Catherine M. Otto - Columbia University · aortic valve and root areas, calculation of stroke work loss, or measurement of the energy loss index (10,11). Stroke work ... SAP systolic

doi:10.1016/j.jacc.2006.03.002

2006;47;2141-2151; originally published online May 12, 2006;J. Am. Coll. Cardiol.Catherine M. Otto

Valvular Aortic Stenosis: Disease Severity and Timing of Intervention

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Journal of the American College of Cardiology Vol. 47, No. 11, 2006© 2006 by the American College of Cardiology Foundation ISSN 0735-1097/06/$32.00P

TATE-OF-THE-ART PAPER

alvular Aortic Stenosisisease Severity and Timing of Intervention

atherine M. Otto, MD, FACCeattle, Washington

Standard echocardiographic evaluation of aortic stenosis (AS) severity includes measurementof aortic velocity, mean transaortic pressure gradient, and continuity equation valve area.Although these measures are adequate for decision making in most patients, there is no singlevalue that defines severe stenosis. Aortic stenosis affects not just the valve, but the entirevascular system, including the left ventricle (LV) and systemic vasculature. More sophisticatedmeasures of disease severity might explain the apparent overlap in hemodynamic severitybetween symptomatic and asymptomatic patients and might better predict the optimal timingof valve replacement. There have been several approaches to evaluation of stenosis severitybased on valve hemodynamics, the ventricular response to increased afterload, ventricular-vascular coupling, or the systemic functional consequences of valve obstruction, such asexercise testing and serum brain natriuretic peptide levels. Aortic valve replacement isindicated when symptoms due to severe AS are present. In most asymptomatic patients, therisk of surgery is greater than the risk of watchful waiting so that management includespatient education, periodic echocardiography, and cardiac risk factor modification. Manyadults with AS have comorbid conditions that affect both the diagnosis and management ofthe valve disease, including aortic regurgitation, aortic root dilation, hypertension, coronaryartery disease, LV dysfunction, and atrial fibrillation. Comorbid conditions should beevaluated and treated based on established guidelines, although awareness of the potentialeffects of therapy in the presence of valve obstruction is needed. (J Am Coll Cardiol 2006;

ublished by Elsevier Inc. doi:10.1016/j.jacc.2006.03.002

47:2141–51) © 2006 by the American College of Cardiology Foundation

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ortic stenosis (AS) most often is due to calcification of aongenitally bicuspid or normal trileaflet valve. Calcifichanges are due to an active disease process characterized byipid accumulation, inflammation, and calcification (1).

nce initiated, progressive leaflet calcification and fibrosisventually result in reduced leaflet motion with obstructiono left ventricular (LV) outflow (2–4). Aortic stenosis oftens first diagnosed by the finding of a murmur on ausculta-ion. However, while a soft murmur with a physiologic split2 reliably excludes severe stenosis and a grade 4 murmurith diminished carotid upstrokes confirms severe obstruc-

ion, between these extremes physical examination is notccurate for evaluation of disease severity.

VALUATION OF DISEASE SEVERITY

tandard approach. Echocardiography is the clinicaltandard for evaluation of adults with suspected or knownalvular AS. Anatomic images show the etiology of AS,evel of obstruction, valve calcification, leaflet motion,nd aortic root anatomy. The LV response to chronicressure overload, and other hemodynamic consequencesf AS, also can be evaluated. Basic hemodynamic param-

From the Division of Cardiology, Department of Medicine, University of Wash-ngton, Seattle, Washington.

pManuscript received November 4, 2005; revised manuscript received December 14,

005, accepted January 2, 2006.

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ters include maximum aortic velocity, mean transvalvu-ar gradient, and continuity equation valve area. All ofhese measures have been well validated compared withnvasive data and, more importantly, as predictors oflinical outcome.

