Ebook ASE''s Comprehensive echocardiography textbook (2nd edition): Part 2

Section
Aortic Stenosis
XV

94

Aortic Stenosis Morphology
Steven A. Goldstein, MD

CONGENITAL AORTIC STENOSIS

Natural History of Bicuspid Aortic Valves

Bicuspid Aortic Valve

Although a few patients with BAV may go undetected or without
clinical consequences for a lifetime, most will develop complications. The most important clinical consequences of BAV are valve
stenosis, valve regurgitation, infective endocarditis, and aortic
complications such as dilatation, dissection, and rupture
(Box 94.2). Estimates of the prevalence of these complications
and outcomes have varied depending on the era of the study, the
cohort selected, and the method used to diagnose BAV (clinical
exam vs. cardiac catheterization vs. echocardiography). Several
large recent studies have helped to better define the unoperated
clinical course in the modern era.17–19
Isolated AS is the most frequent complication of BAV, occurring in approximately 85% of all BAV cases.10,18–20 Bicuspid aortic
valve accounts for the majority of patients aged 15 to 65 years with
significant AS. The progression of the congenitally deformed valve
to AS presumably reflects its propensity for premature fibrosis,
stiffening, and calcium deposition in these structurally abnormal
valves.

Aortic regurgitation, present in approximately 15% of patients
with BAV,10 is usually due to dilation of the sinotubular junction of
the aortic root, preventing cusp coaptation. It may also be caused by
cusp prolapse, fibrotic retraction of the leaflet(s), or damage to the
valve from infective endocarditis. Aortic regurgitation tends to
occur in younger patients than does AS.
Why some patients with a BAV develop stenosis and others
regurgitation is not clear. As mentioned, rarely, patients may not
develop hemodynamics consequences. Roberts and colleagues
reported three congenital BAVs in nonagenarians who underwent
surgery for AS.21 Why some patients with a congenital BAV do
not become symptomatic until they are in their 90s and why others
become symptomatic in early life is also unclear.

Congenital aortic valve malformation reflects a phenotypic continuum of unicuspid valve (severe form), bicuspid valve (moderate
form), tricuspid valve (normal, but may be abnormal), and the rare
quadricuspid forms. Bicuspid aortic valves (BAVs) are the result of
abnormal cusp formation during the complex developmental process. In most cases, adjacent cusps fail to separate, resulting in
one larger conjoined cusp and a smaller one. Therefore, BAV (or
bicommissural aortic valve) has partial or complete fusion of two
of the aortic valve leaflets, with or without a central raphe, resulting
in partial or complete absence of a functional commissure between
the fused leaflets.1
The generally accepted prevalence of BAV in the general population is 1% to 2%, making it the most common congenital heart
defect. Information on the prevalence of BAV comes primarily
from pathology centers.1–7 Valvular aortic stenosis (AS), a chronic
progressive disease, usually develops over decades. Box 94.1 lists
the most common etiologies of valvular AS, as illustrated in
Figure 94.1. The majority of cases of AS are acquired and result
from degenerative (calcific) changes in an anatomically normal trileaflet aortic valve that becomes gradually dysfunctional over time.

Congenitally abnormal valves may be stenotic at birth but usually
become dysfunctional during early adolescence or early adulthood.
A congenitally bicuspid aortic valve is now the most common
course of valvular AS in patients under the age of 65. Rheumatic
AS is now much less common than in prior decades and is virtually
always accompanied by mitral valve disease. Other forms of
nonvalvular left ventricular outflow obstruction (e.g., discrete subvalve AS, hypertrophic cardiomyopathy, and supravalve AS) are
discussed in other chapters.
The most reliable estimate of BAV prevalence is often considered to be the 1.37% reported by Larson and Edwards.4 The authors
have a special expertise in aortic valve disease and amassed 21,417
consecutive autopsies with 293 BAVs. An echocardiographic survey of primary school children demonstrated a BAV in 0.5% of
males and 0.2% of females.8 A more recent study detected 0.8%
BAVs in nearly 21,000 men in Italy who underwent echocardiographic screening for the military.9 Table 94.1 summarizes data
on the prevalence of bicuspid valves. Bicuspid aortic valve is seen
predominantly in males, with a 2:1 male-to-female ratio.10–12
Although BAV may occur in isolation, it may also be associated
with other congenital cardiovascular malformations, including
coarctation, patent ductus arteriosus, supravalve AS, atrial septal
defect, ventricular septal defect, sinus of Valsalva aneurysm, and
coronary artery anomalies.1,13–16 There are also several syndromes
in which BAV is a part of left-sided obstructive lesions of left
ventricular inflow and outflow obstruction, including Shone syndrome (multiple left-sided lesions of inflow and outflow obstruction), Williams syndrome (supravalvular stenosis), and Turner
syndrome (coarctation).

Echocardiographic Features of Bicuspid Aortic Valves
The roles of echocardiography in the detection and evaluation are
listed in Box 94.3. The diagnosis of a BAV can usually be made by
transthoracic echocardiography (TTE). When adequate images are
obtained, sensitivities and specificities of up to 92% and 96%,
respectively, have been reported for detecting BAV.22–24 The most

reliable and useful views are the parasternal short-axis and longaxis views. The echocardiographic features and their respective
views are summarized in Box 94.3. The parasternal short-axis view
(SAX) is extremely useful to examine the number and position of
the commissures, the opening pattern, the presence of a raphe, and
the leaflet mobility. In contrast to the normal tricuspid aortic valve
(TAV), which opens in a triangular fashion with straightening of the
leaflets (see Fig. 94.1; Fig. 94.2, A), the BAV opens in an elliptical
(“fish-mouth” or “football”) shape with curvilinear leaflets (see
Fig. 94.1; Figs. 94.3 and 94.4). There is typically a raphe, a fibrous
ridge that represents the region where the cusps failed to separate.10,25 The raphe is usually distinct and generally extends from

389


390

SECTION XV Aortic Stenosis
TABLE 94.1 Prevalence of Bicuspid Aortic Valves (BAV)

Box 94.1 Aortic Stenosis: Etiology
1. Congenital (unicuspid, bicuspid, quadricuspid)
2. Degenerative (sclerosis of previously normal valve)
3. Rheumatic

the free margins to the base of the leaflet. Calcification commonly
occurs first along this raphe, ultimately hindering the motion of the
conjoined cusp.26 Rarely, the leaflets are symmetric and there is no
raphe—a “pure” bicuspid valve. Note that a false-negative diagnosis may occur when the raphe gives the appearance of a third coaptation line. In diastole, the normal trileaflet aortic valve appears like
a “Y” (inverted “Mercedes-Benz” sign), with the commissures at
10, 2, and 6 o’clock (see Figs. 94.1 and 94.2, B). When the commissures are deviated from those clock-face position, one should suspect a BAV and evaluate carefully. An additional short-axis feature

is a variable degree of leaflet redundancy. In patients with very little
redundancy of the leaflet margins, the development of stenosis is
likely, whereas a significantly redundant leaflet with associated
prolapse is more likely to lead to regurgitation.
The morphologic patterns of BAV vary according to which
commissures have fused, and a number of classifications have been
devised that pertain to the orientation of the leaflets1,10,27,28
(Fig. 94.5, Table 94.2). Fusion of the right and left cusps is the most
common morphologic type.28,29 In an echocardiographic study by
Brandenburg and colleagues,23 the posterior commissure was
located at 4 or 5 o’clock and the anterior commissure was located
at 9 or 10 o’clock when the valve is viewed in a parasternal shortaxis view. The second most frequent type, fusion of the right and
noncoronary cusps, has been linked to aortic arch involvement30–33
and may also be related to an increased risk of AS and regurgitation
compared with the other anatomic types.29 The least common type is
fusion of the left and noncoronary cusps.28 Michelena and colleagues
similarly classified BAVs as typical (right-left coronary cusp fusion)
if the commissures were at 4 and 10 o’clock, 5 and 11 o’clock, or 3 to
9 o’clock (anterior–posterior cusps) and atypical (right-noncoronary
cusp fusion) if the commissures were at 1 and 7 o’clock or 12 and
6 o’clock.19
Normal

Rheumatic

Author

Year

(n)

BAV
Prevalence

Method

Reference

Wauchope
Gross
Larson and
Edwards
Datta et al
Pauperio
et al
Basso et al
Nistri et al

1928
1937
1984

9,996
5,000
21,417

0.5
0.56
1.37

Autopsy
Autopsy
Autopsy

2
3
4

1988
1999

8,800
2,000

0.59
0.65

Autopsy
Autopsy

5
6

2004
2005

817
20,946

0.5

0.8

2D-echo
2D-echo

8
9

Box 94.2 Complications of Bicuspid Aortic Valves
Valve complications
• Stenosis
• Regurgitation
• Infection (endocarditis)
Aortic complications
• Dilatation
• Aneurysm
• Dissection
• Rupture

Box 94.3 Bicuspid Aortic Valve: Role of Echocardiography
•
•
•
•
•
•

Detection of bicuspid aortic valve
Evaluation for aortic stenosis/regurgitation
Careful measurements of aortic root and ascending aorta

Search for coarctation
Screening first-degree family members
Surveillance—following valve dysfunction and aortopathy

Calcific

Bicuspid

Figure 94.1. Diagram illustrating the diastolic (top row) and systolic (bottom row) appearances of a normal aortic valve and the three common
etiologies of valvular aortic stenosis. (Modified from Baumgartner H, Hung J, Bermejo J, et al. Echocardiographic assessment of valve stenosis:
EAE/ASE recommendations for clinical practice. Eur J Echocardiogr 10:1–25, 2009.)


Aortic Stenosis Morphology

391

94

A

B

Figure 94.2. Transthoracic echocardiogram (short-axis view) of a normal tricuspid aortic valve. A, In diastole, the normal trileaflet valve appears like a
“Y” with the commissures at 10, 2, and 6 o’clock. B, In systole, the valve opens in a triangular fashion with straightening of the leaflets.

n
P

P

R

L
270 (86%)

R

L
37 (12%)

315

P

R

L
8 (3%)

Figure 94.5. Variations in bicuspid valves. Relative positions of raphe
and conjoined cusp. (Adapted from Sabet HY, Edwards WD, Tazelaar HD,
et al. Mayo Clin Proc 1999;74:14-26a).

Figure 94.3. Transesophageal echocardiogram (cross section) of a
bicuspid aortic valve that illustrates the elliptical (“fish-mouth” or “football”) shape with curvilinear leaflets in systole.

