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(Circulation. 1997;96:3409-3415.)
© 1997 American Heart Association, Inc.

Articles

Grading of Mitral Regurgitation by Quantitative Doppler Echocardiography

Calibration by Left Ventricular Angiography in Routine Clinical Practice

Karl S. Dujardin, MD; Maurice Enriquez-Sarano, MD; Kent R. Bailey, PhD; Rick A. Nishimura, MD; James B. Seward, MD; ; A. Jamil Tajik, MD

From the Division of Cardiovascular Diseases and Internal Medicine (K.S.D., M.E.-S., R.A.N., J.B.S., A.J.T.) and the Section of Biostatistics (K.R.B.), Mayo Clinic and Mayo Foundation, Rochester, Minn.

	Abstract

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Background Quantitative Doppler echocardiography and proximal flow convergence methods are validated techniques for quantifying mitral regurgitation. However, the clinical interpretation of the values calculated is hindered by the absence of calibration of ranges of severity in large numbers of patients.

Methods and Results In 180 consecutive patients (men, 62%; mean age±SD, 66±11 years), the results of Doppler quantification of isolated mitral regurgitation were calibrated by use of left ventricular angiographic grading performed within 3 months in routine practice and without intervening events. The thresholds of the quantitative variables corresponding to the angiographic grades were identified by maximizing the sum of sensitivity and specificity and minimizing their difference. The mitral regurgitation grade by angiography was 2.7±1.3. The mean value and correlation with angiographic grades for effective regurgitant orifice were 43±37 mm and r=.79 (P<.0001); for regurgitant volume, 62±45 mL and r=.80 (P<.0001); and for regurgitant fraction, 45±17% and r=.78 (P<.0001). Despite some overlap, differences between mitral regurgitation grades were all significant (all P<.05). The thresholds for severe mitral regurgitation (grade 4) were 60 mL, 50%, and 40 mm² for regurgitant volume, regurgitant fraction, and orifice, respectively.

Conclusions In routine practice in large numbers of patients in a clinical laboratory, Doppler echocardiographic quantification of mitral regurgitation shows highly significant correlation with qualitative angiographic grades. Despite an expected overlap between classes, the calibration by angiography of grading ranges for the quantitative variables provides a framework for their interpretation and allows the definition in clinical practice of thresholds for severe mitral regurgitation.

Key Words: angiography • echocardiography • mitral valve • regurgitation

	Introduction

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In patients with mitral regurgitation, the degree of regurgitation is a major determinant of the natural history. Patients with mild mitral regurgitation have excellent survival,¹ whereas those with severe regurgitation observed medically experience excess mortality and high morbidity.² Surgery, especially repair,³ can treat mitral regurgitation successfully; however, it carries a small but definite risk⁴ and therefore should be reserved for patients with a severe degree of mitral regurgitation. Consequently, determining the degree of regurgitation is a crucial part of the clinical evaluation of patients with mitral regurgitation.^{4 5} Although color flow Doppler echocardiography is very sensitive, it is limited by several pitfalls in assessing the degree of mitral regurgitation.^{6 7 8}

To define the degree of regurgitation quantitatively, new methods^{9 10} and new concepts^{11 12} using Doppler echocardiography have allowed the measurement of RVol, RF,^{13 14 15} and ERO, a measure of lesion severity.^{11 12} These methods have been validated and their accuracy verified in confirmatory studies.^{11 12 13 14 15} They can be used alternatively or in combination to define the degree of mitral regurgitation as values of RVol, RF, and ERO. However, because of their more recent application, a calibration and clinical perception of the values of these quantitative variables—particularly the thresholds corresponding to severe mitral regurgitation—have not been fully developed. Preliminary values of these thresholds based on the physiological consequences of regurgitation have been suggested,¹² but because of the limitations of pilot studies (ie, small numbers and possible selection bias), the calibration of a gradation framework in routine practice is warranted.

