Morphology of the Aortic Valve

Distinguishing bicuspid from tricuspid aortic valve is essential before TAVR. Although multiple imaging modalities can assess the morphology of the aortic valve and root, the diagnosis of bicuspid aortic valve is typically made using echocardiography. The short-axis views of the valve in systole should image a typical “fish-mouth” appearance of valve opening and absence of opening at the raphe. Systolic doming from the long-axis view may be another clue of a bicuspid valve. In patients with good-quality transthoracic images who do not have dense calcification, diagnostic sensitivity and specificity for identification of a bicuspid valve are >70% and >90%, respectively, but diagnostic uncertainty may remain in 10% to 15% of patients after echocardiography. In the setting of calcification with reduced leaflet excursion in systole, the abnormal motion of the two cusps may not be appreciated, and color Doppler may be helpful in distinguishing immobile trileaflet aortic valves without commissural fusion from bicuspid valves with fusion; color Doppler flow in all three commissures should be seen with trileaflet valves.

In addition to determining the number of cusps, the location and severity of calcium are important aspects of morphologic assessment. The prognostic importance of valve calcium by echocardiography has long been recognized, but MSCT has become the primary imaging modality for quantification of calcium burden. Ectopic calcification of the left ventricular outflow tract (LVOT) is predictive of PAR. In addition, in patients with low flow, the severity of calcification may help distinguish those patients with true severe AS from those patients with pseudosevere AS. Sex-specific criteria have been established, with aortic valve calcium cutoffs for severe AS of ≥1,275 arbitrary units in women and 2,065 arbitrary units in men. Interestingly, aortic valve calcium is also lower in women after indexing to body size or annular area, consistent with findings of increased fibrosis in women.

Assessment of Severity of AS

Echocardiography is used to assess valve morphology and severity of stenosis, as well as the cardiac response to AS, including left ventricular (LV) remodeling and function, mitral valve regurgitation, and pulmonary hypertension. Recent updates to the American Society of Echocardiography and European Society of Echocardiography guidelines, as well as an associated letter to the editor, review the echocardiographic parameters and acquisition recommendations. These parameters can be divided into flow-dependent measurements and flow-independent measurements and are summarized in Table 1 .

The greatest error in the aortic valve area (AVA) calculation is the squared LVOT diameter measurement. There are important caveats about the measurement of the LVOT diameter in the setting of AS ( Figure 2 , Table 2 ).

• •
  

  LVOT diameter should be measured at early to mid-systole (when the elliptical LVOT is more circular) from the image that provides the largest diameter.

  
  
• •
  

  LVOT diameter should be measured from the inner edge to inner edge from where the anterior (right coronary) cusp meets the ventricular anteroseptum, to the posterior “virtual annulus” where the posterior interleaflet triangle meets the anterior mitral leaflet. Avoid measuring the ectopic calcium as a border of the LVOT.

  
  
• •
  

  LVOT diameter measured below the aortic annulus underestimates catheter-derived AVA. This may be particularly true in the setting of a sigmoid septum.

  
  
• •
  

  AVA calculated with LVOT diameter measured at the level of the aortic annulus is more accurate and reproducible.

  
  
• •
  

  Because the greatest error in AVA calculation is the squared LVOT diameter measurement, using the ratio of V _LVOT /V _{AS jet} or VTI _LVOT /VTI _{aortic valve} can be a good indicator of AVA. A Doppler velocity index of ≤0.25 indicates severe stenosis.

Transthoracic and transesophageal echocardiographic optimization of LVOT measurement. Simultaneous biplane imaging from transthoracic (A,B) as well as transesophageal (C,D) imaging shows that an appropriately centered aortic valve in the long-axis view ( A or C ) will image the right coronary cusp (RCC) hinge point anteriorly ( B or D ) and the interleaflet trigone (between the left coronary cusp [LCC] and noncoronary cusp [NCC]) posteriorly. The maximum sagittal plane LVOT diameter ( yellow arrow ) should be measured from the inner edge to inner edge of the RCC hinge point/septal border to the posterior trigone/anterior mitral leaflet border. Importantly, the LVOT diameter measurement should avoid including ectopic calcium on the anterior mitral valve leaflet.

