1 Why is cardiac auscultation so difficult?

Cardiac sounds are often at the threshold of audibility. The human ear can only perceive sounds between 20 and 20,000   Hz: it can neither reach beyond (as dolphins and whales do) nor go below it (as elephants often do). Yet, in this range, it has a preferential bandwidth of 1000–5000   Hz, corresponding to that of the human voice. Yet, most cardiac sounds are <500   Hz. In fact, many are so low pitched to be almost inaudible (S₃ or S₄ can be <100   Hz).

Cardiac sounds are crammed in a very little time interval. At a rate of 70/minute, a cycle of 0.8 seconds can easily harbor four to five sounds, many barely detectable.

Hospital rooms are noisy.

Patients’ hair and respiration create misleading artifacts.

The obesity epidemic has given many patients a much fattier chest muffler.

Pathology has shifted from rheumatic to coronary, thus reducing the pool of teaching patients.

Our ever-increasing fascination with the inanimate and the machine (and the sophistication of technology), compounded by:

Medicolegal issues (which have made imaging a self-protecting necessity)

Patients’ demands and expectations

Reduced emphasis on bedside skills during training andreduced availability of teachers

Time constraints (which make resorting to technology an ever-increasing need)

2 How can you make auscultation a little easier?

3 What are the normal heart sounds?

They are the first (S₁) and second (S₂) heart sounds.

4 What are the hemodynamic and acoustic characteristics of the cardiac cycle?

The cardiac cycle starts with contraction of the atria (S₄), which completes the ventricular diastolic filling and results in electrical activation (and contraction) of the ventricles themselves. This, in turn, closes the atrioventricular valves (S₁) and starts the isometric phase of systole. Opening of the semilunar valves (which may cause ejection sounds/clicks) signals the beginning of isotonic contraction, with expulsion of ventricular content into the great vessels. Closure of the semilunar valves (S₂), and subsequent reopening of the atrioventricular valves, restarts diastole, and the cycle begins anew. Note that diastole is always longer than systole, unless the heart rate exceeds 120/minute. Knowledge of the interrelationship between intracardiac pressure and valve motions is crucial for understanding heart sounds and murmurs.

5 What are the cardiac areas?

They are areas of chest wall projection that correspond to the four cardiac valves (see Chapter 12, questions 1 and 2). In a clockwise fashion:

6 Where is S₁ best heard?

At the apex (for its mitral component) and over the subxiphoid/epigastrium (for the tricuspid).

7 How is S₁ generated?

By the vibration of valves, ventricles, and blood that coincides with:

1. Closure of the atrioventricular (A-V) valves

2. Opening of the semilunar valves. This in turn leads to two separate sounds, caused by:

Opening of the semilunar valves per se

Blood being ejected into the large vessels

In the absence of pathology, only A-V closure is responsible for S₁. Semilunar opening is silent.

8 Which characteristics of S₁ are clinically valuable and should therefore be identified?

The most valuable is intensity (and variations thereof). The next most valuable is splitting.

9 How do you tell S₁ from S₂?

The area of greatest intensity is different (apical for S₁ and basilar for S₂), and so is the timing (beginning of the short interval for S₁ versus beginning of the long interval for S₂). Finally, S₁ is lower pitched and longer than S₂, but still high pitched enough to require the diaphragm.

10 What is the significance of S₂ being louder than S₁ at the apex?

It suggests two possible explanations:

11 Which factors are responsible for the loudness of S₁?

In addition to shape and thickness of the chest wall, three major factors play a role:

1. The rate of rise in left ventricular pressure: This is a function of ventricular contractility, with stronger contractions causing a faster rise in left ventricular pressure and thus brisker and more forceful A-V closure. Hence, a loud S₁ is typical of the hyperkinetic heart syndrome, whereas a soft (muffled) S₁ is instead common in congestive heart failure, whose failing ventricles can only generate a slow rise in systolic pressure.

2. The separation between atrioventricular leaflets at the onset of ventricular systole: The closer the leaflets, the softer S₁ is; conversely, the wider apart the leaflets, the louder S₁ is. This mechanism feeds into two other important variables:

The duration of the P-R interval: A short P-R forces the ventricles to contract while the leaflets are still widely separated, so that their closure occurs on a steeper part of the left ventricular pressure curve. This, in turn, means a more forceful and louder closure. Conversely, a long P-R provides enough time for the leaflets to come close to each other, thus softening S₁. A muffled S₁ used to be quite common in rheumatic fever with first- degree A-V block. The progressive P-R lengthening of the Wenckebach phenomenon may also gradually (and increasingly) soften S₁.

The atrioventricular pressure gradient: A large A-V pressure gradient keeps the leaflets widely separated until ventricular pressure rises high enough to shut them close. Since the closure takes place on a steeper part of the left ventricular pressure curve, it will be forceful and loud. Hence, the longer the ventricle has to contract in order to close the A-V valve, the louder S₁ will be. This is quite common in mitral stenosis, where it contributes to the loudness of S₁.

3. The thickness of the atrioventricular leaflet: The thicker the leaflets, the louder S₁ is (banging hardbacks against each other generates more noise than banging paperbacks). Still, a soft S₁ may indicate leaflets that are too rigid. Hence, a thickened and stenotic mitral valve may generate a booming S₁ early on in the disease, but a softer (or absent) S₁ when the leaflets get eventually calcified and fixed.

12 What factors can affect the rate of rise of ventricular pressure?

The most important is contractility. An increase in left ventricular contractility (because of exogenous or endogenous inotropics) will intensify the mitral component of S₁. Conversely, a decrease in contractility (because of congestive heart failure) will soften it.

13 Which diseases present with a variable intensity of S₁?

Heart blocks, such as second degree (i.e., Mobitz I or Wenckebach) and third degree:

Table 11-1 Intensity of S₁

14 What was the role of Morgagni in describing complete heart block?

He had actually reported it almost 100 years before Adams and Stokes, in a merchant from Padua whom he had evaluated: “When visiting by way of consultation, I found with such a rarity of the pulse that within the 60th part of an hour the pulsations were only 22. And this rareness, which was perpetual, was perceived to be even more considerable, as often as many as two (epileptic) attacks were at hand. So that the physicians were never deceived from the increase of the rareness they foretold a paroxysm to be coming on.”

15 Who was Mobitz?

Woldemar Mobitz was a German cardiologist who during the first half of the 20th century linked his name to various arrhythmias and to the eponymous second-degree A-V block.

16 What is the intensity of S₁ in atrial fibrillation?

Variable. This is due to the irregular ventricular rate, which may catch the A-V valves widely open, partially closed, or in between.

17 How can you separate the variable S₁ of atrial fibrillation from that of complete A-V block?

In atrial fibrillation, the rhythm is irregularly irregular, whereas in third degree, A-V block is a regular bradycardia (due to either nodal or ventricular “escape”).

18 How is S₁ in mitral stenosis (MS)?

Booming (in 90% of the patients). A loud S₁ should always alert the clinician to the possibility of MS and thus prompt a search for its associated diastolic rumble. Conversely, a soft S₁ argues against the presence of uncomplicated MS (i.e., one where the valve is still relatively pliable). The loud S₁ is usually the result of:

19 What other conditions can be associated with a loud S₁?

In addition to mitral stenosis and the hyperkinetic heart syndrome, a loud S₁ is often encountered in:

20 Which conditions can be associated with a soft S₁?

Other than calcific mitral stenosis, a soft S₁ is usually heard in either early closure of the mitral valve (aortic regurgitation) or late closure (prolonged P-R interval). Alternatively, a soft or absent S₁ can result from inadequate left ventricular contraction because of congestive heart failure, myocardial infarction, or left bundle branch block (where the left ventricle not only contracts ineffectively, but also late, with M₁ following T₁; “M” for mitral and “T” for tricuspid).