Because qualitative angiography has long been used in routine practice to assess mitral regurgitation,^{16 17} a clinical perception of the grades of mitral regurgitation, which is widely shared and comprehended, has formed despite the pitfalls of the method.¹⁸ Therefore, notwithstanding these pitfalls and the fact that angiographic grading is not a gold standard, it is a unique method to calibrate newer quantitative methods and to translate the perception of angiography to quantitative variables. Performed in routine practice, to avoid selection biases, this calibration should allow development of a framework for interpreting quantitative measurements of mitral regurgitation.

Therefore, our prospective experience with both Doppler echocardiographic quantification and angiographic assessment of mitral regurgitation obtained in routine practice was used to determine (1) thresholds of quantitative variables corresponding best to each angiographic grade and (2) a definition, based on these criteria, of severe mitral regurgitation as encountered in clinical practice.

	Methods

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Study Patients
The inclusion criteria were that (1) patients had isolated, pure mitral regurgitation; (2) they underwent routine transthoracic echocardiographic quantification of mitral regurgitation by either quantitative Doppler or the flow-convergence method or both between September 1990 and March 1996; and (3) they had left ventricular angiography and quantitative Doppler echocardiography within 3 months of each other. Excluded were patients who (1) developed new cardiac events or underwent a therapeutic cardiac intervention such as valve repair or replacement, bypass surgery, or percutaneous angioplasty between the echocardiographic examination and catheterization; (2) had associated aortic valve disease, mitral stenosis, or constrictive pericarditis; or (3) had a change in systolic blood pressure 30 mm Hg between the two studies.

Echocardiographic Analysis
A comprehensive Doppler echocardiographic examination was performed and analyzed as described previously.^{19 20 21} The mechanism of mitral regurgitation was determined on the basis of the two-dimensional appearance of the left ventricle, subvalvular apparatus, and valve leaflets and the dimension of the mitral annulus. Organic mitral regurgitation was characterized by intrinsic valvular disease, and ischemic/functional mitral regurgitation was characterized by normal valves, enlarged annulus, and global or regional left ventricular dysfunction. Quantification of mitral regurgitation was performed by two methods.

Quantitative Doppler method. As previously described,^{15 20} two-dimensional and Doppler echocardiography were used to make annular cross-sectional area and TVI measurements to calculate the mitral and aortic stroke volumes. Next, the Doppler RVol, RF, and ERO were calculated as follows: RVol=(mitral-aortic) stroke volume; RF=RVol/mitral stroke volume; and ERO=RVol/regurgitant TVI, where regurgitant TVI is the TVI (ie, stroke distance in centimeters) of the mitral regurgitant jet obtained by continuous-wave Doppler.

Proximal isovelocity area method. This method used the proximal flow convergence^{22 23 24} and was performed as previously described²⁴ : regurgitant flow=2xr²xV_r, where r is radius of proximal flow convergence and V_r is aliasing velocity; ERO=regurgitant flow/peak regurgitant velocity; RVol=EROxregurgitant TVI; and RF=RVol/[(regurgitant+aortic) stroke volumes].

Final quantitative values. The final quantitative values of RVol, RF, and ERO were either the mean of those calculated by the two methods or the values calculated by the method used. Both methods were used in 40 patients, quantitative Doppler was used exclusively in 85, and proximal flow convergence was used exclusively in 55.

Angiographic Assessment
In each patient, left ventriculography was performed in a biplane 30° right and 60° left anterior oblique projection with 50 mL of iopamidol (100% concentrated) injected over 3 to 4 seconds and recorded on a 35-mm cinefilm at 60 frames per second. The angiographic severity of mitral regurgitation was graded according to a historically accepted grading scheme^{16 17} in four grades (1, 2, 3, and 4, from mild to severe). The left ventricular angiogram was interpreted at the time of catheterization by an experienced angiographer who reviewed the 35-mm film without knowledge that the data would be analyzed for the present study.

Statistical Methods
Group results were reported as mean±SD for continuous variables and as percentages for categorical variables. Group comparison relied on the standard t test or, for multiple group comparisons, on ANOVA. The relation between angiographic severity of mitral regurgitation and RVol, RF, and ERO was examined by use of the Spearman rank-order correlation.

