aortic regurgitation, vena contracta area, vena contracta width, live three-dimensional echocardiography

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1 RESEARCH FROM THE UNIVERSITY OF ALABAMA AT BIRMINGHAM Assessment of Aortic Regurgitation by Live Three-Dimensional Transthoracic Echocardiographic Measurements of Vena Contracta Area: Usefulness and Validation Ligang Fang, M.D., Ming Chon Hsiung, M.D., Andrew P. Miller, M.D., Navin C. Nanda, M.D., Wei Hsian Yin, M.D., Mason S. Young, M.D., and Dasan E. Velayudhan, M.B.B.S. Division of Cardiovascular Diseases, University of Alabama at Birmingham, Birmingham, Alabama Division of Cardiology, Cheng-Hsin Medical Center, Taipei, Taiwan, Republic of China In this report, we evaluate 56 consecutive adult patients who underwent standard two-dimensional (2D) and live three-dimensional transthoracic echocardiography (3D TTE), as well as left heart catheterization with aortography (45 patients) or cardiac surgery (11 patients), for evaluation of aortic insufficiency. Similar to the method we previously described for mitral insufficiency, aortic regurgitant vena contracta area (VCA) was obtained by 3D TTE by systematic and sequential cropping of the acquired 3D TTE data set. Assessments of aortic regurgitation (AR) by aortography and surgery are compared to measurements of VCA by 3D TTE and to 2D TTE measurements of vena contracta width (VCW). Aortographic or surgical grading correlated well with 2D TTE measurements of VCW (r = 0.92), but correlated better with 3D TTE measurements of VCA (r = 0.95), with improved dispersion between angiographic grades demonstrated by the 3D TTE technique. Live 3D TTE color Doppler measurements of VCA can be used for accurate assessment of AR and are comparable to assessment by aortography. (ECHOCARDIOGRAPHY, Volume 22, October 2005) aortic regurgitation, vena contracta area, vena contracta width, live three-dimensional echocardiography Introduction Assessing severity of aortic regurgitation (AR) accurately has been challenging using various qualitative and quantitative twodimensional transthoracic (2D TTE) color Doppler techniques. 1 Most commonly, the ratio of AR jet width immediately below the aortic valve to the inner left ventricular outflow tract (LVOT) width taken in the same frame is employed. 2,3 Proximal jet width is taken on the ventricular aspect of the aortic valve and essentially represents the vena contracta, which is the size of the jet within the leaflets Address for correspondence and reprint requests: Navin C. Nanda, M.D., University of Alabama at Birmingham, Heart Station SWB/S102, th Street South, Birmingham, Alabama Fax: ; nanda@uab.edu and extending for a small but variable extent into the LVOT. 1 Quantitative assessment using the volumetric approach and proximal flow convergence methods have been described, but are limited in use because they require assumptions that are mostly inaccurate. 1,4 7 Despite a large number of investigational studies, the assessment of AR quantification by various echocardiographic modalities remains challenging without a perfect technique, and current guidelines suggest an integrative approach. 1 Proximal jet or vena contracta width (VCW) is the most time honored of the 2D TTE approaches and has good correlation with angiographic grading and regurgitant orifice area. 2,3,6,7 If the exact size and shape of the vena contracta were available, it would be easy Vol. 22, No. 9, 2005 ECHOCARDIOGRAPHY: A Jrnl. of CV Ultrasound & Allied Tech. 775

2 FANG, ET AL. to measure the regurgitant volume by multiplying the vena contracta area (VCA) with the velocity time integral (VTI) of the continuous wave Doppler waveform of the AR jet. However, in the parasternal long-axis or apical views, only one dimension of the AR jet is visualized, and hence its size or area cannot be measured unless an assumption is made regarding its shape. Generally, VCA is considered circular or elliptical, but this is mostly an incorrect assumption. 