21 Which atrioventricular valve closes first?

The mitral, followed by the tricuspid (high pressure beds always close earlier). Since mitral closure is much louder than tricuspid, the first component of S₁ is usually referred to as M₁ and predominates in the formation of the sound.

22 Which semilunar valve opens first?

The pulmonic, followed by the aortic (low pressure beds always open earlier). As for the intensity, the aortic ejection sound is usually louder than the pulmonic, but still not enough to become audible in the normal patient.

23 What is the sequence of closure and opening of the various valves at the time of S₁?

In sequence:

The first two events are the only real contributors to S₁, whereas the last two may become audible (as ejection clicks/sounds) in case of disease.

24 What is the significance of a narrowly split S₁?

It reflects the audible separation of M₁ and T₁, a normal phenomenon that may at times be detected by listening over the lower left sternal border/epigastric area (where the tricuspid component is louder and thus easier to separate from its mitral counterpart).

25 Is the tricuspid component of S₁ (T₁) audible at the apex?

No. It is only audible over the lower left sternal border (LLSB). T₁, however, may become audible at the apex in case of (1) thickening of the tricuspid valve leaflets (i.e., early tricuspid stenosis) or (2) right ventricular pressure overload (such as pulmonary hypertension or atrial septal defect).

26 What is the significance of a split S₁ at the base?

It does not indicate the audible separation of M₁ and T₁, but instead the presence of an early ejection sound. This can be of either pulmonic or aortic origin.

27 What is the significance of a widely split S₁ at the LLSB?

It usually indicates a delayed closure of the tricuspid valve, most commonly because of a right bundle branch block. Note that a bundle branch block is also a cause of split S₂.

28 What is the significance of an apparently split S₁ at the apex?

It may represent a normal S₁ that is either preceded by an S₄ or followed by an early systolic (ejection) sound. This is an important differential diagnosis to keep in mind.

29 How can one separate a truly split S₁ from a “pseudo-split” S₁?

A truly split S₁ is usually heard over the lower left sternal border. Conversely, an S₄ of left atrial origin is only audible at the apex, whereas an early systolic click is usually louder over the base. To separate S₄ from an early systolic click, keep in mind that S₄ is lower pitched, best heard with the bell, softer, located before the true S₁, and only heard at the apex. An early ejection click is instead higher pitched, best heard with the diaphragm, louder, located after the true S₁, and best heard at the base (although it can also radiate down to the apex).

30 Where is S₂ best heard?

At the base. More specifically, over the second/third left parasternal interspace for its pulmonic component and over the second or third right parasternal interspace for the aortic one. Because of its medium to high frequency, S₂ requires the diaphragm of the stethoscope.

31 How is S₂ generated?

By sudden deceleration of blood following the closure of aortic (A₂) and pulmonic (P₂) valves.

32 Which of the two semilunar valve closes earlier?

The aortic, due to systemic pressure being normally higher than pulmonic pressure.

33 How clinically useful is S₂?

Very useful. In fact, it has been suggested that careful evaluation of S₂ ranks with electrocardiography and radiology as one of the most valuable routine screening tests for heart disease. (Leatham used to call it “the key to auscultation of the heart”.)

34 Which S₂ characteristics are more valuable clinically?

Sound intensity and sound splitting. Of these, splitting (and variations thereof) is the most informative. This is in contrast to S₁, where intensity (and variations) are the most important.

35 What is a physiologic splitting of S₂?

It is the inspiratory widening of the normal interval between A₂ and P₂. This is triggered by:

Although there is always a small interval between A₂ and P₂, only in inspiration does this get large enough to become audible (i.e., 30–40   msec.)

36 What is the effect of exhalation on semilunar valve closure?

The opposite. It delays A₂ (more venous return to the left side) and anticipates P₂ (less venous return to the right side), so that the interval between the two components becomes too narrow for being appreciated by the human ear.

37 How common is a physiologic splitting of S₂?

Not very common. In a study of 196 normal adults examined in the supine position, only 52.1% had an audible inspiratory split of S₂. Physiologic splitting was much more common in younger individuals (60% of those between ages 21 to 30, and 34% of those older than 50). Indeed, after age 50, S₂ appeared single in more than 60% of subjects, as opposed to 36% for all ages. Hence, in older patients a single S₂ should not be considered evidence for a delayed A₂ (and therefore it should not suggest underlying aortic stenosis [AS] or a left bundle branch block) (see Fig. 11-1).

Figure 11-1 Splitting of S₂.

38 Why does S₂ splitting disappear with aging?

Because of senile emphysema, with greater air muffling of the pulmonic component of S₂.

39 How important is a patient’s position on S₂ splitting?

Very important. A supine position increases venous return, lengthens right ventricular systole, and thus widens the physiologic splitting of S₂. Conversely, a sitting (or standing) position decreases venous return, shortens right ventricular systole, and narrows the physiologic split (Fig. 11-2). This is especially important when analyzing an expiratory splitting of S₂. In a study by Adolph and Fowler, 22/200 (11%) normal subjects had an expiratory split while supine, but only 1/22 maintained it upon sitting or standing. Hence, a true expiratory splitting of S₂ is one that is present both in a recumbent and upright position.

Figure 11-2 Evaluation of audible expiratory splitting of S₂. The presence of expiratory splitting in the supine position is usually abnormal. Sometimes expiratory splitting of S₂ in the supine position disappears when the patient is upright and the S₂ becomes single on expiration. This response is normal. Patients should be examined carefully in the sitting and standing positions whenever S₂ appears to be abnormally split during expiration.

(Adapted from Abrams J: Essentials of Cardiac Physical Diagnosis. Philadelphia, Lea & Febiger, 1987.)

40 What is the significance of a true expiratory splitting of S₂?

It indicates one of three conditions:

With the exception of the wide (physiologic) splitting (that may be normal in the young, but abnormal in those older than 50), both the fixed and the paradoxical splitting reflect cardiovascular pathology.

41 What is a wide (physiologic) splitting of S₂? What causes it?

It is a splitting so wide as to present throughout respiration, albeit still more marked in inspiration. It occurs in (1) delayed closure of the pulmonic valve (delayed P₂), (2) premature closure of the aortic valve (premature A₂), or (3) a combination thereof.

42 What are the causes of delayed closure of the pulmonic valve?

The classic one is a complete right bundle branch block, which delays both the depolarization of the right ventricle and the closure of the pulmonic valve, making the physiologic splitting of S₂ audible both in inspiration and expiration. Loss of pulmonary recoil (because of idiopathic dilation) or severe impedance to right ventricular emptying also can delay the pulmonic closure. The latter can occur in (1) pulmonic stenosis (where the interval between A₂ and P₂ correlates with the severity of stenosis), (2) massive pulmonary embolism, (3) cor pulmonale with right ventricular failure, and (4) atrial septal defect. In pulmonary embolism, an audible expiratory splitting of S₂ (with a loud and palpable P₂) has both diagnostic and prognostic significance, reflecting acute cor pulmonale and usually resolving in hours or days.

43 What are the causes of premature closure of the aortic valve?

The most common is a rapid emptying of the left ventricle, as in severe mitral regurgitation or ventricular septal defect. A premature closure of the aortic valve also can occur in severe congestive heart failure, usually because of a reduction in left ventricular stroke volume. Finally, a widely split S₂ also may occur in tamponade, where expansion of the two ventricles is limited and fixed. During inspiration, the right ventricle fills relatively more, pushing the septum leftward and thus further impairing left ventricular filling. This reduces left ventricular stroke volume, anticipates A₂, and makes S₂ widely split. The opposite occurs in exhalation.