For each quantitative variable (RVol, RF, and ERO), thresholds optimally separating the continuous quantitative variables in correspondence with the angiographic grades were determined sequentially for three levels, that is, for separation of grade 1 from 2, grades 1 and 2 from grades 3 and 4, and grade 3 from 4. The thresholds that best separated these angiographic grades were determined by testing the whole range of each variable by increments of 5 units (ie, 5 mL of RVol, 5% of RF, 5 mm² of ERO) and determining for each level the sensitivity, specificity, negative and positive predictive values, odds ratio, and negative and positive likelihood ratios.²⁵ The candidate thresholds that were considered to best separate the continuous quantitative variables in correspondence with the angiographic grades were those with the highest sum of sensitivity and specificity and the lowest value of their difference. If more than one value met these criteria, the final choice was made by prioritizing sensitivity. However, the results of alternative choices of interest were also presented. ROC curves were calculated for the diagnosis of grade 3 or 4 mitral regurgitation for the three quantitative variables, and the areas under the curves, which represent the diagnostic value of the quantitative variables, were compared by the paired t test. To determine the range of uncertainty of the thresholds between grades, the analysis was repeated with logistic regression between the angiographic grade (dependent, classified as grade 1 versus 2 to 4, 1 to 2 versus 3 to 4, and 1 to 3 versus 4) and quantitative degree of mitral regurgitation (independent), and the thresholds for each grade with their standard errors (by ANCOVA) were determined. All probability values were two-tailed, and a value of P<.05 was considered significant.

	Results

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Patient Characteristics
The 180 patients (112 men and 68 women) included were 26 to 89 years old (mean, 66±11 years). The mechanism of mitral regurgitation was ischemic/functional (n=84) or organic (n=96). Of these patients, 133 were in sinus rhythm, 39 in atrial fibrillation, and 8 in paced rhythm. The absolute value of the delay between the echocardiographic study and angiography was 34±8 days. Systolic blood pressure was 130±20 mm Hg at echocardiography and 134±22 mm Hg at angiography (P<.001). The difference was small but, because of the large number of patients, reached statistical significance. The RVol, RF, and ERO in the overall population are presented in Table 1.

View this table: [in this window] [in a new window]   Table 1. Mean±SD for the Quantitative Variables Corresponding to Each Angiographic Grade

Calibration of Echocardiographic Quantification With Angiographic Grades
The mitral regurgitation grade by angiography was 2.7±1.3. The distribution of patients among the four angiographic grades and the values of RVol, RF, and ERO for each angiographic grade are summarized in Table 1 and demonstrate significant differences between grades (overall P<.001, P<.001, and P<.001 for RVol, RF, and ERO, respectively; all-group comparison, P<.05). Significant correlation was found between angiographic grades and ERO (r=.79, P<.0001) (Fig 1), RVol (r=.80, P<.0001) (Fig 2), and RF (r=.78, P<.0001) (Fig 3). There were notable overlaps between grades (Figs 1 through 3), as expected, but despite this, the differences between each angiographic grade in terms of RVol, RF, and ERO were significant (Table 1, all P<.05). Possible threshold values for ERO, RVol, and RF corresponding to each angiographic grade are listed in Table 2, with the descriptors of their diagnostic values. The thresholds that were finally selected as best separating the grades at each level are in boldface in Table 2 and summarized in Table 3. The superimposition of the selected thresholds on the scatterplots is shown in Figs 1B, 2B, and 3B for ERO, RVol, and RF, respectively. The area under the ROC curves for the diagnosis of grade 3 to 4 mitral regurgitation was 0.93 for RVol, which was not significantly different from 0.92 for ERO (P=.08) and 0.90 for RF (P=.08) (Fig 4). The use of logistic regression to determine the thresholds for the four grades yielded results similar to those of the analysis based on the diagnostic value and, most importantly, demonstrated that despite the overlap, the standard errors of the thresholds were narrow (for RVol, 28±2.2, 47±2.7, and 62±3.4 mL; for RF, 31±3.4%, 42±1.4%, and 49±1.4%; for ERO, 17±2, 31±2.2, and 43±2.7 mm² for the thresholds of grades 2, 3, and 4, respectively). No interaction was found between the type of regurgitation (organic or ischemic/functional) and the thresholds defined (P=.08, .63, and .19, respectively, for RVol, RF, and ERO).

