Limitations of echocardiography in the assessment of aortic valve disease

ABBREVIATIONS

AR                          aortic regurgitation

AS                          aortic stenosis

AVA                        aortic valve area

DSE                        dobutamine stress echocardiography

EACTS                   European Association for Cardio-Thoracic Surgery

ESC                        European Society of Cardiology

LV                           left ventricle/left ventricular

LVOT                      left ventricular outflow tract

TEE                        transoesophageal echocardiography

TTE                        transthoracic echocardiography

Introduction

Aortic valve disease constitutes an important cause of cardiovascular morbidity and mortality [1]. As the key imaging modality for the evaluation of aortic valve disease, echocardiography has a significant impact on clinical decision making. Therefore, it is essential to avoid common sources of error and acknowledge substantial limitations of routinely used echocardiography measurements.

Aortic Stenosis

The ESC/EACTS guidelines define haemodynamic parameters for the assessment of aortic stenosis (AS) severity [2]. These primarily include peak aortic jet velocity, mean transaortic pressure gradient, and aortic valve area (AVA) calculated by the continuity equation.

Peak Aortic Jet Velocity

Peak aortic jet velocity increases with narrowing of the aortic valve and is a robust measure of AS severity. Particular attention must be paid to align the Doppler beam with the AS jet correctly, as errors may lead to a substantial underestimation of true aortic velocity and thus AS severity. Using a standardised approach, multiple acoustic windows should be obtained to identify the highest transvalvular velocity. Caution is warranted not to confuse the AS signal with an eccentric mitral regurgitation or even tricuspid regurgitation jet. Furthermore, in patients with subvalvular obstruction (e.g., hypertrophic cardiomyopathy), differentiation between left ventricular (LV) outflow obstruction and AS may be challenging. Continuous wave Doppler (e.g., a late-peak, dagger-shaped signal in hypertrophic obstructive cardiomyopathy) and colour Doppler are usually helpful in this setting [3].

As a major limitation, peak aortic jet velocity is highly flow-dependent. This might lead to a profound overestimation of AS severity in case of a high-flow state (e.g., concomitant aortic regurgitation, severe anaemia or thyrotoxicosis) and an underestimation of AVA in patients with low-flow pathology [4]. As a consequence, transthoracic echocardiography (TTE) examination should be repeated after correction of high-/low-flow states. If flow cannot be normalised, evaluation of AS is highly reliant on an integrated approach using additional clinical and imaging parameters.

Mean Transaortic Pressure Gradient

Using the simplified Bernoulli equation, transaortic pressure gradients are derived from aortic jet velocity. Due to the squared relationship between velocity and pressure gradient, any error in aortic jet velocity will inevitably result in an even greater error of the mean transaortic pressure gradient. In this context, it is important to understand that in theory an AVA of 1.0 cm² corresponds to a mean transaortic pressure gradient of 30-35 mmHg, which reflects some degree of discrepancy in the current guidelines [5]. In addition, mean transaortic pressure gradients might be overestimated in patients with a small ascending aorta (<30 mm) due to the phenomenon of pressure recovery [4].

Continuity Equation

AVA calculated by the continuity equation is a relatively flow-independent parameter. However, any measurement error of the different variables of the equation will result in imprecision of the calculated AVA. Left ventricular outflow tract (LVOT) diameter is accepted as being the most critical source of error, as any inaccuracy in LVOT measurement will be squared. Transoesophageal echocardiography (TEE) might be useful to obtain the true LVOT cross-sectional area [4]. In addition, the assumption of a circular LVOT (whereas it actually has an elliptical shape) and a perfectly laminar flow profile constitute inherent limitations of the continuity equation.

Low-Flow, Low-Gradient AS

Classic low-flow, low-gradient AS is defined as an AVA <1.0 cm², a mean transaortic pressure gradient <40 mmHg, a peak aortic jet velocity <4 m/s, and an LV ejection fraction (LVEF) of <50% [2]. After careful exclusion of measurement errors, low-dose dobutamine stress echocardiography (DSE) is usually indicated to differentiate true severe AS from pseudostenosis. Notably, in an important subgroup of approximately 30%, no significant increase in stroke volume (>20%) may be achieved by DSE [6]. AS measurements may therefore still remain discordant even after DSE. In these patients, an integrated approach using additional clinical and imaging parameters should be followed.

Paradoxical Low-Flow, Low-Gradient AS

Paradoxical low-flow, low-gradient AS is defined as an AVA <1.0 cm², a mean transaortic pressure gradient <40 mmHg, a peak aortic jet velocity <4 m/s, an LVEF of ≥50%, and a stroke volume index of <35 ml/m² [2]. In general, these patients are characterised by extensive LV concentric remodelling leading to a small LV cavity, restrictive LV filling pattern, and reduced systolic longitudinal myocardial shortening [7,8]. If paradoxical low-flow, low-gradient AS is encountered, TTE should be able to identify the cause of the low-flow status. Severe AS must be especially questioned in the presence of a peak aortic jet velocity <3 m/s and a mean transaortic pressure gradient <20 mmHg. Due to the limitations of TTE in this patient subgroup, the diagnostic workup should involve additional imaging modalities such as multi-detector computed tomography.

