Aortic Stenosis (Including Evaluation for Transcatheter Aortic Valve Replacement)

Aortic Velocity And Mean Pressure Gradient

The antegrade systolic velocity across the stenotic valve is measured with the use of continuous-wave (CW) Doppler imaging. To obtain the maximum velocity signal, parallel alignment of the Doppler beam with the stenotic jet is mandatory, and multiple acoustic windows must be used. Color flow may help to identify jet direction, but the three-dimensional (3D) orientation of the jet may be unpredictable.

Starting with an apical 5-chamber view, the transducer position is modified in such a way that the Doppler beam is truly parallel to the orientation of the LVOT, including positions somewhat dorsal and lateral to the apex. Gain is decreased, wall filter is high, sweep velocity is maximal, and baseline and scale are optimized to display a clear, smooth signal filling the vertical dimension of the monitor. Frayed signals with blurred borders or peak should be neglected.

Next, multiple right parasternal windows are located with the patient lying on the right side ( Fig. 22.5 ). Color flow is helpful for orientation of the Doppler beam parallel to the jet. Sometimes, a dedicated stand-alone CW Doppler transducer is required to allow unusual positioning and angulation. Rarely, additional acoustic windows (i.e., suprasternal, left parasternal, or subcostal) are necessary.

A meticulous search for the maximum velocity is extremely important to avoid underestimation of AS severity, particularly when morphologic changes or clinical symptoms do not match the recorded velocity. The transducer position in which the highest velocity was recorded should be documented in the report for future studies. Aortic maximum velocity (peak velocity) is measured at the peak of the recorded signal. Post-extrasystolic beats should be neglected, and averaging of at least five beats is mandatory in patients with atrial fibrillation ( Fig. 22.6 ).

Aortic maximum velocity may be directly transformed into maximum gradient by the simplified Bernoulli equation:

where ΔP = pressure gradient, and V ₂ = peak velocity of the stenotic jet. The original Bernoulli equation is a complex formula describing the general relation between velocity and gradient in stenotic lesions, taking into account (among other parameters) flow acceleration and viscous losses that can be neglected in clinical practice. However, the more accurate formula considering pre-stenotic velocity may be sometimes more appropriate:

where ΔP = pressure gradient, V ₂ = peak velocity of the stenotic jet, and V ₁ = pre-stenotic velocity. This equation should be used when V ₁ is greater than 1.2 m/s.

Mean velocity and velocity–time integral (VTI) are obtained by tracing the outer envelope of the signal. The mean of multiple instant velocities (i.e., mean velocity) is calculated and then integrated over time (VTI). The VTI is used for calculation of AVA by the continuity equation . Mean gradient is calculated by averaging the instantaneous gradients over the systolic ejection period derived from the simplified Bernoulli equation, neglecting pre-stenotic velocities.

Aortic maximum velocity and mean pressure gradient are directly derived from the same CW Doppler signal and are closely correlated ( Fig. 22.7 ). The information derived from the two parameters may be considered equivalent, with an aortic maximum velocity of greater than 4 m/s and a mean gradient greater than 40 mmHg indicating severe AS.

Aortic maximum velocity (i.e., peak velocity) is the best validated parameter related to outcomes of patients with AS. A gradual increase of clinical events has been demonstrated with increasing aortic maximum velocity in asymptomatic patients ( Fig. 22.8 and Tables 22.2 and 22.3 ). ^, With peak velocities greater than 4 m/s, 1-year event rates rise substantially, providing a clinical rationale for the currently accepted partition value for severe stenosis. Rapid progression of peak velocity (>0.3 m/s per year) has been identified as a marker for future adverse events. A more rapid progression is seen in patients with higher degrees of calcification and valve obstruction and in patients with coronary heart disease.