8 A short-axis view taken at the level of the aortic valve leaflets on 2D TTE color Doppler would probably delineate the VCA in 3D, but because of cardiac motion, it is difficult to be certain one is not measuring the jet size further downstream where it tends to be larger. Also, it is difficult to be certain that the shortaxis echo plane is exactly parallel to the vena contracta. On the other hand, a pyramidal data set, acquired with live or real-time 3D echo, can be cropped at any desired angle and the plane aligned exactly parallel to the vena contracta in a short-axis plane. Thus, 3D echo obviates the limitations of 2D TTE color Doppler, is a relatively simple technique, and represents a useful supplement to 2D TTE. In the present study, we examine the usefulness of 3D TTE as an alternative modality in assessing AR severity using an improved and comprehensive visualization of vena contracta geometry. Methods This study included 56 patients (36 females, age 58.3 ± 16.6 years) who were referred for echocardiography for evaluation of AR to our institutions and who subsequently underwent cardiac catheterization with aortography and/or cardiac surgery within 72 hours of 3D TTE. Patients included in the study had at least mild AR by 2D TTE. The etiology of AR varied widely and was endocarditis in eight, prolapse in six, bicuspid morphology in seven, rheumatic in four, degenerative in 20, secondary to aortic dilatation or aneurysm in eight and unknown in three. Most had normal left ventricular systolic function (ejection fraction >55% in 50, 45 55% in one, and 33 45% in five) and AR was central in 37 and eccentric in 19. Echocardiography A standard examination was completed on each patient in the left lateral decubitus position using both apical and parasternal views. 2D TTE studies were performed using a 3.5 MHz probe and a commercially available ultrasound system [Philips Sonos 7500 (n = 31 patients), or IE33 (n = 25 patients), Andover, MA]. Vena contracta width was measured as the smallest neck of flow at the level of the aortic valve. 1, 9 In patients with more than one AR jet (three cases), the VCW was taken as the sum of all individual vena contracta widths. After completion of the standard 2D TTE in each patient, live and real-time 3D TTE was then performed in all patients using the same ultrasound system and a 4 MHz 4X transducer capable of providing real-time B-mode and color Doppler 3-dimensional images in apical and parasternal views. Factory defaults on the echocardiographic system were used for acquisition of all images and the Nyquist limit was selected between cm/s as discussed previously. 10 Approximately 5 7 seconds of breath-holding were needed to collect each 3D TTE data set. The 3D data sets were transferred to an offline QLab system for analysis in all 56 patients. Data were stored digitally and subsequently evaluated by two echocardiographers. Measurement of VCA by 3D TTE As shown in Figure 1 and as described previously for mitral regurgitation, 10 systematic cropping of the acquired 3D TTE data set was used to measure VCA. First, from a parasternal long-axis view (55 cases) or from an apical view when the parasternal window was poor (one case), the best AR jet in long axis was obtained by posterior-to-anterior cropping of the 3D TTE data set. Second, the 3D TTE color Doppler data set was cropped from the aortic side to the level of the vena contracta, at or just below the aortic valve leaflets, in a plane that was exactly perpendicular to the AR jet viewed in long axis. The image was then tilted en face, and the cropped portion of the data set was added back to obtain the maximum area of vena contracta viewed in short axis in systole. In patients with multiple AR jets (five cases) the VCA was taken as the sum of all individual vena contracta areas. Measurements of VCA were obtained by off-line analysis on Q-LAB software in all patients. In addition, in 17 patients, VCA was also measured by planimetry via the trace function using the VCR functions on an echocardiographic system and the depth markers for calibration. Aortography AR grading by aortography was performed using the method of Hunt et al ECHOCARDIOGRAPHY: A Jrnl. of CV Ultrasound & Allied Tech. Vol. 22, No. 9, 2005

