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 louder in inspiration than expiration.

80 What is the effect of Valsalva on systolic ejection murmurs?

It depends on the phase (straining or releasing). Overall, all ejection murmurs (except HOCM) fade during straining, due to decreased venous return. Yet, as soon as straining is released, all ejection murmurs intensify, peaking within 2–3 beats (for the pulmonic ejection murmur) or 6–8 beats (for the aortic ejection murmur). The delayed peak of AS is due to the longer time needed for the blood that had been pooled during straining to finally reach the left ventricle and the aorta.

81 What are the three main types of aortic stenosis?

Supravalvular, valvular, and subvalvular. These can be easily separated by evaluating the central arterial pulse (see Chapter 10, questions 18 and 19 and Fig. 10-3). In addition, subvalvular stenosis is further divided into (1) hypertrophic subaortic stenosis (also called HOCM [i.e., hypertrophic obstructive cardiomyopathy]) and (2) fixed, fibrotic subvalvular stenosis.

Figure 12-3

Valvular Aortic Stenosis

83 What is the most common congenital cause of valvular AS?

A bicuspid semilunar valve. This is one of the most frequent congenital heart abnormalities, present in around 2% of the general population. A bicuspid valve may remain completely silent throughout the patient’s life, or simply present as an early systolic (ejection) click. In most cases, however, bicuspid valves stiffen over time, eventually calcifying and stenosing—a not uncommon reason for AS in the elderly. Alternatively, they may fail—usually at an earlier stage in life.

84 What is the progression of valvular changes in aortic stenosis?

Calcific stenosis represents the final stage of an active process that starts with (1) focal thickening of the valvular subendothelium; progresses to (2) mild, irregular thickening of the leaflets, without any outflow obstruction (aortic sclerosis); and eventually results in (3) greater stiffening and calcification, with a reduced valvular area and clinically significant outflow obstruction.

85 Is aortic root dilation a common feature of valvular AS?

Yes. Postobstructive dilation occurs in approximately 25% of patients with AS. Yet, root diameter does not reflect degree of stenosis and does not necessarily result in concomitant regurgitation.

86 What is the link between AS and coronary artery disease (CAD)?

A link almost as strong as the one between aortic sclerosis and CAD—especially in symptomatic patients. CAD occurs in one half of those patients with AS who end up dying or requiring valvular surgery, but only in one fourth of those without adverse outcome. Event-free survival at 3 years is 63% in CAD patients, as opposed to 86% in those without it, confirming its ominous prognosis.

87 How much reduction in valvular area is necessary for the AS murmur to become audible?

At least 50% (the minimum for creating a pressure gradient at rest). Mild disease may produce loud murmurs, too, but usually significant hemodynamic compromise (and symptoms) do not occur until there is a 60–70% reduction in valvular area. This means that early to mild AS may be subtle at rest. Exercise, however, may intensify the murmur by increasing the output and gradient.

88 What is the normal aortic area?

3   cm². A valvular area >1.5   cm² reflects mild disease, 1–1.5   cm² moderate disease, <1.0   cm² severe disease, and <0.7   cm² critical disease. Symptoms usually occur with an orifice <1   cm².

89 What is the frequency of clinically significant outflow obstruction?

1–2% of adults older than 65, with most patients eventually requiring valve replacement.

90 What is the pathophysiology of left ventricular outflow obstruction?

It is a physiology of pressure load, with compensatory hypertrophy and typically well-preserved systolic function—at least initially. This is in contrast to aortic regurgitation (AR), wherein volume load causes instead progressive left ventricular dilation and dysfunction—even in the absence of symptoms. This is why AR with severe ventricular dysfunction may often be asymptomatic, whereas AS with ventricular dysfunction is always symptomatic. Hence, in contrast to AR, the clinical outcome of AS is very closely related to the presence or absence of symptoms: once these occur, outcome is poor, with 2-year survival below 50%. Yet, even advanced and symptomatic AS may greatly benefit from valvular replacement, since the resulting relief in afterload increases systolic function, improves ejection fraction, and dramatically reduces symptoms.

91 Where is the murmur of aortic stenosis louder?

Over the second right parasternal interspace, but also all the way down to the apex. This area of surface projection is referred to as the “sash,” and is much wider than the traditional aortic area.

92 What is the Gallavardin phenomenon?

One noticed in some patients with AS, who may exhibit a dissociation of their systolic murmur into two components:

This phenomenon reflects the different transmission of AS: its medium frequencies to the base, and its higher frequencies to the apex. The latter may become so prominent as to be misinterpreted as a separate apical “cooing” of MR. Gallavardin attributed this finding to solid tissue transmission of the musical components of AS; although more recently, Burch suggested that a concomitant papillary muscle dysfunction might produce real mitral regurgitation.

93 Who was Gallavardin?

One of the premier European cardiologists of his times, but also a refined aesthete and humanist. The son of a homeopathic physician, Louis Gallavardin (1875–1957) was a consummate bedside diagnostician, who contributed enormously to the understanding of hypertension, cardiomyopathy, and coronary artery disease (he antedated Attilio Maseri’s description of vasospasm as one of the causes of myocardial infarction). In this regard, he described a painless variant of exertional angina called “blockpnea” (a term he coined in 1933), a condition characterized by an agonizing feeling of blocked respiration, almost apnea-like, which slows the patient to a standstill. He also reported on valvulopathies, like the pulmonary edema of MS (still called the “reticissimente de Gallavardin”), and the transformation of the harsh murmur of AS into a higher-pitched apical sound (the Gallavardin’s phenomenon, 1925). A modest man with an interest in the humanities, a prodigious memory, and an impressive knowledge of art and books, Gallavardin mustered such a strong respect among peers that he often overrode everybody else’s opinion. This is why it took three decades before Reid and Barlow were eventually able to delineate the true nature of the mid-systolic click, which Gallavardin had erroneously attributed to pleuropericardial lesions.

94 What are the characteristics of the AS murmur?

It is typically crescendo-decrescendo, mid-systolic, medium pitched, harsh, and with a rasping or coarse quality. Note that although absence of a murmur argues strongly against AS, its presence is less of a positive predictor, given the wide differential diagnosis of a systolic murmur.

95 How can one separate the murmur of AS from that of aortic sclerosis?

By the same rules previously outlined for separating pathologic from functional murmurs:

96 Of all these characteristics, which are the most useful for ruling in (or ruling out) aortic stenosis?

The ones arguing most strongly in favor of AS are a reduced/delayed carotid upstroke, a mid to late peak, a soft to absent A₂, a palpable precordial thrill, and an apical–carotid (or brachioradial) delay. Except for the thrill, all other features also have significant likelihood ratios in separating severe AS from mild to moderate disease or from aortic sclerosis. Conversely, lack of radiation to the right carotid artery argues most strongly against AS.

97 What is the apical–carotid and brachioradial delay?

It is a palpable delay between the apical and carotid impulse and between the brachial and radial impulse. Patients with valvular AS may have both.

98 How valuable is a pulse that is parvus and tardus?

Valuable, but mostly in younger subjects because various factors in the elderly may result in a misleadingly brisk carotid upstroke, with early peak and normal amplitude in spite of severe stenosis. Among these are changes in arterial compliance, impedance, concomitant aortic regurgitation, and, more importantly, increased wall stiffness due to coexisting hypertension or atherosclerosis. Hence, the frequent lack of parvus and tardus in older patients.

99 Is the timing of peak intensity always reflective of severity of disease?

No. Although this finding does correspond to the time course of the transvalvular pressure gradient (with progressive delaying in peak corresponding to more severe obstruction), it also is true that early peaks can simply be the result of an increased transvalvular flow rate—as seen, for example, in patients with coexisting aortic regurgitation, a not uncommon event in AS. Peripheral vascular impedance wave reflections (and compliance) also may affect the timing of peak intensity, thus making this finding a less specific predictor of severity in the elderly.

100 And how can one differentiate AS from the other systolic murmurs?

Mitral regurgitation, tricuspid regurgitation, hypertrophic cardiomyopathy, and mitral valve prolapse also can be ruled in (and ruled out) through physical exam—at least by cardiologists, even though the studies supporting this conclusion tend to be smaller and of lower quality. Still, it appears that in the hands (and ears) of specialists, the clinical examination can accurately detect various causes of abnormal systolic murmurs. It also can exclude pathology. In fact, one could state with Etchells that a cardiologist’s assessment of a murmur as “normal” significantly reduces the likelihood of disease, whereas its assessment as being “abnormal” significantly increases it. Whether this conclusion also applies to noncardiologists needs to be determined.

101 Are there any other murmur characteristics that can predict the severity of AS?

Intensity, but only in younger individuals. In older patients, various other factors (such as concomitant obstructive lung disease or obesity) may in fact soften even the most severe of murmurs. Since the bone is a good sound conductor, auscultation over the neck (or right clavicle) may help to restore adequate murmur intensity in these patients. Note that the murmur may soften considerably (and almost disappear) when the failing ventricle becomes unable to overcome a high pressure gradient and thus generate enough turbulence. Hence, soft AS murmurs may paradoxically indicate advanced disease. Still, in asymptomatic patients, absence of a murmur (or a 1/6 grade) argues strongly against the presence of significant obstruction.