44 What is a fixed splitting of S₂? What does it mean?

It is an S₂ that remains audibly split throughout respiration, both in the supine and upright positions, and with a consistent interval between its two components. Although encountered in severe ventricular failure, a fixed splitting of S₂ should suggest a septal defect (most often atrial but occasionally ventricular), especially if associated with pulmonary hypertension. The defect (and its shunt) eliminate the respiratory changes in right and left ventricular stroke volume, thus fixing the S₂ splitting (more rarely, a fixed S₂ split will occur in severe impedance to right ventricular emptying, such as that of pulmonary stenosis, pulmonary hypertension, or massive pulmonary embolism—with or without bundle branch block). These patients cannot cope with the increased venous return of inspiration by increasing right ventricular stroke volume. Hence, they maintain their S₂ widely and persistently split throughout respiration (see Fig. 11-3).

Figure 11-3 The increased inflow into the right atrium on inspiration (vertical solid arrows) causes a decreased flow through the atrial septal defect (ASD) and thus increased flow through the mitral valve.

(Adapted from Constant J: Bedside Cardiology. Boston, Little, Brown, 1976.)

45 What is the differential diagnosis of a fixed splitting of S₂?

A late-systolic click (which precedes S₂) and an early diastolic extra sound (which follows S₂):

46 What about tumor plop and pericardial knock?

They are two other (albeit less common) early diastolic sounds that should be included in the differential diagnosis of a fixed splitting of S₂. The tumor plop is the opening sound of an atrial myxoma. It typically varies with the patient’s position and from cycle to cycle. The pericardial knock is instead a loud apical sound that is widely separated from S₂ (and thus easily differentiated from a fixed splitting of S₂, which is more basilar and closely separated). The knock also comes with signs of constrictive pericarditis, like distended neck veins, hepatomegaly, and leg edema in the absence of crackles.

47 What is a paradoxical splitting of S₂? What does it mean?

A paradoxical (or reversed) splitting indicates a second sound that becomes audibly split only in exhalation, while remaining single in inspiration. It means pathology until proven otherwise. The behavior (opposite to the physiologic inspiratory split of normal subjects—hence, the paradox) usually results from a delay in aortic closure, so that A₂ now follows P₂. Since the respiratory changes of the two valves remain the same, inspiration will narrow their closure, whereas exhalation will widen it. Hence, the expiratory (or paradoxical) splitting.

48 What are the causes of paradoxical S₂ splitting?

49 Is paradoxical S₂ splitting a sign of myocardial ischemia?

Yes. Even though paradoxical splitting of S₂ rarely occurs with stable coronary artery disease, it may often be heard during acute decompensation, such as after exercise or during angina. It also may be heard during the first three days following an acute myocardial infarction (in as many as 15% of patients). Finally, it is commonly heard in elderly hypertensive patients with underlying coronary artery disease and evidence of heart failure.

50 What is the significance of a “single splitting” of S₂?

It refers to either a single S₂ or to an S₂ so narrowly split in inspiration as to be inaudible in its two separate components. A single S₂ is usually due to:

51 Which is louder: A₂ or P₂?

A₂. This is consistent throughout the precordium. In fact, there is only one site where P₂ is loud enough to become audible: the pulmonic area (second or third left parasternal interspace). This is also the only site where physiologic splitting of S₂ can be heard.

52 How can you differentiate the two components of S₂?

By remembering that only A₂ is heard at the apex (in the absence of pulmonary hypertension, P₂ is too soft to be transmitted there). Hence, to tell A₂ from P₂, move the stethoscope from the base to the apex, and then pay attention to which component of S₂ gets softer: if it is the first component, then P₂ precedes A₂; if it is the second component, then A₂ precedes P₂. This maneuver may help differentiate a right bundle branch block (where A₂ precedes P₂) from a left bundle branch block (where P₂ precedes A₂).

53 What is the significance of S₂ physiologically split at the apex?

It suggests pulmonary hypertension, with P₂ so loud to transmit downward. This is common in primary pulmonary hypertension and atrial septal defect, but less common in other conditions.

54 What is the significance of a loud P₂ or A₂?

It suggests increased pressure in the pulmonic or systemic circulation. In fact, S₂ louder than S₁ at the apex also suggests pulmonary or systemic hypertension. Note that high output states may also be associated with a loud S₂, very much like they are associated with a loud S₁. These include aortic regurgitation and atrial or ventricular septal defects.

55 What is the significance of S₂ softer than S₁ at the base?

It depends on which basilar area is involved (and thus on which of the S₂ components is softer). If S₂ is softer than S₁ over the aortic area, then A₂ is diminished, suggesting fibrosis or calcification of the aortic valve (i.e., aortic stenosis). Conversely, if S₂ is softer than S₁ over the pulmonic area, then P₂ is decreased, and the most likely explanation is pulmonic stenosis.

56 What is a “Tambour” S₂?

It is a loud and ringing S₂, very rich in overtones. Tambour (“drum” in French) conveys the peculiar character of this sound, which usually indicates a dilation of the aortic root. In patients with an aortic regurgitation murmur, it suggests Marfan’s syndrome, syphilis (Potain’s sign), or a dissecting aneurysm of the ascending aorta (Harvey’s sign).

57 What makes P₂ louder than A₂?

Pulmonary hypertension. Alternatively, aortic stenosis with reduced valve mobility can make A₂ softer than P₂. Note that, despite conventional teaching, a loud P₂ has not been validated as a clue to pulmonary hypertension. This is in contrast to a palpable P₂ over the pulmonic area, which is indeed a strong predictor of pulmonary systolic pressure >50   mmHg.

58 What are the other precordial findings of pulmonary hypertension?

A right-sided S₄, a pulmonic ejection sound, murmurs of tricuspid and/or pulmonic regurgitation, an audible splitting of S₂ at the apex, and, of course, a palpable P₂.

59 What can soften A₂ or P₂?

In addition to emphysema, the most common cause is reduced pulmonic or systemic pressure. Soft A₂ or P₂ also can be due to reduced mobility of the semilunar valves, from either calcification or sclerosis, an important marker of severe stenosis.

60 What are extra heart sounds?

They are pathologic sounds that may occur in addition to the normal sounds (S₁ and S₂)_. Based on location within the cardiac cycle, extra sounds are classified into systolic (usually referred to as clicks: early systolic, mid systolic, and late systolic) or diastolic (usually referred to as snaps, knocks, or plops) (see Table 11-2 and Fig. 11-4). For each of them, we shall review acoustic characteristics, pathogenesis, and clinical significance.

Figure 11-4 Extra heart sounds. ES – early systolic (ejection) sound, MS – mid-systolic, LS – late systolic, ED – early diastolic, MD – mid-diastolic, LD – late diastolic, S₁ – first sound, S₂ – second sound.

61 Are S₃ and S₄ extra sounds?

They are more heart sounds than extra sounds. Still, they reflect pathology (S₄ always and S₃ most of the times), and thus their significance is closer to that of extra sounds.

62 Where are these extra sounds best heard?

It depends. Snaps, knocks, and “plops” are best heard at the apex, whereas clicks (especially ejection clicks) can be heard at both the base and the apex.

63 Where are S₃ and S₄ best heard?

At the apex, but barely, since their low frequency (20–50   Hz) puts them at the threshold of audibility. Hence, use the bell and remember to palpate: in thin patients they may be more palpable than audible (especially the S₄).