Although echocardiographic guidelines recommend a single diameter measurement of the LVOT to calculate AVA, planimetry of the aortic valve and LVOT area by real-time three-dimensional (3D) methods has been shown to be accurate and reproducible and to compare favorably with MSCT. Some studies suggest that using a direct area measurement of the LVOT in the continuity equation may yield a more accurate measurement of AVA. However, Clavel et al. compared the two methods for calculating AVA: the hybrid multislice computed tomographic planimetered LVOT in the continuity equation and the standard echocardiographic continuity equation. Compared with echocardiographic AVA, the hybrid method did not improve the correlation with transvalvular gradient, concordance between gradient and AVA, or prediction of mortality. Importantly, thresholds for excess mortality differed between techniques: AVA ≤ 1.0 cm ² for the echocardiographic method versus ≤1.2 cm ² for the hybrid method. These findings and other outcomes studies using the echocardiographic method for calculating AVA support the continued use of standard linear LVOT dimension to measure AVA and to guide management as recommended by current guidelines.

Because small-sized patients may not require the same amount of cardiac output as larger patients, the American Society of Echocardiography recommends indexing the valve area to body surface area (BSA), particularly in smaller patients with height < 135 cm (65 in), BSA < 1.5 m ² , or body mass index < 22 kg/m ² . The ACC guidelines use an indexed AVA of ≤0.6 cm ² /m ² to define severe AS. Importantly, indexing to BSA may not be appropriate in obese patients.

Some investigators have suggested that using an indexed cut-off of <0.5 cm ² /m ² may not only reduce inconsistent measurements with unindexed values, but lower indexed AVA cut-offs may also improve the prediction of outcomes.

Low-Gradient, Severe AS

As many as 40% of patients with AS may have discordant Doppler hemodynamics with low mean gradient (<40 mm Hg) in the setting of severely reduced valve area (≤1.0 cm ² ). Many of these patients have low flow, currently defined as a stroke volume index of <35 mL/m ² . Current AHA/ACC guidelines have subdivided the severe, symptomatic AS group of patients (stage D) into three separate categories: high-gradient AS (stage D1); low-flow, low-gradient AS with reduced ejection fraction (EF; stage D2); and low-gradient AS with normal EF (stage D3). Figure 3 shows the suggested approach to these subgroups of severe symptomatic AS.

Classification and characterization of the different types of AS according to AVA, gradient, LVEF, and flow. Classification of types of AS, including only the categories associated with symptoms and/or depressed LVEF. It does not include stage C1 (i.e., patients with high-gradient AS, no symptoms, and preserved LVEF). Question mark indicates stage labels or indications for aortic valve replacement (AVR) that are proposed but are not included in the guidelines and will need to be further tested and validated. AVAi , Indexed AVA; MG , mean gradient; RCT , randomized controlled trial; SVi , stroke volume index.

Reproduced with permission from Clavel et al.

Classic low-flow, low-gradient (mean gradient < 40 mm Hg) AS (AVA ≤ 1 cm ² ) with reduced EF (<50%; stage D2 in the ACC/AHA guidelines) is often associated with coronary artery disease but may have intrinsic disease of the myocardium or afterload mismatch related to severe stenosis. Because valve area has been shown to be flow dependent, multiple studies have used low-dose dobutamine stress echocardiography to increase the transvalvular flow rate while avoiding myocardial ischemia. The protocol for this test is described in the American Society of Echocardiography updated guidelines.

The D3 category of low-gradient, severe AS with normal EF is also known as “paradoxical AS.” Because velocity and gradient are dependent on flow, a number of physiologic situations can result in low flow in the setting of normal EF: tachycardia, bradycardia, hypertension, small ventricular cavity, severe diastolic dysfunction, severe mitral or tricuspid valve disease, pulmonary hypertension, and right ventricular dysfunction. The AHA/ACC guidelines do not advocate using dobutamine stress echocardiography with EF > 50%. Recent studies on the use of quantitative valve calcium scoring by MSCT may be useful.