A

B

The parasternal long-axis (PLAX) view typically shows systolic doming (see Fig. 94.4, B; and Fig. 94.6) due to the limited
valve opening. In a normal TAV, the leaflets open parallel to
the aortic walls. In diastole, one of the leaflets (the larger, conjoined cusp) may prolapse. The PLAX view with color Doppler
is also useful to evaluate for aortic regurgitation (the diastolic aortic regurgitant jet is usually eccentric) and AS (turbulence in the
aortic root and ascending aorta in systole). Last, the PLAX view is

C

Figure 94.4. Bicuspid aortic valve. A, Short-axis view shows “fish-mouth” or football-shaped opening. B, Long-axis view shows systolic doming.
C, Color Doppler shows eccentric aortic regurgitant jet (typical of bicuspid aortic valve).


392

SECTION XV Aortic Stenosis

TABLE 94.2 Distinctive Echocardiographic Features of Bicuspid
Aortic Valves
View
Systolic doming
Eccentric valve closure
Single commissural line in diastole
Two cusps, two commissures
Raphe
Oval opening (football-shaped; fish-mouth, elliptical;
“CBS-eye”)
Unequal cusp size

PLAX

PLAX
SAX
SAX
SAX
SAX
PLAX, SAX

PLAX, Parasternal long-axis; SAX, parasternal short-axis.

Figure 94.7. M-mode echocardiogram (echo) and phonocardiogram
(phono) from a patient with a bicuspid aortic valve. The echo illustrates
an eccentric closure line (green arrows) in both late and early diastolic;
the phono illustrates an aortic ejection sound (indicated by the bottom
of the red arrow) that occurs at the maximal abrupt opening of the aortic
valve (indicated by the red arrowhead).

consequently the jet flow may be abnormal in its direction.31 Hope
and colleagues32 demonstrated two different flow patterns that
were specific to the two most common cusp fusion types. Fusion
of the right-left coronary cusps generated a right-anterior flow
jet, whereas fusion of the right-noncoronary cusps generated a
left-posterior flow jet.
Figure 94.6. Transesophageal echocardiographic longitudinal view of
the aortic root and ascending aorta illustrating the systolic doming of a
bicuspid aortic valve.

also important for sizing the sinus of Valsalva, sinotubular
junction, and ascending aorta. With increasing age, as the leaflets
become thickened, fibrotic, and calcified, systolic doming may
no longer be evident and the typical short-axis appearance of

the BAV may be difficult to distinguish from calcific AS of a
TAV. In fact, there is an inverse association between the degree
of valve stenosis and accuracy of echocardiographically
determined valve structure and etiology.34 The elliptical systolic
opening in the SAX view is not easily appreciated in a severely
stenotic valve. M-mode echo of a BAV may demonstrate an
eccentric closure line (Fig. 94.7), but this sign is not reliable,
and approximately 25% of patients with a BAV have a relatively
central closure line. Moreover, occasionally TAVs can also appear
to have an eccentric closure line depending on image quality and
orientation of the echo beam.
If images are suboptimal or heavily fibrotic/sclerotic, then transesophageal echocardiography (TEE) may improve visualization of
the leaflets and may be helpful for accurate evaluation of the aortic
valve anatomy and confirmation of a BAV. In some instances,
alternative cardiac imaging, such as computed tomography (CT)
or magnetic resonance imaging (MRI), may help confirm BAV
anatomy. More commonly, these imaging modalities are used to
visualize the thoracic aorta.
Recently, phase contrast MRI has demonstrated abnormal flow
patterns in the ascending aorta in patients with a BAV, with or without stenosis or aneurysm.32 Even if the valve orifice is not reduced
(i.e., no stenosis), it is geometrically altered in BAV, and

Coarctation
Bicuspid aortic valve may occur in isolation or in association with
other forms of congenital heart disease. There is a well-documented
association of BAV with coarctation.7,20,24,35–40 An autopsy study
found coexisting coarctation of the aorta in 6% of cases of BAV,1
and an echocardiographic study found coarctation in 10% of
patients with BAV.38 On the other hand, as many as 30% to 70%
of patients with coarctation have a BAV.* Therefore, when a

BAV is detected on an echocardiogram, coarctation of the aorta
should always be sought.

Infective Endocarditis
Patients with BAVs are particularly susceptible to infective endocarditis. Although the exact incidence of endocarditis remains controversial, the population risk, even in the presence of a functionally
normal valve, may be as high as 3% over time.1 The estimated incidence is 0.16% per year in unoperated children and adolescents.41
In adults, the two large case series by Tzemos and Michelena and
their colleagues18,19 suggest that the incidence is 0.3% and 2% per
year, respectively. In a series of 128 microbiologically proven episodes of endocarditis, the commonest predisposing risk factor was
BAV (16.7%).42 In another series of 50 patients with native valve
endocarditis, 12% had BAV.43
In many cases of BAV, endocarditis is the first indication of
structural heart disease. This fact emphasizes the importance of
either clinical or echocardiographic screening for the diagnosis
of BAV. Unexplained systolic ejection sounds (clicks) should
prompt echocardiographic evaluation. Surprisingly, bacterial endocarditis prevention is no longer recommended by the most recent
*References 7, 20, 29, 37, 40.


Aortic Stenosis Morphology

393

TABLE 94.3 Frequency of Aortic Dissection in Persons with a Bicuspid Aortic Valve (BAV)
Author(s)

Year

Frequency of Aortic
Dissection in BAV

Fenoglio
Larsen and Edwards
Roberts and Roberts
Michelena et al

1977
1984
1991
2011

8/152 (5%)
18/293 (6%)
14/328 (4%)
2/416 (0.4%)

94

Population

Reference

Autopsy, !20 years old
Autopsy, all ages
Autopsy, >15 years old
Echocardiography by population-based community cohort

99
4
100

19

American College of Cardiology/American Heart Association
(ACC/AHA) Guideline for BAV.44

4
2

Aortic Complications
Bicuspid aortic valve is associated with several additional abnormalities, including displaced coronary ostia, left coronary artery
dominance, and a shortened left main coronary artery; coarctation
of the aorta; aortic interruption; Williams syndrome; and, most
importantly, aortic dilatation, aneurysm, and dissection. Given
these collective findings, it can be suggested that BAV is the result
of a developmental disorder involving the entire aortic root and
arch. Although the pathogenesis is not well understood, these associated aortic malformations suggest a genetic defect.14
Although less well understood, these aortic complications of
BAV disease can cause significant morbidity and mortality. As
listed in Box 94.2, BAV may be associated with progressive
dilatation, aneurysmal formation, and dissection (Tables 94.3
and 94.4). These vascular complications may occur independent
of valvular dysfunction* and can manifest in patients without significant stenosis or regurgitation. According to Nistri and colleagues, 50% or more of young patients with normally
functioning bicuspid aortic valves have echocardiographic evidence of aortic dilatation.9 Therefore, the size and shape of the aortic root and dimensions should be carefully evaluated and followed
serially. Aortic root dimensions should be performed at the level of
the annulus, sinuses of Valsalva, sinotubular junction (STJ), and
proximal ascending aorta (Fig. 94.8). In BAV (unlike Marfan syndrome, where the dilation is usually more pronounced at the sinus
level), the sinuses are usually normal or mildly dilated and the
aortic dilation is often most pronounced in the ascending aorta distal to the STJ48,49 (Figs. 94.9 and 94.10). Therefore, effort should be
made to image this portion of the aorta. The midportion of the
ascending aorta may not be easily imaged with echocardiography,

and evaluation with CT or MRI may be required.50 The aortic
arch and descending thoracic aorta may also become dilated.
Recently, it has been reported that patients with BAV are also at
increased risk for intracranial aneurysms compared with the general
population.51

1
LV

3
Ao
LA

Figure 94.8. Diagram of a parasternal long-axis view illustrating where
aortic dimension measurements should be made: 1, aortic annulus;
2, midpoint of sinuses of Valsalva level; 3, sinotubular junction level;
4, mid-ascending aorta. Measurements should be made perpendicular
to the long axis of the aorta. Ao, Aortic root; LA, left atrium; LV, left
ventricle.

TABLE 94.4 Frequency of Bicuspid Aortic Valve (BAV) in Aortic
Dissection (Spontaneous, Noniatrogenic Dissection at Autopsy)
Author(s)

Year

Number
BAV/Dissection

Reference

Gore and Seiwert
Edwards
Larson and
Edwards
Roberts and
Roberts
Totals

1952
1978
1984

11/85 13%
11/119 9%
18/161 11%

101
102
4

1991

14/186 7.5%

100

__

54/551 ¼ 10%

__

*References 9, 11, 15, 46, 47

Figure 94.9. A diagram of a thoracic aorta illustrating the most common
type of aortopathy associated with bicuspid aortic valves—normal aortic
root with dilatation beginning at/above the sinotubular junction.

Although BAV aortopathy may share similarities with the
Marfan syndrome, and aortic aneurysms are common in both conditions, a recent retrospective cohort study of 416 consecutive
patients with definite BAV provides evidence that their clinical outcomes are different and that aortic dissection is more common in
Marfan syndrome.18 The risk of aortic dissection in this BAV


394

SECTION XV Aortic Stenosis

Unicuspid Aortic Valve

Asc’g Ao

Figure 94.10. Transesophageal echocardiographic longitudinal view
that shows a markedly dilated ascending aorta (Asc’g Ao) that spares
the aortic root—typical type of aortopathy associated with bicuspid
aortic valve.

Other less common congenital abnormalities of the aortic valve
include the unicuspid valve and quadricuspid valve. The unicuspid

aortic valve (UAV) is a rare congenital malformation seen in
approximately 0.002% of patients referred for echocardiography,
but in as many as 4% to 6% of patients undergoing surgery for
“pure” (isolated) AS.55 Two forms of UAV are recognized: One
has no commissures or lateral attachments to the aorta at the level
of the orifice (acommissural), and the second has one lateral attachment to the aorta at the level of the orifice (unicommissural).56 Both
of these types, like the BAV, produce a dome-shaped opening in
systole57 (Fig. 94.11). The latter is the more common of the two.
AS of an acommissural UAV is quite severe, presents in infancy,
and is seldom, if ever, seen in adults.58 An acommissural type of
UAV has a central round, oval, or triangular opening caused by
underdevelopment of all three cusps, resulting in a “volcano-like”
structure with a small, central orifice (Fig. 94.12, A). Stenosis of an
acommissural valve is typically very severe and occurs during
infancy. In a unicommissural type of UAV, there is usually an
eccentric “teardrop”-shaped opening (see Fig. 94.12, B). The most
common position of the single commissural attachment zone in this
type is posterior59 (Video 94.1). This configuration results in a relatively larger orifice than the acommissural type. As a result, some
patients with a unicommissural UAV live into adulthood before
manifesting valvular obstruction. Like BAV patients, UAV patients
are more often male.59 Compared with patients undergoing surgery
Acommissural

Unicommissural

cohort was approximately 8 times higher than in the general
population, but despite the high relative risk, the absolute incidence
of aortic dissection was very low (given the BAV prevalence of
1.3% of the general population).17

Surveillance (Serial Assessment of Patients
with Bicuspid Aortic Valve)
Because of the risk of progressive aortic valve disease (stenosis
and/or regurgitation) and aortopathy, all BAV patients should
undergo annual imaging, even when asymptomatic. The 2008
focused update of the 2006 ACC/AHA guidelines recommended
monitoring adolescents and young adults, older patients with AS,
and patients with a BAV and dilation of the aortic root and/or
ascending aorta.52 TTE can be used for serial imaging follow-up
of the ascending aorta when the dimensions measured by TTE
and CT or MRI have been confirmed. Following identification of
ascending aortic enlargement in a patient with BAV, repeat imaging at 6 months is recommended. If the aorta remains stable at
6 months and is less than 45 mm in size, and if there is no family
history of aortic dissection, annual imaging is recommended.
Patients who do not meet these criteria should have repeat aortic
imaging with TTE every 6 months. If the aortic root is poorly
visualized on echocardiography, cardiac CT or MRI are excellent
substitutes. TEE is generally not used for serial follow-up of
BAV-related aortopathy because of its semi-invasive nature and
the difficulty of comparing dimensions over time.

