European Heart Journal

European Heart Journal Advance Access originally published online on December 22, 2007
European Heart Journal 2008 29(8):1043-1048; doi:10.1093/eurheartj/ehm543

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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2007. For permissions please email: journals.permissions@oxfordjournals.org

Inconsistencies of echocardiographic criteria for the grading of aortic valve stenosis

Jan Minners^*, Martin Allgeier, Christa Gohlke-Baerwolf, Rolf-Peter Kienzle, Franz-Josef Neumann and Nikolaus Jander

Department of Cardiology, Herz-Zentrum Bad Krozingen, Suedring 15, 79189 Bad Krozingen, Germany

Received 18 May 2007; revised 9 October 2007; accepted 29 October 2007; online publish-ahead-of-print 22 December 2007.

^* Corresponding author. Tel: +49 7633 4020, Fax: +49 7633 402 5219. Email: jan.minners{at}herzzentrum.de

See page 966 for the editorial comment on this article (doi:10.1093/eurheartj/ehn080)

	Abstract

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Aim: The present study tests the consistency of echocardiographic criteria for the grading of aortic valve stenosis.

Methods and results: Current guidelines/recommendations define severe stenosis as an aortic valve area (AVA) <1 cm² (or <0.6 cm² adjusted for body surface area), mean pressure gradient (P_m) >40 mmHg, or peak flow velocity (V_max) >4 m/s. We tested the consistency of the three criteria for the grading of aortic valve stenosis in 3483 echocardiography studies performed in 2427 patients with normal left ventricular (LV) systolic function and a calculated AVA of 2 cm². We calculated curve fits for the relationship between AVA and P_m using the Gorlin equation and between AVA and V_max based on the continuity equation for our study population. An AVA of 1.0 cm² correlated to a P_m of 21 mmHg and a V_max of 3.3 m/s. Conversely, a P_m of 40 mmHg corresponds to an AVA of 0.75 cm² and a V_max of 4.0 m/s to an AVA of 0.82 cm². Consequently, severe stenosis was diagnosed in 69% of patients based on AVA, 45% on V_max, and 40% on P_m. Stroke volume was lower in inconsistently graded patients (65 ± 11 mL vs. consistently graded: 70 ± 14 mL, P < 0.001).

Conclusion: The criteria for the grading of aortic stenosis are inconsistent in patients with normal systolic LV function. On the basis of AVA, a higher proportion of patients is classified as having severe aortic valve stenosis compared with mean pressure gradient and peak flow velocity. Discrepant grading in these patients may be partly due to reduced stroke volume.

Key Words: Aortic valve stenosis • Severity • Grading • Echocardiography

	Introduction

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Evaluation of aortic valve stenosis as based on data obtained from two-dimensional (2D) and Doppler echocardiography plays a key role in the grading of aortic valve stenosis. The parameters referred to in current guidelines/recommendations for the grading of the severity of aortic valve stenosis are aortic valve area (AVA), mean pressure gradient (P_m), and peak flow velocity (V_max)^1–4 with cut-off values for severe aortic valve stenosis of an AVA <1.0cm², P_m >40 mmHg, and V_max >4.0 m/s. In patients with normal left ventricular (LV) function, the three parameters should yield a consistent classification of a particular aortic stenosis as either mild, moderate, or severe.^5–7

Valve replacement is the treatment of choice in patients with syncope, dyspnoea, or angina attributable to aortic valve stenosis, because it improves symptoms and prolongs life.^8–10 In asymptomatic patients, particularly with severe stenosis, and in patients presenting with dyspnoea who are suffering from comorbidities such as chronic obstructive pulmonary disease, hypertension, or obesity correct echocardiographic grading of the severity of aortic valve stenosis is critical in the decision to proceed to valve replacement.

With a perioperative risk of up to 8.8%,¹¹ it is essential that recommendations for the management of these patients are based on reliable parameters. We therefore tested the consistency of the three echocardiographic criteria AVA, P_m, and V_max for the grading of aortic valve stenosis in patients with normal systolic LV function with special focus on the cut-off value for severe stenosis.