102 And what about the intensity of S₂?

Also very important. Although a small number of AS patients may have loud murmurs in spite of mild to moderate disease, loudness together with a soft or absent aortic component of S₂ (A₂) almost always reflects severe obstruction. Conversely, a well-preserved (and physiologically split) S₂ argues strongly against the presence of severe AS. The only exceptions are concomitant mitral regurgitation, pulmonary hypertension, or right ventricular conduction delay.

103 What are the reasons for a soft S₂ in AS?

Either calcification of the aortic cusps (which renders closure inaudible) or a prolongation of left ventricular ejection time (which delays A₂ and thus renders its interval from P₂ too narrowed to be audible). The latter is indeed common in patients with reduced left ventricular function and thus provides an important predictor of disease severity.

104 What about the transmission of the murmur?

Toward the neck and right carotid. Although traditionally linked to AS (and in fact, arguing against it if lacking), this type of transmission does not reflect disease severity.

105 Is there any other acoustic event that may suggest severe AS?

Intuitively, one could think of the S₄ and the early systolic click. And yet:

106 Are there any other findings that do not predict severity of AS?

Narrow pulse pressure, paradoxical splitting of S₂, and third heart sound. Although traditionally linked to AS, these do not correlate with AS severity.

107 How is the point of maximal impulse (PMI) in AS?

There are two major characteristics:

108 How are the neck veins in patients with AS?

They may have a prominent “A” wave, as a result of the “Bernheim phenomenon.”

109 What is the “Bernheim phenomenon”?

It is a phenomenon first described in 1910 by the French physiologist P.I. Bernheim. It consists of an interaction between the left and right ventricle, such that a change in the function of one leads inevitably to an alteration in the function of the other. In other words, a dilation/hypertrophy of the left ventricle would compress the right ventricle, resulting in its impaired filling. This is in part due to the restraining influence of the pericardium (which ensures that any increase in left ventricular volume occurs at the expense of the right ventricle, as a result of leftward shift in the septum), and in part due to the secondary pulmonary hypertension caused by increased left ventricular filling pressure. Hence the prominent “A” wave of patients with AS.

110 What is the “reverse Bernheim phenomenon”?

It is a leftward shift of the interventricular septum, secondary to pressure or volume load of the right ventricle. This causes a decrease in left ventricular size, contractility, compliance, and ejection fraction, as well as an increase in diastolic pressure of the left ventricle—hence, a left ventricular diastolic dysfunction. Although never actually suggested by Bernheim, this phenomenon is noticed in a wide array of pulmonary diseases with right ventricular hypertrophy.

111 What then are the valuable clinical predictors of severe AS?

Clearly, ECG presence of left ventricular hypertrophy or radiologic evidence of valvular calcification. As for the bedside, Otto et al. found the three most useful predictors to be:

Still, no single physical finding has both high sensitivity and specificity for detecting severe valvular obstruction. Some findings (such as murmur grade = 3 or decreased carotid upstroke) have high specificity but lack sensitivity. Others (like murmur peak in mid-to-late systole, or murmur intensity = 2) have high sensitivity but low specificity. Hoagland et al. found predictive value in combining five bedside findings: (1 and 2) reduced and delayed carotid upstroke (2 and 3 points, respectively); (3) murmur loudest over the aortic area (2 points); (4) reduced A₂ (3 points); and (5) radiologic calcification of the valve (4 points). Scores >10 identified severe obstruction, whereas scores <6 identified mild obstruction. Intermediate scores were not helpful.

112 And what about bedside predictors of clinical outcome?

In the same aforementioned study, Otto et al. found the intensity of the systolic murmur, the timing of its peak, the presence of a single S₂, and delayed/reduced carotid amplitude to be all significant univariate predictors of clinical outcome. On multivariate analysis, however, only the carotid upstroke amplitude remained predictive. Hence, physical examination appears to correlate with disease severity and prognosis, but this correlation is not too close. Echocardiography remains, therefore, essential to reliably exclude severe obstruction and to predict clinical outcome.

113 Why is physical examination inadequate in predicting disease severity?

Not because of interobserver variability or examiners’ expertise, but because of the pathophysiology of AS, and its modulating coexisting conditions: old age, emphysema, atherosclerotic changes of the arterial wall, or concomitant AR. As a result, bedside exam has low specificity for detecting severity (due to the many false positives of moderate disease) and occasionally low sensitivity. Yet, it can accurately separate mild from moderate to severe AS.

114 In summary, what is the role of physical examination in valvular AS?

It varies, depending on the clinical situation. In patients with cardiac symptoms, a loud (grade 3 or 4) and late peaking systolic murmur associated with a significantly reduced (and delayed) carotid upstroke strongly argues in favor of severe AS and thus prompts treatment. In this case, bedside findings can be quite specific. In other situations, however (like preoperative evaluation for noncardiac surgery), the goal of the exam may simply be the exclusion of severe disease. In this setting, an early peaking and soft murmur (grade 2 or less) with a normal carotid upstroke and a physiologically split S₂ all argues against significant disease. They are, in fact, very sensitive—yet not 100%. Hence, echocardiography may still be necessary to completely exclude AS.

115 What are the clinical implications for a primary care physician?

First of all, that it is crucial to consider AS in any adult presenting with a systolic murmur and symptoms of outflow obstruction (judge murmurs like people, by the company they keep). Hence, listen (with both the stethoscope and your ears) to what your patients are trying to tell you. Still, beware that early symptoms may be subtle (a mild exercise intolerance, for example, usually ascribed to “getting old”) and that the classic triad of angina, dyspnea, and syncope is usually limited to the most advanced cases. Secondly, keep in mind that it is very difficult to rule out AS only on the basis of auscultation—the major exceptions being a very soft (grade 1/6) systolic murmur or a physiologically split S₂. Hence, rely on ultrasonography to evaluate all symptomatic adults with a systolic murmur. Echo can visualize anatomy, estimate severity of obstruction, and provide crucial monitoring of disease progression.

Aortic Subvalvular Stenosis

117 Where is this murmur best heard?

It depends. When septal hypertrophy obstructs not only left but also right ventricular outflow, the murmur may be louder at the left lower sternal border. More commonly, however, the HOCM murmur is louder at the apex. This may often cause a differential diagnosis dilemma with the murmur of MR.

118 How can one differentiate the systolic ejection murmur of valvular AS from that of HOCM?

119 Does timing of onset of the HOCM murmur reflect severity of disease?

Yes and no. In moderate to severe HOCM, the onset of the murmur is often anticipated, suggesting a severe subaortic pressure gradient. Conversely, early murmurs also may be due to very rapid ejection (in HOCM, 80% of the left ventricular volume is usually ejected during the first half of systole, as compared to only 50% in the normal patient). Rapid ejection can manifest itself with a short and early systolic sound (ejection click) immediately following S₁.

120 What bedside maneuvers can modify the murmur of HOCM?

Maneuvers/factors that change left ventricular (LV) volume: a smaller volume brings the septum closer to the anterior mitral leaflet, thus causing a greater obstruction and a louder murmur. Conversely, a larger LV volume separates the upper septum from the anterior mitral leaflet, thus causing less obstruction and a softer murmur. Note that these are the same maneuvers that can respectively lengthen or soften the findings of mitral valve prolapse (see below, questions 178 and 179).

121 Which factors increase left ventricular volume?

Passive leg raising and standing-to-squatting have excellent sensitivity and specificity for softening the murmur of HOCM (both close to 90%). Hence, absence of softening strongly argues against presence of the disease.

122 Which factors reduce left ventricular volume?

Both Valsalva and squatting-to-standing have excellent specificity for intensifying the murmur of HOCM (both close to 90%, with Valsalva having an even higher positive likelihood ratio). Hence, if positive, both maneuvers argue strongly for the presence of the disease.

123 How accurate are these maneuvers in recognizing HOCM?

Quite accurate. Studies of cardiologists have indeed shown that passive leg raising and squatting-to-standing both have a good likelihood ratio in predicting the presence or absence of the murmur.

124 How does valvular AS respond to these maneuvers?

Very differently. For example, squatting softens HOCM (because it increases left ventricular diameter), whereas it intensifies valvular AS (because it increases both venous return and contractility due to the larger left ventricular diameter). Standing reduces venous return and thus intensifies HOCM (smaller ventricular diameter), whereas it softens valvular AS (through a decreased stroke volume).

125 How does a long diastolic pause after a premature beat affect the murmur of HOCM?

Not in the same way as it affects the murmurs of valvular or subvalvular “fixed” AS. In a study of 14 patients with HOCM, 40 with valvular AS and four with discrete subaortic AS, all experienced increases in left ventricular outflow gradient following a post extrasystolic beat. And yet, while 42 of the 44 (95%) with either valvular AS or discrete subaortic stenosis had increases in murmur intensity, only nine of 14 (64%) with HOCM did. In fact, only two (29%) of seven patients with HOCM and resting gradients of more than 25   mmHg had murmur increases. Hence, the murmur of HOCM does not increase consistently with the magnitude of the outflow tract gradient.

