1 What are the auscultatory areas of murmurs?

The classic ones are shown in Fig. 12-1 and Table 12-1. Auscultation typically starts in the aortic area, continuing in clockwise fashion: first over the pulmonic, then the mitral (or apical), and finally the tricuspid areas. Since murmurs may radiate widely, they often become audible in areas outside those historically assigned to them. Hence, “inching” the stethoscope (i.e., slowly dragging it from site to site) can be the best way not to miss important findings.

Figure 12-1 Sequence of auscultation of the heart. (AR = aortic regurgitation, AS = aortic stenosis, ICS = intercostal space, MR = mitral regurgitation, MS = mitral stenosis, TR = tricuspid regurgitation.)

(From Baliga R: Crash Course Cardiology. St. Louis, Mosby, 2005.)

2 What is Erb’s point?

It is an additional and important area, located over the third/fourth interspace—just left of the sternum. It is named after the German neurologist (and pathologist) Wilhelm Heinrich Erb (1840–1921), who is otherwise more famous for his contributions in the field of neuromuscular dystrophies (Erb was to Germany what Charcot was to France, and Gowers to England. In fact, he was the first clinician to routinely use the reflex hammer in bedside examinations.) His homonymous point is an important site for the detection of aortic sounds and murmurs.

3 How accurate is physical examination in detecting asymptomatic valvular disease?

Quite accurate: in fact, highly specific (98%), fairly sensitive (70%), and with positive and negative predictive values of 92%. Still, accuracy depends on the valve. For example, sensitivity of exam for detecting the typical murmur of aortic stenosis (AS) is quite high (close to 100%), but specificity is much lower (70%) since other diseases (and many functional states) may present with a similar systolic murmur. The detection of moderate to severe mitral regurgitation (MR) has similar accuracy, very much for the same reason. Conversely, detecting moderate to severe tricuspid regurgitation (TR) has much higher specificity (close to 100%) since this murmur benefits from the Rivero-Carvallo confirmation. Specificity is also high for semilunar diastolic murmurs, although sensitivity for pulmonic regurgitation (PR) is only 15% (it is instead much higher for aortic regurgitation, especially if moderate to severe: close to 100%). Hence, detecting the typical murmurs of TR or PR argues very strongly for the presence of the disease. The same can be said of aortic regurgitation (AR). Conversely, absence of a typical murmur argues very strongly against the presence of significant AS or MR, but does not exclude PR or TR since these murmurs are usually very soft. Of course, trivial regurgitations remain findings that are detectable by echo only.

4 What is the clinical significance of murmurs?

It depends on the murmur. For example, even though (almost) all diastolic and continuous findings are pathologic (and thus caused by structural abnormalities of valves, chambers, or great vessels), many systolic murmurs are benign.

5 What, then, should be the approach to a newly detected murmur?

The first step should be to use the cardiovascular exam to separate pathologic from functional murmurs (see below, questions 28–33). This is essential to avoid expensive and possibly dangerous laboratory tests. Then, if the murmur is identified as organic, the physical examination should provide clues to its site of origin, its hemodynamic cause, and, possibly, its severity.

6 Do the acoustic characteristics of the murmur help separate benign from pathologic?

No. Acoustic characteristics per se (like frequency or shape) and even the radiation pattern are usually nonspecific and thus clinically unhelpful. There is only one valuable feature: the intensity of the murmur. Overall, benign murmurs are softer than pathologic ones and never louder than 3/6. Hence, they are never associated with a palpable thrill (which indicates grade 4 or higher).

7 What is a thrill?

It is a palpable vibratory sensation, often compared to the purring of a cat, and typical of murmurs caused by very high pressure gradients. These, in turn, lead to great turbulence and loudness. Hence, thrills are only present in pathologic murmurs whose intensity is >4/6.

8 How are murmurs produced?

All murmurs (whether functional or pathologic) are produced by flow that becomes turbulent enough to cause audible vibrations in the various cardiac structures. Turbulence depends on flow velocity, which, in turn, depends on (1) local or concentric narrowing of vessels or valves (causing a pressure gradient) and (2) a sudden change in vessel diameter.

9 What are the structural abnormalities that produce local narrowing and turbulent flow?

Any of the following abnormalities in the orifice through which blood flows:

In addition to structural abnormalities, abnormal blood viscosity also can cause turbulence and murmurs (the lower the viscosity, the higher the turbulence, and thus the louder the murmur).

10 How are murmurs classified?

The first (and most important) separation is purely clinical: pathologic versus functional. The real classification, however, is based on the phase of the cardiac cycle where the murmur is located. Accordingly, murmurs are divided into systolic, diastolic, and continuous. This is clinically relevant, since diastolic and continuous murmurs are (almost) always pathologic, whereas systolic murmurs are often functional (Fig. 12-2).

