how do we reconcile echocardiography, computed...

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P U B L I S H E D B Y E L S E V I E R

FOCUS ISSUE: IMAGING IN AORTIC STENOSIS: PART II

STATE-OF-THE-ART PAPER

How DoWe Reconcile Echocardiography,Computed Tomography, andHybrid Imaging in Assessing DiscordantGrading of Aortic Stenosis Severity?
Victoria Delgado, MD,a Marie-Annick Clavel, DVM, PHD,b Rebecca T. Hahn, MD,c Linda Gillam, MD,d Jeroen Bax, MD,a
Partho P. Sengupta, MD,e Philippe Pibarot, DVM, PHDb

JACC: CARDIOVASCULAR IMAGING CME/MOC/ECME

CME/MOC/ECME Editor: Ragavendra R. Baliga, MD

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How Do We Reconcile Echocardiography, Computed Tomography, and

Hybrid Imaging in Assessing Discordant Grading of Aortic Stenosis

Severity? will be accredited by the European Board for Accreditation in

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CME/MOC/ECME Objective for This Article: Upon completion, the reader

should be able to: 1) reconcile the discordances in AS severity grading be-

tween the different imaging modalities and parameters; 2) implement a

systematic approach to confirm the validity of the Doppler-echocardio-

graphic measures of AS severity; 3) apply and interpret hybrid (Doppler/

multidetector computed tomography [MDCT]) imaging to corroborate

Doppler-echocardiographicmeasures of AS severity; 4) apply and interpret

stress echocardiography to differentiate true-severe versus pseudo-severe

AS in patients with low LVEF, low-flow, low-gradient AS; and 5) apply

and interpret aortic valve calcium scoring by MDCT to differentiate

severe versus non-severe AS in patients with preserved LVEF and

low-gradient AS.

CME/MOC/ECME Editor Disclosure: JACC: Cardiovascular Imaging

CME/MOC/ECME Editor Ragavendra R. Baliga, MD, has reported that he

has no relationships to disclose.

Author Disclosures: TheDepartmentofCardiologyof theLeidenUniversity

Medical Center has received unrestricted research grants from Biotronik,

Boston Scientific, Edwards Lifesciences, GE Healthcare, and Medtronic.

Drs. Hahn and Pibarot have received a research grant from Edwards Life-

sciences for echocardiography core laboratory analyses in the field of

transcatheter aortic valve replacement. Dr. Delgado has received speaker

fees from Abbott Vascular. Dr. Gillam oversees core laboratories that have

research contractswithEdwardsLifesciences LLCandMedtronic; and is an

advisor to Philips. All other authors have reported that they have no re-

lationships relevant to the contents of this paper to disclose.

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Issue Date: February 2019

Expiration Date: January 31, 2020

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Delgado et al. J A C C : C A R D I O V A S C U L A R I M A G I N G , V O L . 1 2 , N O . 2 , 2 0 1 9

Assessing Discordant Grading of AS Severity F E B R U A R Y 2 0 1 9 : 2 6 7 – 8 2

268

How Do We Reconcile Echo
cardiography,Computed Tomography, and Hybrid Imaging inAssessing Discordant Grading ofAortic Stenosis Severity? Victoria Delgado, MD,a Marie-Annick Clavel, DVM, PHD,b Rebecca T. Hahn, MD,c Linda Gillam, MD,d Jeroen Bax, MD,a
Partho P. Sengupta, MD,e Philippe Pibarot, DVM, PHDb

ABSTRACT

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Up to 40% of patients with aortic stenosis (AS) present with a “discordant grading” usually referred to as “low-gradient

AS.” This article presents a step-by-step integrative approach overview of the utility, limitations, and complementary role

of the different imaging modalities for the assessment of AS severity with a special emphasis on the reconciliation of

discordant grading. The first step is to confirm the validity of echocardiographic measures of AS severity. For example,

hybrid imaging can combine left ventricular outflow tract area measured by 3-dimensional echocardiography or contrast

enhanced multidetector row computed tomography with flow velocities measured by Doppler. The next step is to

differentiate severe from non-severe AS with the use of low-dose dobutamine stress echocardiography, especially in

patients with low left ventricular ejection fraction, low-flow, low-gradient AS. Aortic valve calcium scoring measured by

noncontrast multidetector row computed tomography is preferred in patients with low-gradient AS and preserved left

ventricular ejection fraction as well as in those with inconclusive results with dobutamine stress echocardiography.

(J Am Coll Cardiol Img 2019;12:267–82) © 2019 by the American College of Cardiology Foundation.

A ccurate assessment of aortic stenosis (AS)severity is key for optimal therapeutic deci-sion making. Doppler echocardiography is

the primary imaging modality used for the gradingof AS severity and the main criteria proposed in theguidelines to define severe AS are peak aortic jetvelocity $4 m/s, mean transvalvular gradient (MG)$40 mm Hg, aortic valve area (AVA) <1.0 cm2, andindexed AVA <0.6 cm2/m2 (1,2). In patients with highgradient, there is no ambiguity about the severity ofAS, and aortic valve replacement (AVR) is indicatedif the patient presents with symptoms and/or left ven-tricular (LV) systolic dysfunction; however, up to 40%of patients present with “discordant grading” (i.e. anAVA that is severe [<1.0 cm2 and <0.6 cm2/m2] butwith a low gradient/velocity [<40 mm Hg/<4 m/s]) on

m the aDepartment of Cardiology, Leiden University Medical Centre,

rdiologie et de Pneumologie de Québec/Québec Heart and Lung Institu

lumbia University Medical Center/NY Presbyterian Hospital, New York

alth System, Morristown, New Jersey; and the eWest Virginia Universit

ginia. The Department of Cardiology of the Leiden University Medical Ce

tronik, Boston Scientific, Edwards Lifesciences, GE Healthcare, and M

earch grant from Edwards Lifesciences for echocardiography core labo

lve replacement. Dr. Delgado has received speaker fees from Abbott Vasc

earch contracts with Edwards Lifesciences LLC and Medtronic; and is an

t they have no relationships relevant to the contents of this paper to dis

nuscript received August 17, 2018; revised manuscript received Novembe

Doppler echocardiography (3,4). This discordantgrading pattern, also referred to as “low-gradient AS,”raises uncertainty about the actual severity of thestenosis and thus about the therapeutic managementof the patient if symptomatic. This low-gradient ASentity includes 3 subtypes: 1) classical low-flow (strokevolume index: <35 ml/m2), low-gradient with reducedLV ejection fraction (LVEF <50%); 2) paradoxicallow-flow, low-gradient AS with preserved LVEF; and3) normal-flow (stroke volume index: >35 ml/m2),low-gradient AS. Among patients with low-gradientAS, a substantial proportion (30% to 70%) have truesevere AS and may benefit from AVR (3,4). It is thuscrucial to confirm AS severity in patients withlow-gradient AS, particularly if they present withsymptoms or LV systolic dysfunction.