126 Can the murmur of HOCM be partially related to a murmur of mitral regurgitation?

Yes. In fact, HOCM is often associated with an apical murmur of MR. This is due to the pull-down on the mitral valve (especially its anterior leaflet) by the thickened and hypertrophic left ventricle, which not only causes outlet obstruction but also A-V regurgitation. Evidence of MR is encountered in 75% of all HOCM cases. In these patients, the murmur behaves like the HOCM murmur, insofar as it is delayed in onset and ends before A₂. Hence, if MR spans throughout systole, it is much more likely to be due to primary mitral regurgitation.

127 Are there any other associated physical findings in HOCM?

128 In summary, how accurate is physical exam for the diagnosis of HOCM?

Quite accurate, at least in the hands of cardiologists and when supported by bedside maneuvers such as passive leg raising or squatting-to-standing.

Subvalvular “Fixed”

Aortic Supravalvular Stenosis

131 What are the other characteristics of supravalvular AS?

Male gender plus a number of congenital abnormalities, like hypercalcemia and a peculiar “elfin” facies, with wide-set eyes, upturned nose, patulous lips, baggy cheeks, small chin, and a peculiarly deep, husky voice. These patients also tend to have a stronger pulse (and a higher blood pressure) in the right arm and carotid as compared to the left. Although the ejection murmur may be occasionally accompanied by an aortic regurgitant one, it is almost never associated with an aortic ejection click.

132 How does the murmur of pulmonic stenosis (PS) differ from that of aortic stenosis (AS)?

133 What other auscultatory features can help differentiate pulmonic from aortic stenosis?

Ventricular Septal Defect (VSD)

135 Can the shape of a VSD murmur help identify the type of defect?

Yes. A crescendo-decrescendo murmur usually indicates a defect in the muscular part of the septum. Ventricular contraction closes the hole toward the end of systole, thus causing the decrescendo phase of the murmur. Conversely, a defect in the membranous septum will enjoy no systolic reduction in flow and thus produce a murmur that remains constant and holosystolic.

136 Is there any relationship between the intensity of the murmur and the size of the defect?

No. Murmurs of varying intensity may occur with either small or large defects. Yet, whenever the defect is very large, the intensity of the murmur is usually very loud. Note, however, that a soft murmur may actually occur when very large defects are associated with severe pulmonary hypertension. In this case, the murmur usually follows an ejection sound (which is the hallmark of high pulmonary pressures) and ends with a very loud single S₂, continuing into an early diastolic murmur of pulmonary regurgitation (the Graham Steell murmur).

137 Where is the VSD murmur best heard?

Along the left lower sternal border, often radiating left to right across the chest.

138 How can one differentiate MR from VSD?

The MR murmur can be delayed in onset and exhibit a crescendo pattern toward S₂. This never occurs in a ventricular septal defect: even though some VSD murmurs may exhibit a crescendo pattern, they always start immediately after S₁. Finally, an early crescendo-decrescendo shape is not typical of MR, but is frequently seen in very small congenital muscular VSDs. Hence, the key to the recognition of a VSD murmur is that, in contrast to MR, it always starts immediately after the mitral component of S₁.

139 What is a systolic regurgitant murmur?

One characterized by a pressure gradient that causes a retrograde blood flow across an abnormal opening. This can be (1) a ventricular septal defect, (2) an incompetent mitral valve, (3) an incompetent tricuspid valve, or (4) fistulous communication between a high-pressure and a low-pressure vascular bed (such as a patent ductus arteriosus).

140 Is “regurgitation” the same as “insufficiency”?

Yes and no. All these acoustic events should be called murmurs of regurgitation, since insufficiency (or incompetence) solely defines the anatomic (and functional) features of the valve, and not the blood flow derangement that is the hallmark of true regurgitation: a backflow from a high- to a low-pressure chamber.

141 What are the auscultatory characteristics of systolic regurgitant murmurs?

They tend to start immediately after S₁, often extending into S₂. They also may have a musical quality, variously described as “honk” or “whoop.” This is usually caused by vibrating vegetations (endocarditis) or chordae tendineae (mitral valve prolapse, dilated cardiomyopathy) and may help separate the more musical murmurs of A-V regurgitation from the harsher sounds of semilunar stenosis. Note that in contrast to systolic ejection murmurs like AS or VSD, systolic regurgitant murmurs do not increase in intensity after a long diastole (see questions 26 and 68). In fact, if the intensity of a systolic murmur does increase, but only at the base, then it usually reflects the presence of two murmurs: one of ejection (becoming louder at the base) and one of regurgitation (remaining instead unchanged at the apex). Still, in mitral valve prolapse this rule does not hold, since the regurgitation of MVP is dictated by left ventricular volume: with larger volumes (such as those following a long diastole) causing instead reduced regurgitation, and thus a softer murmur.

I Mitral Regurgitation

143 What is the pathophysiology of MR?

It is a backflow into the atrium, leading eventually to the most pronounced left atrial enlargement of all valvular diseases. This typically comes with atrial fibrillation and increased pulmonary pressure. It also causes chronic volume load to the left ventricle, which, in turn, leads to its compensatory dilatation. Although this manages, at least initially, to maintain cardiac output, it eventually results in electrical irritability (sudden death) and myocardial decompensation.

144 What are the causes of MR?

They vary, depending on patient’s age and acuteness of condition. Overall, MR may be due to diseases of the valve per se (annulus, leaflets, chordae, and papillary muscles) or to alterations in left ventricular function/structure (from ischemic disease or dilated cardiomyopathy). Identification of the mechanism is crucial, since it determines (together with severity) clinical outcome, medical therapy, and the potential need for surgical intervention.

145 What are the most common “valvular” causes of MR in adults?

There are four:

In surgical series, the most common causes of severe MR are (in increasing frequency): endocarditis (10–12%), rheumatic heart disease (3–40%), ischemia (13–30%), and mitral valve prolapse (20–70%). Although the latter is common in surgical series, most patients with MVP only have mild disease, and thus never require surgery.

146 What are the most common “valvular” causes of MR in children?

In infants, the most common is a dysfunction of the papillary muscles, associated with either an anomalous left coronary (arising from the pulmonary artery) or endocardial fibroelastosis. Other congenital abnormalities that can lead to MR are endocardial cushion defect (with a cleft mitral leaflet) and myxomatous degeneration (often associated with Marfan’s; approximately 50% of Marfan patients may have MR). Finally, myocarditis also may cause regurgitation in infants.

147 Can left ventricular dilation and systolic dysfunction cause MR?

Yes. In fact, it is the most common cause of adult MR. Ventricular dilation may be due to cardiomyopathy, or MR per se, since dilation of the atrioventricular ring from MR renders the valve even more incompetent (hence, the dictum: mitral regurgitation begets regurgitation). This, however, usually causes mild regurgitation since the valvular orifice remains otherwise constant. Moreover, systolic contraction of the muscular ring in the annulus behaves like a sphincter, further minimizing regurgitation. That is why annulus calcification in the elderly is such an ominous event: it disables the sphincter and renders the valve truly incompetent. Yet, even this form of MR is only mild to moderate, mostly because the decreased left ventricular function cannot generate massive regurgitation. Hence, the murmur is usually soft. Moreover, patients with MR from cardiomyopathy often have such a low ejection fraction that they cannot afford surgical repair, since the failing valve provides a much-needed low-pressure escape to ventricular emptying.

148 Once the typical murmur is detected and recognized, what is the prognosis of MR?

It depends on the etiology and severity. MR may remain asymptomatic for a long time, with average interval from diagnosis to symptoms of approximately 16 years. This may be even longer in mild to moderate disease since most series are indeed restricted to severe disease. Yet, once symptomatic, severe MR without surgery has poor prognosis, with survival rates of 33% at 8 years, and average mortality of approximately 5% per year. Most deaths are due to pump failure, but sudden death plays a role, too. Other comorbid conditions (such as atrial fibrillation, cerebral ischemic events, and endocarditis) also may worsen outcome.

149 How is MR detected in adults?

It depends:

150 What is the significance of detecting a typical MR murmur?

It strongly argues in favor of MR, with sensitivity and specificity of 80%. Conversely, absence of a murmur does argue against moderate to severe disease.

151 What are the characteristics of the MR murmur?

It is loudest at the apex, radiated to the left axilla or interscapular area, high pitched, plateau, and extending all the way into S₂ (holosystolic). S₂ is normal in intensity, but often widely split.

152 Can the “pitch” identify gradient?

Yes. Pitch depends on pressure gradient and flow. If the gradient is high (and the flow is low), the MR murmur is high pitched. Conversely, if the gradient is low (and the flow is high) the murmur is low pitched. Cases in between tend to have mixed frequency.

153 Can the murmur of MR radiate medially?

Yes. Rupture of the posterior chordae may redirect the regurgitant stream toward the atrial septum and aorta, thus producing a murmur that not only radiates into the neck like AS, but also has its crescendo pattern. Conversely, rupture of the anterior chordae may push the stream posteriorly into the mid-thoracic spine, or even toward the top of the head. At times, it may even direct flow across the chest, resembling a ventricular septal defect, and thus creating issues of differential diagnosis in post infarction patients.

