expiratory splitting; that is, the ability
to hear two distinct sounds during expiration.62,78 To be abnormal, this
finding must be present when the patient is auscultated in the upright and
supine positions, since some young normal subjects have audible
expiratory splitting in the recumbent position that becomes single when
the upright position is assumed.78
The three causes of audible expiratory splitting are 1) wide physiologic
splitting, primarily due to delayed P2; 2) reversed splitting, primarily due to
delayed A2; and 3). narrow physiologic splitting, as seen in pulmonary
Table 1. Wide Physiologic Splitting of the Second Heart Sound
Delayed pulmonic closure
Delayed electrical activation of the right ventricle
Complete right bundle branch block (proximal type)
Left ventricular paced beats
Left ventricular ectopic beats
Prolonged right ventricular mechanical systole
Acute massive pulmonary embolus
Pulmonary hypertension with right heart failure
Pulmonic stenosis with intact septum (moderate to severe)
Decreased impedance of the pulmonary vascular bed (increased hangout)
Normotensive atrial septal defect
Idiopathic dilation of the pulmonary artery
Pulmonic stenosis (mild)
Atrial septal defect, postoperative (70O/o)
Unexplained audible expiratory splitting in normal subject
Early aortic closure
Shortened left ventricular mechanical systole (left ventricular ejection time)
Mitral regurgitation
Ventricular septal defect
Reproduced from Shaver and O’Toole82 with permission.
18
hypertension when A2 and P2 are heard as two distinct sounds during
expiration at a normal splitting interval (Figure 5).62 In Tables 1 and 2, the
common causes of wide physiologic splitting and reversed splitting of $2
are classified according to the abnormality of the cardiac cycle responsible
for the altered timing of A2 and P2. In each table, the cardiac cycle has
been divided into three phases: 1) the electromechanical coupling interval
(time from onset of Q wave to rise of ventricular pressure), 2) ventricular
mechanical systole (the sum of isovolumic contraction time plus ejection
period, minus the hangout interval), and 3) hangout or impedance interval
(the time between the incisura of the arterial trace and ventricular pressure
at the same level as the incisura).
Wide Physiologic Splitting
In the presence of complete right bundle branch block, delayed
electrical activation of the right ventricle causes late onset of right
ventricular contraction and P2 iS delayed, resulting in wide physiologic
splitting.ll Prolonged mechanical right ventricular systole due to outflow
obstruction also results in wide physiologic splitting; this occurs in valvular
or infundibular pulmonic stenosis with an intact ventricular septum
Table 2. Reversed Splitting of the Second Heart Sound
Delayed aortic closure
Delayed electrical activation of the left ventricle
Complete left bundle branch block (proximal type)
Right ventricular paced beats
Right ventricular ectopic beats
Prolonged left ventricular mechanical systole
Complete left bundle branch block (peripheral type)
Left ventricular outflow tract obstruction
Hypertensive cardiovascular disease
Arteriosclerotic heart disease
Chronic ischemic heart disease
Angina pectoris
Decreased impedance of the systemic vascular bed (increased hangout)
Poststenotic dilation of the aorta secondary to aortic stenosis or regurgitation
Patent ductus arteriosus
Early pulmonic closure
Early electrical activation of the right ventricle
Wolff-Parkinson-White syndrome, type B
Reproduced from Shaver and O’Toole80 with permission.
19
(Figure 6).43,8~ However, in infundibular stenosis, valve closure becomes
faint or absent, and this sign is of limited value. The prolongation of right
ventricular systolic ejection increases linearly with the degree of
obstruction, and as a result, the width of the splitting interval during
expiration in pulmonic valvular stenosis correlates well with the
transvalvular gradient.43 In some patients with acute and chronic elevation
of afterload, as seen with acute massive pulmonary embolus or pulmonary
hypertension in the face of right ventricular failure, pulmonic closure is
also delayed, resulting in wide physiologic splitting.82-84
Wide, fixed splitting of $2 occurs in normotensive atrial septal defects
(Figure 6).85 Although the right ventricle ejects a larger volume of blood
than the left ventricle, selective prolongation of right ventricular mechanical
systole does not occur in these patients. However, right ventricular ejection
Splitting of the Second Heart Sound
EXPIRATION INSPIRATION
$1 $2 St $2
Normal Splitting
Wide Splitting I~T~~ $1 $2 S~
time is prolonged and is related to alterations in impedance of the
pulmonary vascular bed.S2,86 In patients with atrial septal defects, the
splitting $2 is relatively fixed (movement of less than 20 msec). The most
attractive explanation for this observation is that there are two avenues of
venous return to the right atrium, one from the systemic veins and the
other from the left atrium through the atrial septal defect. During
inspiration, systemic venous return increases and the volume of shunted
blood decreases; during expiration, the reverse occurs. As a result, the
total right ventricular inflow volume is fixed relative to the volume inflow of
the left heart. Alterations in the pulmonary vascular bed secondary to high
flow may persist after atrial septal defect repair, explaining the frequent
occurrence of wide splitting after successful repair.19,69 However, in most
cases, splitting is no longer fixed. When severe pulmonary hypertension
develops in atrial septal defect, narrow or wide splitting of $2 may occur.
Wide splitting of $2 may also be a result of selective shortening of left
ventricular ejection time with a relatively early aortic closure sound (Figure
6). This sequence is a frequent occurrence in severe mitral regurgitation
and ventricular septal defect.s2,69 In both conditions, there is a low
impedance regurgitant or shunt pathway in addition to the usual pathway
of ejection. This combination results in shortened left ventricular systolic
ejection time.
S2

Right Bundle Branch Block

A2 II P2 M1 A2 II P2
Reversed Splitting
Almost all cases of reversed splitting are due to a delay in A2. The result
is a reversed sequence of closure sounds, with P2 preceding A2. At the
bedside, this is recognized by paradoxical movement of A2 and P2 with
respiration (Figure 5).87 During inspiration, P2 moves toward A2 and the
$1 $2 St $2
splitting interval narrows, whereas during expiration, the two components
separate and audible expiratory splitting is present. Paradoxical splitting of
Atrial Septal Defect
~ .,,...J I.I.III. $2 frequently indicates significant underlying cardiovascular disease.
Both right ventricular ectopic and paced beats produce a delay in onset
of left ventricular contraction, resulting in reversed splitting.~ The most
Mitral Regurgitati°nIor
Ventricular Septal Defect
II
A2 P2
II
A2 P2
common cause of reversed splitting is complete left bundle branch block,
which can be due either to delayed activation of the left ventricle as seen
in proximal block or a prolonged mechanical systole (primarily isovolumic
contraction time) as seen in the peripheral block and invariably associated
Figure 6. Wide splitting of second heart sound (S2) may be due to delayed closure of with significant left ventricular dysfunction.14,32,80 In most cases of left
pulmonic valve as in right bundle branch block, pulmonic stenosis, and atrial septal defect,
or to early closure of aortic valve as in mitral regurgitation and ventricular septal defect. In
bundle branch block, varying degrees of both mechanisms exist, with one
atrial septal defect, splitting is both wide and fixed. $1, first heart sound; A2, aortic valve predominating.
closure sound; P2, pulmonic valve closure sound; T1, tricuspid valve closure sound; M~, Reversed splitting in patients with left ventricular outflow tract
mitral valve closure sound. obstruction is most obvious in congenital valvular aortic stenosis or
hypertrophic obstructive cardiomyopathy, since A2 is well-preserved. In
both conditions, the delayed A2 is the result of a large systolic pressure
gradient and prolonged left ventricular relaxation.e8,89 In valvular aortic
20 21
 stenosis with marked poststenotic dilation, a prolonged hangout interval
may also play a role in this delay.90,91 Reversed splitting in valvular aortic
stenosis in the absence of a conduction defect means hemodynamically
significant obstruction at the aortic valve. --lOOmmHg
In hypertensive cardiovascular disease, splitting is usually physiologic
with increased A2 intensity. However, occasionally reversed splitting does $1 A2P2 Sl P2
occur. The acute elevation of afterload caused by intravenous
administration of methoxamine produces reversed splitting in normal
subjects due to prolonged left ventricular ejection and isovolumic
contraction times.92 Reversed splitting has also been reported in ischemic
I II ! I!
heart disease and during angina.93,94 The latter is extremely uncommon
and has rarely been documented. It is most likely due to prolonged A2 P2 - 20msec
isovolumic contraction time of the ischemic left ventricle, although during
A2P2 =50rr/sec
angina, it may also be due to an increase in systemic arterial pressure or
transient left bundle branch block.95 _100
Decreased impedance in the systemic vascular bed may also contribute LV
to delayed A2, as seen in poststenotic dilation of the aorta, chronic aortic
regurgitation, and patent ductus arteriosus.80,96 Reversed splitting has also PA
been reported in cases of type B Wolff-Parkinson-White syndrome where
early activation of the right ventricle through an accessory pathway has
caused P2 to occur prematurely.g7,98

Narrow Physiologic Splitting

Narrow physiologic splitting is a common finding in severe pulmonary
hypertension, where both A2 and P2 are easily heard during expiration,
even though the splitting interval is less than 30 msec because of
increased intensity and high-frequency composition of P2.83,99 Wide
splitting of $2 with an increased pulmonary component can also be heard
in pulmonary hypertension. Shapiro and associates~ have suggested that
a wide split in this setting may indicate a more severely compromised EKG
ventricle. Similar observations have been made by Perloff,83 who states
that wide persistent splitting is a useful sign of abnormal right ventricular
performance in patients with primary pulmonary hypertension. To reconcile Figure 7. Sound-pressure correlates recorded by high-fidelity, catheter-tipped
these different responses in splitting when pulmonary hypertension micromanometers in two patients with severe pulmonary hypertension. Left panel: Narrow
develops, it is essential to understand that duration of right and left physiologic splitting (less than 30 msec) is present. Right panel: Wide splitting is shown.
There is marked reduction in hangout interval in both patients. In left panel, duration of left
ventricular mechanical systole is normally nearly equal and that a potential and right ventricular (LV and RV) systole is nearly equal, and narrow splitting of second
interval (the normally wide right-sided hangout interval) can be encroached heart sound results. In right panel, significant prolongation of RV mechanical systole
on as pulmonary hypertension progressively decreases capacitance and beyond LV systole delays pulmonic valve closure sound (P2), resulting in wide splitting of
increases resistance of the pulmonary vascular bed.63,6~ Figure 7 shows second heart sound. $1, first heart sound; A2, aortic valve closure sound; PA, pulmonary
the sound and pressure correlates of two patients with severe pulmonary artery.
hypertension, one with narrow splitting and one with wide splitting. Marked
narrowing of the normally wide right-sided hangout interval is common in
both patients. In the left panel, duration of right and left ventricular systole
is nearly equal at the time of the pulmonary artery incisura; the splitting