Of these measures, aortic velocity is the most reproduciblend is the strongest predictor of clinical outcome. Aorticelocity allows classification of stenosis as mild (2.6 to 3.0 m/s),oderate (3 to 4 m/s), or severe (�4 m/s). Leaflet thickening

nd calcification with adequate leaflet motion and a velocity2.5 m/s is called aortic sclerosis. Maximum transaortic

ressure gradient (�P) is calculated from velocity (V) based onhe simplified Bernoulli equation:

�Pmax � 4Vmax2

ean gradient is determined by tracing the continuous-ave Doppler curve to average the instantaneous gradientsver the ejection period.Aortic valve area (AVA) is calculated based on the

rinciple that volume flow proximal to the valve equalsolume flow through the narrowed orifice (Fig. 1). Volumeow is calculated as the cross-sectional area (CSA) of flowimes the velocity-time integral (VTI) of flow at that site. Inhe left ventricular outflow tract (LVOT), flow just proximalo the stenotic valve is relatively laminar with a flat velocity

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AVA � VTIAS � CSALVOT � VTILVOT

r

AVA � (CSALVOT � VTILVOT) ⁄ VTIAS

n clinical practice, maximum velocities often are substi-uted for VTIs, in the simplified continuity equation:

igure 1. Standard evaluation of aortic stenosis (AS) severity is based on meong-axis view for calculation of a circular cross-sectional area (CSA), out

Abbreviations and AcronymsAR � aortic regurgitationAS � aortic stenosisAVA � aortic valve areaAVR � aortic valve replacementCSA � cross-sectional areaLV � left ventricle/ventricularLVOT � left ventricular outflow tractVTI � velocity-time integralZva � valvulo-ventricular impedance�P � pressure gradient

aximum aortic jet (AS-Jet, Vmax) from the continuous-wave Doppler recordingn the continuity equation for aortic valve area (AVA).

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AVA � (CSALVOT � VLVOT) ⁄ VAS

further simplification of the continuity equation is theimensionless ratio of outflow tract to aortic velocity:

Velocity ratio � (VLVOT)/VAS

his ratio reflects the relative valve size compared with therea of the patient’s outflow track (i.e., is effectively indexedor body size) and is particularly useful when images ofutflow tract diameter are suboptimal. This ratio ap-roaches 1 with a normal valve. A ratio �0.25 indicates aalve area 25% of expected, corresponding to severe stenosis.he accuracy of all these Doppler measures of stenosis

everity is highly dependent on meticulous attention toechnical details and a comprehensive examination by anxperienced echocardiographer.

hy measure stenosis severity? The clinical utility ofeasuring stenosis severity is two-fold: to reliably predict

he optimal timing of valve replacement and to ensure thatalve disease is the cause of the patient’s symptoms. Despiteur reliance on conventional measures of hemodynamic

ment of left ventricular outflow tract (LVOT) diameter (D) in a parasternaltract velocity (V) from an apical approach using pulsed Doppler, and the

asureflow

. Either velocity-time integrals (VTIs) or maximum velocities can be used

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everity for clinical decision making, it is clear that there iso single value for velocity, gradient, or valve area thatefines symptom onset in an individual patient. In prospec-ive studies, there is a marked overlap in measures ofemodynamic severity between asymptomatic and symp-omatic patients (2,3,5). This overlap persists using valverea (which corrects for cardiac output) and using indexedalve area (corrected for body size). This apparent paradoxuggests that current measures of severity are too simplisticnd do not take into account the interaction between thealve, LV, and peripheral vasculature. There are three basicpproaches to defining an ideal measure of stenosis severityhat would reliably predict symptom onset and clinicalutcome: evaluation of the valve, the ventricle, or theentricular-vascular coupling.tenosis severity defined by valve hemodynamics. Evenhen velocities and calculated �Ps are measured correctly,

his data may not accurately classify disease severity. Veloc-ty reflects the conversion of potential (or pressure) energynto kinetic energy as the high-velocity jet passes throughhe narrowed orifice. Downstream from the orifice, the flowtream expands and decelerates with a corresponding de-rease in kinetic and increase in potential energy, a phe-omenon called “pressure recovery” (6,7). Thus, the net �Petween the LV and the mid-ascending aorta is lower thanhe pressure drop immediately adjacent to the valve.oppler measures velocity at the narrowest orifice, thusoppler �Ps are higher than the net �P (Fig. 2). The

linical impact of pressure recovery usually is small but can

igure 2. Schematic representation of the flow and static pressure acrossystole. AA � aortic cross-sectional area; AVA � effective aortic valve arystolic pressure; MGnet � transvalvular pressure gradient after pressure

valvulo-arterial impedance. From Briand et al. (12), with permission.