View larger version (24K): [in this window] [in a new window]   Figure 1. A, Scatterplot (diamonds are mean±SD) and B, box plot of mean ERO for each angiographic grade. Horizontal lines in B delineate thresholds of mean ERO that best separate grades.

View larger version (23K): [in this window] [in a new window]   Figure 2. A, Scatterplot (diamonds are mean±SD) and B, box plot of mean RVol for each angiographic grade. Horizontal lines in B delineate thresholds of mean RVol that best separate grades.

View larger version (22K): [in this window] [in a new window]   Figure 3. A, Scatterplot (diamonds are mean±SD) and B, box plot of mean RF for each angiographic grade. Horizontal lines in B delineate thresholds of mean RF that best separate grades.

View this table: [in this window] [in a new window]   Table 2. Diagnostic Value of the Thresholds of Doppler Quantitative Variables Corresponding to the Angiographic Mitral Regurgitation Grades1

View this table: [in this window] [in a new window]   Table 3. Selected Ranges for Grading Severity of Mitral Regurgitation

View larger version (17K): [in this window] [in a new window]   Figure 4. ROC curves for diagnosis of grade 3 or 4 mitral regurgitation for three quantitative variables. Area under curve for each variable suggests that quantitative methods are an excellent test to discriminate grades 1 and 2 from grades 3 and 4.

	Discussion

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The present study calibrated quantitative echocardiographic measures of degree of mitral regurgitation using angiographic grades and (1) defined ranges of the quantitative indexes corresponding with satisfactory diagnostic value to angiographic grades and (2) determined that thresholds for severe (grade 4) mitral regurgitation are RVol 60 mL per beat, RF 50%, and ERO 40 mm².

Importance of Grading Mitral Regurgitation
The degree of mitral regurgitation is a determinant of outcome in terms of both morbidity and mortality. Patients with mild mitral regurgitation do not usually develop left ventricular remodeling,^{12 26} whereas left ventricular dysfunction is a frequent and serious complication of severe mitral regurgitation.^{4 5} Moreover, in patients with predominantly mild regurgitation, survival is excellent,¹ whereas in those with predominantly severe regurgitation, excess mortality and high morbidity are noted.² Surgical correction of mitral regurgitation is highly successful³ ; however, the operative risk of valve repair or replacement, despite recent improvements, is still not negligible.^{3 4 27} Therefore, surgery, particularly for patients with no or minimal symptoms,²⁸ should be considered mostly for patients with well-documented severe mitral regurgitation.

Methods of Grading Mitral Regurgitation
Semiquantitative methods for the assessment of mitral regurgitation often show disagreement,²⁹ and all these techniques have important theoretical and practical limitations. Semiquantification by the echocardiographic color flow-jet area method has pitfalls in that it tends to underestimate the severity of eccentric jets^{6 7} and to overestimate the severity of central jets.⁸ Quantitative methods allow the measurement of RVol and RF to assess volume overload and also the measurement of ERO area, a surrogate of lesion severity.^{11 12} Because quantitative methods have only recently been introduced into routine practice,^{9 10 13 15} a clinical comprehension and perception of the values calculated have not yet developed. Calibration of quantitative indexes was tentatively defined by determining thresholds associated with marked degrees of left ventricular enlargement and elevation of pulmonary artery pressure,^{12 14} but full documentation of a gradation framework is warranted.

Left ventricular angiography can define the degree of mitral regurgitation based on the retrograde opacification of the left atrium,^{16 17} but it is limited by its invasive nature and small inherent risk^{30 31} and thus cannot be used for regular follow-up. Another limitation is the frequent disagreement with the findings of other methods,²⁹ and even in simultaneous studies, only modest correlations with quantitative indexes have been obtained.^{18 32 33} Therefore, the capacity of left ventricular angiography as a gold standard and accurate reference method in validation studies is questionable. However, one of its major merits is the historic use, which has created a clinical perception of the semiquantitative grading scale that is used to report angiographic degrees of mitral regurgitation.^{16 17 29} Therefore, left ventricular angiography is an essential tool for calibration of quantitative methods to define corresponding grading frameworks³⁴ and to translate the perception of angiography to values reported by quantitative methods.

