European Heart Journal Advance Access originally published online on March 13, 2008
European Heart Journal 2008 29(8):966-968; doi:10.1093/eurheartj/ehn080
Severe aortic stenosis with low gradient and apparently preserved left ventricular systolic function—under-recognized or overdiagnosed?
Med. Klinik 2, Universitätsklinikum Erlangen, Ulmenweg 18, D-91054 Erlangen, Germany
* Corresponding author. Tel: +49 9131 853 5301: Fax +49 9131 853 5303, Email: frank.flachskampf{at}uk-erlangen.de
This editorial refers to ‘Inconsistencies of echocardiographic criteria for the grading of aortic valve stenosis’
by J. Minners et al., on page 1043
Footnotes
The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology.
The accurate diagnosis of aortic stenosis and its severity is one of the major feats of echocardiography, with an ever increasing importance due to the prevalence of this disease in our ageing population. Since the diagnosis of severe aortic stenosis in the presence of symptoms is usually an indication for aortic valve replacement,1 echocardiographic assessment, which is often the definitive test of severity, represents a decisive step in the management of these patients.
The study of Minners et al.2 therefore is highly relevant to daily practice in the echo lab, and, indeed, clinical cardiology. The authors point out a vexing problem with the current definitions of severe aortic stenosis in the presence of a preserved systolic left ventricular function: in many patients with apparently severe aortic stenosis, a discrepancy exists between the degree of severity based on transvalvular velocities, or the gradients derived from these, and the degree of severity based on the stenotic valve area calculated by the continuity equation. Current European and American guidelines both recommend a valve area cut-off of <1 cm2, or, indexed for body surface area, <0.6 cm2/m2 for severe aortic stenosis.1,3 The ESC guidelines further state that ‘Severe aortic stenosis is unlikely if cardiac output is normal, and there is a mean pressure gradient <50 mmHg’. The American guidelines, slightly differently, set the threshold at a peak transvalvular velocity of 4 m/s (corresponding to a peak gradient of 64 mmHg, usually with a mean gradient slightly higher than half the peak gradient) or a mean gradient >40 mmHg in the presence of a ‘normal’ cardiac output.
In the present study of 2427 patients with aortic stenosis and preserved left ventricular systolic function at a referral centre, a surprisingly large subset of patients (30%) had a valve area calculated by the continuity equation <1 cm2, but a mean gradient <40 mmHg.
Common wisdom teaches that this discrepancy would imply a decrease in stroke volume as the result of impaired left ventricular systolic function. In such a scenario, the severity of aortic stenosis cannot be judged by transvalvular velocity or gradient, and the valve area—measured by the continuity equation or by direct planimetry in a short axis view—must be used to evaluate severity. However, the present study aimed to exclude such patients, although ejection fraction was not formally calculated and fractional shortening was used instead. This leaves us with the possibility that these patients had a reduced stroke volume for reasons other than impaired ejection fraction (e.g. small left ventricular volumes). The fact that functional impairment of the hypertrophied ventricle may not be reflected in ejection fraction or similar measures, such as fractional shortening in the present study, has been observed before.4 Furthermore, cardiac output decreases with age, with a ‘normal’ value for those over 70 years old cited as 2.5 L/(min m2).5 The reasons for this have been ascribed to a lower metabolic rate with increasing age, but may also be due to increased peripheral resistance, arterial stiffening, and other factors.6 To exemplify the consequences, consider an 80-year-old woman with aortic stenosis and a body surface area of 1.75 m2. According to the cited literature, her cardiac output might be in range of 4.4 L/min, giving a stroke volume of 49 mL at a heart rate of 90/min. Assuming a 0.8 cm2 valve area (0.5 cm2/m2, well in the severe range) and an ejection time of 0.3 s, working the Gorlin formula backwards, one finds a stunningly low mean gradient of 21 mmHg. Is such a stroke volume realistic with preserved left ventricular systolic function? In the present study's huge database, a stroke volume of 44 mL would indeed be within two standard deviations of the mean stroke volume. It would also fit within these limits in the recent study of Hachicha and co-workers of ‘paradoxical low-flow, low-gradient severe aortic stenosis despite preserved ejection fraction’.6 In fact, these authors observed a mean cardiac index as low as 2.15 L/(m2 min) in these patients, with mean stroke volumes of 56 ± 10 mL and mean gradients 32 ± 17 mmHg in spite of valve areas 
0.6 cm2/m2 and ejection fraction >50%. Importantly, these patients, who were very similar to the patients with ‘discrepant’ valve areas and gradients in the present study of Minners et al., had a lower overall survival than their counterparts with apparently matched valve areas and gradients, despite a normal ejection fraction in both groups. Other groups have made similar observations,7 emphasizing that a low gradient does not somehow ‘cancel’ the importance of a severely stenotic valve area. Thus, it is important to realize that especially in old, small-sized patients, the gradients in severe aortic stenosis may be deceptively low. This observation may have been masked in the past, perhaps because such patients formerly were seen less frequently in the echo and cathetherization laboratories, and therefore severe aortic stenosis in clinical routine became associated with much higher gradients.