Continuity Equation Aortic Valve Area

If LV function and output are reduced, additional, less flow-dependent parameters to define AS severity are required. To this end, AVA is calculated from the continuity equation, which is based on the consideration that the same stroke volume passes through the LVOT and the aortic valve (see Figs. 22.3 and 22.4 ). Stroke volume in echocardiography is measured as the product of the VTI of flow and the cross-sectional area; therefore, the equation is

where A ₁ = LVOT area; VTI ₁ = pre-stenotic VTI of flow within the LVOT; A ₂ = AVA; and VTI ₂ = VTI of the stenotic jet through the aortic valve. Measurement of A ₁ and VTI ₁ is described later. Three of the four components of the continuity equation can be measured directly, and AVA can be calculated as follows:

Because the ejection times of flow within the LVOT and through the aortic valve are considered equal, the maximum (or mean) velocities may be used instead of VTIs, further simplifying the equation:

Use of maximum velocities results in a slightly higher AVA than when mean velocities are used because the former reflect the largest possible AVA at maximum flow, whereas mean velocities yield an average AVA over the whole systolic period.

To account for differences in body surface area (BSA), an indexed AVA (AVAi) may be calculated:

Severe AS is indicated by an AVA smaller than 1.0 cm ² or an AVAi smaller than 0.6 cm ² /m2.

LV Outflow Tract Velocity

The pre-stenotic velocity V ₁ is measured within the LVOT using PW Doppler in an apical 5-chamber or 3-chamber view. The transducer position should be optimized in such a way that the Doppler beam is truly parallel to the orientation of the LVOT and includes positions somewhat dorsal and lateral to the apex. Gain is decreased, wall filter is low, sweep velocity is maximal, and baseline and scale are optimized to display a clear, smooth, and laminar flow signal filling the vertical dimension of the monitor. An optimal laminar flow signal shows no spectral dispersion, with a sharp rim and a black center.

The sample volume should be placed as close to the aortic valve as possible. The correct position of the sample volume can be reached by moving it slowly from the aortic valve into the LVOT while the flow signal is changing from turbulent to laminar; the first position with laminar flow is used for measurements.

Mean velocity and VTI are obtained by tracing the outer envelope of the signal. As with aortic velocity, the mean of multiple instant velocities is calculated (mean velocity) and integrated over time (VTI). The VTI ₁ is used for the calculation of AVA. It is also required for the calculation of stroke volume (see Fig. 22.3 ). The correctness of LVOT velocity may be checked by identifying its maximal velocity within the CW signal or with color Doppler ( Fig. 22.9 ).

LV Outflow Tract Diameter

The LVOT diameter is measured in a zoomed parasternal long-axis view at mid-systole (the time of its maximal size). Several attempts may be necessary to obtain the maximal anterior-posterior diameter. Measurements should be performed as close to the aortic valve as possible (reflecting the position of the sample volume used for recording pre-stenotic LVOT velocity), from inner edge to inner edge of the septal wall to the fibrous aortic-mitral continuity parallel to the aortic valve. Optimal image quality is necessary to correctly identify tissue–blood interfaces. Localized calcification protruding to the LVOT should be excluded from the measurement ( Fig. 22.10 ). LVOT area is calculated as follows:

${\text{A}}_1={\text{πr}}^2$

where A ₁ = area of LVOT, and r = radius (= diameter/2). LVOT area is required for the calculation of AVA and stroke volume. The AVA has been linked to outcomes for patients with AS, but its gradual impact on prognosis is less strong than with peak velocity in asymptomatic patients (see Table 22.3 ). However, the assessment of AVA is mandatory to estimate AS severity in any situation when flow is out of the normal range.

Stroke Volume Index

Reduced transvalvular flow may occur in patients with apparently normal systolic LV function, and stroke volume index (SVI) has become an important parameter in evaluating AS severity. Low-flow/low-gradient severe AS with preserved ejection fraction (EF) is considered a distinct presentation of severe AS (stage D3) with a unique pathway of concentric LV remodeling. ^,

Stroke volume is calculated from the product of the pre-stenotic VTI and the LVOT area and is usually indexed to BSA. An SVI at rest of at least 35 mL/m ² is considered normal, whereas an SVI of less than 35 mL/m ² implies low flow.

AVA and stroke volume are calculated using the measurements of pre-stenotic VTI and LVOT diameter volume (see Fig. 22.3 ). The AVA always contains information on stroke volume. For this reason, measurement error, typically underestimation of the LVOT diameter, results in underestimation of the AVA and stroke volume. Stroke volume should be checked using 2D or 3D ventricular volumes. Concordance of Doppler and anatomic stroke volume may provide more robust evidence of a low-flow state. Indirect signs, including atrial fibrillation, severe hypertrophy, and mitral or tricuspid regurgitation, may help to confirm reduced transvalvular flow.