Normal-Flow, Low-Gradient AS

Normal-flow, low-gradient AS is defined as an AVA <1.0 cm², a mean transaortic pressure gradient <40 mmHg, peak aortic jet velocity <4 m/s, an LVEF of ≥50%, and a stroke volume index of ≥35 ml/m² [2]. Normal-flow, low-gradient AS is usually a result of measurement errors and inconsistent cut-off values for AVA, peak jet velocity, and mean transaortic pressure gradient. Notably, according to the current ESC/EACTS guidelines these patients should not undergo aortic valve replacement.

Planimetry

Planimetry using TEE may be an acceptable alternative in selected AS patients if TTE examination is not feasible or inconclusive [4]. However, it should be acknowledged that planimetry has an inherent level of imprecision, as severe valve calcification causes shadows and artefacts that may significantly limit the correct delineation of the AVA. Furthermore, it is challenging in many cases to truly identify the minimal orifice area correctly, especially in bicuspid valves. The use of 3D-TEE might be helpful in these patients.

Arrhythmia

Atrial fibrillation is frequently found in patients with AS [9]. In this setting, AS assessment should preferably be repeated after rhythm control. If sinus rhythm cannot be restored, measurements should be averaged over at least five beats after adequate heart rate control. In case of premature contractions, both the extra and the following heartbeat provide a velocity and pressure gradient that are non-representative and should therefore not be used.

Aortic Regurgitation

Echocardiography plays a key role in the evaluation of aortic regurgitation (AR) and timing of intervention. The accurate assessment of AR is challenging and always requires a comprehensive approach. TTE examination involves the evaluation of aortic valve morphology, AR jet characteristics, LV geometry and function as well as aortic root and ascending aorta [10].

Colour Flow Doppler

Colour flow Doppler is the primary parameter used to visualise AR and should be obtained using multiple acoustic windows to adequately locate the origin and direction of the jet. Importantly, the length of the AR jet is highly dependent on diastolic pressure gradient and LV compliance and is not a reliable parameter of AR severity [10]. Colour flow Doppler is particularly limited in the presence of eccentric AR or multiple jets. Accordingly, jet width to LVOT ratio is usually also inconclusive in very eccentric AR or in case of multiple AR jets. Moreover, it might be invalid in patients with very small or very large LVOT diameters.

While Vena contracta is widely used, small errors may severely influence AR grading. Therefore, precise measurement in a zoomed, parasternal long-axis view is of paramount importance. In addition, the Nyquist limit should be kept to 50-60 cm/s to avoid overestimation of the AR jet.

Flow convergence (proximal isovelocity surface area [PISA]) may be used for the evaluation of AR severity, yet it is not valid in the presence of multiple jets, or when the convergence zone is not hemispheric in shape. In patients with concomitant AS, flow convergence may be substantially limited by artefacts caused by aortic valve calcifications. Moreover, small errors in radius measurement may lead to excessive errors in effective regurgitant orifice area (EROA) due to the squared relationship.

Pulsed Wave Doppler

Aortic holodiastolic flow reversal in the descending aorta may be visible using pulsed wave Doppler from the suprasternal window. However, this may also be present in other pathologies (e.g., patent ductus arteriosus, reduced compliance of the aorta, aortic dissection). Furthermore, in severe AR or bradycardia, there may be a pressure equalisation between the aorta and the LV causing a flow reversal that is not holodiastolic [10].

Continuous Wave Doppler

Signal density of AR using continuous wave Doppler reflects the volume of regurgitation. While high signal density is usually consistent with significant AR, it cannot differentiate between moderate and severe AR.

Pressure half-time is widely used in the assessment of AR. However, since this parameter is substantially affected by LV compliance, patients with severe chronic AR but compensated ventricular function may have a longer pressure half-time, suggesting only moderate AR. In contrast, in patients with mild AR and severe diastolic dysfunction or vasodilator therapy, pressure half-time may be shortened, which potentially leads to an overestimation of AR [11,12].

TEE

Both 2D- and 3D-TEE improve diagnostic accuracy in a number of AR pathologies including aortic root dilatation, cusp prolapse, endocarditis, and aortic dissection. The diagnostic value of TEE in defining the mechanisms of AR is particularly important in patients undergoing surgical treatment. TEE should always be used in addition to TTE if severe AR is suspected, if TTE only allows suboptimal echocardiographic images or in case of inconclusive TTE findings (e.g., discordance between LV dilatation and functional parameters of AR severity). Furthermore, TEE should also be employed in patients with bicuspid aortic valve or multi-valvular disease. Moreover, TEE is indicated if the morphology of the aortic root and ascending aorta cannot be accurately assessed by TTE [13].

Conclusion

Echocardiography is the key imaging modality for the diagnosis and evaluation of aortic valve disease. Standardised measurements in accordance with ESC/EACTS guidelines should be obtained to minimise common sources of error. Due to methodological limitations of echocardiography, measurements should always be interpreted in the clinical context as part of an integrative approach.