Figure 12-2 Phonocardiographic description of pathologic cardiac murmurs.

(From James EC, Corry RJ, Perry JF: Principles of Basic Surgical Practice. Philadelphia, Hanley & Belfus, 1987.)

Systolic murmurs are then further classified into ejection and regurgitant. This division, first proposed by Leatham in 1958, is based on the murmur’s length and relationship to S₂. It defines ejection murmurs as forward flowing, crescendo-decrescendo, early to mid systolic, and ending always before S₂. Conversely, it defines regurgitant murmurs as backward flowing, plateau shaped, spanning throughout systole, and always incorporating S₂. Still, regurgitant murmurs also may be limited to late systole. In fact, they may even last beyond S₂. Yet, their hallmark remains the extension into the S₂. Although clinically valuable (regurgitant murmurs tend to be pathologic, whereas ejection murmurs are often functional), Leatham’s classification is impractical since some regurgitant murmurs may have an ejection quality. Moreover, it relies on the bedside identification of S₂, which is not always easy. Hence, today’s preference is for separating murmurs only on the basis of systolic timing (early, mid, late, and holo) and by using as reference points both S₁ and S₂. Accordingly:

11 What are continuous murmurs?

They are sounds that originate outside the heart chambers and thus do not respect the systolic and diastolic boundaries of the cardiac cycle. Hence, they are driven by pressure gradients that persist throughout systole and diastole. This is what differentiates them from murmurs that occur both in systole and diastole (such as the to-and-fro of combined aortic stenosis and regurgitation) and what makes them resemble the noise of a train in tunnel or a machine.

12 Why are systolic murmurs much more common than diastolic ones?

Because gradients generated in systole are much higher than those generated in diastole. Hence, systolic murmurs are more hemodynamically likely to occur. This is also why diastolic events (whether at rest or after exercise) should always be considered pathologic. Unless pathology is present, diastolic pressure gradients are too small to generate sound.

13 Can exercise increase the intensity of a diastolic murmur?

Yes and no. Any increase in cardiac output (like the one of exercise, fever, or anemia) may enhance the hemodynamic likelihood of any murmur. Yet, this phenomenon still plays a greater role in systole rather than diastole.

14 Once the phase of the cardiac cycle has been identified, which other characteristics of a murmur should be analyzed and described?

1. The timing: Murmurs can span throughout systole (holosystolic) or diastole (holodiastolic), or they may occur only in the early, mid, or late phases of each interval:

Systolic murmurs: Holosystolic and late systolic murmurs are clinically more important than early or mid-systolic murmurs because they are usually pathologic. Since benign systolic murmurs are flow generated, and since flow is maximal during the early part of systole, all benign systolic murmurs tend to be short and early peaking. They are never beyond S₂. In fact, a murmur that touches S₂ (whether holosystolic or late systolic) is pathologic and reflective of atrioventricular (A-V) regurgitation. Conversely, a murmur that occurs during the first half of systole (whether early or mid-systolic) is often benign and reflective of semilunar ejection. Hence, the longer the murmur, the worse the disease.

Diastolic murmurs: Early diastolic murmurs (starting immediately after S₂) reflect semilunar regurgitation, whereas mid- to late-diastolic murmurs (starting slightly after S₂) reflect A-V stenosis. Mid- to late-diastolic murmurs may extend into S₁ as a result of presystolic accentuation (due to strong atrial contraction), but are never truly holodiastolic. Conversely, murmurs of severe semilunar regurgitation may cover the entire length of diastole. This may provide useful clues to differential diagnosis. Note, however, that holodiastolic murmurs can be so faint in late diastole to become almost inaudible.

2. The intensity (or loudness): Traditionally graded by the Levine system from 1/6 to 6/6:

1/6: A murmur so soft as to be heard only intermittently and always with concentration and effort. Never immediately.

2/6: A murmur that is soft but nonetheless audible immediately, and on every beat.

3/6: A murmur easily audible and relatively loud

4/6: A murmur relatively loud and associated with a palpable thrill (always pathologic)

5/6: A murmur loud enough that it can be heard even by placing the edge of the stethoscope’s diaphragm over the patient’s chest

6/6: A murmur so loud that it can be heard even when the stethoscope is not in contact with the chest, but held slightly above its surface

15 Are shape and frequency of a murmur clinically useful?

Not much. Although ejection murmurs tend to be typically crescendo-decrescendo (i.e., diamond-shaped), even regurgitant murmurs (such as the plateau of mitral regurgitation) may at times exhibit a late systolic accentuation. Frequency is instead more useful since it tends to correlate with flow velocity, which, in turn, correlates with pressure gradient. Hence, murmurs generated by high pressure gradients (such as AR) tend to be higher pitched (>300   Hz) than murmurs generated by low pressure gradients (such as MS), which are instead just 30–100   Hz. Because the human ear does not perceive well frequencies that are low, murmurs in this range are faint and subtle.

