Euroean Heart Journal (2008) 29, 1043 1048 doi:10.1093/eurheartj/ehm543 CLINICAL RESEARCH Valvular heart disease Inconsistencies of echocardiograhic criteria for the grading of aortic valve stenosis Jan Minners*, Martin Allgeier, Christa Gohlke-Baerwolf, Rolf-Peter Kienzle, Franz-Josef Neumann, and Nikolaus Jander Deartment of Cardiology, Herz-Zentrum Bad Krozingen, Suedring 15, 79189 Bad Krozingen, Germany Received 18 May 2007; revised 9 October 2007; acceted 29 October 2007; online ublish-ahead-of-rint 22 December 2007 See age 966 for the editorial comment on this article (doi:10.1093/eurheartj/ehn080) Aim The resent study tests the consistency of echocardiograhic criteria for the grading of aortic valve stenosis.... Methods Current guidelines/recommendations define severe stenosis as an aortic valve area (AVA),1cm 2 (or,0.6 cm 2 and results adjusted for body surface area), mean ressure gradient (DP m ).40 mmhg, or eak flow velocity (V max ).4 m/s. We tested the consistency of the three criteria for the grading of aortic valve stenosis in 3483 echocardiograhy studies erformed in 2427 atients with normal left ventricular (LV) systolic function and a calculated AVA of 2cm 2. We calculated curve fits for the relationshi between AVA and DP m using the Gorlin equation and between AVA and V max based on the continuity equation for our study oulation. An AVA of 1.0 cm 2 correlated to a DP m of 21 mmhg and a V max of 3.3 m/s. Conversely, a DP m of 40 mmhg corresonds to an AVA of 0.75 cm 2 and a V max of 4.0 m/s to an AVA of 0.82 cm 2. Consequently, severe stenosis was diagnosed in 69% of atients based on AVA, 45% on V max, and 40% on DP m. Stroke volume was lower in inconsistently graded atients (65 + 11 ml vs. consistently graded: 70 + 14 ml, P, 0.001).... Conclusion The criteria for the grading of aortic stenosis are inconsistent in atients with normal systolic LV function. On the basis of AVA, a higher roortion of atients is classified as having severe aortic valve stenosis comared with mean ressure gradient and eak flow velocity. Discreant grading in these atients may be artly due to reduced stroke volume. ----------------------------------------------------------------------------------------------------------------------------------------------------------- Keywords Aortic valve stenosis Severity Grading Echocardiograhy Introduction Evaluation of aortic valve stenosis as based on data obtained from two-dimensional (2D) and Doler echocardiograhy lays a key role in the grading of aortic valve stenosis. The arameters referred to in current guidelines/recommendations for the grading of the severity of aortic valve stenosis are aortic valve area (AVA), mean ressure gradient (DP m ), and eak flow velocity (V max ) 1 4 with cut-off values for severe aortic valve stenosis of an AVA,1.0cm 2, DP m.40 mmhg, and V max.4.0 m/s. In atients with normal left ventricular (LV) function, the three arameters should yield a consistent classification of a articular aortic stenosis as either mild, moderate, or severe. 5 7 Valve relacement is the treatment of choice in atients with syncoe, dysnoea, or angina attributable to aortic valve stenosis, because it imroves symtoms and rolongs life. 8 10 In asymtomatic atients, articularly with severe stenosis, and in atients resenting with dysnoea who are suffering from comorbidities such as chronic obstructive ulmonary disease, hyertension, or obesity correct echocardiograhic grading of the severity of aortic valve stenosis is critical in the decision to roceed to valve relacement. With a erioerative risk of u to 8.8%, 11 it is essential that recommendations for the management of these atients are based on reliable arameters. We therefore tested the consistency of the three echocardiograhic criteria AVA, DP m, and V max for the grading of aortic valve stenosis in atients with normal systolic LV function with secial focus on the cut-off value for severe stenosis. * Corresonding author. Tel: þ49 7633 4020, Fax: þ49 7633 402 5219. Email: jan.minners@herzzentrum.de Published on behalf of the Euroean Society of Cardiology. All rights reserved. & The Author 2007. For ermissions lease email: journals.ermissions@oxfordjournals.org.