22 23
interval is narrow. In contrast, the right panel shows prolongation of right
ventricular mechanical systole in the face of chronic pressure overload; the
net effect is a delayed P2, resulting in wide splitting. Thus, a spectrum of
the width of splitting may be seen in pulmonary hypertension, depending
on the degree of selective prolongation of right ventricular systole, always
in the setting of a narrow hangout interval.
Fixed splitting has occasionally been documented in severe right
ventricular failure secondary to pulmonary hypertension. This has usually
been attributed to inability of the compromised right ventricle to accept the
augmented venous return associated with inspiration. Another factor,
altered pulmonary vascular impedance associated with severe pulmonary
hypertension, has also been shown to play an important role in the
diminished inspiratory split observed in such cases.F4
Single Second Heart Sound
The conditions that delay A2 (listed in Table 2) may produce a single S2
when the splitting interval becomes less than 30 msec. Conditions in
which one component of $2 is either absent or inaudible will also produce
a single $2 (i.e., severe tetralogy of Fallot and severe semilunar valve
stenosis). In Eisenmenger’s ventricular septal defect, a loud single sound
is heard because A2 and P2 occur simultaneously. Probably the most
common cause of an apparently single $2 is inability to hear the fainter of
the two components of the sound (usually P2) because of emphysema,
obesity, or respiratory noise. A single $2 is also common in individuals
over 40 years 01d.73,79
Opening Snaps
Opening of the normal atrioventricular valve is usually silent. However,
with thickening and deformity of the valve (usually rheumatic in origin), a
sound is generated in early diastole similar to ejection sounds originating
from deformed semilunar valves. Margolies and WolferthlOO proposed that
the mechanism of production was a sudden stopping of the opening
movement of the valve, and further noted that the sound was absent in
patients whose valves were markedly thickened and immobile. This
mechanism was confirmed by hemodynamic and angiographic studies
that showed sudden checking of early diastolic descent of the funnel-
shaped stenotic valve when its elastic limit was met.29,101 Phonoechocardi-
ography has given an even more precise correlation of the opening snap
with maximal opening motion of the anterior mitral valve leaflet.30,102
24
The opening snap is a crisp, sharp sound that can be heard in the
midprecordial location. It is usually best heard from the left sternal border
to just inside the apex. It may often be heard at the base of the heart,
does not vary with respiration, and is frequently not well heard at the
maximal intensity of the diastolic murmur. The diastolic rumble generally
follows the opening snap by a short interval. Although the opening snap is
at times difficult to separate from P2, usually during continuous inspiration,
it is possible on inspiration to hear the trill of three sounds occurring in
rapid sequence in the pulmonary area, and only two components on
expiration (Figure 8).
As with valvular ejection sounds, the intensity of the mitral opening snap
correlates well with the mobility of the valve, as a loud opening snap is
found in mobile stenotic valves with good excursion, while with severe
calcific fixation of the valve, the opening snap is absent. Intensity of M1
parallels the intensity of the opening snap; mobile valves with a loud
opening snap have an accentuated MI. Immobile valves with a decreased
or absent opening snap have marked attenuation of M1. Although the
presence of valvular calcification decreases valve mobility and audibility of
the opening snap, the sound is actually found in 50-60% of patients with
calcific valves. An opening snap may also be present in pure mitral
regurgitation of rheumatic origin with typical doming of the deformed valve.
Although often identified by phonocardiography, the opening snap is
difficult to hear at bedside because it may be overshadowed by the loud
P2 and $3 gallop that is common in this condition.
Opening Snap (O.S.)
Expiration Inspiration
S1 S2 S1 S2
A2 P2
Figure 8. Opening snap (OS) of mitral valve is high-pitched and best heard between apex
and left sternal border, and may frequently radiate to pulmonic area. It is best differentiated
from pulmonic valve closure sound (P~) by listening for aortic valve closure sound (A2) and
OS occurring in rapid succession on inspiration. $1, first heart sound; $2, second heart
sound.
25
 The opening snap follows A2 by 30-150 msec. In patients with mild
mitral stenosis, the interval is usually longer, whereas in more severe Diastolic Filling Sounds
stenosis, the A2-0pening snap interval is shorter. Several investigators
S1 S2 S1 S2
have attempted to use this interval to predict the level of left atrial pressure
and severity of the obstruction.103-105 Since opening snaps occur at the
maximal mitral opening shortly after left ventricular-left atrial pressure a.S
Atrial gallop
crossover, the following factors influence timing of the opening snap Presystolic gallop
relative to A2: 1) rate of left ventricular pressure decline, 2) level of left ‘% S2 ,% S2
ventricular pressure at the time of A2, and 3) level of left atrial pressure. b. S3
Increasing severity of mitral stenosis is usually accompanied by increasing Ventricular gallop
left atrial pressure and therefore a shortening of the A2-0pening snap
interval. Because this interval is multifactorially determined, there is S1 S2 S1 S2
imperfect correlation between the A2-0pening snap interval and the mitral c. Pericardial knock
valve area.106,107 However, since this interval can, with some practice, be (K)
fairly well estimated with auscultation, the opening snap and its timing
become an important finding in diagnosis and assessment of pure mitral S1
stenosis. d. Quadruple rhythm $4
Tricuspid valve stenosis can also produce an opening snap, but this ~
sound is frequently undetected because mitral stenosis, which is almost
invariably present, overshadows tricuspid stenosis.~08,~09 The maximum S1 S2 $1 $2
intensity of the tricuspid opening strap tends to be closer to the left sternal e. Incomplete
border and, unlike the mitral opening snap, increases with inspiration. summation gallop
When present, it generally follows the mitral opening snap.
An early diastolic sound can also be caused by right or left ventricular ‘% S2 $1 S2
myxoma, the tumor "plop" occurring at the maximal diastolic descent of
f. Summation gallop
the myxoma.~o Opening snaps are rarely found in patients with normal (SG)
valves, although they have been described in situations where there is
high flow across the atrioventricular valve.Ill These snaps have been
described in large atrial septal defect where the sound is coincident with Figure 9. a. Fourth heart sound ($4) occurs in presystole and is frequently called atrial or
maximal opening of the tricuspid valve.85,1~2 Other conditions in which presystolic gallop, b. Third heart sound ($3) occurs during rapid phase of ventricular filling.
opening snaps have been described in normal atrioventricular valves It is normal and commonly heard in children and young adults, disappearing with
include large ventricular septal defects, thyrotoxicosis, and tricuspid atresia increasing age. In middle age, it is called pathologic $3 or ventricular gallop and indicates
with a large atrial septal defect.~ ventricular dysfunction or atrioventricular valve incompetence, c. in constrictive pericarditis,
sound in early diastole (K) is earlier, louder, and higher pitched than usual pathologic S~.
d. Quadruple rhythm results if both $4 and $3 are present, e. At faster heart rates, these
sounds occurring in rapid succession may give illusion of mid-diastolic rumble, f. When
Third and Fourth Heart Sounds heart rate is sufficiently fast, two rapid phases of ventricular filling reinforce each other and
loud summation gallop (SG) may appear; this may be louder than either S~ or S4 alone.
$3 and $4 are low-frequency sounds related to early and late diastolic $1, first heart sound; $2, second heart sound.
filling of the ventricle (Figure 9). They are called gallop sounds in
pathologic conditions, and their presence alerts the clinician to S,~ gallops is responsible for "rumbles" described in hyperkinetic states
abnormalities of ventricular function or compliance or both. The presence such as anemia and hyperthyroidism. If the heart rate becomes faster,
of both sounds in certain conditions results in a quadruple rhythm. With these two sounds may fuse, and a very loud summation gallop appears
tachycardia, diastole is shortened and these two sounds may be closer in mid-diastole, often louder than either of its components.
together. In rapid succession, the impression is frequently that of a low-
pitched, mid-diastolic murmur. The incomplete summation of the $3 and
27
26
The Third Heart Sound
Physiologic Third Heart Sound
The physiologic S3 is a benign finding commonly heard in children,
adolescents, and young adults.113,114 It is rarely present after age 40 and,
when present, .is often associated with a thin, asthenic body type.115 It is a
low-frequency sound that follows A2 by 120-200 msec during the rapid
filling wave as recorded on the apexcardiogram.l~ It is a dull, low-pitched
sound heard best at the apex with the subject lying on the left side with
the stethoscope bell pressed lightly against the skin. It waxes and wanes
during respiration and is most audible at the beginning of expiration. It
differs from the pathologic $3 primarily by the "company it keeps."117,~18
Pathologic Third Heart Sound
There is general agreement that the pathologic S3 is an exaggeration of
the physiologic $3 and that the two have a common mechanism of
production.8,~9,120 Although genesis of the $3 remains controversial, three
major mechanisms of production have been proposed: the valvular theory,
the ventricular theory, and the impact theory. Phonoechocardiographic
studies have shown that the valvular theory, implicating diastolic tensing of
the atrioventricular valves at the end of rapid ventricular filling, is no longer
tenable.~8,12~-123 The second theory, supported by several recent studies,
indicates that these sounds originate within the left or right ventricle or
their walls.~24-129 The dynamic interplay between the force of delivery of
blood into the ventricle and the ability of the ventricle to accept this flow is
considered the important factor in genesis of this sound. $3 occurs when
the ventricle suddenly reaches its elastic limit and abruptly decelerates
early diastolic blood flow, thereby setting the entire cardiohemic system
into vibration. The resultant $3 may be caused by very rapid filling into a
ventricle, as with high-output states and atrioventricular valvular
regurgitation, or by a normal or less than normal rate of filling into the
ventricle with decreased compliance, as in patients with hypertrophic
cardiomyopathy. Likewise, decreased rates of filling into overfilled ventricles
with large end-systolic volumes, as seen in patients with poor ventricular
function and heart failure, may produce this sound.130 Although this
mechanism is likely responsible for the sound recorded within the
ventricular cavity and epicardial surface, Reddy and associates~31-136
found convincing data that the sound heard with the stethoscope is due to
the dynamic impact of the heart against the chest wall. The force of
impact and resultant intensity of $3 are dependent primarily on the size of
the heart, its motion within the thorax, and the chest wall configuration.
This theory explains the $3 frequently present in hyperdynamic states as
28
well as those with an increased end-systolic volume secondary to poor left
ventricular function. In the latter situation, the space between the enlarged
heart and lateral chest wall is diminished, facilitating a more forceful
impact in early diastole.
The most common cause of the pathologic $3 is ventricular dysfunction,
which results in poor systolic contraction, increased end-diastolic and end-
systolic volume, decreased ejection fraction, and high atrial filling
pressures. The causes of this ventricular dysfunction include ischemic
heart disease, idiopathic dilated cardiomyopathy, end-stage valvular and
congenital heart disease, and severe systemic and pulmonary
hypertension.
Like the physiologic $3, the pathologic sound is heard best at the apex
and may be heard more easily with the patient turning or turned to the left
side. When present, this sound is more constant than the physiologic $3
and has less respiratory variation. Both intensity and timing of this sound
are related to the patient’s volume status. With diuresis, the $3 may
decrease in intensity or disappear, and tends to move away from A2.
Careful attention to these subtle changes is a simple and accurate way to
follow the response to therapy in patients with congestive heart failure. A
loud, persistent $3, seen with acute myocardial infarction or
cardiomyopathy, is an ominous sign associated with high mortality,
whereas prompt subsidence of this sound with therapy suggests a more
favorable outlook.~25,~37 The pathologic $3 may be faint and easily
overlooked unless the clinician listens intently in a quiet room with the
stethoscope bell pressed lightly on the skin while the patient lies in the left
lateral position. Maneuvers that increase venous return, such as passive
leg raising, are helpful in increasing intensity of sound, while decreased
venous return, as with an upright posture, will decrease intensity.138 The
right ventricular $3 is found in right-sided cardiac disease with failure and
is best heard at the xyphoid or the left lower sternal border. It usually has
a striking respiratory variation, becoming much louder on inspiration.
A prominent $3 is frequently heard in hyperkinetic states and
atrioventricular valve incompetence resulting from excessively rapid early
diastolic filling. In these conditions, this sound does not necessarily imply
congestive heart failure, and these patients may maintain normal
myocardial contractility for years after $3 is detected.~39
Pathologic $3 can also be heard in restrictive and hypertrophic
cardiomyopathy and tends to occur sooner after A2. At times, these
sounds actually simulate a short diastolic rumble due to the duration of
low-frequency vibrations.
29
Pericardial Knock
The pericardial knock is an early diastolic sound that is a valuable
diagnostic adjunct in identification of pericardial constriction. It usually
occurs approximately 0.08-0.12 second after the beginning of $2. Because
of this time relation, this sound is sometimes confused with the opening
snap of mitral stenosis or an $3 gallop (Figure 9). In general, however, the
pericardial sound appears earlier than the pathologic $3, is of higher
frequency, is more widely transmitted, and may even exceed other heart
sounds in intensity. The pericardial knock usually increases in intensity
with inspiration and occurs near the nadir of the Y descent of the jugular
venous pulse. Atrial fibrillation is common in both severe constrictive
pericarditis and mitral stenosis, and the differential diagnosis may be
difficult because a loud early diastolic sound is present in both conditions.
However, careful attention to the classic contour of the jugular venous
pulse will usually allow the correct diagnosis of constrictive pericarditis at
the bedside.
The pericardial knock has many hemodynamic similarities to the
physiologic or pathologic $3, and it is likely that they have a common
mechanism of production. Both the apexcardiogram and the ventricular
pressure curve show an exaggeration of the rapid early pressure rise
typical of the pathologic $3. The pericardial knock also coincides with
termination of the rapid volume filling of the ventricles.140 Consistent with
the impact theory of the production of gallop sounds, the knock also
occurs simultaneously with the diastolic impulse peak of the
apexcardiogram.13~ In patients in whom the pericardium has been
stripped, the sound may remain, occurring later in time at an interval
characteristic of the typical ventricular gallop, further confirming a common
genesis of these sounds.141
The Fourth Heart Sound
Low-frequency sounds resulting from atrial contraction are normally
neither palpable nor audible. However, under pathologic conditions,
forceful atrial contraction generates a low-frequency sound ($4) just before
$1. This sound is also frequently called the atrial diastolic gallop or
presystolic gallop. Audibility of the $4 depends on its intensity and
frequency as well as its separation from $1. $4 follows onset of the P wave
by approximately 70 msec; the degree of separation from $1 is primarily
determined by the PR interval. A loud $1 may also mask the audibility of a
softer preceding $4. Its presence depends on effective atrial contraction
and disappears after atrial fibrillation.
30 31
The $4 or presystolic gallop is heard best at the point of maximal
impulse, with the patient turned in the left lateral position. It varies
considerably with respiration and is usually heard best during expiration.
Both intensity and timing of this sound are closely related to end-diastolic
volume of the ventricle. Maneuvers that increase venous return increase
audibility by enhancing intensity of the sound and causing it to occur
earlier, thereby further separating it from $1.22 Decreased venous return
does the opposite.
Fourth sounds are usually accompanied by a palpable presystolic apical
impulse; the right-sided $4 is usually heard best at the lower left sternal
border, tends to increase with inspiration, and is associated with a
prominent A wave in the jugular venous pulse. Production of the S~ is
similar to the $3. Ventricular origin due to abrupt deceleration of the atrial
contribution to late diastolic filling and the impact theory have both been
proposed.129,131 It is likely that the former is responsible for sounds
recorded within the ventricular cavities or their epicardial surfaces,
whereas the latter is a mechanism for the $4 heard at the chest wall.
As opposed to the physiologic $3, which is common in children and
young adults, an audible $4 is rare in normal subjects. Thus, its presence,
particularly when associated with a presystolic apical impulse, is
abnormal. 142,143
An abnormal $4 is frequent in any condition that causes a significant
decrease in ventricular compliance. Forceful left atrial contraction into a
hypertrophied noncompliant left ventricle secondary to severe
hypertension, left ventricular oufflow obstruction, or hypertrophic
cardiomyopathy ordinarily produces an early and easily audible S,
associated with a prominent apical presystolic impulse. Goldblatt and
associates1~4 reported that an $4 in patients with aortic stenosis correlates
with a peak systolic gradient of 70 mm Hg or more and left ventricular
end-diastolic filling pressure of 13 mm Hg or greater. This observation has
subsequently been modified by Caulfield et a!,145 who reported that an $4
is good evidence of significant aortic stenosis only in patients under age
40. An $4 is often present in ischemic heart disease in the early phases of
acute transmural myocardial infarction, during acute episodes of angina,
and in patients with prior myocardial infarction with significant left
ventricular dysfunction. However, such a sound is not common in patients
with significant coronary artery disease in the absence of left ventricular
dysfunction or acute ischemia.13~ Pathologic fourth heart sounds are
commonly present and often associated with an $3 producing a quadruple
rhythm in patients with left ventricular aneurysm and end-stage idiopathic
or ischemic cardiomyopathy. In these conditions, tachycardia or a
prolonged PR interval or both may be present, and $3 and S~ may fuse,
creating a loud summation gallop.
 A prominent S4 may also be caused by excessively rapid late diastolic
filling resulting from vigorous atrial systole, as seen in hyperkinetic states
or acute atrioventricular valve incompetence.146,147 S3 is often associated
with these conditions. With an increase in heart rate, incomplete
summation may occur, mimicking a diastolic rumble, or complete fusion
may take place, generating a loud summation gallop (Figure 9). There may
be a rather marked variation in the intensity of each of these diastolic
sounds, depending on the heart rate. For example, an early diastolic
summation sound may become audible for the first time during
tachycardia, although neither the S3 nor the S4 alone is sufficient to
produce an audible sound. In other situations, a pathologic S3 suddenly
becomes much louder when the rate reaches a point where atrial systole
summates with rapid ventricular filling, although atrial systole alone is not
forceful enough to create an S4. During rapid tachycardia, carotid sinus
pressure may be helpful in dissecting ventricular and atrial components of
a diastolic rumble or summation gallop.
Presystolic and isolated diastolic fourth sounds, as well as summation
gallops, may be heard with varying degrees of heart block. First-degree
heart block facilitates audibility of S4 because it further separates S4 from
Sl. In 2:1 heart block, a previously absent S4 may now be present in
presystole because of increased diastolic volume secondary to
bradycardia. In this situation, isolated fourth sounds may also be audible
during diastole. With complete heart block, fourth sounds may be heard
randomly throughout diastole and may also result in a loud summation
gallop, when atrial contraction summates with rapid early ventricular filling.
Extracardiac Sounds
Pericardial Friction Rubs
Inflammation of the pericardial sac with or without fluid may produce a
friction rub. Characteristically, these friction sounds are very high-pitched
and scratchy, seem close to the ear, and are frequently best heard with
the patient leaning forward or lying prone in deep expiration. The rub
occurs during three intervals of the cardiac cycle when the heart moves
relative to the pericardial sac: During atrial systole, ventricular systole, and
finally during the diastolic wave of rapid ventricular filling. The usual
friction rub occurs during the first two intervals, although three component
rubs may be heard. Three-component friction rubs are common in uremic
pericarditis when a hyperkinetic hypertrophied ventricle is present. With
myocardial infarction, pericardial rubs may be evident during the first week
and last only a few hours.
32
Pulmonic ejection murmurs frequently have a scratchy sound and may
be misinterpreted as friction rubs. The short, scratchy pulmonic ejection
murmur heard in hyperthyroidism (Means Lerman sign) is frequently
mistaken for a pericardial rub.148 However, a scratchy sound should not be
considered a friction rub unless both a systolic and a diastolic component
are heard.
Many clinicians still believe that pericardial friction rubs are not heard
when there is a large amount of fluid in the sac. This is not so because
some points of the visceral and parietal pericardial surfaces are in contact
despite large collections of fluid.
Mediastinal Crunch: Hamman’s Sign
When there is air in the mediastinum, a series of crunching sounds
occurs from time to time, related indirectly to heartbeat and respiratory
excursions.~49 These sounds are characteristically random but most
frequently occur with ventricular systole. Crepitation in the neck due to
subcutaneous air confirms the diagnosis of mediastinal emphysema. The
patient may be aware of the sound and may describe the position or
respiratory phase in which it occurs. Both pericardial friction rubs and
mediastinal crunching sounds due to air in the mediastinum are common
after cardiac surgery.
Pacemaker Sounds
Cardiac pacing from the right ventricular apexoccasionally produces a
brief, high-frequency sound that occurs synchronously with the pacer
impulse just before S~.15o These sounds are due to stimulation of the
intercostal nerves next to the endocardial electrodes, which results in
contraction of the intercostal muscles. Frequently, twitching of the muscle
can be observed. The presence of this sound should always suggest
possible myocardial perforation by the endocardial lead, although this is
not always the case. Stimulation of the pectoral muscles and diaphragm
also reportedly produces this extracardiac sound. These sounds have also
been observed in patients with transthoracically placed epicardial leads.
33