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e significant with mild stenosis and a small aortic root (8)r with a doming congenitally stenotic valve (9).Approaches to more accurate measurement of overall

entricular workload include correction of �P based onortic valve and root areas, calculation of stroke work loss, oreasurement of the energy loss index (10,11). Stroke work

oss—the ratio of the mean transaortic �P to mean LVressure—is a strong predictor of clinical outcome (11). Thenergy loss index (ELI) is calculated from AVA and the areaf the aorta at the level of the sinotubular junction (Aa) as12):

ELI � ��AVA � Aa�/�Aa � AVA��/BSA

oth stroke work loss and the energy loss index avoid errorsue to pressure recovery, but these ratios only reflect theteady component of potential energy loss and do notccount for kinetic energy, pulsatile flow, or downstreamascular compliance.

Although valve area seems like the most straightforwarday to evaluate disease severity, the actual extent of leafletpening is an elusive measurement in patients with calcificS where the primary process is increased leaflet stiffnessithout commisural fusion (13). Early in the disease pro-

ess, the valve leaflets are flexible so that AVA increases ashe force of ventricular contraction increases, resulting in anncrease in stroke volume with only a modest increase inelocity. With disease progression, the stiff leaflets become

ft ventricular (LV) outflow tract, aortic valve, and ascending aorta during., the cross-sectional area of the vena contracta); LVSP � left ventricularery (i.e., net MG); MGvc � transvalvular pressure gradient at the vena

the leea (i.erecov

e vena contracta; SV � stroke volume; SVi � stroke volume index; ZVA

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2144 Otto JACC Vol. 47, No. 11, 2006Aortic Stenosis June 6, 2006:2141–51

xed so that valve area fails to increase, despite an increasen volume flow across the valve.

However, measurement of the dynamic change in AVA ishallenging because it requires precise measurements at twoow rates, and the observed changes are close to the limitsf measurement variability. Valve flexibility also can bestimated from the variability in valve opening during aingle systolic ejection period (14). Again, although concep-ually sound, clinical utility is problematic due to measure-ent variability. More sophisticated approaches to evalua-

ion of instantaneous AVA, flow rate, and �P have providednsight into the dynamics of calcific valve disease but are notlinically applicable (Fig. 3) (15). Compared with valve area,here is no clear advantage to the concept of valve resistance,nd there are some concerns with the assumptions under-ying this calculation (15).

Direct imaging of valve area is helpful only in anccasional individual because reverberations and shadowingue to valve calcification limit accuracy. Even with optimal

mages, effective orifice area is not identical to anatomicrifice area, due to contraction of the flow stream as it passeshrough the orifice, particularly when the three-dimensionalalve shape is flat, as seen with calcific valve disease (9).V response to chronic pressure overload. The secondpproach to defining stenosis severity focuses on the effectsf outflow obstruction on the LV. This approach is based onhe recognition that LV dysfunction is the main adverseonsequence of AS, with initial symptoms often due toiastolic dysfunction. Earlier detection of myocardial dia-tolic or systolic dysfunction might identify the optimaliming of valve replacement (16).

Total LV load is complex and includes the effects of walltress, ventricular geometry, and mitral valve competency inddition to the degree of outflow obstruction. Mid-walleridional wall stress is the most appropriate measure of

entricular afterload. However, calculation requires echocar-iographic epicardial and endocardial border tracing alongith noninvasive calculation of LV systolic pressure as the

um of transvalvular �P and systemic blood pressure (17).hus, if wall stress is determined, it typically is calculatednly at end-systole, rather than instantaneously over theardiac cycle. There is little recent outcome data on walltress as a predictor of clinical outcome. However, theoncept of ventricular load as the optimal measure of diseaseemains theoretically appealing. Perhaps if newer imagingechniques allow accurate noninvasive phasic measurementf ventricular load, the utility of this parameter in predictinglinical outcome can be studied further.entricular-vascular coupling. The third approach to

valuation of stenosis severity is to develop an index thatncludes the degree of valve obstruction, ventricular re-ponse, and systemic vasculature impedance. This approachs a variant of the ventricular-vascular coupling concept with

