We found that AVA derived from 2D continuity equation correlates only modestly with that derived from 3D colour Doppler and that significant discrepancies between both methods are predicted by presence of USH, representing distorted LVOT geometry. We demonstrate that RT3DE measurement of LVOT SV agrees better with the gold standard of aortic flow probe measurement in an animal model of varying LVOT geometry than 2DE. In addition, there was a better agreement of RT3DE derived AVA using colour Doppler with an independent anatomical standard, AVA guided by RT3DE planimetry.
Two-dimensional Doppler continuity equation
2DE derived continuity equation is still the current most utilized method in obtaining AVA since it is non-invasive, practical, and easily employed.1
However, its pitfalls are well known due to the inherent assumptions and simplifications. For instance, the LVOT cross-sectional area calculation assumes a circular shape for the LVOT and errors in measuring the LVOT diameter are squared in the computation of AVA. In addition, the determination of LVOT velocity by 2DE is performed using another echocardiographic window and so differs in timing and location as the LVOT area measurement. Flow velocity varies within the LVOT, having a non-uniform pattern with lower velocities at the vessel periphery, higher velocities at the centre especially in the septal and posterior area.10–14
Values obtained are thus dependent upon the position of pulse wave Doppler sampling area. In addition, significant USH may be associated with mild LVOT obstruction and introduce error. Pulse wave velocity determination may also be angle-dependent,15
inaccurate especially in low-output states10
and large sampling volumes may be required for reliable estimates of mean velocity.11,12
Geometric assumptions may not be valid in asymmetric LVOT shapes such as that seen with USH. Indeed, in our experimental studies where USH was simulated, the 2DE derived LVOT SV correlated poorly to flow probe compared to 3DE colour Doppler.
Three-dimensional Doppler continuity equation
Using RT3DE to measure AVA, these shortfalls can be circumvented altogether. RT3D colour Doppler can overcome inaccuracies of spectral Doppler for SV calculation.16
By directly measuring the LVOT SV, 3D acquisitions overcome geometric assumptions that the LVOT cross-sectional area is circular. Indeed, we found that in more than half of our cases, the LVOT is either oval or irregular in shape. This is consistent with other studies which found the majority of LVOT to be oval.17
Furthermore, with a 3D hemispheric sampling curve capturing velocities within the LVOT, varying velocities within the entire systole will be sampled and angle-dependency is less important in contrast to a planar sampling area, since velocities will project perpendicularly onto the hemispheres. Previous work has also shown less dependency with 3D methods of flow volume computation compared to 2D Doppler, though this was not performed in real time.18
Depending on whether the longer or shorter diameter of the oval cross-section was measured on 2DE, over- or under-estimation of the SV may result, compared to 3D Doppler. As the actual flow across the LVOT is directly quantitated, non-simultaneous separated measurements of stroke distance and cross-sectional area are therefore not necessary, reducing error.
When discrepancies between 2D and 3D continuity equation derived areas were analysed, the sole predictor was the degree of USH. In patients with no significant LVOT USH, discrepancies were lower and calculation of AVA2D may be sufficient. However, with USH, clinical differences between AVA3D-SV and AVA2D appeared determined by the LVOT geometry.
Recently, the use of live 3D colour Doppler in the assessment of LVOT CO has been shown to correlate well with flow probe (r2
= 0.93 or r2
= 0.99 after averaging the measurements) in normal juvenile pigs.5
The same group also showed good correlation between 3DE SV calculation and 2DE pulsed wave SV estimation in humans aged 28 ± 20.5 yrs with normal LVOT and aortic valve (r2
In a patient study, using thermodilution as the gold standard for comparison, 3D Doppler derived CO correlated better, with smaller bias and narrower limits of agreement compared to 2D Doppler derived CO.19
These studies demonstrated the validity of SV calculation using 3DE. They are consistent with our data which showed similarly excellent correlation of r2
= 0.95 even in the setting of USH.