Velocity Ratio

Calculation of LVOT area is a problem for AVA assessment because interobserver reproducibility of the LVOT diameter measurement is low and because the LVOT anatomy is oval rather than circular. The velocity ratio (VR), based on maximal pre-stenotic and stenotic velocities or VTIs, has been used as a simplified measure of AS severity that is less flow dependent than aortic maximum velocity or mean pressure gradient:

Neglecting LVOT size is a limitation for small and very large LVOTs. However, VR is a helpful parameter in the longitudinal follow-up of patients because the LVOT size in an individual can be expected to remain constant over time. A velocity ratio smaller than 0.25 indicates severe stenosis.

VR based on maximal velocities can frequently be estimated directly from the CW Doppler signal because the pre-stenotic velocity is apparent as a bright area at its base. The VR may be used as a control for the measurement of pre-stenotic velocity in general, but it becomes essential in patients with atrial fibrillation, when subsequent beats vary widely and VR is otherwise difficult to assess (see Fig. 22.6 ). In that case, at least five simultaneous VR values are calculated from different CW Doppler signals. VR, as part of the continuity equation, may then be used to calculate the AVA in atrial fibrillation.

VR can be used to predict clinical outcomes in asymptomatic patients and to address discrepancies between echocardiographic parameters of AS severity. However, it does not outperform peak velocity or mean gradient as a prognostic marker. ^,

Tee Planimetry Valve Area

Multiplane TEE allows detailed visualization of valve morphology. Planimetry (i.e., tracing of the anatomic AVA) can be performed in most cases and may be very useful in the context of discrepancies between hemodynamic parameters of stenosis severity in patients with moderate to severe stenosis on transthoracic evaluation. Even without direct measurement of the anatomic AVA, valve morphology provides some information on AS severity.

For planimetry, the aortic valve is displayed in the center of an exact long-axis view, which is the basis for a zoomed short-axis view perpendicular to it. Image parameters are adjusted carefully. Exact recognition of tissue–blood borders in moving loops is a prerequisite for adequate tracing in frozen images ( Fig. 22.11 ). The anatomic AVA is traced in mid-systole, and several measurements may be required, particularly when there is severe calcification. In bicuspid valves with domed morphology, the maximum flow restriction occurs at the tip of the cusps, and meticulous inspection of the smallest orifice in short-axis views at the highest point in direction of flow is mandatory to avoid overestimation of anatomic AVA. Synchronous display of two perpendicular planes may help to define the appropriate short-axis view for planimetry.

TEE enables a clear delineation of LVOT morphology, which can be difficult to assess in transthoracic echocardiographic (TTE) views. The LVOT is displayed, and its diameter is measured as described for the transthoracic approach. This may be helpful in the setting of additional LVOT obstruction due to a fibrous membrane or a systolic anterior movement (SAM) of parts of the mitral valve. Most importantly, it allows remeasurement of the LVOT diameter in excellent image quality and may therefore serve as a control for TTE assessment and recalculation of the AVA by combining the TTE Doppler parameters with the LVOT diameter from TEE if necessary (see Fig. 22.11 ).

Modern matrix-array transducers capture real-time volume-rendering images and allow off-line volumetric quantification from a 3D data set. This may help to define anatomic AVA with TEE in difficult cases (e.g., bicuspid valves; see Fig. 22.2 ). Despite remaining limitations due to severe calcifications, the overall feasibility of this approach was shown to be good.

Measurement Variability And Errors

Aortic maximum velocity and mean pressure gradient are robust measures of AS severity when the maximal jet velocity has been successfully identified from multiple acoustic windows (see Fig. 22.5 ). Intraobserver and interobserver variability in the assessment of Doppler recordings and measurements are high (coefficient of correlation = 0.9, coefficient of variation, 3.7%–7.7%). The continuity equation yields reliable values for AVA (provided all its components have been assessed correctly) and represents the second most important measure of AS severity, with higher variability due to more complex measurements.