Anterior
mitral
leaflet

Dome
(“volcano,” no
lateral attachments)

(“Exclamation point”

one lateral attachment)

Figure 94.11. Diagram of the two types of unicuspid aortic valves
(see text).

Family Screening of Patients with BAV
BAV appears inheritable and was present in 9.1% of first-degree
relatives in one study.38 Although the current ACC/AHA guidelines on valve disease52 do not recommend screening for relatives
of individuals with BAV, the ACC/AHA guidelines on congenital
heart disease53 and thoracic aortic disease54 do recommended
echocardiographic screening of first-degree relatives (class I; level
of evidence C).

A

B

Figure 94.12. Diagram illustrating the two types of unicuspid aortic
valves. A, Unicommissural valve has a teardrop opening and a lateral
attachment. B, Acommissural valve illustrating a central round/oval
opening at the top of a conical or dome-shaped valve.


Aortic Stenosis Morphology

for BAV and TAV disease, unicommissural UAV patients present
about 2 decades earlier than patients with BAV60 and 3 decades earlier than patients with TAV.61 Unicommissural UAV patients usually require surgery in the third decade of life.
In a UAV, the coronary arteries are generally in the normal
position.58 Aortopathy similar to that seen with a BAV may be
present.56 Unicuspid aortic valves usually have severe, diffuse

calcification, and distinguishing a UAV from a BAV can be challenging (see Fig. 94.12). TEE is more accurate for making this
distinction.56,62,63

Quadricuspid Aortic Valve
Quadricuspid aortic valve (QAV) is a rare congenital cardiac
abnormality with a prevalence that ranges from 0.008% to
0.043%, according to autopsy and echocardiography series
(Table 94.5).64,65 A much higher incidence was reported by Olson
and colleagues in a review of 225 patients undergoing surgery for
pure aortic regurgitation.66 Most cases historically were discovered
incidentally at surgery or postmortem examination. However, the
majority of cases are now diagnosed antemortem by echocardiography.67,68 Because of further advances in imaging, including TEE,
CT, and MRI, more cases are being detected, which is likely to alter
the incidence of QAV.69–71
Based on the relative size of the cusps and their equality,
Hurwitz and Roberts delineated seven morphologic subtypes of
QAV (types A through G), ranging from four cusps of equal size
to four unequal cusps.72 The most common configuration appears
to be that of four equal or nearly equal cusps (Table 94.6).72–74
The QAV may function normally—most commonly when the
cusps are relatively equal in size.64,73 In general, valve dysfunction
is seldom present or minimal during childhood or adolescence.64,65,72,75 Aortic valve dysfunction is usually due to aortic
regurgitation (Table 94.7) and tends to occur later in life, a

395

TABLE 94.7 Function of Quadricuspid Aortic Valves
Valve Function

N

%

AR
AS + AR
AS
Normal

115
13
1
25

75%
8%
1%
16%

From Tutarel, J Heart Valve Dis 13:534-537, 2004 (Reference 67).

consequence of progressive leaflet thickening with resultant
incomplete coaptation (Video 94.2). Unlike BAV, the association
of ascending aortic aneurysm is extremely rare.
The characteristic echocardiographic finding is an “X”-shaped
pattern in diastole in short-axis views (formed by the commissural
lines of the closed QAV), compared with the “Y” in normal trileaflet valves (Fig. 94.13). Because valve dysfunction may occur with
advancing age, clinical and echocardiographic follow-up is
recommended.
Although QAV is usually an isolated anomaly,64,72,73 various
cardiac and noncardiac anomalies have been reported in association

with it (Box 94.4).76–78 The most prevalent cardiac malformations
associated with QAV are coronary artery anomalies, which have
been reported in 10% of cases.67,79–83
In summary, QAV is a rare congenital disorder, usually diagnosed in adulthood, with a potential for complications—mainly
aortic regurgitation. QAVs often require surgery, usually in the
fifth and sixth decades, and therefore need close follow-up.

TABLE 94.5 Quadricuspid Aortic Valve—Prevalence
Author

Year

Method

n

%

Ref.

Simonds
Simonds

1923
1923

0/2000
2/25,666

Feldman et al

Feldman et al
Olson et al

1990*
1990†
1984

Autopsy
Autopsy
(literature
review)
2D-echo
2D-echo
Surgery for
pure AR

0.000%
0.008%
0.013%
0.043%
1%

64
64
65
66
66

8/60,446
6/13,805

2/225

AR, Aortic regurgitation
*1982-1988

†

1987-1988

Figure 94.13. Quadricuspid aortic valve. Transesophageal echocardiographic short-axis view (37 degrees) illustrates failure of leaflet coaptation
in diastole (arrow) with a square central opening and typical X-shaped
configuration of the four commissures.
TABLE 94.6 Quadricuspid Aortic Valves: Morphologic Types
Anatomic Variation—Cusps

N

4 equal
3 equal, 1 smaller
2 equal larger and 2 equal smaller
1 large, 2 intermediate, 1 small
3 equal and 1 larger
2 equal, 2 unequal smaller
4 unequal

51
43
10
7
4

4
5

From Hurwitz LE, Roberts WC: Quadricuspid semilunar valve, Am J
Cardiol 31:623-626, 1973 (Reference 72).

Box 94.4 Cardiac and Noncardiac Abnormalities Associated
with Quadricuspid Valve
1.
2.
3.
4.
5.
6.

Patent ductus arteriosus
Hypertrophic cardiomyopathy
Subaortic stenosis
Ehlers-Danlos syndrome
Coronary ostium displacement
Ventricular septal defect

94


396

SECTION XV Aortic Stenosis

CALCIFIC (DEGENERATIVE) AORTIC STENOSIS

Calcific AS is the most common etiology of valvular AS in elderly
patients. The prevalence of calcific AS increases with age.84 AS has
a prevalence of about 5% in individuals age 65 or older and about
10% in individuals age 80 years or older. AS is the most common
indication for valve replacement surgery and the second most
common indication for surgery in older adults, surpassed only by
coronary artery bypass grafting.85 Calcific AS affects men and
women equally.
Because the prevalence of AS increases with age and because
calcification occurs in regions of mechanical stress, AS was previously thought to be a degenerative disorder caused by passive
“wear and tear.” However, the view that aortic valve calcification
is a passive consequence of cellular aging has been challenged. AS
is now considered to be an active process with some similarities to
atherosclerosis, including inflammation, lipid infiltration, and dystrophic calcification.86–90 Therefore, the term calcific AS seems
more appropriate than degenerative AS. Currently, the pathology
of calcific aortic valve disease is an area of active research.91,92
Calcific AS results from slowly progressing fibrosis and calcification, which occurs over several decades, leading to variable
degrees of thickening and rigidity of the aortic valve cusps. This
process begins with aortic valve sclerosis that does not limit flow
through the aortic orifice. The morphologic hallmark is the formation of calcified masses along the aortic side of the cups. The earliest
deposits occur at the cusp attachments and along the line of cusp
coaptation—the sites of greatest bending and unbending during
valve opening and closing.93 Irregular leaflet thickening and focal
increased echogenicity (calcifications) are the echocardiographic
hallmarks of calcific AS. These focal areas of thickening are

Stenotic unicuspid AV

typically seen in the center of the valve cusps. The degree of calcification is best assessed in the parasternal short-axis view.
The degree of calcification can be qualitatively classified as mild

(small isolated spots or nodules), moderate (multiple larger nodules), and severe (extensive thickening and calcification of all of
the cusps).89,94
The degree of leaflet calcification is a marker of disease progression and should be reported.94,95 As the leaflets become more
sclerotic, they become progressively more rigid and less mobile
and begin to obstruct flow. Increases in aortic transvalvular flow
velocity mark the progression from aortic sclerosis to AS. In the
most severe cases, the aortic root appears to be filled with dense,
amorphous echoes that have little or no motion. In some patients,
one of the leaflets may become immobile while the others move
freely. When only one leaflet is immobile, there is usually only a
mild increase in transaortic velocity (mild AS). Unlike rheumatic
AS, commissural fusion is usually absent or only minimal in calcific AS. The valve orifice tends to be triradiate—three slitlike
openings in systole (Figs. 94.14, E and 94.15).96 Calcification often
extends onto the base of the anterior mitral leaflet. Calcification
may also extend from the valve cusps into the ventricular septum
and may induce conduction abnormalities.

RHEUMATIC AORTIC STENOSIS
Rheumatic AS has become uncommon in the developed world,
although it remains a significant cause of AS worldwide. In adults
undergoing aortic valve replacement for symptomatic AS in the
United States, calcific tricuspid AS accounts for 5% of cases, bicuspid AS for 36%, and rheumatic AS for 9%.97 Aortic rheumatic valve
disease is never isolated, but is virtually always associated with

Stenotic bicuspid AV

A

C

B

D

Stenotic tricuspid AV

E

Figure 94.14. Gross pathology specimens of stenotic aortic valves (AVs), including unicuspid, bicuspid, and tricuspid valves. The two unicuspid AVs
(A and B) are unicommissural with lateral attachments; the two bicuspid valves (C and D) have raphes (arrows); tricuspid valve (E) does not have fused
commissures and shows the slitlike orifices resulting from bulky calcific deposits that restrict leaflet motion. (Courtesy of Dr. Renu Virmani, CVPath
Institute, Gaithersburg, Md.)


Aortic Stenosis Morphology

Figure 94.15. Gross pathology specimen of a calcific (degenerative)
trileaflet aortic valve that illustrates absence of commissural fusion and
a triradiate orifice, each of which are slitlike. (Courtesy of Dr. Renu
Virmani, CVPath Institute, Gaithersburg, Md.)