1044 J. Minners et al Methods From our database, we identified 6152 consecutive echocardiograhy studies erformed between 1994 and 2004 demonstrating normal LV function and a calculated AVA of 2 cm 2. 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 DP m,10 mmhg (n ¼ 1420), a more than mild mitral or aortic regurgitation (1019), eak flow velocity,0.8 and.1.5 m/s in the LV outflow tract (LVOT, 125), a LVOT diameter of,15 mm, (4) or incomlete data (101) were excluded. The remaining 3483 echocardiograhic studies erformed in 2427 atients were included in the analysis. Echocardiograhy was erformed following the guidelines for the clinical alication of echocardiograhy. 12 V max was recorded by aligning the continuous wave (CW) beam arallel to the stenotic jet using the best of multile windows. The velocity curve was traced and DP m was calculated automatically from the mean of a series of instantaneous velocities (v i ) of a single beat measured during the systolic ejection eriod using the simlified Bernoulli equation (DP m ¼ 4 ðv1þ2 þðv 2Þ 2 þðv 3Þ 2...: ðv nþ 2 n ). AVA was calculated from the continuity equation (v 1 A1 ¼ v 2 A 2, i.e. AVA¼ A 1 v 1 /v 2 ). In atients with atrial fibrillation, DP m was calculated from a reresentative (average) beat. For the calculation of AVA, the relation of v 1 /v 2 was obtained from reeated CW Doler 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) v 1 was measured by ulsed wave (PW) Doler just below the aortic valve. The samle volume was laced 1 cm below the aortic valve and then slowly moved toward the valve until an increase in velocity and sectral broadening was seen. Thereafter, the samle volume was moved back until a narrow band of flow velocity was obtained. Flow velocity in the aortic valve v 2 was obtained from CW Doler of the stenotic jet. LVOT area A 1 was calculated as A 1 ¼ *r 2. LVOT diameter (D ¼ 2*r) was measured by 2 D-Echo ( inner edge ) in early systole just below the aortic valve using the largest of reeated measurements in the arasternal long-axis view. Stroke volume was calculated from LVOT diameter and mean flow velocity in the LVOT assuming an ejection eriod of 0.33 s SV ¼ v mean(lvot) 0.33 (d (LVOT) /2) 2. Gorlin and Gorlin were the first to systematically study the relationshi between AVA and DP m through cardiac valves obtained at surgery or autosy. The resulting Gorlin equation AVA ¼ CO/SEP HR=44:3 ffiffiffiffiffiffiffiffi DP m (CO, cardiac outut; SEP, systolic ejection eriod; and HR, heart rate) yields an anatomic AVA which is usually larger than the effective AVA derived from Doler echocardiograhy. 5,7,13 Assuming a cardiac outut of 6 L, a systolic ejection eriod of 0.33 s, and a heart rate of 80 beats er minute and substituting increasing values for DP m as outlined by Carabello 6 the redicted relationshi between DP m and the anatomic AVA was calculated. A fitted curve was then constructed for echocardiograhic data airs AVA vs. DP m from our study oulation. The continuity equation describes the relationshi 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 redicted relationshi between flow velocity and AVA was calculated. Finally, a fitted curve was constructed for data airs AVA vs. V max from our atients. The fitted curve for data airs AVA and DP m was constructed using non-linear regression (BMDP Statistical Software Inc.) based on the formula AVA ¼ = ffiffiffiffiffiffiffiffi DP m with AVA as the deendent and DP m as the indeendent variable. The modelling arameter was equied with a start value of 5.0. No rovisions were made in this model to account for the fact that some measurements were not indeendent from each other (3483 echos in 2427 atients). An analysis limited to either the first or the last available study er atient did not change the results. Remaining statistics were calculated using SPSS software (version 12.0.1) with continuous variables resented as mean + standard deviation and categorical variables as roortions. A P-value of,0.05 was considered statistically significant. Results Aortic valve area vs. mean ressure gradient Clinical and echocardiograhy data of our study oulation are summarized in Table 1. To establish the relationshi between the valve area obtained by substitution into the Gorlin formula with the valve area calculated from echocardiograhic in vivo measurements we scatter-lotted DP m vs. AVA values from our atients (Figure 1). A fitted curve for the 3483 data