3 3D TTE VENA CONTRACTA AREA FOR AR Figure 1. Live three-dimensional color Doppler transthoracic echocardiographic technique for assessment of aortic regurgitation (AR) vena contracta. The three-dimensional color Doppler data set showing AR (A) is cropped using an oblique plane to the level of the vena contracta (arrowhead, B) and tilted to view it en face (C, D).The vena contracta is then planimetered. AO = aorta; LA = left atrium; LV = left ventricle; RV = right ventricle. Figure 4. Live three-dimensional transthoracic echocardiographic assessment of aortic valve perforations in two patients with endocarditis. Left: Two perforations (numbered 1 and 2) demonstrated by cropping of the three-dimensional color Doppler data set. Right: Arrowheads demonstrate multiple perforations in a patient with almost totally destroyed aortic cusps at surgery. Vol. 22, No. 9, 2005 ECHOCARDIOGRAPHY: A Jrnl. of CV Ultrasound & Allied Tech. 777

4 FANG, ET AL. Statistics Statistical calculations were performed using the program Statistica (Statsoft, Tulsa, OK). Spearman rank correlations between TTE measurements and aortographic grading of AR were calculated. Measurements by two echocardiographers blinded to each others results and the aortographic and surgical findings, and by one echocardiographer after a1month time delay with blinding to previous results were compared to obtain interobserver and intraobserver variability, respectively. For all measurements a P-value of less than 0.05 was considered significant. Results Aortography revealed grade I AR in 12 patients, grade II in 8, grade III in 14, and grade IV in 11 patients. An additional 11 patients underwent surgery without angiography, during which severe AR was verified by direct inspection. 2D TTE measurements of VCW were obtained in all patients and ranged from 0.14 to 1.2 cm. 3D TTE measurements of VCA were likewise obtained in all participants and ranged from 0.07 to 1.53 cm 2. Comparisons of AR assessment by 3D and 2D TTE with aortography revealed highest agreement for the 3D TTE measurements. VCA from 3D TTE closely correlated with angiographic grading (r s = 0.95, P < 0.001; Fig. 2), with little overlap evident between grades of AR. When criteria of <0.2 cm 2 for grade I, cm 2 for grade II, cm 2 for grade III, and >0.6 cm 2 for grade IV AR were utilized, only two patients did not match angiographic and VCA grades. Whether the regurgitant jet was central or eccentric did not affect VCA grading. VCW by 2D TTE correlated well (r s = 0.92, P < 0.001; Fig. 3), but with more overlap between aortographic grades of AR. Interobserver and intraobserver variability was very low for 3D TTE measurements of VCA (r = 0.95 and r = 0.95). Further, consistent with our past results, 10 the on-line processing procedure for calculating VCA was valid and reproducible. Measurements of 3D TTE VCA obtained on the echocardiographic n=56 rs=0.947 p< D VCA(cm2) aortic root angio grade Figure 2. Shows the correlation between live three-dimensional transthoracic color Doppler echocardiographic measurements of aortic regurgitation vena contracta (3D VCA) and aortic root angiographic grading. The open circles denote patients with eccentric aortic regurgitant jets; closed circles denote central jets. 778 ECHOCARDIOGRAPHY: A Jrnl. of CV Ultrasound & Allied Tech. Vol. 22, No. 9, 2005

5 3D TTE VENA CONTRACTA AREA FOR AR n=56 rs=0.917 p< VCW (cm) aortic root angio grade Figure 3. Shows the correlation between aortic regurgitation vena contracta widths (VCW) measured by two-dimensional transthoracic color Doppler echocardiography and aortic root angiographic grades of aortic regurgitation. The open circles denote patients with eccentric aortic regurgitant jets; closed circles denote central jets. system by manual processing agreed closely with off-line measurements of VCA by 3D TTE using the Q-LAB software (r = 0.96). 