397

rheumatic mitral valve disease. Rheumatic valvular dysfunction
may affect not only an anatomically normal TAV, but also a
congenital BAV.
Similar to rheumatic mitral valve disease, rheumatic aortic
valve deformities are characterized by diffuse cuspal thickening
that extends to their free edges and by commissural fusion. These
features contrast with the morphologic features of degenerative

(calcific) AS, which manifests basal calcific nodules, minimal or
no involvement of the free edges, and no commissural fusion.
The acquired commissural fusion in rheumatic AS may affect
one, two, or all three commissures and is usually distinguishable
from the commissural fusion of congenital valve abnormalities.
The commissural fusion, which begins at the annulus and progresses toward the center, often affects each commissure equally,
producing a small, central, circular or triangular orifice (see
Fig. 94.1; Fig. 94.16). Subsequent calcium deposition occurs secondarily. Commissural fusion is the primary lesion of AS, as
opposed to fibrosis/sclerosis, shortening, and retraction of the
cusps, which produce rheumatic aortic regurgitation. Interestingly,
the sole pathognomonic feature of rheumatic valve disease, the
Aschoff granuloma, is virtually never found in aortic valve tissue.98
Please access ExpertConsult to see Videos 94.1 and 94.2.

REFERENCES

A

B
Figure 94.16. A, Typical rheumatic aortic stenosis with commissural
fusion resulting in a central triangular (as shown here) or oval or circular
(not shown) orifice as shown in the transesophageal echocardiogram.
B, A pathologic specimen from a different patient.

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Quantification of Aortic Stenosis Severity
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Quantification of Aortic Stenosis Severity
Steven A. Goldstein, MD

Aortic stenosis (AS) is the most common cardiac valve lesion in
developed countries, including North America and Europe, with
an incidence of 2% to 9% in elderly patients older than age
65 years.1 Moreover, the incidence is increasing as the population
ages. Aortic sclerosis, the precursor of AS, is present in nearly one
third of patients older than age 65 years.
AS is suspected clinically when a harsh systolic ejection
murmur is heard, a delayed carotid upstroke is palpated, or when
typical symptoms (angina pectoris, exertional dyspnea, or exertional syncope) occur. However, the clinical diagnosis of AS can
be challenging. Clinical signs and symptoms are limited for distinguishing critical AS from noncritical AS, and these signs have
reduced sensitivity and specificity in the elderly.2,3 Cardiac catheterization, once considered the gold standard for quantitation of AS,
is invasive, and the frequency of complications increases with age.4
Omran et al. demonstrated evidence of acute, focal embolic events
on magnetic resonance imaging in 22% of 152 patients who underwent retrograde catheterization.5
In contrast, echocardiography provides noninvasive assessment
of both valve morphology and hemodynamics. Because of its versatility, noninvasiveness, reproducibility, and accuracy, current
guidelines endorse echocardiography as the diagnostic method of
choice for the assessment and management of AS.6,7 Cardiac
catheterization is no longer recommended and is only performed
in a limited subset of patients in whom echocardiography is nondiagnostic or discrepant with clinical parameters.6,7 In most situations, transthoracic echocardiography (TTE) is sufficient, and it is
the current standard procedure for assessing both severity and serial
evaluations of AS. Moreover, the prediction of clinical outcomes of
patients with AS has been studied mainly using TTE.8–10
Precise assessment of AS severity is necessary for clinical
decision-making. The primary hemodynamic parameters recommended for the quantitation of AS severity are peak jet velocity,
transaortic gradients, and aortic valve area (AVA) calculated by
the continuity equation.11 Box 95.1 lists the echocardiographic
and Doppler parameters that should be evaluated in patients with
valvular AS. These are subsequently discussed in the following.

NORMAL AORTIC VALVE
Two-Dimensional Echocardiography
The normal aortic valve is composed of three leaflets or cusps (the
left, right, and noncoronary cusps [NCCs]) of equal or nearly equal
size. Two-dimensional (2D) TTE of the normal aortic valve in the
parasternal long-axis (PLAX) view shows two leaflets: (1) the right

Box 95.1 Echo-Doppler Parameters to Evaluate in Aortic
Valve Stenosis
1. Two-dimensional (2D) measurement of the left ventricular outlet
tract (LVOT) diameter and aortic annulus
2. LVOT velocity (V1)—by pulsed wave Doppler
3. Velocity across the aortic valve (V2 or Vmax) by continuous wave
Doppler (from apex, right parasternal view, suprasternal notch,
subxiphoid view)
4. Calculation of peak instantaneous gradient and mean gradient
5. Calculation of aortic valve area by the continuity equation
6. Dimensionless index
7. M-mode/2D measurements of left ventricular size
8. Calculation of LV mass
9. Assessment of aortic insufficiency
10. Assessment of other cardiac defects

coronary cusp, which is the most anterior cusp; and (2) either the
noncoronary cusp [NCC] (most commonly) or the left coronary
cusp. Normal aortic valve cusps appear thin and delicate. In the
PLAX view, the cusps open rapidly in systole and appear as parallel
lines close to the aortic walls (Fig. 95.1). In diastole, the leaflets
come together and appear as a linear density in the center of the
aortic root, parallel to the aortic walls. The aortic leaflets are seldom seen during the opening and closing because their motion is

very rapid relative to the frame rate of the 2D ultrasound system.
In the short-axis (SAX) view, the three thin leaflets open in systole
to form a triangular or circular orifice (Fig. 95.2). During diastole,
the closure lines of the three leaflets form a Y shape (an inverted
Mercedes Benz sign). Sometimes, there is a slight thickening of
the mid-portion of each closure line formed by nodules known as
the nodules of Arantius. In the SAX view, the NCC is located
posteromedially. The atrial septum always points to the NCC.
The left coronary cusp is located posterolaterally.

M-Mode Echocardiography
M-mode echocardiography of the aortic valve is formed by directing the M-mode echo beam through the aortic leaflets. This can be
done from both the PLAX and SAX views. At the onset of systole,
the leaflets open rapidly and become parallel to, and nearly oppose,
the walls of the aortic root (Fig. 95.3). They remain open

95


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SECTION XV Aortic Stenosis

Figure 95.1. Transesophageal echocardiogram, longitudinal view
(similar to transthoracic parasternal long-axis view) of a normal tricuspid
aortic valve illustrates normal opening with the leaflets parallel to the
aortic root walls.

throughout systole and rapidly close again at end-systole, forming a
box or parallelogram. Normally, these leaflets show fine, regular

vibrations during systole. These fine vibrations actually indicate
that the leaflets are thin, and are able to luff, like a sail, due to
the rapid flow through them on one side (their ventricular surface)
and eddy currents swirling behind the leaflets on the aortic side,
resulting in opposing forces that cause these vibrations. During
diastole, the coapted leaflets form a single (or sometimes multiple
parallel) central closure line(s) midway between the aortic walls
(see Fig. 95.3). The left ventricular ejection time can be measured
from the point of the cusp opening to the point of the cusp closing.
A rough estimate of the severity of AS can be obtained by noting
the maximal degree of separation of the leaflets at the onset of systole. In patients with valvular AS, the thickened leaflets (due to
fibrosis and/or calcium) appear as dense echoes in both systole
and diastole. In systole, the thickened rigid leaflets fail to open
widely. The distance between the anterior cusp (right coronary
cusp) and the posterior cusp (usually the NCC; sometimes, the left
coronary cusp) is reduced or not even visible, which suggests moderate or severe AS (Fig. 95.4). In the absence of a bicuspid valve, a
maximal opening of the leaflets of at least 1.5 cm virtually excludes
significant valvular AS.12,13 When any of the three leaflets opens
normally and/or maximally, regardless of the degree of limitation
of the other two, the degree of AS is not more than mild.

QUANTITATIVE DIAGNOSIS OF AORTIC STENOSIS
With the development of acquired AS, the cusps became thickened,
and their motion is restricted. The degree of thickening and restriction progresses as the severity of AS increases. In severe AS,
the leaflets become markedly thickened and calcified, and there
is nearly a total lack of mobility. Identification of individual cusps
is often difficult or impossible. Moreover, attempts to planimeter
the aortic valve orifice by TTE have been largely unsuccessful.14
Nevertheless, a qualitative estimation (gestalt) of AS severity
should be attempted and correlated with quantitative methods.

If leaflet separation is at least 15 mm or if at least one cusp moves
normally, critical AS is highly unlikely. As will be discussed later,
planimetry is, however, possible in the majority of patients by
using TEE.

A

QUANTITATIVE DOPPLER ASSESSMENT
OF SEVERITY OF AORTIC STENOSIS
The previously mentioned 2D and M-mode features are useful for
detecting AS, but they are unreliable for quantitating AS. The
severity of AS is determined by a combination of 2D and Doppler
echocardiography. As the aortic valve becomes stenotic, and
obstruction to blood flow occurs, a pressure gradient develops
across the valve. This obstruction is associated with an increase
in transaortic jet velocity. The primary routine parameters used
to quantitate AS include the peak aortic jet velocity, the mean pressure gradient, and the AVA.

Transaortic Velocities

B
Figure 95.2. Transthoracic echocardiogram (short-axis view) of a normal tricuspid aortic valve. A, In systole, the valve opens in a triangular
fashion with straightening of the leaflets. B, In diastole, the normal trileaflet valve appears like a “Y,” with the commissures at 10 o’clock,
2 o’clock, and 6 o’clock.

Transaortic jet velocities are directly obtained using a continuous
wave (CW) Doppler probe. To obtain the highest velocity, the angle
of interrogation should be as parallel to flow as possible. Therefore,
multiple transducer windows should be used to obtain the Doppler
signal that is aligned most parallel to the direction of the stenotic

jet. These windows include the apical 3- and 5-chamber views,
the right sternal border, the suprasternal notch (SSN), and subxiphoid views. A careful, thorough, meticulous manipulation of the
transducer is necessary to achieve optimal alignment and to determine the highest velocity possible (Fig. 95.5). The highest velocity
obtained from any window is used in the calculation of the gradient


Quantification of Aortic Stenosis Severity

401

95

Figure 95.3. M-mode echocardiogram of an aortic valve illustrating the rapid opening slope of the aortic leaflets at the onset of systole, the leaflets
aligned parallel to the aortic walls throughout systole (white arrows), and the central closure line in diastole (yellow arrow).

Figure 95.4. M-mode echocardiogram from a patient with moderate aortic stenosis. The maximal opening between the anterior (right coronary cusp)
leaflet and a posterior leaflet (noncoronary cusp) (yellow arrow) is less than 5 mm.

and the aortic valve area. Lower values from the other windows are
ignored. Using a nonimaging CW Doppler probe (so-called Pedoff
probe or pencil probe) is recommended because it is smaller, easier
to manipulate between the ribs and the SSN, and has a higher
signal-to-noise ratio.