airs was constructed showing an excellent correlation with the redicted one derived from the Gorlin formula (fitted: AVA ¼ 4:77= ffiffiffiffiffiffiffi dp m redicted: AVA ¼ 5:13= ffiffiffiffiffiffiffi dp m). An AVA of 1 cm 2 corresonds to a DP m of 26 mmhg on the redicted and a DP m of 22.8 mmhg on the fitted curve. Conversely, a DP m of 40 mmhg yielding a redicted AVA of 0.81 cm 2 generates an in vivo AVA of 0.75 cm 2. Therefore, both theoretical considerations based on anatomical valve area as Table 1 Clinical and echocardiograhy data of 3483 echocardiograhy studies in 2427 atients Clinical data Mean + SD... Age, years 69 + 12 Female, % 44.6 Height, cm 167.2 + 11 Weight, kg 79 + 16 Echocardiograhy Left ventricular end-diastolic diameter, mm 47.7 + 5.3 Left ventricular end-systolic diameter, mm 29.1 + 4.8 Shortening fraction, % 39.1 + 6.2 Aortic root, mm 40.5 + 6.3 Ascending aorta, mm 33.4 + 4.8 Left ventricular outflow tract Diameter, mm 20.1 + 1.6 V max, m/s 1.0 + 0.16 V mean, m/s 0.69 + 0.11 Aortic valve V max, m/s 3.9 + 0.9 V mean, m/s 2.7 + 0.7 dp m, mmhg 36.1 + 17.9 Area, cm 2 0.87 + 0.3 V aortic valve /V LVOT 3.8 + 1.1 Stroke volume, ml 72 + 15 V, velocity; LVOT, left ventricular outflow tract.
Inconsistencies of echocardiograhic criteria 1045 Figure 1 Valve area vs. mean ressure gradient of 3483 echocardiograhic studies in atients with aortic valve stenosis and normal left ventricular function. The redicted values from the Gorlin equation (assuming normal cardiac outut, for details see text) and the fitted curve of the study oulation are resented. Quadrants are based on cut-off values for severe aortic stenosis as stated in current guidelines. The ercentages corresond to atients er quadrant. Data airs ositioned in the left uer and right lower quadrant indicate consistent grading of aortic valve stenosis for valve area and mean ressure gradient. Thirty er cent of atients are diagnosed with severe stenosis based on aortic valve area and not-severe stenosis based on mean ressure gradient. well as in vivo data reflecting effective valve area demonstrate that an AVA of 1 cm 2 is related to a DP m well below the 40 mmhg stated in current guidelines. Consequently, 30% of our atients were diagnosed with severe aortic valve stenosis based on the AVA criterion but not-severe stenosis based on DP m. A subset of our atient oulation had more than one echocardiograhic assessment. Because not all echocardiograhic assessments were indeendent from each other, we erformed an analysis limited to either the first or the last available study er atient (n ¼ 2427) which did not change the results (data not shown). Since smaller atients might tolerate a smaller AVA it has been suggested that correction for body surface area (BSA) may imrove grading of aortic stenosis. However, correction for BSA did not markedly change results with resect to the comarison of AVA and DP m (39% of atients with a BSA-adjusted AVA of 0.6 cm 2 /m 2 or less had a DP m below 40 mmhg). Aortic valve area vs. eak flow velocity Substituting increasing aortic flow velocities into the continuity equation v 1 A 1 ¼ v 2 A 2 and assuming constant LVOT diameter and flow (20 mm and 1 m/s, resectively) generates the redicted relationshi between AVA and V max (Figure 2). Under these Figure 2 Valve area vs. eak flow velocity. The redicted values from the continuity equation (assuming normal stroke volume, for details see text) and the fitted curve for the study oulation are resented. Quadrants are based on cut-off values for severe aortic stenosis as stated in current guidelines. The ercentages corresond to atients er quadrant. Data airs ositioned in the left uer and right lower quadrant indicate consistent grading of aortic valve stenosis for valve area and eak flow velocity. Twenty five er cent of atients are diagnosed with severe stenosis based on aortic valve area and notsevere stenosis based on eak flow velocity. theoretical conditions, the cut-off value for severe aortic stenosis of an AVA of 1 cm 2 corresonds to a V max of 3.1 m/s. The fitted curve for 3483 studies again demonstrates an excellent correlation with the redicted values (fitted: AVA ¼ 3.26/V max ; redicted: AVA ¼ 3.14/V max ). The fitted curve consequently yields a V max of 3.26 m/s for an AVA of 1 cm 2. Both the theoretical (3.1 m/s) and the in vivo value (3.3 m/s) for severe stenosis are ositioned below the 4.0 m/s indicated in current