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Quantitation of aortic regurgitation by Doppler echocardiography: A practical approach
CURRICULUM IN CARDIOLOGY
Quantitation of aortic regurgitation by Doppler echocardiography: A practical approach Melda Samilgil Dolan, MD, Ramon Castello, MD, Jeanette A. St. Vrain, RDMS, Frank Aguirre, MD, and Arthur J. Labovitz, MD St. Louis, Mo.
Doppler echocardiography is the most common noninvasive method used to quantitate aortic regurgitation. In early studies both pulsed and continuous wave Doppler were shown to be accurate methods of quantifying aortic insufficiency when compared to results of cardiac catheterization studies. 1 Doppler color flow mapping has become the standard for the quantitation of aortic insufficiency because good correlation between color flow Doppler parameters and the angiographic grading of aortic insufficiency 2-s has been shown. The most commonly used color flow parameters have been validated in small series of patients. Therefore, in most echocardiographic laboratories, both echocardiographic Doppler modalities (i.e., continuous wave and color flow mapping) are used in conjunction to quantitate aortic regurgitation. In addition, although both Doppler methods have been compared to the angiographic results independently, no studies have compared the two echocardiographic techniques for such evaluation. Thus the purpose of the present study was to compare these cardiac Doppler modalities to determine which method best predicts angiographic severity of aortic regurgitation. METHODOLOGY Patients. The study group consisted of all patients
who underwent both transthoracic echocardiography and cardiac catheterization with aortic root injections at our institution within a 2-week period between August 1988 and February 1993. Absence of significant changes in clinical status between the two procedures, including medication and rhythm changes, was required. The two studies were perFrom Saint Louis University Health Sciences Center. Received for publication Aug. 23, 1994; accepted Oct. 3, 1994. Reprint requests: Ramon Castello, MD, Division of Cardiology, FDT-14, Saint Louis University Medical Center, 3635 Vista Ave. at Grand Blvd., St. Louis, MO 63110-0250. AM HEART J 1995;129:1014-20. Copyright ® 1995 by Mosby-Year Book, Inc. 0002-8703/95/$3.00 + 0 4/1/61997
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formed within 48 hours in 48 % of the patients, with a mean time interval of 5 + 4 days for the entire group. The 161 patients (92 women and 69 men) who met the entry criteria ranged in age from 23 to 92 with a mean age of 64 + 15 years. All patients had evidence of aortic regurgitation on the basis of aortic root injections. Ninety-six patients had isolated aortic regurgitation and 20 had concomitant aortic stenosis. Twenty-two patients had associated mitral regurgitation and 5 had associated mitral stenosis. Nine patients had mitral valve prosthesis, 6 had aortic valve prosthesis and 3 had both mitral and aortic valve prosthesis. The mean left ventricular ejection fraction was 51.6% _+ 8.2%. In all patients, aortic regurgitation was chronic. One hundred forty patients had normal sinus rhythm. The remaining 21 patients exhibited atrial fibrillation. Echocardiographic
studies. A l l studies were per-
formed with commercially available systems (Hewlett-Packard Sonos 500, 1000, and 1500, Acuson X P 128, or VingMed 700 and 750) with 2.5 mHz transducers and recorded on 0.5-inch (1.27 cm) VHS videotapes for off-line review and analysis. Throughout all studies, particular care was taken to optimize the variables regarding the individualized appropriate instrument settings for mapping and scaling of velocity, gain, depth, and sector angle. Color flow analysis. The studies were analyzed by two independent observers who were unaware of the results of angiographic grading. All measurements were obtained off-line by using a commercially available echocardiographic analysis system ( G T I Freeland). The height of the regurgitant jet (JH), defined as the anteroposterior diameter of the jet at its origin in the left ventricular outflow tract, was measured from the parasternal long axis. The same frame at the same location at which the J H was obtained was used to measure the anteroposterior diameter of ventricular outflow tract (LVOH). The J H / L V O H ratio was calculated in each case (Fig. 1). From the parasternal short-axis view, the area of the regurgitant jet (JASA) was planimetered. The
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Fig. 1. Color flow measurements of patient with 3+ aortic regurgitation from parasternal long axis. Note that anteroposterior diameter of jet at its origin JH (short arrows) was measured at same location as LVOH (long arrows). In this patient, JH/LVOH ratio was calculated as 0.41.
same frame at which JASA was obtained was used to measure the area of the left ventricular outflow area (LVOA). The JASA/LVOA ratio was calculated (Fig. 2). The apical four-chamber view was used to measure the area of the regurgitant jet (JA). The area of left ventricle (LVA) from the same frame was measured, and the JA/LVA ratio was calculated for each patient. The individual values of the above-mentioned variables corresponding to three cycles were averaged in patients with sinus rhythm. In patients with atrial fibrillation, five cardiac cycles were averaged. Continuous wave Doppler analysis. C o n t i n u o u s wave
Doppler recordings were obtained from the cardiac apex from either the apical five-chamber or the apical long-axis view. Color flow was used to align the Doppler beam parallel to flow. Continuous wave Doppler signals of early diastolic flow reversal were defined as aortic insufficiency. The slope of diastolic deceleration was determined as the slope of a straight line drawn along the peak velocities throughout diastole as previously described. ~ (Fig. 3). Pressure half-time was defined as the time required for the initial early diastolic transvalvular pressure gradient to be halved. 9,10 All values for the continuous-wave
Doppler parameters were the average of three consecutive beats in patients with sinus rhythm. In patients with atrial fibrillation, five cardiac cycles were averaged. Cardiac catheterization. Cardiac catheterization was performed in a routine fashion by either the brachial or the femoral artery approach. Angiographic aortic valve regurgitation was diagnosed from the aortic root angiograms performed in 60-degree left anterior oblique view. The severity of aortic regurgitation (0 to 4+) was graded according to standard criteria 11 by one observer unaware of the results of the echocardiographic studies. Interobserver and intraobserver variabilities. To determine the interobserver variability, color and continuous wave Doppler measurement were obtained by a second observer in 26 randomly selected studies without knowledge of the previous measurements. To determine intraobserver variability, the same 26 patients were reanalyzed by the first observer 4 weeks later. Observer variability was defined as the absolute difference between two observations divided by the mean and expressed as a percentage. Statistics. All values are expressed as mean + SD. Correlations between continuous wave Doppler and
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Fig. 2. Color flow measurements of patient with 2+ aortic regurgitation from short axis. JASA/LVOA ratio was calculated as 0.25 in this patient. LA, Left atrium; RVOT, right ventricular outflow tract.
