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Role of Echocardiography in Aortic Stenosis
Role of Echocardiography in Aortic Stenosis Natesa G. Pandian, Alamelu Ramamurthi, Sarah Applebaum PII: DOI: Reference:
S0033-0620(14)00070-X doi: 10.1016/j.pcad.2014.05.006 YPCAD 594
To appear in:
Progress in Cardiovascular Diseases
Please cite this article as: Pandian Natesa G., Ramamurthi Alamelu, Applebaum Sarah, Role of Echocardiography in Aortic Stenosis, Progress in Cardiovascular Diseases (2014), doi: 10.1016/j.pcad.2014.05.006
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Natesa G. Pandian, MD, FACC
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Role of Echocardiography in Aortic Stenosis
Alamelu Ramamurthi, MD
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Sarah Applebaum, MS
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Tufts Medical Center Tufts University School of Medicine
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Boston, MA
Correspondance: Natesa G. Pandian, MD, FACC Tufts Medical Center 800 Washington Street, Boston, MA 02111
Email: [email protected] Phone: 617 875 5755 FAX: 617 636 8070
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Abstract
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Aortic stenosis is a valve disorder that includes not only valve narrowing but also changes in the
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left ventricle and intracardiac hemodynamics. Older patients with aortic stenosis often have co-
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existing pathologic disorders, which influence the pathophysiology, symptom expression and prognosis. There is also increasing awareness that severe aortic stenosis could be associated
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with low transvalvular pressure gradient caused by a variety of mechanisms. Surgical and
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transcutaneous valve replacements are currently available interventions for patients with severe aortic stenosis. This article reviews the role of echocardiography in the comprehensive
Keywords:
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Echocardiography
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assessment of aortic stenosis, its severity and associated pathophysiologic abnormalities.
Aortic stenosis
Aortic valve disease Low gradient aortic stenosis Valve disease
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Role of Echocardiography in Aortic Stenosis
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During the last decade, new insights on the clinical features, presentation, and prognosis of
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patients with aortic stenosis (AS), and the emerging option of transcutaneous aortic valve implantation (TAVI) in selected patients have placed emphasis on the need to approach aortic
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stenosis not just in terms of valve stenosis and gradients, but much more comprehensively. The
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etiology of AS include congenital lesions, commonly a bicuspid aortic valve, degenerative calcification of the valve cusps, rheumatic fever-related commissural fusion, and rare systemic
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or therapy-induced mechanisms. Severe AS, if uncompensated and uncorrected, leads to disabling symptoms and decreased survival.1,2 For optimal clinical decision making,
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comprehensive diagnostic evaluation of patients with aortic valve disease requires assessment
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of the morphology of the valve, severity of the valve lesion, size of the aorta, systemic arterial afterload, impact on LV size and function, consequences of abnormal LV function and
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hemodynamics on pulmonary artery pressures, right ventricular size and function, and coexistent disorders. Echocardiography, with its two- and three-dimensional imaging capabilities, and various Doppler modalities, allows for examination of the valve pathology, as well as hemodynamics, and has therefore become the diagnostic method of choice, and the guide for optimal management of patients with AS. Echocardiographic data should be integrated with the clinical features of a patient, other imaging, and, when needed, catheterization findings in order to approach AS in a syndromatic fashion. This article will review the role of echocardiography in patients with AS.
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Assessment of the severity of aortic stenosis
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Normal aortic valve area (AVA) is considered to range from 2 to 4.5 cm2. This observation is
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based on a few reports from a small series of subjects. As AVA progressively decreases, it
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results in an increasing pressure gradient between the LV and aorta, and an increasing flow velocity across the valve. In the past, the severity of AS was determined by invasively
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measuring cardiac output and pressure gradients across the valve, and employing Gorlin
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equation, or other similar equations, to derive the AVA. Such methods of obtaining AVA, however, were poorly validated and their accuracy never appropriately tested in the setting of
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abnormal flow states, increased afterload, or co-existent disorders.
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Aortic Valve Pathology
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Two-dimensional and three-dimensional imaging portrays the pathology of a stenotic aortic valve. The number of valve cusps, valve thickening, commissural fusion, calcific burden on the
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valve, and restricted motion are visualized in the long-axis and short-axis imaging planes. 3-5 (Figure 1). In most adult patients with AS, the valve has three thickened and calcified cusps. Valve thickening and calcification may involve all cusps or only part of the valve. A bicuspid valve has two cusps with complete or partial fusion in the conjoint cusp, and an oval appearance. The raphe is generally directed towards the pulmonic valve or tricuspid valve direction. If stenosis is not severe, the valve exhibits systolic bowing in the long-axis view that gives a clue to the bicuspid nature of the valve.
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Aortic valve area can be measured by planimetry, except in the presence of a markedly calcified
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or deformed valve. 6-8 Three-dimensional imaging is helpful in correctly representing the valve
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in an optimal orientation. 5 In addition to the valve area, other measurements of importance include diameters of the aortic ring and aortic root at the level of the sinus of Valsalva, sino-
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tubular junction, and proximal ascending aorta. If surgical replacement or transcatheter
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implantation is considered, these parameters have implications on the choice of the valve prosthesis. In patients with bicuspid aortic valve, which is often associated with a
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morphologically weak aortic wall that may dilate into an aneurysm and risk rupture, the
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dimensions of the aortic root and ascending aorta should be noted and monitored.