3D TTE evaluation provided additional value in identifying mechanism of AR in a number of patients. Specifically, surgical findings of valve perforations, total or almost total cusp destruction, and bicuspid valves were identified by 3D TTE in all cases with specific mention of these pathologies. In four cases with operative findings of a perforation in one or more coronary cusps, 3D TTE revealed perforations in the cusp(s) identified by the surgeon. In five cases that the surgeon denoted as totally or almost totally destroyed cusps, 3D TTE demonstrated multiple perforations (one case) or torrential AR (four cases, Fig. 4). Finally, in all eight cases identified as bicuspid aortic valve at the time of surgery, 3D TTE diagnosed this morphology correctly. Discussion The current report demonstrates the feasibility and potential clinical importance of assessing AR by VCA measurements obtained from a live 3D TTE examination. Further, we demonstrate validation of this new technique with the time-honored standards of aortography and surgery. Since a plane created from the 3D data set can be ensured to encompass the flow convergence, the vena contracta and the regurgitant jet, the vena contracta, defined as the smallest neck of the flow region at the aortic valve, can be obtained with confidence. By using imaging planes exactly perpendicular to the AR jet in long axis, the entirety of the vena contracta can be appreciated and planimetered. This measured VCA signifies the actual regurgitant hole in the aortic orifice in diastole, and is an accurate, reproducible, and quantitative measure of AR. Previously, AR grading systems have been described for different imaging modalities. Aortography is the time-honored standard, 11 but is limited by technical factors such as different background densities between two orthogonal projections, dysrhythmias, and is especially variable in patients with enlarged ventricles. 12 Doppler echocardiography and measurement of the VCW has become the preferred technique for evaluation of AR. 13 Two approaches have been described: (1) measurement of the proximal-jet-width-to-lvot-width and (2) measurement of VCW alone. Current recommendations include use of both of these similar indices, Vol. 22, No. 9, 2005 ECHOCARDIOGRAPHY: A Jrnl. of CV Ultrasound & Allied Tech. 779

6 FANG, ET AL. along with other echocardiographic clues including left atrial size and aortic flow reversal. 1 These techniques are limited though by the use of a 2D plane to describe and quantify a 3D object. Even attempts at capturing the complex geometry of the vena contracta by obtaining a short-axis view of the aortic valve are hampered by the limitations of 2D echocardiography. As mentioned above in the original work by Byard et al. 2 and Perry et al. 3 (from our Echo Lab), the AR jet in short axis did not correlate as well with the aortographic criteria of AR severity as the proximal jet width divided by LVOT width, probably because of the difficulty in ascertaining that one was measuring the jet width or vena contracta at the level of the aortic valve and not further downstream. 3 Also, it is difficult to align the 2D TTE short-axis plane exactly parallel to the vena contracta or proximal jet width imaged in short axis, especially in patients with eccentric AR. The ability of 3D echocardiography to dissect the complex geometry of a regurgitant jet offer great promise for accurate quantification of its severity. Initial in vitro studies with 3D echocardiography demonstrated this theoretical advantage, with quantification of both the vena contracta size and characterization of the flow convergence region. 14 Taking 3D TTE quantification of VCA to the bedside, we utilized this technique previously in the assessment of mitral regurgitation and demonstrated improved correlation with and better dispersion between angiographic grades of insufficiency. 