Table h Interobserver and intraobserver variability in color
and continuous flow Doppler measurements r
JH Intraobserver Interobserver JH/LVOH Intraobserver Interobserver JASA/LVOA Intraobserver Interobserver Slope Intraobserver Interobserver
Variability (%)
99 99
7 _+3 8 _+3
99 99
6 _+ 3 6+3
98 97
10 _+ 3 12 + 2
99 98
5+4 7+3
color Doppler p a r a m e t e r s and the angiographic grading were obtained by using the P e a r s o n correlation and linear regression analysis, p Values <0.05 were considered significant. Analysis of variance was perf o r m e d when multiple m e a s u r e m e n t s were compared. S t u d e n t t test was applied where appropriate. OBSERVATIONS Interobserver and intraobserver variability. Interob-
server and intraobserver variability (Table I) was as-
sessed by linear regression between m e a s u r e m e n t s and also as a percentage of variability for the color flow Doppler and the continuous wave variables. T h e maximal height of the regurgitant jet at its origin (JH) at the left ventricular outflow t r a c t was adequately measured in 156 (97 % ) of the 161 patients. T h e maximal JA from short axis could be obtained in 152 (94%) patients. T h e jet area from the apical four-chamber view could be obtained in 150 (93 %) patients, b u t the entire left ventricle could be visualized in only 140 (86 % ). Color flow Doppler measurements vs angiographic grading. Significant correlations were found between
the color flow Doppler p a r a m e t e r s and the degree of aortic regurgitation assessed by the aortic root angiograms (Fig. 4). T h e best correlation was obtained with the ratio of the m a x i m u m J H to the L V O H expressed as a percentage (r = 0.91, p = 0.0001). B y using 25 % and 40 % as cut points for the J H / L V O H ratio, a good discrimination among regurgitation groups was obtained (Fig. 5). A 40 % cut point for J H / L V O H ratio provided a very good discrimination between angiographic 1 to 2+ and 3 to 4+ groups. Forty-five of the 48 patients with 3 to 4+ aortic regurgitation had the J H / L V O H ratio >40 % (sensitivity 94 %, specificity 97 %, positive predictive valve
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Fig. 3. Continuous wave Doppler tracings from patient with 2+ aortic regurgitation. A/, Aortic insufficiency.
94%, accuracy 96%). However, 25% as another cut point for the J H / L V O H ratio also permits a very good separation of mild aortic regurgitation from moderate and severe forms. Sixty-one of the 64 patients with mild aortic regurgitation had an J H / L V O H ratio <25 % (sensitivity 95 %, specificity 96 %, positive predictive value 94 %, accuracy 96 % ). The simple measurement of absolute J H at the left ventricular outflow tract had a strong correlation with the angiographic severity of aortic regurgitation (r = 0.89; Fig. 6). The J H in the 108 patients with 1+ and 2+ aortic regurgitation ranged from 0.11 to 0.86 cm (mean 0.5 + 0.18), whereas the J H in the 48 patients with 3 and 4+ aortic regurgitation ranged from 0.78 to 1.81 cm (mean 1.03 +_ 0.22). A cut point of 0.8 cm for J H provided very good discrimination between the angiographic 1 to 2+ and 3 to 4+ groups. It was highly sensitive (97 % ), highly specific (98 % ), and highly accurate (97 %) to separate 1 to 2+ from 3 to 4+ aortic regurgitation. The JASA/LVOA ratio also correlated highly with the angiographic grading (r = 0.86, p = 0.0001). For this ratio, the best cut point obtained was 25 %, which provided good discrimination between groups 1 to 2 and 3 to 4 aortic regurgitation (although with considerable overlap). The cut point of 25% for JASA/ LVOA also provided a good separation between the angiographic 1 to 2+ and 3 to 4+ groups, with sensitivity 92 %, specificity 97 %, and accuracy 93 %. Among other color flow parameters, the J A / L V A ratio was quite variable in all grades of aortic regur-
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Fig. 4. Comparison of color Doppler and continuous Doppler parameters correlations vs angiographic grading of aortic insufficiency. All correlations were expressed as correlation coefficient. Note that color Doppler parameters have higher correlations with angiographic grading of aortic regurgitation than continuous Doppler parameters.
gitation, with a very wide range of values within the groups. However, there was a significant and fairly good correlation with the angiographic grading (r = 0.75, p = 0.0001). No cut points provided a good discrimination among groups for JA/LVA ratio.