154 Are all MR murmurs plateau?

No. Shape depends on where the murmur starts in systole. Late starters usually extend into S₂; conversely, early starters immediately follow S₁. Hence, the shape of MR can be plateau, crescendo-decrescendo, crescendo (starting at mid-systole), and even decrescendo (starting after S₁ and ending toward mid-systole). Usually, the loudest MR murmurs are holosystolic and crescendo-decrescendo (yet not as pronounced as the crescendo-decrescendo pattern of AS).

155 Can the MR murmur extend beyond S₂?

Yes. This occurs when left ventricular pressure remains higher than left atrial pressure, even after aortic closure, thus leading to a post-S₂ ongoing regurgitation.

156 What are the best bedside predictors of MR severity?

The same predictors of murmur severity in general: intensity and length. Hence, the louder (and longer) the MR murmur, the worse the regurgitation. Intensity is a particularly strong predictor of severity, especially in MR due to neither ischemia nor dilated cardiomyopathy. In a study of 170 consecutive patients, none of those with silent disease had a regurgitant volume >50   mL, and only one had a regurgitant fraction >40% (similar data were found for AR patients—see below, questions 236 and 237). Yet, since murmur grading is rather subjective, interobserver variability may be an issue, as can be obesity and emphysema.

157 What is the implication for the clinician?

That one should pay closer attention to murmur intensity: a murmur grade 4 or louder has a positive predictive value of 91% for severe MR. Conversely, a murmur grade <2 argues so strongly against significant regurgitation (predictive value of 97%) to make unnecessary any repeat confirmatory testing. Finally, a grade 3 murmur (which occurs in more than one third of MR patients) may reflect any degree of regurgitation, prompting a search for other signs of severity.

158 What are the other bedside signs of severe MR?

159 So what is the role of echocardiography in MR?

It allows an accurate evaluation of the presence, severity, and cause of MR. Hence, it should be obtained in all suspicious systolic murmurs, either because of their intermediate or high intensity (i.e., >3/6) or because of concomitant symptoms and findings.

160 Since both MR and AR cause similar peripheral findings, how can you separate the two?

Both conditions cause left ventricular volume load and thus resemble each other peripherally. Yet, the arterial pulse is brisk and single in MR, but often bisferiens in AR. The PMI is enlarged, sustained, and downward/laterally displaced in both processes; yet only in MR does it often present with an early diastolic extra impulse (S₃-like). Finally, neck veins are usually normal in both.

161 Can a murmur of severe regurgitation be nonetheless soft and almost silent?

Yes. In addition to obesity or emphysema, its most common reason is acute MR from transient papillary muscle ischemia. Most of these patients have silent but severe regurgitation, manifesting itself as either paroxysmal nocturnal dyspnea or “flash pulmonary edema” (conversely, transient ischemia in chronic MR presents as a new, loud, and symptomatic murmur). In addition to the dramatic presentation, the only other clues to diagnosis are a large left ventricle and a widely split S₂.

162 Can the shape of the murmur differentiate the various causes of regurgitation?

Yes. Plateau murmurs are more likely to be rheumatic, whereas murmurs that start in mid-systole and “grow” into S₂ are more likely to be due to either mitral valve prolapse or papillary muscle dysfunction. Because in this case the papillary muscle is not contracting well, its chordae become progressively longer as the ventricle gets smaller. This causes a murmur that grows louder throughout systole, is crescendo-like, and often has a cooing character—like the cry of a seagull.

163 Is there any bedside maneuver that can help identify papillary muscle dysfunction?

Passive leg raising for 20   seconds. This increases left ventricular volume and thus may elicit the murmur of papillary muscle dysfunction. Passive leg raising comes in handy in patients with angina and left ventricular failure who have transient and subtle MR.

164 Can you separate MR of ruptured chordae from MR of dysfunctional papillary muscles?

Yes. Dysfunctional papillary muscle(s) are either asymptomatic or presenting with mild congestive failure. Ruptured chordae (or papillary muscles) present instead much more dramatically, with an intense MR murmur (3/6 or greater), a loud S₃, and a flash pulmonary edema. In fact, the large amount of backflow in these patients may even increase atrial pressure so rapidly to eventually slow regurgitation early on in systole. Hence, the MR murmur typically starts immediately after S₁ and then softens (and even disappears) at mid-systole. This is the opposite of the murmur of dysfunctional papillary muscle, which starts instead at mid-systole, has a crescendo pattern, and usually ends at S₂ (although it also may last into mid-systole or even stay holosystolic). Patterns of radiation also may be unusual in ruptured chordae tendineae (see question 153). Finally, the MR of ruptured chordae is often associated with an S₄. This is due to the Starling’s effect of a dilated atrium, which results in greater contractility and thus a stronger (and louder) systole. S₄ is instead rare in MR from dysfunctional papillary muscles, and is almost absent in rheumatic disease.

165 What is the cause of ruptured chordae tendineae?

Usually, infective endocarditis. Very often, however, the rupture is idiopathic. In this case, the valve (or chordae) has a congenital myxomatous degeneration that makes it more prone to spontaneous rupture, especially during unusual strains. This is especially common in MVP.

166 What are the characteristics of the acute MR murmur?

The foremost is the patient’s instability due to incapacity of the normal-sized left atrium to accommodate the regurgitating stream. As a result, acute MR patients are often in florid pulmonary edema, with pulmonary hypertension and distended neck veins. In addition, the acute MR murmur tends to be very short, and even absent, since the left atrium and ventricle often behave like a common chamber, with no pressure gradient between them. Hence, in contrast to that of chronic MR (which is either holosystolic or late systolic) the acute MR murmur is often early systolic (exclusively so in 40% of cases) and is associated with an S₄ in 80% of the patients.

167 Is the murmur of MR increased or softened by respiration?

It depends on the phase of respiration, and its effect on right- and left-sided venous return. Usually, MR is softened by inhalation, whereas TR is heightened. The opposite occurs in exhalation.

168 What are the effects of other bedside maneuvers/vasoactive drugs on the intensity of MR?

To understand these effects, one has to remember that in MR the left ventricle has two possible discharge outlets: a high resistance bed (the aorta) and a low resistance bed (the left atrium). Increases in peripheral vascular resistance (by vasopressors, but also handgrip or squatting) will increase regurgitation and heighten the murmur. Conversely, they will soften AS.

169 What is the effect on MR of standing?

It increases peripheral vascular resistance, but its effect on the murmur depends on the etiology of MR. If primarily due to a dilated left ventricle, the murmur will get softer during standing (because decreased venous return causes a reduction in ventricular size). If, on the other hand, MR is due to other reasons, then the murmur will get louder during standing (because the increased peripheral vascular resistance increases the degree of regurgitation). This effect may nonetheless be upset by the drop in venous return caused by standing, and thus the intensity of the murmur may stay unchanged. Finally, if MR is due to MVP, a smaller left ventricle (as in standing) will cause more prolapse. Hence, standing may prolong and intensify the MVP murmur.

170 In summary, how accurate is physical examination for diagnosing MR?

It depends. In the ears of cardiologists, the absence of an apical late systolic/holosystolic murmur strongly argues against the presence of MR (except in acute MI). Cardiologists also can accurately distinguish left-sided regurgitant murmurs (like MR and VSD) by using transient arterial occlusion. Noncardiologists (especially house officers) are instead much less accurate.

II Mitral Valve Prolapse

172 What is the underlying abnormality of MVP?

A redundancy of one or both mitral leaflets, causing a systolic ballooning (and posterosuperior prolapsing) into the left atrium. This may present with a sharp mid- (or late) systolic click, possibly followed by a regurgitant murmur. Women are twice as often affected by MVP, which may even be familial (with autosomal dominant inheritance). Although systolic clicks had been known for decades, they were incorrectly given an extracardiac origin—mostly through the influence of Gallavardin. It was Reid and Barlow who first correctly interpreted them as due to MVP.

173 Which leaflet is most commonly involved?

Usually the posterior, which often has a myxomatous degeneration. This is commonly seen in Marfan patients, who indeed often have MVP. Yet, most MVP patients have no features of Marfan’s, although 20–30% do have some of its minor traits, such as tall stature, low body mass index, straight backs, pectus excavatum, scoliosis, greater arm span than height, and unusual joint flexibility.

174 Is myxomatous degeneration limited to the mitral valve?

No, it often extends to the tricuspid valve.