If both flow and gradient are used to subcategorize patients with severe AS, then four categories may be generated ( Figure 3 ). The four different hemodynamic categories of patients with AS on the basis of flow (normal, >200 mL/sec) and gradient (high, >40 mm Hg): normal flow and high gradient, normal flow and low gradient, low flow and high gradient, and low flow and low gradient. The normal-flow, low-gradient entity is more difficult to explain, but this may be related to the use of stroke volume to define “normal flow” (i.e., stroke volume index ≥ 35 mL/m ² ). Flow (in milliliters per second) is calculated as stroke volume divided by ejection time. It is possible that patients with normal flow and low gradient have normal stroke volume in the setting of a prolonged ejection time, thus resulting in a low gradient.

Planimetry

Two-dimensional (2D) and 3D echocardiographic direct planimetry of the stenotic valve orifice can be also used to determine stenosis severity. Using 2D transthoracic echocardiographic planimetered AVA, Okura et al. showed that 2D transthoracic echocardiographic planimetry of AVA had a low standard error of estimates compared with valve area measured using transesophageal echocardiographic planimetry, the continuity equation, or the Gorlin equation (0.04, 0.09, and 0.10 cm ² , respectively). Importantly, planimetry and the Gorlin equation both measure the anatomic AVA, as the latter uses a correction coefficient for flow contraction. This flow contraction leads to the formation of the “vena contracta” beyond the anatomic orifice area. The area of the vena contracta represents the effective orifice area calculated by the continuity equation and is theoretically different from the area measured by planimetry. Multiple studies have suggested that 3D planimetered AVA may be more accurate, allowing alignment of the tips of all leaflets in the short-axis view. These measurements may be larger than 2D measurements and show a lower mean difference with continuity equation calculations.

Other Measures of AS Severity

Although measures of valve resistance, pressure recovery, energy loss, and arterial compliance and impedance are not recommended for routine clinical use, some may have significant prognostic information in certain subgroups of patients.

Differences in catheterization and echocardiographically measured gradients can arise in the setting of downstream pressure recovery. This net pressure drop between the left ventricle and the ascending aorta is the pathophysiologically relevant measurement and more representative of the geometric valve area. The energy loss index (ELI) is another measure that attempts to account for the total fluid mechanical energy loss related to both valve area and ascending aortic area. The ELI is calculated as ELI = [effective orifice area × A _A /A _A − effective orifice area]/BSA. Similar to valve area, it is less flow dependent than gradient or peak velocity, takes into account pressure recovery, and is roughly equivalent to effective orifice area measured by catheterization. Using the ELI, a substudy of the Simvastatin and Ezetimibe in Aortic Stenosis trial reclassified 47.5% of patients from severe to nonsevere AS. The energy loss is most significant in small aortas (<30 mm). An ELI of ≤0.5 to 0.6 cm ² /m ² is consistent with severe AS.

Finally, an index of global LV hemodynamic load, valvuloarterial impedance (Z _va ), accounts for both the load of the aortic valve and the increase in vascular resistance. An increase in systemic vascular resistance may be a compensatory mechanism in the setting of reduced transvalvular flow. Concomitant arterial hypertension is found to be present in a large proportion (35%–51%) of patients with AS. Z _va is calculated as Z _va = systolic blood pressure + ΔP _mean /stroke volume index. Several investigators have shown that the risk for mortality was increased with an increase in Z _va . Hachicha et al. found an increase in mortality of 2.76-fold in patients with Z _va ≥ 4.5 mm Hg · mL ⁻¹ · m ² and by 2.30-fold in those with Z _va between 3.5 and 4.5 mm Hg · mL ⁻¹ · m ² after adjusting for other risk factors.

Stress Testing in AS

The indications for stress testing for severe AS include determination of the etiology of symptoms in the setting of nonsevere disease, confirmation of asymptomatic status in the setting of severe disease, and evaluation of patients with concomitant valvular and myocardial dysfunction.

Because of the poor prognosis associated with symptom onset, determination of symptom status is an important role for stress testing in patients reporting no symptoms with severe AS. A number of parameters have been used to indicate a positive exercise treadmill test in the setting of AS:

• •
  

  development of symptoms (limiting breathlessness, chest pain or tightness, dizziness, and syncope);

  
  
• •
  

  development of arrhythmias (three consecutive ventricular premature beats or other complex ventricular arrhythmias);

  
  
• •
  

  blood pressure failing to increase by 20 mm Hg or a decrease in blood pressure of ≥10 mm Hg; and

  
  
• •
  

  development of horizontal or down-sloping ST-segment depression (≥1 mm in men, ≥2 mm in women) or ST-segment depression ≥ 5 mm measured 80 msec after the J point.