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roach has the potential advantage that it should apply toatients with concurrent conditions that affect the ventricler vasculature. In clinical practice, few patients have “iso-ated AS”; most have some degree of aortic regurgitationAR) and many have hypertension and/or coronary arteryisease. Challenges in applying the ventricular vascularoupling concept to AS are that complete analysis requiresecording high-fidelity instantaneous pressure and flow dataith complex frequency analysis of the data (18). In addi-

ion, previous models of ventricular vascular coupling were

igure 3. Hemodynamic data in a model of aortic stenosis were obtainedsing a dual micromanometer catheter and a transit time flow probe. (A)he simultaneous instantaneous electrocardiogram, aortic and left ventric-lar (LV) pressures, transaortic volume flow (Q), and aortic pressureradient (�P) are shown. During late ejection P is negative. (B) The phaseiagram of �P-Q for this cardiac cycle demonstrates the nonlinearity andime dependence of the �P-Q relationship. EKG � electrocardiogram.rom Bermejo et al. (15), with permission.

nitially developed to be applied in patients with systemicarol Waksmonski on October 20, 2006

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2145JACC Vol. 47, No. 11, 2006 OttoJune 6, 2006:2141–51 Aortic Stenosis

ypertension. These models, therefore, assumed that theontribution of the aortic valve was negligible.

The research group in Quebec (12,19) has proposed aodified ventricular-vascular coupling approach based on

valvulo-arterial impedance” (Zva), which incorporates theegree of valve stenosis and the systemic arterial complianceFig. 2). This calculation is based on the net mean gradient�Pnet), the systolic arterial pressure (SAP), and the indexedtroke volume (SVi) as:

Zva � �SAP � �Pnet�/SVi

he �Pnet takes into account post-stenotic pressure recov-ry, based on measurement of the aortic CSA at theinotubular junction (AoA):

�Pnet � Doppler �Pmean � �4v2 � �2�AVA/AoA�� �1 � AVA/AoA���

n a series of 208 adults with AS, Zva was the strongestredictor of LV dysfunction, even when the energy lossndex and systemic arterial compliance were included in thenalysis (12). A Zva �5.0 mm Hg/ml/m2 is suggested asndicating excessive total ventricular load. Further studiesre needed to determine if this approach reliably predictslinical outcome.

ther diagnostic modalities. Cardiac catheterization nows rarely used for evaluation of AS and is reserved for cases

igure 4. Suggested approach to evaluation of adults with severe aortic ste

ollow-up; LV � left ventricular; Vmax � maximum velocity.

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here echocardiographic data are nondiagnostic (�1% ofases in experienced centers) or when clinical and echocar-iographic data are discrepant. When catheterization iserformed, care is needed to obtain an accurate transaorticP and volume flow rate.Newer imaging approaches, including multi-slice com-

uted tomography and cardiac magnetic resonance imagingan provide anatomic and hemodynamic evaluation oftenotic valves. These approaches are not yet widely avail-ble, and the role of these approaches for evaluation of ASs unclear.

IMING OF VALVE SURGERYymptomatic patients. Aortic valve replacement is indi-ated for severe symptomatic AS (20,21). The classicalymptoms of AS are angina, syncope, and heart failure.owever, most prospectively followed patients presentith more subtle symptoms, typically decreased exercise

olerance, or dyspnea on exertion (2). It is not uncommonor patients to decrease their activity level below theirymptom threshold—a careful history comparing currentnd last year’s activity levels is needed to recognize thathese patients, in fact, are symptomatic. The risk ofudden death is high once any symptom is present, sohat valve surgery is appropriate with even mild symp-oms (Fig. 4) (21,22–26).

When symptoms are present, valve area is �1 cm2, andoppler velocity is �4 m/s, the decision to proceed with

. Additional considerations include comorbidities and patient preferences.

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alve replacement is straightforward. However, some pa-ients have symptoms with a valve area between 1 and 1.5m2 or with a velocity between 3 and 4 m/s (Fig. 5). In theseatients, careful evaluation, including coronary angiography,or other causes of the symptoms is needed. It also isppropriate to seek objective evidence of clinical decompen-ation, such as pulmonary congestion on chest radiography,n elevated serum brain natriuretic peptide level, or reducedxercise tolerance, to ensure that symptoms are trulyresent. With clear symptoms that have no other explana-ion, valve replacement surgery should be considered if thealve shows significant calcification, even with only “mod-rate” stenosis.symptomatic patients. In asymptomatic patients, the

isks of valve surgery are weighed against the risk of andverse outcome without surgical intervention. Aortic valveepair is not an option, so that the long-term durability andisks of a prosthetic valve also must be considered. Inddition, the severity of native valve stenosis should exceedhe functional stenosis of the prosthetic valve that would bemplanted.