ContinuouswaveDopplerparametersvsangiographic grading
Deceleration slope. There was a good correlation (r = 0.70, p = 0.0001) between the angiographic degree of regurgitation and the deceleration slope (Fig. 7). The slopes were significantly lower in patients with mild aortic insufficiency (1.95 +_ 0.47 m/sec 2)
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than in patients with angiography graded 3 to 4+ (3.08 _+ 0.7 m/sec 2) aortic insufficiency ( p < 0.01). With previously established conventional cut points of 2 m/sec 2 and 3 m/sec 2, the separation of different angiographic groups was not excellent, although an increasing deceleration slope was seen with increasing regurgitation severity. Patients with 4+ aortic regurgitation had significantly greater slopes than those with moderate and mild aortic regurgitation (3.68 + 0.50 m/sec2). However, 3 m/sec t as a cut point for separating severe aortic regurgitation from mild and moderate forms was highly specific (97 % ) and accurate (86 % ). Pressure half-time. There was a fair although significant correlation between the pressure half-time
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Fig. 7. Comparison of deceleration slopes as measured from continuous wave Doppler and angiographic grading of aortic insufficiency (A/). and the severity of aortic regurgitation (r = -0.62, p = 0.0001; Fig. 4). Although this parameter did not allow good separation of different degrees of regurgitation, the patients with mild aortic regurgitation had longer pressure half-times than patients with moderate or severe regurgitation (353 + 99 vs 232 + 58 msec, p < 0.001). COMMENTS
Continuous wave Doppler echocardiography, which differs from pulsed Doppler in its enhanced ability to resolve high velocities and provide assessment of pressure differences between the aorta and left ventricle throughout diastole, has traditionally been used to quantify the degree of aortic insufficiency. Early studies documented the usefulness of this Doppler technique to quantify the degree of aortic regurgitation by assessing the rate by which the aortic and left ventricular pressures equilibrate during diastole. ~ These studies have shown that the deceleration slope is a good indicator, although not an excellent discriminator, of the different degrees of aortic regurgitation. The present study, continuing these early results, found the accuracy of the slope for predicting severe aortic regurgitation to be very high. The pressure half-time did not show such a good correlation. Likewise, this index was not a good discriminator between different grades of aortic regurgitation. In a series of 26 patients, Miyatake et al. 3 used the regurgitant color flow area and demonstrated that the more severe the aortic regurgitation, the larger the regurgitant jet by color flow mapping. The maximal length of the regurgitant jet into the left ventricle from the long-axis view was not an adequate pa-
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rameter for grading aortic regurgitation as compared with angiography. 2 More recently, Perry et al., s in a series of only 30 patients, compared the color flow parameters with the angiographic grading. These authors found that short-axis area of the jet at its origin immediately below the aortic valve was the most accurate predictor of aortic regurgitation severity. Similarly, in our series of 161 patients the ratio of the JASA to the short-axis area of the left ventricle outflow tract also had a very close correlation with angiographic grading (r = 86). However, this parameter could only be obtained in 94 % of our patients. The measurements of the jet at its origin (JH) will provide the most accurate estimation of aortic regurgitation in obtaining either J H / L V O H or JASA/ LVOA ratios. In proving this hypothesis, Switzer et al., 7 used an in vitro model to find that JH, when measured at its origin, was the best predictor of regurgitant volume, which was the only function of the size of valvular defect. Likewise, in our study the parasternal long-axis view demonstrated that the origin of regurgitant jet at the left ventricle outflow tract resulted in the highest correlation with anglographic grading (r = 0.91). Theoretically, short axis is the only acoustic window that allows approach of the jet relatively as deflection of two planes; therefore the values from the short axis view should be superior to t h e values obtained from the parasternal long-axis view, which is a deflection of only one plane. However, adequate images were obtained more frequently from the parasternal long-axis (97 % ) than from the parasternal short-axis (94 % ) views. Our data suggest the superiority of the parasternal long-axis view because of the excellent correlation with angiographic grading and because it could be obtained in virtually all patients (97 %). Some investigators have measured the regurgitant JA in LV from the apical four-chamber views and used it as a predictor of the severity of aortic regurgitation. Yock et al. 12 pointed out that the measurement of JA by color flow mapping from this window is difficult because it commonly merges with the mitral flow. These difficulties were confirmed in our large series of patients as described earlier. The use of this color flow parameter rendered the least power to separate different degrees of aortic regurgitation, making it unacceptable. Perry et al. s also found poor correlation between JA in L ¥ and anglographic severity. The relative merging of the aortic regurgitant jet and transmitral filling flow was the main difficulty in an adequate measurement of the
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regurgitant JA from a four-chamber window in our study. Study limitations. A variety of technical and physiologic factors have the potential to affect our results. The influence of technical variables such as color gain settings and transducer frequencies is well established. 13-16 Baumgartner et al. 17 emphasized that as long as instrument settings have not been standardized to obtain reproducible color flow estimates, the use of information derived from color Doppler grading criteria will be adversely affected by the differences in instrument setting and differences between the ultrasound devices. In the present study, the instrument settings for gain, width, sector angle, and ultrasound equipment were not identical. Because this study is retrospective, standardization of these parameters was impossible. The availability of optimal images led us to establish the adequate instrument settings for the individual studies. In addition, the angiographic and echocardiographic studies were not performed simultaneously. It is well established that the size of the jet area by color imaging is influenced by loading conditions, is Although special care was taken to include patients with no differences in clinical status between the echocardiographic and the angiographic studies, a hemodynamic identity cannot be warranted. In the present study, we compared the ech(~derived parameters with a semiquantitative method, that is, aortic root injection. Croft et al. 19 showed that, even when aortic root angiography is done by experienced cardiologists, the regurgitation can still either be overestimated or underestimated. On the other hand, very few studies had documented the correlation between aortic root-injected-derived results and regurgitant volumes in the quantification of aortic regurgitation. 19' 2o However, the use of the regurgitant volume instead of angiographic grading of aortic regurgitation as a standard reference will not provide practical standardization. Even the very slightest alterations in the calculation of either stroke volume or cardiac output will cause significant errors in the calculations of regurgitant volume. Also, atrial fibrillation or mitral regurgitation will adversely affect the predictive accuracy of the calculations for regurgitant volume. Because the present study includes cases with mitral regurgitation (14%) and atrial fibrillation (13%), the use of aortic root injection should be considered a valid reference method. Conclusions. Our data suggest that color Doppler echocardiography is superior to continuous wave Doppler parameters for the quantification of aortic regurgitation. The ratio of the J H at its origin in left
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ventricular outflow tract to left ventricular outflow tract diameter obtained from the parasternal longaxis view was found to be the best predictor of aortic regurgitation when compared to angiography. The measurement of the absolute JH at its origin appears to be the simplest and the most practical method not only to detect aortic regurgitation, but also to discriminate accurately between mild and moderate or severe aortic regurgitation. Our data also indicate that the JA/LVOH ratio is very helpful as a predictor of severity of angiographic grading. However, as previously described, 8 this parameter is limited by technical difficulties. Planimetry is required, which should be considered a disadvantage of the method. The deceleration slope, the best continuous Doppler parameter, has a high predictive accuracy for severe aortic regurgitation, but it has an inferior discriminating power compared to the color flow Doppler parameters. SUMMARY
Aortic regurgitation is most frequently assessed noninvasively by Doppler echocardiography by use of continuous wave and Doppler color flow mapping. To compare both Doppler methods, 161 patients who had undergone cardiac catheterization and complete echocardiographic studies were studied. The continuous wave parameters analyzed included the slope of the diastolic deceleration and the pressure half-time of the regurgitant jet. From color flow Doppler, conventional parameters such as JH and its ratio to LVOH, JASA and its ratio to LVOA, and the regurgitant JA and its ratio to the LVA were obtained. The JH/LVOH was the color flow parameter that best correlated with angiography (r = 0.91). A ratio of --<25 % was used to predict mild aortic regurgitation with 96 % accuracy. A ratio of > 4 0 % was also used to predict severe aortic regurgitation (3 to 4+) with 96% accuracy. Absolute JH at the origin of the regurgitant jet was the second best color flow parameter that correlated with angiography (r = 0.89). When continuous wave-derived slope was used, a significant overlap among different degrees of aortic regurgitation was observed. Predictive accuracy for mild aortic regurgitation was 70 % by using a slope <2 m/sec 2 and 86 % for severe aortic regurgitation when using a slope >3 m/sec 2. In conclusion, color flow Doppler appears to be superior to continuous wave Doppler in the assessment of aortic regurgitation. The JH/LVOH appears to be the best color parameter for quantifying aortic regurgitation. The measurement of the absolute JH at its origin appears to be the simplest and most practical method for assessing the degree of aortic regurgitation.