Heart Murmurs
A cardiac murmur is defined as "a relatively prolonged series of audible
vibrations of varying intensity (loudness), frequency (pitch), quality,
configuration, and duration."151 Although the exact physical principles that
govern production of murmurs have long been debated, most authorities
now agree that turbulence is primarily responsible for most murmurs.8,152
Turbulence arises when blood velocity exceeds a critical level due to high
flow, when flow is through an irregular or narrow area, or a combination of
both. Leatham153 has attributed production of murmurs to three main
factors: 1) high flow rate through normal or abnormal orifices, 2) forward
flow through a constricted or irregular orifice or into a dilated vessel or
chamber, and 3) backward or regurgitant flow through an incompetent
valve, septal defect, or patent ductus arteriosus. A combination of these
factors is frequent.
To facilitate description, communication, and comparison of heart
murmurs, they must be classified by timing (systolic or diastolic), intensity,
location, and radiation. It is also important to note the effect of respiration
on a murmur and its constancy over repeated examination.
There is seldom confusion about systole and diastole, since at normal
heart rates, systole is considerably shorter than diastole. However, at rapid
heart rates, the durations of the two intervals are similar. Under these
circumstances, the fact that $2 is the louder heart sound heard at the
base is usually the determining factor. An exception to this rule is severe
mitral stenosis, when the mitral valve closure sound may be louder than
the aortic closure sound, even at the base. Once $2 is identified, murmurs
or extra sounds can be properly located in the cardiac cycle as systolic or
diastolic. If the murmur or sound in question is at the apex, proper timing
can be ensured by the inching technique popularized by Levine and
Harvey.2 Essentially, this technique consists of the clinician slowly moving
the stethoscope down from the base to the apex and mentally noting the
cardiac cycle, using $2 as a reference point. With sinus tachycardia,
carotid sinus pressure may temporarily slow the rate, making it possible to
differentiate systole from diastole. If extra systoles occur, the first sound
after the compensatory pause will be S~.
The most popular classification of murmur intensity is described by
Freeman and Levine.~54 Systolic murmurs are graded 1-6. A grade 1
murmur is audible only after the listener has tuned in. Grade 2 is the
faintest systolic murmur, audible immediately after placing the stethoscope
34 35
on the chest. Grade 5 is a loud murmur that cannot be heard with the
stethoscope removed from the chest wall but can be heard with just the
edge of the stethoscope touching the skin. A grade 6 murmur is audible
with the stethoscope removed from the chest wall. Grades 3 and 4 are
intermediate. Experience has shown that systolic murmurs of grade 3 or
more in intensity are usually hemodynamically significant. Systolic thrills
are usually associated with grade 4 or louder murmurs.
As Leatham153 points out, a murmur’s intensity varies directly with the
velocity of blood flow across the murmur production area. The velocity, in
turn, is directly related to the pressure head that drives the blood across
the murmur-producing area. For example, high flow velocity through a
small ventricular septal defect produces a loud murmur, whereas high flow
at low velocity through an atrial septal defect produces no murmur. The
frequency composition of a murmur is directly related to velocity of blood
flow, as is intensity of the murmur.~55 Low flow velocity resulting from a
small pressure head across a stenotic mitral valve produces a low-pitched
rumbling murmur, whereas the large diastolic pressure head across an
incompetent semilunar aortic valve causes a high-pitched murmur.
The intensity of a murmur as heard at the chest wall is also determined
by the transmission characteristics of the tissues intervening between the
source of the murmur and the stethoscope. Obesity, emphysema, and
significant pleural or pericardial effusion will decrease the intensity of the
murmur, whereas a thin, asthenic body type will often accentuate it. The
location and radiation of a murmur is multifactorially determined by site of
origin, intensity, direction of blood flow, and physical characteristics of the
chest.~56 The duration and time intensity contour (murmur "envelope") of a
specific murmur is intimately related to the instantaneous pattern of blood
flow velocity causing the murmur.
Systolic Murmurs
Systolic murmurs may be categorized as midsystolic ejection or
pansystolic regurgitant. Although any single categorization has serious
deficiencies, the classification popularized by Leatham~53 is attractive
because it has a physiologic as well as a descriptive basis. Systolic
ejection murmurs are due to flow across the left or right ventricular outflow
tract, whereas systolic regurgitant murmurs are due to retrograde flow from
a high-pressure cardiac chamber to a low-pressure chamber.
Systolic Ejection Murmurs
The systolic ejection murmur begins shortly after pressure in the left or Midsystolic Ejection Murmur
right ventricle exceeds aortic or pulmonic diastolic pressure sufficiently to
open the aortic or pulmonic valve. The result is a delay between $1, which
occurs shortly after atrioventricular pressure crossover, and beginning of
the murmur (Figure 10). The murmur then waxes and wanes in a
crescendo-decrescendo fashion described as "diamond-shaped." The
murmur ends before closure of the semilunar valve from the side where it
originates. The contour of the time intensity pattern or envelope of the
murmur corresponds to the contour of flow velocity, and the murmur is
heard when the sound produced during peak turbulence exceeds the
audible threshold.157 Thus, not only is the overall intensity of the murmur Aorta
proportional to the rate of ventricular ejection, but its shape depends on
instantaneous flow velocity during the ejection period. As seen in Figure
11, during normal left ventricular ejection, a disproportionately large
percentage of the stroke volume occurs in early systole. When flow velocity
exceeds the murmur threshold, a short ejection murmur results, and its
envelope corresponds to the flow velocity pattern. If the ventricle’s stroke
volume is increased, the ejection pattern is exaggerated; the resultant
murmur tends to peak early in systole and fade halfway through the
ejection phase. Such murmurs have been described as "kite-shaped" and
are common in high-output states, aortic regurgitation, or heart block,
where stroke volume is high. The flow characteristics of normal right
ventricular ejection are somewhat different in that ejection rates are not
nearly as high and the flow curve peaks later, with a more rounded
contour.158 This flow pattern may explain long systolic ejection murmurs
heard in patients with atrial septal defects and the straight-back syndrome,
where only minimal gradients are found across the right ventricular outflow L.V.
tract. With true outflow obstruction, rapid early ejection is no longer
possible, and the flow pattern becomes rounded, resulting in the more
symmetrical murmur of aortic stenosis. In this situation, the instantaneous
flow pattern is determined by the instantaneous pressure gradient between
the left ventricle and the central aorta.
The intensity of an ejection murmur closely parallels changes in cardiac
output. Any condition that increases forward flow, such as exercise,
anxiety, fever, or increased stroke volume associated with the long diastolic
filling period after a premature beat, increases murmur intensity. S2
Conditions that decrease cardiac output, such as congestive heart failure,
S1
I~-blockade, or other negative inotropic agents, decreases murmur
intensity. At bedside, the intimate flow relation, particularly with beat-to-
Figure 10. Midsystolic ejection murmurs occur during ventricular ejection. As a result,
beat variations, usually allows the clinician to distinguish between the onset of murmur is separated from first heart sound ($1) by period of isometric contraction,
systolic ejection murmur and the systolic regurgitant murmur. and murmur, which is crescendo-decrescendo in nature, stops before respective semilunar
valve closure. LV, left ventricle; $2, second heart sound.