16 What about location and radiation of a murmur?

They are both important in differentiating systolic murmurs. For example, the MR murmur has an apical location and radiation to the axilla, whereas the AS murmur has a basilar location and radiation to the neck. Still, murmurs do not necessarily present with consistent location and radiation. For example, a TR murmur can at times be louder at the apex rather than the tricuspid area, especially when an enlarged right ventricle has posteriorly displaced the left ventricle.

17 And what about the “quality” of a murmur?

This also might help. For example, a rough and harsh systolic murmur would argue in favor of aortic stenosis, whereas a blowing and musical murmur would suggest instead mitral regurgitation. These characterizations may at times get carried away, leading to colorful descriptions—like the occasional seagull murmur of aortic regurgitation, a raucous sound resembling the call of a seagull that is produced by the eversion (or retroversion) of the right anterior aortic cusp.

18 Which interventions and maneuvers can be used at the bedside to modify the intensity and characteristics of murmurs and make them more easily recognizable?

Quite a few, all time honored and often linked to the name of the physician who first described them. They are primarily aimed at modifying preload (Valsalva and Rivero-Carvallo), afterload (handgrip), or both (squatting and standing). In addition, variations in length of cardiac cycle can affect not only preload and afterload, but also contractility.

19 What is the effect of respiration on murmurs?

It depends. Initially noted by Pierre Potain in 1866 (and then rediscovered by Carvallo in 1946 and Leatham in 1954), respiration has important effects on murmurs’ intensity (not to mention on the splitting of S₂) because of its associated swings in intrathoracic pressure and venous return. As a result, all right-sided findings (with the exception of the pulmonic ejection sound) get louder on inspiration (because of greater venous return to the right ventricle). Conversely, all left-sided findings either soften or stay the same (because of decreased left-sided venous return, caused by lung pooling—or, alternatively, because of the inspiratory interposition of the pulmonary appendage between the cardiac apex and chest wall). This physiologic principle provides the basis for the Rivero-Carvallo sign/maneuver: an increase in intensity of the holosystolic murmur of TR during (or at the end of) a deep inspiration—a highly specific (100%) but not too sensitive (60%) tool for the bedside separation of TR from MR. In a study by Cha et al. of 35 patients with valvular disease, all 19 with Rivero-Carvallo had TR on ventriculography. Yet, of the 16 without Rivero-Carvallo, only five had normal ventriculography; five had 1+ regurgitation, and six had 3+/4+ regurgitation. Hence, Rivero-Carvallo is a reliable indicator of TR, but its absence does not exclude it. Since it may be difficult to hear the changes in murmur intensity during normal respiration, auscultation should always be carried out in two phases: first at the end of a deep inspiration (while the patient is in post inspiratory apnea [i.e., holding breath for 3 to 5   seconds]) and then at the end of a deep expiration (while the patient is in post expiratory apnea for 3–5   seconds). The loudness of the systolic murmur should then be compared between the two phases, remembering that TR will get louder in held-inspiration (and, possibly, higher pitched, too), whereas MR will remain unchanged or soften. Held exhalation is also useful when searching for either a pericardial rub, the soft murmur of aortic regurgitation, or the faint pulmonic mid-systolic murmur of a patient with loss of thoracic kyphosis (i.e., straight back syndrome murmur).

20 What is the reversed Rivero-Carvallo sign?

It is an inspiratory reduction in murmur intensity—reported in patients with hypertrophic obstructive cardiomyopathy (HOCM).

21 Who was Carvallo?

José Manuel Rivero Carvallo was a staff physician at the Instituto Nacional De Cardiologia “Ignacio Chavez” of Mexico City. Born in 1905, he reported his sign in 1946 as a way to separate tricuspid from mitral regurgitation. In medical folklore, he subsequently acquired a partner (Dr. Rivero, at times cited also as Rivera), who was actually just one of Carvallo’s middle names. As a result, his sign/maneuver is often referred to as the Rivero-Carvallo sign.

22 What is the effect of Valsalva on sounds and murmurs?

Valsalva not only has important hemodynamic effects (that can be used for the recognition of congestive heart failure—see Chapter 2, questions 121–127), but may also elicit a diagnostic auscultatory response in patients with HOCM or mitral valve prolapse (MVP). This is mediated by a reduction in left ventricular diameter (caused by the strain), which in turn increases the left ventricular gradient of HOCM, thus intensifying its subvalvular systolic ejection murmur. This is the opposite of what happens to other murmurs of left ventricular outflow obstruction (such as, for example, valvular AS or PS), which instead soften with Valsalva (because of decreased venous return, with a resulting decrease in transvalvular gradients). The strain phase of Valsalva also anticipates the prolapse of a floppy mitral valve (by making the ventricle smaller, and thus “loosening up” the chordae tendineae). As a result, the click will occur earlier, and the murmur will lengthen. Hence, only two murmurs get enhanced by the straining phase of Valsalva: HOCM and MVP. In HOCM, the murmur gets louder, whereas in MVP it gets longer. Note that the release period of Valsalva may have opposite effects, based on the site of origin of the acoustic event being examined: right-sided murmurs will generally revert to their baseline intensity within 2–3 cardiac cycles, whereas left-sided murmurs will instead take a little longer (up to 5–10 cardiac cycles).