W e t h a n k our s o n o g r a p h e r s for their technical expertise, K a t h y B a n k e r for secretarial assistance, a n d J a m e s J. D o l a n for e x p e r t editorial assistance.
REFERENCES
1. Labovitz AJ, Ferrara RP, Kern MJ, Bryg RJ, Mrosek DG, Williams GA. Quantitative evaluation of aortic insufficiency by continuous-wave Doppler echocardiography. J Am Coll Cardiol 1986;8:1341-7. 2 . Omoto R, Yakote Y, Takamoto S, Kyo S, Ueda K, Asano H, Namekawa K, Kasai C, Kondo Y, Kovano A. The development of real time two dimensional Doppler echocardiograpby and its clinical significance in acquired valvular diseases. Jpn Heart J 1984;25:325-40; 3. Miyatake K, Okamoto M, Kinoshita N, Izumi S, Owa M, Takao S, Sakakibara H, Nimura Y. Clinical applications of a new type of real time two-dimensi0nal Doppler flow imaging system. Am J Cardiol 1984;54: 857-68. 4. Pearlman AS, Otto CM, Janko CL. Direction and width of aortic regurgitation jets: assessment by Doppler color flow mapping [Abstract]. J Am Coll Cardiol 1986;7:100. 5. Perry GJ, Helmcke F, Nanda NC. Color Doppler assessment of aortic insufficiency in two orthogonal planes [Abstract]. J Am Coll Cardiol 1986;7:101. 6. Bolger AF, Eigler NL, Pfaff JM. Relationship of color Doppler jet area to flow volume: reliability and limitations [Abstract]. Circulation 1986;74:II-216. 7. Switzer DF, Yoganathan AP, Nanda NC, Woo Y-R, Ridgway AJ. Calibration of color Doppler flow mapping during extreme hemodyaamic conditions in vitro: a foundation for a reliable quantitative grading system for aortic incompetence. Circulation 1987;75:837. 8. Perry GJ, Helmcke F, Nanda NC, Byard C, Soto B. Evaluation of aortic insufficiency by Doppler color flow mapping. J Am Coll Cardiol 1987;9:952-9. 9. Hatle L, Angelsen B, Tromsdal A. Noninvasive assessment of atrioventricular pressure half-time by Doppler ultrasound. Circulation 1979; 60:1096-104. 10. Bryg RJ, Labovitz AJ, Nelson JG, Kennedy HL, Williams GA. Comparison of Doppler echocardiography and two-dimensional echocardiography in the measurement of mitral valve area and mitral stenosis. Clin Res 1984;32:152. 11. Grossman W, Baum DS. Cardiac catheterization, angiography and intervention. 4th ed. Philadelphia: Lea & Febiger, 1991;576-7. 12. Yock PG, Segal J, Teirstein PS, Schnittinger I, Popp RL. Doppler color flow mapping: Utility in valvular regurgitation [Abstract]. Circulation 1984;70:38. 13. Smith MD, Grayburn PA, Spain MG, De Maria AN. Observer variability in the quantitation of Doppler color flow jet areas for mitral and aortic regurgitation. J Am Coll Cardiol 1988;11:579. 14. Bolger AF, Eigler NL, Pfaff JM, Resser KJ, Maurer G. Computer analysis of Doppler color flow mapping images for quantitative assessment of in vitro fluid jets. J Am Cull Cardiol 1988;12:450-7. 15. Stewart WJ, Schiavone WA, From JA, Castle T, Salcedo EE. In vitro studies of Doppler color flow mapping: dependence of spatial distribution on instrument setting. Circulation 1985;72(suppl III):98. 16. Hoit BD, Jones M, Eidbo EE, Elias W, Sahon DJ. Sources of variability for Doppler color flow mapping of regurgitant jets in an animal model of mitral regurgitation. J Am Coil Cardiol 1989;13:1631-6. 17. Baumgartner H, Schima H, Kuhn P. Importance of technical variable for quantitative measurements by Color Doppler imaging. Am J Cardiol 1991;67:314-5. 18. Spain MG, Smith MD, Kwan OL, DeMaria AN. Effect of isometric exercise of mitral and aortic regurgitation as assessed by color Doppler flow imaging. Am J Cardiol 1990;65:78-83. 19. Croft CH, Lipscomb K, Mathis K, Firth BG, N/cod P, Tilton G, Winniford MD, Hillis D. Limitations of qualitative angiographie grading in aortic or mitral regurgitation. Am J Cardiol 1984;53:1593-8. 20. Hunt D, Baxley WA, Kennedy JW, Judge TP, Williams JE. Quantitative evaluation of cine-aortography in the assessment of aortic regurgitation. Am J Cardiol 1973;31:696-700:
Quantitation of aortic regurgitation by Doppler echocardiography: A practical approach Melda Samilgil Dolan, MD, Ramon Castello, MD, Jeanette A. St. Vrain, RDMS, Frank Aguirre, MD, and Arthur J. Labovitz, MD St. Louis, Mo.