Pilot studies on new quantitative methods did not define ranges of degree of mitral regurgitation, for several reasons. First, the studies consisted of small populations of patients.^{12 13 15 35 36} Second, the pitfalls of the quantitative methods were not fully determined in the initial pilot studies, precluding meaningful comparison with angiography,^{9 10 37} but more recent studies have defined the field of applicability of the quantitative methods.^{12 14 22 38} Third, restrictive inclusion criteria of pilot studies^{23 24 35 36} necessary for validation of quantitative methods may induce a selection bias,^{39 40} leading to results that may not reflect the framework of gradation in routine practice. Therefore, calibration of quantitative measurements of mitral regurgitation using angiographic grades obtained in routine practice, as reported for the first time here, is essential. By design, without restrictive inclusion, a notable overlap between grades is expected.^{18 41 42} Despite this expected overlap, adequate correlations were found. Also, all angiographic grades showed significant differences in RVol, RF, and ERO, demonstrating that a statistical (in addition to visual) separation between grades is present. Furthermore, the diagnostic values of the thresholds defined in this study were good, allowing these thresholds to be used for the interpretation of quantitative data in routine clinical practice. Of note, regurgitation may not always be graded similarly by ERO and by RVol or RF. For any given ERO, higher afterload may result in higher RVol.⁴³ Nevertheless, the present framework should allow enhanced comprehension of the results of quantitative methods and, in particular, of the role of lesion severity^{11 12} and loading conditions^{26 43} in the overall severity of mitral regurgitation.

What Is Severe Mitral Regurgitation?
The ROC curves in Fig 4 suggest that the quantitative methods are an excellent test to distinguish grade 1 to 2 from grade 3 to 4. This implies that several candidate threshold values can be identified that have both good sensitivity and good specificity to separate between grades, as reported in Table 2. For example, for the threshold separating grade 3 from grade 4, an ERO of 50 mm² prioritized specificity but had a low sensitivity, and a threshold of 40 mm² prioritized sensitivity with some loss in specificity. The final choice is to be made by each physician depending on the goals defined for routine clinical practice. The boldface values in Table 2 represent our final choice, based mostly on prioritizing sensitivity for severe degrees of mitral regurgitation.

Table 3 summarizes these choices. The thresholds of RVol 60 mL/beat, RF 50%, and ERO area 40 mm² provide a relatively high sensitivity for severe, grade 4 mitral regurgitation. The corresponding thresholds for mitral regurgitation of grade 3 or 4 are 45 mL/beat, 40%, and 30 mm², respectively. These thresholds are close to the ranges defined previously on the magnitude of the pathophysiological consequences of mitral regurgitation.¹² They are also consistent with the limited data previously available with other quantitative methods.^{32 33 44} Ultimately, the exact definition of severe mitral regurgitation should be determined by the influence of the degree of volume overload (RVol and RF) and lesion severity (ERO) on long-term outcome. However, follow-up since the inception of the most applicable methods is limited and cannot provide this crucial outcome information at the present time.^{9 10 11 12} Therefore, the present calibration of quantitative measures of the degree of mitral regurgitation by angiography represents a unique possibility of defining a framework of gradation and is essential for the clinical use of quantitative data. Such a framework, congruent with the long-used and well-perceived semiquantitative gradation, should allow a better perception of the values calculated by quantitative Doppler echocardiographic methods and improve communication between physicians.²⁹

Study Limitations
Not all patients in the present study had results of quantification by two methods. However, the two Doppler echocardiographic methods used to calculate ERO, RVol, and RF show high correlations in the present study (r=.94, P<.0001; r=.93, P<.0001; r=.92, P<.0001, respectively), as in previous studies,¹⁴ and no significant difference in their results (P=.09, P=.84, and P=.10, respectively). Also, the ROC curves of RVol, RF, and ERO for the separation of grade 1 to 2 from grade 3 to 4 did not differ between the two methods. Therefore, the methods used do not represent a limitation but rather reflect the use of quantification of regurgitation in routine practice.