	Methods

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From our database, we identified 6152 consecutive echocardiography studies performed between 1994 and 2004 demonstrating normal LV function and a calculated AVA of 2 cm². Normal LV function was defined as normal global systolic LV function with fractional shortening 30% without regional wall motion abnormalities. Ejection fraction was not determined routinely. Patients with P_m <10 mmHg (n = 1420), a more than mild mitral or aortic regurgitation (1019), peak flow velocity <0.8 and >1.5 m/s in the LV outflow tract (LVOT, 125), a LVOT diameter of <15 mm, (4) or incomplete data (101) were excluded. The remaining 3483 echocardiographic studies performed in 2427 patients were included in the analysis.

Echocardiography was performed following the guidelines for the clinical application of echocardiography.¹² V_max was recorded by aligning the continuous wave (CW) beam parallel to the stenotic jet using the best of multiple windows. The velocity curve was traced and P_m was calculated automatically from the mean of a series of instantaneous velocities (v_i) of a single beat measured during the systolic ejection period using the simplified Bernoulli equation . AVA was calculated from the continuity equation (v₁ x A1 = v₂ x A₂, i.e. AVA = A₁ x v₁/v₂). In patients with atrial fibrillation, P_m was calculated from a representative (average) beat. For the calculation of AVA, the relation of v₁/v₂ was obtained from repeated CW Doppler signals with simultaneous visualization of the maximum velocity of both the stenotic valve and the LV outflow tract. Flow velocity in the LV outflow tract (LVOT) v₁ was measured by pulsed wave (PW) Doppler just below the aortic valve. The sample volume was placed 1 cm below the aortic valve and then slowly moved toward the valve until an increase in velocity and spectral broadening was seen. Thereafter, the sample volume was moved back until a narrow band of flow velocity was obtained. Flow velocity in the aortic valve v₂ was obtained from CW Doppler of the stenotic jet. LVOT area A₁ was calculated as A₁ = *r². LVOT diameter (D = 2*r) was measured by 2 D-Echo (‘inner edge’) in early systole just below the aortic valve using the largest of repeated measurements in the parasternal long-axis view.

Stroke volume was calculated from LVOT diameter and mean flow velocity in the LVOT assuming an ejection period of 0.33 s SV = v_mean(LVOT) x 0.33 x x (d_(LVOT)/2)².

Gorlin and Gorlin were the first to systematically study the relationship between AVA and P_m through cardiac valves obtained at surgery or autopsy. The resulting Gorlin equation (CO, cardiac output; SEP, systolic ejection period; and HR, heart rate) yields an anatomic AVA which is usually larger than the effective AVA derived from Doppler echocardiography.^5,7,13 Assuming a cardiac output of 6 L, a systolic ejection period of 0.33 s, and a heart rate of 80 beats per minute and substituting increasing values for P_m as outlined by Carabello⁶ the predicted relationship between P_m and the anatomic AVA was calculated. A fitted curve was then constructed for echocardiographic data pairs AVA vs. P_m from our study population.

The continuity equation describes the relationship between flow velocity and an effective AVA. On the basis of the continuity equation and assuming a LVOT diameter of 20 mm and maximal flow within the LVOT of 1 m/s, the predicted relationship between flow velocity and AVA was calculated. Finally, a fitted curve was constructed for data pairs AVA vs. V_max from our patients.

The fitted curve for data pairs AVA and P_m was constructed using non-linear regression (BMDP Statistical Software Inc.) based on the formula with AVA as the dependent and P_m as the independent variable. The modelling parameter p was equipped with a start value of 5.0. No provisions were made in this model to account for the fact that some measurements were not independent from each other (3483 echos in 2427 patients). An analysis limited to either the first or the last available study per patient did not change the results. Remaining statistics were calculated using SPSS software (version 12.0.1) with continuous variables presented as mean ± standard deviation and categorical variables as proportions. A P-value of <0.05 was considered statistically significant.