10 In this report, our comparison of AR assessed by 3D TTE measurements of VCA and by aortography or surgery suggests a new index of AR. We propose the following criteria for VCA assessment of AR: <0.2 cm 2 for grade I, cm 2 for grade II, cm 2 for grade III, and >0.6 cm 2 for grade IV. Using these criteria, we demonstrate good correlation with and nearly perfect separation between angiographic grades in this set of patients (Fig. 2) and, when compared with the commonly employed 2D TTE measurement of VCW, VCA by 3D TTE is the best method for delineating AR grade by aortography. We acknowledge several limitations in this report. First, our report is a descriptive one. It includes a smaller sample size and only shortterm follow up. Further use of this technique in a larger population might yield provocative prognostic information. Second, the technology is still maturing. The current frame rate and color pixel size still limit signal resolution and might blur the actual dimensions of the effective regurgitant orifice or hole in the valve in patients with mild insufficiency. As the technology continues to advance, including the refinement of truly live 3D TTE to permit immediate quantification of VCA, this limitation should become a historical footnote. Finally, the question of how to handle multiple jets is yet a conundrum. In this study, we added their areas, but validation of this measure is needed in a larger group of patients with multiple regurgitant jets. Building upon our previous experience with mitral regurgitation, 3D TTE assessment of VCA provides an accurate measure of the aortic regurgitant orifice that incorporates the full geometry of this valvular lesion. Assessment of VCA by 3D TTE offers the potential for a simple, quantifiable measure of AR that is independent of load and might offer prognostic information if evaluated in studies with long-term follow up. Further study of this technique as a reproducible measure of valvular insufficiency is warranted. Conclusion Live 3D TTE quantification of VCA is a useful and accurate measure of aortic regurgitation. References 1. Zoghbi WA, Enriquez-Sarano M, Foster E, et al: Recommendations for evaluation of the severity of native valvular regurgitation with two dimensional and Doppler echocardiography. J Am Soc Echo 2003;16: Byard CE, Perry GJ, Roitman DI, et al: Quantitative assessment of aortic regurgitation by color Doppler. Circulation 1985;72: Abstract III Perry GJ, Helmcke F, Nanda NC, et al: Evaluation of aortic insufficiency by Doppler color flow mapping. J Am Coll Cardiol 1987;9: Rokey R, Sterling LL, Zoghbi WA, et al: Determination of regurgitant fraction in isolated mitral or aortic regurgitation by pulsed Doppler two dimensional echocardiography. J Am Coll Cardiol 1986;7: Enriquez-Sarano M, Bailey KR, Seward JB, et al: Quantitative Doppler assessment of valvular regurgitation. Circulation 1993;87: Enriquez-Sarano M, Seward JB, Bailey KR, et al: Effective regurgitant orifice area: A noninvasive Doppler development of an old hemodynamic concept. JAm Coll Cardiol 1994;23: Tribouilloy CM, Enriquez-Sarano M, Fett SL, et al: Application of the proximal flow convergence method to calculate the effective regurgitant orifice area in aortic regurgitation. JAmColl Cardiol 1998;32: Shiota T, Jones M, Delabays A, et al: Direct measurement of three-dimensionally reconstructed flow convergence surface area and regurgitant flow in aortic 780 ECHOCARDIOGRAPHY: A Jrnl. of CV Ultrasound & Allied Tech. Vol. 22, No. 9, 2005

7 3D TTE VENA CONTRACTA AREA FOR AR regurgitation: In vitro and chronic animal model studies. Circulation 1997;96: Tribouilloy CM, Enriquez-Sarano M, Bailey KR, et al: Assessment of severity of aortic regurgitation using the width of the vena contracta: A clinical color Doppler imaging study. Circulation 2000;102: Khanna D, Vengala S, Miller AP, et al: Quantification of mitral regurgitation by live three-dimensional transthoracic echocardiographic measurements of vena contracta area. Echocardiography 2004;21: Hunt D, Baxley WA, Kennedy JW, et al: Quantitative evaluation of cineaortography in the assessment of aortic regurgitation. Am J Cardiol 1973;31: Croft CH, Lipscomb K, Mathis K, et al: Limitations of qualitative angiographic grading in aortic or mitral regurgitation. Am J Cardiol 1984;53: Enriquez-Sarano M, Tajik AJ, et al: Aortic regurgitation. N Engl J Med 2005;351: Irvine T, Li XN, Rusk R, et al: Three dimensional colour Doppler echocardiography for the characterisation and quantification of cardiac flow events. Heart 2000;84:ii2 ii6. Vol. 22, No. 9, 2005 ECHOCARDIOGRAPHY: A Jrnl. of CV Ultrasound & Allied Tech. 781

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