175 Who was Barlow?

John Brereton Barlow was chief of cardiology at Witwatersrand University in South Africa (Witwatersrand is Afrikaans for “white water reef”—under which the gold lies, since the homonymous and nearby mountain range is the source of 40% of all the gold ever mined on earth). Born in Cape Town in 1924, Barlow became well known because of his rugby skills, which eventually gained him a university admission to Johannesburg. As a med student, he became known for his frequent reference to rare and bizarre syndromes, which eventually earned him the nickname of “canary” (the South African equivalent of our “zebra,” since over there zebras are not a rarity, whereas canaries are. In a tribute to his reputation as eccentric, Barlow later on kept canaries outside his office). After serving in the British Army during World War II, he graduated from medical school and then trained for 3 years in Soweto, and 3 more years in London, under Sir John McMichael. It was there that he learned to challenge conventional wisdom (holy cows make great burgers), a penchant that eventually helped him make his most iconoclastic observation: that the mid- and late systolic click(s) were not extracardiac in origin (as Gallavardin had suggested), but due instead to “billowing” (and regurgitation) of the mitral leaflet. Although this had already been suggested by John Reid in the 1950s, it was so controversial that Barlow’s initial paper was rejected by Circulation, and eventually printed in short form in the Maryland State Medical Journal and the American Heart Journal (1963). The term mitral valve “prolapse,” however, was introduced by John Michael Criley during Barlow’s 1964 visit to Johns Hopkins. Criley also was the one to point out that the phenomenon was not due to filling of a subvalvular ventricular aneurysm (as Barlow had initially thought), but to a prolapsing of the mitral leaflet. Barlow accepted this observation and always credited Criley. Still, he never liked the term prolapse, preferring instead “billowing.” As a physician, he was the ultimate clinical cardiologist, in the classical and bedside-oriented British style. He practiced in Johannesburg for over 40 years, caring for underprivileged Soweto children and influential politicians like 1993 Nobel laureate Nelson Mandela. His passion for auscultation (and the bedside) was reflected in the Oslerian dedication of his textbook, Perspectives on the Mitral Valve: “To all students of medicine who listen, look, touch, and reflect; may they hear, see, feel, and comprehend.”

176 What are the characteristics of the mitral valve prolapse murmur?

It is a mitral regurgitant murmur—hence, loudest at the apex, mid to late systolic in onset (immediately following the click), and usually extending all the way into the second sound (A₂). In fact, it often has a crescendo shape that peaks at S₂. It is usually not too loud (never greater than 3/6), with some musical features that have been variously described as whoops or honks (as in the honking of a goose). Indeed, musical murmurs of this kind are almost always due to MVP.

177 Can mitral valve prolapse be silent? Can anything make it louder?

Click and murmur may often be absent. Bedside maneuvers, such as mild exercise, may, however, bring them back—either together or separately. Various positions and different phases of respiration can do the same—mostly by changing left ventricular size, since a larger ventricle pulls down on the ballooning valve, thus delaying/preventing its prolapse. This “trimming of the sail” through tense chordae can postpone (and possibly eliminate) the click. It also can shorten the murmur. Conversely, a smaller ventricle facilitates the posterior ballooning of the valve, thus causing earlier and more severe regurgitation. Hence, an earlier click and a longer murmur.

178 Which bedside maneuvers can reduce left ventricular size?

Inspiration, tachycardia (from mild exercise), standing (after squatting), and the straining phase of Valsalva. In other words, the same maneuvers previously described for HOCM. These reduce left ventricular size through a decrease in preload, thus anticipating click, lengthening murmur, and making both more audible. Squatting-to-standing also makes the murmur louder.

179 Which bedside maneuvers can increase left ventricular size?

Exhalation, bradycardia, passive leg raising, and squatting. These all delay the click, shorten the murmur, and lessen the severity of regurgitation. Drugs that slow heart rate (and thus enlarge the left ventricle) also will do the same. Hence, the common use of beta blockers in MVP.

180 In summary, how accurate is physical examination for the diagnosis of MVP?

It depends on the examiner. If a cardiologist hears a systolic click (with or without a murmur), then the likelihood of echocardiographic MVP is very high. Conversely, absence of both click and murmur strongly argues against MVP. Finally, presence of a holosystolic murmur without a click significantly increases the likelihood of long-term complications from MVP, such as cardiac death, progressive regurgitation requiring surgery, endocarditis, and systemic embolism; absence of both click and murmur makes instead these complications much less likely.

181 Do patients with an isolated click necessarily develop regurgitation?

No. When followed for as long as 8 years, they do not develop significant regurgitation. Hence, clickers tend to stay clickers, which may have importance for prophylaxis (see Chapter 11).

182 And what about the need for valvular replacement in patients with a murmur?

Still relatively low. Overall, MVP is associated with mild to moderate regurgitation, as indicated by the mid to late onset of the murmur. With time, regurgitation may worsen, but this is still rare, with only 3% of patients eventually requiring valve replacement. Severe but initially asymptomatic MVP also has a favorable 5-year outlook, with only one third of patients becoming symptomatic enough to require surgery. In fact, a much more common cause of severe regurgitation is rupture of malformed chordae, resulting in a flail leaflet. This has a poor 10-year outcome, independent of symptoms (90% of patients die or undergo surgery). Finally, an even more frequent reason for surgery is infective endocarditis, often the presenting manifestation of a previously silent MVP.

183 What is the differential diagnosis of MVP?

The most important is papillary muscle dysfunction from infarction/ischemia, since this, too, can cause “prolapse.” These patients are usually older (and more symptomatic) than those with MVP. HOCM also may prolapse the mitral valve, usually because of the unequal length of the chordae tendineae. Finally, a split S₁ or ejection sounds (early systolic clicks) may need to be differentiated from the click of MVP, which is later in systole and changed by maneuvers.

184 Can bedside maneuvers identify a murmur of papillary muscle dysfunction?

Yes, since this neither lengthens nor intensifies with sitting, standing, or Valsalva.

III Tricuspid Regurgitant (TR) Murmur

186 What is the most common cause of pulmonary hypertension in the United States?

Left ventricular failure. Think of pulmonary hypertension in terms of (1) post capillary etiologies (left ventricular failure, mitral stenosis, cor triatriatum, veno-occlusive pulmonary disease); (2) capillary etiologies (pulmonary obstructive, restrictive, and vascular diseases); and (3) pre-capillary etiologies (pulmonary emboli and primary pulmonary hypertension).

187 Where is the TR murmur best heard?

Over the left lower sternal border or the epigastric/subxiphoid area. At times, however, it may be best heard over the apex—especially when the right ventricle has become large enough to displace the left ventricle laterally and posteriorly. Occasionally, a TR murmur can be heard only over the free edge of the liver—especially in patients with “muffling” by chronic obstructive pulmonary disease (COPD) and air trapping.

188 What are the diagnostic features of a TR murmur?

It depends. If caused by pulmonary hypertension, it has a typical holosystolic duration with inspiratory accentuation (Rivero-Carvallo sign, positive in 2/3 of patients). Often, there is a whooping or honking quality. Note that the murmur remains intensified as long as inspiration is held, since right ventricular return is indeed increased throughout inspiration. The murmur may also intensify in response to other maneuvers that increase right-sided venous return, like having the patient bend the knees toward the chest, passively elevate the legs, or engage in mild exercise. Finally, presence of a typical murmur argues strongly in favor of TR, whereas its absence does not exclude it.

189 How can one differentiate TR from MR?

By their different area of maximal intensity. Still, a very enlarged right ventricle may at times expand leftwards and thus replace the left ventricle in its apical location. Conversely, a very enlarged left ventricle (as often seen in MR) may expand rightwards and thus confuse the listener. Hence, the easiest way to separate these two murmurs is indeed the inspiratory maneuver of Rivero-Carvallo, which intensifies only TR. Other useful findings are hepatic pulsatility (30–91% of TR patients—usually arguing in favor of moderate-to-severe disease with specificity >90%) and response to the abdominojugular reflux (MR elicits no response, whereas TR induces a positive reflux with concomitant increase in murmur intensity—Vitum sign, 60% sensitivity and 100% specificity). Neck vein examination can be helpful, too, since 70–85% of TR patients will have typical giant V waves with deep Y descents (i.e., the Lancisi sign, from Giovanni Lancisi, physician to three popes). This is often associated with the flickering of earlobes from regurgitating blood (80% sensitivity). MR patients have neither of these findings. Finally, TR gets louder within 1   second into the release phase of Valsalva, whereas MR takes longer (3   seconds).

190 Does the Lancisi sign predict severity?

No. A giant systolic “V” wave may be absent in regurgitations so severe to prevent the diastolic collapse of the vein (i.e., in patients with persistently high central venous pressure [CVP]). It may instead be very prominent in patients whose regurgitation is too mild to cause high CVP.

191 How can one measure central venous pressure (CVP) in TR?

With great difficulty. Estimation of CVP in TR can be misleading because of the interference by the large systolic regurgitant wave, which makes reading venous diastolic pressure much more complicated. To overcome this problem, you should rely on mean venous pressure. This is determined by identifying the patient’s position in which the systolic regurgitant wave becomes visible: the more upright this position is, the higher the diastolic central venous pressure will be.

192 What are the other bedside findings of chronic TR?

90% of patients have distended neck veins, plus peripheral edema and/or ascites.

193 In summary, how accurate is physical examination for the diagnosis of TR?

Once again, it depends on the examiner. Overall, cardiologists can accurately detect the murmur of moderate to severe TR, especially if using quiet inspiration and sustained abdominal pressure.

194 How does acute TR differ from its chronic counterpart?

In many ways. Whenever regurgitation is sudden, its murmur is typically limited to early systole, and often decrescendo because right atrial pressure rises so rapidly to eventually stop backflow at mid-systole—a phenomenon similar to that behind acute MR (see question 166). In fact, whenever regurgitation is so severe that the atrium and ventricle become a single chamber, the murmur of TR (and MR) is absent. This may occur in patients whose chordae rupture. Finally, many of the peripheral manifestations of TR (leg edema, ascites, pulsatile liver), and even some of its jugular findings, may be absent acutely, since pulmonary pressure remains low and TR less prominent.