Pressure Gradients
The highest transaortic jet velocity (Vmax) measured by Doppler
reflects the pressure gradient according to the Bernoulli equation.
The maximum pressure gradient (△ Pmax) across the stenotic
aortic valve can be calculated by using the simplified Bernoulli

402

SECTION XV Aortic Stenosis

equation that ignores viscous losses and the effects of flow acceleration. These can be neglected in the usual clinical setting:
Maximal pressure gradient (ΔPmax) = 4 (Vmax)2

However, when the proximal or left ventricular outflow tract
(LVOT) velocity (VLVOT) exceeds 1.5 m/sec, the modified
Bernoulli ejection should be used:
Δ Pmax = 4 (Vmax2 − VLVOT2)

A

Apical 4-chamber Vmax = 3.6 m/sec
Pedoff probe

B

Right sternal border Vmax = 3.9 m/sec
Pedoff probe

The mean pressure gradient is obtained by a manual tracing of the
Doppler velocity envelope. The ultrasound machine’s software
integrates the instantaneous velocities throughout systole and provides a mean value. Both peak and mean gradients should be
reported. A mean gradient more than 40 to 50 mm Hg is consistent
with severe AS (Table 95.1). However, because calculated pressure
gradients depend not only on the degree of stenosis, but also on
(flow stroke volume and/or cardiac) output, higher gradients than

those outlined in Box 95.1 may occur in patients with altered volume flow rates. Examples of increased flow rates occur in aortic
regurgitation, anemia, and pregnancy. In these situations, relatively
high-pressure gradients may be present, although the degree of AS
may only be mild. In contrast, patients with significant left ventricular systolic dysfunction, small left ventricles, high systemic vascular resistance, or mitral regurgitation may have relatively low
gradients despite severe AS. The accuracy of Doppler-derived peak
instantaneous maximal and mean pressure gradients has been
validated with simultaneous cardiac catheterization data15,16
(Figs. 95.6 and 95.7). It is important to recognize that the peak
instantaneous systolic pressure gradient measured by Doppler is
higher than the peak-to-peak gradient obtained during cardiac
catheterization (Fig. 95.8). Potential sources of error in Doppler
assessment of transaortic gradients are listed in Box 95.2.
Doppler measurement of gradients may be limited by TEE
because of the difficulty in aligning the echo beam parallel to
the stenotic jet from standard esophageal views. However, in the
majority of cases, the deep transgastric view can be used to obtain
accurate maximal velocities and gradients (Fig. 95.9). A second
useful view can be obtained by slight clockwise rotation of the
TEE probe from a standard gastric longitudinal view of the left
ventricle (Fig. 95.10).

Aortic Valve Area by Continuity Equation
Echo-Doppler assessment of the severity of AS includes the calculation of aortic valve area using the continuity equation. The continuity principle, based on the conservation of mass, states that the
TABLE 95.1 Grading the Severity of Aortic Stenosis

C

Suprasternal notch Vmax = 4.3 m/sec

Figure 95.5. Continuous wave Doppler tracings from a patient with

severe aortic stenosis illustrate the importance of using multiple transducer positions to obtain the highest (maximal) transaortic velocity. A,
Apical 4-chamber view using imaging probe detects a velocity of
3.6 m/s. B, A slightly higher velocity (3.9 m/sec) is obtained from the
right sternal border using a nonimaging (Pedoff) probe. C, The highest
velocity (4.3 m/sec) was obtained from the suprasternal notch using a
nonimaging probe.

Characteristic

Mild

Moderate

Severe

Aortic jet velocity (m/sec)
Mean gradient* (mm Hg)
Mean gradient† (mm Hg)
Aortic valve area (cm2)
Dimensionless index

2.6–2.9
<20
<30
>1.5
-

3.0–4.0
20–40
30–50

1.0–1.5
-

>4.0
>40
>50
<1.0
<0.25

*According to American Heart Association/American College of
Cardiology guidelines.7
†

According to European Society of Cardiology guidelines.6


Quantification of Aortic Stenosis Severity

Simultaneous
Max gradient (Doppler), mm Hg

Figure 95.6. Good correlation between
Doppler- and catheter-derived peak instantaneous gradients (Max gradient) when
performed simultaneously (left) versus nonsimultaneously (right). The dotted lines represent the regression lines, and the solid
lines represent the lines of identity. (Modified
from Currie PJ, Hagler DJ, Seward JB, et al.
Instantaneous pressure gradient: a
simultaneous Doppler and dual catheter
study. J Am Coll Cardiol 7:800-806, 1986.)

403

Nonsimultaneous

95

160

120

80

n = 49
r = 0.94
SEE = 10

40

n = 49
r = 0.80
SEE = 17

0
0

40

80

120

160

0

40

80

120

160

Max gradient (catheter), mm Hg

Max
160

120

80
n = 100
r = 0.95
SEE = 10

40

Mean

120

Mean gradient (Doppler) mm Hg

Max gradient (Doppler) mm Hg

Figure
95.7. Good
correlation
between Doppler- and catheterderived maximal and mean gradients
when obtained simultaneously in 100
patients. The dotted lines represent
the regression line, and the solid lines
represent the line of identity. (Modified
from Currie PJ, Seward JB, Reeder
GS, et al. Continuous-wave Doppler
echocardiographic assessment of
severity of calcific aortic stenosis. Circulation 71:1162-1169, 1985.)

80

40

n = 100
r = 0.94
SEE = 10

0

0
0

40

80

120

160

0

40

flow volumes (Q) at different sites in a closed system, like the heart,
are identical:

80

120

Mean gradient (cath) mm Hg

Max gradient (cath) mm Hg

The continuity equation can be rearranged as follows:
CSA2 =

CSA1 × TVI1
T VI2

In the case of AS, site 1 is the LVOT, and site 2 is the stenotic aortic

orifice. Thus, the continuity equation can be re-stated as:

AV area =

In the case of AS, the stroke volume proximal to the aortic valve in
the LVOT, or Q1, must equal the stroke volume through the stenotic
aortic valve (Q2). Because stroke volume is the product of the crosssectional area (CSA) and the time-velocity integral (TVI) at that
point, the continuity equation can be stated as:
Q1 − CSA1 × TVI = CSA2 × T VI2

CSALVOT × TVILVOT
T VIAS

Therefore, to calculate the AVA, three measurements must be
obtained (Fig. 95.11):
1. CSA of the LVOT (CSALVOT);
2. TVI of the LVOT (TVILVOT);
3. TVI of the aortic stenotic jet (TVIAS).


404

SECTION XV Aortic Stenosis

Peak-to-peak
Peak
instantaneous

Figure 95.8. Simultaneous left ventricular (white trace)–aortic (yellow
trace) pressures. The gray-hatched area between these two tracings

represents the pressure gradient throughout systole. Note that the
peak instaneous gradient measured by Doppler (green arrow) is higher
than the peak-to-peak gradient measured by catheterization (yellow
arrow). Also note that the peak-to-peak gradient is artificial (the peak
left ventricular pressure and the peak aortic pressures occur at
different times).

Box 95.2 Sources of Error in Doppler Assessment
of Transvalvular Gradient Overestimation Compared
with Catheter Gradient
• Failure to account for increased subvalvular velocity
• Recording the wrong gradient (mitral regurgitation)
• Nonrepresentative selection of velocity (arrhythmias—highest
velocity often incorrectly selected)
• Pressure recovery in patients with small aorta (<3.0 cm)

The CSA of the LVOT is obtained from the PLAX view. The
LVOT region should be zoomed, and the maximum inner-edge
to inner-edge diameter should be measured just below the insertion
of the aortic valve leaflets in mid-systole.
The TVILVOT is obtained from an apical window (apical
5-chamber or 3-chamber view), using pulsed wave Doppler, placing
the sample volume (use a small sample volume) just proximal to the
stenotic aortic valve, and tracing the waveform. This waveform
should yield the highest velocity laminar flow immediately proximal
to the flow acceleration that occurs as the sample volume approaches
the stenotic valve. This can be accomplished by placing the sample
volume in the LVOT (beneath the stenotic valve), slowly inching
toward the stenotic valve, and recording the enveloped (laminar)
velocity profiles at each step until flow acceleration (spectral broadening) occurs. The sample volume should then be backed up (i.e.,

moved apically) until a smooth, laminar velocity curve without spectral broadening is detected, which indicates a position proximal to the
flow acceleration zone (Fig. 95.12). This represents the correct LVOT
velocity tracing. Next, using CW Doppler from multiple transducer
positions (as discussed in the previous section), the maximal TVIAS
is obtained. The highest transaortic velocity and TVI from any of
the transducer positions should be used to calculate the AVA.
Although TVI is preferred, the peak velocity can also be used in the
continuity equation. The use of velocity is more practical in patients
with atrial fibrillation, when 5 to 10 consecutive beats should be measured and averaged.11 A sample calculation of the AVA using the continuity equation and velocity instead of TVI is as follows:
• LVOT diameter: 2.0 cm;
• LVOT velocity: 1.0 m/sec;
• AS peak jet velocity: 4.0 m/sec
AV area = CSALVOT ×

AV area =

TVLVOT
VAo

(3.14) (1.0)2 (1.0)
4.0

= 0.8 cm2

Deep transgastric view

Figure 95.9. Continuous Doppler tracing from a deep transgastric transesophageal echocardiographic view, which detects a transaortic
velocity (V2) of 4.5 m/sec in a patient with severe aortic stenosis.

Quantification of Aortic Stenosis Severity

405

95

Vmax = 4.2 m/sec
TVI

= 121 sec

Figure 95.10. Transesophageal echocardiogram continuous wave Doppler tracing from a standard gastric longitudinal view with slight clockwise
rotation in a patient with severe aortic stenosis revealing a maximal velocity (Vmax) of 4.2 m/sec and time-velocity integral of 121 sec.

a

A2 x V2
A 1 x V1
LV
LA

A2 =

A1 x V1
V2

b

c
Figure 95.11. The continuity equation as applied to valvular aortic stenosis: A1 Â V1 ¼ the flow volume in the left ventricular outflow tract and

A2 Â V2 ¼ the flow volume across the stenotic aortic valve. The stenotic
aortic valve area (A2) can be calculated from the continuity equation.

d

LIMITATIONS AND PITFALLS IN THE ECHODOPPLER QUANTITATION OF AORTIC STENOSIS
Calculation of the AVA by the continuity equation requires painstaking attention to detail in the measurement of the three previously
mentioned parameters. Good correlation between echocardiographically and catheter-derived valve area has been demonstrated17–19 (Fig. 95.13). The primary cause of inaccuracy with
the continuity equation is error in the measurement of the LVOT
diameter. Because the square of the radius is used in the continuity
equation, even minor errors in the measurement of the LVOT diameter may result in substantial error in the calculation of the AVA.

Figure 95.12. The method used to obtain the optimal left ventricular
outflow tract (LVOT) velocity (V1) for the continuity equation. The pulsed
wave Doppler sample volume is initially placed in the LVOT (a), serially
moved toward the aortic valve (b and c) until the sample volume enters
the flow convergence region (d), and the spectral display demonstrates
spectral broadening. The sample volume should then be moved back
(apically) slightly until spectral broadening disappears. This is the optimal
LVOT velocity (c; yellow arrow).