Doppler echocardiography is the most common noninvasive method used to quantitate aortic regurgitation. In early studies both pulsed and continuous wave Doppler were shown to be accurate methods of quantifying aortic insufficiency when compared to results of cardiac catheterization studies. 1 Doppler color flow mapping has become the standard for the quantitation of aortic insufficiency because good correlation between color flow Doppler parameters and the angiographic grading of aortic insufficiency 2-s has been shown. The most commonly used color flow parameters have been validated in small series of patients. Therefore, in most echocardiographic laboratories, both echocardiographic Doppler modalities (i.e., continuous wave and color flow mapping) are used in conjunction to quantitate aortic regurgitation. In addition, although both Doppler methods have been compared to the angiographic results independently, no studies have compared the two echocardiographic techniques for such evaluation. Thus the purpose of the present study was to compare these cardiac Doppler modalities to determine which method best predicts angiographic severity of aortic regurgitation. METHODOLOGY Patients. The study group consisted of all patients
who underwent both transthoracic echocardiography and cardiac catheterization with aortic root injections at our institution within a 2-week period between August 1988 and February 1993. Absence of significant changes in clinical status between the two procedures, including medication and rhythm changes, was required. The two studies were perFrom Saint Louis University Health Sciences Center. Received for publication Aug. 23, 1994; accepted Oct. 3, 1994. Reprint requests: Ramon Castello, MD, Division of Cardiology, FDT-14, Saint Louis University Medical Center, 3635 Vista Ave. at Grand Blvd., St. Louis, MO 63110-0250. AM HEART J 1995;129:1014-20. Copyright ® 1995 by Mosby-Year Book, Inc. 0002-8703/95/$3.00 + 0 4/1/61997
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formed within 48 hours in 48 % of the patients, with a mean time interval of 5 + 4 days for the entire group. The 161 patients (92 women and 69 men) who met the entry criteria ranged in age from 23 to 92 with a mean age of 64 + 15 years. All patients had evidence of aortic regurgitation on the basis of aortic root injections. Ninety-six patients had isolated aortic regurgitation and 20 had concomitant aortic stenosis. Twenty-two patients had associated mitral regurgitation and 5 had associated mitral stenosis. Nine patients had mitral valve prosthesis, 6 had aortic valve prosthesis and 3 had both mitral and aortic valve prosthesis. The mean left ventricular ejection fraction was 51.6% _+ 8.2%. In all patients, aortic regurgitation was chronic. One hundred forty patients had normal sinus rhythm. The remaining 21 patients exhibited atrial fibrillation. Echocardiographic
studies. A l l studies were per-
formed with commercially available systems (Hewlett-Packard Sonos 500, 1000, and 1500, Acuson X P 128, or VingMed 700 and 750) with 2.5 mHz transducers and recorded on 0.5-inch (1.27 cm) VHS videotapes for off-line review and analysis. Throughout all studies, particular care was taken to optimize the variables regarding the individualized appropriate instrument settings for mapping and scaling of velocity, gain, depth, and sector angle. Color flow analysis. The studies were analyzed by two independent observers who were unaware of the results of angiographic grading. All measurements were obtained off-line by using a commercially available echocardiographic analysis system ( G T I Freeland). The height of the regurgitant jet (JH), defined as the anteroposterior diameter of the jet at its origin in the left ventricular outflow tract, was measured from the parasternal long axis. The same frame at the same location at which the J H was obtained was used to measure the anteroposterior diameter of ventricular outflow tract (LVOH). The J H / L V O H ratio was calculated in each case (Fig. 1). From the parasternal short-axis view, the area of the regurgitant jet (JASA) was planimetered. The
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Fig. 1. Color flow measurements of patient with 3+ aortic regurgitation from parasternal long axis. Note that anteroposterior diameter of jet at its origin JH (short arrows) was measured at same location as LVOH (long arrows). In this patient, JH/LVOH ratio was calculated as 0.41.
same frame at which JASA was obtained was used to measure the area of the left ventricular outflow area (LVOA). The JASA/LVOA ratio was calculated (Fig. 2). The apical four-chamber view was used to measure the area of the regurgitant jet (JA). The area of left ventricle (LVA) from the same frame was measured, and the JA/LVA ratio was calculated for each patient. The individual values of the above-mentioned variables corresponding to three cycles were averaged in patients with sinus rhythm. In patients with atrial fibrillation, five cardiac cycles were averaged. Continuous wave Doppler analysis. C o n t i n u o u s wave
Doppler recordings were obtained from the cardiac apex from either the apical five-chamber or the apical long-axis view. Color flow was used to align the Doppler beam parallel to flow. Continuous wave Doppler signals of early diastolic flow reversal were defined as aortic insufficiency. The slope of diastolic deceleration was determined as the slope of a straight line drawn along the peak velocities throughout diastole as previously described. ~ (Fig. 3). Pressure half-time was defined as the time required for the initial early diastolic transvalvular pressure gradient to be halved. 9,10 All values for the continuous-wave
Doppler parameters were the average of three consecutive beats in patients with sinus rhythm. In patients with atrial fibrillation, five cardiac cycles were averaged. Cardiac catheterization. Cardiac catheterization was performed in a routine fashion by either the brachial or the femoral artery approach. Angiographic aortic valve regurgitation was diagnosed from the aortic root angiograms performed in 60-degree left anterior oblique view. The severity of aortic regurgitation (0 to 4+) was graded according to standard criteria 11 by one observer unaware of the results of the echocardiographic studies. Interobserver and intraobserver variabilities. To determine the interobserver variability, color and continuous wave Doppler measurement were obtained by a second observer in 26 randomly selected studies without knowledge of the previous measurements. To determine intraobserver variability, the same 26 patients were reanalyzed by the first observer 4 weeks later. Observer variability was defined as the absolute difference between two observations divided by the mean and expressed as a percentage. Statistics. All values are expressed as mean + SD. Correlations between continuous wave Doppler and
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Fig. 2. Color flow measurements of patient with 2+ aortic regurgitation from short axis. JASA/LVOA ratio was calculated as 0.25 in this patient. LA, Left atrium; RVOT, right ventricular outflow tract.