Leiden, the Netherlands; bInstitut Universitaire de

te, Université Laval, Québec City, Québec, Canada;

, New York; dMorristown Medical Center/Atlantic

y Heart and Vascular Institute, Morgantown, West

nter has received unrestricted research grants from

edtronic. Drs. Hahn and Pibarot have received a

ratory analyses in the field of transcatheter aortic

ular. Dr. Gillam oversees core laboratories that have

advisor to Philips. All other authors have reported

close.

r 12, 2018, accepted November 14, 2018.

AB BR E V I A T I O N S

AND ACRONYM S

2D = 2-dimensional

3D = 3-dimensional

AA = ascending aorta

AS = aortic stenosis

AU = arbitrary unit

AVA = aortic valve area

AVC = aortic valve calcium

AVR = aortic valve

replacement

BSA = body surface area

DSE = dobutamine stress

echocardiography

ELI = energy loss index

LV = left ventricular

LVEF = left ventricular

ejection fraction

LVOT = left ventricular

outflow tract

MDCT = multidetector

computed tomography

MG = mean transvalvular

pressure gradient

TTE = transesophageal

echocardiography

J A C C : C A R D I O V A S C U L A R I M A G I N G , V O L . 1 2 , N O . 2 , 2 0 1 9 Delgado et al.F E B R U A R Y 2 0 1 9 : 2 6 7 – 8 2 Assessing Discordant Grading of AS Severity

269

This article presents an overview of the utility,limitations, and complementarity of the differentimaging modalities for the assessment of AS severitywith a special emphasis on the issue of discordantgrading with echocardiography and betweenmodalities.

The first section of this article is dedicated to theDoppler echocardiographic assessment of AS severityand particularly to the pitfalls in the measurement ofAVA and MG. The low-gradient AS pattern mayindeed be related to an underestimation of AVA and/or an underestimation of MG with echocardiography.This section also covers the role of stress echocardi-ography for the confirmation of AS severity in pa-tients with low-gradient AS (Central Illustration).

The second section describes the utility of hybrid(i.e., multidetector computed tomography [MDCT]Doppler) imaging to corroborate AVA measurementand AS grading severity (Central Illustration). AVA isthe echocardiographic parameter the most prone totechnical errors; the main pitfall in the assessment ofthis parameter is the underestimation of the LVoutflow tract (LVOT) area by 2-dimensional (2D)echocardiography. With hybrid imaging, the LVOTarea is obtained by contrast MDCT. The third sectionpresents the role of aortic valve calcium (AVC) scoringby noncontrast MDCT to confirm AS severity andgrading in patients with low-gradient AS (CentralIllustration).

THE CASE OF DOPPLER

ECHOCARDIOGRAPHY

Since initial studies validating Doppler-derived gra-dients and the continuity equation for calculation ofAVA (5–8), echocardiography has been recognized asthe modality of choice for assessing AS severity. Itsfirst-line status is confirmed in current AmericanCollege of Cardiology/American Heart Association(ACC/AHA) and European Society of Cardiology (ESC)guidelines for valvular heart disease and the 2017appropriate use criteria for multimodality imaging invalvular heart disease (1,2,9). Doppler echocardiog-raphy is typically the workhorse approach, althoughtransesophageal, exercise, and pharmacologic stresstechniques may also be helpful and 3-dimensional(3D) echocardiography is playing an increasinglyimportant role, particularly in transcatheter AVR.

Echocardiography provides a wealth of anatomicand functional information; is free of radiation; iswidely available, lending itself to bedside applica-tions; and is relatively inexpensive. Its widespreaduse for decades has provided a wealth of prognosticinformation that is available with no other technique.

In addition to assessing hemodynamics andcalculating AVA, this noninvasive test as-sesses valve morphology as well as the car-diac response to AS, including LV remodelingand both systolic and diastolic function,mitral regurgitation, and pulmonary hyper-tension. Concomitant changes in the struc-ture of the proximal aorta are alsoidentifiable. According to ACC/AHA guide-lines (1,10), cardiac catheterization should beused to assess AS severity in the setting ofinadequate echocardiographic assessment ordiscrepant clinical/echocardiographic dataonly.

ROUTINE ECHOCARDIOGRAPHIC

MEASURES OF AS SEVERITY

Several echocardiographic parameters can beused to evaluate the hemodynamic severityof AS; how to obtain these parameters is well-described in joint American and Europeanguidelines and will not be detailed here (11).These can be divided into 2 general categories(Table 1): flow-dependent and “relativelyflow-independent.” Flow-dependent mea-surements are obtained from continuous-
wave Doppler across the stenotic aortic valve andinclude peak jet velocity as well as peak and MGsderived using the Bernoulli equation with severe ASassociated with peak and mean gradients $64and $40 mm Hg, respectively, and a peak jetvelocity $4 m/s. The most widely used “relativelyflow-independent” measurements include AVAcalculated from the continuity equation (12–15) andthe Doppler velocity index. The continuity equationcalculation of AVA uses the conservation of massprinciple and normalizes for flow resulting in an ac-curate assessment of stenosis in different flow states.These parameters are not strictly flow independent,but they are much less flow dependent than the MG orpeak jet velocity. Table 2 shows the basic measure-ments required to assess both flow-dependent andflow-independent parameters.
A velocity of 4 m/s correlates well with a MG of 35to 40 mm Hg (16), but a peak jet velocity of 4.0 m/sand MG of 40 mm Hg correlate by continuity equationand Gorlin equation to an AVA closer to 0.8 cm2 ratherthan the 1.0 cm2 cutoff used to define severe AS incurrent guidelines (16). Nonetheless, numerous out-comes studies have shown that a continuity equationvalve area of <1.0 cm2 predicts outcomes; thus, AVAremains a reliable tool for diagnosis and managementof these patients (17,18). Some authors have

CENTRAL ILLUSTRATION Algorithm for the Multimodality Imaging Assessment of Patients WithDiscordant Grading of AS Severity at Doppler Echocardiography

DISCORDANT GRADING - LOW GRADIENT AS at TTEAVA ≤1.0 cm2, AVAi <0.6 cm2/m2, MG <40 mm Hg (See Tables 1 & 2)