36 37
 Innocent Murmurs. Innocent murmurs are always systolic ejection in
nature and occur without evidence of physiologic or structural
Left Ventricular Ejection Dynamics abnormalities in the cardiovascular system when peak flow velocity in early
systole exceeds the murmur threshold.159 These murmurs are less than
grade 3 in intensity and vary considerably with body position, level of
activity, and from one examination to the next. They are not associated
with a thrill or radiation to the carotid arteries or axilla. They may originate
Murmur "envelope" from flow across either the normal left or right ventricular outflow tract and
always end well before semilunar valve closure.
Innocent murmurs are found in approximately 30-50% of all children;
the vibratory systolic (Still’s) murmur is common, especially in children
aged 3-8 years.160 It has a very distinct quality described as groaning,
croaking, buzzing, or twanging and is heard best along the left sternal
border at the third or fourth interspace. It disappears at puberty. Although
Murmur t h r e s h o I d~1~ its exact cause is controversial, most authorities agree that this murmur
originates from flow across the left ventricular outflow tract. Innocent
murmurs have also been attributed to flow across a normal right
Flow v.elocity ventricular outflow tract and are called innocent pulmonic murmurs
because the site of their maximal intensity is heard best in the pulmonic
area at the second left interspace, with radiation along the left sternal
border. These are low- to medium-pitched, with a blowing quality, and are
common in children, adolescents, and young adults. In adults over 50,
innocent murmurs due to flow across the left ventricular outflow tract are
often heard and may be of high frequency, with a musical quality. They are
frequently auscultated best at the apex. They may be associated with a
Central ~ tortuous dilated sclerotic aortic root, often in the presence of systolic
aorta hypertension. Since both innocent and pathologic ejection murmurs have
the same production mechanism, it is not the nature of the murmur itself
that allows the differential diagnosis but rather associated cardiac findings.
Thus, it is the company the murmur keeps that allows the differential
diagnosis from the pathologic systolic ejection murmur; the innocent
Left murmur must occur during an otherwise normal cardiovascular
ventricle Normal Increased Outflow examination (Figure !2).161
stroke volume obstruction The supraclavicular arterial murmur or bruit is common in normal
individuals, particularly children and adults.IS2 These murmurs are
Figure 11. Left ventricular ejection dynamics are illustrated by simultaneous recording of maximal in intensity above the clavicles and tend to be louder on the right,
left ventricular and aortic pressure, aortic flow velocity, and time intensity envelope of although they are often heard bilaterally. The murmur begins shortly after
murmur. During normal left ventricular ejection (left panel), peak flow velocity is early, with $1, is diamond-shaped, and usually occupies less than half of systole.
two thirds of ventricular volume ejected during first half of systole. Murmur threshold may
Hyperextension of the shoulders is a simple bedside maneuver that
be exceeded during early peak flow and corresponding murmur envelope is inscribed.
Center panel shows exaggeration of normal left ventricular ejection pattern, with large generally decreases intensity of the murmur and often causes it to
stroke volume as seen in high-output states. With critical left ventricular outflow obstruction disappear completely.
(right panel), rapid early ejection is no longer possible; flow velocity is increased and
contour becomes rounded and prolonged, producing typical diamond-shaped murmur of
aortic obstruction.

38 39
 Functional Systolic Ejection Murmurs. Systolic ejection murmurs
produced by high cardiac output states are functional and flow-related but
Differential Diagnosis of the Innocent Murmur are not categorized as innocent murmurs because of their associated
CONDITION EXPIRATION INSPIRATION NOTES
altered physiologic state.159 They include cardiac flow murmurs associated
with thyrotoxicosis, anemia, fever, pregnancy, exercise, and peripheral
$1
A2 A1 Physiologic $3 arteriovenous fistula (Figure 12). These murmurs are often grade 3 and
Innocent so metim es occasionally grade 4 in intensity; however, they always end well before $2
Cardiac Murmur I ,,lllli,,, II I .,,lit,,,, II present
P~ and are only rarely confused with obstruction of the left or right ventricular
outflow tract. They are best interpreted when considering the patient’s
A2 Loud St;S3 overall condition.146 The large stroke volume associated with marked
and $4
High Output
State | I A~ ’’
,=lllll=,,, I ,’llltll’,, I I I often present bradycardia also produces a functional ejection murmur due to the large
$4 P2 $3 $4 P2 S3 stroke volume. When found in complete heart block with atrioventricular
Loud Tt ; wide,
Tt Tt fixed splitting dissociation, beat-to-beat changes in murmur intensity are due to the
of $2; tricuspid random contribution of atrial systole to left ventricular filling. The large
Atrial Septal flow rumble
Defect sometimes heard forward stroke volume associated with significant aortic regurgitation also
M1 P2 M t P2 in diastole produces a prominent systolic ejection murmur. Even though there is no
A A2
significant gradient across the left ventricular outflow tract, the intensity of
Midsystolic this murmur may be grade 4 or 5 and is occasionally associated with a
Mitral Valve click followed
Prolapse by murmur thrill. However, this murmur is rarely confused with significant valvular
C P2 C P2
Loud aortic obstruction because of the peripheral findings of wide-opening aortic
S1 A2 $1 A1 valvular ejection regurgitation. In addition, it always ends well before aortic closure and is
sound and A2;
Mild Valvular soft ARmurmur clearly separated from the early diastolic regurgitant murmur.
Aortic Stenosis commonly present Patients with hemodynamically significant atrial septal defects have a
AVES P2 AVES P1 in diastole
Pulmonic valvular
functional pulmonic ejection murmur due to increased flow across the
St
A2
$1 A2 ejection right ventricular outflow tract. Often grade 3 or 4 in intensity, this murmur
Mild Valvular
Pulmonic
Stenosis IPVES
II P2 PVES
II
I ,,,11!,,,,,, P2
sound loud on
expiration only;
wide physiologic
splitting of $2
ends well before $2 and is differentiated from an innocent murmur by
associated abnormal physical findings. Wide, fixed splitting of $2 is
present, together with a prominent tricuspid closure sound and a
A2 Paradoxical hyperdynamic parasternal impulse (Figure 12).85 Prominent systolic
A2 splitting of
Hypertrophic $4 commonly ejection murmurs, often grade 3 or 4, are heard in patients with straight-
Cardiomyopathy heard back syndrome, pectus excavatum, or both.163 At times, it is difficult to
$4 P2 $4 P2
distinguish this condition from an atrial septal defect because audible
expiratory splitting may be present, and a prominent pulmonary artery
Figure 12. Differential diagnosis of innocent murmur versus pathologic systolic murmur by
the company the murmur keeps. Innocent murmur must be found in otherwise normal shadow is seen on the chest x-ray film due to the narrow anterior-posterior
cardiovascular examination. $1, first heart sound; $2, second heart sound; $3, third heart diameter. The correct bedside diagnosis can usually be made by careful
sound; S4, fourth heart sound; A2, aortic valve closure sound; P2, pulmonary valve closure examination of the spinal column, thoracic cage, and sternum.
sound; T1, tricuspid valve closure sound; M1, mitral valve closure sound; C, midsystolic
nonejection sound; AVES, aortic valvular ejection sound; PVES, pulmonic valvular ejection Ejection Murmurs Secondary to Dilated Great Vessels. Dilation of the
sound; AR, aortic regurgitation.
aortic root from hypertension, arteriosclerosis, or frank aneurysm formation
often produces a short ejection murmur, usually grade 2 or 3 in intensity.
In an elderly person, it is auscultated best at the apex, having a high-
frequency composition. Similar short pulmonary systolic ejection murmurs
may also be caused by right ventricular ejection into a massively dilated
pulmonary artery, as in idiopathic dilation of the pulmonary artery.46 A