23 Does S₂ change with Valsava?

Yes, a widely split (but nonetheless normal) S₂ will be eliminated by the straining phase of Valsalva, whereas the fixed S₂ splitting of atrial septal defect will remain unchanged.

24 What are the effects of posture on murmurs?

Sitting, squatting, and standing all have profound effects on murmur characteristics. Many flow-related functional murmurs, for example, disappear upon sitting or standing (because of decreased venous return). The same occurs to the pseudo-fixed S₂ splitting of youth—separating it from the truly fixed split of atrial septal defect. Squatting/standing also can modify the findings of MVP and HOCM because squatting increases both afterload (by compressing femoral and iliac arteries) and preload (by squeezing abdominal venous content into the chest). This causes an increase in left ventricular diameter, which in turn softens the murmur of HOCM (less outflow obstruction) and shortens the one of MVP (more traction on the prolapsing valve through the tense chordae tendineae). Leg-raising in supine patients would do very much the same: increased venous return (and left ventricular volume/diameter) would soften HOCM and shorten MVP. Conversely, rapidly standing after 30   seconds of squatting would elicit a sudden drop in both afterload and preload, which, in turn, would decrease left ventricular diameter and thus intensify the murmur of HOCM and lengthen the one of MVP (anticipating its associated click).

25 What is isometric hand grip? What does it do to the murmur?

Isometric hand grip is carried out by asking the patient to lock the cupped fingers of both hands into a grip, and then trying to pull them apart. The resulting increase in peripheral vascular resistance intensifies MR (and ventricular septal defect) while softening instead AS (and aortic sclerosis). Hence, a positive hand grip argues strongly in favor of MR. The same effect can be achieved by inflating above systolic levels two blood pressure cuffs around the patient’s arms. The resulting increase in murmur intensity is even more specific for MR.

26 What about variations in cardiac cycle?

They also modify murmur intensity. For example, a longer diastolic pause (such as that following a premature beat) intensifies the murmur of AS because of lower systemic vascular resistances (due to the longer time available for aortic run-off into peripheral arteries) and higher left ventricular volume. This, in turn, increases contractility through Starling physiology, eventually resulting in higher transvalvular pressure gradients and thus a louder murmur. This triple phenomenon (lower afterload, higher preload, and increased contractility) also can be observed in situations of atrial fibrillation, where long and short cardiac cycles alternate randomly. Conversely, a murmur of atrioventricular regurgitation (like MR) tends to remain constant after a premature beat because the ejecting chamber has two available outlets: a normal forward/ejection one (large vessel) and an abnormal backwards/regurgitant one (atrium). This offsets the increase in ventricular contractility induced by a long diastole and thus keeps unchanged the intensity of a regurgitant murmur—even after a long diastolic phase. For instance, in the case of MR, the left ventricle can discharge into the left atrium (low pressure bed) or the aorta (high pressure bed). The percentage of blood ejected into each of these outlets depends on their relative resistance. After a long diastole (such as that following a premature beat), aortic resistance is decreased proportionally more than the atrial one (because even though the left atrium keeps filling during a long diastole, the aorta keeps emptying). As a result, although left ventricular volume is indeed higher after a premature beat (and so is contractility), proportionally more blood will be ejected into the aorta than into the atrium. This means that the regurgitant volume (and the intensity of the accompanying mitral murmur) will stay the same.

27 What are functional murmurs?

They are benign findings caused by turbulent ejection into the great vessels. Functional murmurs have no clinical relevance, other than getting into the differential diagnosis of a systolic murmur.

28 How can physical examination help differentiate functional from pathologic murmurs?

There are two golden and three silver rules.

1. The first golden rule is to always judge (systolic) murmurs like people: by the company they keep. Hence, murmurs that keep bad company (like symptoms; extra sounds; thrill; abnormal arterial or venous pulse, ECG, or chest x-ray) should be considered pathologic until proven otherwise. These murmurs should receive lots of evaluation, technology-based included.

2. The second golden rule is that a diminished or absent S₂ usually indicates a poorly moving and abnormal semilunar valve. This is the hallmark of pathology. As a flip side, functional systolic murmurs are always accompanied by a well-preserved S₂, with normal split.