CONFIRM ACCURACY OF TTE MEASUREMENTS(See Table 3)

CORROBORATE AVA BY HYBRID MDCT-DOPPLER IMAGINGHybrid AVA <1.2 cm2 (See Figure 2)

CONFIRM AS SEVERITY

STEP 1:

STEP 2:

STEP 3:

LOW GRADIENT ASwith PRESERVED LVEF

AORTIC VALVE CALCIUMSCORE BY MDCT:

Severe AS:AVC ≥2000 AU in men,

≥1200 AU in women(See Figure 3)

(if stress echois inconclusive)

*

DOBUTAMINE STRESS ECHOSevere AS:

MG ≥40 mm Hgand AVA <1.0 cm2

Projected AVA <1.0 cm2

LOW GRADIENT ASwith REDUCED LVEF

Rest Stress

Delgado, V. et al. J Am Coll Cardiol Img. 2019;12(2):267–82.

AS ¼ aortic stenosis; AU ¼ arbitrary unit; AVA ¼ aortic valve area; AVC ¼ aortic valve calcification; AVAi ¼ indexed aortic valve area; MDCT ¼ multidetector computed

tomography; MG ¼ mean transvalvular pressure gradient; TTE ¼ transthoracic echocardiography.

TABLE 1 Echocardiographic Parameters Used to Assess the Severity of Aortic Stenosis

Mild Moderate Severe

Structural assessment � Mild leaflet calcification orthickening with reduction insystolic motion

� Mild-to-moderate leaflet calcificationof a bicuspid or tricuspid valve with somereduction in systolic motion or

� Rheumatic valve changes with commis-sural fusion

� Severe leaflet calcification or congenitalstenosis with severely reduced leafletopening

� Planimetered AVA <1.0 cm2

Quantitative parameters(flow-dependent)

Peak velocity 2.0-2.9 m/s 3-3.9 m/s $4 m/s

MG <20 mm Hg 20-39 mm Hg $40 mm Hg

Quantitative parameters(flow-independent)

Doppler index >0.5 0.25-0.5 <0.25

AVA >1.5 cm2 1.0-1.5 cm2 <1.0 cm2

AVA index* >0.90 cm2/m2 0.60-0.90 cm2/m2 <0.6 cm2/m2†

*Indexing the valve area is particularly important in smaller patients with height <135 cm (65 in.), BSA <1.5 m2, or BMI <22 kg/m2. †Cutoff used in setting of BMI <30 kg/m2. In the setting of aBMI $30 kg/m2, a cutoff #0.5 cm2/m2 may be more appropriate.

AVA ¼ aortic valve area; BMI ¼ body mass index; BSA ¼ body surface area; MG ¼ mean gradient.



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TABLE 2 Measurements and Calculations Required to Assess Hemodynamic Severity of Aortic Stenosis

Parameter Example Calculation

LVOT diameterMeasured at or just below the level of the aortic

annulus (A). In the setting of ectopic calcification inthe LVOT or annulus, the diameter measurementshould ignore this calcium and measure to the baseof the anterior mitral valve leaflet (B).

LVOT area ¼ 0.785 �(diameter)2

Pulsed wave spectral DopplerLaminar flow just proximal to flow acceleration. The

modal velocity should be traced to measure theLVOT VTI and not the faint higher velocity profile.(A, red line) An incorrectly traced Doppler signal.Reducing the gain or increasing the reject willresult in a (B, green tracing) modal velocity spec-tral profile.

LVOT SV ¼ LVOT area �LVOT VTI

Continuous wave spectral DopplerPerformed from any imaging window that obtains the

highest velocity, with the densest, most uniformcontinuous wave spectral profile. (A) Apical win-dows may not yield a higher velocity than a(B, right parasternal window) nonapical window.Peak velocity, peak and MG, and aortic VTI aremeasured.

Aortic valve area ¼ LVOT SVO aortic VTI

Doppler velocity index ¼LVOT VTI O aortic VTI

Continuous wave spectral Doppler, ejection dynamicsAT >110 ms and AT/ET ratio >0.36 suggests severe AS

Ratio ¼ AT/ET

AT ¼ acceleration time; ET ¼ ejection time; LVOT ¼ left ventricular outflow tract; MG ¼ mean gradient; SV ¼ stroke volume; VTI ¼ velocity time integral.


271

suggested decreasing the AVA cutpoint from 1.0 to0.8 cm2 to reconcile the AVA/MG cutpoints andtherefore reduce the proportion of patients withdiscordant grading (19–21). Several recent studiesreported however that patients with AVA between0.8 and 1.0 cm2 and low gradient are at increased riskof cardiac events and exhibit improved survival withAVR (22,23). It thus appears preferable to maintainthe status quo with regard to AVA (<1.0 cm2) and MG($40 mm Hg) cutpoint values of AS severity and usethe AVA threshold as a sensitive marker and the MGthreshold as a specific marker of severe AS.

There are a number of reasons for discordancebetween velocities and gradients and AVA. A sys-tematic assessment of the cause for discordance mayuncover errors that, when corrected, result inconcordant parameters. The 2 most frequent reasonsfor discordance are the incorrect measurement ofeither velocities or LVOT diameter. Current guide-lines recommend a multiwindow approach to imagingthe peak transaortic velocities (11). Failure to imagefrom nonapical windows may result in underestima-tion of the peak velocities in up to 50% of cases, as

reported in 1 study (24). The more acute the aorticroot angulation as measured by 2D echocardiography,the more likely a nonapical window will yield thehighest values of peak velocity. In fact, if only apicalwindows were used, 8% of patients in that studywould have been misclassified from high-gradientsevere AS to low-gradient severe AS, and another15% with severe AS (AVA: <1.0 cm2) were mis-classified as having moderate AS (AVA: >1.0 cm2).