For patients with negative stress test results, outcomes may still not be benign, with the associated risk for symptom onset as well as sudden death. In patients with moderate or severe AS, an increase in mean gradient of ≥18 to 20 mm Hg during exercise testing predicts a higher risk for progression to symptoms and adverse events. To test the hypothesis that TAVR in asymptomatic patients may improve long-term outcomes compared with watchful waiting, the Early-TAVR clinical trial ( ClinicalTrials.gov identifier NCT03042104 ) is currently enrolling.

Detection of Associated Ventricular and Valvular Abnormalities

An essential part of the evaluation of every patient with AS is the assessment of chamber sizes, ventricular function, and concomitant valvular disease.

In chronic AS, changes in LV geometry are both adaptive and pathologic. As the pressure overload increases, an increase in wall thickness maintains normal wall stress and EF. Both an increase in wall thickness with normal LV mass (concentric remodeling) and increased LV mass (concentric hypertrophy) are frequently seen. Increased wall thickness in AS has been associated with impaired calcium handling, cytoskeletal changes, apoptosis, and increased collagen fiber deposition. These changes result in detectable reduced deformation characteristics and chamber compliance, before any change in EF. This cascade of events eventually leads to decreased stroke volume and increased filling pressure, resulting in heart failure with preserved EF. Thus strain imaging as well as diastolic function parameters may be early markers of abnormal LV function. Importantly, the European Association of Cardiovascular Imaging and American Society of Echocardiography consensus on the standardization of strain imaging defines deformation imaging terminology, the type of stored data that are used for quantitative analysis, the modality of measuring basic parameters, the definitions of parameters, and the results output with the aim of reducing intervendor variability.

Morphology of the Aortic Valve

Distinguishing bicuspid from tricuspid aortic valve is essential before TAVR. Although multiple imaging modalities can assess the morphology of the aortic valve and root, the diagnosis of bicuspid aortic valve is typically made using echocardiography. The short-axis views of the valve in systole should image a typical “fish-mouth” appearance of valve opening and absence of opening at the raphe. Systolic doming from the long-axis view may be another clue of a bicuspid valve. In patients with good-quality transthoracic images who do not have dense calcification, diagnostic sensitivity and specificity for identification of a bicuspid valve are >70% and >90%, respectively, but diagnostic uncertainty may remain in 10% to 15% of patients after echocardiography. In the setting of calcification with reduced leaflet excursion in systole, the abnormal motion of the two cusps may not be appreciated, and color Doppler may be helpful in distinguishing immobile trileaflet aortic valves without commissural fusion from bicuspid valves with fusion; color Doppler flow in all three commissures should be seen with trileaflet valves.

In addition to determining the number of cusps, the location and severity of calcium are important aspects of morphologic assessment. The prognostic importance of valve calcium by echocardiography has long been recognized, but MSCT has become the primary imaging modality for quantification of calcium burden. Ectopic calcification of the left ventricular outflow tract (LVOT) is predictive of PAR. In addition, in patients with low flow, the severity of calcification may help distinguish those patients with true severe AS from those patients with pseudosevere AS. Sex-specific criteria have been established, with aortic valve calcium cutoffs for severe AS of ≥1,275 arbitrary units in women and 2,065 arbitrary units in men. Interestingly, aortic valve calcium is also lower in women after indexing to body size or annular area, consistent with findings of increased fibrosis in women.

Assessment of Severity of AS

Echocardiography is used to assess valve morphology and severity of stenosis, as well as the cardiac response to AS, including left ventricular (LV) remodeling and function, mitral valve regurgitation, and pulmonary hypertension. Recent updates to the American Society of Echocardiography and European Society of Echocardiography guidelines, as well as an associated letter to the editor, review the echocardiographic parameters and acquisition recommendations. These parameters can be divided into flow-dependent measurements and flow-independent measurements and are summarized in Table 1 .

The greatest error in the aortic valve area (AVA) calculation is the squared LVOT diameter measurement. There are important caveats about the measurement of the LVOT diameter in the setting of AS ( Figure 2 , Table 2 ).