Table h Interobserver and intraobserver variability in color
and continuous flow Doppler measurements r
JH Intraobserver Interobserver JH/LVOH Intraobserver Interobserver JASA/LVOA Intraobserver Interobserver Slope Intraobserver Interobserver
Variability (%)
99 99
7 _+3 8 _+3
99 99
6 _+ 3 6+3
98 97
10 _+ 3 12 + 2
99 98
5+4 7+3
color Doppler p a r a m e t e r s and the angiographic grading were obtained by using the P e a r s o n correlation and linear regression analysis, p Values <0.05 were considered significant. Analysis of variance was perf o r m e d when multiple m e a s u r e m e n t s were compared. S t u d e n t t test was applied where appropriate. OBSERVATIONS Interobserver and intraobserver variability. Interob-
server and intraobserver variability (Table I) was as-
sessed by linear regression between m e a s u r e m e n t s and also as a percentage of variability for the color flow Doppler and the continuous wave variables. T h e maximal height of the regurgitant jet at its origin (JH) at the left ventricular outflow t r a c t was adequately measured in 156 (97 % ) of the 161 patients. T h e maximal JA from short axis could be obtained in 152 (94%) patients. T h e jet area from the apical four-chamber view could be obtained in 150 (93 %) patients, b u t the entire left ventricle could be visualized in only 140 (86 % ). Color flow Doppler measurements vs angiographic grading. Significant correlations were found between
the color flow Doppler p a r a m e t e r s and the degree of aortic regurgitation assessed by the aortic root angiograms (Fig. 4). T h e best correlation was obtained with the ratio of the m a x i m u m J H to the L V O H expressed as a percentage (r = 0.91, p = 0.0001). B y using 25 % and 40 % as cut points for the J H / L V O H ratio, a good discrimination among regurgitation groups was obtained (Fig. 5). A 40 % cut point for J H / L V O H ratio provided a very good discrimination between angiographic 1 to 2+ and 3 to 4+ groups. Forty-five of the 48 patients with 3 to 4+ aortic regurgitation had the J H / L V O H ratio >40 % (sensitivity 94 %, specificity 97 %, positive predictive valve
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Fig. 3. Continuous wave Doppler tracings from patient with 2+ aortic regurgitation. A/, Aortic insufficiency.
94%, accuracy 96%). However, 25% as another cut point for the J H / L V O H ratio also permits a very good separation of mild aortic regurgitation from moderate and severe forms. Sixty-one of the 64 patients with mild aortic regurgitation had an J H / L V O H ratio <25 % (sensitivity 95 %, specificity 96 %, positive predictive value 94 %, accuracy 96 % ). The simple measurement of absolute J H at the left ventricular outflow tract had a strong correlation with the angiographic severity of aortic regurgitation (r = 0.89; Fig. 6). The J H in the 108 patients with 1+ and 2+ aortic regurgitation ranged from 0.11 to 0.86 cm (mean 0.5 + 0.18), whereas the J H in the 48 patients with 3 and 4+ aortic regurgitation ranged from 0.78 to 1.81 cm (mean 1.03 +_ 0.22). A cut point of 0.8 cm for J H provided very good discrimination between the angiographic 1 to 2+ and 3 to 4+ groups. It was highly sensitive (97 % ), highly specific (98 % ), and highly accurate (97 %) to separate 1 to 2+ from 3 to 4+ aortic regurgitation. The JASA/LVOA ratio also correlated highly with the angiographic grading (r = 0.86, p = 0.0001). For this ratio, the best cut point obtained was 25 %, which provided good discrimination between groups 1 to 2 and 3 to 4 aortic regurgitation (although with considerable overlap). The cut point of 25% for JASA/ LVOA also provided a good separation between the angiographic 1 to 2+ and 3 to 4+ groups, with sensitivity 92 %, specificity 97 %, and accuracy 93 %. Among other color flow parameters, the J A / L V A ratio was quite variable in all grades of aortic regur-
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Fig. 4. Comparison of color Doppler and continuous Doppler parameters correlations vs angiographic grading of aortic insufficiency. All correlations were expressed as correlation coefficient. Note that color Doppler parameters have higher correlations with angiographic grading of aortic regurgitation than continuous Doppler parameters.
gitation, with a very wide range of values within the groups. However, there was a significant and fairly good correlation with the angiographic grading (r = 0.75, p = 0.0001). No cut points provided a good discrimination among groups for JA/LVA ratio.