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Severity of Aortic Stenosis
Patients with severe AS can be categorized as mild (AVA > 1.5), moderate (AVA 1.0-1.5), or
Severe AS can be further divided into those with normal flow and high gradient (mean
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severe (AVA ≤ 1.0 or AVAi ≤ 0.6 cm2/m2) based on AVA and various other empirical criteria. 9-
gradient above 40 mm Hg), and those with low flow and low gradient (mean gradient 40 mm Hg or less). Reflection on the mechanism of low gradient is needed in gauging the prognosis and deciding on appropriate therapy. Flow Velocity and Pressure Gradients in Aortic Stenosis As determined by the Doppler echocardiographic approach, the severity of aortic stenosis is discerned by deriving flow velocity, stroke volume, pressure gradient, and quantitation of aortic valve area (Figure 2). A maximum aortic flow velocity of < 3 m/s, 3.0-3.9 m/s, and > 4 m/s) is
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thought to indicate mild, moderate, and severe AS, respectively. The shape of the maximum
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aortic flow velocity profile gives a clue to the stenosis severity. In mild to moderate aortic
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stenosis, the maximum flow velocity is commonly noted during the early phase of ejection time, whereas the maximum flow velocity in severe AS occurs at mid-ejection phase (Figure 3).
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However, it should be noted that an early peaking profile might be seen despite severe AS. If
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there is significant co-existent mitral regurgitation, the forward flow may decrease during the systolic phase if a sizable amount leaks into the left atrium, thereby distorting velocity since it is
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determined by flow rate. The ratio of proximal and distal velocity-time integral (VTI) is an index of AS severity, with an index of 0.25 pointing to severe AS. Using the maximum velocity profile
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of flow recorded distal to the valve, both maximum instantaneous and mean gradients are
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calculated using a modified Bernoulli equation, 4 × (V22-V11), or simply 4×V22, where V1 is the
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velocity proximal to the valve and V2 is the distal velocity 11. The Doppler method’s accuracy of calculating pressure gradients has been validated by simultaneous catheter-derived valve
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gradients. 12 Notice should be made to the differences in maximum instantaneous gradient as deduced from Doppler versus the peak-to-peak gradient deduced from the catheterization method. While mean gradients by Doppler and catheterization are similar, the maximum gradients are not. Doppler method yields the true maximum gradient, while the peak-to-peak gradient measured between LV and aortic pressure via catheterization is lower. Mean gradients of < 20 mm Hg, 20-39 m/s and >40 mm Hg are considered to indicate mild, moderate, and severe AS, respectively. Although the AHA/ACC/ASE guidelines state that severe AS is associated with flow velocity of > 4 m/s, peak gradient of > 65 mm Hg, and mean gradient of > 40 mm Hg, 9 it would be a folly to rely on velocities and gradients alone, unless the aortic flow
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velocity is more than 5 m/s in the setting of a normal stroke volume (SV). Efforts should be
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made to obtain aortic valve area in patients with AS because a low forward SV due to a variety
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of disorders could result in lower velocities and lower pressure gradients despite the presence
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of severe AS. Aortic Valve Area and AVA index
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The aortic valve area indexed to the body size is the best indicator of the severity of AS. The
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AVA can be derived from Doppler hemodynamic data (Effective or Functional AVA) or by planimetry (Anatomic AVA). In order to calculate the aortic valve area by Doppler
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hemodynamics, stroke volume must first be determined by multiplying the LV outflow area
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(from its diameter, use radius [r] to find area via πr2) by the VTI of proximal flow profile; then, employing the concept of the continuity equation, AVA is calculated by dividing the stroke
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volume by VTI of the maximum distal flow velocity profile (Figure 2). Potential technical errors
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that need to be avoided in the Doppler method include wrong measurements of LV outflow diameter and incorrect recordings of flow velocities. The assumption in computing the stroke volume in the LV outflow is that the outflow area is circular. This may not be valid if asymmetrical hypertrophy of the basal ventricular septum is present. 3D imaging could provide the correct area of the outflow directly and obviate the need to rely on the outflow diameter. Another potential pitfall is misjudging the maximum velocity profile. Interrogation of the flow profile in parasternal, apical, suprasternal, and subcostal acoustic windows is essential so as not to miss the maximum flow profile. An appraisal of the ratio of V1 to V2 velocity provides another index of severity, with a ratio of < 0.25 indicating severe AS and > 0.50 pointing to mild. Doppler
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recording measures the maximum pressure difference between the LA and the vena contracta
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located immediately beyond the orifice. As the flow jet decelerates beyond, a fall in kinetic
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energy results in recovery of some pressure and thus a rise in aortic static pressure. 13 Therefore, the effective afterload caused by the stenotic valve may be slightly lower than that
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depicted by the Doppler derived pressure gradient. Nevertheless, this overestimation does not
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provoke a major practical problem, except in the setting of a small aorta or a prosthetic valve. The anatomic AVA is obtained from the short-axis two- or three-dimensional images by tracing
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the orifice border when it is maximally open during systole. 6-8 Transesophageal imaging reliably
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depicts the valve area in more than 90% of patients with AS. In about 75% of all AS patients, AVA can be measured by planimetry on transthoracic images. Emphasis should be placed on
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ensuring that the measurement is at the valve tip level and not across the body of the valve,
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and on employing optimal ultrasound gain and dynamic range. In patients with moderate and severe AS, anatomic AVA is not influenced by changes in stroke volume and is therefore reliable
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even in the setting of a low stroke volume. While the determination of AVA is an essential component of the assessment of AS, with an AVA < 1 cm2 considered severe, it is more appropriate to calculate AVA indexed to body size, specifically body surface area. An AVA index (AVAi) of < 0.6 cm2/m2 is considered to be a marker of severe AS. Criteria for assessing the severity of AS in the current era are listed in Table 2. Exercise echocardiography yields additional information in asymptomatic AS patients 14. The patient’s effort tolerance, the change in valve gradient and the degree of myocardial response to increased demand are parameters that have prognostic and therapeutic implications. It is worth noting that the
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“conventional criteria” employed in the past to evaluate AS may not be valid in all patients,
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Low Flow, Low Gradient, Severe AS with Low or Normal LV EF
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particularly in those with a low flow state. This issue is discussed below.