406

SECTION XV Aortic Stenosis

Echo AV area (cm2)

2.0

1.5

1.0

0.5
n = 100
r = 0.83
0
0

0.5

1.0

Cath AV area

1.5

2.0

(cm2)

Figure 95.13. Good correlation between catheterization (cath)-derived
aortic valve (AV) area and Doppler echocardiography (Echo)-derived
area using left ventricular outflow tract and transaortic valve time-velocity
integral ratio in 100 patients. Mean SEE was 0.19 cm2. (Modified from
Oh JK, Taliercio CP, Holmes DR Jr, et al. Prediction of the severity of aortic stenosis by Doppler aortic valve area determination, J Am Coll Cardiol
11:1227-1234, 1988.)

There is a tendency to underestimate the LVOT for several reasons.

First, the LVOT may be elliptical rather than circular, and in such
instances, the smallest diameter is usually measured in the PLAX
view.20 -24 Second, in patients with calcific AS, blooming and
reverberations from the calcified aortic annulus, and often from
the extension of calcium onto and/or into the base of the anterior
mitral leaflet, can artificially make the LVOT appear smaller than
its actual size, especially when using low-frequency transducers
and high-gain settings (Fig. 95.14). Technical tips to avoid this
potential problem include using as high a frequency transducer
as possible, imaging the LVOT as close to the center of the sector
as possible (axial resolution is superior to lateral resolution), and
using relatively low-gain settings. Last, especially in elderly
patients, the upper (basal) septum may bulge into the LVOT, making this measurement difficult.
Theoretically, the LVOT diameter (LVOTd) should be measured in mid-systole, at the same time in the cardiac cycle that
the LVOT velocity is measured. However, sometimes, the image
quality is suboptimal in mid-systole, and the outflow tract is imaged
more clearly at end-diastole. Skjaerpe et al suggested that the
LVOTd could be measured at end-diastole.17 When accurate measurement of the LVOTd is not possible, one should not guess or use
an assumed diameter (e.g., 2.0 cm), as some have recommended.
In this situation, the dimensionless index (DI), or velocity ratio,
may be used as an alternative to the AVA. This simplified parameter avoids the necessity to accurately measure LVOTd and is
independent of cardiac output. This Doppler-only method uses
the following equation:
DI =

T VILVOT
T VIAS

A DI of <0.25 is consistent with severe AS (see Table 95.1).
The second parameter subject to limitations is the LVOT

velocity (so-called V1). The method recommended to measure
this parameter has been discussed. However, this parameter may
not be measurable in several situations. The most common pitfall
occurs when there is associated subaortic stenosis that may cause
high-velocity turbulent flow in the LVOT, precluding accurate
measurement of V1. The strut of a bioprosthetic mitral valve
may protrude into the LVOT, creating turbulence, which occurs
less commonly.

A

LVOTd = 2.0 cm

B
Figure 95.14. A, Zoomed parasternal long-axis view of the left ventricular outflow tract (LVOT) illustrates a chunk of calcium protruding into the
LVOT. This view might yield an incorrectly small LVOT diameter (LVOTd)
because the calcium does not represent the entire perimeter of the
orifice. B, A slightly altered view misses this chunk of calcium and yields
a larger and more accurate diameter of 2.0 cm.

Other parameters used for quantitating AS are the transaortic
velocity (Vmax, or so-called V2) and the transaortic pressure gradient derived from V2. Underestimation of this velocity and pressure may occur if there is poor alignment of the Doppler beam (not
parallel to the stenotic aortic jet). This potential problem can be
minimized by using multiple transducer positions, as discussed earlier. Overestimation of the true velocity and pressure gradient is
less common than underestimation. This may be due to mistaking
a mitral regurgitant (MR) jet (or rarely at tricuspid regurgitant jet)
for the aortic stenotic jet, especially when using a nonimaging
probe. These three jets are similar in direction as seen from apical
views. Sweeping the transducer back and forth to distinguish which
jet is which may help to avoid this pitfall. A second clue to help

distinguish these jets is their duration. Mitral and tricuspid regurgitant jets are always longer than the AS jet because they include isovolumic contraction and isovolumic relaxation. In addition, the MR
jet has a higher velocity because the left ventricular–left atrial gradient is higher than the left ventricular–aortic gradient in systole.
Another method to distinguish the AS jet from the MR jet is the
associated diastolic signals in the tracing. The MR jet is associated
with mitral flow, whereas the AS jet is not and may be associated


Quantification of Aortic Stenosis Severity
TABLE 95.2 Factors Helping to Differentiate an Aortic Stenotic
Jet from Mitral Regurgitant Jet
Characteristic

AS

MR

Shape

Early systolic peak
when AS is less
than severe;
but parabolic in
severe AS
AS shorter than MR
(no flow during
isovolumic
periods)
Gap between end of
AS and mitral inflow
(IVRT)

AS < MR

Parabolic
Peaks in mid to late systole
(exception acute, severe
MR)

Duration

Diastolic signals
Velocity

MR longer than AS
(includes IVCT and
IVRT)
End of MR jet is
continuous with mitral
inflow
MR > AS

AS, Aortic stenosis; IVCT, isovolumic contraction time; IVRT, isovolumic
relaxation time; MR, mitral regurgitation.

with aortic regurgitation (AR) if AR is present (Table 95.2). A rare
situation may occur when a high-velocity jet from a stenotic arch
vessel is mistaken for an AS jet from the SSN transducer position.
These potential pitfalls are summarized in Box 95.3. In the presence
of atrial fibrillation or frequent premature ventricular contractions,
averaging the velocity from 5 to 10 consecutive beats is recommended (Fig. 95.15). The use of the highest velocity alone results
in overestimating the gradient and underestimating the AVA calculated by the continuity equation. The effect of systemic blood pressure on the assessment of the mean pressure gradient and AVA

remains controversial.25,26
Recommendations for measuring and recording valve morphology and echo-Doppler parameters in patients with AS are
listed in Table 95.3. Given the potential therapeutic and prognostic importance of these echocardiographic parameters and their
potential limitations, they should only be reported when imaging
is adequate and there is a high level of confidence in their accuracy. If the level of confidence of these measurements is reduced,
or if there is a discrepancy between the echo-Doppler and clinical
or catheterization data, the raw data of all of the echocardiographic measurements should be reviewed carefully and critically. Other diagnostic modalities may be considered to further
assess the morphology and hemodynamics of the stenotic aortic
valve. These may include transesphogeal echocardiography
(TEE), magnetic resonance imaging, and rarely, cardiac catheterization as outlined in the American Heart Association/American
College of Cardiology and European Society of Cardiology
guidelines.6,7,11

Box 95.3 Potential Pitfalls of Doppler-Derived Gradients
in Aortic Stenosis
• Poor alignment of Doppler beam (improper intercept angle
between the aortic stenosis [AS] jet and Doppler beam)
• Left ventricular outlet tract (LVOT) velocity may be important
(cannot be ignored if >1.4 m/s)
• Mitral regurgitant jet may be mistaken for aortic jet
• Subaortic obstruction may preclude measurement of LVOT velocity
• Comparison with catheter gradients (peak instantaneous vs peakto-peak)
• Beat-to-beat variability (atrial fibrillation, premature ventricular
contractions)

407

PLANIMETRY OF AORTIC VALVE ORIFICE
Theoretically, the aortic valve orifice can be measured by planimetry using TTE in a manner similar to that used for assessing the orifice area in mitral stenosis. However, this method is unreliable in
calcific AS for several reasons: (1) because of the inability to determine whether the plane of imaging is at the leaflet tips where maximum stenosis occurs, and that it is parallel to the orifice; and (2)

planimetry is difficult due to poor cusp definition from heavy calcium deposition, acoustic shadowing, and reverberation artifact.27
Because of its superior resolution and unobstructed visualization, TEE provides excellent views of the aortic valve leaflets as
they open and close throughout the cardiac cycle. Therefore, unlike
with TTE, direct measurement of the aortic valve area by TEE planimetry can be performed with excellent correlation with cardiac
catheterization using the Gorlin equation and with echo-Doppler
using the continuity equation.28–30 Planimetry by TEE has also
been shown to correlate well with planimetry by computed tomography.31 To measure the AVA accurately, the image plane must be
located at the tips of the aortic valve leaflets. This measurement
requires a careful technique to produce the correct imaging angle
and plane. It is useful to begin with a longitudinal view (usually
between 110 and 150 degrees) to align the aortic root perpendicular
to the echo beam and to place the aortic valve at or near the center of
the sector (Fig 95.16, A). This takes advantage of the axial resolution and provides the optimal plane parallel to the aortic annulus
and valve. Subsequently, the image plane can be rotated 90 degrees
to view the aortic valve in a precise SAX view (Fig. 95.16, B).
Alternately, the biplane function of newer ultrasound machines
can be used to achieve this view. Slight withdrawal and advancement of the TEE probe cranially and caudally is useful to find
the smallest orifice at the maximal leaflet tip separation. The smallest systolic orifice is frequently found at a plane slightly higher
than the Mercedes Benz sign visualized in diastole. The view
should image all three cusps simultaneously. Color Doppler may
aid in determining the stenotic orifice. Adjusting the gain settings
(reduce gain without losing definition of the leaflet and commissural edges) may help delineate the true margins of the orifice
for planimetry. The smallest orifice area at the time of maximal
opening in early-to-mid systole should then be planimetered.

THREE-DIMENSIONAL ASSESSMENT
OF THE AORTIC VALVE AREA
Real-time, 3-dimensional TTE (RT3D TTE) has the potential to
overcome a shortcoming of 3D-TTE by providing imaging at any
plane. The cropping plane in the 3D dataset can provide a true en face

view aligned exactly to image the smallest stenotic aortic valve orifice for planimetry. Several studies have documented superior accuracy of planimetry by RD3D TTE compared with conventional
2D-TTE.22,32–36 Therefore, RT3D TTE can, in some situations,
overcome some of the limitations of the continuity equation; the
AVA can be reliably evaluated when valvular AS co-exists with
hypertrophic obstructive cardiomyopathy, discrete subaortic stenosis, or supravalvular AS. In addition, the evaluation of AS severity by
the continuity equation may be enhanced by using a RT3D TTE
approach for the measurement of the LVOT diameter or CSA.36

OTHER METHODS OF MEASURING AORTIC
STENOSIS SEVERITY
Several additional echocardiographic parameters have been proposed to better define the severity of AS and/or its risk. Those
include valve resistance,37–41 the energy loss index,42–44 stroke
work loss,45–47 and valvuloarterial impedance.48–51 However, their
utility and prognostic significance remain to be proven in

95


408

SECTION XV Aortic Stenosis

2.1 m/sec

1.5 m/sec
3.4 m/sec

3.4 m/sec

2.0 m/sec

2.7 m/sec

2.7 m/sec
2.7 m/sec

3.2 m/sec

1.5 m/sec

Average Vmax (V2) = 2.5 m/sec

Figure 95.15. Continuous wave Doppler tracings using a nonimaging probe from the right sternal border illustrating the beat-to-beat variability of the
transaortic velocities. Ten consecutive beats were averaged (average Vmax ¼ 2 m/sec).