Pre-stenotic flow tends to be overestimated because Doppler echocardiography measures flow velocity at the center of the LVOT, erroneously assuming a homogeneous and flat velocity profile. However, the LVOT area is commonly underestimated because of its oval shape, with the shorter anterior-posterior diameter measured in 2D echocardiography. It has been suggested that slight overestimation of pre-stenotic flow may be compensated by slight underestimation of LVOT area. ^,

The most important measurement errors are Doppler misalignment with aortic flow, caused by not using multiple windows (see Fig. 22.5 ), and underestimation of LVOT diameter, caused by not carefully searching for the widest anterior-posterior distance (see Fig. 22.10 ). LVOT velocity should always be checked for correctness (see Fig. 22.9 ).

Effect of Transaortic Flow

Aortic maximum velocity and mean pressure gradient are extremely flow dependent. Low-flow and high-flow states have to be considered when interpreting these measures with respect to AS severity because they can result in a gradient that is lower or higher, respectively, than that expected from the calculated AVA. Up to 30% of patients with AS present with low-flow states and reduced or normal EF. Recent guidelines , , recommend the assessment of SVI to identify these patients, with a cutoff value of 35 mL/m ² or less. High flow may be seen in up to 15% of patients, including those with aortic regurgitation, end-stage renal failure, arteriovenous fistula, fever, or anemia, but occasionally the reason may be unidentifiable. A maximum LVOT velocity greater than 1 m/s may suggest an SVI of 58 mL/m ² or higher, which may be the clue to identifying a high-flow state. However, a cutoff value analogous to the one used to identify low flow has not been validated.

AVA is used as a less flow-dependent measure of AS severity. However, opening of stiff, calcified cusps depends to a certain degree on opening forces and may be incomplete with low flow. This is particularly important if a small AVA is observed in combination with a low mean gradient due to impaired LV function. Stimulation of LV contractility with dobutamine is used to increase transvalvular flow and assess AS severity under normalized flow conditions; this discriminates fixed AS from pseudosevere AS by demonstrating opening reserve with increasing opening forces. Flow rate (FR), measured in milliliters per second, also accounts for the time of flow through the stenotic valve. It therefore mirrors opening forces more accurately than stroke volume does:

or, alternatively,

where SV is stroke volume, ET is ejection time, A ₁ is the LVOT area, and V _1mean is the mean velocity within the LVOT. The AVA reflects true AS severity down to an FR of 200 mL/s, and dobutamine stimulation may be required only if FR at rest is below this value.

Adjustment For Body Size

Aortic maximum velocity and mean pressure gradient are body size–independent measures of AS severity. In contrast, AVA exhibits a strong correlation to body size. AVAi successfully eliminates this correlation and improves comparability among patients with different body sizes. Small patients have lower oxygen needs, smaller heart chambers, and lower stroke volumes than larger individuals, producing lower mean pressure gradients.

An AVA of 0.9 cm ² has different hemodynamic implications in small compared with larger individuals, representing moderate stenosis in the former and severe stenosis in the latter. However, the general use of the recommended partition value for AVAi (0.6 cm ² /m ² for severe stenosis) overestimates stenosis severity in patients with higher BSA, partially due to obesity, and it is useful only in small patients (BSA < 1.6 cm ² ). Normalization to height may be an appropriate alterative for obese patients. The velocity ratio may be used as an alternative measure of AS severity, independent of body size and flow and not requiring measurement of LVOT with its potential limitations. ^,

Concurrent Hypertension

Uncontrolled hypertension may lead to reduced stroke volume, reduced mean gradient, and a smaller AVA compared with blood pressure in the normal range. Blood pressure should be below 140/90 mmHg when AS severity is assessed. Blood pressure at the time of echocardiography should be reported.

Anatomic Versus Effective Aortic Valve Area And Pressure Recovery

The continuity equation calculates an effective AVA, which is slightly smaller than the anatomic AVA because flow further converges downstream of the anatomic orifice (vena contracta) before turbulent flow appears in the ascending aorta ( Fig. 22.12 ). The magnitude of disparity between the effective and the anatomic AVA depends on orifice size and shape, showing increasing differences in small valve areas, flat geometry, and eccentric jets. Significant differences between anatomic and effective AVA are typically observed in patients with bicuspid valves and eccentric jets.