41
40
short systolic ejection murmur frequently associated with a prominent late
pulmonary ejection sound may also be present in dilation of the
pulmonary artery secondary to severe pulmonary hypertension of any
cause. The etiology of this murmur is identified by the associated physical
findings of severe pulmonary hypertension, which are always present,
including a prominent parasternal impulse with increased intensity of the
pulmonary component of $2, which is well-heard at the apex. There are
prominent A waves in the neck and a right-sided $4 that increases with
inspiration when the ventricular septum is intact. The early diastolic
murmur of pulmonary regurgitation secondary to severe pulmonary
hypertension is often present. If pulmonary hypertension is associated with
intracardiac shunting, cyanosis is frequently present.
Ejection Murmurs Secondary to Left Ventricular Outflow Tract
Obstruction. Obstructed left ventricular outflow may be congenital or
acquired and may be located at the valvular, supravalvular, or subvalvular
level.lr~ Stenosis is occasionally present at more than one level.
The murmur of the stenotic left ventricular outflow tract, regardless of
site, is crescendo-decrescendo, and its contour closely parallels the
instantaneous pressure gradient. As long as cardiac output is maintained,
there is an excellent correlation between intensity and length of the
murmur and severity of obstruction (Figure 13). The valvular aortic
stenosis murmur is heard best at the second right and second and third
left intercostal spaces and radiates widely into the neck and along the
great vessels. If loud enough, it may be heard over the cervical vertebrae,
the base of the skull, or as far distally as the olecranon process. When the
murmur radiates to the apex, the high-frequency components predomi-
nate; the apical murmur has a higher pitch and, frequently, a musical
composition.165 This characteristic change of pitch between proximal and
distal radiation of the murmur is often a source of confusion during
auscultation. Despite the urge to designate it a separate murmur, repeated
observations show that this murmur, regardless of its timbre or harmonics,
retains its diamond-shaped configuration whenever it is heard or recorded.
The differential diagnosis of a murmur heard at the cardiac apex in
aortic stenosis may be difficult. At times, the ejection murmur is heard
predominantly or exclusively at the apex and retains its diamond
configuration. However, neither semilunar valve closure sound may be
audible, the most helpful finding in defining a murmur as ejection in
nature. Since an additional mitral regurgitation murmur is frequently heard
in patients with aortic stenosis, the differential diagnosis is even more
important. Fortunately, systolic ejection murmurs vary greatly with
changing cycle lengths, unlike regurgitant murmurs.166 In the presence of
atrial fibrillation or frequent extrasystoles, this differing response to
variations in cycle length may be helpful. As heart rate changes, the
42
Valvular Aortic Stenosis, Valvular Aortic Stenosis,
Mobile Valve. Progressive Calcific Fixation
SI E $2 S1 E= _
SEM
Mild
A2 P2 A2 P2
Moderate~
Severe-- Sever~
S~
$4
Figure 13. Left panel: In valvular aortic stenosis with mobile valve, both aortic valvular
ejection sound (Ei) and aortic valve closure sound (A2) are well preserved, even with
moderate-to-severe stenosis. As severity of obstruction increases, duration of murmur
increases and A2 is progressively delayed, leading to reversed splitting with paradoxical
movement in severe cases. With left ventricular hypertrophy, prominent fourth heart sound
($4) develops and intensity of first heart sound ($1) decreases. Right panel: In adults,
particularly the elderly patient with valvular aortic stenosis, progressive calcific fixation of
valve occurs over time, resulting in decreased intensity or complete disappearance of aortic
valvular ejection sound. Likewise, there is progressive decrease in intensity of A2 and
although reversed splitting occurs, it is more difficult to appreciate at bedside since, in
addition to diminished A~, pulmonic valve closure sound (P=) may also be enveloped by
murmur. In both situations, murmur is crescendo-decrescendo, ending before A2, and its
intensity correlates well with severity of obstruction if cardiac output is maintained. When
cardiac output is depressed, severity of obstruction correlates best with murmur’s duration.
SEM, systolic ejection sound; S~, second heart sound.
regurgitant murmur changes only slightly, whereas there is a very obvious
and startling change in intensity of the ejection murmur. Under these
circumstances, the apical murmur may be identified as radiation of an
ejection murmur or an additional regurgitant murmur of mitral regurgi-
tation. This same effect may also be obtained pharmacologically by
inhalation of amyl nitrite, which lowers peripheral vascular resistance and
increases cardiac output. With an increase in the mean ventricular
43
ejection rate, the aortic stenosis murmur becomes much louder, whereas
the mitral regurgitation murmur usually decreases or changes little in Pulmonic Stenosis Tetralogy of Fallot
intensity.
A loud valvular ejection sound is the hallmark of congenital valvular $1 S2 S1 S2
aortic stenosis and is also present in rheumatic valvular aortic stenosis as
long as the valve is mobile.38 This sound is absent in both congenital Mild
supravalvular aortic stenosis and fixed subvalvular aortic stenosis. When
the stenotic rheumatic or congenital aortic valve becomes immobile due to A2
P.Ej
calcific fixation, the ejection sound decreases in intensity or may
$1 S2 S1 S2
completely disappear. With a progressive increase in severity of left
ventricular outflow obstruction, the duration of left ventricular ejection is
prolonged, resulting in narrow, single, or reversed splitting of $2 (Figure Moderate
13). When the aortic stenosis murmur is accompanied by reversed
splitting of $2 with paradoxical movement, severe obstruction is always
present. If this combination occurs without a diastolic aortic regurgitation
murmur but with a quick-rising carotid pulse, the diagnosis of obstructive
hypertrophic cardiomyopathy should be considered.
Severe
Ejection Murmurs Secondary to Right Ventricular Outflow Tract
Obstruction. Obstructions to right ventricular outflow are congenital P2 A.Ej A2
anomalies and may occur at the level of the valve, the infundibulum, or the
proximal or distal branches of the pulmonary artery. Isolated infundibular P.Ej = Pulmonary Ejection A.Ej = Aortic Ejec’tion
pulmonic stenosis with an intact septum is rare. Pulmonary obstruction at (Valvular) (Root)
this level is usually associated with a large ventricular septal defect
(tetralogy of Fallot). In pure valvular pulmonic stenosis with an intact Figure 14. In valvular pulmonic stenosis with intactventricular septum, right ventricular
ventricular septum, the right ventricular ejection phase lengthens as the systolic ejection becomes progressively longer, with increasing obstruction to flow. As a
result, murmur becomes louder and longer, enveloping aortic valve closure sound (A2).
obstruction becomes more severe. As a result, the pulmonic closure Pulmonic valve closure sound (P2) occurs later and splitting becomes wider but is more
sound is progressively delayed, splitting widens, and the lengthening difficult to hear, because A2 is lost in murmur and P2 becomes progressively fainter and
pulmonic murmur progressively encroaches on, masks, and finally lower pitched. As pulmonic diastolic pressure progressively decreases, isometric
completely envelops the aortic closure sound (Figure 14).43 At the same contraction shortens until pulmonary valvular ejection sound fuses with first heart sound
time, pulmonic closure that is normal or increased in intensity in mild ($1). In severe pulmonic stenosis with concentric hypertrophy and decreasing right
ventricular compliance, fourth heart sound ($4) appears. In tetralogy of Fallot with
pulmonic stenosis becomes progressively fainter, and in the most severe increasing obstruction at pulmonic infundibular area, more and more right ventricular blood
cases, may become inaudible (although it can usually be recorded on is shunted across silent ventricular septal defect, and flow across obstructed outflow tract
phonocardiogram). With progressively severe pulmonic valve obstruction, decreases. Therefore, with increasing obstruction, murmur becomes shorter, earlier, and
the rising right ventricular end-diastolic pressure approximates or exceeds fainter. P2 is absent in severe tetralogy of Fallot, large aortic root receives almost all cardiac
pulmonary artery end-diastolic pressure and causes the pulmonary valve output from both ventricular chambers, and aorta dilates and is accompanied by root
ejection sound, which does not vary with respiration. S~, second heart sound.
to partially open before onset of systole. As a result, when contraction
starts, the valve has a shorter distance of excursion remaining, and the
ejection sound migrates toward $1 and may fuse with it. In severe
pulmonic valvular stenosis, a forceful right atrial contraction may actually
exceed right ventricular end-diastolic pressure, causing doming of the
stenotic valve in late diastole, and a presystolic click becomes audible.43,44
With progressive right ventricular hypertrophy and decreased compliance
associated with severe pulmonic stenosis, a right-sided $4 associated with

44 45
a prominent A wave in the neck occurs. Isolated infundibular pulmonic Pansystolic Regurgitant Murmurs
stenosis causes the same murmur, but the pulmonic valvular ejection
sound and the pulmonic closure sound are absent. Pansystolic regurgitant murmurs are produced by retrograde flow from a
high-pressure chamber to one of lower pressure.153 Mitral regurgitation,
The hemodynamic situation is quite different in tetralogy of Fallot.167,168 tricuspid regurgitation, and ventricular septal defect murmurs are classic
Here the murmur is due to right ventricular outflow obstruction, usually examples. Since there is usually a high-pressure differential between the
primarily infundibular, and as a result, the pulmonary closure sound is two chambers throughout systole, the murmurs are holosystolic in
absent in all but the mildest cases. The more severe the obstruction, the duration, high-pitched and blowing in quality, with a plateau-like
lower the blood flow across the pulmonary outflow tract, and the more configuration. Pansystolic regurgitant murmurs begin with $1 and continue
blood is shunted through the septal defect, which is a silent avenue of
up to and through the aortic closure sound. In mitral regurgitation, the
escape. With increasing severity of pulmonic infundibular obstruction, the murmur continues through the aortic closure sound because left
murmur shortens, and cyanosis deepens (Figure 14). During hypercyanotic ventricular pressure is still higher than left atrial pressure after aortic valve
episodes in children with tetralogy of Fallot, the murmur may actually
disappear. In the most severe forms of tetralogy of Fallot with pulmonary
atresia, frequently called pseudotruncus arteriosus, there is no flow across
the pulmonary valve and no systolic ejection murmur. Instead, there is a Pansystolic Regurgitant Murmur
continuous murmur of increased flow through the enlarged bronchial
arteries.
It should be remembered that the aorta is large and somewhat
transposed in tetralogy of Fallot. A very clear aortic closure sound is heard
in the pulmonic area, but it is single and due to aortic valve closure. An
aortic root ejection sound can frequently be heard in the same area,
originating from the dilated aorta. In adults, an ejection sound may also Aorta
indicate valvular obstruction in addition to infundibular stenosis.45
Both valvular pulmonic stenosis and isolated infundibular pulmonic
stenosis with intact septum can be differentiated from tetralogy of Fallot by
noting marked intensification of the ejection murmur after inhalation of
amyl nitrite. In contrast, the tetralogy of Fallot murmur shortens and
decreases in intensity.IS9
In branch stenosis of the pulmonary artery, there is a systolic murmur of L.A
varying intensity at the upper left sternal border that is widely transmitted
to the right chest, back, and both axillae. The murmur is usually less
harsh and higher pitched than a valvular stenosis murmur. With more I
L.Vo
peripheral branch stenosis, systolic ejection murmurs or even continuous I
murmurs may be heard over the lung fields. The wide radiation of this
murmur is particularly helpful in alerting the clinician to this type of right-
sided obstruction.