TABLE 95.3 Recommendations for Date Recording and Measurement for Aortic Stenosis Quantitation (European Association of Echocardiography/
American Society of Echocardiography Recommendation)
Date Element

Recording

Measurement

LVOT diameter

2D parasternal long axis view
Zoom mode
Adjust gain to optimize the blood–tissue interface

LVOT velocity

Pulsed wave Doppler
Apical long axis or 5-chamber view
Sample volume positioned just on LV side of valve and moved
carefully into the LVOT is required to obtain laminar flow curve
Velocity baseline and scale adjusted to maximize size of velocity
curve
Time axis (sweep speed) 100 mm/sec
Low wall filter setting
Smooth velocity curve with a well-defined peak and a narrow
velocity range at peak velocity
CW Doppler (dedicated transducer)
Multiple acoustic windows (e.g., apical, suprasternal, right
parasternal, etc.)
Decrease gains, increase wall filter, adjust baseline, and scale to
optimize signal
Gray-scale spectral display with expanded time scale
Velocity range and baseline adjusted so velocity signal fits and fills
the vertical scale
Parasternal long- and short-axis views
Zoom mode

Inner edge to inner edge
Mid-systole
Parallel and adjacent to the aortic valve or at the site of velocity
measurement (see text)
Diameter is used to calculate a circular CSA
Maximum velocity from peak of dense velocity curve
VTI traced from modal velocity

AS jet velocity

Valve anatomy

Maximum velocity at peak of dense velocity curve
Avoid noise and fine linear signals
VTI traced from outer edge of dense signal curve
Mean gradient calculated from traced velocity curve

Identify number of cusps in systole, raphe if present
Assess cusp mobility and commissural fusion
Assess valve calcification

AS, aortic stenosis; CSA, cross-sectional area; CW, continuous wave; LV, left ventricular; LVOT, left ventricular outflow tract; VTI, velocity-time integral;
2D, two dimensional.
With permission from the European Society of Cardiology6 and the American Society of Echocardiography.7


Quantification of Aortic Stenosis Severity
Figure 95.16. The methodology
used for planimetry of the aortic valve
orifice by transesophageal echocardiogram. A, In a longitudinal (longaxis) view, the aortic valve should be
placed as close to the center of the
sector as possible (to take advantage
of axial resolution). B, The image
plane (arrow) should then be rotated
90 degree to obtain a short-axis view
and the plane moved cranially and
caudally to obtain the smallest orifice.
The aortic valve can then be

planimetered.

409

95

A

TABLE 95.4 Serial Echocardiography in Valvular Aortic Stenosis
Severity of Aortic Stenosis

Serial Echocardiography

Mild
Moderate
Severe

Every 3–5 yrs
Every 1–2 yrs
Yearly

Echocardiography should be performed more frequently if there is a
change in signs or symptoms.
Adapted from AHA/ACC Valvular Disease Guidelines. J Am Coll Cardiol
48:el-148, 2006.

large-scale prospective trials, and their clinical relevance has not
yet been established.
Cardiac magnetic resonance imaging52 and computed tomography31,53,54 have also been used to evaluate aortic valve area.
However, these methods have not been fully validated and are

subject to some of the same limitations of echocardiography
(e.g., heavily calcified valve).

SERIAL EVALUATION OF AORTIC STENOSIS
Valvular aortic stenosis is a progressive disease, and an increase is
severity is inevitable; however, the rate of progression is variable
among individuals with AS. Because of the inability to predict this
individual variability, serial clinical and echocardiographic followup is recommended in all patients with AS, as outlined in Table 95.4.

PHYSIOLOGIC CONSEQUENCES OF AORTIC
STENOSIS
For complete assessment of a patient with AS, not only the appearance of the valve and its area and gradient, but also the physiologic
consequences of the stenosis, should be evaluated and reported.
These include the degree of hypertrophy (i.e., left ventricular
mass), systolic and diastolic dysfunction, degree of left atrial
enlargement, and pulmonary hypertension.

Left Ventricular Systolic Dysfunction
The chronic pressure overload imposed by valvular AS leads to
concentric left ventricular hypertrophy (LVH). This increase in
wall thickness is an adaptive process that maintains normal wall
stress. However, as the stenosis progresses, this initially adoptive
process eventually becomes deleterious. The progressive LVH,
increasing afterload, and increasing wall stress lead to compromised coronary flow reserve and subendocardial ischemia.55,56
Even in the absence of significant epicardial coronary artery narrowing, the increased muscle mass, the increased wall stress, and
the result of ventricular pressure compressing the microcirculation
will ultimately lead to myocardial fibrosis and gradually cause

B

reduced systolic and diastolic function.57 The development of
diffuse myocardial fibrosis is believed to be an essential step in
the transition from cardiac adaptation to cardiac failure.58
Left ventricular systolic dysfunction usually occurs late in the disease course of AS. Early, the left ventricular ejection fraction (LVEF)
is preserved by the increased wall thickness that maintains wall stress
and is, therefore, an insensitive measure of the early maladaptive process within the myocardium. However, there is recent awareness of
subclinical left ventricular dysfunction in AS that can be detected
by global left ventricular longitudinal strain (GLS).59–67 Furthermore,
impaired GLS has been independently associated with poor long-term
outcome.66,67 Lancellotti et al. have demonstrated that the presence of
impaired GLS in asymptomatic patients with moderate-to-severe AS
is independently associated with the development of symptoms, need
for aortic valve replacement, and death.68

Left Ventricular Diastolic Dysfunction
In patients with AS, diastolic dysfunction begins at an earlier stage
than the decrease in the LVEF.69 Abnormal measures of diastolic
function are common in patients with AS. At an early stage, the
compensatory LVH of AS is associated with impaired relaxation.
This filling pattern is common in mild and moderate AS. As the
degree of AS progresses, the degree of diastolic dysfunction also
increases. The dyspnea that often accompanies severe AS is typically attributed to the outflow obstruction; however, diastolic dysfunction likely also contributes to this symptom. These patients
often have pseudonormal or restrictive filling patterns suggesting
an elevated filling pressure.69–71 In addition, the early diastolic
Doppler tissue velocity of the mitral annulus (e0 ) is decreased
and may increase after aortic valve replacement.72
Preliminary data from the Mayo Clinic demonstrated that
among asymptomatic patients with severe AS, those with an
enlarged left atrium were more likely to develop symptoms than
those with a smaller left atrium. Moreover, left atrial diameter

was a strong independent prediction of all-cause mortality after
adjusting for age, AVA, peak aortic valve velocity, and mean gradient. Their findings support the importance of diastolic function in
these patients and they recommend comprehensive assessment of
diastolic function, including left atrial size.73

Pulmonary Hypertension
Severe pulmonary hypertension (PHTN) is an expected finding in
patients with mitral valve disease, especially mitral stenosis. However, severe PHTN is not widely associated with severe AS. Nevertheless, it has been reported in up to 34% of patients before aortic
valve replacement for AS.74–76 Although the etiology of PHTN in
severe AS remains unclear, it is associated with systolic and/or diastolic dysfunction.77,78 Moderate or severe mitral regurgitation may
also contribute to elevated left atrial and pulmonary artery pressure.
When present, severe PHTN portends a poor prognosis and significantly increases morbidity and mortality.79


410

SECTION XV Aortic Stenosis

AORTIC VALVE SCLEROSIS
Aortic valve thickening (fibrosis and/or sclerosis) without stenosis
(i.e., without pressure gradient) is common in elderly adults. AS is
present in approximately 25% to 30% of adults older than age
65 years and in nearly 50% of adults older than age 85 years.80–82
Aortic valve sclerosis is generally defined as focal or diffuse thickening of the aortic cusps with minimal or no restriction of leaflet
motion and a peak transvalvular velocity by Doppler of <2 m/sec.
The focal areas of thickening are usually irregular and nonuniform,
and involve the base and center of the valve cusps rather than the
leaflet edges and commissures.
Aortic sclerosis is an asymptomatic condition that is usually
detected either as a short, systolic ejection murmur or as an incidental finding on echocardiography performed for other indications.

Until recently, aortic valve sclerosis was considered to be a physiologic result of aging without clinical relevance. However, aortic
valve sclerosis may be important as a marker for increased cardiovascular risk, including progression to AS.83–86
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Asymptomatic Aortic Stenosis
Helmut Baumgartner, MD

Aortic stenosis (AS) has become the most frequent valvular heart
disease in the adult population; it occurs primarily as calcific AS
at an advanced age. The prevalence in the population older than

65 years has been reported to be in the range of 2% to 7%.1 It is
the characteristic systolic murmur that draws in the general attention and guides a diagnostic workup. Doppler echocardiography is
the ideal tool to confirm the diagnosis and to quantify AS by calculating the pressure gradients (Fig. 96.1) and valve area. During a
long initial period, which is characterized by an increased outflow
tract obstruction that results in an increasing left ventricular pressure load, patients remain asymptomatic, and acute complications
are rare. However, as soon as symptoms, such as exertional dyspnea, angina, or dizziness and syncope occur, outcome becomes
dismal. The average survival after symptom onset has been
reported to be less than 2 to 3 years.2 In this situation, aortic valve
replacement (AVR) results in dramatic improvement, not only in
symptoms, but also in long-term survival.2 Thus, there is general
agreement that surgery should be strongly recommended in symptomatic patients.3,4 In contrast, the management of asymptomatic
patients with severe AS remains a matter of controversy.2–4
Because of the widespread use of Doppler echocardiography, it
is estimated that approximately 50% of patients who present with
severe AS are asymptomatic. Thus, cardiologists are frequently

faced with the difficult decision whether to operate on asymptomatic patients with severe AS.