3. The three silver rules are:

All holosystolic (or late systolic) murmurs are pathologic.

All diastolic murmurs are pathologic.

All continuous murmurs are pathologic.

These silver rules are rooted in the pathogenesis of cardiac murmurs, which, in turn, relates to intracardiac pressure gradients and blood flow velocity. These are both maximal in early systole while tapering off during late systole and diastole. Hence, murmurs should never be generated during late systole or diastole. In fact, they should never touch the S₂. If so, they reflect a high pressure gradient and thus a structural cardiac abnormality. This is also why benign systolic murmurs should always be “ejection” (i.e., with a crescendo-decrescendo shape) and not holosystolic (i.e., starting with S₁ and ending with S₂—in plateau fashion). Hence, pay close attention to S₂, both in regard to intensity (with soft or absent S₂ arguing in favor of pathology) and in regard to its relation of the murmur (with murmurs that incorporate S₂ being more likely pathologic).

29 Are these rules written in stone?

Of course not. Yet, they remain useful for the practicing physician—simple but not simplistic. As such, keep them in mind at the bedside.

30 So what should functional murmurs be like?

They should be systolic, short, soft (typically <3/6), early peaking (never passing mid-systole), predominantly circumscribed to the base, and associated with a well-preserved and normally split-second sound. They should have an otherwise normal cardiovascular exam and often disappear with sitting, standing, or straining (as, for example, following a Valsalva maneuver).

31 What should be the characteristics of “bad” systolic murmurs?

They should be long, loud (and in fact, pathologic by definition if loud enough to generate a thrill—see below), late peaking, nonlocalized, and associated with a soft-to-absent S₂ that does not normally split. They also should be accompanied by other abnormal findings/symptoms.

32 What are the synonyms for functional murmurs?

Innocent, physiologic, benign, and systolic flow related.

33 Can functional murmurs occur outside systole?

Very rarely. Some innocent murmurs may indeed be continuous, and a few can even be diastolic (in a survey of 12,000 South African children, innocent mid-diastolic murmurs had an 0.3% prevalence). Yet, these are the exceptions that confirm the basic rule: murmurs that are either continuous or diastolic should be considered pathologic until proven otherwise.

34 What are the causes of benign diastolic murmurs?

Rapid ventricular filling—very much like the physiologic S₃. In fact, these benign diastolic murmurs are always associated with either a physiologic S₃ or some other type of benign rumbling murmur of filling (like Still’s—see below, questions 46–50). They never occur in isolation.

35 What are the clinical implications of functional murmurs?

They are five:

36 How common are these functional murmurs?

Extremely common. In young adults, systolic murmurs have a 5–52% prevalence, with echocardiography being normal in 86–100%. They also are extremely commonly in pregnant women, with as many as 80% having a benign ejection murmur during gestation. Finally, systolic murmurs are present in 29–60% of elderly medical outpatients or nursing home residents (see aortic sclerosis, questions 56–65), with echocardiography being normal in 44–100% of cases. Hence, functional murmurs are the most common heart murmurs encountered by the generalist. Indeed, each of us probably had a functional murmur at some point in life.

37 Why are these murmurs better heard in children than adults?

Because they are soft enough to be more easily detectable in thin subjects. Moreover, children have higher flow velocity, faster circulatory time, and more angulated great vessels—all facilitating the production of these findings. Hence, functional murmurs can be encountered in 40–50% of children between the ages of 2 and 14. In fact, in a study of more than 12,000 South African schoolchildren, functional murmurs had an astounding prevalence of 72%.

38 Can functional murmurs occur immediately after birth?

Not really. Functional murmurs are very rare up to 2 years of age. Hence, a murmur in a very small child should be considered pathologic until proven otherwise.

39 Is high flow velocity present in nonpediatric patients?

Yes. For example, in tachycardia, anemia, fever, or, quite simply, during and after exercise.

40 How significant is a murmur that appears only after exercise, anemia, or fever?

It might still be quite significant because:

41 Are there other conditions where a higher stroke volume causes an ejection murmur?

Yes. Patients with shunts, for example (due to atrial septal defect, ventricular septal defect, or patent ductus arteriosus), often present with benign systolic ejection murmurs over the base, all caused by an increase in pulmonary flow and stroke volume. Similarly, a bicuspid aortic valve (one of the most common congenital valvular abnormalities) also may be responsible for a benign ejection murmur. This is usually best heard over the second right interspace and is due to “doming” of the valve from an increased flow—not necessarily to an abnormal pressure gradient.

42 Is a functional murmur always caused by an increase in flow velocity?

Not necessarily. Although benign flow murmurs are much more likely in situations of increased flow velocity, they also may occur when flow decreases—for example, in patients with a dilated aortic or pulmonic root, which decelerates ventricular ejection. Hence, it is the rapid change in flow velocity (whether an increase or a decrease) that produces the murmur.