• •
  

  LVOT diameter should be measured at early to mid-systole (when the elliptical LVOT is more circular) from the image that provides the largest diameter.

  
  
• •
  

  LVOT diameter should be measured from the inner edge to inner edge from where the anterior (right coronary) cusp meets the ventricular anteroseptum, to the posterior “virtual annulus” where the posterior interleaflet triangle meets the anterior mitral leaflet. Avoid measuring the ectopic calcium as a border of the LVOT.

  
  
• •
  

  LVOT diameter measured below the aortic annulus underestimates catheter-derived AVA. This may be particularly true in the setting of a sigmoid septum.

  
  
• •
  

  AVA calculated with LVOT diameter measured at the level of the aortic annulus is more accurate and reproducible.

  
  
• •
  

  Because the greatest error in AVA calculation is the squared LVOT diameter measurement, using the ratio of V _LVOT /V _{AS jet} or VTI _LVOT /VTI _{aortic valve} can be a good indicator of AVA. A Doppler velocity index of ≤0.25 indicates severe stenosis.

Transthoracic and transesophageal echocardiographic optimization of LVOT measurement. Simultaneous biplane imaging from transthoracic (A,B) as well as transesophageal (C,D) imaging shows that an appropriately centered aortic valve in the long-axis view ( A or C ) will image the right coronary cusp (RCC) hinge point anteriorly ( B or D ) and the interleaflet trigone (between the left coronary cusp [LCC] and noncoronary cusp [NCC]) posteriorly. The maximum sagittal plane LVOT diameter ( yellow arrow ) should be measured from the inner edge to inner edge of the RCC hinge point/septal border to the posterior trigone/anterior mitral leaflet border. Importantly, the LVOT diameter measurement should avoid including ectopic calcium on the anterior mitral valve leaflet.

Although echocardiographic guidelines recommend a single diameter measurement of the LVOT to calculate AVA, planimetry of the aortic valve and LVOT area by real-time three-dimensional (3D) methods has been shown to be accurate and reproducible and to compare favorably with MSCT. Some studies suggest that using a direct area measurement of the LVOT in the continuity equation may yield a more accurate measurement of AVA. However, Clavel et al. compared the two methods for calculating AVA: the hybrid multislice computed tomographic planimetered LVOT in the continuity equation and the standard echocardiographic continuity equation. Compared with echocardiographic AVA, the hybrid method did not improve the correlation with transvalvular gradient, concordance between gradient and AVA, or prediction of mortality. Importantly, thresholds for excess mortality differed between techniques: AVA ≤ 1.0 cm ² for the echocardiographic method versus ≤1.2 cm ² for the hybrid method. These findings and other outcomes studies using the echocardiographic method for calculating AVA support the continued use of standard linear LVOT dimension to measure AVA and to guide management as recommended by current guidelines.

Because small-sized patients may not require the same amount of cardiac output as larger patients, the American Society of Echocardiography recommends indexing the valve area to body surface area (BSA), particularly in smaller patients with height < 135 cm (65 in), BSA < 1.5 m ² , or body mass index < 22 kg/m ² . The ACC guidelines use an indexed AVA of ≤0.6 cm ² /m ² to define severe AS. Importantly, indexing to BSA may not be appropriate in obese patients.

Some investigators have suggested that using an indexed cut-off of <0.5 cm ² /m ² may not only reduce inconsistent measurements with unindexed values, but lower indexed AVA cut-offs may also improve the prediction of outcomes.

Low-Gradient, Severe AS

As many as 40% of patients with AS may have discordant Doppler hemodynamics with low mean gradient (<40 mm Hg) in the setting of severely reduced valve area (≤1.0 cm ² ). Many of these patients have low flow, currently defined as a stroke volume index of <35 mL/m ² . Current AHA/ACC guidelines have subdivided the severe, symptomatic AS group of patients (stage D) into three separate categories: high-gradient AS (stage D1); low-flow, low-gradient AS with reduced ejection fraction (EF; stage D2); and low-gradient AS with normal EF (stage D3). Figure 3 shows the suggested approach to these subgroups of severe symptomatic AS.