	Results

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Aortic valve area vs. mean pressure gradient
Clinical and echocardiography data of our study population are summarized in Table 1. To establish the relationship between the valve area obtained by substitution into the Gorlin formula with the valve area calculated from echocardiographic in vivo measurements we scatter-plotted P_m vs. AVA values from our patients (Figure 1). A fitted curve for the 3483 data pairs was constructed showing an excellent correlation with the predicted one derived from the Gorlin formula (fitted: predicted: ). An AVA of 1 cm² corresponds to a P_m of 26 mmHg on the predicted and a P_m of 22.8 mmHg on the fitted curve. Conversely, a P_m of 40 mmHg yielding a predicted AVA of 0.81 cm² generates an in vivo AVA of 0.75 cm². Therefore, both theoretical considerations based on anatomical valve area as well as in vivo data reflecting effective valve area demonstrate that an AVA of 1 cm² is related to a P_m well below the 40 mmHg stated in current guidelines. Consequently, 30% of our patients were diagnosed with severe aortic valve stenosis based on the AVA criterion but not-severe stenosis based on P_m.

View this table: [in this window] [in a new window]   Table 1 Clinical and echocardiography data of 3483 echocardiography studies in 2427 patients

 

View larger version (38K): [in this window] [in a new window] [Download PowerPoint slide]   Figure 1 Valve area vs. mean pressure gradient of 3483 echocardiographic studies in patients with aortic valve stenosis and normal left ventricular function. The predicted values from the Gorlin equation (assuming normal cardiac output, for details see text) and the fitted curve of the study population are presented. Quadrants are based on cut-off values for severe aortic stenosis as stated in current guidelines. The percentages correspond to patients per quadrant. Data pairs positioned in the left upper and right lower quadrant indicate consistent grading of aortic valve stenosis for valve area and mean pressure gradient. Thirty per cent of patients are diagnosed with severe stenosis based on aortic valve area and not-severe stenosis based on mean pressure gradient.

 
A subset of our patient population had more than one echocardiographic assessment. Because not all echocardiographic assessments were independent from each other, we performed an analysis limited to either the first or the last available study per patient (n = 2427) which did not change the results (data not shown).

Since smaller patients might tolerate a smaller AVA it has been suggested that correction for body surface area (BSA) may improve grading of aortic stenosis. However, correction for BSA did not markedly change results with respect to the comparison of AVA and P_m (39% of patients with a BSA-adjusted AVA of 0.6 cm²/m² or less had a P_m below 40 mmHg).

Aortic valve area vs. peak flow velocity
Substituting increasing aortic flow velocities into the continuity equation v₁ x A₁ = v₂ x A₂ and assuming constant LVOT diameter and flow (20 mm and 1 m/s, respectively) generates the predicted relationship between AVA and V_max (Figure 2). Under these theoretical conditions, the cut-off value for severe aortic stenosis of an AVA of 1 cm² corresponds to a V_max of 3.1 m/s. The fitted curve for 3483 studies again demonstrates an excellent correlation with the predicted values (fitted: AVA = 3.26/V_max; predicted: AVA = 3.14/V_max). The fitted curve consequently yields a V_max of 3.26 m/s for an AVA of 1 cm². Both the theoretical (3.1 m/s) and the in vivo value (3.3 m/s) for severe stenosis are positioned below the 4.0 m/s indicated in current guidelines. Conversely, a V_max of 4.0 m/s giving a predicted AVA of 0.81 cm² results in an in vivo AVA of 0.82. Similar to the finding above involving P_m 25% of our patients were diagnosed with severe aortic valve stenosis based on the AVA criterion but had not-severe stenosis based on V_max.

View larger version (39K): [in this window] [in a new window] [Download PowerPoint slide]   Figure 2 Valve area vs. peak flow velocity. The predicted values from the continuity equation (assuming normal stroke volume, for details see text) and the fitted curve for the study population are presented. Quadrants are based on cut-off values for severe aortic stenosis as stated in current guidelines. The percentages correspond to patients per quadrant. Data pairs positioned in the left upper and right lower quadrant indicate consistent grading of aortic valve stenosis for valve area and peak flow velocity. Twenty five per cent of patients are diagnosed with severe stenosis based on aortic valve area and not-severe stenosis based on peak flow velocity.