Underestimation of the LVOT diameter contributessignificantly to discordant AS parameters. Althoughthe guidelines allow measurements of the LVOTdiameter to be performed up to 1.0 cm apical to theannulus, historically, the LVOT measurement hasbeen taken at the annulus (5,13,14), and outcomesdata upon which the guidelines are based use thismeasurement to calculate AVA (17,18). Using theannulus also makes sense knowing the relevantanatomy. The aortic annulus is primarily composed ofthe fibrous interleaflet trigones, (25) and varies lesswith the cardiac cycle (in fact, becoming more circularin systole) and thus can be more accurately andreproducibly measured (5,26,27). At a distance of 0.5

TABLE 3 Checklist for the Verification of the Accuracy of the Measurement of LVOT Area for the Calculation of Aortic Valve Area for the Assessment of

Aortic Stenosis Severity

List of Actions Interpretation and Caveats

Use the mid-systolic image that bisects the LVOT in its largest dimension(i.e., the plane that bisects the right coronary cusp hinge point anteriorly andthe interleaflet triangle between the left and noncoronary cusps posteriorly)

If 2 leaflets are well visualized both anteriorly and posteriorly, this may not be theplane providing the largest diameter and the LVOTd may be underestimated fromthis view

Measure the LVOTd at the aortic annulus (not 0.5-1.0 cm below) Look for the hinge point of the right coronary cusp anteriorly and measure to themitral-aortic curtain, perpendicular to the long-axis of the aorta

In presence of LVOT ectopic calcification, use the plane that bisects the largestdiameter but excludes the calcification from the LVOTd measurement

Calculate predicted LVOTd using the formula:LVOTd ¼ (5.7 � BSA) þ 12.1

If the LVOTd measured at the annulus is 2 mm smaller or larger than the predictedLVOTD, suspect error in the measurement of LVOTD

Note: the formula may overestimate the LVOTd in obese individuals

Calculate DVI using the formula:DVI ¼ VTILVOT/VTIAoV

If AVA is <1.0 cm2 and indexed AVA <0.6 cm2/m2, but DVI is >0.25, suspectunderestimation of LVOTd

Corroborate calculation of LVOT area obtained by 2D TTE with other modalities3D TTE or TEE

MDCT

Accuracy of 3D TTE is determined by the echogenicity of the patientMDCT planimetered LVOT area may be larger than LVOT area calculated using a

linear diameter

Corroborate measure of LVOT SV by other methodsBiplane Simpson

3D TTE volumes

Biplane Simpson may underestimate SVAccuracy of 3D TTE is determined by the echogenicity of the patient

Corroborate measure of AVA by other methodsPlanimetry of AVA by TTE or TEE

Hybrid MDCT-Doppler: LVOT area is measured by MDCT and used inthe continuity equation to calculate the “hybrid” AVA

The “anatomic” AVA measured by planimetry is often larger than the “effective” areameasured by the continuity equation because of the flow contraction that occursdownstream of the valve orifice

The hybrid method systematically measures larger AVAs and therefore a larger cutoffvalue (i.e., <1.2 cm2 vs. 1.0 cm2) should be used to define severe aortic stenosis (18)

In presence of discordant grading (small AVA with low gradient): calculateindexed AVA using the formula:AVA/BSA (in cm2/m2)

A small AVA in a small patient may correspond to a moderate AS. In such patients, theAVA is <1.0 cm2 suggesting severe AS, but the indexed AVA is >0.6 cm2/m2 with alow gradient (<40 mm Hg) suggests that the stenosis is in fact nonsevere

Note: The indexed AVA may overestimate the severity of AS in obese patients

Adapted with permission from Hahn et al. (29).

3D ¼ 3-dimensional; AVA ¼ aortic valve area; BSA ¼ body surface area; DVI ¼ Doppler velocity index; LVOTd ¼ left ventricular outflow tract diameter; MDCT ¼ multidetector computed tomography;SV ¼ stroke volume; TTE ¼ transthoracic echocardiography; TEE ¼ transesophageal echocardiography; VTIAoV ¼ aortic valve flow velocity-time integral; VTILVOT ¼ left ventricular outflow tract velocity-timeintegral; other abbreviations as in Table 2.



272

to 1.0 cm apical to the annulus, one-half of the LVOTis composed of septal myocardium of varying thick-ness and function and the other one-half by themitral-aortic curtain. Caballero et al. (28) found thatmeasurements at the level of the annulus resulted inthe best correlation between 2D and 3D transesophagealechocardiographic dimensions. A checklist for deter-mining the accuracy of the LVOT measurement wasrecently published and is reproduced in Table 3 (29).

The use of 3D imaging has been proposed to pro-vide a more accurate measure of LVOT cross-sectionalarea for calculating AVA by the continuity equation(30,31). Many of these studies, however, compareAVA calculated using the continuity equation, whichmeasures the effective orifice area (or vena contracta)with an anatomic orifice area (i.e., planimetered AVAon computed tomography). The effective orificearea is expected to be smaller than the anatomicarea; differences can be explained by physiology.Numerous outcomes studies have shown that acontinuity equation valve area <1.0 cm2 predictsoutcomes; thus, AVA by standard Doppler echocar-diography remains a reliable tool for diagnosis andmanagement of these patients (17,18). Because the

greatest error in the AVA calculation is the squaredLVOT diameter measurement, Doppler velocity in-dex, which incorporates only transvalvular and LVOTvelocities, is a useful alternative (31–33). If the AVAis <1.0 cm2 but the Doppler velocity index is >0.25,one should suspect an underestimation of LVOTdiameter and reassess this measure. The Dopplervelocity index also has some limitations, however,with the main 1 being that it is dependent on LVOTsize (26). Hence, an index >0.25 does not necessarilyexclude the presence of a severe AS if the LVOTdiameter <2.0 cm.

In addition to measurement or acquisition errors,understanding the physiologic requirements of bodysize may also explain some discordant measure-ments. Because small-sized patients may not requirethe same amount of cardiac output as larger patients,the American Society of Echocardiography recom-mends indexing the valve area by body surfacearea (BSA), particularly in patients with a height<135 cm (65 inches), BSA <1.5 m2, or body massindex <22 kg/m2 (11). The ACC guidelines use anindexed AVA #0.6 cm2/m2 to define severe AS, andrecent studies suggest that for all body sizes,


273

indexing to the BSA (and not body mass index)effectively removes the confounding effect of bodysize on the calculation of AVA (34). This same groupshowed, however, that using an indexed AVA #0.6cm2/m2 increased the prevalence of severe AS,particularly in patients with a BSA >1.75 m2, withoutimproving the predictive accuracy of AVA for aorticvalve–related events and cardiovascular death (35). Arecent study showed that in a population of smallpatients (mean BSA: 1.50 � 0.15 m2), indexed AVAwas predictive of outcomes and the event-free sur-vival of patients with an indexed AVA $0.6 cm2/m2

was better than that for those with an indexedAVA <0.6 cm2/m2 (86% vs. 41% at 3 years; p < 0.01)(36). Others have suggested that an indexedAVA #0.5 cm2/m2 may be a more appropriate cutoffvalue for severe AS in most patients (26,35). Furtherstudy is clearly warranted to understand the role ofindexing for body size and whether a single cutoffvalue can be used for all patients.