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One concern of relying on the aortic valve area as a marker of AS severity is that the valve orifice area calculation could be erroneous in the setting of LV dysfunction and low stroke
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volume, as the valve may fail to open fully due to a low flow state. This impression came to be
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accepted from observations in the catheterization laboratory that used Gorlin equation to derive the AVA. 15,16 This should not be surprising since one of the essential components of
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Gorlin equation is that the mean gradient can be expected to decrease if the flow is low.
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Conversely, however, the anatomic orifice area of a thick, calcified valve does not change with alterations in flow. 17,18 This has been demonstrated by recording aortic valve area in patients
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with AS at various flow rates. Thus, in patients with low flow states, deriving anatomic AVA by
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transesophageal or transthoracic echocardiography is a reliable approach to assess the severity of AS. Dobutamine stress echocardiography is another option in a low flow scenario. With dobutamine, the stroke volume can be increased to a normal or acceptable level, and AVA recalculated during stress. 19,20 Another advantage of dobutamine stress testing is the opportunity to assess myocardial contractile reserve. Patients with contractile reserve have a better outlook with intervention than those without. 21
Despite severe AS, mean gradient could be low not only due to systolic LV dysfunction, but also
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due to other mechanisms (Figure 4). Severe diastolic LV dysfunction from varied causes can
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impede LV filling and compromise forward stroke volume. Likewise, severe systolic and/or
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diastolic RV dysfunction can lead to low stroke volume. Coexistent mitral stenosis can result in decreased LV filling; mitral regurgitation can steal the stroke volume away from the aorta; and
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tricuspid disorders can operate through similar mechanisms.
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It is also important to realize that, despite normal LV ejection fraction (EF), low gradient may be
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encountered in severe AS when the LV afterload is high or when the ventricle is anatomically small (referred to as, “paradoxical low flow AS”). 22-24, 24a Increased afterload offers resistance to
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LV ejection, while a small ventricle fills less and offers reduced forward SV; often these two exist together, and are frequently observed in elderly patients. Therefore, one should assess
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the total hemodynamic burden on the left ventricle. Energy loss index (ELI) is a parameter that
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expresses the LV workload. 25 It can be calculated by gauging the cross-sectional area of the
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aorta (Aa) from its diameter and using the equation: ELI = (AVA × Aa)/(Aa – AVA)/body surface area. Global (valvular + arterial) hemodynamic load to the LV should also be assessed in patients with AS. Valvulo-arterial impedance (Zva) provides such an index; it is calculated by dividing estimated LV systolic pressure (systolic arterial pressure + mean transvalvular gradient) by the indexed stroke volume.23 Zva over 5 is considered to be high. This index appears to have prognostic implications and thus should be integrated in the overall decision-making process.
Echocardiographic Guidance for Interventions
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The options for interventions in patients with AS include surgical aortic valve replacement
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(SAVR) or transcutaneous aortic valve implantation 26,27. In patients undergoing SAVR,
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intraoperative TEE is often employed to reassess aortic root and aortic valve anatomy, evaluate surgical efficacy, and recognize immediate, post-operative complications, such as paravalvular
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regurgitation (Figure 5). The measurements of the aortic ring and ascending aorta, as
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mentioned earlier, are important to deciding the type and size of the prosthesis for patients, in whom TAVI is considered. During the procedure, whether via a transfemoral or transapical
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approach, TEE is useful in displaying the position of the delivery catheters and placement of the valve. 28,29 Additionally, post-procedure complications, such as paravalvular regurgitation,
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myocardial perforation, and hemopericardium, are instantly recognized.
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The Syndrome of Degenerative Calcific Aortic Stenosis
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Elderly patients with AS often have other disorders beyond aortic valve narrowing. 30,31
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Hypertension and atherosclerosis are associated with increased afterload to the ventricle. LV diastolic and systolic function could be abnormal secondary to AS, as well as to concomitant hypertension, ischemic heart disease, or other disorders. Co-existent degenerative mitral valve disease of varying severity could be present. Pulmonary hypertension, right ventricular dysfunction, and tricuspid regurgitation could be present. These associated disorders could influence the degree of hemodynamic perturbances, symptom expression, and clinical outlook. Degenerative calcific AS in older patients should be considered as more of a syndrome rather than just a valve disease. Awareness of various facets of this syndrome should be considered in the clinical evaluation of a patient with AS. Two-dimensional and Doppler examination provides
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comprehensive information to assess both the severity of AS and all the non-valvular
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derangements associated with valve stenosis.
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Co-existent Valve Disease
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Aortic regurgitation (AR) could be associated with AS in some patients. While AS is predominantly a pressure overload disorder, AR adds volume overload to the left ventricle in
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addition to pressure overload. If moderate or more severe AR is present, the aortic valve
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velocities and gradients increase because of increased forward SV. The anatomic AVA should still be reliable under this circumstance. The decision of when to intervene in a patient with
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such mixed valve disease should be made on the overall clinical picture that incudes symptoms,
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LV size and function, and other co-existent issues. Elderly patients with degenerative, calcific AS frequently have degenerative mitral valve disease as well, either in the form of mitral stenosis
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or regurgitation. The morphologic and functional severity of the mitral valve disease should be
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assessed to understand its contribution to the pathophysiology and symptoms. If there is significant mitral valve disease, the patient may not derive benefits from aortic valve intervention alone.
The Left Ventricle and Other Disorders The volumes and ejection fraction of the LV should be quantified since they have prognostic and therapeutic implications. Valve intervention is recommended if LV EF is less than 50%. Recent work employing speckle tracking echocardiography and cardiac magnetic resonance suggests that those with severe AS may have abnormal left ventricle even when the EF is
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normal.32,33 LV longitudinal strain of less than -15 appears to connote an adverse outcome with
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normal longitudinal strain resting around -20. This measurement is expected to become a
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standard approach to identifying early LV dysfunction and may influence therapeutic decision making in the future. Echocardiographic parameters of diastolic dysfunction, measures of
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pulmonary artery pressures,34 and RV function are important in the overall assessment of a
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patient with AS.
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Management Implications of Echocardiographic Findings of Aortic Stenosis Patients with AS of mild and moderate severity should be followed medically with periodic
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clinical and echocardiographic examinations. Echocardiographic evaluation annually or every 6
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months is prudent when AS is moderate since the stenosis severity can rapidly progress in some patients. Gauging the calcium burden and velocity increase is useful in identifying such patients.
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In patients with severe AS but with no symptoms, exercise echocardiography allows for an
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objective assessment of the effort tolerance and hemodynamic response to exercise. Left ventricular contractile reserve assessed by dobutamine stress echocardiography has prognostic implications in patients with severe AS and a low gradient. In older patients with co-existent disorders, echocardiographic and clinical evaluation provides a detailed portrait of the patient’s illness and guides therapeutic decision-making on the type of treatment.
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Figure Legends:
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Figure 1. Two- and three-dimensional images of the aortic valve. A) Normal aortic valve; B) Moderate
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aortic stenosis (AS) with decreased valve area; C) Severe AS with markedly decreased valve area; D) A bicuspid aortic valve with mild AS; E) Three-dimensional image of the same valve; F)
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Three-dimensional image of a severely stenotic valve.
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Figure 2.
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The method of deriving aortic valve area by continuity equation. Left: LA outflow diameter measurement to derive LV outflow area (A1); Middle: Pulsed Doppler recording of LV outflow
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flow velocity profile to obtain the velocity time integral (VTI1) to calculate the stroke volume;
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Figure 3.
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Right: Distal maximal flow velocity recording by continuous wave Doppler to derive VTI 2.
Hemodynamics in aortic stenosis. Top panel: Maximum velocity profiles of mild AS with a velocity of 2 m/s (left), moderate AS with a velocity of 3.2 m/s (middle), and severe AS with a velocity of 4.4 m/s (right). Bottom left: Schematic left ventricular and aortic pressure waveforms of normal (left) and in an example of severe AS. On the right are Doppler recording of a patient with severe AS. Maximum instantaneous gradient is derived by using the formula 4xV2 and mean gradient from the mean of multiple instantaneous gradients from the profile. Mean gradients by Doppler and pressure recordings are similar but the peak to peak gradient obtained from the invasive pressure recordings is lower than that obtained by Doppler.
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Figure 4.
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Schematic portraying multiple mechanisms that can result in a low gradient across the aortic
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valve despite severe AS.
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Figure 5.
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Transesophageal echocardiographic images during transcutaneous aortic valve implantation.
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A) Image showing a stenotic aortic valve with a guide-wire across. LA=left atrium; LV=left ventricle; Ao=aorta. B) Catheter with the prosthesis across the valve (arrow). C) 3-dimensional
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image during inflation of the prosthesis (arrow). D) A short-axis view of the prosthesis after implantation. E) Significant paravalvular regurgitation noted (arrow). F) 3-dimensional image
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showing paravalvular regurgitation.
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Table 1. Comprehensive Echocardiographic Evaluation of Aortic Stenosis
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Aortic valve anatomy
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Number of cusps, calcium burden, aortic valve area by planimetry
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Hemodynamic Measurements
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LV outflow velocity time integral proximal to the valve
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Flow velocity and velocity time integral (VTI) across the aortic valve
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Proximal to distal VTI ratio
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Maximum instantaneous gradient and mean gradient
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Aortic valve area by continuity equation
Energy Loss Index
Valvulo-arterial impedance (global hemodynamic load, Zva)
Other Data
Aortic ring, sinus of Valsalva, Sino-tubular junction, and ascending aorta diameters
LV volume and ejection fraction, LV longitudinal strain
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Measures of diastolic dysfunction
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Pulmonary artery systolic pressure
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Right ventricular size and function
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Coronary artery disease and other co-existing disorders
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Table 2. Suggested Criteria for Grading the Severity of Aortic Stenosis
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_____________________________________________________________________________________ Moderate AS
Mild thickening of the valve
Mild-moderate valve thickening/calcification
Mild restriction to opening
Moderate restriction to opening
Aortic Vmax 2 m/s or less
Aortic Vmax 3-3.9 m/s
Mean Pressure Gradient < 20 mm Hg
Mean Pressure Gradient 20-39 mm Hg
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Mild AS
Aortic Valve Area > 1.5 cm2
Aortic Valve Area < 1 cm2 ; AVAi 0.7-1.0 m2/m2
Severe AS with Normal Flow
Marked restriction to opening
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SVi >35 mL/m2
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Severe thickening/calcification of the valve
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Aortic >Vmax 4 m/s
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_____________________________________________________________________________________ Severe AS with Low Flow Severe thickening/calcification of the valve Marked restriction to opening SVi <35 mL/m2 Aortic Vmax 3 - 4 m/s Mean Pressure Gradient 20-40 mm Hg
Aortic Valve Area < 1 cm2; AVAi < 0.6 m2/m2
Aortic Valve Area < 1 cm2 ; AVAi < 0.6 m2/m2
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Mean Pressure Gradient >40 mm Hg
(Abbreviations as in text)
S0033-0620(14)00070-X doi: 10.1016/j.pcad.2014.05.006 YPCAD 594
To appear in:
Progress in Cardiovascular Diseases
Please cite this article as: Pandian Natesa G., Ramamurthi Alamelu, Applebaum Sarah, Role of Echocardiography in Aortic Stenosis, Progress in Cardiovascular Diseases (2014), doi: 10.1016/j.pcad.2014.05.006
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Natesa G. Pandian, MD, FACC
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Role of Echocardiography in Aortic Stenosis
Alamelu Ramamurthi, MD
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Sarah Applebaum, MS
From
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Tufts Medical Center Tufts University School of Medicine
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Boston, MA
Correspondance: Natesa G. Pandian, MD, FACC Tufts Medical Center 800 Washington Street, Boston, MA 02111
Email: [email protected] Phone: 617 875 5755 FAX: 617 636 8070
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Abstract
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Aortic stenosis is a valve disorder that includes not only valve narrowing but also changes in the
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left ventricle and intracardiac hemodynamics. Older patients with aortic stenosis often have co-
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existing pathologic disorders, which influence the pathophysiology, symptom expression and prognosis. There is also increasing awareness that severe aortic stenosis could be associated
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with low transvalvular pressure gradient caused by a variety of mechanisms. Surgical and
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transcutaneous valve replacements are currently available interventions for patients with severe aortic stenosis. This article reviews the role of echocardiography in the comprehensive
Keywords:
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Echocardiography
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assessment of aortic stenosis, its severity and associated pathophysiologic abnormalities.
Aortic stenosis
Aortic valve disease Low gradient aortic stenosis Valve disease
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Role of Echocardiography in Aortic Stenosis
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During the last decade, new insights on the clinical features, presentation, and prognosis of
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patients with aortic stenosis (AS), and the emerging option of transcutaneous aortic valve implantation (TAVI) in selected patients have placed emphasis on the need to approach aortic
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stenosis not just in terms of valve stenosis and gradients, but much more comprehensively. The
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etiology of AS include congenital lesions, commonly a bicuspid aortic valve, degenerative calcification of the valve cusps, rheumatic fever-related commissural fusion, and rare systemic
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or therapy-induced mechanisms. Severe AS, if uncompensated and uncorrected, leads to disabling symptoms and decreased survival.1,2 For optimal clinical decision making,
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comprehensive diagnostic evaluation of patients with aortic valve disease requires assessment
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of the morphology of the valve, severity of the valve lesion, size of the aorta, systemic arterial afterload, impact on LV size and function, consequences of abnormal LV function and
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hemodynamics on pulmonary artery pressures, right ventricular size and function, and coexistent disorders. Echocardiography, with its two- and three-dimensional imaging capabilities, and various Doppler modalities, allows for examination of the valve pathology, as well as hemodynamics, and has therefore become the diagnostic method of choice, and the guide for optimal management of patients with AS. Echocardiographic data should be integrated with the clinical features of a patient, other imaging, and, when needed, catheterization findings in order to approach AS in a syndromatic fashion. This article will review the role of echocardiography in patients with AS.
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Assessment of the severity of aortic stenosis
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Normal aortic valve area (AVA) is considered to range from 2 to 4.5 cm2. This observation is
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based on a few reports from a small series of subjects. As AVA progressively decreases, it
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results in an increasing pressure gradient between the LV and aorta, and an increasing flow velocity across the valve. In the past, the severity of AS was determined by invasively
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measuring cardiac output and pressure gradients across the valve, and employing Gorlin
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equation, or other similar equations, to derive the AVA. Such methods of obtaining AVA, however, were poorly validated and their accuracy never appropriately tested in the setting of
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abnormal flow states, increased afterload, or co-existent disorders.
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Aortic Valve Pathology
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Two-dimensional and three-dimensional imaging portrays the pathology of a stenotic aortic valve. The number of valve cusps, valve thickening, commissural fusion, calcific burden on the
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valve, and restricted motion are visualized in the long-axis and short-axis imaging planes. 3-5 (Figure 1). In most adult patients with AS, the valve has three thickened and calcified cusps. Valve thickening and calcification may involve all cusps or only part of the valve. A bicuspid valve has two cusps with complete or partial fusion in the conjoint cusp, and an oval appearance. The raphe is generally directed towards the pulmonic valve or tricuspid valve direction. If stenosis is not severe, the valve exhibits systolic bowing in the long-axis view that gives a clue to the bicuspid nature of the valve.
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Aortic valve area can be measured by planimetry, except in the presence of a markedly calcified
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or deformed valve. 6-8 Three-dimensional imaging is helpful in correctly representing the valve
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in an optimal orientation. 5 In addition to the valve area, other measurements of importance include diameters of the aortic ring and aortic root at the level of the sinus of Valsalva, sino-
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tubular junction, and proximal ascending aorta. If surgical replacement or transcatheter
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implantation is considered, these parameters have implications on the choice of the valve prosthesis. In patients with bicuspid aortic valve, which is often associated with a
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morphologically weak aortic wall that may dilate into an aneurysm and risk rupture, the
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dimensions of the aortic root and ascending aorta should be noted and monitored.
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Severity of Aortic Stenosis
Patients with severe AS can be categorized as mild (AVA > 1.5), moderate (AVA 1.0-1.5), or
Severe AS can be further divided into those with normal flow and high gradient (mean
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10,10A
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severe (AVA ≤ 1.0 or AVAi ≤ 0.6 cm2/m2) based on AVA and various other empirical criteria. 9-
gradient above 40 mm Hg), and those with low flow and low gradient (mean gradient 40 mm Hg or less). Reflection on the mechanism of low gradient is needed in gauging the prognosis and deciding on appropriate therapy. Flow Velocity and Pressure Gradients in Aortic Stenosis As determined by the Doppler echocardiographic approach, the severity of aortic stenosis is discerned by deriving flow velocity, stroke volume, pressure gradient, and quantitation of aortic valve area (Figure 2). A maximum aortic flow velocity of < 3 m/s, 3.0-3.9 m/s, and > 4 m/s) is
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thought to indicate mild, moderate, and severe AS, respectively. The shape of the maximum
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aortic flow velocity profile gives a clue to the stenosis severity. In mild to moderate aortic
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stenosis, the maximum flow velocity is commonly noted during the early phase of ejection time, whereas the maximum flow velocity in severe AS occurs at mid-ejection phase (Figure 3).
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However, it should be noted that an early peaking profile might be seen despite severe AS. If
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there is significant co-existent mitral regurgitation, the forward flow may decrease during the systolic phase if a sizable amount leaks into the left atrium, thereby distorting velocity since it is
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determined by flow rate. The ratio of proximal and distal velocity-time integral (VTI) is an index of AS severity, with an index of 0.25 pointing to severe AS. Using the maximum velocity profile
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of flow recorded distal to the valve, both maximum instantaneous and mean gradients are
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calculated using a modified Bernoulli equation, 4 × (V22-V11), or simply 4×V22, where V1 is the
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velocity proximal to the valve and V2 is the distal velocity 11. The Doppler method’s accuracy of calculating pressure gradients has been validated by simultaneous catheter-derived valve
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gradients. 12 Notice should be made to the differences in maximum instantaneous gradient as deduced from Doppler versus the peak-to-peak gradient deduced from the catheterization method. While mean gradients by Doppler and catheterization are similar, the maximum gradients are not. Doppler method yields the true maximum gradient, while the peak-to-peak gradient measured between LV and aortic pressure via catheterization is lower. Mean gradients of < 20 mm Hg, 20-39 m/s and >40 mm Hg are considered to indicate mild, moderate, and severe AS, respectively. Although the AHA/ACC/ASE guidelines state that severe AS is associated with flow velocity of > 4 m/s, peak gradient of > 65 mm Hg, and mean gradient of > 40 mm Hg, 9 it would be a folly to rely on velocities and gradients alone, unless the aortic flow
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velocity is more than 5 m/s in the setting of a normal stroke volume (SV). Efforts should be
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made to obtain aortic valve area in patients with AS because a low forward SV due to a variety
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of disorders could result in lower velocities and lower pressure gradients despite the presence
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of severe AS. Aortic Valve Area and AVA index
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The aortic valve area indexed to the body size is the best indicator of the severity of AS. The
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AVA can be derived from Doppler hemodynamic data (Effective or Functional AVA) or by planimetry (Anatomic AVA). In order to calculate the aortic valve area by Doppler
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hemodynamics, stroke volume must first be determined by multiplying the LV outflow area
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(from its diameter, use radius [r] to find area via πr2) by the VTI of proximal flow profile; then, employing the concept of the continuity equation, AVA is calculated by dividing the stroke
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volume by VTI of the maximum distal flow velocity profile (Figure 2). Potential technical errors
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that need to be avoided in the Doppler method include wrong measurements of LV outflow diameter and incorrect recordings of flow velocities. The assumption in computing the stroke volume in the LV outflow is that the outflow area is circular. This may not be valid if asymmetrical hypertrophy of the basal ventricular septum is present. 3D imaging could provide the correct area of the outflow directly and obviate the need to rely on the outflow diameter. Another potential pitfall is misjudging the maximum velocity profile. Interrogation of the flow profile in parasternal, apical, suprasternal, and subcostal acoustic windows is essential so as not to miss the maximum flow profile. An appraisal of the ratio of V1 to V2 velocity provides another index of severity, with a ratio of < 0.25 indicating severe AS and > 0.50 pointing to mild. Doppler
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recording measures the maximum pressure difference between the LA and the vena contracta
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located immediately beyond the orifice. As the flow jet decelerates beyond, a fall in kinetic
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energy results in recovery of some pressure and thus a rise in aortic static pressure. 13 Therefore, the effective afterload caused by the stenotic valve may be slightly lower than that
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depicted by the Doppler derived pressure gradient. Nevertheless, this overestimation does not
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provoke a major practical problem, except in the setting of a small aorta or a prosthetic valve. The anatomic AVA is obtained from the short-axis two- or three-dimensional images by tracing
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the orifice border when it is maximally open during systole. 6-8 Transesophageal imaging reliably
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depicts the valve area in more than 90% of patients with AS. In about 75% of all AS patients, AVA can be measured by planimetry on transthoracic images. Emphasis should be placed on
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ensuring that the measurement is at the valve tip level and not across the body of the valve,
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and on employing optimal ultrasound gain and dynamic range. In patients with moderate and severe AS, anatomic AVA is not influenced by changes in stroke volume and is therefore reliable
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even in the setting of a low stroke volume. While the determination of AVA is an essential component of the assessment of AS, with an AVA < 1 cm2 considered severe, it is more appropriate to calculate AVA indexed to body size, specifically body surface area. An AVA index (AVAi) of < 0.6 cm2/m2 is considered to be a marker of severe AS. Criteria for assessing the severity of AS in the current era are listed in Table 2. Exercise echocardiography yields additional information in asymptomatic AS patients 14. The patient’s effort tolerance, the change in valve gradient and the degree of myocardial response to increased demand are parameters that have prognostic and therapeutic implications. It is worth noting that the
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“conventional criteria” employed in the past to evaluate AS may not be valid in all patients,
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Low Flow, Low Gradient, Severe AS with Low or Normal LV EF
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particularly in those with a low flow state. This issue is discussed below.