S1 A2
Figure 15. Pansystolic regurgitant murmur of mitral regurgitation begins with.and may
replace first heart sound ($1). This murmur continues up to and through aortic valve
closure sound (A2), as ventricular pressure continues to exceed left atrial (LA) pressure.
Murmur has plateau configuration and varies little with respiration. LV, left ventricle.

46 47
closure, and regurgitation continues (Figure 15). In ventricular septal
defect, the same pressure differential occurs after aortic closure. In this
condition, left ventricular pressure is still higher than right ventricular
pressure at the time of aortic closure, and the murmur continues. In
tricuspid regurgitation, the murmur continues through aortic closure up to
and enveloping the pulmonic closure sound.
Mitral Regurgitation. The mitral regurgitation murmur is blowing in
character and is heard best at the apex, radiating well into the axillae.
When the murmur is loud, it may actually replace $1; only the loudest
murmurs are associated with a thrill. This murmur frequently has a late
systolic accentuation, particularly in pansystolic prolapse of the mitral
valve, varies little with respiration, and is frequently accompanied by a
loud early diastolic filling sound ($3) and a short diastolic rumble. When
the filling sound becomes loud and high-pitched, it may be confused with
$2; if so, it will be thought that the murmur stopped long before aortic
closure, and it may be confused with an ejection murmur. In contrast to
the systolic ejection murmur, there is little variation in intensity with varying
cycle lengths.IF0 Murmur intensity is directly related to the pressure
gradient between the left ventricle and the left atrium. Therefore,
vasoactive drugs such as amyl nitrite, which decrease the left ventricular-
left atrial gradient, produce a decrease in the intensity of the murmur,
whereas vasoconstrictive agents such as neosynephrine increase the
gradient, resulting in increased murmur intensity.
Tricuspid Regurgitation. The tricuspid regurgitation murmur is best
heard at the lower left sternal border, but with a large right ventricle, it may
be heard laterally to the midclavicular line. This means that the right
ventricle occupies the region of the cardiac apex. Although occasionally
heard more laterally, this murmur does not radiate well into the axillary
region. Even when the tricuspid regurgitation murmur is heard best at the
apex, it can still be identified, since it characteristically is strongly
influenced by respiration.~71,~72 During continuous accentuated respiration,
the murmur is heard to increase at the beginning of inspiration and to
fade during early expiration. In severe heart failure, this respiratory
variation may be absent, but it reappears as compensation improves. It is
likely that in severe decompensation, little augmentation of venous return
and right ventricular filling occurs with inspiration. Simultaneous
observation of the jugular venous pulse while auscultating this murmur will
be of further help in defining its origin. A prominent V wave with a rapid Y
descent is seen, which is augmented with inspiration. It is extremely
important to differentiate the tricuspid regurgitation murmur from the mitral
regurgitation murmur. In patients with rheumatic mitral stenosis,
accompanying mitral regurgitation may be a contraindication to mitral
48
commissurotomy or valvuloplasty and rather indicates the need for valve
replacement. On the other hand, tricuspid regurgitation in mitral stenosis
is usually due to right ventricular hypertension with a secondarily dilated
tricuspid ring; since this sequence is the result of severe mitral stenosis, it
usually regresses after successful relief of the mitral obstruction, as there
is a subsequent fall in pulmonary artery pressure.~73 In this situation, mitral
commissurotomy or valvuloplasty to relieve mitral obstruction may be the
treatment of choice. Although not generally appreciated, pure tricuspid
regurgitation can give rise to a short diastolic rumble initiated by a right
ventricular gallop, much like the rumble that occurs in pure mitral
regurgitation. Both the gailop and the subsequent rumble increase on
inspiration.IF4
Ventricular Septal Defect. The pansystolic murmur of ventricular septal
defect is heard best just off the sternal border in the fourth, fifth, and sixth
intercostal spaces and is usually accompanied by a prominent thrill.~75,~76
The murmur does not radiate to the axillae, as with mitral regurgitation,
and does not have the respiratory variation characteristic of tricuspid
regurgitation. Wide physiologic splitting with an easily heard P2 is usual,
with significant left-to-right shunting. When the shunt is large, there is a left
ventricular $3 followed by a short mitral flow rumble. The systolic murmur
is due to high-velocity flow from the high-pressure left ventricle to the lower
pressure right ventricle, and its intensity correlates poorly with the degree
of shunting. For example, a grade 5 murmur may be associated with a
very high velocity flow through a small, hemodynamically insignificant
muscular ventricular septal defect.177 On the other hand, an equally loud
murmur associated with a thrill may be present with a large defect, having
massive left-to-right shunting. However, when the defect is very large, left
and right ventricular pressure is equal. As a result, no murmur is
produced across the defect; instead, a short pulmonary ejection murmur is
present secondary to severe pulmonary hypertension (Eisenmenger’s
ventricular septal defect).~78 The typical pansystolic murmur of ventricular
septal defect is very sensitive to vasoactive agents; with administration of
amyl nitrite, there is a marked decrease in both left ventricular-right
ventricular pressure gradient and intensity of the murmur.
Variations of the Pansystolic Regurgitant Murmur
Early Systolic Regurgitant Murmurs. Rarely, a regurgitant murmur
may be confined to early systole, as in the presence of a small ventricular
septal defect. This murmur begins in the usual manner, at onset of
ventricular systole, and stops suddenly in early or midsystole (Figure
6).~79,~80 The murmur ceases because ventricular size decreases as
ejection continues, and the small defect is sealed shut as the ventricular
49
septum thickens during systole, resulting in cessation of flow through the
defect. This murmur is important because it is typical of the type of
ventricular septal defect that may disappear with age. Variants of the Pansystolic Regurgitant Murmur
In contrast to the classic pansystolic murmur of chronic mitral Pansystolic Murmur
regurgitation, acute severe mitral regurgitation may appear as an early Sl S2 Sl S2
systolic murmur, ending well before aortic closure.181-183 Conditions
Mitral Regurgitation
causing acute mitral regurgitation include spontaneous rupture of a Tricuspid Regurgitation
chordae tendinae of a myxomatous valve, acute or subacute bacterial Ventricular Septal Defect
endocarditis of the mitral valve, papillary muscle rupture or dysfunction
Early Systolic Murmur
secondary to acute myocardial infarction, and rupture of the mitral
apparatus due to trauma.184-187 In each of these conditions, large volume Sl $2 $1 S2
flow regurgitates into the relatively normal left atrium, which has not had
Small Ventricular Septal
time to make the adaptive changes in compliance that occur in long- Defect
standing chronic mitral regurgitation. As a result, an extremely high V
wave is generated in the left atrium, abolishing the left ventricular-left atrial
gradient during the latter part of systole, resulting in termination of S2 $2
retrograde flow and abbreviation of the systolic murmur (Figure 16).
Audible expiratory splitting with an accentuated 92 is present, and a loud Acute Mitral Regurgitation
$4 is recorded at the apex. $4 associated with a prominent presystolic
impulse on palpation is an important clue indicating acute mitral
Late Systolic Murmur
regurgitation since it is rarely present in chronic mitral regurgitation.1"7 The
$2
systolic murmur of acute mitral regurgitation may have classic radiation to Mitral Valve Prolapse
Sl S2 $1

the axillae and back, but on occasion the murmur is conducted to the
base of the heart and great vessels, simulating aortic stenosis. The quick-
rising carotid pulse with rapid runoff, as well as wide physiologic splitting
of acute mitral regurgitation, readily allows differentiation from aortic
stenosis.188
The systolic murmur of organic tricuspid regurgitation is often not
impressive and is heard as an early systolic murmur ending well before
A2, even in severe regurgitation.189 In this situation, right ventricular
pressure is normal and massive regurgitation may be present, with only a
small pressure gradient between the right ventricle and the right atrium.
This small pressure head results in low-velocity flow, minimal turbulence,
and a soft abbreviated murmur. The murmur retains the characteristic
inspiratory augmentation seen in right-sided regurgitant murmurs and is
frequently associated with $4, which increases in intensity with inspiration.
Large V waves are readily apparent in the jugular venous pulse, which is
also augmented with inspiration, and are helpful in making this subtle
diagnosis.
Papillary Muscle Dysfunction
Figure 16. In addition to classic pansystolic regurgitant murmur seen in mitral
regurgitation, tricuspid regurgitation, and ventricular septal defect, variations exist. In
patients with small ventricular septal defects, murmur that starts with first heart sound ($1)
may suddenly stop during early or midsystole, purportedly because ventricular volume
becomes smaller after maximal ejection, defect seals shut, and murmur ceases. In acute
mitral regurgitation, regurgitant murmur may end well before aortic valve closure sound as
a result of extremely high left atrial V wave, which abolishes left ventricular-left atrial
pressure gradient during late systole. $1 may be soft if flail mitral leaflet is present and is
preceded by prominent fourth heart sound ($4). Audible expiratory splitting with
accentuated pulmonic valve closure sound is present. Midsystolic to late systolic regurgitant
murmurs may be due to papillary muscle dysfunction and prolapse of mitral or tricuspid
valve. In latter conditions, valve is competent in early systole, but as ventricular volume
decreases, leaflets become incompetent and murmur begins, building in late systole and
becoming maximal at time of second heart sound ($2).

Midsystolic and Late Systolic Regurgitant Murmurs. Midsystolic

murmurs can occur with mitral regurgitation due to papillary muscle
dysfunction, as originally described by Bumh et al.~90 The timing of this
murmur may also be late systolic, and may be intermittent or constant,