Classification and characterization of the different types of AS according to AVA, gradient, LVEF, and flow. Classification of types of AS, including only the categories associated with symptoms and/or depressed LVEF. It does not include stage C1 (i.e., patients with high-gradient AS, no symptoms, and preserved LVEF). Question mark indicates stage labels or indications for aortic valve replacement (AVR) that are proposed but are not included in the guidelines and will need to be further tested and validated. AVAi , Indexed AVA; MG , mean gradient; RCT , randomized controlled trial; SVi , stroke volume index.

Reproduced with permission from Clavel et al.

Classic low-flow, low-gradient (mean gradient < 40 mm Hg) AS (AVA ≤ 1 cm ² ) with reduced EF (<50%; stage D2 in the ACC/AHA guidelines) is often associated with coronary artery disease but may have intrinsic disease of the myocardium or afterload mismatch related to severe stenosis. Because valve area has been shown to be flow dependent, multiple studies have used low-dose dobutamine stress echocardiography to increase the transvalvular flow rate while avoiding myocardial ischemia. The protocol for this test is described in the American Society of Echocardiography updated guidelines.

The D3 category of low-gradient, severe AS with normal EF is also known as “paradoxical AS.” Because velocity and gradient are dependent on flow, a number of physiologic situations can result in low flow in the setting of normal EF: tachycardia, bradycardia, hypertension, small ventricular cavity, severe diastolic dysfunction, severe mitral or tricuspid valve disease, pulmonary hypertension, and right ventricular dysfunction. The AHA/ACC guidelines do not advocate using dobutamine stress echocardiography with EF > 50%. Recent studies on the use of quantitative valve calcium scoring by MSCT may be useful.

If both flow and gradient are used to subcategorize patients with severe AS, then four categories may be generated ( Figure 3 ). The four different hemodynamic categories of patients with AS on the basis of flow (normal, >200 mL/sec) and gradient (high, >40 mm Hg): normal flow and high gradient, normal flow and low gradient, low flow and high gradient, and low flow and low gradient. The normal-flow, low-gradient entity is more difficult to explain, but this may be related to the use of stroke volume to define “normal flow” (i.e., stroke volume index ≥ 35 mL/m ² ). Flow (in milliliters per second) is calculated as stroke volume divided by ejection time. It is possible that patients with normal flow and low gradient have normal stroke volume in the setting of a prolonged ejection time, thus resulting in a low gradient.

Planimetry

Two-dimensional (2D) and 3D echocardiographic direct planimetry of the stenotic valve orifice can be also used to determine stenosis severity. Using 2D transthoracic echocardiographic planimetered AVA, Okura et al. showed that 2D transthoracic echocardiographic planimetry of AVA had a low standard error of estimates compared with valve area measured using transesophageal echocardiographic planimetry, the continuity equation, or the Gorlin equation (0.04, 0.09, and 0.10 cm ² , respectively). Importantly, planimetry and the Gorlin equation both measure the anatomic AVA, as the latter uses a correction coefficient for flow contraction. This flow contraction leads to the formation of the “vena contracta” beyond the anatomic orifice area. The area of the vena contracta represents the effective orifice area calculated by the continuity equation and is theoretically different from the area measured by planimetry. Multiple studies have suggested that 3D planimetered AVA may be more accurate, allowing alignment of the tips of all leaflets in the short-axis view. These measurements may be larger than 2D measurements and show a lower mean difference with continuity equation calculations.

Other Measures of AS Severity

Although measures of valve resistance, pressure recovery, energy loss, and arterial compliance and impedance are not recommended for routine clinical use, some may have significant prognostic information in certain subgroups of patients.

Differences in catheterization and echocardiographically measured gradients can arise in the setting of downstream pressure recovery. This net pressure drop between the left ventricle and the ascending aorta is the pathophysiologically relevant measurement and more representative of the geometric valve area. The energy loss index (ELI) is another measure that attempts to account for the total fluid mechanical energy loss related to both valve area and ascending aortic area. The ELI is calculated as ELI = [effective orifice area × A _A /A _A − effective orifice area]/BSA. Similar to valve area, it is less flow dependent than gradient or peak velocity, takes into account pressure recovery, and is roughly equivalent to effective orifice area measured by catheterization. Using the ELI, a substudy of the Simvastatin and Ezetimibe in Aortic Stenosis trial reclassified 47.5% of patients from severe to nonsevere AS. The energy loss is most significant in small aortas (<30 mm). An ELI of ≤0.5 to 0.6 cm ² /m ² is consistent with severe AS.