ContinuouswaveDopplerparametersvsangiographic grading
Deceleration slope. There was a good correlation (r = 0.70, p = 0.0001) between the angiographic degree of regurgitation and the deceleration slope (Fig. 7). The slopes were significantly lower in patients with mild aortic insufficiency (1.95 +_ 0.47 m/sec 2)
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than in patients with angiography graded 3 to 4+ (3.08 _+ 0.7 m/sec 2) aortic insufficiency ( p < 0.01). With previously established conventional cut points of 2 m/sec 2 and 3 m/sec 2, the separation of different angiographic groups was not excellent, although an increasing deceleration slope was seen with increasing regurgitation severity. Patients with 4+ aortic regurgitation had significantly greater slopes than those with moderate and mild aortic regurgitation (3.68 + 0.50 m/sec2). However, 3 m/sec t as a cut point for separating severe aortic regurgitation from mild and moderate forms was highly specific (97 % ) and accurate (86 % ). Pressure half-time. There was a fair although significant correlation between the pressure half-time
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Fig. 7. Comparison of deceleration slopes as measured from continuous wave Doppler and angiographic grading of aortic insufficiency (A/). and the severity of aortic regurgitation (r = -0.62, p = 0.0001; Fig. 4). Although this parameter did not allow good separation of different degrees of regurgitation, the patients with mild aortic regurgitation had longer pressure half-times than patients with moderate or severe regurgitation (353 + 99 vs 232 + 58 msec, p < 0.001). COMMENTS
Continuous wave Doppler echocardiography, which differs from pulsed Doppler in its enhanced ability to resolve high velocities and provide assessment of pressure differences between the aorta and left ventricle throughout diastole, has traditionally been used to quantify the degree of aortic insufficiency. Early studies documented the usefulness of this Doppler technique to quantify the degree of aortic regurgitation by assessing the rate by which the aortic and left ventricular pressures equilibrate during diastole. ~ These studies have shown that the deceleration slope is a good indicator, although not an excellent discriminator, of the different degrees of aortic regurgitation. The present study, continuing these early results, found the accuracy of the slope for predicting severe aortic regurgitation to be very high. The pressure half-time did not show such a good correlation. Likewise, this index was not a good discriminator between different grades of aortic regurgitation. In a series of 26 patients, Miyatake et al. 3 used the regurgitant color flow area and demonstrated that the more severe the aortic regurgitation, the larger the regurgitant jet by color flow mapping. The maximal length of the regurgitant jet into the left ventricle from the long-axis view was not an adequate pa-
Volume 129, Number 5 American Heart Journal
rameter for grading aortic regurgitation as compared with angiography. 2 More recently, Perry et al., s in a series of only 30 patients, compared the color flow parameters with the angiographic grading. These authors found that short-axis area of the jet at its origin immediately below the aortic valve was the most accurate predictor of aortic regurgitation severity. Similarly, in our series of 161 patients the ratio of the JASA to the short-axis area of the left ventricle outflow tract also had a very close correlation with angiographic grading (r = 86). However, this parameter could only be obtained in 94 % of our patients. The measurements of the jet at its origin (JH) will provide the most accurate estimation of aortic regurgitation in obtaining either J H / L V O H or JASA/ LVOA ratios. In proving this hypothesis, Switzer et al., 7 used an in vitro model to find that JH, when measured at its origin, was the best predictor of regurgitant volume, which was the only function of the size of valvular defect. Likewise, in our study the parasternal long-axis view demonstrated that the origin of regurgitant jet at the left ventricle outflow tract resulted in the highest correlation with anglographic grading (r = 0.91). Theoretically, short axis is the only acoustic window that allows approach of the jet relatively as deflection of two planes; therefore the values from the short axis view should be superior to t h e values obtained from the parasternal long-axis view, which is a deflection of only one plane. However, adequate images were obtained more frequently from the parasternal long-axis (97 % ) than from the parasternal short-axis (94 % ) views. Our data suggest the superiority of the parasternal long-axis view because of the excellent correlation with angiographic grading and because it could be obtained in virtually all patients (97 %). Some investigators have measured the regurgitant JA in LV from the apical four-chamber views and used it as a predictor of the severity of aortic regurgitation. Yock et al. 12 pointed out that the measurement of JA by color flow mapping from this window is difficult because it commonly merges with the mitral flow. These difficulties were confirmed in our large series of patients as described earlier. The use of this color flow parameter rendered the least power to separate different degrees of aortic regurgitation, making it unacceptable. Perry et al. s also found poor correlation between JA in L ¥ and anglographic severity. The relative merging of the aortic regurgitant jet and transmitral filling flow was the main difficulty in an adequate measurement of the
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regurgitant JA from a four-chamber window in our study. Study limitations. A variety of technical and physiologic factors have the potential to affect our results. The influence of technical variables such as color gain settings and transducer frequencies is well established. 13-16 Baumgartner et al. 17 emphasized that as long as instrument settings have not been standardized to obtain reproducible color flow estimates, the use of information derived from color Doppler grading criteria will be adversely affected by the differences in instrument setting and differences between the ultrasound devices. In the present study, the instrument settings for gain, width, sector angle, and ultrasound equipment were not identical. Because this study is retrospective, standardization of these parameters was impossible. The availability of optimal images led us to establish the adequate instrument settings for the individual studies. In addition, the angiographic and echocardiographic studies were not performed simultaneously. It is well established that the size of the jet area by color imaging is influenced by loading conditions, is Although special care was taken to include patients with no differences in clinical status between the echocardiographic and the angiographic studies, a hemodynamic identity cannot be warranted. In the present study, we compared the ech(~derived parameters with a semiquantitative method, that is, aortic root injection. Croft et al. 19 showed that, even when aortic root angiography is done by experienced cardiologists, the regurgitation can still either be overestimated or underestimated. On the other hand, very few studies had documented the correlation between aortic root-injected-derived results and regurgitant volumes in the quantification of aortic regurgitation. 19' 2o However, the use of the regurgitant volume instead of angiographic grading of aortic regurgitation as a standard reference will not provide practical standardization. Even the very slightest alterations in the calculation of either stroke volume or cardiac output will cause significant errors in the calculations of regurgitant volume. Also, atrial fibrillation or mitral regurgitation will adversely affect the predictive accuracy of the calculations for regurgitant volume. Because the present study includes cases with mitral regurgitation (14%) and atrial fibrillation (13%), the use of aortic root injection should be considered a valid reference method. Conclusions. Our data suggest that color Doppler echocardiography is superior to continuous wave Doppler parameters for the quantification of aortic regurgitation. The ratio of the J H at its origin in left
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ventricular outflow tract to left ventricular outflow tract diameter obtained from the parasternal longaxis view was found to be the best predictor of aortic regurgitation when compared to angiography. The measurement of the absolute JH at its origin appears to be the simplest and the most practical method not only to detect aortic regurgitation, but also to discriminate accurately between mild and moderate or severe aortic regurgitation. Our data also indicate that the JA/LVOH ratio is very helpful as a predictor of severity of angiographic grading. However, as previously described, 8 this parameter is limited by technical difficulties. Planimetry is required, which should be considered a disadvantage of the method. The deceleration slope, the best continuous Doppler parameter, has a high predictive accuracy for severe aortic regurgitation, but it has an inferior discriminating power compared to the color flow Doppler parameters. SUMMARY
Aortic regurgitation is most frequently assessed noninvasively by Doppler echocardiography by use of continuous wave and Doppler color flow mapping. To compare both Doppler methods, 161 patients who had undergone cardiac catheterization and complete echocardiographic studies were studied. The continuous wave parameters analyzed included the slope of the diastolic deceleration and the pressure half-time of the regurgitant jet. From color flow Doppler, conventional parameters such as JH and its ratio to LVOH, JASA and its ratio to LVOA, and the regurgitant JA and its ratio to the LVA were obtained. The JH/LVOH was the color flow parameter that best correlated with angiography (r = 0.91). A ratio of --<25 % was used to predict mild aortic regurgitation with 96 % accuracy. A ratio of > 4 0 % was also used to predict severe aortic regurgitation (3 to 4+) with 96% accuracy. Absolute JH at the origin of the regurgitant jet was the second best color flow parameter that correlated with angiography (r = 0.89). When continuous wave-derived slope was used, a significant overlap among different degrees of aortic regurgitation was observed. Predictive accuracy for mild aortic regurgitation was 70 % by using a slope <2 m/sec 2 and 86 % for severe aortic regurgitation when using a slope >3 m/sec 2. In conclusion, color flow Doppler appears to be superior to continuous wave Doppler in the assessment of aortic regurgitation. The JH/LVOH appears to be the best color parameter for quantifying aortic regurgitation. The measurement of the absolute JH at its origin appears to be the simplest and most practical method for assessing the degree of aortic regurgitation.