If symptom status is unclear, exercise testing may beelpful to determine exercise duration and the hemody-amic changes. Patients with reduced exercise tolerance, alunted blood pressure rise (�20 mm Hg), or abnormalymptoms with exertion should be considered symptomaticnd referred for valve surgery (22–24). Exercise-inducedT-segment depression is frequently present and is notredictive of symptom onset or the presence of coronary

igure 5. Suggested approach to evaluation of adults with moderate aorticf newer parameters discussed in the text, evaluation of the extent of leaflet cx � diagnosis; Rx � therapy; other abbreviations as in Figure 4.

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iously in patients with severe AS and is reserved for the6% of cases where symptom status is unclear (21).Serum brain natriuretic peptide levels may be helpful

hen symptom status is unclear, although caution is neededs brain natriuretic peptide levels also are elevated withther cardiac conditions and in response to some medica-ions (25). Brain natriuretic peptide levels are higher inatients with symptomatic AS compared with those withsymptomatic severe disease and correlate with symptomeverity (26).

Even with severe valve obstruction, the risk of suddeneath is low (�1%) in the asymptomatic patient. In theory,arlier surgery might prevent ventricular systolic or diastolicysfunction, but outcome data addressing this issue are notvailable. Although the risk of surgery is �1% in a 55-year-ld man with no other medical conditions, predicted oper-tive mortality rises to 7% for an 85-year-old woman withypertension and coronary disease and exceeds 24% for an0-year-old man with coronary disease, prior cardiac sur-ery, and renal dysfunction (27). Taken together, in theatient with asymptomatic AS, the balance is shifted to-ards watchful waiting until symptoms supervene. Appro-riate management includes patient education about symp-oms and the importance of promptly seeking medicalttention once symptoms are present, periodic echocardiog-aphy, and cardiovascular risk factor reduction.

There are some exceptions. In patients with asymptom-tic moderate-to-severe AS who are undergoing otherardiac surgery, valve replacement should be considered. In

sis (AS). *Additional evaluation of AS severity may include measurementation, cardiac catheterization, and/or dobutamine stress echocardiography.

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2147JACC Vol. 47, No. 11, 2006 OttoJune 6, 2006:2141–51 Aortic Stenosis

ejection fraction �50%) develops in the absence of symp-oms (20). Because ventricular function may improve afterelief of the increased afterload due to AS, valve replacements appropriate. Some guidelines suggest that valve surgery iseasonable with severe stenosis and evidence of rapid pro-ression or severe calcification (21). Valve surgery also maye considered in patients with severe stenosis when there isn expected delay in surgical intervention once symptomsccur, for example a patient living in a remote area. Someenters advocate exercise testing in patients with severe ASo detect subclinical symptoms. The value of this approachikely is related to the patient’s understanding of the diseaserocess, personal awareness of symptoms, and the physi-ian’s ability to obtain an accurate history. In asymptomaticatients, brain natriuretic peptide levels predict symptomnset, as well as post-operative survival and ventricularunction, but data do not yet support using brain natriureticeptide levels to recommend surgery in an asymptomaticatient (25,28,29).

ROBLEMATIC CLINICAL SITUATIONS

ombined stenosis and regurgitation. Most patients withS have at least mild coexisting AR. These patients can be

valuated and managed using standard diagnostic ap-roaches. Echocardiographic measures of stenosis severityemain accurate even with combined AS and AR. In theseatients, the issue is that symptom onset or ventricularysfunction may occur with only “moderate” AS due to theombined effects of ventricular pressure and volume over-oad. There are no established guidelines for timing of

igure 6. Example of decision making with moderate aortic stenosis (AS)ortic valve, but aortic velocity is only 3.7 m/s, mean gradient 34 mm Hgontract of 5 mm, and holodiastolic flow reversal in the descending aorta. Ho that aortic valve replacement is appropriate. EF � ejection fraction; ES

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rinciples for isolated AS or AR are still applicable. It alsos helpful to quantitate the degree of AR, in addition to theeverity of stenosis. Surgical intervention is appropriate inatients with combined moderate AS/AR when symptomsre present, LV systolic function is reduced, or at the timef other cardiac surgery (Fig. 6).ortic root disease. The underlying etiology of AS is aicuspid valve in over 50% of adults including about 60% ofhose presenting at age 50 to 70 years and about 40% ofhose �70 years of age (30). Patients with a bicuspid aorticalve have an abnormal aorta with an increased risk forortic dilation and dissection (31). After aortic valve re-lacement, the strongest risk factor for aortic dissection is aicuspid aortic valve.Evaluation of aortic root anatomy and dimensions should

e standard in all patients with aortic valve disease. In someases, the timing of surgery will be driven by progressiveoot dilation, even when valve dysfunction is not severe.

hen valve disease is the primary indication for surgicalntervention, concurrent aortic root replacement should beonsidered if significant aortic dilation is present.

ypertension. Aortic valve disease and hypertension areoth prevalent in older adults and occur together in 35% to5% of AS patients (2–5). The presence of hypertensionffects decision making in patients with AS in two reciprocalays: hypertension may mask the severity of stenosis, and

he presence of stenosis may affect the optimal treatment ofypertension. In addition, the combination of AS andypertension, in effect, “double-loads” the ventricle; totalfterload includes both the valve obstruction and the ele-

aortic regurgitation (AR). This 59-year-old man has a markedly calcifiedvalve area is 1.3 cm2. Moderate regurgitation also is present with a venaer, significant left ventricular dilation and systolic dysfunction are present,end-systolic dimension.

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2148 Otto JACC Vol. 47, No. 11, 2006Aortic Stenosis June 6, 2006:2141–51

The complex changes that occur with AS plus hyperten-ion remain incompletely understood. However, recenttudies suggest that, for a given valve area, transaortic �Pnd velocity are reduced when systemic vascular compliances decreased. In this situation, stenosis severity may benderestimated, particularly at catheterization where “re-overed” pressure, rather than vena contracta pressure, isecorded. Although AVA better reflects the degree of valvearrowing, data still may be inaccurate (Fig. 7). To avoidhese errors, evaluation of AS severity should be performedfter treatment to reduce blood pressure to a normotensivetate (19).

Traditionally, treatment of hypertension in patients withS has been controversial due to the possible hypotensive

igure 7. This 82-year-old woman underwent echocardiography for evaluaiew (top) with reduced systolic opening in the long-axis view (bottom), witays later, a lower pressure gradient and lower stroke volume were recorderessure recovery and severe hypertension (blood pressure [BP] 194 systol

gradient; Mn � mean; Pk � peak; SV � stroke volume; Vmax � max

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urrent data suggest that valve opening and stroke volumean increase in response to a decrease in total afterload,xcept with very severe disease, suggesting that medicalherapy of hypertension in patients with asymptomatic ASs reasonable and may decrease overall LV load (32–34).

owever, caution is needed. Antihypertensive medicationshould be started at very low doses and slowly titrated to aherapeutic level. It is unclear if specific medications, such asngiotensin-converting enzyme inhibitors, which mightoth treat hypertension and prevent ventricular remodeling,re preferable in patients with valve disease (35).oronary artery disease. Although angina is one of the

ypical symptoms of AS, it can be a diagnostic challenge toecide whether angina is due to valve obstruction or

f a systolic murmur. The valve was heavily calcified as seen the short-axisppler data consistent with severe stenosis. At cardiac catheterization severale apparent discrepancy in the catheterization data most likely is related toing catheterization). AoV � aortic valve; AVA � aortic valve area; Gradvelocity; VTI � velocity time integral.

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tudies, about 30% of patients with mild-to-moderate ASave clinical evidence of coronary disease; at pre-operativeatheterization, significant coronary disease is present inbout 50% (2,3,5). In a patient with severe AS and angina,alve replacement is indicated with pre-operative coronaryngiography to evaluate for possible bypass grafting at theime of surgery. In patients with angina but only mildtenosis, evaluation and treatment of coronary disease, usingtandard approaches, is appropriate. Decision making isore difficult when angina is present in a patient withoderate AS. One approach is coronary angiography fol-

owed by percutaneous revascularization to see if symptomsesolve. Persistent angina without flow-limiting coronaryesions suggests the cause may be valve obstruction. Func-ional studies to evaluate for regional ischemia are some-imes helpful but are limited by lower diagnostic accuracy inhe presence of AS.V dysfunction. In prospective studies, LV systolic dys-

unction is an uncommon consequence of AS (about 5% ofatients). However, patients may first present with heartailure and be found to have an abnormal aortic valve. Inhese patients, a low antegrade velocity and �P may be seen,ven when severe stenosis is present. Although DopplerVA calculations accurately reflect the extent of valvepening, leaflet motion may be reduced due to a low volumeow rate across the valve, even when stenosis is not severe.

igure 8. Dobutamine stress echocardiography was requested in this 52-yeentricular dysfunction, and a calcified aortic valve. With dobutamine, ej

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onversely, LV dysfunction may be due to the highfterload imposed by severe valve obstruction. It is impor-ant to identify which patients have severe stenosis ashese patients will benefit from valve replacement with ancceptable operative mortality, an improved long-termurvival, and an increase in ejection fraction (36). Inontrast, patients with primary myocardial dysfunctionnd concurrent mild or moderate AS benefit less fromurgical intervention (37).

The diagnostic approach starts with conventional mea-ures of AS severity, evaluation for other causes of LVysfunction (such as coronary disease), and assessment ofalve calcification. If it remains unclear whether the primaryrocess is severe stenosis versus primary ventricular dysfunc-ion, dobutamine stress echocardiography may be helpful37,38). Pressure gradient, valve area, and ejection fractionre measured at rest and with incremental doses of dobut-mine (up to a maximum of 20 �g/kg/min). With flexiblealve leaflets, AVA and ejection fraction increase in con-unction with the increase in cardiac output, indicating thattenosis is not severe. Therapy for primary ventricularysfunction is appropriate in these patients. With severetenosis, AVA does not increase despite an increase injection fraction because the leaflets are rigid and cannotpen any further (Fig. 8). These patients are likely to benefitrom valve replacement. In patients with no improvement in

man with a history of radiation therapy with heart failure symptoms, leftfraction (EF) and stroke volume (SV) increased, indicating contractile

ar-oldection

lar outflow tract [LVOT] diameter 2.2 cm), so calculated aortic valve areastiff inflexible leaflets. AS-Jet � aortic jet.

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jection fraction or cardiac output with dobutamine—aondition called “lack of contractile reserve”—outcomes areoor with either medical or surgical therapy.trial fibrillation. Atrial fibrillation occurs in only 5% of

dults with AS, but management is challenging. Evaluationf AS may be misleading if there is a short R-R interval dueo a rapid ventricular response. Ideally, Doppler evaluationverages several beats when heart rate is controlled. Inatients with mild-to-moderate AS, management of atrialbrillation is based on established clinical guidelines withwareness of the possible hemodynamic effects of medica-ions in the presence of AS. In patients with severe stenosis,trial fibrillation may be the first sign of clinical decompen-ation; symptoms often persist despite rate control, prompt-ng valve surgery.

UTURE DIRECTIONS

urrently, standard noninvasive measures of AS severity—et velocity, mean gradient, and valve area—suffice in mostatients. In the future, complex measures that integrate theentricular, valvular, and vascular components of the diseaseay allow optimal timing of intervention. The clearest

ndication for valve replacement is symptoms due to outflowbstruction. However, if better valve substitutes can bemplanted at low risk, the balance might shift toward earlierntervention to prevent adverse effects on the myocardiumnd ventricular geometry.

eprint requests and correspondence: Dr. Catherine M. Otto,ivision of Cardiology, Box 356422, University of Washington,

eattle, Washington 98195. E-mail: [email protected].

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doi:10.1016/j.jacc.2006.03.002

2006;47;2141-2151; originally published online May 12, 2006;J. Am. Coll. Cardiol.Catherine M. Otto

Valvular Aortic Stenosis: Disease Severity and Timing of Intervention

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