Finally, an index of global LV hemodynamic load, valvuloarterial impedance (Z _va ), accounts for both the load of the aortic valve and the increase in vascular resistance. An increase in systemic vascular resistance may be a compensatory mechanism in the setting of reduced transvalvular flow. Concomitant arterial hypertension is found to be present in a large proportion (35%–51%) of patients with AS. Z _va is calculated as Z _va = systolic blood pressure + ΔP _mean /stroke volume index. Several investigators have shown that the risk for mortality was increased with an increase in Z _va . Hachicha et al. found an increase in mortality of 2.76-fold in patients with Z _va ≥ 4.5 mm Hg · mL ⁻¹ · m ² and by 2.30-fold in those with Z _va between 3.5 and 4.5 mm Hg · mL ⁻¹ · m ² after adjusting for other risk factors.

Stress Testing in AS

The indications for stress testing for severe AS include determination of the etiology of symptoms in the setting of nonsevere disease, confirmation of asymptomatic status in the setting of severe disease, and evaluation of patients with concomitant valvular and myocardial dysfunction.

Because of the poor prognosis associated with symptom onset, determination of symptom status is an important role for stress testing in patients reporting no symptoms with severe AS. A number of parameters have been used to indicate a positive exercise treadmill test in the setting of AS:

• •
  

  development of symptoms (limiting breathlessness, chest pain or tightness, dizziness, and syncope);

  
  
• •
  

  development of arrhythmias (three consecutive ventricular premature beats or other complex ventricular arrhythmias);

  
  
• •
  

  blood pressure failing to increase by 20 mm Hg or a decrease in blood pressure of ≥10 mm Hg; and

  
  
• •
  

  development of horizontal or down-sloping ST-segment depression (≥1 mm in men, ≥2 mm in women) or ST-segment depression ≥ 5 mm measured 80 msec after the J point.

For patients with negative stress test results, outcomes may still not be benign, with the associated risk for symptom onset as well as sudden death. In patients with moderate or severe AS, an increase in mean gradient of ≥18 to 20 mm Hg during exercise testing predicts a higher risk for progression to symptoms and adverse events. To test the hypothesis that TAVR in asymptomatic patients may improve long-term outcomes compared with watchful waiting, the Early-TAVR clinical trial ( ClinicalTrials.gov identifier NCT03042104 ) is currently enrolling.

Detection of Associated Ventricular and Valvular Abnormalities

An essential part of the evaluation of every patient with AS is the assessment of chamber sizes, ventricular function, and concomitant valvular disease.

In chronic AS, changes in LV geometry are both adaptive and pathologic. As the pressure overload increases, an increase in wall thickness maintains normal wall stress and EF. Both an increase in wall thickness with normal LV mass (concentric remodeling) and increased LV mass (concentric hypertrophy) are frequently seen. Increased wall thickness in AS has been associated with impaired calcium handling, cytoskeletal changes, apoptosis, and increased collagen fiber deposition. These changes result in detectable reduced deformation characteristics and chamber compliance, before any change in EF. This cascade of events eventually leads to decreased stroke volume and increased filling pressure, resulting in heart failure with preserved EF. Thus strain imaging as well as diastolic function parameters may be early markers of abnormal LV function. Importantly, the European Association of Cardiovascular Imaging and American Society of Echocardiography consensus on the standardization of strain imaging defines deformation imaging terminology, the type of stored data that are used for quantitative analysis, the modality of measuring basic parameters, the definitions of parameters, and the results output with the aim of reducing intervendor variability.