guidelines. Conversely, a V max of 4.0 m/s giving a redicted AVA of 0.81 cm 2 results in an in vivo AVA of 0.82. Similar to the finding above involving DP m 25% of our atients were diagnosed with severe aortic valve stenosis based on the AVA criterion but had not-severe stenosis based on V max. Mean ressure gradient vs. eak flow velocity Mean ressure gradient (DP m ) is calculated from mean flow velocity (V mean ) using the simlified Bernoulli equation DP m ¼ 4 ðv1þ2 þðv 2Þ 2 þðv 3Þ 2...: ðv nþ 2 n. Plotting DP m vs. V max results in the relationshi deicted in Figure 3. Given the above equation and bearing in mind that V mean and V max are closely correlated with an r ¼ 0.92 in our study oulation the fitted curve illustrates the excellent correlation between the two arameters (r ¼ 0.94, P, 0.01). Imortantly with resect to current guidelines, a mere
1046 J. Minners et al Figure 3 Mean ressure gradient vs. eak flow velocity. Data airs ositioned in the right uer and left lower quadrant indicate consistent grading of aortic valve stenosis for mean ressure gradient and eak flow velocity. 6% of atients with severe aortic valve stenosis based on V max have a DP m below 40 mmhg demonstrating that the cut-off values for the two arameters DP m and V max unlike AVA yield highly consistent results. Summarizing the discreancies between criteria for severe aortic valve stenosis, we calculated the ercentage of atients diagnosed with severe stenosis for each arameter. This ercentage ranged from 40% for DP m to 76% for BSA-adjusted AVA (Table 2). Low flow aortic valve stenosis Since discreancies between AVA and DP m may be caused by low flow in the resence of reserved LV systolic function, 14 we calculated stroke volumes for our study oulation. Stroke volume was significantly lower in atients graded inconsistently (AVA,1.0 cm 2 and DP m,40 mmhg) comared with atients in whom grading was consistent (AVA,1.0 cm 2 and DP m.40 mmhg, 65 + Table 2 Percentage of atients diagnosed with severe aortic stenosis deending on which echocardiograhic criterion was used Guidelines/ Parameter Patients with recommendations severe stenosis... AHA/ACC 3 AVA,1.0 cm 2 69% ESC 2 AVA/BSA,0.6 cm 2 76% Otto 4 V max.4.0 m/s 45% AHA/ACC 3 DP m.40 mmhg 40% AVA, aortic valve area; BSA, body surface area; V max, eak flow velocity; DP m, mean ressure gradient. Figure 4 Stroke volume from 3349 echocardiograhic studies in atients with aortic valve stenosis. Quadrants corresond to Figure 1 reflecting consistent and inconsistent grading of severe aortic valve stenosis based on current guidelines. 3 AVA, aortic valve area; DP m, mean ressure gradient, *P, 0.001 between grous. 11 ml vs. 70 + 14 ml, resectively, P, 0.001, Figure 4) indicating that low flow does contribute to the discreancies between the two arameters. Discussion The resent analysis highlights inconsistencies in the grading of aortic valve stenosis in atients with normal LV function in articular with resect to AVA and the cut-off value for severe stenosis. The 1998 ACC/AHA guidelines for the management of atients with valvular heart disease, the ESC recommendation on the management of the asymtomatic atient with valvular heart disease 2002 and recommendations from Otto form the basis of the recently udated ACC/AHA guidelines. 1 3 In the latter ublication, the cut-off values for the grading of the severity of aortic valve stenosis were changed. For examle, the definition of severe aortic valve stenosis currently includes an AVA,1.0 cm 2, DP m.40 mmhg, or V max.4.0 m/s introducing somewhat stricter cut-off values for severe stenosis from the revious AVA 1.0 cm 2 and DP m.50 mmhg. 1 Although these changes have reduced the discreancies between the three criteria for the assessment of the severity of aortic valve stenosis, the results from more than 3400 echocardiograhy assessments resented in this aer show that major inconsistencies ersist and AVA continues to overestimate the severity of disease when comared to the two other arameters. In the management of atients with aortic valve stenosis, symtoms attributable to aortic stenosis (syncoe, angina, and dysnoea) determine which atient should undergo valve relacement. On the other hand, decisions on management of asymtomatic atients articularly with severe stenosis are more difficult and exact grading becomes more imortant. Risk of raid rogression of disease, imminent heart failure and sudden death must be weighed against erioerative morbidity and mortality, valve deterioration, and roblems associated with ossible long-term anticoagulation. 3,10 Various smaller studies suggested that it was safe to withhold surgery in atients until symtoms occur. 15 17 On the other hand, Rosenhek et al. 18 roosed that