The patients included in the present study had chronic mitral regurgitation; therefore, the thresholds defined for severe mitral regurgitation apply primarily to chronic and not to acute mitral regurgitation. Future studies should analyze the pathophysiology of acute mitral regurgitation to better define specific diagnostic criteria.

A change in loading conditions between echocardiography and angiography could account for some of the misclassifications between quantification and angiographic grade observed in this study.⁴³ Despite a significant difference between systolic blood pressure at the time of echocardiography and angiography, the absolute difference was small and the hemodynamic conditions were clinically similar. In routine practice, these tests are rarely performed simultaneously, and despite possible changes in loading conditions, the interpretation of the nonsimultaneous grading guides all clinical decisions. Therefore, the design of the present study is highly relevant to routine clinical practice.²⁹

Furthermore, the aim of the present study was not to validate the quantitative methods, which have been endorsed in multiple studies from various medical centers,^{6 9 10 11 12 13 15 41 42} but rather to calibrate for the first time ranges of severity. Angiography may be conducive to misclassifications, which may partly explain the overlap observed,¹⁸ but these random misclassifications, which may reduce the coefficient of correlation, have little effect on the determination of the thresholds⁴⁵ corresponding to the four grades and therefore do not hinder the present calibration. This is confirmed by the narrow standard error of the thresholds defined by the logistic regression, further emphasizing that the overlap does not represent a significant limitation of the present study.

Clinical Implications
Despite an overlap between angiographic grades, as expected in routine practice, the diagnostic value of the quantitative Doppler variables is excellent, as demonstrated by the ROC curves. Therefore, in most cases, duplication of gradation does not appear to be indispensable. The calibration of quantitative Doppler echocardiographic measures of the degree of mitral regurgitation by angiographic grading provides grading ranges for the quantitative variables and should allow an improved perception of the meaning and interpretation of the measured values. On the basis of this calibration, patients with RVol 60 mL, RF 50%, and ERO 40 mm² are classified as having severe mitral regurgitation.

	Selected Abbreviations and Acronyms

 

ERO = effective regurgitant orifice RF = regurgitant fraction ROC = receiver operating characteristic RVol = regurgitant volume TVI = time velocity integral

	Acknowledgments

 
Dr Dujardin was supported by a fellowship from the Belgian American Educational Foundation.

	Footnotes

 
Reprint requests to Maurice Enriquez-Sarano, MD, Mayo Clinic, 200 First St SW, Rochester, MN 55905.

Received January 30, 1997; revision received May 29, 1997; accepted July 3, 1997.

	References

Top Abstract Introduction Methods Results Discussion References

 

1. Wilson MG, Lim WN. The natural history of rheumatic heart disease in the third, fourth, and fifth decades of life, I: prognosis with special reference to survivorship. Circulation. 1957;16:700-712.[Medline] [Order article via Infotrieve]
   
2. Ling LH, Enriquez-Sarano M, Seward JB, Tajik AJ, Schaff HV, Bailey KR, Frye RL. Clinical outcome of mitral regurgitation due to flail leaflet. N Engl J Med. 1996;335:1417-1423.[Abstract/Free Full Text]
   
3. Enriquez-Sarano M, Schaff HV, Orszulak TA, Tajik AJ, Bailey KR, Frye RL. Valve repair improves the outcome of surgery for mitral regurgitation: a multivariate analysis. Circulation. 1995;91:1022-1028.[Abstract/Free Full Text]
   
4. Enriquez-Sarano M, Tajik AJ, Schaff HV, Orszulak TA, Bailey KR, Frye RL. Echocardiographic prediction of survival after surgical correction of organic mitral regurgitation. Circulation. 1994;90:830-837.[Abstract/Free Full Text]
   