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One concern of relying on the aortic valve area as a marker of AS severity is that the valve orifice area calculation could be erroneous in the setting of LV dysfunction and low stroke
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volume, as the valve may fail to open fully due to a low flow state. This impression came to be
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accepted from observations in the catheterization laboratory that used Gorlin equation to derive the AVA. 15,16 This should not be surprising since one of the essential components of
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Gorlin equation is that the mean gradient can be expected to decrease if the flow is low.
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Conversely, however, the anatomic orifice area of a thick, calcified valve does not change with alterations in flow. 17,18 This has been demonstrated by recording aortic valve area in patients
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with AS at various flow rates. Thus, in patients with low flow states, deriving anatomic AVA by
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transesophageal or transthoracic echocardiography is a reliable approach to assess the severity of AS. Dobutamine stress echocardiography is another option in a low flow scenario. With dobutamine, the stroke volume can be increased to a normal or acceptable level, and AVA recalculated during stress. 19,20 Another advantage of dobutamine stress testing is the opportunity to assess myocardial contractile reserve. Patients with contractile reserve have a better outlook with intervention than those without. 21
Despite severe AS, mean gradient could be low not only due to systolic LV dysfunction, but also
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due to other mechanisms (Figure 4). Severe diastolic LV dysfunction from varied causes can
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impede LV filling and compromise forward stroke volume. Likewise, severe systolic and/or
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diastolic RV dysfunction can lead to low stroke volume. Coexistent mitral stenosis can result in decreased LV filling; mitral regurgitation can steal the stroke volume away from the aorta; and
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tricuspid disorders can operate through similar mechanisms.
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It is also important to realize that, despite normal LV ejection fraction (EF), low gradient may be
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encountered in severe AS when the LV afterload is high or when the ventricle is anatomically small (referred to as, “paradoxical low flow AS”). 22-24, 24a Increased afterload offers resistance to
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LV ejection, while a small ventricle fills less and offers reduced forward SV; often these two exist together, and are frequently observed in elderly patients. Therefore, one should assess
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the total hemodynamic burden on the left ventricle. Energy loss index (ELI) is a parameter that
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expresses the LV workload. 25 It can be calculated by gauging the cross-sectional area of the
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aorta (Aa) from its diameter and using the equation: ELI = (AVA × Aa)/(Aa – AVA)/body surface area. Global (valvular + arterial) hemodynamic load to the LV should also be assessed in patients with AS. Valvulo-arterial impedance (Zva) provides such an index; it is calculated by dividing estimated LV systolic pressure (systolic arterial pressure + mean transvalvular gradient) by the indexed stroke volume.23 Zva over 5 is considered to be high. This index appears to have prognostic implications and thus should be integrated in the overall decision-making process.
Echocardiographic Guidance for Interventions
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The options for interventions in patients with AS include surgical aortic valve replacement
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(SAVR) or transcutaneous aortic valve implantation 26,27. In patients undergoing SAVR,
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intraoperative TEE is often employed to reassess aortic root and aortic valve anatomy, evaluate surgical efficacy, and recognize immediate, post-operative complications, such as paravalvular
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regurgitation (Figure 5). The measurements of the aortic ring and ascending aorta, as
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mentioned earlier, are important to deciding the type and size of the prosthesis for patients, in whom TAVI is considered. During the procedure, whether via a transfemoral or transapical
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approach, TEE is useful in displaying the position of the delivery catheters and placement of the valve. 28,29 Additionally, post-procedure complications, such as paravalvular regurgitation,
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myocardial perforation, and hemopericardium, are instantly recognized.
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The Syndrome of Degenerative Calcific Aortic Stenosis
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Elderly patients with AS often have other disorders beyond aortic valve narrowing. 30,31
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Hypertension and atherosclerosis are associated with increased afterload to the ventricle. LV diastolic and systolic function could be abnormal secondary to AS, as well as to concomitant hypertension, ischemic heart disease, or other disorders. Co-existent degenerative mitral valve disease of varying severity could be present. Pulmonary hypertension, right ventricular dysfunction, and tricuspid regurgitation could be present. These associated disorders could influence the degree of hemodynamic perturbances, symptom expression, and clinical outlook. Degenerative calcific AS in older patients should be considered as more of a syndrome rather than just a valve disease. Awareness of various facets of this syndrome should be considered in the clinical evaluation of a patient with AS. Two-dimensional and Doppler examination provides
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comprehensive information to assess both the severity of AS and all the non-valvular
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derangements associated with valve stenosis.
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Co-existent Valve Disease
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Aortic regurgitation (AR) could be associated with AS in some patients. While AS is predominantly a pressure overload disorder, AR adds volume overload to the left ventricle in
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addition to pressure overload. If moderate or more severe AR is present, the aortic valve
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velocities and gradients increase because of increased forward SV. The anatomic AVA should still be reliable under this circumstance. The decision of when to intervene in a patient with
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such mixed valve disease should be made on the overall clinical picture that incudes symptoms,
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LV size and function, and other co-existent issues. Elderly patients with degenerative, calcific AS frequently have degenerative mitral valve disease as well, either in the form of mitral stenosis
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or regurgitation. The morphologic and functional severity of the mitral valve disease should be
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assessed to understand its contribution to the pathophysiology and symptoms. If there is significant mitral valve disease, the patient may not derive benefits from aortic valve intervention alone.