195 What are the causes of a diastolic murmur?

Primarily two, both pathologic:

196 How are diastolic murmurs classified?

By their timing. Hence, the most important division is between murmurs that start just after S₂ (i.e., early diastolic—reflecting semilunar regurgitation) versus those that start a little later (i.e., mid to late diastolic, often with a presystolic accentuation—reflecting atrioventricular stenosis).

I Mitral Stenosis

198 Where is the murmur of MS best heard?

“/>At the apex, but a bit more medially than normal, since the left ventricle of MS is smaller. Hence, before listening to the apex with your bell, carefully palpate the PMI with the patient in left-lateral decubitus position.

199 What is the timing of the diastolic murmur of MS? What is its relationship to S₂?

The MS murmur is mid to late diastolic, insofar as it does not immediately follow S₂ (like the murmur of semilunar regurgitation), but is instead separated by a little pause. In fact, it often follows the opening snap (which may or may not be audible) and then rumbles through diastole.

200 What is the shape of the diastolic rumble of MS?

It has an initial crescendo pattern with a mid-diastolic peak (since the most rapid phase of ventricular filling occurs in early diastole), followed by a decrescendo phase and a final presystolic accentuation. This late diastolic “crescendo” has been traditionally attributed to a forceful left atrial contraction, but probably has a different mechanism, since it also can be heard in patients without a valid atrial contraction (like those in atrial fibrillation). Hence, it is probably due to a further increase in mitral narrowing caused by the onset of ventricular systole.

201 What is the pitch of the MS rumble?

Very low. The MS murmur is so low pitched to be detectable only in left lateral decubitus, by the bell, and after paying extraordinary attention because the rumble is more the result of flow than of a true atrioventricular pressure gradient. In fact, even in severe MS the maximum gradient is only 30   mmHg at the beginning of diastole and 10   mmHg at the end of it. This is definitely much lower than the peak gradient encountered in significant systolic obstruction, such as that of AS (where it may easily reach 50   mmHg). Since murmurs produced by flow tend to be lower pitched than those produced by gradient, the MS murmur has typical low frequencies. This has led to many adjectives, such as rumbling and laboring, first used by Austin Flint in 1884.

202 Is a very intense murmur reflective of more severe stenosis?

It depends. If the patient does not have concomitant mitral regurgitation, a loud murmur (usually accompanied by a thrill [i.e., >4/6]) does indeed reflect severe stenosis. Conversely, a loud murmur also indicates absence of significant pulmonary hypertension—which is a good prognostic sign because a reduction of flow from the right into the left chambers (as the result of severe pulmonary hypertension) would actually decrease the intensity of the MS rumble.

203 What are the other physical findings of mitral stenosis?

204 Which maneuvers can be used to intensify the MS rumble?

First of all, maneuvers that can bring the left ventricle closer to the chest wall, and thus to the stethoscope. The most common is the left-lateral decubitus. Maneuvers that increase cardiac output (and thus flow across the stenotic valve) also can intensify the murmur. For example, asking the patient to engage in brief exercise (such as getting up from bed) immediately before auscultation. Or listening while the patient is squatting during a hand-grip maneuver. Finally, listening while the patient is raising the straightened legs also may enhance the murmur. If this is too cumbersome, one may simply ask the patient to raise his or her legs while keeping the knees bent toward the chest. At times, even a few bouts of coughing or the completion of a Valsalva straining maneuver (with auscultation carried out during the release phase) may do the trick.

205 And what about respiration?

Exhalation also can increase murmur intensity because it not only causes the heart to get closer to the stethoscope (due to diminished lung aeration), but it also squeezes blood from the lungs into the left chambers, thus increasing flow across the stenotic valve. Overall, left-sided findings intensify in expiration, whereas right-sided findings intensify in inspiration. The reasons are physiologically different, but grounded on the same principle: increased venous return.

206 What is then the best strategy to detect the MS murmur?

The best strategy consists of listening over the apex, with the patient in the left lateral decubitus position, at the end of exhalation, and after a short exercise. Finally, applying the bell with very light pressure also may help (strong pressure will instead completely eliminate the low frequencies of MS).

207 And what about the concomitant presence of mitral regurgitation?

If the patient also were to have MR, the MS murmur would be louder independent of the pressure gradient because MR increases not only left ventricular size (thereby bringing the left ventricle closer to the stethoscope), but also left atrial volume (due to the regurgitation). This, in turn, increases diastolic flow through the stenotic mitral valve, and thus the MS rumble.

208 Which conditions are instead associated with a softer murmur of MS?

The most common is emphysema. Low transvalvular flow also may soften the murmur. Though severe MS is typically the reason for this, severe pulmonary hypertension, cardiomyopathy, and concomitant tricuspid stenosis may do it, too. Finally, a large right ventricle (which is the end result of pulmonary hypertension) may displace posteriorly its left-sided counterpart, thus pushing it away from the anterior wall—and the stethoscope. This, in turn, will make the MS murmur softer.

209 What is the effect of atrial fibrillation on the intensity of MS?

It softens the murmur. This is due to its tachycardia and also to the absence of a valid atrial contraction (which can increase cardiac output by about 25% in patients with significant MS).

II Mitral Diastolic Flow Murmur

III Tricuspid Diastolic Murmurs

212 Where are these murmurs mostly heard?

Over the right ventricular area (i.e., the epigastrium/subxiphoid site), but also over the lower parasternal areas (left and right). Note that whenever the right ventricle is very dilated, it may actually displace backwards the left ventricle and position itself over the true apex.

213 What are the most common causes of a tricuspid diastolic flow murmur?

It depends. Increased flow through the tricuspid valve may occur in atrial septal defects, and thus produce a diastolic flow rumble. A similar rumble also may occur in situations of TR, also as a result of increased diastolic flow. Both these murmurs can be intensified by minimal exercise, like holding up the patient’s legs, bending them backwards, or simply having the patient take deep inspirations (panting). Still, the major differential diagnosis for a diastolic flow murmur is stenosis of the corresponding valve (i.e., tricuspid stenosis [TS]). The hallmark of TS is its very accentuated presystolic component, which is typical of it, and absent in tricuspid diastolic flow murmurs. Also, TS tends to occur without S₃, whereas the tricuspid diastolic flow murmur is often accompanied by it.

214 How frequently does tricuspid stenosis occur in patients with MS?

In as many as 5%. It is usually detected over the same area of tricuspid diastolic flow murmurs.

215 How can one differentiate TS from MS?

In addition to having different locations, the TS murmur increases with inspiration, whereas the one of MS softens (Rivero-Carvallo phenomenon). The murmur of TS also is louder in the right-lateral decubitus position, whereas that of MS is louder in the left-lateral decubitus position. Finally, the MS murmur tends to have a low-pitched quality, whereas the one of TS has instead a more scratchy quality.

I Aortic Regurgitation (AR)

217 What are its causes?

Primarily two: (1) aortic cusp disease and (2) aortic root dilation. Before antibiotics, the two most common forms of adult AR were rheumatic fever (through its direct cusps’ involvement) and syphilis (through its root dilation). Although they both remain leading causes of AR worldwide, nowadays the most common mechanism in the West is a “leaky” bicuspid valve. This usually starts to fail in the fourth or fifth decade of life and eventually progresses to full-blown AR over a few years. A failed bicuspid valve was rumored to be behind Arnold Schwarzenegger’s 1997 surgery.

218 How does rheumatic fever cause aortic regurgitation?

By an inflammatory shrinkage/retraction of the cusps, which prevents the leaflets from fully juxtaposing. Inflammation also may fuse the commissures, resulting in combined AS and AR.

219 What are the other “valvular” causes of AR?

The major ones are:

220 What are the “root” causes of aortic regurgitation?

Several—all related to an enlarged ascending aorta. The most common are degenerative aortic dilation of the elderly, cystic medial necrosis of Marfan’s, syphilitic aortitis, and dissection of the ascending aorta. Root diseases have recently become more frequent than cusps diseases.

221 What about hypertension?

Severe hypertension also may cause aortic regurgitation (in as many as 60% of patients), usually because of either a bicuspid aortic valve or a dilation of the aortic ring. Most of the time, however, the leakage is minimal and mostly limited to an echocardiographic finding.

222 Is there any way to separate at the bedside “valvular” AR from “root” AR?

Location. Proctor Harvey proposed in 1963 that valvular AR tends to be loudest over the Erb’s point (left parasternal area), whereas “root” AR over the aortic area (right parasternal area). This is intuitive if one considers the anatomy. Note that a tambour S₂ (loud and ringing sound, with rich aortic overtones) suggests the presence of a dilated aortic root, serving as a drum-like (“tambour” in French) echoing chamber for the vibration of the regurgitating flow. Indeed, a bruit de tambour (“sound of drum”) used to be a typical 19th-century finding of syphilitic aortitis.