64 Which bedside maneuvers can intensify S₃ and S₄?

Maneuvers that increase venous return, intracardiac blood volume, and flow across the atrioventricular valves (Fig. 11-5). These include (1) leg raising, (2) mild exercise (such as assuming the left lateral decubitus—or even coughing a few times may unmask a gallop), (3) abdominal compression, (4) the release phase of Valsalva, and (5) respiration. Held-exhalation tends to intensify the left-sided S₃ and S₄ (with S₄ increasing in early exhalation and S₃ in end-exhalation), whereas held-inspiration tends to intensify the right-sided S₃ and S₄. Conversely, maneuvers that decrease venous return, intracardiac blood volume, and transvalvular flow (such as sitting, standing, and the strain phase of Valsalva) will soften a pathologic S₃ or S₄ and totally eliminate a physiologic S₃. Note that all these maneuvers increase (or decrease) the intensity of both S₄ and S₃, but they will do so much more dramatically with S₃.

Figure 11-5 Use of the lateral decubitus position in detection of S₃ and S₄. Upper, The left ventricular apex is identified first by careful palpation. Lower, The bell of the stethoscope is then applied directly over the apical impulse, using the lightest pressure possible to create a skin seal. This technique enhances audibility of low-frequency cardiac sounds (e.g., S₃, S₄, mitral diastolic murmurs).

(Adapted from Abrams J: Prim Cardiol, 1982.)

(1) Diastolic Extra Sounds

Third Heart Sound (S₃)

67 How easy is it to detect an S₃?

Not easy at all, since the sound is low pitched and often of such a varying intensity to be fleeting. Not surprisingly, variability in detection can be quite wide, with individual skills and experience playing a major role. Among four trained observers examining 81 hospitalized patients, agreement was only 48–73% for pairs of observers. Hence, S₃ is valuable but frustrating. Still, it should be sought aggressively in any patient suspected of congestive failure.

68 How is S₃ best detected?

In left-lateral decubitus and by holding the bell very gently over the apex. This will bring the ventricle closer to the chest wall, thus improving sound transmission. Of course, asking the patient to turn on the side after a negative supine exam requires a high index of suspicion. A high index of suspicion also is needed for other “bedside maneuvers” that may elicit the S₃.

69 Why the bell?

Because it filters out all the extraneous high frequencies, thus making the feeble S₃ more easily detectable. Given its low pitch, S₃ may be inaudible through the diaphragm. In fact, it may be inaudible even through the bell when too much pressure is applied (thus transforming it into a diaphragm). This little trick can be used to confirm that the sound in question is indeed an S₃, and not, for example, a higher-pitched extra sound—like an opening snap.

70 How is S₃ after an extra systole?

Louder. The mechanism is the same: increased ventricular filling following the premature beat.

71 Should S₃ be pursued over the point of maximal apical impulse (PMI)?

Yes. In fact, at times S₃ is too soft to be heard anywhere else. That the PMI is the best area of auscultation derives directly from the site of origin of S₃, the left ventricular wall.

72 Can S₃ be palpable?

Yes. In thin patients with left ventricular hypertrophy, S₃ may be more palpable than audible—especially in left-lateral decubitus.

73 Can S₃ be transmitted to the supraclavicular fossa?

This has indeed been reported, usually on the right side, and occasionally all the way up into the right internal jugular vein. The same transmission has been reported for S₄.

74 Which is easier to detect: S₃ or S₄?

S₄. It is higher pitched and louder, even though not quite as long (the S₃ is often prolonged by a series of low-pitched and humming vibrations, rumble-like—see question 90).

75 How is S₃ produced?

Not by the left ventricle hitting against the chest wall, but instead by the sudden and abnormal deceleration in left ventricular flow that coincides with the end of rapid filling. This occurs in patients with abnormal left ventricular compliance or increased left ventricular preload (the latter can be physiologic in young and bradycardic athletes, and pathologic in atrioventricular regurgitation or left-to-right shunt). Either mechanism will make S₃ more detectable, through greater intensity (higher preload) or higher frequency (abnormal compliance).

76 Why does S₃ occur in early diastole?

Because it coincides with the rapid (and passive) phase of ventricular filling, which occurs in early diastole just after the opening of the A-V valves. This normally accounts for 80% of ventricular filling, with the other 20% taking place much later in diastole, and at the time of atrial contraction (active filling). This late phase coincides with the atrial kick, and is heralded not by S₃ but by S₄. Hence, S₃ signals the phase of early (or passive) ventricular filling, whereas S₄ indicates the phase of late (or active) ventricular filling. Both sounds occur within the ventricle.

77 Is S₃ always a gallop?

No. A gallop is any triple lilt whose cadence resembles the canter of a horse. Accordingly, a ventricular gallop (i.e., a gallop produced by S₃) is only one of three forms of gallop (see also S₄ and summation gallop). The sine qua non for a gallop is its lilt, which usually requires S₁ and S₂ to be almost as soft as the pathologic extra sound. It also requires a relatively fast heart rate, even though gallops can at times be rather slow, as long as they maintain the necessary cadence. Still, tachycardia remains the prerequisite for the summation gallop (see questions 81–84).

78 Can a gallop be physiologic?

No, a gallop is always pathologic. Hence, S₃ can be physiologic and yet not be a gallop, whereas the S₃ “gallop” is always pathologic. Whether due to S₃ or S₄, a gallop is usually ominous.

79 Who first used the term gallop?

Pierre Carl Potain, who in the second half of the 19th century wrote about the “triple bruit du coeur” and the “bruit de galop”—an expression of his teacher, Jean-Baptiste Bouillard (in addition to describing both S₃ and S₄, Potain also contributed to the measurement of blood pressure).

80 What are the most important gallops?

The ventricular gallop (where the lilt is due to a third heart sound, together with a soft S₁ and S₂) and the atrial gallop (where the lilt is instead due to a fourth heart sound, together with S₁ and S₂). Traditionally, we try to mimic these rhythms by saying in a cadenced fashion: Ken-tù-cky (for an early diastolic, or S₃, gallop) and Tèn-ne-ssee (for a late diastolic, or S₄, gallop). Finally, there is a third and less common gallop, called summation.

81 What is a summation gallop?

It is the peculiar lilt of very tachycardic patients, who have both atrial and ventricular gallops. Often referred to as “S₇” (S₃ + S₄), the summation gallop owes its genesis to a tachycardia-induced shortening of diastole, causing the merge of S₃ and S₄ into a single extra sound (S₇).

82 What are the causes of a summation gallop?

Diseases causing both a stiff and a failing ventricle, like hypertensive congestive heart failure. A summation gallop also may occur in hypertrophic cardiomyopathy and in first-degree A-V block (where the prolonged P-R moves the S₄ backward in diastole, thus merging it with S₃).

83 What are the acoustic characteristics of a summation gallop?

It is higher pitched, longer, and louder than either S₃ or S₄ (in fact, often louder than S₁ and S₂). It also is easily palpable. Given its longer duration (and its location in early/mid-diastole), S₇ can often be misinterpreted as a mid-diastolic rumble. It can, however, be easily recognized as a combination of two separate acoustic events by simply slowing the heart rate. This can be done with a cautious carotid massage (beware of elderly and possibly atherosclerotic patients).

84 Is a quadruple rhythm the same as a summation gallop?

No. A quadruple rhythm is a gallop lilt characterized by both S₃ and S₄, each separately audible. This is usually caused by a rate not fast enough to produce summation. More than the galloping of a horse, a quadruple rhythm resembles the steel-rail humming of a passing train.