Inconsistencies of echocardiograhic criteria 1047 asymtomatic atients with severe aortic valve stenosis (V max 5.0 + 0.6 m/s) resenting with moderate to severe calcification together with a raid increase in V max may benefit from surgery rior to the develoment of symtoms. In addition, a recent ublication reorting on more than 600 atients with a V max.4.0 m/s and a follow-u of 5 years indicates that in these atients cardiac death is common (19%/5 years of follow-u) and the likelihood of remaining free of surgery or cardiac death is low (25%/5 years of follow-u). 19 The Euroean Society of Cardiology working grou on valvular heart disease recommends intervention in asymtomatic atients with an AVA,1.0 cm 2 (,0.6 cm 2 corrected BSA) in the resence of an abnormal resonse to exercise, moderate to severe calcification, and raid rogression of V max (.0.3 m/s/year) or deressed LV function. 2 Lancellotti et al. 20 have recently shown that an AVA of,0.75 cm 2 redicts death or valve relacement within 15 months of follow-u in atients with a athological 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-u. 17 In addition, atients with comorbidities such as COPD, obesity, or hyertension may rove articularly difficult to manage due to the non-secificity of the symtom dysnoea. Therefore, findings on echocardiograhy may become critical in deciding on whether these atients should be subjected to the risk of valve relacement. Consequently, defining consistent cut-off values for severe aortic stenosis as a ossible indicator for surgery is more than an academic exercise. Two factors hel to at least artially exlain the discreancies in the grading of aortic valve stenosis resented in this aer. First, the effective valve area derived from Doler echocardiograhy is usually smaller than the anatomic valve area as measured by lanimetry, at autosy, 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 exlaining the differences between redicted 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, Doler echocardiograhic measurements with lower (effective) valve areas usually rovide the information for clinical decision making. These theoretical considerations together with clinical data 18,19 and the data resented in this aer suort the adjustment of the AVA cut-off value for severe stenosis to 0.8 cm 2. Secondly, low flow, low gradient aortic valve stenosis artly accounts for the differences found in our study. Stroke volume was slightly but significantly lower in inconsistently graded atients suorting the concet that low flow contributes to the differences in grading of aortic valve stenosis. However, since the overla between the two grous was large and the exact quantification of stroke volume by echocardiograhy is often difficult the correct grading of the individual atient may be roblematic. We therefore concur with Hachicha et al. 14 that every effort should be made to identify this clinically imortant subset of atients with aortic valve stenosis. A limitation of the resent study is its retrosective nature over a decade. It thus comrises diverse levels of technical exertise in acquiring Doler echocardiograhy measures as well as hard- and software develoments which may have contributed to scatter. Furthermore, the accuracy of the calculation of the redicted curves is limited by the use of standard values for cardiac outut, ejection time, flow in the LVOT etc. This may increase the correlation between the redicted and the fitted curves; however, it does not influence the main message of the resent aer 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 atients with normal LV systolic function are inconsistent. On the basis of AVA, a higher roortion of atients is classified as having severe aortic valve stenosis comared with mean ressure gradient and eak flow velocity. An AVA cut-off value for severe stenosis of 0.8 cm 2 may be more aroriate. Since discreant grading may be artly due to reduced stroke volume, every effort should be made to identify atients with low flow, low gradient aortic valve stenosis. Conflict of interest: none declared. References 1. 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