43 What are the functional murmurs caused by reduced flow velocity?

The most common is aortic sclerosis, wherein the aorta is dilated and tortuous.

44 How many types of functional murmurs are known?

There are four systolic murmurs and two continuous murmurs. There also is a very rare functional diastolic murmur of children, always associated with either Still’s or a physiologic S₃.

In order of frequency, the four systolic murmurs are:

The first three occur in children and adolescents, whereas the fourth one is typical of the elderly.

The two functional continuous murmurs are:

45 What is the mechanism responsible for the generation of these functional murmurs?

It depends of the phase of the cardiac cycle:

46 What is Still’s murmur?

It is the quintessential innocent murmur, a mid-systolic ejection finding caused by flow across the aortic valve. It is best heard over the middle or lower left sternal border, although it often spills to the right upper sternal edge. It is soft and low pitched, with a somewhat musical quality—like plucking a rubber band or a string. In fact, it has been variously described as vibratory, twanging string, and fiddle-like. It is up to grade 3 in intensity (usually less), becomes louder with fever and increased cardiac output, and may be absent at times, usually when the child sits up or lies down. It was first described in 1909 by Dr. Still, who wrote in his pediatric textbook Common Disorders and Diseases of Childhood: “I should like to draw attention to a particular bruit which has somewhat of a musical character, but is neither of sinister omen nor does it indicate endocarditis of any sort. Its characteristic feature is a twangy sound, very like that made by twanging a piece of tense string. Whenever may be its origin, I think it is clearly functional, that is to say, not due to any organic disease of the heart either congenital or acquired.”

47 Who has it?

One third of all children between 2 and 5. In fact, Still’s is the most common innocent murmur of preschool-aged children. It also can be heard in young adults, even though it usually disappears at puberty.

48 What causes it?

No one knows for sure. Echo has failed to show anatomic differences between children with and children without the murmur, except for a recent report by Schwartz et al., who did find a smaller mean ascending aorta (relative to body surface area) in Still’s. These children also had higher peak ascending and descending aortic velocity, suggesting that the smaller aorta may cause faster blood flow, and thus the murmur. Whatever its origin, Still’s remains entirely benign.

49 What does it mean prognostically?

It means nothing. Children with Still’s are normal and thus should be neither restricted in their physical activity, nor should they require endocarditis prophylaxis. Even more importantly, Still’s should never be mentioned on insurance forms, school sports clearances, and dental visits.

50 Who was Still?

Sir Frederick George Still (1868–1941) was England’s first professor of childhood medicine. A good-looking and shy man, who loved children but could not stand their mothers, Dr. Still received a solidly humanistic education, graduated from Guy’s Hospital in London, and then became house physician at the Hospital for Sick Children, where he remained for the rest of his career. It was during medical school that he compiled 22 cases of children with rheumatoid arthritis, lymphadenopathy, and hepatosplenomegaly, which eventually became his doctor of medicine thesis (thus giving him, with Raynaud and Tooth, the distinction of an eponym after a medical school thesis). Dr. Still was a workaholic with a penchant for the classics, who never married but lived with his widowed mother until she died, taking her religiously to church every Sunday morning. Famous among London children for his waiting room full of toys, he retired in 1937—knighted by George VI for having been the personal physician to princesses Elizabeth and Margaret. He spent the last 4 years of his life in Salisbury, Rhodesia, where he fly fished a lot and taught English at the local church. He also wrote poetry, and the year he died he published a volume titled Childhood and Other Poems, which included the following lines:

51 What is a pulmonary systolic ejection murmur?

It is Still’s right-sided counterpart: a systolic ejection murmur caused by flow across the pulmonic valve. It is heard over the mid to upper left sternal border, using the diaphragm due to its high frequency. P₂ is well preserved and normally split. Very common in thin adolescents, a variety of this murmur can be heard in patients with thoracic malformations that bring the pulmonary artery closer to the chest wall, such as pectus excavatum or straight back. Louder in the supine position, the pulmonary systolic ejection murmur fades upon sitting or standing.

52 What is the supraclavicular arterial bruit?

It is a murmur caused by ejection into the large vessels of the aortic arch and is best heard above (and not below) the clavicles, louder on the right because of the brachiocephalic arteries’ branching.

53 What is a venous hum?

It is a continuous and physiologic venous sound—not uncommon in children, but rare in adults. For a more extensive description, refer to Chapter 10, questions 120–123.

54 What is a mammary soufflé?

Not a fancy French dish, but a systolic-diastolic murmur heard over one or both breasts in late pregnancy, and typically disappearing at end of lactation. It is caused by increased flow along the mammary arteries, which explains why its systolic component starts just a little after S₁. It can be obliterated by pressing (with finger or stethoscope) over the area of maximal intensity.