85 What is a physiologic S₃?

It is the sound often heard in healthy children and young adults, usually in association with a venous hum or an innocent systolic murmur. A physiologic S₃ occurs in 20–90% of young volunteers, usually thin and with more rapid early diastolic left ventricular inflow. It also can occur in athletes, especially if bradycardic. It is due to a more energetic expansion and filling of the left ventricle, probably caused by higher cardiac output (and lower heart rate). It typically softens (or disappears) upon assuming an upright position (because of the decreased venous return). Given the slowing of ventricular relaxation associated with aging (which delays diastolic filling), S₃ in those older than 40 should be considered pathologic until proven otherwise.

86 Can a physiologic S₃ occur in any other situation?

Yes. It can occur in patients with increased sympathetic tone or higher catecholaminemia, causing rapid circulation time and tachycardia (hyperkinetic heart syndrome).This, for example, affects 80% of pregnant women. An S₃ of this type often coexists with a cervical venous hum.

87 What is the clinical significance of a pathologic S₃?

It reflects either (1) increased ventricular preload (i.e., diastolic overload) or (2) reduced ventricular function (i.e., systolic impairment, with decreased myocardial contractility and low ejection fraction). The first (and less common) mechanism plays a role in high output failure; the second (and more common) plays instead a role in the low output failure of dilated cardiomyopathy (conversely, hypertrophic cardiomyopathy is more often associated with S₄).

88 How does a pathologic S₃ differ from a physiologic S₃?

A pathologic S₃ is softer, lower pitched, and more likely associated with a gallop. It also is longer. At times, however, the two may be indistinguishable. Hence, the best differentiating feature is “the company it keeps”: a pathologic S₃ comes with symptoms or abnormal signs.

89 Why is the pathologic S₃ softer and lower pitched?

Because of reduced ventricular contractility. This also causes the tachycardia and softer S₁/S₂ of these patients. Altogether, these findings make the pathologic S₃ more subtle and elusive.

90 What is the low-pitched diastolic murmur that often follows a pathologic S₃?

It is the sound produced by the sudden rush of blood across the A-V valve. This low-pitched, short, early diastolic rumble often occurs in situations of ventricular dysfunction or increased transmitral flow, as in cases of regurgitation. It may even present in patients who lack an S₃. It is, however, rarely encountered in association with a physiologic S₃. Hence, the presence of an early diastolic rumble and an S₃ should be considered pathologic until proven otherwise.

91 What are the hemodynamic implications of an S₃?

They depend on the mechanism responsible for its generation.

92 Does the presence of S₃ predict higher levels of B-type natriuretic peptide (BNP)?

Yes, and intuitively so, considering that both findings originate from increased left ventricular end-diastolic pressure. In a study of 100 consecutive adults presenting to a cardiology clinic, Marcus et al. noted that BNP levels were significantly higher in patients with S₃ as compared to those without S₃ (476 ± 290   pg/mL versus 175 ± 198   pg/mL, p <.0005). Overall, presence of S₃ had 41% sensitivity and 97% specificity for detecting elevated BNP levels (with a positive predictive value of 96% and a negative predictive value of 49%). Only one patient with S₃ had a BNP level <100   pg/mL (which in this study was the cut-off for congestive heart failure).

93 So what are the clinical implications of S₃?

Quite a few. S₃ is such an accurate predictor of poor systolic function (and elevated atrial pressure) that its absence argues in favor of an ejection fraction >30%. In patients with congestive heart failure, S₃ is the best predictor for response to digitalis and overall mortality. If associated with elevated jugular venous pressure, it predicts more frequent hospitalizations and worse outcome. S₃ also is the most significant predictor of cardiac risk during noncardiac surgery. Even in the absence of other signs of decompensation, it can identify patients at risk of perioperative or postoperative failure and infarction. If preoperative diuresis is not instituted, it also can predict mortality. Finally, presence of S₃ in mitral regurgitation reflects worse disease (i.e., higher filling pressure, lower ejection fraction, and more severe regurgitation).

94 Which conditions are responsible for an S₃ of diastolic overload?

95 What about the diastolic overload of aortic regurgitation (AR)?

In contrast to mitral regurgitation, presence of S₃ in chronic AR does indicate left ventricular dysfunction. In fact, it may help with selecting patients for catheterization and valve replacement.

96 What is the effect of pulmonary hypertension on the S₃ due to diastolic overload?

It depends. If the diastolic overload is caused by a left-to-right shunt (such as VSD or PDA), the development of pulmonary hypertension will gradually decrease the shunt and thus reduce the transmitral flow across. This will progressively soften S₃ and eventually eliminate it—an important clue to the development of Eisenmenger’s syndrome. In these patients, the return of an audible S₃ usually indicates development of a new right-sided (and not left-sided) failure.

97 What is Eisenmenger’s syndrome?

It is any left-to-right shunt complicated by pulmonary hypertension, shunt reversal, and cyanosis. This is usually more common with patent ductus arteriosus or ventricular septal defects, and less with atrial septal defects. The syndrome was first described by the German physician Victor Eisenmenger (1864–1932).

98 Is S₃ common in aortic stenosis (AS)?

No, it’s actually uncommon. When present, it indicates ventricular decompensation and elevated filling pressure. Aortic stenosis is otherwise more frequently associated with S₄.

99 How common is S₃ during a myocardial infarction?

Not uncommon in the early stages, but resolving in matter of days or weeks. In fact, a persistent post infarction S₃ has ominous implications, predicting greater myocardial damage, higher likelihood of congestive heart failure, and worse mortality.

100 Is S₃ always generated by the left ventricle?

No. It also can be generated by the right ventricle, through the same mechanisms of either ventricular dysfunction/flaccidity or increased transvalvular flow.

101 Which disease processes are associated with a right-sided S₃?

Processes characterized by either increased blood flow across the tricuspid valve (because of severe TR) or increased impedance to right ventricular emptying (because of cor pulmonale or massive pulmonary embolism).

102 How can you differentiate right from left ventricular S₃?

Mostly through the different location (the right-sided S₃ is best heard over the left lower sternal border/epigastric area, and not at the apex). Response to respiration also will be different (Fig. 11-6): the right-sided S₃ gets louder with inspiration, whereas the left-sided gets louder with exhalation (Carvallo maneuver). Finally, a right-sided S₃ is often associated with a parasternal “lift” (see Chapter 10, Cardiovascular Exam, question 129).

Figure 11-6 Where to listen for right-sided S₃ or S₄. Note the use of the bell of the stethoscope.

(Adapted from Tilkian AG, Conover MB: Understanding Heart Sounds, 3rd ed. Philadelphia, WB Saunders, 1993.)

103 What is the differential diagnosis of S₃?

104 How can S₃ be further differentiated from an opening snap (OS)?

S₃ occurs a little later in diastole than OS (and much later than the split S₂): 120   msec after A₂ (and often even later), as opposed to 100   msec for OS. Although this may seem trifling to the untrained ear, it can actually help differentiate the two sounds. In addition, S₃ is softer, lower pitched, and heard through the bell. Finally, because the left ventricle is usually small in mitral stenosis, OS tends to be a little closer to the left sternal border than S₃ (which is instead loudest at the apex).

105 How common is S₃ in mitral stenosis (MS)?

Very uncommon. In fact, presence of S₃ argues strongly against significant stenosis because the valvular obstruction of MS prevents the rapid left ventricular early diastolic filling that is so crucial for the genesis of S₃.

Fourth Heart Sound (S₄)

107 How is S₄ best detected?

Very much like the S₃: over the apex, through the bell, and in left lateral decubitus. Note that S₄ (and S₃) are often inaudible in a supine position and become transiently more evident only upon assuming a left-lateral decubitus position. As in the case of S₃, a firm pressure on the bell will usually soften or eliminate S₄.