When the sources of possible error in measurementof velocity/gradient or LVOT, as well as the contri-bution of body size, have been eliminated and thereremains discordance with low gradient but a smallAVA, then the most common etiology for this scenariois low flow.

Semiquantitative continuous-wave Doppler parame-ters of the ejection dynamics transvalvular velocitymay also be useful to corroborate stenosis severity,particularly in patients with low-gradient AS(Table 2). An acceleration time >110 ms or accelera-tion time/LV ejection time ratio >0.36 has beenassociated with hemodynamically severe AS andworse outcomes (37).

STRESS ECHOCARDIOGRAPHY FOR AS WITH

DISCORDANT MEASURES OF SEVERITY

Although exercise stress testing is contraindicated inpatients with symptomatic AS, pharmacologic stressechocardiography plays an important role, particu-larly in those with a low gradient (<40 mm Hg)despite AVAs in the severe range.

AS is a hemodynamically heterogeneous entity.Current ACC/AHA guidelines have subdivided thesevere, symptomatic AS group of patients into 3separate categories: high-gradient AS; “classical”low-flow, low-gradient AS with reduced LVEF; andlow-gradient AS with normal LVEF. The latter groupof patients can be further divided on the basis ofpreserved (normal-flow) versus reduced (paradoxicallow-flow) stroke volume using a stroke volume index

cutoff of 35 ml/m2. The stroke volume index is a goodmarker of LV pump function and outflow and is apowerful predictor of prognosis both prior and afterAVR. The mean transvalvular flow rate (stroke vol-ume divided by ejection time) is also important froma diagnostic standpoint because the mean gradient isnot only directly related to the stroke volume but alsoinversely related to the ejection time (inverselyrelated). A low-flow state as defined by a mean flowrate <200 ml/s is associated with worse prognosis andwith higher likelihood of “pseudo-moderate”gradient and/or pseudo-severe AVA (38–40).

Dobutamine stress echocardiography (DSE) is animportant tool in patients with classical (low LVEF)low-flow, low-gradient AS to assess the presence offlow reserve and to differentiate true versus pseudosevere stenosis (Central Illustration). DSE is, however,not recommended for patients with paradoxical(preserved LVEF) low-flow, low-gradient AS.Although AVA is relatively flow independent, whenflow is reduced, anatomically narrowed valves mayfail to reach their maximal potential opening. DSE isthus used to increase the transvalvular flow ratewhile avoiding myocardial ischemia. With normalizedflow, a patient with true severe AS will increasethe mean gradient and continue to have a smallcalculated AVA. If the patient has pseudo-severe AS,the valve area will increase with gradients remaininglow.

In the setting of LVEF <50%, the goal of DSE is todetermine if AVA will increase with higher (by at least20%) transvalvular flow rates and improved systolicperformance. Studies have shown that LV flowreserve resulting in an increase in strokevolume $20% is associated with better outcomes withAVR compared with medical therapy (41,42). Subse-quent studies have shown that although patientswithout flow reserve on DSE have high operative andshort-term mortality, survivors still benefit from AVR,with significantly lower 5-year mortality comparedwith medical management (43). Recent studies incontemporary surgical and transcatheter AVR series,however, reported low procedural and 1-year mor-tality rates in patients low LVEF, low-flow, low-gradient AS and did not find any association betweenflow reserve on DSE and outcomes (44–46). Hence,the main interest and purpose of DSE is to confirm thepresence of severe AS and the assessment of flowreserve appears to have fewer clinical implicationsnowadays.

The LV myocardial response to DSE, however, isnot always consistent, and suboptimal increases in

FIGURE 1 Measurement of the LVOT by Echocardiography

A B

LVOT 19 mm LVOT 17 mm

LVOT 19 mm

(A) On conventional 2-dimensional transthoracic echocardiography, from the parasternal long-axis view, the aortic valve is zoomed in to

obtain a better view of the LVOT. In the zoomed view, the diameter of the LVOT can be measured (double arrowhead). Two-dimensional

echocardiography assumes a circular anatomy of the LVOT. (B) The LVOT, however is oval, and with 3-dimensional transthoracic echocar-

diography, the off-axis planes can be avoided by placing the plane that bisects the LVOT correctly. (B, top) The orthogonal plane bisects the

LVOT in the maximum anteroposterior diameter, whereas at the bottom, the plane bisects the LVOT off-axis, leading to smaller LVOT

diameter in the orthogonal parasternal long-axis view. This leads to a significant underestimation of the aortic valve area. LVOT ¼ left

ventricular outflow tract.



274

flow rate may prevent the accurate interpretation ofthis test. To overcome this limitation, the projectedAVA at a standardized normal flow rate has beensuggested as an alternative approach (44).

PARADOXICAL LOW-FLOW, LOW-GRADIENT AS.

In paradoxical low-flow, low-gradient AS with pre-served LVEF, a number of physiologic situationscan result in low flow in the setting of normalLVEF: tachycardia (47), bradycardia (48), hyperten-sion (49–51), small ventricular cavity (52), severediastolic dysfunction, severe mitral or tricuspid valvedisease (53), pulmonary hypertension, and rightventricular dysfunction (54). The ACC/AHA guide-lines do not advocate using DSE with LVEF >50%.Recent studies suggest that quantitative valve cal-cium scoring by MDCT may be useful, as discussed ina later section (55–57).

Patients with severe AS but normal flow and lowgradient are particularly vexing. This discordancein parameters may be related to inherent in-consistencies in the accepted grading scheme becausean AVA of 1.0 cm2 actually corresponds to mean gra-dients of 30 to 35 mm Hg (not 40 mm Hg) in normalflow conditions or to reduced arterial compliance thatresults in faster and earlier arterial pulse wavereflection from the periphery and ensuing dampeningof the transvalvular gradients. The normal-flow, low-gradient entity may also be related to measurementerrors that result in underestimation of stroke volumeand thus AVA and/or underestimation of gradient orfailure to account for the importance of body size. It isalso possible that patients with “normal flow/lowgradient” have normal stroke volume in the setting ofa prolonged ejection time, resulting in a low gradient.

FIGURE 2 Measurement of AVA by Hybrid Imaging

A C

E F

DB

LVOT 21 mm Mean gradient 36 mmHg Svi 38 ml/m2

AVA 0.93 cm2

487.7 HU ± 80.0446 mm2

AVA 0.49 cm2

Example of a patient with low-gradient normal flow severe aortic stenosis, with a calculated AVA of 0.49 cm2 based on 2-dimensional transthoracic echocardiography.