55 What can one do to sort out functional murmurs from pathologic ones?

1. Start with history, specifically:

Family history (i.e., does any other family member have heart disease?)

Past medical history (antenatal and perinatal, postnatal, infancy, and childhood history)

Personal history (age murmur first heard, history of central cyanosis, feeding difficulties, poor weight gain). Also, benign murmurs should never present with cardiac symptoms, such as dyspnea, angina, lightheadedness, fatigue, failure to thrive, and cyanosis.

2. Then continue with the physical examination, looking for clubbing and cyanosis and any abnormalities in the following areas of the cardiovascular exam:

Respiratory pattern

Blood pressure

Peripheral pulses

Neck veins exam

Palpation of the precordium

Palpation of the liver edge (look for hepatomegaly and a positive abdominojugular reflux)

Auscultation of heart sounds

Assessment of second heart sound (intensity, splitting, relation to the murmur)

3. Then carefully evaluate the murmur in its main characteristics, especially:

Area of maximum intensity

Timing and peak

Intensity

Quality and shape

Transmission

Variations with respiration

Variations with exercise

Variations with Valsalva maneuver (remember that the pulmonary ejection, the Still’s murmur, and the venous hum all disappear with the onset of Valsalva, whereas the murmurs of HOCM and MVP increase—see question 22)

Postural changes (supine position increases preload and thus exaggerates flow murmurs; squatting/standing enhances HOCM and MVP)

Response to pharmacologic agents (nowadays this is rapidly fading)

4. Finally, gather simple laboratory tests (such as an electrocardiogram or a chest x-ray), and look for any associated “bad company.”

56 What is the most common systolic ejection murmur of the elderly?

The murmur of aortic sclerosis. This is an early peaking systolic murmur that is so age related as to affect 21–26% of persons older than 65, and 55–75% of octogenarians (conversely, the prevalence of aortic stenosis is 2% and 2.6%, respectively).

57 Why does the murmur of aortic sclerosis peak early?

Because it is due to flow and velocity and not to a transvalvular pressure gradient. And since the greatest fraction of ventricular ejection occurs in the first half of systole, flow, velocity, and intensity of the murmur also will peak in early systole. Moreover, since the integrity of the valve is maintained in aortic sclerosis, the intensity of S₂ also will be preserved.

58 What are the risk factors for aortic sclerosis?

Age (twofold higher risk for each 10-year increase in age), male gender (twofold excess risk), current smoking (35% increase in risk), and a history of hypertension (20% increase in risk). Other significant factors include height and hypercholesterolemia. In fact, risk factors associated with aortic sclerosis (and stenosis) are quite similar to risk factors associated with atherosclerosis.

59 What causes the murmur of aortic sclerosis?

Either a degenerative change of the aortic valve or abnormalities of the aortic root. The latter may be diffuse (such as a tortuous and dilated aorta) or localized (like a calcific spur or an atherosclerotic plaque that protrudes into the lumen, creating a turbulent bloodstream).

60 What are the degenerative changes of the aortic valve that can cause aortic sclerosis?

Mostly a senile degeneration of the leaflets, with thickening, fibrosis, and occasionally calcification. This can stiffen the valve, and yet not cause a transvalvular pressure gradient. In fact, commissural fusion is typically absent in aortic sclerosis.

61 What are the prognostic implications of aortic valve sclerosis?

Serious. In a study of more than 5000 adults followed for approximately 5 years, aortic sclerosis carried a 40% increased risk of myocardial infarction and a trend toward an increased risk of angina, heart failure, and stroke. Note that other “benign” conditions similarly devoid of hemodynamic consequences, such as mitral annular calcification (MAC) and aortic root sclerosis (ARS), also carry a higher risk of aortic atheromatous disease.

62 How frequent are MAC and ARS?

Quite frequent, at least when sought by transesophageal echocardiography. Prevalence of MAC and ARS beyond the fifth decade is 30% and 48%, respectively.

63 What is the reason for the worse clinical outcome of patients with aortic sclerosis?

It is neither hemodynamic instability (in fact, the valve abnormality is relatively benign) nor a progression to true AS (in a study of more than 2000 patients, progression occurred in only 16%—with most stenoses being mild). Instead, it is a concomitant and subclinical coronary artery disease (CAD). In fact, aortic sclerosis serves as a marker not only for the presence of CAD, but also of systemic inflammation. And since inflammation may stiffen valvular leaflets but also cause atheromatosis, aortic sclerosis identifies subjects at risk of adverse cardiovascular events.

64 Is there any evidence for this “inflammatory” theory?

Aortic sclerosis patients indeed have higher inflammatory markers, such as increased serum levels of C-reactive protein and fibrinogen. In fact, their risk of cardiovascular death increases with each tertile of C-reactive protein.