Predeployment Imaging

The comprehensive intraoperative preprocedural evaluation is summarized in Table 4 . Preprocedural assessment of aortic root anatomy and dimensions is paramount to the selection of the appropriate prosthesis. Several factors are considered when selecting an optimal prosthetic valve for a patient: aortic annulus and geometry, aortic root and LVOT anatomy, angulation of the aorta (aortoventricular angle), coronary height, and amount and distribution of calcification. Undersizing a prosthetic valve may lead to PAR or device embolization, while oversizing may result in aortic root rupture, coronary ostia occlusion, or conduction abnormalities. Evaluation of the aortic root starts with measurement of the aortic annulus. Various vendor-specific annular measurement packages measure maximum and minimum diameters, perimeter, and area of the aortic annulus. Although the word annulus implies a circular structure, there is no histologic or anatomic boundary to define it and to guide measurement. Rather, the measurements are performed in a virtual plane defined by the nadirs of the semilunar leaflet attachments. Traditionally, the aortic annulus has been described by a single measurement from 2D transthoracic echocardiography (TTE) or TEE. However, the three-dimensionality and the complexity of the aortic root anatomy can be adequately appreciated only by using a 3D imaging modality. This has been investigated in studies that showed that the incidence of more than mild PAR was significantly lower when sizing of the aortic annulus was performed using MSCT compared with sizing performed by 2D echocardiography. Two-dimensional echocardiography consistently underestimates the size of the aortic annulus for several reasons: (1) a linear dimension assumes a circular geometry of the annulus, while a growing body of literature has shown that it is nearly uniformly oval shaped ; (2) the long-axis or sagittal plane in which the measurement is performed may be not bisect the maximum dimension of the annulus (i.e., imaging of the hinge point to hinge point rather than hinge point to fibrous trigone); and (3) the measurement in the long-axis view generally represents the smaller diameter of the noncircular annulus.

Three-dimensional echocardiography overcomes the limitations of 2D imaging by allowing measurements of the annular area and perimeter. Although 3D TTE lacks the spatial resolution for adequate measurements of the aortic root, several recent studies have shown that measurements performed by multiplanar reconstruction of 3D transesophageal echocardiographic data sets yields comparable results with those obtained using MSCT, at the same time avoiding the risks associated with exposure to radiation and contrast dye. Multiplanar reconstruction of a 3D data set facilitates direct measurements of the major and minor diameters, as well as annular area and perimeter from an on-axis short-axis plane ( Figure 4 A). Other investigators have used vendor-specific software originally designed for the mitral valve to indirectly planimeter the annulus ( Figure 4 B) and proved that annular measurements by both 3D TEE and MSCT predicted mild or greater PAR with equivalent accuracy.

Multiplanar reconstruction of a 3D data set by two methods. (A) Multiplanar reconstruction of the virtual annular plane ( red box ) obtained by aligning the long-axis transverse plane ( green box ) and coronal plane ( blue box ). The annulus is measured by direct planimetry. (B) Indirect planimetry method, which uses a mitral valve software package, QLAB MVQ software (Philips Medical Systems, Andover, MA), thus tricking the system into measuring the aortic annulus as if it were a mitral annulus. The top two quadrants of (B) show the positioning of the “anterior” (A), “posterior” (P), “posteromedial” (PM), and “anterolateral” (AL) annular indicators. On successive rotations of the two orthogonal long-axis planes ( green and red boxes ), the annular plane is identified and automatically shown in the annular short axis of the blue plane ( blue dots ). The complete the annular plane is created without actually planimetering on the annular short axis and is thus an “indirect” planimetric method. Both methods yield the annular area, perimeter, and maximum and minimum dimensions of the annulus.

Besides dimensions of the aortic annulus, other measurements of the aortoannular complex should be performed, such as the size of the sinuses of Valsalva, diameter of the aorta at the sinotubular junction, and the distance of the coronary artery ostia from the annulus. Because the left coronary artery ostium lies in the coronal plane, the coronary height can be measured only by multiplanar reconstruction ( Figure 5 ). Data from a large multicenter registry of coronary obstruction after TAVR, showed the left coronary artery was most commonly involved (88.6%), with lower mean left coronary artery ostia height (10.6 ± 2.1 vs 13.4 ± 2.1 mm, P < .001) and sinus of Valsalva diameter (28.1 ± 3.8 vs 31.9 ± 4.1 mm, P < .001) compared with control subjects. The distribution of calcium in the aortic root, extension into the LVOT and aortomitral curtain, and proximity of calcium to the coronary artery ostia should also be described. LVOT morphology with the presence of basal septal hypertrophy as well as the presence of midventricular hypertrophy is important to assess, as the development of subvalvular dynamic obstruction with hemodynamic instability after valve deployment has been described.

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