223 What is the pathophysiology of chronic AR?

In chronic AR, the left ventricle (LV) receives blood from both the atrium and aorta. This results in a volume load that, over time, leads to the greatest ventricular enlargement of any heart disease (which, in the past, led to the creation of the colorful term “ox-like heart”—“cor bovinum”). Although the LV end-diastolic volume becomes quite large, LV compliance also increases. As a result, LV end-diastolic pressure remains near normal, and LV hypertrophy is in fact minimal. Regurgitant flow, however, may be huge. In severe cases, regurgitant flow may exceed 20   L/min, with total LV output of almost 30   L/min. Eventually, a persistent rise in preload and afterload leads to myocardial dysfunction and a drop in cardiac output. This process of decompensation, however, is gradual and always precedes the onset of symptoms. Ultimately, the rise in left-ventricular end-diastolic pressure causes an increase in left-atrial, pulmonic, right-ventricular, and right-atrial pressures. Detection of the onset of LV dysfunction is crucial for timing surgery. Note that the cor bovinum (i.e., a heart of >500   g) was a common outcome of aortic regurgitation only historically. In fact, recent data from Germany (Fluri et al.) suggest that not only this condition is decreasing in frequency (from one in four to one in five of all “cardiac” autopsies), but it is also becoming increasingly associated with nonvalvular risk factors, such as coronary atherosclerosis, hypertension, COPD, and male gender. It is also being found at a more advanced age, suggesting the beneficial impact of recent therapeutic interventions (like ACE-inhibitors, beta blockers, statins, PTCA, and cardiac surgery).

224 What are the symptoms of AR?

Most patients are asymptomatic, and the diagnosis is usually established through detection of the typical diastolic murmur during a routine physical exam. In fact, in contrast to acute AR, chronic AR may be present for years before its initial symptom (exertional dyspnea) develops. This will then evolve into orthopnea and paroxysmal nocturnal dyspnea. The patient’s awareness of the heartbeat (due to left ventricular enlargement, heart pounding, and palpitations) is also a frequent AR symptom, whereas chest pain tends to be much less common than in AS: only 20% of patients experience it (with evidence of coronary artery disease in 10% of these cases). Still, nocturnal angina (often accompanied by diaphoresis) is not uncommon and usually due to diastolic hypotension triggered by sleep-related bradycardia. Some patients with AR also may report abdominal pain, presumably due to splanchnic ischemia.

225 What are the “central” signs of chronic AR?

226 What are the typical auscultatory findings of AR?

Depending on severity, there may be up to three murmurs (one in systole and two in diastole) plus an ejection click. Of course, the typical auscultatory finding is the diastolic tapering murmur, which, together with the brisk pulse and the enlarged/displaced PMI, constitutes the bedside diagnostic triad of AR. A characteristic early diastolic murmur argues very strongly in favor of the disease.

227 What is the click of AR?

It is an early systolic ejection sound caused by one of three mechanisms: (1) a bicuspid semilunar valve, (2) a brisk and turbulent ejection (usually indicative of a large regurgitation), or (3) a dilated aortic root. The latter is not uncommon in severe AR and leads to further regurgitation.

228 What about the systolic murmur?

It may be caused by concomitant AS, but most commonly indicates severe regurgitation,followed by an increased systolic flow across the valve. Hence, it is often referred to as “comitans” (Latin for companion). It provides an important clue to the severity of regurgitation. Hence, semilunar regurgitation is diagnosed in diastole (by the presence of an early diastolic and tapering murmur), but its severity is assessed in systole (by the presence of a concomitant ejection flow murmur and, possibly, of an early systolic click).

229 Is there any way to separate the comitans murmur of AR from the systolic murmur of AS?

The flow murmur of AR tends to be shorter than that of AS, with louder S₂ and brisker pulse.

230 What about the two diastolic murmurs?

They are (1) the tapering diastolic murmur of aortic regurgitation per se and (2) the rumbling diastolic murmur of Austin Flint (i.e., functional mitral stenosis).

231 What are the characteristics of the decrescendo murmur of AR?

The major one is that it starts immediately after the aortic component of S₂ (i.e., in early diastole) and that it tapers. If AR is trivial, the murmur may be short enough to be only early diastolic. At times, just an echo finding. Hence, absence of a murmur excludes moderate to severe disease.

232 Where is it best heard?

Usually over Erb’s point (third or fourth interspace, left parasternal line), but at times also over the aortic area, especially when a tortuous and dilated root pushes the ascending aorta anteriorly and to the right. This is common in case of ascending aortic aneurysm or severe atherosclerotic disease. Occasionally, the murmur is best heard at the apex, and at times even near the axilla or mid-left thorax (Cole-Cecil murmur). In fact, the surface projection of the AR murmur is the famous “sash” (i.e., an oblique line that goes from the aortic area to the apex).

233 What is the typical pitch of the AR murmur?

Variable and depending on the severity of regurgitation. Mild disease has a high-pitched, blowing, and musical murmur. Severe AR, on the other hand, has only a few medium- to high-pitched components. Occasionally, the diastolic murmur acquires a very musical quality, like a seagull cry or “dove-coo” murmur. This has been shown by echo to coincide with the coarse fluttering of the aortic posterior wall during the opening of the mitral valve—which explains why a triphasic dove-coo murmur is rare in patients with AR of rheumatic origin, who often have concomitant mitral involvement, hampering its diastolic opening and thus limiting aortic root vibrations.

234 What maneuvers can increase the loudness of a soft AR murmur?

Positional maneuvers. The decrescendo diastolic murmur of AR is best heard by having the patient sit up and lean forward while holding breath in exhalation. Using the diaphragm and pressing hard on the stethoscope also may help since this murmur is rich in high frequencies. Finally, increasing peripheral vascular resistances (by having the patient squat) will also intensify the murmur.

235 How do you differentiate the MS murmur from that of AR?

AR starts immediately after the aortic component of S₂, whereas MS is always delayed a little, often heralded by an opening snap. In addition, MS has a presystolic accentuation that AR lacks.

236 What auscultatory characteristics of AR correlate with severity of regurgitation?

The major ones are length (the longer the diastolic murmur, the worse the AR) and intensity.

237 How does intensity of AR predict severity?

The louder the murmur, the worse the regurgitation. In fact, this is a characteristic that AR shares with MR: a murmur grade of 3 or louder carries a high probability of severe regurgitation, with a positive predictive value of 79%. Conversely, a murmur grade <1 argues so strongly against significant regurgitation that confirmatory testing may not even be required. Finally, a grade 2 murmur (which is quite frequent, occurring in more than one third of all AR patients) may reflect any degree of regurgitation. In this case, other signs of severity should be pursued, such as length of the diastolic murmur, concomitant systolic flow murmur/ejection sound, and presence of Austin Flint. Still, the longer and the louder the murmur of AR, the worse the disease.

238 What is Austin Flint (A-F)?

It is a mitral stenosis–like diastolic rumble, best heard at the apex, and due to the regurgitant aortic stream preventing full opening of the anterior mitral leaflet. It was first described by the homonymous cardiologist during the height of the American Civil War.

239 How common is this finding?

Rare in mild disease, but it can occur in more than 50% of moderate to severe AR cases.

240 Is the presence of an Austin Flint murmur an indication of severe regurgitation?

Yes, but not necessarily. Although A-F usually requires an aortic regurgitant volume of at least 50   mL, it also has been reported in patients with moderate regurgitation. Still, its presence does indicate a high left ventricular end-diastolic pressure and a high left atrial mean pressure.

241 How can one differentiate the A-F murmur from one of mitral stenosis?

Whereas the murmur of MS is mid-diastolic with a presystolic accentuation, the A-F murmur is presystolic in only half of the cases (the other half has both the mid-diastolic and presystolic components). In addition, A-F usually lacks the opening snap (which is instead common in MS), while it may have instead an S₃ (which is extremely rare in MS). Finally, reducing aortic pressure (and thus AR) tends to attenuate (or eliminate) the Austin Flint murmur, while instead intensifying the rumble of MS. Of course, an echo of the mitral valve would definitively differentiate the two.

242 Who was Austin Flint?

He was a Massachusetts cardiologist, who was greatly influenced at Harvard by one of the first American followers of Laënnec. A superb clinician and teacher, Flint taught in Buffalo (where he helped create the local medical college), Chicago, New Orleans, and finally New York, where he was professor of medicine at Bellevue before moving to Long Island Hospital, where he died of a stroke in 1886, at age 74. A proponent of European diagnostic methods (who wrote that “the diagnosis of cardiac disease is for the most part based on physical signs”), Flint popularized the binaural stethoscope and became so well respected as to eventually be referred to as “the American Laënnec.” His many contributions were mostly in cardiology, but he also forayed into pulmonary medicine, authoring the (in)famous term of “bronchovesicular breath sounds.” Eventually, he ascended to the presidency of the American Medical Association. He had a son (whom in a fit of creativity he named Austin) who graduated from Jefferson Medical College of Philadelphia and became a well-respected physiologist and cofounder of New York University.