65 What should one do in clinical practice?

One should identify aortic sclerosis (by looking for its normal carotid pulse and typical soft and early peaking systolic ejection murmur). Once this has been confirmed, CAD should be ruled out and risk factor modification implemented, like smoking cessation and hypertension/hypercholesterolemia control. It is humbling to think that a new screening procedure for coronary risk in asymptomatic patients may now simply rely on the effective use of good old stethoscopy.

66 How common are systolic murmurs?

Extremely common, especially if ejection. Hence, the need to separate functional from pathologic.

67 What are the causes of a systolic murmur?

1. Ejection (i.e., increased “forward” flow over a semilunar valve). This can be:

Physiologic: Normal valve, but flow high enough to cause turbulence (anemia, exercise, fever, and other hyperkinetic heart syndromes)

Pathologic: Abnormal valve, with or without outflow obstruction (i.e., aortic stenosis versus aortic sclerosis)

2. Regurgitation: “Backward” flow from a high- into a low-pressure bed. Although this is usually due to incompetent A-V valves (mitral/tricuspid), it also can be due to ventricular septal defect.

68 What characteristics of a systolic murmur help differentiate ejection from regurgitation?

69 What is the precision of physical examination for the evaluation of systolic murmurs?

Precision (i.e., interobserver agreement) varies depending on finding and observer (most studies have evaluated cardiologists). Overall, precision of examination for any systolic murmur is only fair in the clinical setting (kappa, 0.30). Precision for a loud systolic murmur (grade 2 or louder) also is only fair in the clinical setting (kappa, 0.29). Precision for a late peaking systolic murmur is instead excellent (kappa, 0.74). Finally, precision for a systolic click is good (agreement of 85%).

70 What is the definition of an ejection murmur?

It is a systolic murmur that is produced by forward blood flow—usually across the semilunar valves and into one of the large vessels.

71 What are the characteristics of an ejection murmur?

72 Are all ejection murmurs crescendo-decrescendo?

They tend to be because murmur intensity is regulated by the transvalvular pressure gradient, which, in turn, depends on velocity and acceleration of flow. Whenever these increase, the pressure gradient also increases, and so does the intensity of the murmur. For instance, in the ejection murmur of AS, the pressure gradient (and loudness) builds up during the very first part of ventricular contraction and peaks around mid-systole. By then the ventricle starts losing contractility; flow velocity and acceleration decrease; the pressure gradient diminishes, and the intensity of the murmur abates. This is reflected by the decrescendo pattern of the murmur’s second half.

73 What is the pitch of a systolic ejection murmur?

Low to medium. This can help differentiate ejection from regurgitant murmurs, which tend instead to be higher pitched.

74 In addition to pitch, are there other differences between ejection and regurgitant murmurs?

75 Everything else being equal, is the intensity of an ejection murmur related to its severity?

Yes. The louder the murmur, the higher the transvalvular pressure gradient. This rule of thumb requires, of course, that other parameters of murmur intensity (such as thickness of chest wall, degree of emphysema) remain constant. When this is the case, a softer murmur (such as a grade 2 or less) argues in favor of a lower pressure gradient than a louder murmur (grade 4 or higher). The only exception is congestive heart failure, where reduction in contractility softens ejection murmurs without necessarily indicating a lower transvalvular pressure gradient.

76 Does loudness of an ejection murmur always predict severity of disease?

No. Many factors may intensify an ejection murmur without necessarily reflecting worse disease. In addition to obvious conditions (such as a thin chest wall or a dilated aortic/pulmonic root), all high-output states tend to cause louder ejection murmurs that do not necessarily reflect higher pressure gradients. Instead, they indicate high flow velocity, as in the hyperkinetic heart syndrome.

77 What are the effects of respiration on left-sided ejection murmurs?

Inspiration decreases flow into the left-sided chambers. Hence, in AS it will decrease transvalvular flow, pressure gradient, and murmur intensity. Exhalation does instead the opposite.

78 What is the effect of inspiration on right-sided ejection murmurs like pulmonic stenosis?

It intensifies it because of increased right-sided venous return. Yet, this may be counterbalanced by lung expansion, which interposes a larger cushion of air between the heart and stethoscope. Since this is usually more an issue in the upper half of the chest (where the base of the heart is located), the inspiratory intensification of PS may be best heard in the lower chest.

79 What is the effect of standing on the intensity of a PS murmur?

It magnifies the respiratory variations. This is counterintuitive, considering that standing decreases right ventricular stroke volume (due to reduced venous return). Still, the inspiratory increase in return (and pulmonary blood flow) tends to be proportionally higher while standing. Hence, the right-sided ejection murmur of PS will be proportionally