(A) Tricuspid aortic valve with limited opening. (B) The LVOT is measured on a zoomed parasternal view. (C, D) The mean transvalvular gradient and the pulsed wave

recording of the LVOT and stroke volume index, respectively. (E) After aligning the multiplanar reformation planes on the multidetector row computed tomography

data, (F) the cross-sectional area of the LVOT can be measured and included in the continuity equation resulting in an AVA of 0.93 cm2. AVA ¼ aortic valve area;

Svi ¼ stroke volume index; other abbreviation as in Figure 1.


275

OTHER MEASURES OF AS SEVERITY. A less widelyused measure of AS severity is aortic valve resistance,which is the pressure gradient/flow rate ratio. Byechocardiography, it is simply calculated as: 1.333�4Vpeak2/(area LVOT�velocity LVOT), in which Vpeakindicates peak velocity. As such, valve resistance is afunctional index of hemodynamic impairment andmay be less flow dependent than AVA (58). The en-ergy loss index (ELI) is another measure that attemptsto account for the total fluid mechanical energy lossrelated to both AVA and ascending aorta area (59).The ELI is calculated as: ELI ¼ [AVA � AA/AA � AVA]/BSA, where AA is the cross-sectional area of theascending aorta. Similar to AVA, it is less flowdependent than gradient or peak velocity, takes intoaccount pressure recovery, and is roughly equivalentto AVA measured by catheter (60). Using ELI, a

substudy of the SEAS (Simvastatin Ezetimibe in AorticStenosis) trial reclassified 47.5% of patients from se-vere to nonsevere AS (61). The energy loss is mostsignificant in patients with small aortas (<30 mm). AnELI #0.5 to 0.6 cm2/m2 is consistent with severe AS(61,62).

WHEN ARE COMPLEMENTARY MODALITIES FOR

ASSESSING AS SEVERITY MOST HELPFUL?

When imaging features, peak, MGs, and AVA areconsistent and unequivocally identify AS as severe,complementary imaging modalities are typically notrequired other than to plan transcatheter in-terventions. Similarly, in the patient with low-flow,low-gradient severe AS in whom stroke volumeincreases with an intervention, typically dobutamine,and gradients rise correspondingly, additional

FIGURE 3 Utility of Aortic Valve Calcification Score Measured by MDCT to Predict Hemodynamic and Clinical Outcomes in AS

7

6

5

4

3

Peak

Aor

tic J

et V

eloc

ity, (

m/s

)

Aortic Valve Calcification, (AU)

Associations Between Aortic Valve CalcificationLoad and Peak Aortic Jet Velocity

A B

D

Thresholds Identifying Severe Aortic Stenosis inWomen and Men

Effects of AVC Burden on Survival in Patientswith AS Under Medical Treatment

C Impact of AVC Burden on Mortality in Patients with AS,by Sex

WOMEN MEN

Follow-Up (Years)

Surv

ival

Unde

r Med

ical

Tre

atm

ent,

(%)

2

10 2000

Women; r = 0.75; p < 0.0001Men; r = 0.74; p < 0.0001

Pcov < 0.0001

4000 6000 8000 10000

100

Women

Men

Sex

0.91

0.92

-

-

0.90

0.89

AUC

1,274 AU

1,377 AU

1,200 AU

2,000 AU

2,065 AU

2,062 AU

AVC Thresholds

Clavel 2014

Reference

Pawade 2018

ESC/EACTS Guidelines

ESC/EACTS Guidelines

Clavel 2014

Pawade 2018

80

60

40

20

00 1 2 3 4 5

417 300

No193

41 ±6%

78 ±6%

p < 0.0001Adjusted p = 0.03

Severe AVC:101 70 50

377 125 65 32 18 13


Rela

tive

Risk

of M

orta

lity

4.000Clavel 2014 Pawade 2018

1.000

0.125

500010

001500

20002500

30003500

4000


Rela

tive

Risk

of M

orta

lity

4.000

1.000

0.125

500010

001500

20002500

30003500

4000

Yes

Clavel 2014 Pawade 2018

(A) AVC has been demonstrated to be lower in women than in men for the same AS severity, as measured by peak aortic jet velocity (69). (B) Sex-specific thresholds

have been derived and validated (57,70), (C) which have been confirmed by mortality studies (70,71) (D) in which severe AVC had an independent impact on mortality

(71). AS ¼ aortic stenosis; AU ¼ arbitrary unit; AUC ¼ area under the curve; AVC ¼ aortic valve calcification; EACTS ¼ European Association for Cardio-Thoracic Surgery;

ESC ¼ European Society of Cardiology.



276

imaging will not be required. As discussed next,however, complementary imaging modalities may behelpful in other scenarios of low-gradient AS. Inva-sive hemodynamic assessment by left heart cathe-terization may also be considered in patients withdiscordant or uncertain grading of AS severity onDoppler echocardiography; however, this method isnot without risk for the patients and does not obviatethe need for dobutamine stress to confirm AS severityin patients with low states.

THE CASE OF HYBRID

MDCT-DOPPLER IMAGING

Accurate and reproducible measurement of the LVOTwith 2D echocardiography remains challenging. The

LVOT has an oval rather than circular geometry, andits area is a key measurement in the grading of AS(Figure 1A). The anteroposterior diameter, which issmaller than the septal to lateral diameter (in thecoronal plane), is generally used to measure the LVOTarea by 2D echocardiography. It is difficult to ascer-tain, however, that the anteroposterior diameter isappropriately measured because off-axis views arenot infrequent and may lead to significant underes-timation of the diameter and subsequently underes-timate the stroke volume and AVA (Figure 1B). Thismay be particularly challenging in sequential echo-cardiograms performed for AS severity surveillance.Data acquisition with different ultrasound systemsand different operators may result in different LVOTdiameter measurements. To minimize the impact of

FIGURE 4 Echocardiographic and Tomographic Measurements in a Low-Flow, Low-Gradient Patient With AS and Preserved LV Ejection Fraction

A EMan - 69 years old — Low-Flow, Low-Gradient Aortic Stenosis

Ao Valve measurements:Vpeak: 2.7m/sVTI: 65.7cmMean Gradient: 18 mmHgAVA: 0.96cm2

LVOT measurements:

VTI: 20.1cmSV: 63.1mlSVi: 31.6ml/m2

LVOTd: 2.0cm

cm/s

-80

-240

-160

-320

55bpm75mm/s-120

-100

-80

-40

-20

-60

cm/s

55bpm75mm/s

Echocardiography:LV Ejection Fraction: 65%Stroke Volume Index: 31.6 ml/m2

Flow rate: 180 ml/s

Stroke VolumeLV ejection time

Flow rate =

Computed Tomography:Aortic Valve Calcification: 1306 AU

AVC density: 403 AU/cm2

D

B

FC

Aortic Valve Area: 0.96 cm2

Indexed Aortic Valve Area: 0.48 cm2/m2

Mean gradient: 18 mm Hg

A 69-year-old man with preserved LV ejection fraction. In the (A) parasternal short-axis and (B) long-axis views, the valve appears to be thickened and calcified. (B) The

LVOTd is measured at 2.0 cm. The (C) pulsed-wave and (D) continuous-wave Doppler measurements demonstrated a low MG and a small aortic valve area. The stroke

volume index is <35 ml/m2, demonstrating a low-flow state, which is confirmed by a mean transvalvular flow rate of 180 ml/s. (E, F) The noncontrast MDCT shows a

moderately calcified aortic valve, with an AVC at 1,306 AU. Even after dividing the AVC by the surface of the aortic annulus area (calculated with echocardiography),

the AVC density remained in the nonsevere range. LVOTd ¼ left ventricular outflow tract diameter; MG ¼ mean transvalvular pressure gradient; MDCT ¼ multi-

detector row computed tomography; SV ¼ stroke volume; Vpeak ¼ peak aortic jet velocity; VTI ¼ velocity-time integral; other abbreviations as in Figures 1 to 3.


277

this problem in the stroke volume and AVA calcula-tion, current recommendations advocate the use ofsame LVOT diameter over time (11).

The use of 3D imaging techniques including 3Dtransesophageal echocardiography (TTE), MDCT, orcardiac magnetic resonance permits the reconstruc-tion of the LVOT plane where the cross-sectional areacan be measured. By introducing this value of LVOTarea into the continuity equation, a “hybrid” AVA canbe obtained that may be helpful to corroborate ASseverity in patients with discordant grading on TTE(Central Illustration). Several studies have shown theimpact of using 3D planimetered LVOT area on thegrading of AS (18,63–65). Ng et al. (63) demonstrated,in a study including 53 patients with severe ASreferred for transcatheter AVR, that 2D TTE under-estimated significantly the LVOT area and AVA

compared with 3D TTE and MDCT. By introducing theLVOT area planimetered on 3D TTE or MDCT re-constructions into the continuity equation, 25% of thepatients would have been reclassified into moderateAS (using a cutoff value <1 cm2 to define severe AS)(63). In a subsequent study by O’Brien et al. (64),including 51 patients with severe AS, the use of MDCTLVOT planimetered area into the continuity equationled to significantly larger AVA compared with stan-dard Doppler echocardiography (0.86 � 0.28 cm2 vs.0.67 � 0.13 cm2; p < 0.001). The percentage of pa-tients with severe AS and congruent AVA <0.8 cm2

and Doppler velocity index #0.25 increased from 59%to 92% when using hybrid MDCT-Doppler imagingversus standard echocardiography (64). These resultswere confirmed and extended by Kamperidis et al.(65) in a study of 191 patients with severe AS and

FIGURE 5 Echocardiographic and Tomographic Measurements in a Normal-Flow, Low-Gradient Patient With AS and Preserved LV Ejection Fraction

A

E

Woman - 69 years old — Normal-Flow, Low-Gradient Aortic Stenosis

Ao Valve measurements:Vpeak: 3.4m/sVTI: 87.2cmMG: 28 mmHgAVA: 0.89cm2

AVAi: 0.49cm2/m2

LVOT measurements:

VTI: 24.7cmSV: 77.6mlSVi: 43.1ml/m2

LVOTd: 2.0cm

cm/s

-100

-200

-300

63bpm150mm/s

-120

-80

-40

40

-61.6cm/s

+61.6

cm/s

63bpm150mm/s

Echocardiography:LV Ejection Fraction: 70% Stroke Volume Index: 43.1 ml/m2 Flow rate: 259 ml/s

Mean gradient: 28 mm Hg Indexed Aortic Valve Area: 0.49 cm2/m2

Blood Pressure: 140/60 mm Hg — Arterial compliance 0.5 ml/mm Hg/m2

Computed Tomography:Aortic valve Calcification: 1377 AU

AVC density: 398 AU/cm2

D

B

FC

A 69-year-old woman with preserved LV ejection fraction. In the (A) parasternal short-axis and (B) long-axis views, the valve appears thickened and calcified. (B) The

LVOTd is measured at 2.0 cm. (C) The pulsed-wave and (D) continuous wave Doppler demonstrated a low MG and small AVA. The stroke volume index is >35 ml/m2,

suggesting a normal flow, which is confirmed by a flow rate at 259 ml/s. (E, F) The noncontrast MDCT show a severely calcified aortic valve, with an AVC at 1,377 AU.

Even after dividing the AVC by the surface of the aortic annulus (calculated at echocardiography), the AVC density remained in the severe range. AVAi ¼ indexed aortic

valve area; other abbreviations as in Figures 2 to 4.



278

preserved LVEF (88 patients with low gradient).When using hybrid MDCT-Doppler imaging (Figure 2),52% of patients with normal-flow, low-gradient ASand 12% of patients with low-flow, low-gradient ASwould have been reclassified into moderate AS (AVA>1 cm2). Finally, Clavel et al. (18) reported that thecorrelations between transthoracic echocardiographyAVA and hybrid MDCT-Doppler AVA with MG werecomparable (r ¼ 0.65 and r ¼ 0.61, respectively). Incontrast to previous studies, the use of hybrid MDCT-Doppler AVA did not result in significant reclassifi-cation of patients because the percentage of patientswith concordant AVA #1 cm2 and MG $40 mm Hg orAVA >1 cm2 and MG <40 mm Hg (moderate AS) usingMDCT was comparable to that obtained with echo-cardiography (70% vs. 74%, respectively; p ¼ 0.15)(18). Furthermore, the prognostic value of the hybridAVA was similar to that of the standard TTE AVA butthe optimal threshold to predict outcomes was larger

(1.2 vs. 1.0 cm2) (Table 3). This difference in the cutoffvalues is related to the fact that hybrid MDCT-Dopplerimaging systematically measures larger values of AVAcompared with echocardiography. For this reason,several investigators suggested to apply largerseverity cutpoint values (<1.2 cm2) to define severeAS when using hybrid imaging (18,66). Other mea-sures based on MDCT, such as the AVC score, mayalso help to corroborate the severity of AS, as dis-cussed in the next section (11,57).