108 Can S₄ be palpable?

Yes, as a presystolic movement. This is best detected in the left-lateral decubitus position and over many cardiac cycles (because of its respiratory variation). In fact, S₄ is often easier to palpate than S₃, thus allowing for a bedside differentiation between these two diastolic extra sounds. A palpable S₄ should always be considered pathologic (conversely, an S₄ that is only audible can often be a simple by-product of aging).

109 How common is S₄? Can it be normal?

It depends on the method used to detect it. By phonocardiography, it is so common that it may indeed reflect no true pathology. In fact, S₄ can be recorded in 75% of normal middle-aged subjects, as a response to the effects of aging on ventricular compliance. Still, an audible, loud, and even palpable S₄ reflects almost always an underlying pathology—independent of the patient’s age. Even in older adults (where it may be common even in the absence of clear-cut pathology), the presence of a distinctly audible S₄ should suggest underlying disease. Indeed, follow-up of these “normal” patients usually reveals coronary artery pathology.

110 Can S₄ occur in younger individuals?

Yes. It has been recorded in younger subjects with no clear underlying pathology, but just an increase in blood flow.

111 What are the auscultatory differences between S₃ and S₄?

S₄ is higher pitched, louder, shorter, and, of course, differently timed, since it is late diastolic and thus preceding S₁ (which serves as an important reference point). S₃ is instead early diastolic and thus following S₂. Both vary with respiration (S₃ more prominently than S₄).

112 Why is S₄ late diastolic?

Because it is generated immediately before ventricular systole. Hence, it is presystolic.

113 How is S₄ produced?

By atrial contraction, primarily left sided, but at times right sided, too. Yet, it is not generated by atrial systole per se, but by the resulting forceful tension of the ventricle/A-V valve apparatus. Hence, S₄ is often more persistent than S₃, since its reason (strong atrial contraction) is usually chronic.

114 What is the hemodynamic significance of an S₄?

Not as ominous as that of S₃. S₄ corresponds to an increase in late ventricular diastolic pressure, but in contrast to S₃, it reflects normal atrial pressure, normal cardiac output, and normal ventricular diameter. It also is associated with loud S₁ and S₂, since ventricular systole is usually adequate, and many patients are even hypertensive.

115 What are the clinical implications of S₄?

More benign that those of S₃, insofar as S₄ has no adverse postoperative implications. It is even questionable whether it predicts severity of AS. It simply indicates a hypertrophic but compensated ventricle, with reduced ventricular distensibility and decreased passive filling in early to mid-diastole. This places greater demand on the atria, which now have to handle 30–40% of the entire ventricular filling (instead of the usual 20%). The resulting stronger atrial kick will rush blood into the noncompliant ventricle and thus produce S₄, which in tachycardic patients may assume a gallop cadence. Hence, S₄ indicates diastolic rather than systolic dysfunction.

116 Which disease processes can cause an S₄?

Diseases with ventricles so thick to require a strong atrial contraction (in fact, P waves may also become prominent). Among these are:

117 What happens when these hypertrophic ventricles fail?

Once ventricular hypertrophy evolves into ventricular failure (with a dilated and flaccid ventricle), the S₄ gradually softens and eventually disappears, leaving in its place an S₃. Hence, S₄ implies an earlier, more compensated (and less severe) ventricular dysfunction.

118 How common is S₄ in myocardial infarction (MI)?

Very common early on, and overall benign, given the ventricular stiffness of ischemia. Yet the presence of S₄ at more than 1 month after MI does predict higher 5-year mortality.

119 Can S₄ occur in mitral regurgitation?

Only if acute. Otherwise, mitral regurgitation is typically associated with an S₃.

120 Can a right-sided S₄ be differentiated from a left-sided one?

Yes. Like the right-sided S₃, a right-sided S₄ is best heard over the lower-left sternal border or subxiphoid areas. At times, it may even be heard over the neck veins. Also, a right-sided S₄ is commonly associated with other signs of right ventricular strain, like distended neck veins with large A or V waves, a loud P₂, and a right ventricular heave. Finally, as with all right-sided findings, a right-sided S₄ is usually louder in inspiration.

121 Can patients with atrial fibrillation have an S₄?

No, since they cannot muster an adequate atrial contraction. The same applies to atrial flutter.

122 What is the differential diagnosis of an S₄?

Opening Snap

123 What is an opening snap?

It is a pathologic, loud, snapping, short, high-pitched, and early diastolic extra sound of patients with mitral (or tricuspid) stenosis. It is loudest over the lower left sternal border (a little less at the apex), and is best heard by either using the diaphragm or by applying firm pressure on the bell (thus converting it into a diaphragm). It is produced by the tensing and deceleration of a stenotic but still mobile A-V valve (Fig. 11-7). In this, it resembles the snapping of a sail that is filling with wind. Note that in mitral stenosis, much of the snapping is produced by the filling of the anterior leaflet, which is larger and more mobile than the posterior.

Figure 11-7 Cause of the opening snap. The belly of the stenotic mitral valve (mostly the anterior leaflet) bulges downward with a jerk to produce a clicking or snapping sound as it opens. Therefore, it also must close with a snap as it domes upward.

(Adapted from Constant J: Bedside Cardiology. Boston, Little, Brown, 1976.)

124 Why are these sounds called “snaps”?

Because of convention. Extra sounds produced by the atrioventricular valves are normally referred to as snaps (if occurring in diastole and caused by the abnormal opening of the leaflets) and clicks (if occurring in systole and caused by the prolapse and backward ballooning of the leaflets). Clicks of A-V prolapse are usually mid- to late-systolic, although they also can be early systolic, but in this case, they are more commonly due to abnormal semilunar ejection and thus referred to as ejection sounds.

125 Is the opening of a normal atrioventricular valve audible?

No. Only in patients with hyperkinetic heart syndrome, the increase in blood flow may render it audible. This, however, represents more the exception than the rule. In all other cases, an audible sound of A-V opening indicates thickening and stiffening of leaflets, making them behave like a sail that suddenly fills under wind—with ballooning, billowing, and a final snap caused by the tight grip of the chordae.

126 How can one distinguish an opening snap from the closing of S₂?

By their different timing. There is usually enough separation between the closing of the aortic valve (A₂) and the opening of the mitral valve to make them perceived as two separate acoustic events. This interval is around 100   ms and is commonly referred to as the A₂–OS.

127 Does the timing of OS (i.e., the length of A₂–OS) reflect the severity of stenosis?

Yes: the earlier the snap, the worse the stenosis. OS timing is controlled by:

128 Does the intensity of OS reflect the severity of stenosis?

Yes. A soft (or absent) snap suggests a stiff and poorly mobile mitral valve, usually calcific (although it also might reflect the thickness of the chest wall, or the degree of emphysema). Other conditions that also may soften OS include heart failure, a very large right ventricle (which pushes the left ventricular wall away from the chest surface), and pulmonary hypertension (that reduces flow at both the mitral and pulmonic levels). Conversely, increased venous return (and raised left atrial pressure) increases the intensity of the snap. This can occur after leg raising or mild exercise, like turning from supine to the left decubitus position.

129 How common is an opening snap in patients with mitral stenosis?

Common. In the absence of calcification, it occurs in 75–90% of all patients. It usually reflects a milder form of the disease and thus is absent in more advanced (and calcific) cases.