Some of the energy loss in the stenotic jet is reconverted to pressure energy in the ascending aorta. This phenomenon, called pressure recovery , leads to a lower net gradient between the LV and aorta than that measured in the immediate vicinity of the aortic valve (see Fig. 22.12 ). This may explain some differences in mean pressure gradient between catheter and Doppler measurements: Doppler imaging does not account for pressure recovery, whereas catheter pressures are usually recorded in the aorta, after pressure recovery has occurred.

The extent of this phenomenon depends on the difference between the stenotic orifice and the cross-sectional area of the ascending aorta. The smaller the valve orifice relative to the size of the aorta, the more turbulence will occur and the less energy will be available to be recovered as pressure. Significant amounts of pressure recovery are observed in the setting of mild to moderate AS when the ascending aorta is relatively small (<30 mm).

To account for pressure recovery, the energy loss index (ELI) has been proposed. It represents a virtual AVA (adjusted for BSA), assuming that the net gradient was the consequence of a stenosis without the existence of pressure recovery (see Fig. 22.12 ). ELI is calculated as follows:

where A _a = the cross-sectional area of the ascending aorta at the sinotubular junction and AVAi = AVA indexed by BSA.

Besides its theoretical advantages, ELI can provide prognostic information. However, it does not outperform other measures of AS severity in patients with mild to moderate AS.

Discordance Between Measures Of Aortic Stenosis Severity

Severe AS is defined as a V _max greater 4 m/s and a mean gradient greater than 40 mmHg. The corresponding value for AVA is less than 1 cm ² (see Table 22.1 ). Frequently, discordance between mean pressure gradient and AVA is observed, resulting in uncertainty about AS severity (see Fig. 22.7 ). Any discordance should prompt meticulous review of all measurements involved. However, discordance may persist despite correct assessment of all required components ( Table 22.4 ).

In most discrepant cases, an AVA of less than 1.0 cm ² indicates severe AS, whereas a mean pressure gradient of less than 40 mmHg points to a nonsevere stenosis. This discordance may be related to low-flow states causing a relatively low mean gradient despite a severely stenotic aortic valve, a combination that may occur with reduced or with normal EF (stages D2 and D3, respectively). First, it may be recognized by direct signs (SVI ≤ 35 mL/m ² ) or indirect signs of a reduced flow, which have to be carefully searched for or ruled out. Second, it may be the consequence of small body size, making the use of AVAi necessary for small patients. Third, having excluded the aforementioned reasons for discordance, an inherent inconsistency between AVA and mean pressure gradient partition values for severe stenosis as outlined in the current guidelines , should be considered. A mean gradient of 40 mmHg correlates with an AVA of 0.8 to 0.9 cm ² (rather than 1.0 cm ² ) in normal flow conditions (i.e., normal EF and normal SVI). Conversely, an AVA of 1.0 cm ² correlates with a mean gradient close to 30 mmHg (not 40 mmHg), meaning that an AVA of less than 1.0 cm ² indicates severe AS at an earlier stage of disease than a mean pressure gradient of greater than 40 mmHg. ^,

Discordance of AVA and mean gradient in normal flow states is called normal-flow/low-gradient severe AS ; it shares many characteristics with moderate AS and does not require aortic valve replacement (AVR). ^{, ,} The complex overlay and interactions of various phenomena in low-gradient AS often demand additional diagnostic modalities to confirm AS severity. TEE and calcium scoring by computed tomography (CT) (discussed later) seem to be most helpful in this condition.

In some cases, a reverse discordance is observed, with a mean pressure gradient greater than 40 mmHg, indicating severe AS, but an AVA greater than 1.0 cm ² , pointing to a nonsevere stenosis. It can be explained by high flow, including cardiac and noncardiac causes, as discussed earlier. It is also seen in congenital AS cases, which often exhibit eccentric jets. These jets immediately strike the aortic wall, leading to less pressure recovery and higher gradients than in a comparable AVA, and the Doppler gradient seems to represent the true AS severity. The velocity ratio may also be used because it represents a measure of AS severity independent of body size and flow. ^,