Stroke volume calculation
Besides using 2D or 3D Doppler to assess left ventricular SV, other non-invasive echocardiographic methods include left ventricular volume calculations from 2D end-diastolic and end-systolic frames, by the summation of disks. These are prone to errors due to difficulties in defining the LV borders20
or abnormal ventricular geometry. 3D assessment of chamber volumes provides a better alternative without geometric assumption.21
However, it is more time-consuming and less direct than 3D Doppler assessments. Earlier studies have used older 3D-based methods relying on reconstruction of multiple 2D slices obtained with electrocardiographic gating. These are now superseded by real-time 3D techniques. Notwithstanding this, calculation of SV using end-diastolic and end-systolic LV volumes would also be inaccurate in the presence of valvular regurgitations or intracardiac shunts.
Unlike 2D transthoracic aortic valve planimetry, 3D planimetry allows for alignment of cropping planes to measure the smallest anatomical orifice in systole at the time point when the valve is maximally opened. We have reported that 3D planimetry of the aortic valve correlated and agreed better with AVA derived from 3D colour Doppler than from 2D continuity equation. This further supports the utility of 3D Doppler measurements in AS patients. We found that in about 20% of our full volume 3D dataset, planimetry of the aortic valve was suboptimal, mainly due to poor resolution, lower anatomical visualization, and heavy valvular calcification. However, even in these patients, we are able to obtain adequate Doppler signals to fill the LVOT area. The Doppler analyses should be independent of ability to visualize the aortic valve though this was not verified systematically.
Recently, cardiac magnetic resonance22
and computer tomography23
have also been used to evaluate AVA. Previous small studies have also highlighted the use of 3D planimetry of the aortic valve in AS by transesophageal24,25
reconstruction and live transthoracic echocardiograms.26
Traditionally, the Gorlin-derived AVA has been used as a ‘gold standard’. However, the Gorlin-derived AVA also has inherent limitations.27,28
In clinical practice, to obtain the Gorlin equation derived area, it is difficult to place the catheter in the vena contracta as this is not visualized during catheterization and the jet displaces the catheter. Consequently, catheter pressures are limited by measurements in the ascending aorta after pressure recovery has occurred.28
It is expected that continuity equation derived effective AVA will be smaller than AVA by planimetry because of the contraction phenomenon. At the same time, effective orifice area may be dynamic during the cardiac cycle and changes in effective orifice area may be flow-related.29
This is demonstrated to be related mainly to the formation of vortices at low flow rates which can result in an even smaller effective area.30,31
Indeed, beyond planimetered orifice area, other factors such as valve shape32
may be important in determining impact of AS on patient haemodynamics.
Though 3D acquisitions are real-time, off-line SV computation and cropping for 3D full volume are still necessary. However, these processes are not lengthy and do not require extensive experience. High flow velocities over the Nyquist limit may result in inaccurate flow-volume computation. This can be compensated by baseline shift of the velocities to incorporate aliased velocities into the flow profile. In addition, one can adjust the tissue colour Doppler display priority so that colour Doppler signals fill the LVOT without excessive bleeding into the tissue. Inter-observer and intra-observer variability from our results showed reasonable consistency in this study.
In our animal validation model, balloon inflation of the upper septum to simulate USH may result in ‘non-physiologic’ shapes of the septum. However, it achieved our aim of distorting the upper septum and allowed variable changes in LVOT geometry.
In our clinical studies, we have included patients with irregular cardiac rhythm such as atrial fibrillation. This constituted a small subgroup of studies (6%) and does not predict discrepancies between 2D and 3D quantification. RT3DE cropping method to assess AVA by planimetry may have limited applications as some of the aortic valves are heavily calcified and hence have limited resolution of the valve orifice. AVA determination using cardiac magnetic resonance or computed tomography may be employed to obtain an independent parameter. However, these are not validated and have similar limitations.
It can be difficult to align planimetry plane to the narrowest aortic valve orifice using transesophageal echocardiograms. Since we analysed a wide range of aortic valve stenosis, only a proportion of patients underwent aortic valve replacement subsequently. Surgical correlation was therefore not available though this in itself may not be optimal since surgical specimens will be friable and may not represent the real-life opening of the valve subjected to haemodynamic stress. Indeed, a significant limitation of this study is the absence of an optimal gold standard.