ARGUMENTS FOR SURGERY IN ASYMPTOMATIC
AORTIC STENOSIS
Risk of Sudden Cardiac Death
Sudden death is the major concern when asymptomatic patients
with severe AS are followed conservatively. However, this risk
appears to be low. In addition, several studies that evaluated
patients with nonsevere AS did not report sudden deaths. Some prospective studies also reported on the outcomes of sizeable cohorts
of patients with severe AS (peak aortic jet velocity !4.0 m/sec).
Pellikka et al5 observed 2 sudden deaths among 113 patients during
a mean follow-up of 20 months. Both patients, however, developed
symptoms at least 3 months before death. In another study, 1 case of
sudden death, which was not preceded by symptoms, was reported

among 104 patients who were followed for a mean of 27 months.6
In a later retrospective study of 622 patients with a mean follow-up
of 5.4 Æ 4.0 years, Pellikka et al7 reported the rate of sudden death
to be 1% a year. However, in almost half of the patients who died
suddenly, information on the patient’s status was missing for the

96


412

SECTION XV Aortic Stenosis

Vpeak 4.6 m/sec
p mean 54 mm Hg

outcomes and had no survival advantage with AVR, which suggests
that they had additional unrecognized cardiac disease and that the
LV dysfunction was not caused by AS.
Nevertheless, there is concern that myocardial fibrosis and
severe LV hypertrophy, which may not be reversible after delayed
surgery, could adversely affect postoperative long-term outcomes.
In symptomatic patients, myocardial fibrosis, as detected by magnetic resonance delayed gadolinium enhancement, has been
reported to be irreversible and to predict adverse postoperative outcomes with regard to improvement of symptoms, LV function, and
survival.12,13 However, no data are available for asymptomatic
patients with regard to whether irreversible fibrosis, which may
be associated with worse outcomes, is already present during the
asymptomatic phase of the disease. Excessive LV hypertrophy
has been shown to be primarily associated with earlier symptom
development.14 However, it remains unknown whether a certain

cutoff for the extent of hypertrophy is associated with a worse outcome when surgery is delayed until symptoms develop.

Vpeak 5.3 m/sec
p mean 75 mm Hg

Surgical Considerations

Figure 96.1. Continuous wave Doppler recordings of an asymptomatic
patient with severe aortic stenosis. Note that the recording from a right
parasternal approach (bottom) yielded significantly higher velocities
(peak velocity 5.3 m/sec, mean gradient 75 mm Hg) than those obtained
from an apical approach (4.6 m/sec, 54 mm Hg).

year preceding the event. In a recent prospective study by Rosenhek
et al, in patients with extremely severe (peak jet velocity !5.0 m/
sec) but asymptomatic AS who were followed for a median of
41 months, only one case of sudden death was reported.8 Importantly, a small but still significant risk of sudden death (0.3%–
0.4%) was also reported even after surgery for congenital AS.9
Thus, prevention of sudden death is certainly not a strong argument
for surgery in asymptomatic patients.
Unfortunately, patients do not always promptly report their
symptoms. In addition, patients may need to wait several months
for surgery in some countries. However, mortality has been
reported to be high in the months after symptom onset. For example, in a Scandinavian study,10 7 of 99 patients with severe AS who
were scheduled for surgery died during an average waiting period
of 6 months.

Risk of Irreversible Myocardial Damage
In contrast to valvular regurgitation, patients with asymptomatic
severe AS who have developed impaired systolic left ventricular

(LV) function are extremely uncommon. In a recent study11 of
9940 patients with severe AS, only 43 (0.4%) had asymptomatic
LV dysfunction (ejection fraction <50%). These patients had poor

Patients with severe symptoms have been found to have a significantly higher operative mortality than those with no or mild symptoms (i.e., 2% for New York Heart Association [NYHA] functional
classes I or II compared with 3.7% and 7.0% for NYHA functional
classes III and IV).15 In addition, urgent or emergency valve
replacement carries a significantly higher risk than elective surgery.15 Nevertheless, individual operative risk must always be carefully weighed against the potential benefit and may be significantly
higher in elderly patients, particularly when comorbidities are
present. A review of Medicare data16 involving more than 142,000
patients indicated that the average in-hospital mortality for postAVR in patients older than age 65 years is 8.8% (and as high as
13% in low-volume surgical centers). In addition, prosthetic
valve–related long-term morbidity and mortality must also be taken
into account. Thromboembolism, bleeding, endocarditis, valve
thrombosis, paravalvular regurgitation, and valve failure occur at
a rate of at least 2% to 3% per year, and death directly related to
the prosthesis has been reported at a rate of up to 1% per year.3

Duration of the Asymptomatic Phase
Studies have reported a very rapid progression and early symptom
development in asymptomatic severe AS, with up to 80% of the
patients requiring AVR within 2 years.17 Such observations have
also raised the question whether it is worthwhile to delay surgery
in asymptomatic patients with severe AS. However, other investigators have reported better outcomes, with individual outcomes
varying widely. For example, survival free of death or valve
replacement indicated by the development of symptoms was
56 Æ 5% at 2 years in one series of asymptomatic severe AS.6 These
discrepant results may be explained by the fact that, in some studies, patients underwent surgery without having developed symptoms, whereas these interventions were counted as events. Thus,
the event-free survival reported in the literature has to be interpreted with caution.

Studies Reporting Better Outcome with Early
Surgery in Asymptomatic Severe Aortic Stenosis
Two studies reported better outcomes in asymptomatic severe AS
when surgery was performed before symptom onset, which advocated early AVR.18,19 However, these retrospective studies had
major limitations.20 In particular, both studies had poor followup quality and included patients who developed symptoms, but
who did not undergo surgery in the “conservatively treated” groups.
Data presented by Brown et al18 support the notion of waiting for


Asymptomatic Aortic Stenosis

symptoms, rather than operating early. In that study, patients who
underwent surgery and who presented with symptoms and patients
who underwent surgery while still being asymptomatic did not differ with regard to operative mortality and long-term outcome,
although symptomatic patients had a worse risk profile. Thus, there
was apparently no benefit from early surgery, and the authors’ data
interpretation may be misleading.
In summary, the arguments for surgery in asymptomatic AS are
relatively weak. Therefore, the current clinical practice guidelines
recommend surgery only in asymptomatic patients with a high likelihood of rapid hemodynamic progression (class IIb) or very severe
AS, which is defined as a peak transvalvular velocity of more than
5 m/sec, a mean gradient of more than 60 mm Hg, and an aortic
valve area of less than 0.6 cm2 (class IIb).3 The European guidelines have also added the following criteria as class IIb: markedly
elevated brain natriuretic peptide (BNP), an increase in the mean
gradient of more than 20 mm Hg with exercise, and excessive
LV hypertrophy.4 The European guidelines define very severe
AS as peak velocity more than 5.5 m/sec.4

PREDICTORS OF OUTCOME AND RISK
STRATIFICATION IN ASYMPTOMATIC SEVERE

AORTIC STENOSIS
Although it appears unlikely from current data that the potential
benefits of AVR can outweigh the risk of surgery and the long-term
risk of prosthesis-related complications in all asymptomatic
patients, concerns remain when waiting for symptoms to appear.
The ideal approach would be to refer patients for surgery before
symptom onset. Many risk predictors have been identified over
the years (Box 96.1). However, it has to be emphasized that these
risk predictors have, in general, been found to predict event-free
survival, with the most frequent event being symptom development, which indicates the need for surgery. No studies have demonstrated that surgery at an asymptomatic stage when such risk
predictors are present improves outcome compared with waiting
for symptoms. Thus, it is not surprising that guideline committees
only accepted some of these criteria, and only as class II indications
when surgical risk is low (Table 96.1).

Box 96.1 Predictors of Outcome in Aortic Stenosis
CLINICAL
• Age
• Atherosclerotic risk factors
ECHOCARDIOGRAPHIC
Transvalvular velocity and/or gradient at rest
Aortic valve area at rest
Extent of valve calcification
Hemodynamic progression rate
Increase of gradient with exercise
LV hypertrophy
LV ejection fraction
Myocardial deformation parameters of systolic and diastolic
LV function
• Degree of concomitant functional mitral regurgitation*

• Pulmonary artery pressure*
•
•
•
•
•
•
•
•

OTHERS
• Neurohormones (BNP/NT-pro-BNP)
• Myocardial fibrosis demonstrated by CMR late enhancement)*
*No data for asymptomatic aortic stenosis (AS)
BNP, Brain natriuretic peptide; CMR, cardiac magnetic resonance,
LV, left ventricular; NT-pro-BNP, N-terminal BNP.

413

TABLE 96.1 Recommendations for Isolated Aortic Valve Replacement
in Asymptomatic Aortic Stenosis (no indication for bypass surgery,
other valve surgery or aortic surgery)
Class

ACC/AHA Guidelines3

ESC Guidelines4

I

Pts. with reduced syst. LV
function (LVEF <0.50)

Pts. with red. syst. LV
function (LVEF <0.50)
Pts. who develop symptoms
during exercise testing
Pts. with a decrease in blood
pressure below baseline
during exercise testing
Pts. with severe valve
calcification and a rate of
peak velocity progression
!0.3 m/sec per year if
surgical risk is low
Pts. with very severe AS
(peak velocity >5.5 m/
sec) if surgical risk is low
Low surgical risk and 1 or
more of the following
findings:
• Markedly elevated
natriuretic peptide levels
(repeated
measurement, no other
explanation)
• Increase in mean
gradient >20 mm Hg
with exercise
• Excessive LVH without

hypertension

IIa

IIb

Pts. with abnormal response
to exercise (symptoms,
hypotension)
Pts. with high likelihood of
rapid progression (age,
CAD, calcification). Pts. with
extremely severe AS (valve
area <0.6 cm2, mean
gradient >60 mm Hg, peak
velocity > 5 m/sec) and
expected operative
mortality 1%

ACC, American College of Cardiology; AHA, American Heart Association;
AS, aortic stenosis; CAD, coronary artery disease; EF, ejection fraction;
ESC, European Society of Cardiology; LV, left ventricular; LVH, left
ventricular hypertrophy; pts., patients.

ECHOCARDIOGRAPHY AT REST
Peak aortic jet velocity,6–8,17 valve calcification,6 LVEF,7 rate of
hemodynamic progression,6 LV hypertrophy,14 and myocardial
deformation parameters of systolic and diastolic LV function21
have been reported to be predictors of outcome. The following
studies have reached clinical impact for the recommendations of

surgery.
Rosenhek et al. reported the outcome of 116 asymptomatic
patients with very severe AS, which was defined by a peak aortic
jet velocity of 5.0 m/sec or more.8 During a median follow-up of
41 months, 90 patients developed symptoms and underwent AVR,
whereas 6 patients died. Patients with velocities of 5.5 m/sec or more
had a particularly poor outcome, with only 25% surviving 2 years
without developing symptoms and requiring surgery. The study confirmed previous publications that reported peak aortic jet velocity to
be a strong independent predictor of event-free survival. There was
only 1 sudden death observed among these 116 patients, despite their
having very severe AS. The other five deaths were due to myocardial
infarction in one patient and congestive heart failure in four patients.
Of these four elderly patients, three died of multiorgan failure
associated with sepsis. Thus, the study confirmed that watchful
waiting is safe in asymptomatic patients. The fact that symptom-free
survival is, on average, short in patients with velocities of 5.5 m/sec
or more may, however, justify considering elective AVR as long as
surgical risk is low.
Aortic valve calcification has become a powerful independent
predictor of outcome.6 Event-free (death or symptoms requiring
surgery) survival at 4 years was 75 Æ 9% in patients with no or only
mild calcification versus 20 Æ 5% in those with moderately or

96