The Left Ventricle and Other Disorders The volumes and ejection fraction of the LV should be quantified since they have prognostic and therapeutic implications. Valve intervention is recommended if LV EF is less than 50%. Recent work employing speckle tracking echocardiography and cardiac magnetic resonance suggests that those with severe AS may have abnormal left ventricle even when the EF is
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normal.32,33 LV longitudinal strain of less than -15 appears to connote an adverse outcome with
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normal longitudinal strain resting around -20. This measurement is expected to become a
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standard approach to identifying early LV dysfunction and may influence therapeutic decision making in the future. Echocardiographic parameters of diastolic dysfunction, measures of
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pulmonary artery pressures,34 and RV function are important in the overall assessment of a
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patient with AS.
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Management Implications of Echocardiographic Findings of Aortic Stenosis Patients with AS of mild and moderate severity should be followed medically with periodic
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clinical and echocardiographic examinations. Echocardiographic evaluation annually or every 6
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months is prudent when AS is moderate since the stenosis severity can rapidly progress in some patients. Gauging the calcium burden and velocity increase is useful in identifying such patients.
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In patients with severe AS but with no symptoms, exercise echocardiography allows for an
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objective assessment of the effort tolerance and hemodynamic response to exercise. Left ventricular contractile reserve assessed by dobutamine stress echocardiography has prognostic implications in patients with severe AS and a low gradient. In older patients with co-existent disorders, echocardiographic and clinical evaluation provides a detailed portrait of the patient’s illness and guides therapeutic decision-making on the type of treatment.
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Figure Legends:
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Figure 1. Two- and three-dimensional images of the aortic valve. A) Normal aortic valve; B) Moderate
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aortic stenosis (AS) with decreased valve area; C) Severe AS with markedly decreased valve area; D) A bicuspid aortic valve with mild AS; E) Three-dimensional image of the same valve; F)
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Three-dimensional image of a severely stenotic valve.
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Figure 2.
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The method of deriving aortic valve area by continuity equation. Left: LA outflow diameter measurement to derive LV outflow area (A1); Middle: Pulsed Doppler recording of LV outflow
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flow velocity profile to obtain the velocity time integral (VTI1) to calculate the stroke volume;
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Figure 3.
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Right: Distal maximal flow velocity recording by continuous wave Doppler to derive VTI 2.
Hemodynamics in aortic stenosis. Top panel: Maximum velocity profiles of mild AS with a velocity of 2 m/s (left), moderate AS with a velocity of 3.2 m/s (middle), and severe AS with a velocity of 4.4 m/s (right). Bottom left: Schematic left ventricular and aortic pressure waveforms of normal (left) and in an example of severe AS. On the right are Doppler recording of a patient with severe AS. Maximum instantaneous gradient is derived by using the formula 4xV2 and mean gradient from the mean of multiple instantaneous gradients from the profile. Mean gradients by Doppler and pressure recordings are similar but the peak to peak gradient obtained from the invasive pressure recordings is lower than that obtained by Doppler.
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Figure 4.
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Schematic portraying multiple mechanisms that can result in a low gradient across the aortic
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valve despite severe AS.
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Figure 5.
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Transesophageal echocardiographic images during transcutaneous aortic valve implantation.
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A) Image showing a stenotic aortic valve with a guide-wire across. LA=left atrium; LV=left ventricle; Ao=aorta. B) Catheter with the prosthesis across the valve (arrow). C) 3-dimensional
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image during inflation of the prosthesis (arrow). D) A short-axis view of the prosthesis after implantation. E) Significant paravalvular regurgitation noted (arrow). F) 3-dimensional image
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showing paravalvular regurgitation.
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Fig 1
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Fig 2
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Fig 3
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Fig 4
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Fig 5
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Table 1. Comprehensive Echocardiographic Evaluation of Aortic Stenosis
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Aortic valve anatomy
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Number of cusps, calcium burden, aortic valve area by planimetry
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Hemodynamic Measurements
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LV outflow velocity time integral proximal to the valve
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Flow velocity and velocity time integral (VTI) across the aortic valve
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Proximal to distal VTI ratio
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Maximum instantaneous gradient and mean gradient
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Aortic valve area by continuity equation
Energy Loss Index
Valvulo-arterial impedance (global hemodynamic load, Zva)
Other Data
Aortic ring, sinus of Valsalva, Sino-tubular junction, and ascending aorta diameters
LV volume and ejection fraction, LV longitudinal strain
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Measures of diastolic dysfunction
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Pulmonary artery systolic pressure
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Right ventricular size and function
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Coronary artery disease and other co-existing disorders
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Table 2. Suggested Criteria for Grading the Severity of Aortic Stenosis
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_____________________________________________________________________________________ Moderate AS
Mild thickening of the valve
Mild-moderate valve thickening/calcification
Mild restriction to opening
Moderate restriction to opening
Aortic Vmax 2 m/s or less
Aortic Vmax 3-3.9 m/s
Mean Pressure Gradient < 20 mm Hg
Mean Pressure Gradient 20-39 mm Hg
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Mild AS
Aortic Valve Area > 1.5 cm2
Aortic Valve Area < 1 cm2 ; AVAi 0.7-1.0 m2/m2
Severe AS with Normal Flow
Marked restriction to opening
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SVi >35 mL/m2
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Severe thickening/calcification of the valve
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Aortic >Vmax 4 m/s
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_____________________________________________________________________________________ Severe AS with Low Flow Severe thickening/calcification of the valve Marked restriction to opening SVi <35 mL/m2 Aortic Vmax 3 - 4 m/s Mean Pressure Gradient 20-40 mm Hg
Aortic Valve Area < 1 cm2; AVAi < 0.6 m2/m2
Aortic Valve Area < 1 cm2 ; AVAi < 0.6 m2/m2
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Mean Pressure Gradient >40 mm Hg
(Abbreviations as in text)