243 Which other bedside findings correlate with severity of regurgitation?

Hill’s sign. If >60   mmHg, it argues very strongly in favor of severe regurgitation (see Chapter 2, questions 110–115). So does a diastolic blood pressure <50   mmHg and a pulse pressure >80   mmHg. Conversely, a diastolic blood pressure >70 and a pulse pressure <60 argue strongly against severe disease. Finally, absence of an enlarged or sustained apical impulse also argues against severe disease. Yet, these predictors of severity only apply to patients with chronic AR. Acute AR is very different.

244 What are the other auscultatory findings of AR?

Softness of S₁ and loudness of S₂ (due to increased elastic aortic recoil). S₂ also is single in AR. Note that in more severe AR, S₂ tends to become muffled.

245 And how about the presence of S₃ in AR?

S₃ gallops may occur in patients with pure AR, although they usually are much more common in patients with multivalvular disease. In isolated AR, S₃ reflects left ventricular dysfunction rather than more severe regurgitation. Hence, it may help in selecting patients for catheterization and surgery.

246 What are the “peripheral” signs of AR?

They are a plethora of eponyms, many going back more than 150 years, and most being just curious observations that, with a few exceptions, do not correlate with disease severity. Instead, they correlate with the wide pulse pressure of AR and its brisk arterial rise that can cause visible (and palpable) jolts. In fact, jolts of this sort have been reported even for the cervix and spleen. We reviewed some of these findings in the Vital Signs and Arterial Pulse sections of Chapters 2 and 10. Here are some more:

All these visible (and palpable) signs are enhanced by exercise, as a result of increased pulse pressure. In addition, there are two more peripheral findings that are instead exclusively auscultatory (see Chapter 10, questions 33–36): (1) Traube pistol shot sound(s) and (2) Duroziez double murmur. Both have sensitivity of 37–55% and specificity of 63–98% for AR. Neither predicts severity.

247 What is Quincke’s pulse (sign)?

It is another peripheral AR sign, albeit a vastly discredited one, since it is totally nonspecific. It consists of alternate reddening and blanching of the fingernails, coinciding with each cardiac cycle, and is easily visualized by lightly compressing the nail bed with a glass slide. It can occur in anyone with a hyperkinetic heart. In fact, even the ingestion of a few strong espressos might do it. An equivalent of this is the so-called lighthouse sign (flushing and blanching of the forehead and face). Similarly nonspecific is the lip pulsation of AR patients.

248 Who was Quincke?

Heinrich Irenaeus Quincke (1842–1922) was the son of a prominent German physician, who studied under Virchow and Helmholtz and went on to become a rather fussy gentleman with a penchant for horseback riding and argumentative conversations. Quincke taught in Vienna, Berlin, and Bern, until eventually taking the chair of internal medicine at the University of Kiel. He remained there until he retired as emeritus in 1908. His most notable contribution is neither the description of capillary pulsations in aortic regurgitation nor the description of angioneurotic edema (none of which was a first), but his introduction of the lumbar puncture as a diagnostic and therapeutic technique. Quincke also was the first to advocate surgical drainage of lung abscesses and better positioning of bronchiectatic patients for easier expectoration.

249 What are the signs of acute and severe AR?

Sudden and severe AR does not allow time for ventricular adaptation and enlargement. Hence, LV diameter remains small, and pulse pressure actually narrows. As a result, stroke volume cannot increase adequately and thus forward cardiac output declines. To compensate for the reduced stroke volume, the heart rate increases sharply. Eventually, rising LV end-diastolic pressure leads to early closure of the mitral valve. Hence, the murmur of acute AR is almost never holodiastolic, but instead early to mid-diastolic and thus more difficult to recognize. In fact, the most typical auscultatory sign of sudden and severe AR is a soft or absent S₁, due to premature mitral closure. Still, the hallmark is clinical instability. Patients are typically tachycardic, orthopneic, cyanotic, clammy, vasoconstricted, and gravely ill—often in overt failure or shock.

250 What are the causes of “acute” AR?

251 What are the morbidity and mortality of AR ?

It varies. Acute AR carries a grave prognosis unless promptly corrected. Chronic AR is instead well tolerated, with less than 4% of patients per year requiring surgical replacement. The 10-year survival rates are 85–95% in mild disease, and 50% in moderate disease. But average survival decreases to less than 2 years after onset of congestive heart failure.

II Pulmonary Regurgitation

253 What is the Graham Steell murmur?

It is an early diastolic, tapering, high-pitched, and blowing murmur of pulmonic regurgitation (PR). It is due to pulmonary hypertension, which, in the 1888 description by Graham Steell, was the result of mitral stenosis. It is best heard over the second left interspace and thus may be confused for the murmur of AR—except that PR typically intensifies with held inspiration (Rivero-Carvallo).

254 Who was Graham Steell?

A Scottish physician and the author of a 1906 cardiology textbook that won the praise of Sir James MacKenzie. The son of a sculptor and the nephew of the Scottish National Gallery curator, Steell grew up in Edinburgh, where he also attended medical school. He subsequently transferred to Manchester, where he became the leading cardiologist of Northern England. A charismatic bedside teacher, but a boring lecturer whose classes often went unattended, Steell was a champion boxer as a youth, an animal lover, and one of the first promoters of physical exercise as the key to a long and productive life. His commitment served him well, since he lived into his 90s.

255 What are the other findings of a PR murmur?

They are the typical findings of pulmonary hypertension: loud P₂, a pulmonic ejection sound, distended neck veins, and a possible murmur of tricuspid regurgitation. In fact, a PR murmur occurs in 12% of patients with tricuspid regurgitation. Note that a PR murmur also can be heard in fluid-overloaded renal patients, just before their dialysis session.

256 How sensitive is this murmur for pulmonic regurgitation?

Not much, only 10% because the lower pressures of the pulmonary circuit make this murmur much softer than the one of AR and thus harder to detect. This is especially true in PR from endocarditis, which has lower pulmonary pressures and thus a murmur that is even softer and later starting. Hence, absence of a PR murmur does not exclude PR.

257 Is a PR murmur common in pulmonary embolism (PE)?

Usually not. In fact, findings of pulmonary hypertension are not too common in pulmonary embolism: distended neck veins (3%), loud pulmonary component of S₂ (19–57%), S₄ or S₃ (6–34%) are overall rare. Similarly rare are the findings of thrombotic disease, such as a swollen and tender calf (15–52%) or unilateral leg swelling (16%), although their specificity is usually much higher than the sensitivity, so that they achieve a positive likelihood ratio of 2.6.

258 What about the other findings of PE?

The only one that is common is tachycardia (81%), which has low specificity but a positive likelihood ratio (2.5). Everything else is much less frequent: respiratory rate >25 (48%), pleural rub (4–18%), use of accessory respiratory muscles (17%), cyanosis (3–19%), fever (7%), and diaphoresis (11–36%). Note that some misleading findings (like chest wall tenderness) can be present in up to one tenth of patients with PE, thus contributing to the difficulty of the diagnosis.

259 What are continuous murmurs?

They are systolic murmurs that go beyond S₂, thus extending into diastole. This is due to their extracardiac origin, usually from an abnormal communication between high- and low-pressure beds (which explains their ongoing gradient and sound). Although not really “murmurs that never end,” they are present throughout systole and diastole—as high-pitched noises that peak late in systole (around S₂) and then soften immediately afterwards, ending before the next S₁. Note that murmurs that cover systole and diastole but are not continuous are called instead “to-and-fro”—as, for example, the murmur of aortic stenosis and regurgitation, or the murmur of aortic regurgitation with its concomitant systolic ejection flow. They are so-called because their flow goes in opposite direction during systole as compared to diastole.

260 If continous murmurs are extracardiac, what conditions are responsible for them?

Conditions of:

261 Why are these murmurs continuous?

Because their pressure gradient persists throughout systole and diastole, thus causing a no-stop flow that is always turbulent and noisy. In PDA, this never-ending stream of high-pressure/high-oxygen blood between the aorta and pulmonary artery eventually leads to pulmonary hypertension. This, in turn, gradually decreases the pressure gradient between the two vessels, eventually fading the diastolic component of the murmur. After reversal of the shunt, the murmur will cease altogether, while the patient becomes cyanotic and findings of severe pulmonary hypertension ensue. This is the Eisenmenger’s syndrome (i.e., pulmonary hypertension from an initial left-to-right shunt that has evolved into shunt reversal and cyanosis). First described by the homonymous Austrian physician (1864–1932), Eisenmenger’s from PDA is often associated with clubbing, which, like cyanosis, involves the feet but not the hands since the reversed shunt only affects the dependent portion of the aorta (see “differential clubbing,” question 105 in Chapter 13).

262 What is the Nicoladoni-Israel-Branham sign?

It is a circulatory phenomenon initially observed in angioma racemosum of the extremities, but it is present in all arteriovenous fistulas, whether pathological or surgical: compression of the fistula causes a reflex bradycardia whenever there is significant flow through the fistula. First described by Nicoladoni in 1875 (and then by Israel in 1877 and Branham in 1890), it was subsequently rediscovered by Wigdorowitsch in 1915.

263 What is the differential diagnosis of “lots of noise” throughout the cardiac cycle?

“Noise” throughout systole and diastole usually reflects four possible processes (see Fig. 12-3):