50 51
occurring with ischemia or infarction of either the posterior medial or
anterolateral papillary muscle. These murmurs are often transient and
provoked by episodes of ischemia.
Mitral valve prolapse is the most frequent cause of late systolic
murmurs; indeed, this entity is one of the most common causes of systolic
murmurs seen in clinical practice. It is best heard at the apex and often
has a tendency to crescendo in late systole (Figure 16). It is frequently
introduced or accompanied by single or multiple nonejection clicks. At
times, these clicks occur independently without an accompanying murmur.
Echocardiographic studies have shown that the click occurs near the time
of maximal prolapse in midsystole, and the late systolic murmur continues
up to and through A2 due to prolapse of the leaflets during the remainder
of systole.
The timing and intensity of these murmurs vary with physiologic and
pharmacologic maneuvers that alter the end-diastolic volume of the left
ventricle (Figure 3). These murmurs are also sensitive to conditions that
alter the peripheral vascular impedance and to changes in myocardial
contractility.57 These variations in timing and duration of the murmur can
be most easily understood by considering mitral valve prolapse a condition
in which the valve is too big for the ventricle. This valvuloventricular
disproportion is manifested at a given geometric size and configuration
during left ventricular emptying. Situations that decrease end-diastolic
volume, decrease peripheral vascular impedance, or increase contractility
allow the heart to reach this size and geometry earlier in systole, resulting
in earlier onset of the click and a longer murmur. Increased heart size and
peripheral vascular impedance and decreased contractility will have the
opposite effect, with the click moving toward $2 and the murmur becoming
shorter. These dynamic changes can best be heard at the bedside by
examining the patient in the supine, left lateral, sitting, and standing
positions, and during prompt squatting. Inhalation of amyl nitrite is also
helpful at the bedside, causing the murmur to become earlier, longer, and
at times pansystolic, with the click migrating toward $1. Late systolic
murmurs may also originate from prolapse of the tricuspid valve.IF4
Systolic "Whoop" or "Honk." Occasionally, a loud musical or
sonorous vibratory systolic murmur may be heard at the apex in patients
undergoing an otherwise normal cardiovascular examination.2,~9~ These
murmurs are loud, high-pitched, musical, and frequently intermittent and
are heard best at the apex in late systole. They may vary strikingly with
respiration, from beat to beat, and from examination to examination. Often,
nonejection sounds are also auscultated. These murmurs are associated
with ballooning of the mitral valve or mitral regurgitation, or both, and their
unusual quality is secondary to high-frequency vibrations of the mitral
apparatus.192,193 The systolic whoop or honk, together with a late systolic
52 53
murmur, with or without associated clicks, is part of the continuum
representing abnormalities of the mitral apparatus of varying etiologies.
Similar honking noises, with or without clicks, may originate in the
tricuspid valve and have also been produced by transvenous catheters
situated across the valve. Murmurs of tricuspid origin are best auscultated
at the fourth left intercostal space and have the typical inspiratory
augmentation of tricuspid murmurs.
r~urmurs of Hypertrophic Obstructive Cardiomyopathy
Frequently during auscultation, the skilled clinician has difficulty
deciding whether the systolic murmur found in hypertrophic
cardiomyopathy is an ejection or regurgitation.~94 Simultaneous sound,
pressure, and echocardiographic recordings have given insight into the
mechanism of this systolic murmur, demonstrating that systolic anterior
motion of the mitral apparatus impinges on the massively thickened
ventricular septum, producing high-velocity flow in middle and late
systole.195 This results in a typical midsystolic ejection murmur, usually with
its maximal intensity at the left sternal edge. However, varying degrees of
mitral regurgitation may also be present during systole due to the distorted
mitral apparatus, resulting in a middle to late systolic regurgitant murmur.
Thus, the resulting auscultated murmur is the summation of both murmurs
as transmitted to the chest wall.196-198 When auscultated at the base, the
murmur is usually an ejection, whereas it becomes more regurgitant as
the stethoscope is inched toward the apex.
In patients with dynamic left ventricular outflow gradients, the intensity of
both the systolic ejection murmur and the mitral regurgitant murmur varies
directly with the magnitude of the pressure gradienU94,195,~99 Thus,
physiologic and pharmacologic interventions that increase the pressure
gradient increase the intensity of the precordial murmur and vice versa.
Decreases in left ventricular preload and afterload or increases in left
ventricular contractility are associated with increases in the pressure
gradient and the murmur, whereas increases in left ventricular preload and
afterload or decreases in contractility will decrease the pressure gradient
and murmur intensity.195,196,199,200 For example, both upright posture and
the strain phase of the Valsalva maneuver decrease venous return, and
the murmur increases in intensity. While reclining or with prompt
squatting, augmented venous return increases left ventricular preload, and
the murmur decreases in intensity. Vasoactive drugs such as amyl nitrite
decrease blood pressure, and a marked increase in intensity of the
murmur occurs, whereas vasoconstrictive drugs such as phenylephrine
increase afterload, decreasing or abolishing the murmur. It should be
noted that the response of the hypertrophic cardiomyopathy murmur to
vasoactive agents is exactly opposite to that of the pansystolic regurgitant
murmurs of mitral regurgitation and ventricular septal defect.200
 In the absence of a left ventricular outflow gradient, the hypertrophic
cardiomyopathy murmur is less impressive, although a short ejection
murmur is usually recorded due to rapid early left ventricular ejection.201
There is also little variation in intensity of this murmur with changes in
preload, afterload, or contractility. In most patients with hypertrophic
cardiomyopathy murmurs, massive left ventricular hypertrophy is present,
and a prominent presystolic impulse associated with a left ventricular $4 is
the rule when normal sinus rhythm is present.
Diastolic Murmurs
Diastolic murmurs have two basic mechanisms of production: Diastolic
filling murmurs or rumbles due to forward flow across the atrioventricular
valves, and diastolic regurgitant murmurs due to retrograde flow across an
incompetent semilunar valve.2o2
Diastolic Filling Murmurs (Rumbles)
Diastolic rumbles are caused by forward flow across the atrioventricular
valves, and their onset is delayed from their respective closure sounds by
isovolumic relaxation. Following this period, when atrial pressure exceeds
declining ventricular pressure, the atrioventricular valves open and filling
begins. The two phases of rapid ventricular filling are early diastole and
presystole. These murmurs tend to be most prominent during these two
filling periods. Because flow velocity is relatively low, these murmurs have
a low-frequency content and rumble.
Mitral Stenosis
The mitral stenosis rumble is heard best at the apex or slightly medial to
the apex impulse. It is preceded by an opening snap (if the valve is
mobile) and continues throughout diastole, with presystolic accentuation
when obstruction is severe (Figure 17). In significant mitral stenosis, rapid
early diastolic filling does not occur, and it has been stated that a filling
sound from the left side is not heard. However, in young patients with
significant mitral stenosis, $3 gallops have been recorded, superimposed
on early diastolic vibrations of the rumble, and are attributed to coupling of
the active heart with the chest wa11.132 Since increased flow across the
relatively normal valve may produce murmurs of higher frequency and
amplitude than the murmur of true stenosis, a loud rumble is not
correlated with severe obstruction. On the other hand, the length of the
diastolic murmur correlates directly with severity of obstruction (Figure 17).
54 55
Diastolic Filling Murmur (Rumble)
Mitral Stenosis
Mild
s~ s2
A2 P2 A2 P2
Figure 17. In mild mitral stenosis, diastolic gradient across valve is limited to two phases
of rapid ventricular filling in early diastole and presystole. Rumble occurs during either or
both periods. As stenotic process becomes severe, large gradient exists across valve during
entire diastolic filling period and rumble persists throughout diastolic filling period. As left
atrial pressure becomes higher, time from aortic valve closure sound (A2) to opening snap
(OS) shortens. In severe mitral stenosis, secondary pulmonary hypertension results in
louder pulmonic valve closure sound (P~) and splitting interval usually narrows. S1, first
heart sound; S~, second heart sound.
Length of a given diastolic rumble should be carefully observed. Therefore,
in atrial fibrillation, the clinician must listen, long enough to hear several
series of slower beats with long diastolic filling times, since, during
tachycardia, a rumble of mild mitral stenosis may continue to S~ because
of the short diastolic flow period. Carotid sinus pressure with temporary
slowing of the heart may uncover the true potential length of the diastolic
rumble. In normal sinus rhythm, the presystolic murmur crescendos up to
$1. Although some components of the rumble may be attributed to
increased flow secondary to left atrial systole, phonoechocardiographic
studies suggest that this murmur is also due to high-velocity antegrade
flow through a progressively narrowing mitral orifice during early
ventricular systole.203 This latter mechanism is also responsible for the
crescendo presystolic murmur observed in patients with mitral stenosis
and atrial fibrillation after a short cycle length.204
 Obstruction of the mitral orifice can also be produced by a left atrial
tumor, and the diastolic rumble is very similar to that produced by mitral
stenosis.11o A loud tumor "plop" is present instead of the opening snap,
and the presystolic crescendo murmur occurs as the protruding tumor
mass rapidly returns through the mitral orifice into the left atrium during
early ventricular systole. A systolic murmur of mitral regurgitation may also
be present, and both murmurs may vary from examination to examination
and with changes in posture.
Tricuspid Stenosis
The tricuspid stenosis murmur is usually heard in the xiphoid area, just
off the sternal border. Since right atrial systole occurs earlier than left, in
the presence of tricuspid stenosis, the presystolic murmur may have a
diamond configuration, even with normal PR intervals, and presystolic
accentuation of the diastolic rumble may actually have passed before
$1.205 This early presystolic diamond-shaped murmur with inspiratory
augmentation, together with a large A wave in the neck, is helpful in
uncovering tricuspid stenosis in the presence of mitral stenosis.206 When
atrial fibrillation is present, the tricuspid murmur is in mid-diastole with the
typical inspiratory augmentation. However, it is often difficult to hear and
must be sought with a high index of suspicion, since both the presystolic
murmur and large A waves alerting the clinician to this diagnosis are
absent.207
Diastolic Rumbles Due to High Flow Across
the Atrioventricular Valve
High-velocity flow across the normal or a regurgitant atrioventricular
valve may result in short mid-diastolic rumbles, often introduced by an $3,
and should not be confused with murmurs produced by true obstructions
of the atrioventricular valves. Such rumbles are common in both
ventricular septal defect and patent ductus arteriosus due to a large flow
across the mitral valve secondary to the left-to-right shunt.~76,208 Likewise,
the left-to-right shunt in the large atrial septal defect produces a tricuspid
rumble.85 Similar low-pitched rumbles may also be present in hyperkinetic
states. Phonoechocardiography has shown that these murmurs occur
during the rapid closing motion of the mitral valve, suggesting a functional
obstruction during rapid early diastolic filling.209 Short diastolic rumbles
after an $3 are characteristic of severe mitral and tricuspid regurgitation;
the latter point is not generally appreciated. In the past, patients with pure
mitral regurgitation or pure tricuspid regurgitation and short diastolic
rumbles were thought to have a combination of regurgitation and stenosis
of the atrioventricular valve. The tricuspid flow rumble, in contrast to the
mitral flow rumble, increases in intensity with inspiration and is associated
56 57
with prominent V waves in the neck.
Flow across an atrioventricular valve that is distorted but not
hemodynamically stenotic to a significant extent may result in a short
diastolic rumble during early rapid filling or in presystole as a result of
atrial contraction. Mitral valvulitis during acute rheumatic fever may cause
such a short rumble (Carey Coombs murmur).2~o The combination of an
$3 with a short rumble indicates that there is not enough obstruction of the
valve to alter the characteristics of rapid early ventricular filling.
Austin Flint Murmur
In severe aortic regurgitation, early diastolic ventricular filling occurs
simultaneously from the left atrium and the aortic root. The anterior leaflet
of the mitral valve forms a curtain that separates the inflow and outflow
tracts of the left ventricle; as aortic regurgitation contributes to rapid
ventricular filling, the rapidly increasing left ventricular volume causes the
mitral valve to partially close in middle and late diastole. As a result, flow
from the atrium to the ventricle occurs through a partially narrowed orifice,
and a rumbling murmur develops.21~-2~3 Flint214 described an apical
presystolic murmur observed in two patients with considerable aortic
regurgitation and no evidence of mitral stenosis at autopsy. Since its
original description, the timing of this murmur has been extended to
include a mid-diastolic component. It is best heard at the apex and has
many of the qualities of the mitral stenosis murmur; however, it is
introduced by an $3 rather than by an opening snap, and S~ is of normal
or decreased amplitude.2~5 Maneuvers or pharmacologic agents that
increase the degree of aortic regurgitation, such as hand grip or
vasoconstrictive drugs, will increase intensity of the rumble, whereas
vasodilating agents such as amyl nitrite will decrease intensity.2~2,216 In the
most severe cases of aortic regurgitation, particularly acute, the presystolic
component of the Austin Flint murmur is lost. In this situation, there is
marked elevation of left ventricular end-diastolic pressure, and the reverse
pressure gradient between the left ventricle and the left atrium causes
premature closure of the mitral valve.
Diastolic Regurgitant Murmurs
Pandiastolic Aortic Regurgitant Murmurs. When the aortic valve
becomes incompetent during diastole, a blowing, high-pitched diastolic
murmur ensues (Figure 18). Isovolumic relaxation of the ventricle is very
rapid. A high gradient quickly develops between the aorta and the left
ventricle, and the murmur builds to maximum intensity almost
instantaneously. Thereafter, as the gradient between the two chambers
slowly falls, the murmur is decrescendo up to the next S~. The murmur of