130 How can one distinguish the pulmonary sound of a split S₂ from an opening snap?

With difficulty. Both P₂ and OS are high pitched and short. And the time interval between A₂ and P₂ is similar to that between A₂ and OS (both are 30–100   msec). Hence, to separate P₂ from OS, you should rely on (1) the area of maximum intensity (OS is louder at the lower left sternal border/apex, whereas P₂ is louder at the base); (2) the respiratory variations (in the absence of left bundle branch block, the expiratory widening of a “split S₂” is more likely to represent an opening snap than an A₂–P₂ complex); and (3) the intensity of S₁ (a soft S₁ tends to exclude an opening snap). In case of pulmonary hypertension, the best way to differentiate P₂ from OS is not the apical intensity of the sound (which can be quite loud), but its respiratory variations.

131 What is a tricuspid opening snap?

It is the opening sound of a stenotic tricuspid valve. This may occur in 5% of MS patients.

132 How can one differentiate a mitral from a tricuspid opening snap?

By respiration. Like all right-sided findings, the tricuspid opening snap is louder in inspiration. The OS of mitral stenosis is instead louder in exhalation.

Pericardial Knock

134 How is the pericardial knock produced?

By sudden deceleration of the left ventricle, as it encounters a thick and calcific pericardium. This is a mechanism similar to that of S₃, even though the deceleration of the knock is even more abrupt—hence, its loudness.

135 Is the pericardial knock common in acute pericarditis?

No. It is always absent in acute/subacute pericarditis (where, instead, the rub is a more typical finding). Even in tamponade, knocks are absent. Conversely, they are encountered in 30–90% of patients with chronic calcific and constrictive pericarditis. This used to be the sequela of an old tuberculous process, but nowadays is usually the result of coronary artery bypass surgery.

136 What other physical findings may accompany constrictive pericarditis?

137 What is the differential diagnosis of a pericardial knock?

S₃ and opening snap (OS). The knock occurs later than OS and is much louder and higher pitched than S₃. Since it can be well heard over the pulmonic area, it also may need to be differentiated from a split S₂, which has respiratory variations, lack of transmission to the apex, and shorter interval.

Mitral (or Tricuspid) Valve Myxoma

(2) Systolic Extra Sounds

140 What is the mechanism of production?

Ejection sounds are produced by blood flowing across the semilunar valves and into the large vessels (Fig. 11-8). Thus, they are normal, but usually inaudible, components of S₁. Only in disease, however, they become loud enough to be identifiable as separate acoustic events. In patients with no cardiovascular pathology, ejection sounds are usually the result of a hyperkinetic heart syndrome. In patients with cardiovascular pathology, they reflect instead one of two processes:

Figure 11-8 Origin of ejection sounds. A, Ejection sound or click produced by the opening motion of a thickened, often stenotic aortic or pulmonary valve. B, Ejection sound produced by the sudden tensing of the proximal aorta or pulmonary artery during early ejection. This is usually associated with a dilated and/or hypertensive great vessel.

(Adapted from Abrams J: Essentials of Cardiac Physical Diagnosis. Philadelphia, Lea & Febiger, 1987.)

141 How do you distinguish an aortic from a pulmonic ejection sound?

142 Can an ejection sound be accompanied by a systolic murmur?

Yes. In fact, ejection sounds due to a bicuspid valve are often immediately followed by an ejection murmur. This is caused by a relative stenosis of the bicuspid valve, leading, in turn, to a post-stenotic dilation of the aortic (or pulmonic) root. The dilation further enhances the ejection sound, thus perpetuating the cycle. Hence, an ejection sound identifies a concomitant systolic murmur as pathologic and places the cause of the stenosis at the valvular level.

143 And so, what causes an aortic ES?

144 Where is the aortic ES best heard?

It depends. In patients with semilunar valve disease, it is well heard at the base, but even better at the apex. In some cases, the apex may actually be the only area where the ES is detectable. This is also true in patients with emphysema. When the ES originates from the aortic root, it is best heard throughout the sash area of aortic projection (from the apex to the right shoulder), with highest intensity at the base. The aortic ejection sound is also best heard with the patient sitting up and in held exhalation.

145 What is the significance of an aortic ejection sound in aortic stenosis?

It argues in favor of valvular AS (ejection sounds are absent in both subvalvular and supravalvular AS). More importantly, an ejection sound argues in favor of a bicuspid aortic valve.

146 What is the clinical significance of the intensity of an aortic ES?

It reflects the mobility of the valve; therefore, ES will soften with fibrosis and disappear with calcification (usually indicating a transvalvular gradient >50   mmHg)—hence, the higher prevalence of ejection sounds in young individuals, whose stenotic valves tend to be more pliable and mobile than those of the elderly.

147 Can the opening of a pulmonary bicuspid valve be responsible for an ejection sound?

Yes. In patients with valvular pulmonic stenosis, the sudden opening and upward movement of a dome-shaped valve will generate an ejection sound.

148 Does a pulmonic ejection sound indicate severity of pulmonary stenosis (PS)?

To the contrary. It indicates mild to moderate disease (which is intuitive, since ejection sounds reflect mobility of the valve). Only rarely does it correlate with right ventricular pressure >70   mmHg. In more severe PS cases, the ES tends to occur earlier, either merging with S₁ or preceding it.

149 What is the significance baseline of the intensity of a pulmonic ES?

Not as valuable as that of an aortic ES. In fact, a softer click may occur in both mild and severe forms of valvular PS. Still, given the baseline intensity of the click, this will vary with respiration (louder in exhalation and softer in inspiration), as does the intensity of the systolic ejection murmur that may accompany it.

150 What causes a nonvalvular pulmonic ejection sound?

Two possible mechanisms, both taking place in the pulmonary artery:

151 What is the differential diagnosis of an ejection click?

The most difficult is its differentiation from a split S₁. Less difficult is the separation from either S₄ (softer, lower pitched, preceding S₁, and best detected through the bell) or a mid/late systolic click (high pitched and loud as the ejection sound, but timed a bit later in systole).

152 What is the Means-Lerman scratch of hyperthyroidism?

It is a raspy and scratchy systolic sound heard over the pulmonary artery of patients with hyperthyroidism. Described in 1932 by the American physicians J. Lerman and J.H. Means, it resembles a combination ejection murmur/ejection sound. It also can resemble a pericardial friction rub, since it has similar grating qualities and an increase in exhalation. In fact, the Means-Lerman scratch is caused by the rubbing of a hyperdynamic pericardium against the pleura. It is less common than the other cardiovascular findings of hyperthyroidism, such as tachycardia (with 90% of patients having a resting heart rate >90 beats/minute); bounding peripheral pulses; wide pulse pressure; active precordium; louder heart sounds; and a systolic ejection murmur (in up to 50% of cases). Moreover, Means-Lerman is not exclusive of thyrotoxicosis, having been described in other hyperdynamic conditions, such as anemia or fever.

Mid- to Late-Systolic Click

154 What is the clinical significance of a single (or multiple) mid- to late-systolic click(s)?

It indicates the presence of mitral (or tricuspid) valve prolapse (MVP). In fact, simple identification of a typical click and/or murmur complex suffices—no further testing is needed.

155 What are the auscultatory characteristics of a systolic click due to MVP?

The major one is variability from cycle to cycle: in intensity, number, and timing. Clicks also may acquire association with late-systolic murmur and even fade enough to elude unskilled clinicians. At times, they may be multiple, further confusing the inexperienced observer.

156 Why do clicks of mitral valve prolapse not occur in early systole?

Because they have different modes of generation:

Yet, as always in medicine, there are exceptions that confirm the rule. Some clicks of prolapse, for example, may either follow or overlap with S₁ (thus creating a loud summation sound). These are usually caused by a billowing so severe to occur even in the large and distended ventricle of early systole.