5. Enriquez-Sarano M, Tajik AJ, Schaff HV, Orszulak TA, McGoon MD, Bailey KR, Frye RL. Echocardiographic prediction of left ventricular function after correction of mitral regurgitation: results and clinical implications. J Am Coll Cardiol. 1994;24:1536-1543.[Abstract]
   
6. Enriquez-Sarano M, Tajik AJ, Bailey KR, Seward JB. Color flow imaging compared with quantitative Doppler assessment of severity of mitral regurgitation: influence of eccentricity of jet and mechanism of regurgitation. J Am Coll Cardiol. 1993;21:1211-1219.[Abstract]
   
7. Chen CG, Thomas JD, Anconina J, Harrigan P, Mueller L, Picard MH, Levine RA, Weyman AE. Impact of impinging wall jet on color Doppler quantification of mitral regurgitation. Circulation. 1991;84:712-720.[Abstract/Free Full Text]
   
8. McCully RB, Enriquez-Sarano M, Tajik AJ, Seward JB. Overestimation of severity of ischemic/functional mitral regurgitation by color Doppler jet area. Am J Cardiol. 1994;74:790-793.[Medline] [Order article via Infotrieve]
   
9. Bargiggia GS, Tronconi L, Sahn DJ, Recusani F, Raisaro A, De Servi S, Valdes-Cruz LM, Montemartini C. A new method for quantitation of mitral regurgitation based on color flow Doppler imaging of flow convergence proximal to regurgitant orifice. Circulation. 1991;84:1481-1489.[Abstract/Free Full Text]
   
10. Recusani F, Bargiggia GS, Yoganathan AP, Raisaro A, Valdes-Cruz LM, Sung HW, Bertucci C, Gallati M, Moises VA, Simpson IA, Tronconi L, Sahn DJ. A new method for quantification of regurgitant flow rate using color Doppler flow imaging of the flow convergence region proximal to a discrete orifice: an in vitro study. Circulation. 1991;83:594-604.[Abstract/Free Full Text]
    
11. Vandervoort PM, Rivera JM, Mele D, Palacios IF, Dinsmore RE, Weyman AE, Levine RA, Thomas JD. Application of color Doppler flow mapping to calculate effective regurgitant orifice area: an in vitro study and initial clinical observations. Circulation. 1993;88:1150-1156.[Abstract/Free Full Text]
    
12. Enriquez-Sarano M, Seward JB, Bailey KR, Tajik AJ. Effective regurgitant orifice area: a noninvasive Doppler development of an old hemodynamic concept. J Am Coll Cardiol. 1994;23:443-451.[Abstract]
    
13. Blumlein S, Bouchard A, Schiller NB, Dae M, Byrd BF III, Ports T, Botvinick EH. Quantitation of mitral regurgitation by Doppler echocardiography. Circulation. 1986;74:306-314.[Abstract/Free Full Text]
    
14. Enriquez-Sarano M, Bailey KR, Seward JB, Tajik AJ, Krohn MJ, Mays JM. Quantitative Doppler assessment of valvular regurgitation. Circulation. 1993;87:841-848.[Abstract/Free Full Text]
    
15. Rokey R, Sterling LL, Zoghbi WA, Sartori MP, Limacher MC, Kuo LC, Quinones MA. Determination of regurgitant fraction in isolated mitral or aortic regurgitation by pulsed Doppler two-dimensional echocardiography. J Am Coll Cardiol. 1986;7:1273-1278.[Abstract]
    
16. Grossman W, Dexter L. Profiles in valvular heart disease. In: Grossman W, ed. Cardiac Catheterization and Angiography. 2nd ed. Philadelphia, Pa: Lea & Febiger; 1980:305-324.
    