Early Diastolic Murmur
S~ $2 S~ $2
Pulmonic regurgitation
(with pulmonary
hypertension)
S1 S2 Sl S2
(without pulmonary
hypertension)
Figure 18. In aortic regurgitation or pulmonic regurgitation secondary to pulmonary
hypertension, murmur begins almost simultaneously with second heart sound ($2). Since
gradient between aorta and left ventricle is maximal almost instantaneously and then slowly
decreases, murmur is also high-pitched, slow decrescendo. In contrast, organic pulmonary
regurgitation without pulmonary hypertension is manifested by murmur that starts later and
has rapid crescendo with longer decrescendo. This murmur is lower pitched than usual
early diastolic blowing murmur because regurgitant flow is across lower pressure system
with small gradient. $1, first heart sound.
aortic regurgitation characteristically has the highest pitch of the
commonly heard cardiac murmurs and lies in the frequency range to
which the ear is most sensitive. Yet this murmur is frequently missed
because the listener’s attention is directed toward the lower-pitched heart
sounds and systolic murmurs. At other times it is missed because the
examiner does not actually listen for it. Although the frequency of the
murmur is in the range of the human ear, the amplitude of the vibrations
may be very small and the murmur faint. The murmur may be overlooked
if the examiner does not listen with the patient sitting up and leaning
forward, and if the diaphragm of the stethoscope is not pressed firmly
against the chest wall. In addition, since the murmur has a pitch similar to
that of respiratory sounds, the clinician should listen with the patient in
deep, fixed expiration.
In a given individual, the degree of aortic regurgitation is directly
proportional to the pressure head driving the flow in a retrograde fashion.
Pharmacologic agents or maneuvers that increase or decrease the
diastolic aortic-left ventricular pressure gradient will increase or decrease
intensity of the regurgitant murmur. Prompt squatting often elicits a faint
aortic regurgitant murmur at the bedside, whereas inhalation of amyl nitrite
.markedly decreases its intensity. The mild aortic regurgitation murmur
often disappears during the latter stages of pregnancy, when peripheral
vascular resistance is low. The etiology of aortic regurgitation usually
cannot be determined by the quality of the murmur, except in the
presence of a cooing dove or musical diastolic murmur, which usually
denotes rupture or retroversion of the aortic cusps. Such ruptures occur
58
secondary to trauma or bacterial endocarditis and occasionally in the
presence of arteriosclerosis of the aortic valve.217 Retroversion and
subsequent rupture of the aortic valve with a musical murmur is also a
complication of syphilitic aortic regurgitation.218 Syphilis widens the aortic
root and spreads the commissures; since the leaflets lack proper support,
the edges become rolled, and at times the right anterior cusp may be
caught in the regurgitant stream and retroverted. A murmur heard best to
the right of the sternum should alert the clinician to an aortic root etiology
of regurgitation.219 It should be stressed that this finding is helpful only if
present, as aortic regurgitation secondary to dilation of the aortic root may
have the usual radiation, with peak intensity to the left of the sternum.220
Abbreviated Aortic Diastolic Murmurs. The murmur of very mild aortic
regurgitation may be abbreviated and may end by mid-diastole. It is typical
of the functional aortic regurgitant murmur of systemic hypertension. As
the volume of blood in the aorta decreases during diastole, the aortic ring
becomes smaller and the aortic left ventricular diastolic gradient
decreases with disappearance of the murmur as retrograde flow ceases.
The acute aortic regurgitation murmur may also be abbreviated.33 High
volume retrograde flow into a ventricle that has not had time to adapt to
the large volume results in elevation of left ventricular end-diastolic
pressure, with equilibration of the aortic and left ventricular end-diastolic
pressure. Retrograde flow ceases and the murmur disappears in the latter
part of systole. Associated findings in acute aortic regurgitation are a soft
or absent S~ and disappearance of the presystolic component of the
Austin Flint murmur. Acute aortic regurgitation is mostcommonly caused
by valvular endocarditis, trauma, acute aortic root dissection, and
dehiscence of an aortic prosthetic valve.
Pandiastolic Pulmonary Regurgitant Murmurs. Pulmonary
regurgitation is most commonly found in severe pulmonary hypertension
and dilation of the pulmonary artery with inadequate coadaptation of the
pulmonary leaflets. The regurgitant murmur of pulmonary hypertension
(Graham Steell murmur) is similar in both frequency and contour to that of
aortic regurgitation because similar hemodynamics produce both murmurs
(Figure 18).22~ Thus, these cannot be differentiated by their quality or
location on the chest wall. Aortic regurgitation is easily diagnosed when
the peripheral findings of severe regurgitation are present. Likewise,
pulmonary regurgitation is easily identified by the company it keeps.
Although significant pulmonary hypertension is frequently associated with
rheumatic mitral stenosis, the semilunar regurgitant murmur has been
found by careful investigation to usually be that of aortic regurgitation.222
More common causes of the Graham Steell murmur are primary
pulmonary hypertension and Eisenmenger’s syndrome.
59
 Early diastolic murmurs of pulmonary origin are occasionally heard in
end-stage renal failure, particularly in concurrent anemia, hypertension,
and fluid overload. These murmurs are transient in nature and decreased
by diuresis, and reflect correctable pulmonary hypertension.223
Delayed Pulmonary Regurgitant Murmurs. The murmur of organic
pulmonary regurgitation differs in quality and duration when compared
with aortic regurgitation or the Graham Steell murmur of pulmonary
hypertension.224 ,~ shown in Figure 18, the onset of the murmur is
delayed from P2 by a short interval, then builds to a crescendo, followed by
a decrescendo that ends before $1. Since pulmonary artery diastolic
pressure is low in this condition, the pressure gradient from the pulmonary
artery to the right ventricle is very slight, and the murmur is heard only
during the maximal gradient period in early diastole. This type of murmur
may be acquired through, for example, pulmonary valve endocarditis,
carcinoid syndrome, and surgical procedures on the pulmonic valve, or it
may be congenital. It is often associated with a prominent systolic ejection
murmur secondary to a large right ventricular stroke volume.
Continuous Murmurs
A continuous murmur is defined as one that begins in systole and
extends through $2 into part or all of diastole.151 It need not last the entire
cycle; therefore, a systolic murmur that extends into diastole without
stopping at $2 is considered continuous, even if it fades completely before
the subsequent $1.
Continuous Murmurs Due to Rapid Blood Flow
High-velocity flow through veins and arteries may cause a continuous
murmur,225 of which one of the most common types is a cervical venous
hum, a continuous murmur with diastolic accentuation.226 This murmur is
frequently heard in children and is also common in the latter stages of
pregnancy due to increased cardiac output. Venous hums are also
commonly heard in other high cardiac output states, such as thyrotoxicosis
and anemia. It is usually poorly heard in the supine position, and its
presence in this position in an adult strongly suggests a hyperdynamic
circulatory state. Peak intensity is in the supraclavicular fossa just lateral to
the sternocleidomastoid muscle, and this murmur can easily be terminated
by compressing the jugular venous pulse.
Other continuous murmurs due to rapid blood flow include the
mammary souffle, those heard over the thyroid in hyperthyroidism, and
murmurs associated with the hyperemia of neoplasms such as hepatomas
and renal cell carcinomas.
60
Continuous Murmurs Due to High-Pressure Shunts
A continuous murmur may be heard when there is an abnormal
communication from a high-pressure system to a low-pressure system,
with large gradients between the two systems throughout the cardiac
cycle. This type of murmur is heard in the pulmonic area and the left
infraclavicular area in patients with patent ductus arteriosus. The murmur’s
peak intensity occurs at $2, after which it gradually wanes, then terminates
before S~. The length of the murmur is determined by the difference in the
vascular resistance between the greater and lesser circulation.e3 As
pulmonary vascular resistance increases, diastolic pressure in the
pulmonary artery approaches and finally reaches systemic levels,
diminishing and finally abolishing diastolic flow and the diastolic portion of
the murmur. With equilibration of aortic and pulmonic arterial pressure,
systolic flow across the shunt diminishes and finally disappears, leaving
the ductus silent (Eisenmenger’s patent ductus arteriosus). The
continuous murmur may be heard best at the right sternal border in aortic
pulmonary fenestration, rupture of the sinus of Valsalva into the right side
of the heart, and coronary arteriovenous fistula, or in the presence of an
abnormal left coronary artery originating from the pulmonary artery. Other
causes of this murmur include left-to-right shunting through a very small
atrial septal defect, venovenous shunts such as anomalous pulmonary
veins or portal systemic veins, and peripheral arteriovenous fistulas. Large
arteriovenous fistulas between peripheral vessels produce a classic
continuous murmur with systolic accentuation, and these murmurs are
best auscultated at the site of the fistula. Local compression of the veins
may decrease the murmur’s intensity by raising venous pressure and
reducing the arteriovenous pressure gradient, whereas complete
obliteration of the fistula will terminate the murmur. When the shunt is
sizeable, a baroreceptor-mediated reflex bradycardia occurs during acute
compression of the fistula, and on release of the obstruction, a reflex
tachycardia occurs.
The continuous or machinery-type murmur such as that present with
patent ductus arteriosus must be differentiated from the to-fro murmur. The
latter is a combination of an ejection murmur and a semilunar valvular
regurgitant murmur, as shown in Figure 19. Note that the continuous
murmur reaches a crescendo at about the time of $2, whereas the to-fro
murmur has two separate components that can be clearly distinguished by
the presence of a silent period before onset of the regurgitant murmur.
61

Continuous Murmur vs. To-Fro Murmur
Sl $2 $1 $2
Continuous Murmur
$1 $2 81 $2
To-Fro Murmur
Figure 19. During abnormal communication between high-pressure and low-pressure
systems, large pressure gradient exists throughout cardiac cycle, producing continuous
murmur. A classic example is patent ductus arteriosus. At times, this type of murmur is
confused with to-fro murmur, which is a combination of systolic ejection murmur and
murmur of semilunar valve incompetence. A classic example of to-fro murmur is aortic
stenosis and regurgitation. Continuous murmur builds to crescendo around second heart
sound ($2), whereas to-fro murmur has two components. Midsystolic ejection component
decrescendos and disappears as it approaches $2. S1, first heart sound.
Continuous Murmurs Secondary to a Localized Arterial
Obstruction
Partially obstructed arteries usually have only systolic murmurs that are
delayed relative to cardiac systole, depending on the transit time of
pulsatile flow from the heart to the obstruction. However, more severe
localized stenoses of systemic or pulmonary arteries may produce
continuous murmurs if the obstruction is critical and adequate collateral
flow is not available.227 These continuous murmurs are commonly heard
directly over carotid, subclavian, and femoral arteries with severe stenosis.
Continuous murmurs caused by severe obstruction of the renal or
mesenteric arteries can also be heard by careful auscultation over the
back or abdomen, respectively. This type of continuous murmur may also
be heard over the back, midline between the scapulas, in the patient with
coarctation of the aorta when the aortic lumen is so small that a
continuous gradient exists across the constriction. Murmurs produced by
critical obstruction of major coronary arteries are rarely loud enough to be
transmitted to the chest wall; however, when audible, they produce only
diastolic murmurs, even with inadequate collateral circulation,228,229 since
most coronary flow occurs during diastole due to high wall tension in the
left ventricle during systole.
62
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