157 How can one recognize MVP when the click coincides with S₁?

By the combination of a holosystolic murmur of regurgitation plus a loud “S₁” (which is actually the summation of S₁ and click). A loud S₁ is otherwise uncommon in patients with simple MR.

158 What are the acoustic characteristics of the click(s)?

The click(s) is mid to late systolic, loudest over the apex or left sternal border, and at times multiple. In two thirds of the cases, it precedes the murmur; in one third, it immediately follows it.

159 How are these clicks generated?

By the combined backward snapping of a prolapsing mitral leaflet and the sudden stretch of its chordal apparatus (chordal snap). This would also explain the occasional multiple clicks. Yet, some authors have argued that the contraction of the papillary muscles may actually prevent the leaflet from prolapsing directly back into the atrium. In this case, the click might be due to the ballooning of the leaflet itself, very much like the sound of a sail suddenly filled by wind.

160 Which bedside maneuvers can change the timing of an MVP click/murmur?

Maneuvers that modify left ventricular diameter (Fig. 11-9). For a more detailed discussion, please refer to Chapter 12, questions 22, 24, 178, and 179.

Figure 11-9 Variation of the timing of the click and systolic murmur in mitral valve prolapse with changes in body position. The figure indicates the presence of an arbitrary “prolapse threshold” and suggests a relationship between left ventricular size and the mitral valve that affects the timing and extent of leaflet prolapse. Whenever the prolapse threshold is reached during left ventricular systole, the leaflets prolapse, resulting in a click and systolic murmur. If the threshold is achieved in early systole as a result of reduced preload and/or afterload (e.g., standing position), the click moves closer to S₁ and the murmur becomes longer and louder. Conversely, an increase in preload and afterload, such as occurs during squatting, results in the click and murmur appearing later in systole because the prolapse threshold is not reached until later during ejection. Pharmacologic agents also may affect left ventricular filling and outflow resistance and alter ventricular geometry to produce predictable changes in the timing of the click and murmur.

(From Criley JM, Heger J: Prolapsed mitral leaflet syndrome. In Roberts WC [ed]: Congenital Heart Disease in Adults. Philadelphia, FA Davis, 1979, with permission.)

161 Are mid- to late-systolic clicks always associated with a late systolic murmur?

Not at all. If associated, however, they suggest the presence of mitral valve prolapse with regurgitation. Yet, many MVP patients have only the click (or clicks). Since presence of a murmur (and thus regurgitation) may vary from day to day and cycle to cycle, this affects the issue of prophylaxis. Many cases of endocarditis have been documented in patients with only a mid-systolic click, suggesting that regurgitation may only occur at times. Yet, the general consensus is that clickers stay clickers and murmurers stay murmurers.

162 Can patients with MVP present with a diastolic click?

Yes. 5–15% of all MVP patients have indeed an early diastolic click. This is still caused by the ballooning of the mitral leaflet, albeit in a reversed direction.

163 What is the differential diagnosis of a mid-systolic click?

It depends on timing. Earlier clicks tend to be confused with ejection sounds, split S₁, or even S₄ (which, however, is softer and lower pitched). Mid to late clicks, on the other hand, can be confused for a split S₂ or, even for an S₂/opening snap complex. Presence of a late-systolic murmur following the click may further confuse, suggesting an opening snap/diastolic rumble complex. Finally, multiple systolic clicks also may be confused for pericardial friction rubs.

164 What are the auscultatory characteristics of a pericardial friction rub?

It is a scratching, scraping, grating, crackling, crunchy, squeaky, creaking, and typically fleeting noise, heard in patients with inflammation of the pericardial layers. It is very different from a murmur or an extra sound. In fact, it was first described by Collin in 1820 as the “crackling of new leather.” Because of its high frequency, it is best heard by applying firm pressure on the diaphragm of the stethoscope, so that the tensing of the skin may further help transmission.

165 How many components are in a rub?

As many as three: (1) one occurring anywhere in systole, although most commonly in mid-systole (and thus corresponding to ventricular contraction) and (2) two occurring instead in early and late diastole (and thus corresponding respectively to early ventricular filling and atrial contraction). These may give the rub a peculiar lilt, almost gallop-like.

166 Do rubs always present with three components?

No. The systolic component is always present, but the diastolic ones may be absent, especially the atrial. In a review of 100 patients with pericardial friction rubs, Spodick found that around 50% had three components, 30% had two components, and only 15% had just one.

167 Where are rubs best heard?

Throughout the precordium, although more than 80% tend to be louder along the left parasternal area and lower-left sternal border (third and fourth interspaces). Note that rubs vary tremendously from site to site, often being audible in only a very circumscribed area.

168 Can rubs be palpable?

Yes. Very loud rubs can be palpable (the same is true for pleural friction rubs). One fourth of all rubs are, in fact, palpable.

169 What bedside maneuvers can intensify a pericardial friction rub?

The most common is inspiration: in approximately one third of the patients, rubs become louder in deep and held inspiration because the inspiratory descent of the diaphragm stretches the pericardium, thus making the rubbing of the two layers more likely to occur and more intense. Note, however, that rubs also may be enhanced by held exhalation. This brings the heart closer to the chest wall but also increases venous return to the left ventricle, thus better stretching the pericardial layers onto each other. Finally, having the patient sit up, lean forward, and rest on elbows and knees also may increase contact between the visceral and parietal pericardium and thus their rubbing (Fig. 11-10).

Figure 11-10 Alternative position for hearing the pericardial friction rub.

(Adapted from Tilkian AG, Conover MB: Understanding Heart Sounds, 3rd ed. Philadelphia, WB Saunders, 1993.)

170 How can one separate a pericardial from a pleural rub?

By asking patients to hold their breath, first in inspiration and then in exhalation. A pericardial rub will persist in at least one of the two (and usually in both), whereas a pleural rub will disappear. Remember, however, that patients with viral pleuropericarditis or Dressler’s syndrome may actually have both a pleural and a pericardial friction rub.

171 Which disease processes are associated with rubs?

172 Does the presence of a rub exclude a pericardial effusion?

No. One tenth of all rubs will be associated with a pericardial effusion. In fact, rubs can occur in up to one fourth of tamponade cases. Although this is counterintuitive, it reflects a loculated process, capable of compromising ventricular filling (the sine qua non of tamponade) while simultaneously allowing parts of the pericardium to rub against each other. Hence, never exclude tamponade because of a rub. Instead, measure pulsus paradoxus—especially in patients with tachycardia, tachypnea, distended neck veins, and clear lungs (see Chapter 2, questions 93–97).

173 What is the differential diagnosis of a pericardial friction rub?

A three-component rub must be differentiated from the to-and-fro murmur of aortic regurgitation and the continuous murmur of patent ductus arteriosus, and the systo-diastolic murmur of severe mitral regurgitation (see “lots of noise,” Chapter 12, question 263). The scratching and creaking qualities of the rub will usually help recognize it. A three-component rub also may resemble a ventricular gallop (because its early diastolic component coincides with the S₃ timing), especially in tachycardic patients, who, after all, represent the majority of pericarditis cases. To identify the rub, rely on its loudness, high frequency, and typical scratchy quality. A one-component (systolic) rub may pose the greatest diagnostic challenge, since it is often misdiagnosed as a systolic ejection murmur. To sort it out, monitor the sound over time: a rub will usually change in quality and intensity, often acquiring one or two diastolic components.

174 How about constrictive pericarditis?

It presents with a constellation of typical findings (discussed in question 136) that often include a knock, but rarely a rub (present in <5% of the cases).