 
Mean pressure gradient vs. peak flow velocity
Mean pressure gradient (P_m) is calculated from mean flow velocity (V_mean) using the simplified Bernoulli equation . Plotting P_m vs. V_max results in the relationship depicted in Figure 3. Given the above equation and bearing in mind that V_mean and V_max are closely correlated with an r = 0.92 in our study population the fitted curve illustrates the excellent correlation between the two parameters (r = 0.94, P < 0.01). Importantly with respect to current guidelines, a mere 6% of patients with severe aortic valve stenosis based on V_max have a P_m below 40 mmHg demonstrating that the cut-off values for the two parameters P_m and V_max —unlike AVA—yield highly consistent results.

View larger version (32K): [in this window] [in a new window] [Download PowerPoint slide]   Figure 3 Mean pressure gradient vs. peak flow velocity. Data pairs positioned in the right upper and left lower quadrant indicate consistent grading of aortic valve stenosis for mean pressure gradient and peak flow velocity.

 
Summarizing the discrepancies between criteria for severe aortic valve stenosis, we calculated the percentage of patients diagnosed with severe stenosis for each parameter. This percentage ranged from 40% for P_m to 76% for BSA-adjusted AVA (Table 2).

View this table: [in this window] [in a new window]   Table 2 Percentage of patients diagnosed with severe aortic stenosis depending on which echocardiographic criterion was used

 
Low flow aortic valve stenosis
Since discrepancies between AVA and P_m may be caused by low flow in the presence of preserved LV systolic function,¹⁴ we calculated stroke volumes for our study population. Stroke volume was significantly lower in patients graded inconsistently (AVA <1.0 cm² and P_m <40 mmHg) compared with patients in whom grading was consistent (AVA <1.0 cm² and P_m >40 mmHg, 65 ± 11 mL vs. 70 ± 14 mL, respectively, P < 0.001, Figure 4) indicating that low flow does contribute to the discrepancies between the two parameters.

View larger version (12K): [in this window] [in a new window] [Download PowerPoint slide]   Figure 4 Stroke volume from 3349 echocardiographic studies in patients with aortic valve stenosis. Quadrants correspond to Figure 1 reflecting consistent and inconsistent grading of severe aortic valve stenosis based on current guidelines.3 AVA, aortic valve area; Pm, mean pressure gradient, *P < 0.001 between groups.

 

	Discussion

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The present analysis highlights inconsistencies in the grading of aortic valve stenosis in patients with normal LV function in particular with respect to AVA and the cut-off value for severe stenosis.

The 1998 ACC/AHA guidelines for the management of patients with valvular heart disease, the ESC recommendation on the management of the asymptomatic patient with valvular heart disease 2002 and recommendations from Otto form the basis of the recently updated ACC/AHA guidelines.^1–3 In the latter publication, the cut-off values for the grading of the severity of aortic valve stenosis were changed. For example, the definition of severe aortic valve stenosis currently includes an AVA <1.0 cm², P_m >40 mmHg, or V_max >4.0 m/s introducing somewhat stricter cut-off values for severe stenosis from the previous AVA 1.0 cm² and P_m >50 mmHg.¹ Although these changes have reduced the discrepancies between the three criteria for the assessment of the severity of aortic valve stenosis, the results from more than 3400 echocardiography assessments presented in this paper show that major inconsistencies persist and AVA continues to overestimate the severity of disease when compared to the two other parameters.