A second important, and independent, factor to consider is the nature of the effective aortic valve orifice area calculated by the continuity equation. This area is smaller than the anatomic orifice area by a variable ‘coefficient of contraction’ which varies with the morphology of the stenosis and theoretically also with the rheological characteristics of the fluid (blood). In vitro modelling has shown in vitro that the coefficient of contraction may vary by as much as 29%, meaning that for a given anatomical orifice, the effective orifice area (as measured by the continuity equation) may be smaller by almost one-third.8,9 The difference between effective and anatomical area increases with decreasing orifice size and flat (as opposed to tapering) stenosis morphology.
The Gorlin equation is based on the same physical relationships of orifice area, pressure, and flow rate as the Bernoulli and continuity principles used in echocardiography.10 However, in order to improve the correlation with surgical inspection of the anatomical area of the stenosed valve—the ancient ‘gold standard’—the traditional formulation of the Gorlin equation incorporates into the ‘Gorlin constant’ of 44.3 for aortic stenosis a correction factor assumed to correct for the coefficient of contraction and to account for the conversion of units (mmHg instead of Pascal8). Thus, the area calculated from the classic Gorlin formula is by definition higher than the area calculated by continuity. It should be understood that neither of these parameters—if correctly measured—is false, and both are correct in their own right. Since recommended cut-off values for the severity of aortic stenosis are largely based on the clinical experience with Gorlin-calculated areas, the use of the inherently lower continuity-calculated effective orifice areas will lead to a systematic overestimation of stenosis severity. This discrepancy has led Minners et al. to propose to re-introduce a lower area cut-off of 0.8 cm2 for the diagnosis of severe stenosis. This proposal is not supported by any outcome data in the present study and must be viewed with caution. Although, as pointed out, a continuity area of 0.8 cm2 may in many patients correspond to a Gorlin area of 
1 cm2, it seems better to acknowledge that there may be a systematic, but highly variable difference between the two measurements than to postulate a fixed new cut-off for continuity-based valve areas.
Of course, there are other possibilities to ‘mix up the numbers’. No echo measurement is foolproof. The maximal transvalvular velocities may be missed by continuous-wave Doppler, leading to falsely too low gradients. The measurement of left ventricular outflow tract velocities is prone to malposition of the sample volume, to angle error (often unavoidable), and errors occur in the measurement of the diameter of the left ventricular outflow tract, mostly leading to too small outflow tract diameters. Most of these errors lead to falsely too low valve areas by the continuity equation. Thus, all measurements have to be checked critically when ‘the numbers don't add up’. One should also not forget that in problematic cases other diagnostic tools are available to assess aortic stenosis, from a thorough invasive study to computed tomography and magnetic resonance imaging. Nevertheless, it should be well understood that the discrepancies documented by the study of Minners et al. certainly cannot be explained completely by false measurements, but indicate true limitations of the current recommendations.
In summary, Minners and co-workers are to be commended for drawing our attention to the fact that a considerable subset of aortic stenosis patients exists with relatively low gradients in spite of severely stenosed aortic valve area and preserved systolic function. Several reasons contribute to these discrepancies: especially in old patients, the concentrically hypertrophied left ventricle may produce a low stroke volume, translating into deceptive mean and maximal flow velocities and gradients. These ventricles are probably not really functioning normally, and other detrimental factors such as increased afterload may be operative. The current data do not support the notion that this type of aortic stenosis is less severe in a clinical sense than the classic ‘high gradient’ severe aortic stenosis. Furthermore, continuity-based effective valve areas by definition are lower than Gorlin-calculated areas, thus leading to systematic, but variable ‘overestimation’ (in comparison with Gorlin areas) of stenosis severity. Attention to these factors will facilitate the correct interpretation of the sometimes perplexing measurement data.
Conflict of interest: none declared.
Footnotes
The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology.
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