THE CASE OF MDCT AVC SCORING

Quantitation of AVC load by noncontrast MDCT maybe helpful in patients with discordant grading ofAS severity on echocardiography or other imagingmodalities (Central Illustration). AVC scoring by non-contrast MDCT has the advantage of being feasible inalmost all patients; it is independent of


279

hemodynamics and, in particular for transvalvularflow, does not require any contrast or stress agent andis associated with low radiation exposure (<2 mSV).

The method used to assess AVC is the Agatstonmethod described for coronary artery calcificationevaluation in 1990 (67). Briefly, the software iden-tifies as calcification any area of 4 adjacent pixelswith density >130 Hounsfield units. The operator canthen manually select areas of calcification locatedwithin the aortic valve cusps. Measurement of AVCload by noncontrast MDCT is highly reliable andreproducible. Indeed, there is a strong correlationbetween AVC measured by MDCT and the content ofcalcium measured directly in explanted aortic valves(68); moreover, the intraobserver and interobservervariability of AVC measurement is excellent (w5%)(68,69).

AVC correlates well with the hemodynamicseverity of AS (56,68); however, until recently, thesignificant overlap in AVC between patients with he-modynamically severe and those with nonsevere ASmade its implementation difficult in clinical practice.This conundrum has been resolved with the demon-stration that women have a lower AVC load than menfor the same hemodynamic AS severity (Figure 3) (69).This finding led to the derivation of sex-specificthresholds of AVC for the identification of severeAS. Acknowledging this, the 2017 ESC guidelinesrecommend using different cutoff values of AVC toidentify severe AS in women ($1,200 arbitrary units[AU]) and in men ($2,000 AU) (2). The guidelines alsopropose thresholds beyond which the stenosis is verylikely severe ($1,600 AU in women and $3,000 AU inmen) and thresholds below which the stenosis is verylikely not severe (<800 AU in women and <1,600 AUin men). AVC may also be indexed for the cross-sectional area of the aortic annulus to calculate theAVC density. This indexing for aortic annulus, how-ever, does not reconcile the sex-related differences inthe severity thresholds; an AVC density $300 AU/cm2

in women or $500 AU/cm2 in men suggest severe AS.These thresholds of AVC and AVC density wereinitially proposed by Clavel et al. (57) and have beenrecently confirmed in a multicenter study (70)(Figure 3). Moreover, the use of different scanners forimage acquisition and different software for imageanalysis is reported not to have any significant effecton thresholds levels or accuracy of AVC (area underthe curve: $0.89) to identify severe AS (57,70). Thethresholds of AVC have also been validated byoutcome studies demonstrating that patients withsevere AVC experience an excess mortality undermedical management (Figure 3) (70,71). Moreover,

AVC load has prognostic value over clinical andechocardiographic assessment to predict both ASprogression rates and need for AVR (71,72), whichmay help in determining the optimal timing forintervention.

The 2017 ESC guidelines (2) recommend using theAVC measured by noncontrast MDCT to confirm ASseverity in: 1) patients with low LVEF, low flow, lowgradient in whom DSE remains inconclusive and 2)patients with low-gradient AS and preserved LVEF.Figures 4 and 5 present illustrative cases of patientswith paradoxical low-flow, low-gradient AS andnormal-flow, low-gradient AS in whom MDCT-derived AVC was used to confirm AS severity.

As with any imaging modality, the MDCT AVCscore is not a perfect method to assess AS severity.Indeed, this parameter is also subject to measure-ment errors and may underestimate AS severity,particularly in younger women with bicuspid AS (73).In such patients, the fibrotic valvular burden, which isnot captured by MDCT, is likely the main determinantof AS hemodynamic severity.

CONCLUSIONS

Up to 40% of patients present with a discordantgrading of AS (i.e., small AVA and low gradient) atDoppler echocardiography. In these patients, stenosisseverity remains uncertain and echocardiography andadditional imaging modalities may be required toconfirm AS severity and eventual indication for AVR.

The first step in these patients with discordantgrading is to confirm the validity of the echocardio-graphic measurements as described in the beginningof this article (Central Illustration). 1 of the mainsources of errors in stroke volume and AVA estima-tion by transthoracic echocardiography is the mea-surement of the LVOT area (Tables 2 and 3).

The LVOT cross-section is often elliptical; in suchcases, 2D echocardiography, which measures thesmaller diameter of the ellipse, may underestimatethe LVOT area. If the patient still harbors discordantgrading after ruling out measurement errors in theechocardiographic parameters, the second step is toperform hybrid imaging combining LVOT areameasured by contrast-enhanced MDCT or 3D echo-cardiography with flow velocities measured byDoppler to corroborate the measurement of AVA(Central Illustration). As previously noted, however,given that hybrid MDCT-Doppler imaging systemat-ically measures larger values of AVA compared withechocardiography, some studies suggest that largerseverity cutpoint values should be used to define



280

severe AS when using hybrid imaging <1.2 cm2

(18,66).If discordant grading of AS (i.e., small AVA with

nonsevere gradient) persists after step 2, the nextstep (step 3) is to confirm stenosis severity usingother imaging modalities (Central Illustration): 1) low-dose DSE may be used especially in patients with lowLVEF, low-flow, low-gradient AS; 2) AVC scoring bynoncontrast MDCT may be used in patients with low-gradient AS and preserved LVEF as well as in thosewith inconclusive results with DSE. This method isbecoming 1 of the preferred approaches to confirm ASseverity in low-gradient AS and it is now recom-mended in the 2017 European guidelines for thispurpose (2).

There is no single modality and parameter able toaccurately grade AS severity in all patients. In patientswith concordant grading with transthoracic echocardi-ography, no other imaging modality is required toguide therapeutic management. In patients withdiscordant grading, however, a step-by-step integrativeapproach that includes several imaging modalities andparameters should be considered to confirm ASseverity and the need for AVR.

ADDRESS FOR CORRESPONDENCE: Dr. PhilippePibarot, Institut Universitaire de Cardiologie et dePneumologie de Québec, 2725 Chemin Sainte-Foy,Québec City, Québec G1V-4G5, Canada. E-mail:[email protected].

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KEY WORDS aortic stenosis, aortic valvereplacement, computed tomography,Doppler echocardiography, hybrid imaging

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