In the management of patients with aortic valve stenosis, symptoms attributable to aortic stenosis (syncope, angina, and dyspnoea) determine which patient should undergo valve replacement. On the other hand, decisions on management of asymptomatic patients particularly with severe stenosis are more difficult and exact grading becomes more important. Risk of rapid progression of disease, imminent heart failure and sudden death must be weighed against perioperative morbidity and mortality, valve deterioration, and problems associated with possible long-term anticoagulation.^3,10 Various smaller studies suggested that it was safe to withhold surgery in patients until symptoms occur.^15–17 On the other hand, Rosenhek et al.¹⁸ proposed that asymptomatic patients with severe aortic valve stenosis (V_max 5.0 ± 0.6 m/s) presenting with moderate to severe calcification together with a rapid increase in V_max may benefit from surgery prior to the development of symptoms. In addition, a recent publication reporting on more than 600 patients with a V_max >4.0 m/s and a follow-up of 5 years indicates that in these patients cardiac death is common (19%/5 years of follow-up) and the likelihood of remaining free of surgery or cardiac death is low (25%/5 years of follow-up).¹⁹ The European Society of Cardiology working group on valvular heart disease recommends intervention in asymptomatic patients with an AVA <1.0 cm² (<0.6 cm² corrected BSA) in the presence of an abnormal response to exercise, moderate to severe calcification, and rapid progression of V_max (>0.3 m/s/year) or depressed LV function.² Lancellotti et al.²⁰ have recently shown that an AVA of <0.75 cm² predicts death or valve replacement within 15 months of follow-up in patients with a pathological exercise test. Similarly, a V_max of >4.0 m/s is associated with an event-free survival of only 26% after 2 years of follow-up.¹⁷

In addition, patients with comorbidities such as COPD, obesity, or hypertension may prove particularly difficult to manage due to the non-specificity of the symptom dyspnoea. Therefore, findings on echocardiography may become critical in deciding on whether these patients should be subjected to the risk of valve replacement. Consequently, defining consistent cut-off values for severe aortic stenosis as a possible indicator for surgery is more than an academic exercise.

Two factors help to at least partially explain the discrepancies in the grading of aortic valve stenosis presented in this paper. First, the effective valve area derived from Doppler echocardiography is usually smaller than the anatomic valve area as measured by planimetry, at autopsy, and/or during cardiac catheterization. The difference between anatomic and effective valve area (coefficient of contraction) is based on the fact that streamlines continue to converge for a short distance downstream of the stenosis explaining the differences between predicted and fitted curve in Figure 1. Guidelines for the grading of aortic valve stenosis were initially based on data derived from invasive measurements reflecting anatomic valve area. Currently, Doppler echocardiographic measurements with lower (effective) valve areas usually provide the information for clinical decision making. These theoretical considerations together with clinical data^18,19 and the data presented in this paper support the adjustment of the AVA cut-off value for severe stenosis to 0.8 cm².

Secondly, low flow, low gradient aortic valve stenosis partly accounts for the differences found in our study. Stroke volume was slightly but significantly lower in inconsistently graded patients supporting the concept that low flow contributes to the differences in grading of aortic valve stenosis. However, since the overlap between the two groups was large and the exact quantification of stroke volume by echocardiography is often difficult the correct grading of the individual patient may be problematic. We therefore concur with Hachicha et al.¹⁴ that every effort should be made to identify this clinically important subset of patients with aortic valve stenosis.

A limitation of the present study is its retrospective nature over a decade. It thus comprises diverse levels of technical expertise in acquiring Doppler echocardiography measures as well as hard- and software developments which may have contributed to scatter. Furthermore, the accuracy of the calculation of the predicted curves is limited by the use of standard values for cardiac output, ejection time, flow in the LVOT etc. This may increase the correlation between the predicted and the fitted curves; however, it does not influence the main message of the present paper regarding inconsistencies within the cut-off values used for grading of the severity of aortic valve stenosis.

In summary, the criteria for the grading of aortic stenosis in patients with normal LV systolic function are inconsistent. On the basis of AVA, a higher proportion of patients is classified as having severe aortic valve stenosis compared with mean pressure gradient and peak flow velocity. An AVA cut-off value for severe stenosis of 0.8 cm² may be more appropriate. Since discrepant grading may be partly due to reduced stroke volume, every effort should be made to identify patients with low flow, low gradient aortic valve stenosis.

Conflict of interest: none declared.

	References

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