W e t h a n k our s o n o g r a p h e r s for their technical expertise, K a t h y B a n k e r for secretarial assistance, a n d J a m e s J. D o l a n for e x p e r t editorial assistance.
REFERENCES
1. Labovitz AJ, Ferrara RP, Kern MJ, Bryg RJ, Mrosek DG, Williams GA. Quantitative evaluation of aortic insufficiency by continuous-wave Doppler echocardiography. J Am Coll Cardiol 1986;8:1341-7. 2 . Omoto R, Yakote Y, Takamoto S, Kyo S, Ueda K, Asano H, Namekawa K, Kasai C, Kondo Y, Kovano A. The development of real time two dimensional Doppler echocardiograpby and its clinical significance in acquired valvular diseases. Jpn Heart J 1984;25:325-40; 3. Miyatake K, Okamoto M, Kinoshita N, Izumi S, Owa M, Takao S, Sakakibara H, Nimura Y. Clinical applications of a new type of real time two-dimensi0nal Doppler flow imaging system. Am J Cardiol 1984;54: 857-68. 4. Pearlman AS, Otto CM, Janko CL. Direction and width of aortic regurgitation jets: assessment by Doppler color flow mapping [Abstract]. J Am Coll Cardiol 1986;7:100. 5. Perry GJ, Helmcke F, Nanda NC. Color Doppler assessment of aortic insufficiency in two orthogonal planes [Abstract]. J Am Coll Cardiol 1986;7:101. 6. Bolger AF, Eigler NL, Pfaff JM. Relationship of color Doppler jet area to flow volume: reliability and limitations [Abstract]. Circulation 1986;74:II-216. 7. Switzer DF, Yoganathan AP, Nanda NC, Woo Y-R, Ridgway AJ. Calibration of color Doppler flow mapping during extreme hemodyaamic conditions in vitro: a foundation for a reliable quantitative grading system for aortic incompetence. Circulation 1987;75:837. 8. Perry GJ, Helmcke F, Nanda NC, Byard C, Soto B. Evaluation of aortic insufficiency by Doppler color flow mapping. J Am Coll Cardiol 1987;9:952-9. 9. Hatle L, Angelsen B, Tromsdal A. Noninvasive assessment of atrioventricular pressure half-time by Doppler ultrasound. Circulation 1979; 60:1096-104. 10. Bryg RJ, Labovitz AJ, Nelson JG, Kennedy HL, Williams GA. Comparison of Doppler echocardiography and two-dimensional echocardiography in the measurement of mitral valve area and mitral stenosis. Clin Res 1984;32:152. 11. Grossman W, Baum DS. Cardiac catheterization, angiography and intervention. 4th ed. Philadelphia: Lea & Febiger, 1991;576-7. 12. Yock PG, Segal J, Teirstein PS, Schnittinger I, Popp RL. Doppler color flow mapping: Utility in valvular regurgitation [Abstract]. Circulation 1984;70:38. 13. Smith MD, Grayburn PA, Spain MG, De Maria AN. Observer variability in the quantitation of Doppler color flow jet areas for mitral and aortic regurgitation. J Am Coll Cardiol 1988;11:579. 14. Bolger AF, Eigler NL, Pfaff JM, Resser KJ, Maurer G. Computer analysis of Doppler color flow mapping images for quantitative assessment of in vitro fluid jets. J Am Cull Cardiol 1988;12:450-7. 15. Stewart WJ, Schiavone WA, From JA, Castle T, Salcedo EE. In vitro studies of Doppler color flow mapping: dependence of spatial distribution on instrument setting. Circulation 1985;72(suppl III):98. 16. Hoit BD, Jones M, Eidbo EE, Elias W, Sahon DJ. Sources of variability for Doppler color flow mapping of regurgitant jets in an animal model of mitral regurgitation. J Am Coil Cardiol 1989;13:1631-6. 17. Baumgartner H, Schima H, Kuhn P. Importance of technical variable for quantitative measurements by Color Doppler imaging. Am J Cardiol 1991;67:314-5. 18. Spain MG, Smith MD, Kwan OL, DeMaria AN. Effect of isometric exercise of mitral and aortic regurgitation as assessed by color Doppler flow imaging. Am J Cardiol 1990;65:78-83. 19. Croft CH, Lipscomb K, Mathis K, Firth BG, N/cod P, Tilton G, Winniford MD, Hillis D. Limitations of qualitative angiographie grading in aortic or mitral regurgitation. Am J Cardiol 1984;53:1593-8. 20. Hunt D, Baxley WA, Kennedy JW, Judge TP, Williams JE. Quantitative evaluation of cine-aortography in the assessment of aortic regurgitation. Am J Cardiol 1973;31:696-700: