(BQ) Part 2 book ASE''s Comprehensive echocardiography textbook presents the following contents: Aortic stenosis, aortic regurgitation, mitral stenosis, pulmonic regurgitation, prosthetic valves, mitral regurgitation, infective endocarditis, pericardial diseases,...
Trang 1Steven A Goldstein, MD
CONGENITAL AORTIC STENOSIS
Bicuspid Aortic Valve
Congenital aortic valve malformation reflects a phenotypic
contin-uum 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
pro-cess 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
pop-ulation is 1% to 2%, making it the most common congenital heart
defect Information on the prevalence of BAV comes primarily
from pathology centers.1–7Valvular aortic stenosis (AS), a chronic
progressive disease, usually develops over decades.Box 94.1lists
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
tri-leaflet 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
sub-valve AS, hypertrophic cardiomyopathy, and suprasub-valve AS) are
discussed in other chapters
The most reliable estimate of BAV prevalence is often
consid-ered to be the 1.37% reported by Larson and Edwards.4The authors
have a special expertise in aortic valve disease and amassed 21,417
consecutive autopsies with 293 BAVs An echocardiographic
sur-vey of primary school children demonstrated a BAV in 0.5% of
males and 0.2% of females.8A more recent study detected 0.8%
BAVs in nearly 21,000 men in Italy who underwent
echocar-diographic screening for the military.9Table 94.1summarizes 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.1,13–16There are also several syndromes
in which BAV is a part of left-sided obstructive lesions of left
ventricular inflow and outflow obstruction, including Shone
syn-drome (multiple left-sided lesions of inflow and outflow
obstruc-tion), Williams syndrome (supravalvular stenosis), and Turner
syndrome (coarctation)
Natural History of Bicuspid Aortic ValvesAlthough a few patients with BAV may go undetected or withoutclinical consequences for a lifetime, most will develop complica-tions The most important clinical consequences of BAV are valvestenosis, valve regurgitation, infective endocarditis, and aorticcomplications such as dilatation, dissection, and rupture(Box 94.2) Estimates of the prevalence of these complicationsand outcomes have varied depending on the era of the study, thecohort selected, and the method used to diagnose BAV (clinicalexam vs cardiac catheterization vs echocardiography) Severallarge recent studies have helped to better define the unoperatedclinical course in the modern era.17–19
Isolated AS is the most frequent complication of BAV, ring in approximately 85% of all BAV cases.10,18–20Bicuspid aorticvalve accounts for the majority of patients aged 15 to 65 years withsignificant AS The progression of the congenitally deformed valve
occur-to AS presumably reflects its propensity for premature fibrosis,stiffening, and calcium deposition in these structurally abnormalvalves
Aortic regurgitation, present in approximately 15% of patientswith BAV,10is usually due to dilation of the sinotubular junction ofthe aortic root, preventing cusp coaptation It may also be caused bycusp prolapse, fibrotic retraction of the leaflet(s), or damage to thevalve from infective endocarditis Aortic regurgitation tends tooccur in younger patients than does AS
Why some patients with a BAV develop stenosis and othersregurgitation is not clear As mentioned, rarely, patients may notdevelop hemodynamics consequences Roberts and colleaguesreported three congenital BAVs in nonagenarians who underwentsurgery for AS.21Why some patients with a congenital BAV donot become symptomatic until they are in their 90s and why othersbecome symptomatic in early life is also unclear
Echocardiographic Features of Bicuspid Aortic ValvesThe roles of echocardiography in the detection and evaluation arelisted inBox 94.3 The diagnosis of a BAV can usually be made bytransthoracic echocardiography (TTE) When adequate images areobtained, sensitivities and specificities of up to 92% and 96%,respectively, have been reported for detecting BAV.22–24The mostreliable and useful views are the parasternal short-axis and long-axis views The echocardiographic features and their respectiveviews are summarized inBox 94.3 The parasternal short-axis view(SAX) is extremely useful to examine the number and position ofthe commissures, the opening pattern, the presence of a raphe, andthe leaflet mobility In contrast to the normal tricuspid aortic valve(TAV), which opens in a triangular fashion with straightening of theleaflets (seeFig 94.1; Fig 94.2,A), the BAV opens in an elliptical(“fish-mouth” or “football”) shape with curvilinear leaflets (seeFig 94.1; Figs 94.3and94.4) There is typically a raphe, a fibrousridge that represents the region where the cusps failed to sepa-rate.10,25The raphe is usually distinct and generally extends from
389
Trang 2the free margins to the base of the leaflet Calcification commonly
occurs first along this raphe, ultimately hindering the motion of the
conjoined cusp.26Rarely, the leaflets are symmetric and there is no
raphe—a “pure” bicuspid valve Note that a false-negative
diagno-sis may occur when the raphe gives the appearance of a third
coap-tation 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 (seeFigs 94.1and94.2,B) When the
commis-sures are deviated from those clock-face position, one should
sus-pect 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.28,29In 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
short-axis 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.29The least common type is
fusion of the left and noncoronary cusps.28Michelena and colleagues
similarly classified BAVs astypical (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) andatypical (right-noncoronary
cusp fusion) if the commissures were at 1 and 7 o’clock or 12 and
6 o’clock.19
Box 94.1 Aortic Stenosis: Etiology
1 Congenital (unicuspid, bicuspid, quadricuspid)
2 Degenerative (sclerosis of previously normal valve)
3 Rheumatic
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.)
TABLE 94.1 Prevalence of Bicuspid Aortic Valves (BAV)
• 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
Trang 3The parasternal long-axis (PLAX) view typically shows tolic doming (seeFig 94.4,B; and Fig 94.6) due to the limitedvalve opening In a normal TAV, the leaflets open parallel tothe aortic walls In diastole, one of the leaflets (the larger, con-joined cusp) may prolapse The PLAX view with color Doppler
sys-is also useful to evaluate for aortic regurgitation (the diastolic tic regurgitant jet is usually eccentric) and AS (turbulence in theaortic root and ascending aorta in systole) Last, the PLAX view is
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.
Figure 94.3 Transesophageal echocardiogram (cross section) of a
bicuspid aortic valve that illustrates the elliptical (“fish-mouth” or
“foot-ball”) shape with curvilinear leaflets in systole.
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).
Trang 4also 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.34The 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
trans-esophageal 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
with-out stenosis or aneurysm.32Even if the valve orifice is not reduced
(i.e., no stenosis), it is geometrically altered in BAV, and
consequently the jet flow may be abnormal in its direction.31Hopeand colleagues32 demonstrated two different flow patterns thatwere specific to the two most common cusp fusion types Fusion
of the right-left coronary cusps generated a right-anterior flowjet, whereas fusion of the right-noncoronary cusps generated aleft-posterior flow jet
CoarctationBicuspid aortic valve may occur in isolation or in association withother forms of congenital heart disease There is a well-documentedassociation of BAV with coarctation.7,20,24,35–40An autopsy studyfound coexisting coarctation of the aorta in 6% of cases of BAV,1and an echocardiographic study found coarctation in 10% ofpatients with BAV.38On the other hand, as many as 30% to 70%
of patients with coarctation have a BAV.* Therefore, when aBAV is detected on an echocardiogram, coarctation of the aortashould always be sought
Infective EndocarditisPatients with BAVs are particularly susceptible to infective endo-carditis Although the exact incidence of endocarditis remains con-troversial, the population risk, even in the presence of a functionallynormal valve, may be as high as 3% over time.1The estimated inci-dence is 0.16% per year in unoperated children and adolescents.41
In adults, the two large case series by Tzemos and Michelena andtheir colleagues18,19suggest that the incidence is 0.3% and 2% peryear, respectively In a series of 128 microbiologically proven epi-sodes of endocarditis, the commonest predisposing risk factor wasBAV (16.7%).42In another series of 50 patients with native valveendocarditis, 12% had BAV.43
In many cases of BAV, endocarditis is the first indication ofstructural heart disease This fact emphasizes the importance ofeither clinical or echocardiographic screening for the diagnosis
of BAV Unexplained systolic ejection sounds (clicks) shouldprompt echocardiographic evaluation Surprisingly, bacterial endo-carditis prevention is no longer recommended by the most recent
TABLE 94.2 Distinctive Echocardiographic Features of Bicuspid
Aortic Valves
View
Oval opening (football-shaped; fish-mouth, elliptical;
PLAX, Parasternal long-axis; SAX, parasternal short-axis.
Figure 94.6 Transesophageal echocardiographic longitudinal view of
the aortic root and ascending aorta illustrating the systolic doming of a
bicuspid aortic valve.
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).
*References 7 , 20 , 29 , 37 , 40
Trang 5American College of Cardiology/American Heart Association
(ACC/AHA) Guideline for BAV.44
Aortic Complications
Bicuspid aortic valve is associated with several additional
abnor-malities, 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
asso-ciated 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
and94.4) These vascular complications may occur independent
of valvular dysfunction*and can manifest in patients without
sig-nificant stenosis or regurgitation According to Nistri and
col-leagues, 50% or more of young patients with normally
functioning bicuspid aortic valves have echocardiographic
evi-dence of aortic dilatation.9Therefore, the size and shape of the
aor-tic 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
syn-drome, 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
dis-tal to the STJ48,49(Figs 94.9and94.10) 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
Although BAV aortopathy may share similarities with theMarfan syndrome, and aortic aneurysms are common in both con-ditions, a recent retrospective cohort study of 416 consecutivepatients with definite BAV provides evidence that their clinical out-comes are different and that aortic dissection is more common inMarfan syndrome.18 The risk of aortic dissection in this BAV
*References 9 , 11 , 15 , 46 , 47
TABLE 94.3 Frequency of Aortic Dissection in Persons with a Bicuspid Aortic Valve (BAV)
Frequency of Aortic
TABLE 94.4 Frequency of Bicuspid Aortic Valve (BAV) in Aortic
Dissection (Spontaneous, Noniatrogenic Dissection at Autopsy)
LALV
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.
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.
393
Aortic Stenosis Morphology
94
Trang 6cohort 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.52TTE 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
imag-ing 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
Family Screening of Patients with BAV
BAV appears inheritable and was present in 9.1% of first-degree
relatives in one study.38Although the current ACC/AHA
guide-lines on valve disease52do 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)
Unicuspid Aortic ValveOther less common congenital abnormalities of the aortic valveinclude the unicuspid valve and quadricuspid valve The unicuspidaortic valve (UAV) is a rare congenital malformation seen inapproximately 0.002% of patients referred for echocardiography,but in as many as 4% to 6% of patients undergoing surgery for
“pure” (isolated) AS.55Two forms of UAV are recognized: Onehas no commissures or lateral attachments to the aorta at the level
of the orifice (acommissural), and the second has one lateral ment to the aorta at the level of the orifice (unicommissural).56Both
attach-of these types, like the BAV, produce a dome-shaped opening insystole57(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.58An acommissural type ofUAV has a central round, oval, or triangular opening caused byunderdevelopment of all three cusps, resulting in a “volcano-like”structure with a small, central orifice (Fig 94.12,A) Stenosis of anacommissural valve is typically very severe and occurs duringinfancy In a unicommissural type of UAV, there is usually aneccentric “teardrop”-shaped opening (seeFig 94.12,B) The mostcommon position of the single commissural attachment zone in thistype is posterior59(Video 94.1) This configuration results in a rel-atively larger orifice than the acommissural type As a result, somepatients with a unicommissural UAV live into adulthood beforemanifesting valvular obstruction Like BAV patients, UAV patientsare more often male.59Compared with patients undergoing surgery
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
Anteriormitralleaflet
Dome(“volcano,” nolateral attachments)
(“Exclamation point”one lateral attachment)Unicommissural
Figure 94.11 Diagram of the two types of unicuspid aortic valves (see text).
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.
Trang 7for BAV and TAV disease, unicommissural UAV patients present
about 2 decades earlier than patients with BAV60and 3 decades
ear-lier than patients with TAV.61Unicommissural UAV patients
usu-ally 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
chal-lenging (seeFig 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).64,65A much higher incidence was reported by Olson
and colleagues in a review of 225 patients undergoing surgery for
pure aortic regurgitation.66Most cases historically were discovered
incidentally at surgery or postmortem examination However, the
majority of cases are now diagnosed antemortem by
echocardiog-raphy.67,68Because 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.72The 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.64,73In general, valve dysfunction
is seldom present or minimal during childhood or
adoles-cence.64,65,72,75Aortic valve dysfunction is usually due to aortic
regurgitation (Table 94.7) and tends to occur later in life, a
consequence of progressive leaflet thickening with resultantincomplete coaptation (Video 94.2) Unlike BAV, the association
of ascending aortic aneurysm is extremely rare
The characteristic echocardiographic finding is an “X”-shapedpattern in diastole in short-axis views (formed by the commissurallines of the closed QAV), compared with the “Y” in normal trileaf-let valves (Fig 94.13) Because valve dysfunction may occur withadvancing age, clinical and echocardiographic follow-up isrecommended
Although QAV is usually an isolated anomaly,64,72,73variouscardiac and noncardiac anomalies have been reported in associationwith it (Box 94.4).76–78The most prevalent cardiac malformationsassociated with QAV are coronary artery anomalies, which havebeen reported in 10% of cases.67,79–83
In summary, QAV is a rare congenital disorder, usually nosed in adulthood, with a potential for complications—mainlyaortic regurgitation QAVs often require surgery, usually in thefifth and sixth decades, and therefore need close follow-up
diag-TABLE 94.5 Quadricuspid Aortic Valve—Prevalence
0/2000 2/25,666
8/60,446 6/13,805 2/225
AR, Aortic regurgitation
*1982-1988
† 1987-1988
TABLE 94.6 Quadricuspid Aortic Valves: Morphologic Types
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).
TABLE 94.7 Function of Quadricuspid Aortic Valves
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 ).
Figure 94.13 Quadricuspid aortic valve Transesophageal graphic short-axis view (37 degrees) illustrates failure of leaflet coaptation
echocardio-in diastole (arrow) with a square central openechocardio-ing and typical X-shaped configuration of the four commissures.
Box 94.4 Cardiac and Noncardiac Abnormalities Associatedwith Quadricuspid Valve
1 Patent ductus arteriosus
2 Hypertrophic cardiomyopathy
3 Subaortic stenosis
4 Ehlers-Danlos syndrome
5 Coronary ostium displacement
6 Ventricular septal defect
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Aortic Stenosis Morphology
94
Trang 8CALCIFIC (DEGENERATIVE) AORTIC STENOSIS
Calcific AS is the most common etiology of valvular AS in elderly
patients The prevalence of calcific AS increases with age.84AS 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
previ-ously 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
dys-trophic calcification.86–90 Therefore, the termcalcific 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
cal-cification, 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
forma-tion 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.93Irregular leaflet thickening and focal
increased echogenicity (calcifications) are the echocardiographic
hallmarks of calcific AS These focal areas of thickening are
typically seen in the center of the valve cusps The degree of fication 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 nod-ules), and severe (extensive thickening and calcification of all ofthe cusps).89,94
calci-The degree of leaflet calcification is a marker of disease gression and should be reported.94 , 95
pro-As the leaflets become moresclerotic, they become progressively more rigid and less mobileand begin to obstruct flow Increases in aortic transvalvular flowvelocity mark the progression from aortic sclerosis to AS In themost 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 movefreely When only one leaflet is immobile, there is usually only amild increase in transaortic velocity (mild AS) Unlike rheumatic
AS, commissural fusion is usually absent or only minimal in cific AS The valve orifice tends to be triradiate—three slitlikeopenings in systole (Figs 94.14,E and94.15).96Calcification oftenextends onto the base of the anterior mitral leaflet Calcificationmay also extend from the valve cusps into the ventricular septumand may induce conduction abnormalities
cal-RHEUMATIC AORTIC STENOSISRheumatic AS has become uncommon in the developed world,although it remains a significant cause of AS worldwide In adultsundergoing aortic valve replacement for symptomatic AS in theUnited States, calcific tricuspid AS accounts for 5% of cases, bicus-pid AS for 36%, and rheumatic AS for 9%.97Aortic rheumatic valvedisease is never isolated, but is virtually always associated with
A
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.)
Trang 9rheumatic mitral valve disease Rheumatic valvular dysfunctionmay affect not only an anatomically normal TAV, but also acongenital BAV.
Similar to rheumatic mitral valve disease, rheumatic aorticvalve deformities are characterized by diffuse cuspal thickeningthat extends to their free edges and by commissural fusion Thesefeatures 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 affectone, two, or all three commissures and is usually distinguishablefrom the commissural fusion of congenital valve abnormalities.The commissural fusion, which begins at the annulus and pro-gresses toward the center, often affects each commissure equally,producing a small, central, circular or triangular orifice (seeFig 94.1; Fig 94.16) Subsequent calcium deposition occurs sec-ondarily Commissural fusion is the primary lesion of AS, asopposed to fibrosis/sclerosis, shortening, and retraction of thecusps, which produce rheumatic aortic regurgitation Interestingly,the sole pathognomonic feature of rheumatic valve disease, theAschoff granuloma, is virtually never found in aortic valve tissue.98Please access ExpertConsult to see Videos 94.1 and 94.2
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12 Chan KL, Ghani M, Woodend K, et al.: Case-controlled study to assess risk factors for aortic stenosis in congenitally bicuspid aortic valve, Am J Cardiol 88:690–693, 2001.
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aor-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.)
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.
397
Aortic Stenosis Morphology
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41 Gersony WM, Hayes CJ, Driscoll DJ, et al.: Bacterial endocarditis in patients with
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46 Ferencik M, Pape LA: Changes in size of ascending aorta and aortic valve function
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47 Plaisance BR, Winkler MA, Attili AK, et al.: Congenital aortic valve first
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48 Della Corte A, Bancone C, Quarto C, et al.: Predictors of ascending aortic
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51 Schievink WI, Raissi SG, Maya MM, et al.: Screening for intracranial aneurysms
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52 Bonow RO, Carabello BA, Chatterjee K, et al.: 2008 focused update incorporated
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53 Warnes CA, Williams RG, Bashore TM, et al.: ACC/AHA 2008 guidelines for the
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54 Hiratzka LF, Bakris GL, Beckman JA, et al.: 2010 ACCF/AHA/AATS/ACR/
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55 Roberts WC, Ko JM: Frequency by decades of unicuspid, bicuspid, and tricuspid
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56 Tempe DK, Garg M, Tower AS, et al.: Unicuspid aortic valve: transesophageal
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67 Tutarel O: The quadricuspid aortic valve: a comprehensive review, J Heart Valve Dis 13:534–537, 2004.
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70 Hunt GB: Congenital quadricuspid aortic valve detected on chest CT,J Med ing Radiol Oncol 53:380–381, 2009.
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95 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.1Moreover, 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
exer-tional syncope) occur However, the clinical diagnosis of AS can
be challenging Clinical signs and symptoms are limited for
distin-guishing critical AS from noncritical AS, and these signs have
reduced sensitivity and specificity in the elderly.2,3Cardiac
cathe-terization, 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
under-went retrograde catheterization.5
In contrast, echocardiography provides noninvasive assessment
of both valve morphology and hemodynamics Because of its
ver-satility, 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
non-diagnostic or discrepant with clinical parameters.6,7In most
situa-tions, 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
recom-mended 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
coronary cusp, which is the most anterior cusp; and (2) either thenoncoronary cusp [NCC] (most commonly) or the left coronarycusp Normal aortic valve cusps appear thin and delicate In thePLAX view, the cusps open rapidly in systole and appear as parallellines close to the aortic walls (Fig 95.1) In diastole, the leafletscome together and appear as a linear density in the center of theaortic root, parallel to the aortic walls The aortic leaflets are sel-dom seen during the opening and closing because their motion isvery 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 invertedMercedes Benz sign) Sometimes, there is a slight thickening ofthe mid-portion of each closure line formed by nodules known asthe nodules of Arantius In the SAX view, the NCC is locatedposteromedially The atrial septum always points to the NCC.The left coronary cusp is located posterolaterally
M-Mode EchocardiographyM-mode echocardiography of the aortic valve is formed by direct-ing the M-mode echo beam through the aortic leaflets This can bedone 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
Box 95.1 Echo-Doppler Parameters to Evaluate in AorticValve 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
399
Quantification of Aortic Stenosis Severity
95
Trang 12throughout systole and rapidly close again at end-systole, forming abox or parallelogram Normally, these leaflets show fine, regularvibrations during systole These fine vibrations actually indicatethat the leaflets are thin, and are able to luff, like a sail, due tothe 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 Duringdiastole, the coapted leaflets form a single (or sometimes multipleparallel) central closure line(s) midway between the aortic walls(seeFig 95.3) The left ventricular ejection time can be measuredfrom 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 notingthe maximal degree of separation of the leaflets at the onset of sys-tole In patients with valvular AS, the thickened leaflets (due tofibrosis and/or calcium) appear as dense echoes in both systoleand diastole In systole, the thickened rigid leaflets fail to openwidely The distance between the anterior cusp (right coronarycusp) and the posterior cusp (usually the NCC; sometimes, the leftcoronary cusp) is reduced or not even visible, which suggests mod-erate or severe AS (Fig 95.4) In the absence of a bicuspid valve, amaximal opening of the leaflets of at least 1.5 cm virtually excludessignificant valvular AS.12,13When any of the three leaflets opensnormally 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 STENOSISWith the development of acquired AS, the cusps became thickened,and their motion is restricted The degree of thickening and res-triction 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 planimeterthe aortic valve orifice by TTE have been largely unsuccessful.14Nevertheless, a qualitative estimation (gestalt) of AS severityshould be attempted and correlated with quantitative methods
If leaflet separation is at least 15 mm or if at least one cusp movesnormally, critical AS is highly unlikely As will be discussed later,planimetry is, however, possible in the majority of patients byusing TEE
QUANTITATIVE DOPPLER ASSESSMENT
OF SEVERITY OF AORTIC STENOSISThe previously mentioned 2D and M-mode features are useful fordetecting AS, but they are unreliable for quantitating AS Theseverity of AS is determined by a combination of 2D and Dopplerechocardiography As the aortic valve becomes stenotic, andobstruction to blood flow occurs, a pressure gradient developsacross 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 sure gradient, and the AVA
pres-Transaortic VelocitiesTransaortic jet velocities are directly obtained using a continuouswave (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 Dopplersignal that is aligned most parallel to the direction of the stenoticjet These windows include the apical 3- and 5-chamber views,the right sternal border, the suprasternal notch (SSN), and subxi-phoid views A careful, thorough, meticulous manipulation of thetransducer is necessary to achieve optimal alignment and to deter-mine the highest velocity possible (Fig 95.5) The highest velocityobtained from any window is used in the calculation of the gradient
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.
A
B
Figure 95.2 Transthoracic echocardiogram (short-axis view) of a
nor-mal tricuspid aortic valve A, In systole, the valve opens in a triangular
fashion with straightening of the leaflets B, In diastole, the normal
trileaf-let valve appears like a “Y,” with the commissures at 10 o’clock,
2 o’clock, and 6 o’clock.
Trang 13and the aortic valve area Lower values from the other windows are
ignored Using a nonimaging CW Doppler probe (so-calledPedoff
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 GradientsThe highest transaortic jet velocity (Vmax) measured by Dopplerreflects the pressure gradient according to the Bernoulli equation.The maximum pressure gradient (△ Pmax) across the stenoticaortic valve can be calculated by using the simplified Bernoulli
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.
401
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95
Trang 14equation that ignores viscous losses and the effects of flow eration These can be neglected in the usual clinical setting:
accel-Maximal pressure gradient (ΔPmax)= 4 (Vmax)2However, when the proximal or left ventricular outflow tract(LVOT) velocity (VLVOT) exceeds 1.5 m/sec, the modifiedBernoulli ejection should be used:
Δ Pmax = 4 (Vmax2− VLVOT2)The mean pressure gradient is obtained by a manual tracing of theDoppler velocity envelope The ultrasound machine’s softwareintegrates the instantaneous velocities throughout systole and pro-vides a mean value Both peak and mean gradients should bereported A mean gradient more than 40 to 50 mm Hg is consistentwith severe AS (Table 95.1) However, because calculated pressuregradients depend not only on the degree of stenosis, but also on(flow stroke volume and/or cardiac) output, higher gradients thanthose outlined inBox 95.1may occur in patients with altered vol-ume flow rates Examples of increased flow rates occur in aorticregurgitation, anemia, and pregnancy In these situations, relativelyhigh-pressure gradients may be present, although the degree of ASmay only be mild In contrast, patients with significant left ventric-ular systolic dysfunction, small left ventricles, high systemic vas-cular resistance, or mitral regurgitation may have relatively lowgradients despite severe AS The accuracy of Doppler-derived peakinstantaneous maximal and mean pressure gradients has beenvalidated with simultaneous cardiac catheterization data15,16(Figs 95.6 and95.7) It is important to recognize that the peakinstantaneous systolic pressure gradient measured by Doppler ishigher than the peak-to-peak gradient obtained during cardiaccatheterization (Fig 95.8) Potential sources of error in Dopplerassessment of transaortic gradients are listed inBox 95.2.Doppler measurement of gradients may be limited by TEEbecause of the difficulty in aligning the echo beam parallel tothe stenotic jet from standard esophageal views However, in themajority of cases, the deep transgastric view can be used to obtainaccurate maximal velocities and gradients (Fig 95.9) A seconduseful view can be obtained by slight clockwise rotation of theTEE probe from a standard gastric longitudinal view of the leftventricle (Fig 95.10)
Aortic Valve Area by Continuity EquationEcho-Doppler assessment of the severity of AS includes the calcu-lation of aortic valve area using the continuity equation The con-tinuity principle, based on the conservation of mass, states that the
A Apical 4-chamber Vmax = 3.6 m/sec
Figure 95.5 Continuous wave Doppler tracings from a patient with
severe aortic stenosis illustrate the importance of using multiple
trans-ducer 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.
TABLE 95.1 Grading the Severity of Aortic Stenosis
Aortic jet velocity (m/sec) 2.6–2.9 3.0–4.0 >4.0
Trang 15flow volumes (Q) at different sites in a closed system, like the heart,
are identical:
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
cross-sectional area (CSA) and the time-velocity integral (TVI) at that
point, the continuity equation can be stated as:
The continuity equation can be rearranged as follows:
CSA2 = CSA1 × TVI1
1 CSA of the LVOT (CSALVOT);
2 TVI of the LVOT (TVILVOT);
3 TVI of the aortic stenotic jet (TVI )
0
4080120160
n = 49
r = 0.80SEE = 17
Figure 95.6 Good correlation between
Doppler- and catheter-derived peak
instan-taneous gradients (Max gradient) when
performed simultaneously (left) versus
non-
simultaneously(right).Thedottedlinesrepre-sent 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.)
0
4080120160
Max
Max gradient (cath) mm Hg
n = 100
r = 0.95SEE = 10
0
4080
Mean gradient (cath) mm Hg
n = 100
r = 0.94SEE = 10
Figure 95.7 Good correlation
between Doppler- and
catheter-derived 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
Trang 16The CSA of the LVOT is obtained from the PLAX view TheLVOT 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 (apical5-chamber or 3-chamber view), using pulsed wave Doppler, placingthe sample volume (use a small sample volume) just proximal to thestenotic aortic valve, and tracing the waveform This waveformshould yield the highest velocity laminar flow immediately proximal
to the flow acceleration that occurs as the sample volume approachesthe stenotic valve This can be accomplished by placing the samplevolume in the LVOT (beneath the stenotic valve), slowly inchingtoward the stenotic valve, and recording the enveloped (laminar)velocity profiles at each step until flow acceleration (spectral broad-ening) occurs The sample volume should then be backed up (i.e.,moved apically) until a smooth, laminar velocity curve without spec-tral broadening is detected, which indicates a position proximal to theflow acceleration zone (Fig 95.12) This represents the correct LVOTvelocity tracing Next, using CW Doppler from multiple transducerpositions (as discussed in the previous section), the maximal TVIAS
is obtained The highest transaortic velocity and TVI from any ofthe transducer positions should be used to calculate the AVA.Although TVI is preferred, the peak velocity can also be used in thecontinuity equation The use of velocity is more practical in patientswith atrial fibrillation, when 5 to 10 consecutive beats should be mea-sured and averaged.11A sample calculation of the AVA using the con-tinuity 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×TVLVOT
VAo
AV area =(3.14) (1.0)2(1.0)= 0.8 cm2
4.0
Peakinstantaneous
Peak-to-peak
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)
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.
Trang 17LIMITATIONS AND PITFALLS IN THE
ECHO-DOPPLER QUANTITATION OF AORTIC STENOSIS
Calculation of the AVA by the continuity equation requires
pains-taking attention to detail in the measurement of the three previously
mentioned parameters Good correlation between
echocardiogra-phically and catheter-derived valve area has been
demon-strated17–19 (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
diam-eter may result in substantial error in the calculation of the AVA
Vmax = 4.2 m/secTVI = 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.
Figure 95.11 The continuity equation as applied to valvular aortic
ste-nosis: A1V1¼the flow volume in the left ventricular outflow tract and
A2V2¼the flow volume across the stenotic aortic valve The stenotic
aortic valve area (A2) can be calculated from the continuity equation.
405
Quantification of Aortic Stenosis Severity
95
Trang 18There 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,
mak-ing this measurement difficult
Theoretically, the LVOT diameter (LVOTd) should be
mea-sured 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.17When accurate
mea-surement 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
param-eter 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 (seeTable 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
Other parameters used for quantitating AS are the transaorticvelocity (Vmax, or so-calledV2) and the transaortic pressure gra-dient derived from V2 Underestimation of this velocity and pres-sure may occur if there is poor alignment of the Doppler beam (notparallel to the stenotic aortic jet) This potential problem can beminimized by using multiple transducer positions, as discussed ear-lier Overestimation of the true velocity and pressure gradient isless 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 nonimagingprobe These three jets are similar in direction as seen from apicalviews Sweeping the transducer back and forth to distinguish whichjet is which may help to avoid this pitfall A second clue to helpdistinguish these jets is their duration Mitral and tricuspid regurgi-tant jets are always longer than the AS jet because they include iso-volumic contraction and isovolumic relaxation In addition, the MRjet has a higher velocity because the left ventricular–left atrial gra-dient is higher than the left ventricular–aortic gradient in systole.Another method to distinguish the AS jet from the MR jet is theassociated diastolic signals in the tracing The MR jet is associatedwith mitral flow, whereas the AS jet is not and may be associated
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 cm 2 (Modified from
Oh JK, Taliercio CP, Holmes DR Jr, et al Prediction of the severity of
aor-tic stenosis by Doppler aoraor-tic valve area determination, J Am Coll Cardiol
11:1227-1234, 1988.)
LVOTd = 2.0 cm
BA
Figure 95.14 A , Zoomed parasternal long-axis view of the left ular 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
ventric-a lventric-arger ventric-and more ventric-accurventric-ate diventric-ameter of 2.0 cm.
Trang 19with 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 inBox 95.3 In the presence
of atrial fibrillation or frequent premature ventricular contractions,
averaging the velocity from 5 to 10 consecutive beats is
recom-mended (Fig 95.15) The use of the highest velocity alone results
in overestimating the gradient and underestimating the AVA
calcu-lated by the continuity equation The effect of systemic blood
pres-sure on the assessment of the mean prespres-sure gradient and AVA
remains controversial.25,26
Recommendations for measuring and recording valve
mor-phology and echo-Doppler parameters in patients with AS are
listed inTable 95.3 Given the potential therapeutic and
prognos-tic 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
accu-racy 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
echocardio-graphic measurements should be reviewed carefully and
criti-cally 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
catheter-ization as outlined in the American Heart Association/American
College of Cardiology and European Society of Cardiology
guidelines.6,7,11
PLANIMETRY OF AORTIC VALVE ORIFICETheoretically, the aortic valve orifice can be measured by planime-try using TTE in a manner similar to that used for assessing the ori-fice area in mitral stenosis However, this method is unreliable incalcific AS for several reasons: (1) because of the inability to deter-mine whether the plane of imaging is at the leaflet tips where max-imum stenosis occurs, and that it is parallel to the orifice; and (2)planimetry is difficult due to poor cusp definition from heavy cal-cium deposition, acoustic shadowing, and reverberation artifact.27Because of its superior resolution and unobstructed visualiza-tion, TEE provides excellent views of the aortic valve leaflets asthey open and close throughout the cardiac cycle Therefore, unlikewith TTE, direct measurement of the aortic valve area by TEE pla-nimetry can be performed with excellent correlation with cardiaccatheterization using the Gorlin equation and with echo-Dopplerusing the continuity equation.28–30 Planimetry by TEE has alsobeen shown to correlate well with planimetry by computed tomog-raphy.31To measure the AVA accurately, the image plane must belocated at the tips of the aortic valve leaflets This measurementrequires a careful technique to produce the correct imaging angleand plane It is useful to begin with a longitudinal view (usuallybetween 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 ofthe sector (Fig 95.16,A) This takes advantage of the axial resolu-tion and provides the optimal plane parallel to the aortic annulusand 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 machinescan be used to achieve this view Slight withdrawal and advance-ment of the TEE probe cranially and caudally is useful to findthe smallest orifice at the maximal leaflet tip separation The smal-lest systolic orifice is frequently found at a plane slightly higherthan the Mercedes Benz sign visualized in diastole The viewshould image all three cusps simultaneously Color Doppler mayaid in determining the stenotic orifice Adjusting the gain settings(reduce gain without losing definition of the leaflet and commis-sural edges) may help delineate the true margins of the orificefor planimetry The smallest orifice area at the time of maximalopening in early-to-mid systole should then be planimetered
THREE-DIMENSIONAL ASSESSMENT
OF THE AORTIC VALVE AREAReal-time, 3-dimensional TTE (RT3D TTE) has the potential toovercome a shortcoming of 3D-TTE by providing imaging at anyplane The cropping plane in the 3D dataset can provide a true en faceview aligned exactly to image the smallest stenotic aortic valve ori-fice for planimetry Several studies have documented superior accu-racy of planimetry by RD3D TTE compared with conventional2D-TTE.22,32–36 Therefore, RT3D TTE can, in some situations,overcome some of the limitations of the continuity equation; theAVA can be reliably evaluated when valvular AS co-exists withhypertrophic obstructive cardiomyopathy, discrete subaortic steno-sis, or supravalvular AS In addition, the evaluation of AS severity bythe continuity equation may be enhanced by using a RT3D TTEapproach for the measurement of the LVOT diameter or CSA.36
OTHER METHODS OF MEASURING AORTIC STENOSIS SEVERITY
Several additional echocardiographic parameters have been posed to better define the severity of AS and/or its risk Thoseinclude valve resistance,37–41 the energy loss index,42–44 strokework loss,45–47and valvuloarterial impedance.48–51However, theirutility and prognostic significance remain to be proven in
pro-TABLE 95.2 Factors Helping to Differentiate an Aortic Stenotic
Jet from Mitral Regurgitant Jet
when AS is less than severe;
but parabolic in severe AS
Parabolic Peaks in mid to late systole (exception acute, severe MR)
(no flow during isovolumic periods)
MR longer than AS (includes IVCT and IVRT)
Diastolic signals Gap between end of
AS and mitral inflow (IVRT)
End of MR jet is continuous with mitral inflow
AS , Aortic stenosis; IVCT, isovolumic contraction time; IVRT, isovolumic
relaxation time; MR, mitral regurgitation.
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
Trang 202.1 m/sec 1.5 m/sec 3.4 m/sec 2.0 m/sec 2.7 m/sec 3.2 m/sec
1.5 m/sec2.7 m/sec
2.7 m/sec3.4 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 Vmax¼2 m/sec).
TABLE 95.3 Recommendations for Date Recording and Measurement for Aortic Stenosis Quantitation (European Association of Echocardiography/ American Society of Echocardiography Recommendation)
LVOT diameter 2D parasternal long axis view
Zoom mode Adjust gain to optimize the blood–tissue interface
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 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
Maximum velocity from peak of dense velocity curve VTI traced from modal velocity
AS jet 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
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
Valve anatomy Parasternal long- and short-axis views
Zoom mode Identify number of cusps in systole, raphe if presentAssess 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 Cardiology 6 and the American Society of Echocardiography 7
Trang 21large-scale prospective trials, and their clinical relevance has not
yet been established
Cardiac magnetic resonance imaging52 and computed
tomo-graphy31,53,54 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
follow-up 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
appear-ance 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
compro-mised coronary flow reserve and subendocardial ischemia.55 , 56
Even in the absence of significant epicardial coronary artery
nar-rowing, 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
reduced systolic and diastolic function.57 The development ofdiffuse myocardial fibrosis is believed to be an essential step inthe transition from cardiac adaptation to cardiac failure.58
Left ventricular systolic dysfunction usually occurs late in the ease course of AS Early, the left ventricular ejection fraction (LVEF)
dis-is preserved by the increased wall thickness that maintains wall stressand is, therefore, an insensitive measure of the early maladaptive pro-cess within the myocardium However, there is recent awareness ofsubclinical left ventricular dysfunction in AS that can be detected
by global left ventricular longitudinal strain (GLS).59–67Furthermore,impaired GLS has been independently associated with poor long-termoutcome.66,67Lancellotti et al have demonstrated that the presence ofimpaired GLS in asymptomatic patients with moderate-to-severe AS
is independently associated with the development of symptoms, needfor aortic valve replacement, and death.68
Left Ventricular Diastolic Dysfunction
In patients with AS, diastolic dysfunction begins at an earlier stagethan the decrease in the LVEF.69Abnormal measures of diastolicfunction are common in patients with AS At an early stage, thecompensatory LVH of AS is associated with impaired relaxation.This filling pattern is common in mild and moderate AS As thedegree of AS progresses, the degree of diastolic dysfunction alsoincreases The dyspnea that often accompanies severe AS is typi-cally attributed to the outflow obstruction; however, diastolic dys-function likely also contributes to this symptom These patientsoften have pseudonormal or restrictive filling patterns suggesting
an elevated filling pressure.69–71 In addition, the early diastolicDoppler tissue velocity of the mitral annulus (e0) is decreasedand may increase after aortic valve replacement.72
Preliminary data from the Mayo Clinic demonstrated thatamong asymptomatic patients with severe AS, those with anenlarged left atrium were more likely to develop symptoms thanthose with a smaller left atrium Moreover, left atrial diameterwas a strong independent prediction of all-cause mortality afteradjusting for age, AVA, peak aortic valve velocity, and mean gra-dient Their findings support the importance of diastolic function inthese patients and they recommend comprehensive assessment ofdiastolic function, including left atrial size.73
Pulmonary HypertensionSevere pulmonary hypertension (PHTN) is an expected finding inpatients with mitral valve disease, especially mitral stenosis How-ever, severe PHTN is not widely associated with severe AS Nev-ertheless, it has been reported in up to 34% of patients before aorticvalve replacement for AS.74–76Although the etiology of PHTN insevere AS remains unclear, it is associated with systolic and/or dia-stolic dysfunction.77,78Moderate or severe mitral regurgitation mayalso contribute to elevated left atrial and pulmonary artery pressure.When present, severe PHTN portends a poor prognosis and signif-icantly increases morbidity and mortality.79
Figure 95.16 The methodology
used for planimetry of the aortic valve
orifice by transesophageal
echocar-diogram A, In a longitudinal
(long-axis) 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.
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.
409
Quantification of Aortic Stenosis Severity
95
Trang 22AORTIC 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
thick-ening 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
inciden-tal finding on echocardiography performed for other indications
Until recently, aortic valve sclerosis was considered to be a
phys-iologic result of aging without clinical relevance However, aortic
valve sclerosis may be important as a marker for increased
cardio-vascular risk, including progression to AS.83–86
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38 Ho PP, Paulis GL, Lamberton DF, et al.: Doppler derived aortic valve resistance in aortic stenosis: its hemodynamic validation, J Heart Valve Dis 3:283–287, 1994.
39 Bermejo J, Antoranz JC, Burwash IG, et al.: In vivo analysis of the instantaneous transvalvular pressure difference – flow relationship in aortic valve stenosis: implications of unsteady fluid-dynamics for the clinical assessment of disease severity, J Heart Valve Dis 11:557–566, 2002.
40 Kadem JJ, Freyer S, Weisser G, et al.: Correlation of degree of aortic valve nosis by Doppler echocardiogram to quantity of calcium in the valve by election beam tomography, Am J Cardiol 90:554–557, 2002.
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42 Garcia D, Pibarot P, Dumesnil JG, et al.: Assessment of aortic valve stenosis severity: a new index based on the energy loss concept, Circulation 101:765–771, 2000.
43 Garcia D, Dumesnil JG, Durand LG, et al.: Discrepancies between catheter and Doppler estimates of valve effective orifice area can be predicted from the pres- sure recovery phenomenon: practical implications with regard to quantification of aortic stenosis severity, J Am Coll Cardiol 041:435–442, 2003.
44 Bahlmann E, Cramariuc D, Gredts E, et al.: Impact of pressure recovery on cardiographic assessment of asymptomatic aortic stenosis: a SEAS substudy, JACC Cardiovasc Imaging 3:555–562, 2010.
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under-48 Briand M, Dumesnil JG, Kadem L, et al.: Reduced systemic arterial compliance impacts significantly on left ventricular afterload and function in aortic stenosis: implications for diagnosis and treatment, J Am Coll Cardiol 46:291–298, 2005.
49 Hachicha Z, Dumesnil JG, Pibarot P: Usefulness of the valvuloarterial impedance
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50 Levy F, Monin JL, Rusinaru D, et al.: Valvuloarterial impedance does not improve risk stratification in low-ejection fraction, low-gradient aortic stenosis: results from a multicentre study, Eur J Echocardiogr 12:358–363, 2011.
51 Lancellotti P, Magne J: Valvulooarterial impedance in aortic impedance in aortic sis: look at the load, but do not forget the flow, Eur J Echocardiogr 12:354–357, 2011.
steno-52 Reant P, Lederlin M, Lafitte S, et al.: Absolute assessment of aortic valve stenosis
by planimetry using cardiovascular magnetic resonance imaging: comparison with transesophageal echocardiography, transthoracic echocardiography, and car- diac catheterization, Eur J Radiol 59:276–283, 2006.
53 Bouvier E, Logeart D, Sablarolles JL, et al.: Diagnosis of aortic valvular stenosis
by multislice cardiac computed tomography, Eur Heart J 27:3033–3038, 2006.
54 Abdulla J, Silvertsen J, Kofoed KF, et al.: Evaluation of aortic valve stenosis
by cardiac multislice computed tomography compared with echocardiography:
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microcircu-latory dysfunction in patients with aortic stenosis and angiographically normal
coronary arteries, Circulation 105:470–476, 2002.
56 Rajappan K, Rimoldi OE, Camici PG, et al.: Functional changes in coronary
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57 Tzivoni D: Effect of transient ischaemia on left ventricular function and
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58 Creemers EE, Pinto YM: Molecular mechanisms that control interstitial fibrosis in
the pressure-overload heart, Cardiovasc Res 89:265–272, 2011.
59 Poulsen SH, Sogaard P, Nielsen-Kudsk JE, et al.: Recovery of left ventricular
systolic longitudinal strain after valve replacement in aortic stenosis and relation
to natriuretic peptides, J Am Soc Echocardiogr 20:877–884, 2007.
60 Weidemann F, Herrmann S, Stork S, et al.: Impact of myocardial fibrosis
in patients with symptomatic severe aortic stenosis, Circulation 120:577–584,
2009.
61 Delgado V, Tops LV, van Bommel RJ, et al.: Strain analysis in patients with
severe aortic stenosis and preserved left ventricular ejection fraction undergoing
surgical valve replacement, Eur Heart J 30:3037–3047, 2009.
62 Geyer H, Caracciolo G, Abe H, et al.: Assessment of myocardial mechanics using
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63 Herrmann S, Stork S, Niemann M, et al.: Low-gradient aortic valve stenosis
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58:402–412, 2011.
64 Ng AC, Delgado V, Bertini M, et al.: Alternations in multidirectional myocardial
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two-dimensional speckle tracking analysis, Eur Heart J 32:1542–1550, 2011.
65 Miyazaki S, Daimon M, Miyazaki T, et al.: Global longitudinal strain in relation to
the severity of aortic stenosis: a two-dimensional speckle-tracking study,
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66 Dahl JS, Videbaek L, Poulsen MK, et al.: Global strain in severe aortic valve
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67 Kearney LG, Lu K, Ord M, et al.: Global longitudinal strain is a strong
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68 Lancellotti P, Donal E, Magne J, et al.: Impact of global left
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69 Lund O, Flo C, Jensen FT, et al.: Left ventricular systolic and diastolic function
in aortic stenosis Prognostic value after valve replacement and underlying
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70 Hess OM, Villari B, Krayenbuehl HP: Diastolic dysfunction in aortic stenosis, Circulation 87(Suppl IV):73–76, 1993.
71 Villari B, Campbell SE, Hess OM, et al.: Influence of collagen network on left ventricular systolic and diastolic function in aortic valve disease, J Am Coll Car- diol 22:177–184, 1993.
72 Casaclang-Verzosa G, Ommen SR, Oh JK: Effects of aortic valve replacement on annular tissue Doppler velocities (abstr), J Am Soc Echocardiogr 18:41, 2005.
73 Casaclang-Verzosa G, Malouf JP, Scott CG, et al.: Does left atrial size predict mortality in asymptomatic patients with severe aortic stenosis?Echocardiography 27:105–109, 2010.
74 Silver K, Aurigemma G, Krendel S, et al.: Pulmonary artery hypertension in severe aortic stenosis: incidence and mechanism, Am Heart J 125:146–150, 1993.
75 Ben-Dor I, Goldstein SA, Pichard AD, et al.: Clinical profile, prognostic tion, and response to treatment of pulmonary hypertension in patients with severe aortic stenosis, Am J Cardiol 107:1046–1051, 2011.
implica-76 Zlotnick DM, Ouellette ML, Malenka DJ, et al.: Effect of preoperative pulmonary hypertension on outcomes in patients with severe aortic stenosis following surgi- cal aortic valve replacement, Am J Cardiol 142:1635–1640, 2013.
77 Aragam JR, Folland ED, Lapsley, et al Cause and impact of pulmonary sion in isolated aortic stenosis on operative mortality for aortic valve replacement
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78 Faggiano P, Antanini-Canterin F, Ribichini F, et al.: Pulmonary artery sion in adult patients with symptomatic valvular aortic stenosis, Am J Cardiol 85:204–208, 2000.
79 Malouf JF, Enriquez-Sarano M, Pellikka PA, et al.: Severe pulmonary sion in patients with severe aortic valve stenosis: clinical profile and prognostic implications, J Am Coll Cardiol 40:789–795, 2002.
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81 Otto CM, Lind BK, Kitzman DM, et al.: Association of aortic valve stenosis with cardiovascular mortality and morbidity in the elderly, N Engl J Med 341:142–147, 1999.
82 Stewart BF, Siscovick D, Lind BK, et al.: Clinical factors associated with calcific aortic valve disease, J Am Coll Cardiol 29:630–634, 1997.
83 Freeman RV, Otto CM: Spectrum of calcific aortic valve disease: pathogenesis, disease progression, and treatment strategies, Circulation 111:3316–3326, 2005.
84 Agmon Y, Khandheria BK, Meissner I, et al.: Aortic valve sclerosis and aortic atherosclerosis: different manifestations of the same disease? Insights from a population-based study, J Am Coll Cardiol 38:827–834, 2001.
85 Cosmi JE, Kort S, Tunick PA, et al.: The risk of the development of aortic stenosis in patients with “benign “aortic valve thickening, Arch Intern Med 162:2345–2347, 2002.
86 Carabello BA, Paulus WJ: Aortic stenosis, Lancet 373:956–966, 2009.
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%.1It is
the characteristic systolic murmur that draws in the general
atten-tion and guides a diagnostic workup Doppler echocardiography is
the ideal tool to confirm the diagnosis and to quantify AS by
cal-culating 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
pres-sure load, patients remain asymptomatic, and acute complications
are rare However, as soon as symptoms, such as exertional
dys-pnea, 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.2In this situation, aortic valve
replacement (AVR) results in dramatic improvement, not only in
symptoms, but also in long-term survival.2Thus, there is general
agreement that surgery should be strongly recommended in
symp-tomatic patients.3,4In 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 atic patients with severe AS
asymptom-ARGUMENTS FOR SURGERY IN ASYMPTOMATIC AORTIC STENOSIS
Risk of Sudden Cardiac DeathSudden death is the major concern when asymptomatic patientswith severe AS are followed conservatively However, this riskappears to be low In addition, several studies that evaluatedpatients with nonsevere AS did not report sudden deaths Some pro-spective studies also reported on the outcomes of sizeable cohorts
of patients with severe AS (peak aortic jet velocity4.0 m/sec).Pellikka et al5observed 2 sudden deaths among 113 patients during
a mean follow-up of 20 months Both patients, however, developedsymptoms at least 3 months before death In another study, 1 case ofsudden death, which was not preceded by symptoms, was reportedamong 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 5.44.0 years, Pellikka et al7
reported the rate of sudden death
to be 1% a year However, in almost half of the patients who diedsuddenly, information on the patient’s status was missing for the
411
Asymptomatic Aortic Stenosis
96
Trang 24year preceding the event In a recent prospective study by Rosenhek
et al, in patients with extremely severe (peak jet velocity5.0 m/
sec) but asymptomatic AS who were followed for a median of
41 months, only one case of sudden death was reported.8
Impor-tantly, 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
exam-ple, in a Scandinavian study,107 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
outcomes and had no survival advantage with AVR, which suggeststhat they had additional unrecognized cardiac disease and that the
LV dysfunction was not caused by AS
Nevertheless, there is concern that myocardial fibrosis andsevere LV hypertrophy, which may not be reversible after delayedsurgery, could adversely affect postoperative long-term outcomes
In symptomatic patients, myocardial fibrosis, as detected by netic resonance delayed gadolinium enhancement, has beenreported to be irreversible and to predict adverse postoperative out-comes with regard to improvement of symptoms, LV function, andsurvival.12,13 However, no data are available for asymptomaticpatients with regard to whether irreversible fibrosis, which may
mag-be associated with worse outcomes, is already present during theasymptomatic phase of the disease Excessive LV hypertrophyhas been shown to be primarily associated with earlier symptomdevelopment.14However, it remains unknown whether a certaincutoff for the extent of hypertrophy is associated with a worse out-come when surgery is delayed until symptoms develop
Surgical ConsiderationsPatients with severe symptoms have been found to have a signifi-cantly higher operative mortality than those with no or mild symp-toms (i.e., 2% for New York Heart Association [NYHA] functionalclasses I or II compared with 3.7% and 7.0% for NYHA functionalclasses III and IV).15 In addition, urgent or emergency valvereplacement carries a significantly higher risk than elective sur-gery.15Nevertheless, individual operative risk must always be care-fully weighed against the potential benefit and may be significantlyhigher in elderly patients, particularly when comorbidities arepresent A review of Medicare data16involving more than 142,000patients indicated that the average in-hospital mortality for post-AVR in patients older than age 65 years is 8.8% (and as high as13% in low-volume surgical centers) In addition, prostheticvalve–related long-term morbidity and mortality must also be takeninto account Thromboembolism, bleeding, endocarditis, valvethrombosis, paravalvular regurgitation, and valve failure occur at
a rate of at least 2% to 3% per year, and death directly related tothe prosthesis has been reported at a rate of up to 1% per year.3Duration of the Asymptomatic Phase
Studies have reported a very rapid progression and early symptomdevelopment in asymptomatic severe AS, with up to 80% of thepatients requiring AVR within 2 years.17Such observations havealso raised the question whether it is worthwhile to delay surgery
in asymptomatic patients with severe AS However, other gators have reported better outcomes, with individual outcomesvarying widely For example, survival free of death or valvereplacement indicated by the development of symptoms was
investi-565% at 2 years in one series of asymptomatic severe AS.6
Thesediscrepant results may be explained by the fact that, in some stud-ies, patients underwent surgery without having developed symp-toms, whereas these interventions were counted as events Thus,the event-free survival reported in the literature has to be inter-preted with caution
Studies Reporting Better Outcome with Early Surgery in Asymptomatic Severe Aortic StenosisTwo studies reported better outcomes in asymptomatic severe ASwhen surgery was performed before symptom onset, which advo-cated early AVR.18 , 19 However, these retrospective studies hadmajor limitations.20 In particular, both studies had poor follow-
up quality and included patients who developed symptoms, butwho did not undergo surgery in the “conservatively treated” groups.Data presented by Brown et al18support the notion of waiting for
Vpeak 4.6 m/sec
p mean 54 mm Hg
Vpeak 5.3 m/sec
p mean 75 mm Hg
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).
Trang 25symptoms, 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
dif-fer 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
like-lihood 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).3The European
guide-lines 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
develop-ment, which indicates the need for surgery No studies have
dem-onstrated 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)
ECHOCARDIOGRAPHY AT RESTPeak aortic jet velocity,6–8,17valve calcification,6LVEF,7rate ofhemodynamic progression,6 LV hypertrophy,14 and myocardialdeformation parameters of systolic and diastolic LV function21have been reported to be predictors of outcome The followingstudies have reached clinical impact for the recommendations ofsurgery
Rosenhek et al reported the outcome of 116 asymptomaticpatients with very severe AS, which was defined by a peak aorticjet velocity of 5.0 m/sec or more.8During 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 morehad a particularly poor outcome, with only 25% surviving 2 yearswithout developing symptoms and requiring surgery The study con-firmed previous publications that reported peak aortic jet velocity to
be a strong independent predictor of event-free survival There wasonly 1 sudden death observed among these 116 patients, despite theirhaving very severe AS The other five deaths were due to myocardialinfarction in one patient and congestive heart failure in four patients
Of these four elderly patients, three died of multiorgan failureassociated with sepsis Thus, the study confirmed that watchfulwaiting is safe in asymptomatic patients The fact that symptom-freesurvival is, on average, short in patients with velocities of 5.5 m/sec
or more may, however, justify considering elective AVR as long assurgical risk is low
Aortic valve calcification has become a powerful independentpredictor of outcome.6Event-free (death or symptoms requiringsurgery) survival at 4 years was 759% in patients with no or onlymild calcification versus 205% in those with moderately or
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.
TABLE 96.1 Recommendations for Isolated Aortic Valve Replacement
in Asymptomatic Aortic Stenosis (no indication for bypass surgery, other valve surgery or aortic surgery)
I Pts with reduced syst LV
function (LVEF <0.50) Pts with red syst LVfunction (LVEF <0.50)
Pts who develop symptoms during exercise testing
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 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 cm 2 , mean gradient >60 mm Hg, peak velocity>5 m/sec) and expected operative mortality 1%
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 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.
413
Asymptomatic Aortic Stenosis
96
Trang 26severely calcified valves (Fig 96.2) The worse outcome of patients
with more severe calcification appeared to be paralleled by a more
rapid hemodynamic progression However, even in the presence of
calcification, the rate of hemodynamic progression varies
widely.2,6The hemodynamic progression, as determined by serial
echocardiographic examinations, appears to yield important
prog-nostic information beyond the degree of calcification The
combi-nation of a markedly calcified valve with a rapid increase in the
velocity of 0.3 m/sec or more from one visit to the next visit within
1 year identified a high-risk group Approximately 80% of these
patients required surgery or died within 2 years.6Thus,
consider-ation of elective surgery also appears to be justified in this
subgroup
Cioffi et al14evaluated the prognostic impact of an
inappropri-ately high LV mass in 218 patients with asymptomatic AS This LV
mass exceeded 10% of the expected value predicted by height, sex,
and stroke work The authors reported this finding to be an
indepen-dent predictor of the composite endpoint, which included death
from any cause, valve replacement, and hospital admission for
non-fatal myocardial infarction and/or congestive heart failure, when
considering diabetes, peak transvalvular velocity, and the extent
of valve calcification
EXERCISE TESTING
An abnormal response to exercise was found to be an important
pre-dictor of outcomes in asymptomatic AS Amato et al22studied
exer-cise testing in 66 asymptomatic patients with an aortic valve area of
less than 1.0 cm2and followed these patients for 1512 months
Criteria for a positive test was the occurrence of symptoms, new
ST-segment depression, a systolic blood pressure increase of less
than 20 mm Hg, or complex ventricular arrhythmias At 24 months,
event-free survival with events, defined as development of
symp-toms in daily life or death, was 85% in 22 patients with negative
tests, but only 19% in patients with a positive test Although these
results seem impressive, they leave many questions unanswered
The majority of patients with a positive test fulfilled the criterion
of symptom development In particular, three of the patients who
died had symptoms during the test Although the study concluded
that patients with a negative exercise test appeared to have good
out-comes and might not have required surgery, those limited by typical
symptoms should undergo valve replacement The positive tive value of an abnormal blood pressure response and/or ST-segment depression without associated symptoms remained unclear.Das et al23were able to clarify some of these questions In 125patients with asymptomatic AS (effective valve area 0.90.2 cm2
predic-),they assessed the accuracy of exercise testing in predicting symp-tom onset within 12 months Similar to previous reports, approxi-mately one third of the patients were found to develop symptoms onexercise Abnormal blood pressure response, which was morestrictly defined as no increase in systolic blood pressure at peakexercise compared with baseline, was found in 23% of the patients,and an ST-segment depression of more than 2 mm was seen in 26%
of patients There were no deaths during follow-up, but 29% ofthese patients developed spontaneous symptoms Absence of lim-iting symptoms had a high negative predictive accuracy of 87%.However, an abnormal blood pressure response or ST-segmentdepression did not provide a statistically significant benefit abovethe limiting symptoms with respect to predictive accuracy In theabsence of limiting symptoms, only two patients with an abnormalblood pressure response, two patients with ST depression, and onepatient with both developed symptoms during follow-up The neg-ative predictive values were 78% and 77%, and the positive predic-tive values were 48% and 45%, respectively These findings suggestthat an abnormal blood pressure response and ST depression arerather nonspecific findings and do not help in identifying asymptom-atic patients who may benefit from elective valve replacement Evenlimiting symptoms on exercise testing had a positive predictiveaccuracy of only 57% in the study when all patients and all symptomswere included When considering only physically active patientswho are younger than 70 years of age, positive predictive accuracyrose to 79% Apparently, it also matters which symptoms occur onexercise testing; in the entire study group, 83% of patients with diz-ziness developed spontaneous symptoms compared with only 50%
of patients with chest tightness and 54% of patients with ness The most likely explanation for these findings is that breath-lessness on exercise may be difficult to interpret in patients withlow physical activity and especially in older patients (older than
70 years) In this group, it was difficult to decide whether ness with exercise was a symptom of AS
breathless-Thus, exercise testing is primarily helpful in physically activepatients younger than 70 years A normal exercise test indicates
Figure 96.2 Short-axis views obtained in patients with severe aortic stenosis and various degrees of valve calcification Upper left, no calcification; upper right , mild calcification; lower left, moderate calcification; and lower right, severe calcification.
Trang 27a very low likelihood of symptom development within
12 months, and watchful waiting is safe In contrast, clear
symp-tom development on exercise testing in physically active patients
younger than 70 years indicates a very high likelihood of
symp-tom development within 12 months, and valve replacement
should be recommended However, an abnormal blood pressure
response and/or ST-segment depression without symptoms on
exercise have a low positive predictive value and may not justify
elective surgery
INCREMENTAL VALUE OF EXERCISE
HEMODYNAMICS ASSESSED BY DOPPLER
ECHOCARDIOGRAPHY
Lancellotti et al24 found the change in the mean gradient with
exercise to be an independent predictor of event-free survival in
asymptomatic AS Patients with an increase in the mean gradient
of 18 mm Hg or more had markedly worse outcomes than those
with a mean gradient of less than 18 mm Hg Marechaux et al25
confirmed the prognostic value of the exercise-induced increase
in the transvalvular gradient Of 186 asymptomatic patients with
at least moderate AS and a normal LVEF, 135 had a normal
exer-cise test In these patients, an exerexer-cise-induced gradient increase of
more than 20 mm Hg was independently associated with events
(hazard ratio¼3.83), which suggested an additional prognostic
value beyond regular exercise testing
BIOMARKERS
Plasma levels of BNPs have been shown to predict symptom-free
survival in AS.26Patients with BNP levels less than 130 pg/mL or
N-terminal pro-BNP levels less than 80 pmol/L were reported to
be unlikely to develop symptoms within 9 months (they had
symptom-free survival close to 90%), whereas those with higher
levels frequently required surgery within this time period (they
had symptom-free survival of<50%).26
Recent studies confirmedthe prognostic value of BNP measurements in asymptomatic
AS.21,27,28Lancellotti et al21studied the outcome of 126 patients
with asymptomatic AS and reported a BNP level of more than
61 pg/mL as the best cutoff value to predict events Rajani et al27
found that a BNP level of more than 58 pg/mL in 65 patients had
a sensitivity of 86% and specificity of 64% for the development
of symptoms on exercise Monin et al28 prospectively followed
107 patients and reported that the variables that were independently
associated with the development of symptoms or death within
24 months were female sex, peak aortic jet velocity, and BNP
Event-free survival after 20 months was 80% for patients within the
first score quartile compared with only 7% for the fourth quartile
In summary, low and/or normal neurohormones appear to be of
particular value in the management of asymptomatic AS, because
these patients can be safely followed without surgery Elevated
neurohormones indicate that closer evaluation and shorter
follow-up intervals are required Markedly elevated BNP and/or
pro-BNP without other explanation may justify consideration of
early surgery in patients with low operative risk, although cutoff
values need to be better defined
SUMMARY
The current recommendations of the American College of
Cardiol-ogy and the American Heart Association, and those of the European
Society of Cardiology, which slightly differ, are summarized in
Table 96.1 However, it is obvious that echocardiography plays
an important role in management decision-making by providing
information on transvalvular velocities and/or gradients, systolic
LV function, hemodynamic progression, extent of valve tion, and LV hypertrophy
calcifica-REFERENCES
1 Stewart BF, Siscovick D, Lind BK, et al.: Clinical factors associated with calcific aortic valve disease Cardiovascular health study, J Am Coll Cardiol 29:630–634, 1997.
2 Rosenhek R, Maurer G, Baumgartner H: Should early elective surgery be formed in patients with severe but asymptomatic aortic stenosis, Eur Heart J 23:1417–1421, 2002.
per-3 Bonow RO, Carabello BA, Chatterjee K, et al.: 2008 focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart, J Am Coll Cardiol 52:e1–e142, 2008.
4 Vahanian A, Alfieri O, Andreotti F, et al.: Guidelines on the management of vular heart disease (version 2012), Eur Heart J 33:2451–2496, 2012.
val-5 Pellikka PA, Nishimura RA, Bailey KR, Tajik AJ: The natural history of adults with asymptomatic, hemodynamically significant aortic stenosis, J Am Coll Car- diol 15(5):1012–1017, 1990.
6 Rosenhek R, Binder T, Porenta G, et al.: Predictors of outcome in severe, tomatic aortic stenosis, N Engl J Med 343(9):611–617, 2000.
asymp-7 Pelikka PA, Sarano ME, Mishimura RA, et al.: Outcome of 622 adults with asymptomatic, hemodynamically significant aortic stenosis during prolonged follow-up, Circulation 111:3290–3295, 2005.
8 Rosenhek R, Zilberszac R, Schemper M, et al.: Natural history of very severe tic stenosis, Circulation 121:151–156, 2010.
aor-9 Keane JF, Discroll DJ, Gersony WM, et al.: Second natural history study of genital heart defects Results of treatment of patients with aortic valve stenosis, Circulation 87(Suppl):116–127, 1993.
con-10 Lund O, Nielsen TT, Emmertsen K, et al.: Mortality and worsening of prognostic profile during waiting time for valve replacement in aortic stenosis, Thorac Car- diovasc Surg 44:289–295, 1996.
11 Henkel DM, Malouf JF, Connolly HM, et al.: Asymptomatic left ventricular tolic dysfunction in patients with severe aortic stenosis: characteristics and out- comes, J Am Coll Cardiol 60:2325–2329, 2012.
sys-12 Weidemann F, Herrmann S, St €ork S, et al.: Impact of myocardial fibrosis in patients with symptomatic severe aortic stenosis, Circulation 120:577–584, 2009.
13 Azevedo CF, Nigri M, Higuchi ML, et al.: Prognostic significance of myocardial fibrosis quantification by histopathology and magnetic resonance imaging in patients with severe aortic valve disease, J Am Coll Cardiol 56:278–287, 2010.
14 Cioffi G, Faggiano P, Vizzardi E, et al.: Prognostic value of inappropriately high left ventricular mass in asymptomatic severe aortic stenosis, Heart 97:301–307, 2011.
15 National STS, Database STSUS, Database Cardiac Surgery: Aortic Valve Replacement Patients: Preoperative Risk Variables, Chicago, 1997, Society of Thoracic Surgeons, 2000.
16 Goodney PP, O’Connor GT, Wennberg DE, et al.: Do hospitals with low mortality rates in coronary artery bypass also perform well in valve replacement? Ann Thorac Surg 76:1131–1136, 2003.
17 Otto CM, Burwash IG, Legget ME, et al.: Prospective study of asymptomatic vular aortic stenosis Clinical, echocardiographic, and exercise predictors of out- come, Circulation 95(9):2262–2270, 1997.
val-18 Brown ML, Pellikka PA, Schaff HV, et al.: The benefits of early valve ment in asymptomatic patients with severe aortic stenosis, J Thorac Cardiovasc Surg 135:308–315, 2008.
replace-19 Kang DH, Park SJ, Rim JH, et al.: Early surgery versus conventional treatment in asymptomatic very severe aortic stenosis, Circulation 121:1502–1509, 2010.
20 Kaleschke G, Baumgartner H: Asymptomatic aortic stenosis: when to operate? Curr Cardiol Rep 13(3):220–225, 2011.
21 Lancellotti P, Moonen M, Magne J, et al.: Prognostic effect of long-axis left tricular dysfunction and B-type natriuretic peptide levels in asymptomatic aortic stenosis, Am J Cardiol 105:383–388, 2010.
ven-22 Amato MC, Moffa PJ, Werner KE, Ramires JA: Treatment decision in asymptomatic aortic valve stenosis: role of exercise testing, Heart 86:381–386, 2001.
23 Das P, Rimington H, McGrane H, Chambers J: Exercise testing to stratify risk n aortic stenosis, Eur Heart J 26:1309–1313, 2005.
24 Lancellotti P, Lebois F, Simon M, et al.: Prognostic importance of quantitative exercise Doppler echocardiography in asymptomatic valvular aortic stenosis, Circulation 112(Suppl):1377–1382, 2005.
25 Mare´chaux S, Hachicha Z, Bellouin A, et al.: Usefulness of exercise-stress echocardiography for risk stratification of true asymptomatic patients with aortic valve stenosis, Eur Heart J 11:1390–1397, 2010.
26 Bergler-Klein J, Klaar U, Herger M, et al.: Natriuretic peptides predict free survival and postoperative outcome in severe aortic stenosis, Circulation 109:2302–2308, 2004.
symptom-27 Rajani R, Rimington H, Chambers J: B-type natriuretic peptide and tissue Doppler for predicting symptoms on treadmill exercise in apparently asymptomatic aortic stenosis, J Heart Valve Dis 18:565–571, 2009.
28 Monin JL, Lancellotti P, Monchi M, et al.: Risk score for predicting outcome in
Circulation 120:69–75, 2009.
415
Asymptomatic Aortic Stenosis
96
Trang 2897 Risk Stratification —Timing of Surgery
Raphael Rosenhek, MD
Individualized risk assessment is fundamental in the decision-making
process involved in the management of patients with aortic stenosis
Risk assessment is involved at several levels Being aware of the
nat-ural history of aortic stenosis and performing a risk assessment
permits identification of high-risk subgroups of patients who are
likely to become symptomatic in the near future Assessing the risk
of a valve intervention is essential when deciding about early elective
surgery, but also identifies the type of procedure that is best suited for
the patient Finally, being aware of the expected postoperative and/or
postinterventional outcome completes the decision-making process
RISK STRATIFICATION IN ASYMPTOMATIC
AORTIC STENOSIS
A watchful, waiting approach is generally safe for the management
of asymptomatic patients with severe aortic stenosis.1However, the
identification of high-risk patients who would benefit from early
elective surgery is of clinical importance, because the risk of
surgery is higher in the presence of more advanced symptoms
and because patients do not always promptly report the onset of
symptoms.2If waiting lists for surgery are present, a mortality rate
of approximately 15% per year can be anticipated.3Taking into
consideration the risks of surgery and of prosthetic valve
complica-tions, elective surgery may be considered in high-risk subgroups
Exercise testing has become a valuable tool in unmasking latent
symptoms in up to one third of the patients with apparently
asymp-tomatic severe aortic stenosis.4 , 5The presence of symptoms during
exercise testing is a clear indication for surgery A decrease in
blood pressure during exercise is also associated with a high
likelihood of future events
Echocardiography is a valuable tool for risk stratification The
semi-quantitative assessment of aortic valve calcification, which
can be easily performed in a parasternal short-axis view at the aortic
valve level, identifies patients at high risk for the onset of
symp-toms.1The presence of a calcified aortic valve in combination with
a rapid hemodynamic progression (defined as an increase of peak
aortic velocity of>0.3 m/sec per year) identifies a high-risk
sub-group with an 80% likelihood of events occurring within 2 years
Assessing the hemodynamic progression by echocardiography
requires a meticulous search for the peak transaortic gradient and
the recording of the velocity from the same imaging window, which
should be documented in the written report
Aortic jet velocity, which reflects aortic stenosis severity, is
directly related to event-free survival from mild to moderate to
severe aortic stenosis.6 It is of incremental prognostic value in
patients with peak aortic velocities greater than 5.0 or 5.5 m/sec
Elective surgery should be considered in patients with extremely
severe aortic stenosis (class IIa indication) according to American
College of Cardiology/American Heart Association7 and to
European Society of Cardiology/European Association for
Car-dio-Thoracic Surgery (EACTS)8guidelines (Table 97.1)
Additional prognostic parameters that can be assessed with
echocardiography include (1) the presence of excessive left
ven-tricular hypertrophy and (2) an increase in the mean transaortic
gradient by more than 18 to 20 mm Hg with exercise
echocardiog-raphy.9,10All echocardiographic parameters of aortic stenosis may
be complemented by the measurement of brain natriuretic peptide
(BNP) A low BNP value is generally associated with a good
short-term prognosis.11 A risk score integrating the prognostic
information of aortic velocity and BNP has been proposed.12
Recently, it has been suggested that flow rate may also provideadditional prognostic information.13
IMPORTANCE OF THE PREDICTED POSTINTERVENTIONAL SURVIVAL
ON DECISION-MAKINGThe prediction of postinterventional survival is of particularimportance in high-risk groups, such as those with low-flow, low-gradient aortic stenosis In this setting, low-dose dobutamine echo-cardiography provides important prognostic insights It assesses ifthe left ventricle responds to dobutamine, and hence, determinesthe presence of contractile reserve (or flow reserve) In the presence
of a positive contractile reserve, a distinction between true severe nosis (characterized by an increase in the aortic velocity and a smallvalve area) and pseudosevere stenosis (characterized by an increase
ste-in the aortic valve area with ste-increased flow rates) is possible In theabsence of contractile reserve, severe aortic valve calcification mayindicate the presence of severe aortic stenosis.14 Patients whoundergo aortic valve surgery in the presence of true severe low flowand low-gradient aortic stenosis have a significantly improved sur-vival compared with those treated medically.15Patients without con-tractile reserve have a high surgical risk, but they benefit in terms ofimproved survival compared with patients treated medically16and interms of an improvement in left ventricular function.17
In the setting of paradoxical low-flow, low-gradient aorticstenosis, which is characterized by a small valve area and a lowtransvalvular gradient in the presence of a preserved ejection frac-tion and a low-stroke volume (indexed stroke volume<35 mL/m2
),
TABLE 97.1 Indications for Surgery in Aortic Stenosis
Variables
ESC/EACTS 2012
ACC/AHA 2014 Symptoms
Symptoms during exercise testing Asymptomatic and LVEF <50%
Asymptomatic, undergoing other cardiac surgery
I I I I
I I I I Asymptomatic with very severe AS (ESC
5.5 m/sec, ACC 5.0 m/sec) Asymptomatic with blood pressure drop during exercise testing
Asymptomatic with calcified valve +rapid progression (0.3 m/sec per yr)
IIa IIa IIa
IIa IIa IIb
Markedly elevated BNP values without other explanation
Increase of mean gradient with exercise
20 mm Hg Excessive LV hypertrophy in the absence of hypertension
IIb IIb IIb
ACC , American College of Cardiology; AHA, American Heart Association;
AS , aortic stenosis; BNP, brain natriuretic peptide; EACTS, European Association for Cardio-Thoracic Surgery; ESC, European Society of Cardiology; LV, left ventricular; LVEF, left ventricular ejection fraction (Data from Nishimura RA, et al 2014 AHA/ACC Guideline for the management of patients with valvular heart disease J Am Coll Cardiol
2014, and Vahanian A, et al Guidelines on the management of valvular heart disease Eur Heart J 33:2451-2496, 2012.)
416
Trang 29improved survival has been described after aortic valve
replace-ment.18 Currently, surgery may be considered in symptomatic
patients with paradoxical low-flow, low-gradient aortic stenosis
after a careful individualized risk assessment
Transcatheter aortic valve implantation (TAVI) has become an
accepted therapy for inoperable and for high-risk surgical patients
in whom a cardiology team favors this approach.19The Placement
of AoRtic TraNscathetER Valves (PARTNER) trials have
con-firmed a clear survival benefit for TAVI compared with
conserva-tive management in inoperable patients and a comparable survival
between TAVI and surgery in high-risk patients.20 At the same
time, registry data show that the mortality in these high-risk
patients may still be very high, even after a valve procedure, and
that approximately half of the mortality is due to noncardiac
causes.21,22This highlights the importance of the concept of
futil-ity In addition, more severe symptoms are associated with a higher
mortality in these high-risk patients.22
ASSESSING THE RISK OF AN INTERVENTION
Assessing the surgical or interventional risk is an integral part of the
workup of patients with aortic stenosis Early elective surgery in
asymptomatic patients should be an obvious option in patients with
a low surgical risk, but this is less so in patients with many
comor-bidities Several risk scores have been proposed to assess the risk of
heart surgery Although these scores have good discriminatory
values to distinguish between low- and high-risk patients, their
cal-ibration is less precise and do not permit an exact prediction of the
surgical risk, particularly in the high-risk patients.23Specific
con-ditions that may have an important weight in the decision-making,
such as frailty or the presence of a porcelain aorta, are not
accounted for in these scores More recently, risk scores have been
proposed for TAVI procedures
The advances in the therapeutic options for aortic stenosis,
together with the increasing complexity of the patients, emphasize
the role of the cardiology team for an integrated individualized
decision-making process.23After the consideration of the expected
natural history of the disease, of the expected risk of the
interven-tion, and the long-term postprocedural outcome, an individualized
risk assessment will enable the physicians to define the optimal
tim-ing and choice of a procedure under consideration of the patient’s
preferences and life expectancy
REFERENCES
1 Rosenhek R, Binder T, Porenta G, et al.: Predictors of outcome in severe,
asymp-tomatic aortic stenosis, N Engl J Med 343:611–617, 2000.
2 Rosenhek R, Maurer G, Baumgartner H: Should early elective surgery be
performed in patients with severe but asymptomatic aortic stenosis? Eur Heart
J 23:1417–1421, 2002.
3 Lund O, Nielsen TT, Emmertsen K, et al.: Mortality and worsening of prognostic profile during waiting time for valve replacement in aortic stenosis, Thorac Car- diovasc Surg 44:289–295, 1996.
4 Amato MC, Moffa PJ, Werner KE, Ramires JA: Treatment decision in atic aortic valve stenosis: role of exercise testing, Heart 86:381–386, 2001.
asymptom-5 Das P, Rimington H, Chambers J: Exercise testing to stratify risk in aortic stenosis, Eur Heart J 26:1309–1313, 2005.
6 Rosenhek R, Zilberszac R, Schemper M, et al.: Natural history of very severe tic stenosis, Circulation 121:151–156, 2010.
aor-7 Nishimura RA, Otto CM, Bonow RO, et al.: AHA/ACC Guideline for the agement of patients with valvular heart disease, J Am Coll Cardiol 63 (22):2438–2488, 2014.
man-8 Vahanian A, Alfieri O, Andreotti F, et al.: Guidelines on the management of valvular heart disease, Eur Heart J 33:2451–2496, 2012.
9 Lancellotti P, Lebois F, Simon M, et al.: Prognostic importance of quantitative exercise Doppler echocardiography in asymptomatic valvular aortic stenosis,Cir- culation 112:I377–I382, 2005.
10 Marechaux S, Hachicha Z, Bellouin A, et al.: Usefulness of exercise-stress cardiography for risk stratification of true asymptomatic patients with aortic valve stenosis, Eur Heart J 31:1390–1397, 2010.
echo-11 Bergler-Klein J, Klaar U, Heger M, et al.: Natriuretic peptides predict free survival and postoperative outcome in severe aortic stenosis, Circulation 109:2302–2308, 2004.
symptom-12 Monin JL, Lancellotti P, Monchi M, et al.: Risk score for predicting outcome in patients with asymptomatic aortic stenosis, Circulation 120:69–75, 2009.
13 Lancellotti P, Magne J, Donal E, et al.: Clinical outcome in asymptomatic severe aortic stenosis: insights from the new proposed aortic stenosis grading classifica- tion, J Am Coll Cardiol 59:235–243, 2012.
14 Cueff C, Serfaty JM, Cimadevilla C, et al.: Measurement of aortic valve cation using multislice computed tomography: correlation with haemodynamic severity of aortic stenosis and clinical implication for patients with low ejection fraction, Heart 97:721–726, 2011.
calcifi-15 Monin JL, Quere JP, Monchi M, et al.: Low-gradient aortic stenosis: operative risk stratification and predictors for long-term outcome: a multicenter study using dobutamine stress hemodynamics, Circulation 108:319–324, 2003.
16 Tribouilloy C, Levy F, Rusinaru D, et al.: Outcome after aortic valve replacement for low-flow/low-gradient aortic stenosis without contractile reserve on dobuta- mine stress echocardiography, J Am Coll Cardiol 53:1865–1873, 2009.
17 Quere JP, Monin JL, Levy F, et al.: Influence of preoperative left ventricular contractile reserve on postoperative ejection fraction in low-gradient aortic steno- sis, Circulation 113:1738–1744, 2006.
18 Hachicha Z, Dumesnil JG, Bogaty P, Pibarot P: Paradoxical low-flow, low-gradient severe aortic stenosis despite preserved ejection fraction is associ- ated with higher afterload and reduced survival, Circulation 115:2856–2864, 2007.
19 Kodali SK, Williams MR, Smith CR, et al.: Two-year outcomes after transcatheter
or surgical aortic-valve replacement, N Engl J Med 366:1686–1695, 2012.
20 Makkar RR, Fontana GP, Jilaihawi H, et al.: Transcatheter aortic-valve replacement for inoperable severe aortic stenosis, N Engl J Med 366: 1696–1704, 2012.
21 Thomas M, Schymik G, Walther T, et al.: One-year outcomes of cohort 1 in the Edwards SAPIEN Aortic Bioprosthesis European Outcome (SOURCE) registry, Circulation 124:425–433, 2011.
22 Gilard M, Eltchaninoff H, Iung B, et al.: Registry of transcatheter aortic-valve implantation in high-risk patients, N Engl J Med 366:1705–1715, 2012.
23 Rosenhek R, Iung B, Tornos P, et al.: Assessing the risk of interventions in patients with valvular heart disease, Eur Heart J 33:822–828, 2012.
Reduced Left Ventricular Ejection Fraction
Abdellaziz Dahou, MD, MSc, Philippe Pibarot, DVM, PhD, Jean G Dumesnil, MD
Low-flow, low-gradient (LF-LG) aortic stenosis (AS) with a low
left ventricular ejection fraction (LVEF) occurs in approximately
5% to 10% of patients with AS.1,2 These patients represent one
of the most challenging subsets of patients in terms of diagnosis
and treatment LF-LG AS with a low LVEF is generally
character-ized by the combination of an aortic valve area (AVA) compatible
with severe AS (i.e.,1.0 cm2
and/or0.6 cm2
/m2), a low meantransvalvular gradient (i.e.,<40 mm Hg), and a low LVEF (i.e.,
<50 %), with a LF state (i.e., stroke volume index <35 mL/m2and/or cardiac index<3.0 L/min/m2
).3–6The LV systolic tion and ensuing LF state could be the result of an afterload mis-match7caused by the AS itself or could be the consequence of a
dysfunc-417
Low-Flow, Low-Gradient Aortic Stenosis with Reduced Left Ventricular Ejection Fraction
98
Trang 30primary myocardial disease with a coexisting AS The main
diag-nostic challenge in LF-LG AS with a low LVEF is to distinguish
true severe AS from pseudosevere AS (incomplete opening of
the valve due to the LF state) The distinction between these two
enti-ties is crucial for therapeutic decision-making Patients with true
severe AS generally benefit from aortic valve replacement
(AVR), whereas those with pseudosevere AS may not Prognosis
is usually poor (3-year survival rates of<50%) in patients with a
LF-LG that is treated medically, and operative mortality remains
high (range 6%-33%), depending on the presence or the absence
of LV flow reserve and other comorbidities.1,3,8–17Precise
assess-ment of both the severity of aortic valve stenosis and the degree
of myocardial impairment is crucial for optimal risk stratification
and therapeutic management in patients with LF-LG AS and a
reduced LVEF
USEFULNESS OF DOBUTAMINE STRESS
ECHOCARDIOGRAPHY FOR ASSESSING LEFT
VENTRICULAR FLOW RESERVE AND STENOSIS
SEVERITY
Since its first description by de Filippi et al,18low-dose (5-20μg/kg/
min) dobutamine stress echocardiography (DSE) has been shown to
be useful in assessing the presence of LV flow reserve and
distin-guishing true severe AS from pseudosevere AS (Fig 98.1).19,20
For this purpose, it is recommended that longer DSE stages
(5-8 min) be used, with acquisition of images once the heart rate and
hemodynamics have reached a steady state.21,22
ASSESSING LEFT VENTRICULAR FLOW RESERVE
LV flow reserve is defined as a 20% or more increase in stroke ume during DSE; this parameter has been shown to be useful foroperative risk stratification in patients undergoing surgical AVR(seeFig 98.1).3,13Flow reserve has formerly been referred as tocontractile reserve, but recent guidelines20
vol-proposed a change tothis terminology because several mechanisms (besides intrinsiccontractility) may contribute to the lack of stroke volume increaseduring DSE, including (1) afterload mismatch due to an imbalancebetween the severity of the stenosis and myocardial reserve7; (2) aninadequate increase of myocardial blood flow due to associatedcoronary artery disease; and/or (3) irreversible myocardial damagedue to previous myocardial infarction or extensive myocardialfibrosis
Patients with no LV flow reserve (e.g., Case #1,Fig 98.2,A andVideo 98.2,A, B) represent approximately one third of patients with alow LVEF and LF-LG AS These patients have much higher operativemortality (22%-33%) compared with those with flow reserve (5%-8%).3,18,22–24In patients with no LV flow reserve who survive oper-ation, the postoperative improvement in LVEF and symptoms, as well
as the late survival rate, are as good as those in patients with flowreserve13and much better than those in patients with no flow reservewho are treated medically.17Hence, assessment of LV flow reserve byDSE is useful in estimating operative risk, but does not predict recov-ery of LV function, improvement in symptomatic status, and latesurvival after operation.3,9,13,14,23The absence of LV flow reserveshould thus not preclude consideration of AVR in patients withLF-LG AS, but it is a marker for increased operative risk.3,17
As mentioned previously, the percent increase in stroke volumeduring DSE (i.e., the LV flow reserve) is not specific to myocardial
LVEF<50%
AVA≤1.0 (≤0.6 cm2/m2)ΔP<40 mm Hg
±CABG
CHF therapyTAVR?
SAVR (High op risk)?
Pseudo-severe ASNo
Figure 98.1 Algorithm for the nostic and therapeutic management
diag-of patients with low-flow, low-gradient aortic stenosis (AS) with a depressed left ventricular ejection fraction (LVEF) AoV , aortic valve; AVA, aortic valve area; CABG, coronary artery bypass graft; CHF, chronic heart failure; LV, left ventricular; MDCT, multidetector computed tomography; ΔP, mean transvalvular gradient; Projected AVA, projected aortic valve area at normal flow rate (250 mL/sec); SAVR, surgical aortic valve replacement; SV, stroke volume; TAVR, transcatheter aortic valve replacement.
Trang 31contractile reserve and may be influenced by several other factors.
Recent studies25have suggested that a more precise assessment of
LV contractile reserve can be achieved by measuring the changes in
the global longitudinal myocardial strain and strain rate by speckle
tracking imaging during DSE Further studies in a larger number of
patients are needed to determine the incremental prognostic value
of LV contractile reserve assessed using longitudinal strain
param-eters in patients with a low LVEF and LF-LG AS
ASSESSING STENOSIS SEVERITY
In patients with LF-LG AS, the AVA measured at rest is small
(<1.0 cm2
), which suggests severe AS; however, the transvalvular
gradient is also low (<40 mm Hg), which suggests nonsevere AS
However, in LF conditions, the AVA may overestimate and the dient may underestimate the true stenosis severity DSE is helpful
gra-in this context because it reconciles the AVA–gradient discordance,and therefore, corroborates stenosis severity The distinctionbetween true versus pseudosevere stenosis is essentially based onthe changes in the AVA and the gradients that occur with increasingflow rate during DSE (seeFig 98.1) Typically, pseudosevere ASshows a marked increase in the AVA and little or no increase in thegradients in response to increasing flow (e.g., Case #2,Fig 98.3and Video 98.3,A, B), whereas true severe AS shows little or noincrease in the AVA and an increase in the gradients, which is con-gruent with the relative increase in flow (Case #3,Fig 98.4andVideo 98.4,A, B) Several parameters and criteria have been pro-posed in the literature to identify patients with pseudosevere AS
AVA = 0.8 cm 2
SV = 57 mL LVEF = 30%
SV = 34 mL LVEF = 20%
AVA = 0.85 cm 2
SV = 46 mL LVEF = 25-30%
AVA = 1.2 cm 2
Restingecho
Dobutaminestress echo
Figure 98.3 Illustrative case of patient with low-flow, low-gradient aortic stenosis and a reduced left ventricular ejection fraction (LVEF) Case #2:
a patient with pseudosevere stenosis and LV flow reserve on dobutamine stress echocardiography AVA, aortic valve area; LVEF, left ventricular ejection fraction; ΔP, mean transvalvular gradient; SV, stroke volume.
419
Low-Flow, Low-Gradient Aortic Stenosis with Reduced Left Ventricular Ejection Fraction
98
Trang 32during DSE, including a peak stress mean gradient of less than 30 or
less than 40 mm Hg depending on studies, a peak stress AVA of
more than 1.0 or 1.2 cm2, and/or an absolute increase in AVA of
0.3 cm or more.2,3,8,18,23,26 The prevalence of pseudosevere AS
is reported to be between 20% and 35%.18,21,23,27
Because all of the parameters of stenosis severity are
flow-dependent, and the increase in flow during DSE varies extensively
from one patient to another, interpreting the changes in the AVA
and the gradients without considering the relative changes in flow
may often be problematic To overcome this limitation, a new
parameter derived from the DSE, that is, the projected AVA at mal flow rate (AVAProj), has been proposed by the True Or Pseudo-Severe Aortic Stenosis (TOPAS) investigators (Fig 98.5) Thisnew parameter has been shown to be more closely related to actual
nor-AS severity, impairment of myocardial blood flow, and survivalthan the traditional DSE parameters.9,21,22,28 The calculation ofthe AVAProjis particularly helpful when the AVA–gradient dis-cordance, and thus, the uncertainty about actual stenosis severity,persist during DSE (seeFig 98.1) This situation most often occurswhen the flow remains below normal despite dobutamine stress
SV = 53 mL LVEF = 40%
AVA = 0.77 cm 2
SV = 73 mL LVEF = 50%
AVA = 0.75 cm 2
Restingecho
Figure 98.4 Illustrative case of patient with low-flow, low-gradient aortic stenosis and a reduced left ventricular ejection fraction (LVEF) Case #3:
a patient with true-severe stenosis and LV flow reserve AVA, aortic valve area; AV, aortic valve; LVEF, left ventricular ejection fraction; ΔP, mean transvalvular gradient; SV, stroke volume.
Trang 33(e.g., Patients #1 and 4 inFig 98.5,A), or more rarely, when flow
becomes supranormal with dobutamine (e.g., Patient #2 in
Fig 98.5,A) For example, in the case illustrated inFigure 98.5,
B, the flow increased significantly with dobutamine, but it was
not enough to reach the normal range The AVA was 0.70 cm2at
rest and increased up to 0.85 cm2(thus remaining severe) during
DSE, whereas the peak and/or mean gradients increased from
33/21 to 54/32 mm Hg (thus, they remained moderate) In this
patient, the calculation of the AVAProj(0.97 cm2) permitted
recon-ciliation of this stress AVA–gradient discordance, and therefore,
confirmed that the AS was truly severe The cutoff value of
AVA-Projthat has been initially proposed to identify true severe AS is less
than 1.0 cm,2,21which is consistent with the AVA threshold
pro-posed in the guidelines for severe stenosis in patients with a normal
LVEF However, outcome studies9,22,27suggest that less stringent
cutoff values (e.g., AVA or AVAProj 1.2 cm2
) would be moreappropriate for patients with a decreased LVEF This suggestion
is consistent with the concept that the increased load imposed by
moderate AS may be well tolerated by a normal ventricle, but
may be tolerated poorly by a failing ventricle
A substantial proportion of patients with no flow reserve (i.e.,
percent increase in stroke volume <20%) exhibit a significant
increase in the mean transvalvular flow rate (i.e., stroke volume/
LV ejection time) during DSE because of the acceleration in heart
rate and ensuing shortening of the ejection time.21,22This increase
in flow rate is often sufficient to induce conclusive changes in the
AVA and gradient and/or to calculate the AVAProj, which therefore
allows confirmation of stenosis severity Some investigators
rec-ommend halting dobutamine infusion when the heart rate increases
by 10 beats/min or more based on the rationale that little or no
fur-ther increase in stroke volume is expected beyond that point.29
However, significant increase in the mean transvalvular flow rate
may nonetheless occur at higher heart rates due to shortening of
the ejection time Hence, to enable a larger augmentation in the
transvalvular flow rate and thus increase the proportion of
diag-nostic DSE with respect to stenosis severity, other investigators
recommend a more liberal target heart rate (>100 beats/min or
220age) for terminating DSE.22
However, in approximately 10% to 20% of patients with LF-LG
AS, the increase in the mean flow rate induced by low-dose DSE is
not sufficient to induce significant changes in the AVA or gradient,
and to calculate AVAProj In such patients, the distinction between
true severe AS and pseudosevere AS is not feasible, and DSE
remains nondiagnostic (Case #1, seeFig 98.2,A and Video 98.2,
A, B) In these patients or in those with ambiguous results at DSE,
quantification of valve calcification by multidetector computed
tomography (MDCT) may also be helpful to distinguish true severe
AS from pseudosevere AS (seeFig 98.2,B) Cueff et al suggested
that a MDCT aortic valve calcium score of more than 1,650 AU
pro-vided the best accuracy to identify hemodynamically severe AS.30
However, recent studies suggested that lower cutoff values of aortic
valve calcium load should be used in women (1,200 AU) than in men
(2,000 AU) to identify severe AS (seeFig 98.1).31,32
THERAPEUTIC MANAGEMENT
The American College of Cardiology/American Heart Association
guidelines19support using AVR (class IIa; level of evidence C) if
the patient shows a mean gradient of 40 mm Hg or more and an
AVA of 1.0 cm2or less at any DSE stage, whereas the 2012
Euro-pean Society of Cardiology (ESC)/EuroEuro-pean Association for
Cardio-Thoracic Surgery (EACTS) guidelines20 support using
AVR (class IIa; level of evidence C) in the subset of patients with
LV flow reserve Thus, there appears to be a clear consensus that
patients with true severe AS and evidence of LV flow reserve
(e.g., Case #3, seeFig 98.4) should be considered for AVR and that
coronary artery bypass graft surgery should be performed
concom-itantly whenever necessary (seeFig 98.1)
Recent studies22,27suggest that survival is better in patients withpseudosevere AS who receive medical treatment than that inpatients with true severe AS, and that survival is comparable withthat of patients with LV systolic dysfunction and no evidence ofvalve disease Hence, patients with pseudosevere AS (e.g., Case
#2; seeFig 98.2) should probably be managed with heart failuretherapy and followed very closely (seeFig 98.1) However, med-ical therapy failure could be due to the inability of the failing ven-tricle to tolerate the hemodynamic burden imposed by the moderatestenosis and/or to progression of the stenosis to the severe stageduring follow-up, in which case AVR should be re-considered
Patients with no flow reserve represent the most challenginggroup with regard to therapeutic management, but AVR should
be contemplated in those with evidence of true severe AS onDSE or MDCT (e.g., Case #1, seeFig 98.2).22,30Because the oper-ative risk for open heart surgery is generally very high in absence offlow reserve, surgical AVR has received a class IIb (level of evi-dence C) recommendation in the 2012 ESC/EACTS guidelines.20Transcatheter AVR (TAVR) could provide a valuable alternative
to surgical AVR in these patients, although the rates of morbidityand mortality may be higher than those in patients with normal flow(seeFig 98.1).33–35 Recent studies reported a greater and morerapid improvement of LVEF in patients treated by TAVR thanthose treated by surgical AVR.33In contrast, TAVR is associatedwith a higher incidence of paravalvular regurgitation, which mayeventually have a negative impact on outcomes Further studiesare needed to determine whether TAVR provides better outcomesthan surgical AVR in patients with a low LVEF and LF-LG AS, andparticularly in those with no LV flow reserve
CONCLUSIONSLF-LG AS with a reduced LVEF is among the most challengingsituations encountered in patients with valvular heart disease.DSE greatly aids risk stratification and clinical decision-making
in these patients by allowing assessment of LV flow reserve andthe differentiation of true AS versus pseudosevere AS The calcu-lation of AVAProjmay be useful to corroborate stenosis severity inpatients with persisting AVA–gradient discordance at DSE Aorticvalve calcium quantification by MDCT may also be helpful to dif-ferentiate true severe AS versus pseudosevere AS in patients with
no significant increase in flow rate and in whom DSE remainsinconclusive AVR is recommended in patient with true severe
AS and LV flow reserve AVR should also be considered in patientwith evidence of severe AS and no LV flow reserve; however, oper-ative risk is high in these patients TAVR may be a promising alter-native to surgical AVR in patients with LF-LG AS, and particularly
in those with no LV flow reserve
Please access ExpertConsult to view the videos for this chapter.REFERENCES
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trans-2 Kulik A, Burwash IG, Kapila V, et al.: Long-term outcomes after valve ment for low-gradient aortic stenosis: impact of prosthesis-patient mismatch,Cir- culation 114(Suppl 1):I5553–I5558, 2006.
replace-3 Monin JL, Quere JP, Monchi M, et al.: Low-gradient aortic stenosis: operative risk stratification and predictors for long-term outcome: a multicenter study using dobutamine stress hemodynamics, Circulation 108(3):319–324, 2003.
4 Hachicha Z, Dumesnil JG, Bogaty P, Pibarot P: Paradoxical low flow, low ent severe aortic stenosis despite preserved ejection fraction is associated with higher afterload and reduced survival, Circulation 115(22):2856–2864, 2007.
gradi-5 Awtry E, Davidoff R: Low-flow/low-gradient aortic stenosis, Circulation 124 (23):e739–e741, 2011.
6 Baumgartner H, Hung J, Bermejo J, et al.: Echocardiographic assessment of valve stenosis: EAE/ASE recommendations for clinical practice, Eur J Echocardiogr 10 (1):1–25, 2009.
7 Carabello BA, Green LH, Grossman W, et al.: Hemodynamic determinants of prognosis of aortic valve replacement in critical aortic stenosis and advanced con-
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echocardiogra-phy in patients with aortic stenosis and left ventricular dysfunction: predicting
out-come as a function of management strategy, Chest 119(6):1766–1777, 2001.
9 Clavel MA, Fuchs C, Burwash IG, et al.: Predictors of outcomes in flow,
low-gradient aortic stenosis: results of the multicenter TOPAS Study, Circulation 118
(14 Suppl):S234–S242, 2008.
10 Brogan WC, Grayburn PA, Lange RA, Hillis LD: Prognosis after valve
replace-ment in patients with severe aortic stenosis and a low transvalvular pressure
gra-dient, J Am Coll Cardiol 21:1657–1660, 1993.
11 Blitz LR, Gorman M, Herrmann HC: Results of aortic valve replacement for aortic
stenosis with relatively low transvalvular pressure gradients, Am J Cardiol
81:358–362, 1998.
12 Smith RL, Larsen D, Crawford MH, Shively BK: Echocardiographic predictors of
survival in low gradient aortic stenosis, Am J Cardiol 86:804–807, 2000.
13 Quere JP, Monin JL, Levy F, et al.: Influence of preoperative left ventricular
con-tractile reserve on postoperative ejection fraction in low-gradient aortic stenosis,
Circulation 113(14):1738–1744, 2006.
14 Bergler-Klein J, Mundigler G, Pibarot P, et al.: B-type natriuretic peptide in
low-flow, low-gradient aortic stenosis: relationship to hemodynamics and clinical
out-come, Circulation 115(22):2848–2855, 2007.
15 Pai RG, Varadarajan P, Razzouk A: Survival benefit of aortic valve replacement in
patients with severe aortic stenosis with low ejection fraction and low gradient
with normal ejection fraction, Ann Thorac Surg 86(6):1781–1789, 2008.
16 Levy F, Laurent M, Monin JL, et al.: Aortic valve replacement for
low-flow/low-gradient aortic stenosis: operative risk stratification and long-term outcome:
a European multicenter study, J Am Coll Cardiol 51:1466–1472, 2008.
17 Tribouilloy C, Levy F, Rusinaru D, et al.: Outcome after aortic valve replacement
for low-flow/low-gradient aortic stenosis without contractile reserve on
dobuta-mine stress echocardiography, J Am Coll Cardiol 53(20):1865–1873, 2009.
18 deFilippi CR, Willett DL, Brickner E, et al.: Usefulness of dobutamine
echocar-diography in distinguishing severe from nonsevere valvular aortic stenosis in
patients with depressed left ventricular function and low transvalvular gradients,
Am J Cardiol 75:191–194, 1995.
19 Nishimura RA, Otto CM, Bonow RO, et al.: 2014 AHA/ACC guideline for the
management of patients with valvular heart disease: a report of the American
College of Cardiology/American Heart Association Task Force on Practice
Guidelines, J Am Coll Cardiol 63(22):e57–185, 2014.
20 Vahanian A, Alfieri O, Andreotti F, et al.: Guidelines on the management of
val-vular heart disease (version 2012), Eur Heart J 33(19):2451–2596, 2012.
21 Blais C, Burwash IG, Mundigler G, et al.: Projected valve area at normal flow rate
improves the assessment of stenosis severity in patients with low flow,
low-gradient aortic stenosis, Circulation 113(5):711–721, 2006.
22 Clavel MA, Burwash IG, Mundigler G, et al.: Validation of conventional and
sim-plified methods to calculate projected valve area at normal flow rate in patients
with low flow, low gradient aortic stenosis, J Am Soc Echocardiogr 23 (4):380–386, 2010.
23 Nishimura RA, Grantham JA, Connolly HM, et al.: Low-output, low-gradient tic stenosis in patients with depressed left ventricular systolic function: the clinical utility of the dobutamine challenge in the catheterization laboratory, Circulation 106(7):809–813, 2002.
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25 Bartko PE, Heinze G, Graf S, et al.: Two-dimensional strain for the assessment of left ventricular function in low flow-low gradient aortic stenosis, relationship to hemodynamics and outcome, Circ Cardiovasc Imaging 6(2):268–276, 2012.
26 Zuppiroli A, Mori F, Olivotto I, et al.: Therapeutic implications of contractile reserve elicited by dobutamine echocardiography in symptomatic, low-gradient aortic stenosis, Ital Heart J 4(4):264–270, 2003.
27 Fouge`res E, Tribouilloy C, Monchi M, et al.: Outcomes of pseudo-severe aortic stenosis under conservative treatment, Eur Heart J 33(19):2426–2433, 2012.
28 Burwash IG, Lortie M, Pibarot P, et al.: Myocardial blood flow in patients with low flow, low gradient aortic stenosis: differences between true and pseudo-severe aortic stenosis, Heart 94:1627–1633, 2008.
29 Monin JL, Monchi M, Gest V, et al.: Aortic stenosis with severe left ventricular dysfunction and low transvalvular pressure gradients, J Am Coll Cardiol 37 (8):2101–2107, 2001.
30 Cueff C, Serfaty JM, Cimadevilla C, et al.: Measurement of aortic valve cation using multislice computed tomography: correlation with haemodynamic severity of aortic stenosis and clinical implication for patients with low ejection fraction, Heart 97(9):721–726, 2011.
calcifi-31 Katsanos S, Yiu KH, Clavel MA, et al.: Impact of valvuloarterial impedance on year outcome of patients undergoing transcatheter aortic valve implantation, J Am Soc Echocardiogr 26(7):691–698, 2013.
2-32 Clavel MA, Messika-Zeitoun D, Pibarot P, et al.: The complex nature of dant severe calcified aortic valve disease grading: new insights from combined Doppler-echocardiographic and computed tomographic study, J Am Coll Cardiol 62(24):2329–2338, 2013.
discor-33 Clavel MA, Webb JG, Rode´s-Cabau J, et al.: Comparison between transcatheter and surgical prosthetic valve implantation in patients with severe aortic stenosis and reduced left ventricular ejection fraction, Circulation 122(19):1928–1936, 2010.
34 Gotzmann M, Lindstaedt M, Bojara W, et al.: Clinical outcome of transcatheter aortic valve implantation in patients with low-flow, low gradient aortic stenosis, Catheter Cardiovasc Interv 79(5):693–701, 2012.
35 Ben-Dor I, Maluenda G, Iyasu GD, et al.: Comparison of outcome of higher versus lower transvalvular gradients in patients with severe aortic stenosis and low ( <40%) left ventricular ejection fraction, Am J Cardiol 109(7):1031–1037, 2012.
Preserved Left Ventricular Ejection Fraction
Florent LeVen, MD, Philippe Pibarot, DVM, PhD, Jean G Dumesnil, MD
When assessing patients with aortic stenosis (AS), cardiologists
are often confronted with discordant echocardiographic findings,
the most frequent being the combination of a small aortic valve
area (AVA<1.0 cm2
) consistent with severe AS and a low meangradient (<40 mm Hg) consistent with nonsevere AS This situa-
tion raises uncertainty with regard to the actual severity of the
ste-nosis and the potential indication of aortic valve replacement
(AVR) if the patient is symptomatic Such discordance between
AVA (small) and the gradient (low) is often related to the presence
of low left ventricular (LV) outflow Because the pressure gradient
is directly related to the squared function of the transvalvular flow
rate, even a modest decrease in flow can result in an important
reduction in the gradient, which leads to an underestimation of
ste-nosis severity Hence, patients with true severe AS may present
with a low gradient if their transvalvular flow is reduced This
low-flow, low-gradient (LF-LG) condition may occur in the
con-text of either a reduced (i.e., classical LF; see Chapter 98) or
pre-served (i.e., paradoxical LF) LV ejection fraction (LVEF)
(Fig 99.1).1–3The purpose of this chapter is to provide an update
on the Doppler echocardiographic assessment of paradoxicalLF-LG AS
CLINICAL PRESENTATION AND PATHOPHYSIOLOGY OF PARADOXICAL LOW-FLOW, LOW-GRADIENT AORTIC STENOSIS
Paradoxical LF-LG AS is defined as a small AVA (i.e., AVA
<1.0 cm2
and indexed AVA<0.6 cm2
/m2), an LG (i.e.,<40 mmHg), an LF (i.e., stroke volume index [SVi]<35 mL/m2
), and a served LVEF (i.e.,50%) The reported prevalence of this entity isbetween 5% and 25%, and the prevalence has been shown toincrease with older age, female gender, and the concomitant pres-ence of systemic arterial hypertension, metabolic syndrome, ordiabetes.3The cumulative effect of one or more of these factorsfurther contributes to more pronounced and/or exaggerated LV
Trang 35pre-concentric remodeling, the development of myocardial fibrosis,
and as a result, a reduction in the size, compliance, and filling of
the LV cavity (seeFig 99.1).1,4,5Moreover, LV systolic function,
which appears normal when examining the LVEF, is substantially
reduced when considering global LV longitudinal strain, which has
been shown to be more sensitive in detecting alterations of intrinsic
myocardial systolic function.6 , 7Hence, the decrease in stroke
vol-ume in paradoxical LF-LG AS is predominantly due to impaired
LV filling, but also, in part, to abnormal LV emptying.Box 99.1
summarizes the main clinical and Doppler echocardiographic
fea-tures of paradoxical LF-LG AS, andFigure 99.2and Video 99.2,
A-C present an example of a patient with this entity Several other
fac-tors besides the restrictive LV physiology may also contribute to
the reduction of the transvalvular flow rate in AS patients with
pre-served LVEF, including reduced arterial compliance, atrial
fibrilla-tion, and concomitant mitral regurgitafibrilla-tion, mitral stenosis, or
tricuspid regurgitation.1,8,9Hence, it is not surprising that a large
proportion (30%-55%) of patients with AS and preserved LVEF
have a reduced stroke volume (i.e., SVi<35 mL/m2
).3The presence of a LF state in the context of preserved LVEF
complicates the assessment of stenosis severity and therapeutic
decision making, such that patients with paradoxical LF-LG severe
AS have a 40% to 50% lower referral to surgery compared with
patients with the expected normal flow, high-gradient pattern of
AS This is likely due to underestimation of the stenosis severity
in light of the relatively LG However, several studies have
demon-strated that these patients have a worse prognosis compared with
those with normal flow, high-gradient AS, and that they have much
better prognosis when treated surgically versus medically, even after
adjustment for differences in the baseline risk profile.2,4,5,7,9–13
Hence, because of its particular mode of presentation, the
Normal-LVEFNormal-flowHigh-gradient
Normal-LVEF
“Paradoxical”
Low-flowLow-gradient
Figure 99.1 Different patterns of severe aortic stenosis according to flow, gradient, and left ventricular (LV) geometry in cases of preserved left ventricular ejection fraction (LVEF) The majority of patients with severe aortic stenosis (AS) develop LV hypertrophy with normal LV cavity size (left), which allows maintenance of normal LV pump function These patients with severe AS and normal transvalvular flow generally exhibit a high gradient However, patients with a low LVEF and “classical” low-flow, low-gradient AS (middle) are characterized by a dilated LV with markedly decreased LV systolic function, which is most often due to ischemic heart disease and/or to afterload mismatch In contrast, a normal LVEF and “par- adoxical” low-flow, low-gradient AS (right) is characterized by pronounced LV concentric remodeling that leads to impaired filling and reduced pump function Because of the low-flow state, the patients in the two latter categories may present with a low gradient despite the presence of severe ste- nosis (Adapted from Pibarot P, Dumesnil JG Low-flow, low-gradient aortic stenosis with normal and depressed left ventricular ejection fraction, J Am Coll Cardiol 60:1845-1853, 2012.)
Box 99.1 Clinical and Doppler Echocardiographic Features
of Paradoxical Low-Flow, Low-Gradient Aortic Stenosis
• Severely thickened and calcified valve with reduced opening
• AVA <1.0 cm 2 , AVAi <0.6 cm 2 /m 2 , DVI <0.25
• Mean transvalvular gradient <40 mm Hg
• Valvulo-arterial impedance >4.5 mm Hg • mL 1 • m 2 Left Ventricle
• Ejection fraction 50%
• Small cavity size:
• End diastolic diameter <47 mm *
• End diastolic volume <55 mL/m 2 *
• Relative wall thickness ratio >0.5
• Impaired LV filling
• Impaired global longitudinal strain: <15% *
• Stroke volume index <35 mL/m 2
*These values are based on some initial retrospective studies 1 , 5–7 and are given as an indication Further investigations are needed to determine more precise cutpoints AVA, aortic valve area; AVAi, aortic valve area indexed to body surface area; DVI, Doppler velocity index.
423
Low-Flow, Low-Gradient Aortic Stenosis with Preserved Left Ventricular Ejection Fraction
99
Trang 36paradoxical LF-LG entity is often misdiagnosed, which may lead to
underestimation of the stenosis severity and symptoms, and
there-fore, underutilization or inappropriate delay of AVR
ASSESSMENT OF FLOW AND STENOSIS SEVERITY
The main pitfall associated with the echocardiographic diagnosis of
paradoxical LF-LG AS is an error in the calculation of the Doppler
stroke volume due to inaccurate measurement of the LV outflow
tract (LVOT) diameter and/or misplacement of the pulsed wave
Doppler sample volume.3An underestimation of stroke volume
may lead to the erroneous conclusion that patients have paradoxical
LF-LG severe AS, whereas they actually have moderate AS with
normal flow Conversely, an overestimation of stroke volume
may lead to the misidentification and gross underestimation of
the prevalence of the entity.14
Therefore, when confronted with a patient with a discordant
AVA–gradient finding and preserved LVEF, the first step in the
diagnostic and therapeutic management algorithm presented in
Figure 99.3should be to rule out measurement errors in the
estima-tion of stroke volume and to confirm the presence of LF The most
frequent cause of error in the measurement of the Doppler stroke
volume is an underestimation of the LVOT diameter The LVOT
cross section is often elliptical, and the diameter, as measured by
two-dimensional echocardiography in the parasternal long-axis
view, is the anteroposterior diameter, which is generally the smallerdiameter of the ellipse To attenuate this limitation, it is preferable
to measure the LVOT diameter at the base of the aortic valve cusps(where the LVOT is more circular) rather than the 5 to 10 mmbelow the aortic annulus Three-dimensional transthoracic or trans-esophageal echocardiography or multidetector computed tomogra-phy (MDCT) may also be used to obtain a more accurate estimation
of the LVOT cross-sectional area and a more accurate estimation ofthe stroke volume and AVA
Furthermore, when paradoxical LF-LG AS is suspected, surements of LV geometry and function should first be reviewedwith the expectation of finding the typical echocardiographic fea-tures that characterize this entity (i.e., pronounced concentricremodeling, small LV cavity size, and reduced global longitudinalstrain, etc.) (seeBox 99.1andFig 99.3) Second, the measurement
mea-of the LVOT stroke volume by the Doppler method should be tematically corroborated by other means, such as a comparison ofthe LVEF estimated by the Dumesnil method (Doppler stroke vol-ume divided by the LV end-diastolic volume calculated with theTeichholz formula), with the LVEF obtained by the biplane Simp-son or visual method If the LVEF by the Dumesnil method is sub-stantially lower than the LVEF that is estimated to be correct, thenone should strongly suspect that the Doppler stroke volume hasbeen underestimated In contrast, overestimation by the Dumesnilmethod may be due to overestimation of stroke volume, but this is
sys-00
100100
200200
CmS
C M
300
400400
500
C
D
Figure 99.2 Patient with paradoxical low-flow, low-gradient aortic stenosis (AS) This is a case of a 78-year-old woman with a history of calcific AS who
is in New York Heart Association functional class III The parasternal long- and short-axis views show a small left ventricular cavity with pronounced concentric remodeling and a preserved left ventricular ejection fraction (LVEF), and a calcified and thickened aortic valve with restricted opening (A, B and Video 99.2, A-C) This patient underwent low-dose dobutamine stress echocardiography up to 15 μg/kg/min The LVEF increased from 60% to 70%, the stroke volume increased from 42 to 52 mL, the peak and/or mean gradient increased from 51/29 to 94/57 mm Hg (C, D), and the aortic valve area increased slightly from 0.70 to 0.77 cm 2 This is a case of paradoxical low-flow, low-gradient severe AS This patient underwent aortic valve replacement and had a good outcome.
Trang 37less specific because the LVEF measured by the Dumesnil method
may overestimate the true LVEF in cases of very small ventricles.15
Two-dimensional volumetric methods can also be used, but these
should be used with caution because images of the left ventricle
are frequently foreshortened and may lead to gross
underestima-tions of volumes Third, it is important to also identify other
poten-tial causes of LF, such as concomitant systemic arterial
hypertension, mitral regurgitation, tricuspid regurgitation, or atrial
fibrillation If these conditions are present, the anterograde stroke
volume may be reduced despite the absence of some of the typical
features of paradoxical LF-LG described inBox 99.1
The second step in the algorithm (seeFig 99.3) assesses the
presence of symptoms In patients who claim to be asymptomatic
or in those with equivocal symptoms, exercise testing may be sidered to confirm the symptomatic status Patients who are trulyasymptomatic should be managed with close follow-up, and noadditional diagnostic tests are required In the patients who aresymptomatic, the third step of the algorithm assesses for the pres-ence of associated hypertension (seeFig 99.3) Hypertension maycontribute to the LF state and to the symptoms.8Patients with par-adoxical LF-LG often have reduced arterial compliance and/orincreased vascular resistance.1 , 5 , 8 However, because of the LFstate, blood pressure may be lower than expected or pseudonorma-lized, which is similar to what may occur in the case of the trans-valvular gradient As a consequence, the presence and severity ofhypertension may be underestimated in these patients.14,16Hence,blood pressure should be systematically measured at the time ofechocardiographic examination, and arterial compliance and vas-cular resistance should be calculated.1If the presence of hyperten-sion is confirmed, antihypertensive therapy should be instituted oroptimized, and the Doppler echocardiographic parameters andsymptoms should be re-assessed after normalization of the arterialhemodynamics (seeFig 99.3)
con-The fourth and last step of the algorithm is to confirm the nosis severity (seeFig 99.3) Because the transvalvular flow rate isreduced in these patients, it cannot be excluded that the AVA might
ste-be pseudosevere, that is, the flow may not ste-be high enough to fullyopen a valve that is only moderately stenotic, which has beendescribed in patients with classical LF-LG and a reduced LVEF.Exercise stress echocardiography can be useful in patients with
no or equivocal symptoms to confirm their symptomatic statusand to assess the response of the AVA and the gradient to theincreased flow rate and to calculate the projected AVA at a normalflow rate.17Low-dose dobutamine stress echocardiography (start-ing at 2.5μg/kg/min up to a maximum of 20 μg/kg/min) may also
be considered in symptomatic patients (seeFig 99.2), but it should
be used with caution and with close monitoring of blood pressureand LVOT velocity A recent multicenter study reported that stressechocardiography is safe and clinically useful in patients with par-adoxical LF-LG AS.17In this study, 33% of the patients were iden-tified with pseudosevere AS on the basis of the projected AVA atthe normal flow rate, which was similar to what was reported inpatients with classical LF-LG AS.17Dobutamine stress echocardi-ography should not be used in patients with severe LV restrictivephysiology The measurement of aortic valve calcification loadand density by MDCT may be used to corroborate stenosis severity
in patients with paradoxical LF-LG AS, and particularly, in those inwhom stress echocardiography is not feasible or is inconclu-sive.18 , 19Further studies are needed to confirm the clinical useful-ness of stress echocardiography and MDCT in this challengingsubset of patients
Hence, Doppler-echocardiography plays a crucial role for(1) the differential diagnosis between true paradoxical LF-LG
AS and other situations associated with a small AVA and LG;and (2) the confirmation of stenosis severity, and thus, the indica-tion for AVR if the patient is symptomatic In particular, it is impor-tant to distinguish paradoxical LF-LG AS from normal flow, LG
AS with a small AVA.2,3This latter entity may be related to theconfounding effect of small body size (i.e., a small AVA in a patientwith a small body surface area may correlate with moderate AS and
a LG) or inconsistencies in the guideline criteria for severe AS (i.e.,the AVA cutpoint value of 1.0 cm2used to define severe AS cor-responds to a gradient cutpoint value of 30-35 mm Hg).2,3,20THERAPEUTIC MANAGEMENT
The 2012 European Society of Cardiology/European Associationfor Cardio-Thoracic Surgery guidelines21 as well as the 2014American College of Cardiology/American Heart Associationguidelines22 have recognized that paradoxical LF-LG AS is animportant, new entity that requires further investigation, particularly
True-severe
- Dobutamine/exercise stress echo
- AoV calcium scoring by MDCT
Consider surgical or
transcatheter AVR
Rule out pseudo-severe AS:
Discordant echo findings
AVA<1.0 cm2 AVAi<0.6 cm2/m2
MG<40 mm HgSVi<35 ml/m2 LVEF>50%
Figure 99.3 Algorithm for the diagnostic and therapeutic management
of patients with preserved left ventricular ejection fraction (LVEF) who
present with a small aortic valve area but a low gradient *See
Box 99.1 for the clinical and Doppler echocardiographic features of
par-adoxical low-flow, low-gradient (LF-LG) aortic stenosis (AS) † The other
potential causes of LF include reduced arterial compliance, atrial
fibrilla-tion, and concomitant mitral regurgitafibrilla-tion, mitral stenosis, or tricuspid
regurgitation AoV, aortic valve; AVA, aortic valve effective orifice area;
AVAi , AVA index; AVR, aortic valve replacement; MDCT, multidetector
computed tomography; MG, mean transvalvular gradient; SV, stroke
volume.
425
Low-Flow, Low-Gradient Aortic Stenosis with Preserved Left Ventricular Ejection Fraction
99
Trang 38with regard to the impact of AVR; moreover, a class IIa (level of
evi-dence C) indication for AVR has been included in the guidelines,
provided that stenosis severity is carefully confirmed by a
compre-hensive Doppler echocardiographic evaluation (seeFig 99.3) The
multiple studies5,9–13published since the publication of these
guide-lines21,22provide further support for this recommendation
Paradoxical LF-LG AS is associated with several factors (i.e.,
pronounced concentric remodeling, small LV cavity, myocardial
fibrosis, impaired myocardial function, small aortic annulus, etc.)
that may increase the risk of operative mortality and the risk of
prosthesis–patient mismatch.2,23Hence, as in patients with
classi-cal LF-LG AS, transcatheter AVR may also provide a valuable
alternative to surgical AVR in patients with paradoxical LF-LG
AS (seeFig 99.3).13
CONCLUSION
A particular effort should be made to rule out measurement errors in
patients with discordant AVA (small)–gradient (low) findings
Patients with true paradoxical LF-LG AS should receive particular
attention because they generally have a worse prognosis and often
have pseudo-normalization of their transvalvular gradients and
sys-temic blood pressure This may be very insidious because it may
lead to underestimations of both AS and hypertension severity
Patients with paradoxical LF-LG AS who are symptomatic require
further examinations (i.e., stress echocardiography and/or MDCT)
to confirm the stenosis severity and the need for AVR
Transcath-eter AVR may provide a valuable alternative to surgical AVR in
patients with paradoxical LF-LG AS Optimization of
antihyper-tensive therapy should be considered in these patients, regardless
of whether the patient is to be treated conservatively or with
surgi-cal or transcatheter valve replacement
Please access ExpertConsult to view the Videos for this chapter
REFERENCES
1 Hachicha Z, Dumesnil JG, Bogaty P, et al.: Paradoxical low flow, low gradient
severe aortic stenosis despite preserved ejection fraction is associated with higher
afterload and reduced survival, Circulation 115:2856–2864, 2007.
2 Dumesnil JG, Pibarot P, Carabello B: Paradoxical low flow and/or low gradient
severe aortic stenosis despite preserved left ventricular ejection fraction:
implica-tions for diagnosis and treatment, Eur Heart J 31:281–289, 2010.
3 Pibarot P, Dumesnil JG: Low-flow, low-gradient aortic stenosis with normal and
depressed left ventricular ejection fraction,J Am Coll Cardiol 60:1845–1853, 2012.
4 Barasch E, Fan D, Chukwu EO, et al.: Severe isolated aortic stenosis with normal
left ventricular systolic function and low transvalvular gradients:
pathophysio-logic and prognostic insights, J Heart Valve Dis 17:81–88, 2008.
5 Mehrotra P, Jansen K, Flynn AW, et al.: Differential left ventricular remodelling
and longitudinal function distinguishes low flow from normal-flow preserved
ejection fraction low-gradient severe aortic stenosis, Eur Heart J 34:1906–1914, 2013.
6 Adda J, Mielot C, Giorgi R, et al.: Low-flow, low-gradient severe aortic stenosis despite normal ejection fraction is associated with severe left ventricular dysfunc- tion as assessed by speckle tracking echocardiography: a multicenter study, Circ Cardiovasc Imaging 5:27–35, 2012.
7 Lancellotti P, Magne J, Donal E, et al.: Clinical outcome in asymptomatic severe aortic stenosis Insights from the new proposed aortic stenosis grading classifica- tion, J Am Coll Cardiol 59:235–243, 2012.
8 Eleid MF, Nishimura RA, Sorajja P, Borlaug BA: Systemic hypertension in gradient severe aortic stenosis with preserved ejection fraction, Circulation 128:1349–1353, 2013.
low-9 Eleid MF, Sorajja P, Michelena HI, et al.: Flow-gradient patterns in severe aortic stenosis with preserved ejection fraction: clinical characteristics and predictors of survival, Circulation 128:1781–1789, 2013.
10 Clavel MA, Dumesnil JG, Capoulade R, et al.: Outcome of patients with aortic stenosis, small valve area and low-flow, low-gradient despite preserved left ven- tricular ejection fraction, J Am Coll Cardiol 60:1259–1267, 2012.
11 Le Ven F, Freeman M, Webb J, et al.: Impact of low flow on the outcome of high risk patients undergoing transcatheter aortic valve replacement, J Am Coll Cardiol 62:782–788, 2013.
12 Ozkan A, Hachamovitch R, Kapadia SR, et al.: Impact of aortic valve replacement
on outcome of symptomatic patients with severe aortic stenosis with low gradient and preserved left ventricular ejection fraction, Circulation 128:622–631, 2013.
13 Herrmann HC, Pibarot P, Hueter I, et al.: Predictors of mortality and outcomes of therapy in low flow severe aortic stenosis: A PARTNER trial analysis, Circulation 127:2316–2326, 2013.
14 Pibarot P, Dumesnil JG: Paradoxical low-flow, low-gradient aortic stenosis: new evidences, more questions, Circulation 128:1729–1732, 2013.
15 Dumesnil JG, Dion D, Yvorchuk K, et al.: A new, simple and accurate method for determining ejection fraction by Doppler echocardiography, Can J Cardiol 11:1007–1014, 1995.
16 Mohty D, Pibarot P, Echahidi N, et al.: Reduced systemic arterial compliance sured by routine Doppler echocardiography: a new and independent predictor of mor- tality in patients with type 2 diabetes mellitus, Atherosclerosis 225:353–358, 2012.
mea-17 Clavel MA, Ennezat PV, Mare´chaux S, et al.: Stress echocardiography to assess stenosis severity and predict outcome in patients with paradoxical low-flow, low- gradient aortic stenosis and preserved LVEF, J Am Coll Cardiol Imaging 6:175–183, 2013.
18 Katsanos S, Yiu KH, Clavel MA, et al.: Impact of valvuloarterial impedance on 2-year outcome of patients undergoing transcatheter aortic valve implantation,
J Am Soc Echocardiogr 26:691–698, 2013.
19 Clavel MA, Messika-Zeitoun D, Pibarot P, et al.: The complex nature of dant severe calcified aortic valve disease grading: new insights from combined Doppler-echocardiographic and computed tomographic study, J Am Coll Cardiol 62:2329–2338, 2013.
discor-20 Minners J, Allgeier M, Gohlke-Baerwolf C, et al.: Inconsistent grading of aortic valve stenosis by current guidelines: haemodynamic studies in patients with apparently normal left ventricular function, Heart 96:1463–1468, 2010.
21 Vahanian A, Alfieri O, Andreotti F, et al.: Guidelines on the management of vular heart disease (version 2012), Eur Heart J 33:2451–2496, 2012.
val-22 Nishimura RA, Otto CM, Bonow RO, et al.: 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines, J Am Coll Cardiol 63(22):e57–185, 2014.
23 Herrmann S, Stork S, Niemann M, et al.: Low-gradient aortic valve stenosis: cardial fibrosis and its influence on function and outcome, J Am Coll Cardiol 58:402–412, 2011.
in Asymptomatic Aortic Stenosis
Patrizio Lancellotti, MD, PhD, Raluca Dulgheru, MD
Aortic stenosis (AS) is a common and progressive disease.1Aortic
valve replacement (AVR) is the sole effective therapy in
symptom-atic patients, whereas the management of asymptomsymptom-atic patients
with severe AS remains a source of debate.2,3The clinical challenge
that we currently face is the ability to best discriminate if the
asymp-tomatic AS patient might benefit from elective AVR Exercise
test-ing has an established role in the assessment of exercise capacity and
symptomatic status in patients with AS.4–6Several studies have
con-firmed that symptom-limited exercise testing can be performed
safely in patients with AS while providing better risk stratification
than conventional echocardiography.7,8 In the American HeartAssociation/American College of Cardiology (AHA/ACC) guide-lines,3exercise testing is a class IIb recommendation in patients withasymptomatic AS, but it is more strongly advocated in the EuropeanSociety of Cardiology (ESC) guidelines.2However, except for theappearance of early clinical symptoms, exercise testing remains dif-ficult to interpret in elderly patients and in patients with associateddiseases (e.g., chronic obstruction pulmonary disease [COPD], lungdisease, and comorbidities) When combined with echocardiogra-phy, and beyond symptomatic status, exercise testing is helpful in
Trang 39providing information on the true hemodynamic consequences of
AS and additional prognostic information.9–11 From a practical
standpoint, exercise testing is more physiologic than a dobutamine
stress test Supine or semisupine bicycle exercise echocardiography
is the preferred method in Europe because it allows simultaneous,
continuous two-dimensional and Doppler echocardiographic
exam-inations.12To date, per-exercise imaging echocardiography
repre-sents the most common approach for assessing asymptomatic AS
EXERCISE TESTING PROTOCOL
A symptom-limited graded exercise test is recommended At least
80% of the age-predicted heart rate should be reached in the
absence of symptoms The test should be performed under
supervi-sion in a dedicated room with all required facilities The initial
workload of 25 W is maintained for 2 min, and the workload is
increased by 25 W every 2 min An increase by 10 W seems to
be more appropriate in older patients with AS Blood pressure
and a 12-lead electrocardiogram are recorded at rest and at each
step of the test Total exercise time, maximum workload, peak heart
rate, and blood pressure, and the reason for stopping the test should
be recorded (Table 100.1)
EXERCISE ECHOCARDIOGRAPHY PROTOCOL
A complete echocardiographic study should be performed at rest,
before exercise Image acquisitions both at rest and during exercise
are obtained in the same position in a semisupine test Parameters
related to valve hemodynamics, left ventricular (LV) function, and
systolic pulmonary arterial pressure (sPAP) are targeted Apart
from changes in E/e0, which is an estimate of the LV filling pressure
that is obtained at low-level exercise (at approximately 95–105
beats/min, before the e0- and a0-waves merge), all other parameters
should be obtained at each step of the test (baseline, low, medium,
high levels) and at peak exercise The kinetic changes in LV
contractile function, in the aortic mean pressure gradient, and in
the trans-tricuspid pressure gradient need to be assessed(Table 100.2) We recommend the following stepwise imagingsequence: two-dimensional gray-scale loops (frame rate>50–70/sec) of the left ventricle in the 4-, 2-, and 3-chamber views,continuous wave Doppler of the transaortic flow, pulsed waveDoppler of the LV outflow tract, color flow of the mitral valve
to evaluate the presence of secondary mitral regurgitation, andcontinuous wave Doppler of the tricuspid valve to assess thetrans-tricuspid pressure gradient (Fig 100.1) Images and loopsare stored to be analyzed offline after cessation of exercise; usually,
no measurements are performed during image acquisition
CLINICAL AND PROGNOSTIC VALUE Exercise Electrocardiographic ParametersChanges in clinical, electrocardiographic, and echocardiographicparameters during the stress test have been shown to be associatedwith outcomes and subsequent clinical decision-making in asymp-tomatic AS patients Exercise-induced limiting symptoms (dizzi-ness, dyspnea at low workload, angina, or syncope) occur inapproximately 30% to 40% of asymptomatic patients with AS.7The onset of symptoms in individual patients depends on the sever-ity of their AS, as well as on LV function and the status of theperipheral circulation.12When peripheral demands exceed cardiacoutput, symptoms may occur.13 The occurrence of exercise-limiting symptoms predicts the rapid development of symptoms
in daily life, cardiac death (including sudden death), and the needfor AVR,4–7particularly in young, physically active patients (youn-ger than 70 years old).6The occurrence of rapidly reversible dys-pnea at high workloads (close to the age–gender predictedmaximum workloads) is considered to be normal.8An abnormalblood pressure response (<20 mm Hg increase in systolic bloodpressure), ST-depression (>2 mm, horizontal or downsloping), orcomplex ventricular arrhythmia during exercise may predictadverse outcomes in asymptomatic AS patients, but does not seem
to improve the accuracy of the test.2 , 3
Echocardiographic Parameters Valve Compliance and Pressure GradientsRegardless of the echocardiographic data at rest and the exerciseelectrocardiographic results, exercise-induced changes in LV func-tion or indexes of AS severity are independent determinants of poorprognosis (Fig 100.2).8An increase in the mean transaortic pressuregradient by 18 to 20 mm Hg or more during exercise is associatedwith an increased risk of cardiac death, development of spontaneoussymptoms, and a need for AVR.9–14Such an increase in pressure gra-dient reflects the presence of either more severe AS (the more severethe stenosis at rest, the higher the increase in gradient for a given flowrate during exercise) or a noncompliant and rigid aortic valve (no orminimal enlargement of the aortic valve orifice area duringexercise), or both However, the exercise-induced changes in meantransaortic pressure gradient should be interpreted in light of theexercise-induced changes in LV stroke volume and function
Left Ventricular Function and Contractile ReserveDuring exercise, the acute changes in LV load may alter LV adap-tation and promote onset of symptoms.8,13However, changes intransaortic pressure gradients and LV function are not uniform.The heart may adapt successfully, by recruiting LV contractilereserve, to the increased afterload Conversely, when the aorticvalve is no longer compliant, or in cases of severe myocardial dys-function, a mismatch between afterload and contractility mayoccur In some patients, a biphasic response can be observed, with
an initial increase followed by a subsequent decrease in mean
TABLE 100.1 Exercise Testing: Contraindications and Definition
of an Abnormal Exercise Response
Contraindications to
Exercise Test in AS
Causes of Exercise Test Cessation
Abnormal Exercise Test ( ≥1 criteria) Truly symptomatic
in systolic blood pressure
20 mm Hg) Significant ventricular arrhythmia Rarely, significant ST-segment depression
Symptoms: angina, dyspnea, dizziness, syncope or near- syncope
2 mm ST-segment depression in comparison to baseline level Fall or <20 mm Hg rise in systolic blood pressure
Complex ventricular arrhythmias (ventricular tachycardia, >3 premature ventricular complexes in a row)
427
Stress (Exercise) Echocardiography in Asymptomatic Aortic Stenosis
100
Trang 40transaortic pressure gradient that parallels the evolution of LV
con-tractility.15Patients with a decrease or a small increase in LV
ejec-tion fracejec-tion are thus more likely to exhibit an abnormal response to
exercise and cardiac-related events during follow-up.11,12,14Using
tissue Doppler imaging, Van Pelt et al suggested that a postexercise
increase in mitral s0-wave velocity of more than 5 cm/sec might be
a good cutoff value to determine the presence of LV contractilereserve.16 Similarly, by using two-dimensional speckle trackinganalysis, an exercise increase in global longitudinal strain of morethan 1.4% might indicate the presence of LV contractile
TABLE 100.2 Exercise Echocardiography in Aortic Stenosis
Clinical
Major Parameters to be
Asymptomatic
patients Semisupine exercisebicycle
echocardiography (rarely treadmill exercise test)
Clinical
• Symptoms
• Systolic blood pressure
Dizziness, dyspnea, angina, syncope Drop by 20 mm Hg in systolic blood pressure
In both conditions: peripheral demands (vasodilatation) exceed the rise in cardiac output (substantial pump failure)
Dizziness, dyspnea or drop in systolic blood pressure predict the onset of symptoms, cardiac-related death, and the need for AVR
Valve
• Aortic valve area
• Mean transaortic pressure gradient (kinetic
Biphasic response (afterload mismatch):
increase in mean pressure gradient at low-level exercise followed by a drop in the mean pressure gradient at high- peak test due to exhausted LV contractile recruitment (decrease in mean flow rate)
Increase in mean transaortic pressure gradient by >18–20 mm Hg predicts spontaneous symptoms, cardiac-related death, AVR dictated
by symptoms, hospitalization for heart failure
LV function (kinetic of changes)
• LV ejection fraction
• Global longitudinal strain
• Tissue Doppler velocities
Increased: presence of contractile reserve Stable or decreased: absence of contractile reserve
Biphasic response (afterload mismatch):
initial increase in LV function followed by
a decline in LV function at high peak test Worsening in wall motion or in global function: ischemia due to limited coronary flow reserve with or without significant coronary lesion
Decrease/smaller increase in LV ejection fraction predicts spontaneous symptoms, cardiac- related death, abnormal exercise test
Hemodynamic
• Trans-tricuspid pressure gradient (kinetic
of changes)
• Mitral E/e 0 ratio
• Mitral regurgitation
Increased >50 mm Hg: elevated sPAP Rapid increase in sPAP: low pulmonary compliance and markedly increase pulmonary resistance
Increased: elevated LV filling pressure Worsening or occurrence: elevated global afterload
>50 mm Hg in sPAP predicts reduced cardiac-event free survival, high rate
of cardiac death
AVR , aortic valve replacement; LV, left ventricular; sPAP, systolic pulmonary artery pressure.
MPGsPAP
125 W
MPGsPAP
100 W
MPGsPAP
75 W
MPGsPAP
Peak exerciserecovery
Figure 100.1 Stepwise Doppler echocardiography image acquisitions
in patients with aortic stenosis E/e 0
ratio , an estimate of left ventricular ing pressure; LV, left ventricular; MPG , mean transaortic pressure gra- dient; sPAP, systolic pulmonary arte- rial pressure.