17. Sellers RD, Levy MJ, Amplatz K, Lillehei CW. Left retrograde cardioangiography in acquired cardiac disease: technic, indications and interpretations in 700 cases. Am J Cardiol. 1964;14:437-447.[Medline] [Order article via Infotrieve]
    
18. Croft CH, Lipscomb K, Mathis K, Firth BG, Nicod P, Tilton G, Winniford MD, Hillis LD. Limitations of qualitative angiographic grading in aortic or mitral regurgitation. Am J Cardiol. 1984;53:1593-1598.[Medline] [Order article via Infotrieve]
    
19. Nishimura RA, Miller FA Jr, Callahan MJ, Benassi RC, Seward JB, Tajik AJ. Doppler echocardiography: theory, instrumentation, technique, and application. Mayo Clin Proc. 1985;60:321-343.[Medline] [Order article via Infotrieve]
    
20. Lewis JF, Kuo LC, Nelson JG, Limacher MC, Quinones MA. Pulsed Doppler echocardiographic determination of stroke volume and cardiac output: clinical validation of two new methods using the apical window. Circulation. 1984;70:425-431.[Abstract/Free Full Text]
    
21. Tajik AJ, Seward JB, Hagler DJ, Mair DD, Lie JT. Two-dimensional real-time ultrasonic imaging of the heart and great vessels: technique, image orientation, structure identification, and validation. Mayo Clin Proc. 1978;53:271-303.[Medline] [Order article via Infotrieve]
    
22. Pu M, Vandervoort PM, Griffin BP, Leung DY, Stewart WJ, Cosgrove DM III, Thomas JD. Quantification of mitral regurgitation by the proximal convergence method using transesophageal echocardiography: clinical validation of a geometric correction for proximal flow constraint. Circulation. 1995;92:2169-2177.[Abstract/Free Full Text]
    
23. Giesler M, Grossmann G, Schmidt A, Kochs M, Langhans J, Stauch M, Hombach V. Color Doppler echocardiographic determination of mitral regurgitant flow from the proximal velocity profile of the flow convergence region. Am J Cardiol. 1993;71:217-224.[Medline] [Order article via Infotrieve]
    
24. Enriquez-Sarano M, Miller FA Jr, Hayes SN, Bailey KR, Tajik AJ, Seward JB. Effective mitral regurgitant orifice area: clinical use and pitfalls of the proximal isovelocity surface area method. J Am Coll Cardiol. 1995;25:703-709.[Abstract]
    
25. Weissler AM. Assessment and use of cardiovascular tests in clinical prediction. In: Giuliani ER, Gersh BJ, McGoon MD, Hayes DL, Schaff HV, eds. Mayo Clinic Practice of Cardiology. 3rd ed. St Louis, Mo: Mosby; 1996:400-421.
    
26. Bolen JL, Alderman EL. Ventriculographic and hemodynamic features of mitral regurgitation of cardiomyopathic, rheumatic and nonrheumatic etiology. Am J Cardiol. 1977;39:177-183.[Medline] [Order article via Infotrieve]
    
27. Scott WC, Miller DC, Haverich A, Mitchell RS, Oyer PE, Stinson EB, Jamieson SW, Baldwin JC, Shumway NE. Operative risk of mitral valve replacement: discriminant analysis of 1329 procedures. Circulation. 1985;72(suppl II):II-108-II-119.
    
28. Enriquez-Sarano M, Sinak LJ, Tajik AJ, Bailey KR, Seward JB. Changes in effective regurgitant orifice throughout systole in patients with mitral valve prolapse: a clinical study using the proximal isovelocity surface area method. Circulation. 1995;92:2951-2958.[Abstract/Free Full Text]
    
29. Slater J, Gindea AJ, Freedberg RS, Chinitz LA, Tunick PA, Rosenzweig BP, Winer HE, Goldfarb A, Perez JL, Glassman E, Kronzon I. Comparison of cardiac catheterization and Doppler echocardiography in the decision to operate in aortic and mitral valve disease. J Am Coll Cardiol. 1991;17:1026-1036.[Abstract]
    
30. Lozner EC, Johnson LW, Johnson S, Krone R, Pichard AD, Vetrovec GW, Noto TJ. Coronary arteriography 1984-1987: a report of the Registry of the Society for Cardiac Angiography and Interventions, II: an analysis of 218 deaths related to coronary arteriography. Cathet Cardiovasc Diagn. 1989;17:11-14.[Medline] [Order article via Infotrieve]
    
31. Davis K, Kennedy JW, Kemp HG Jr, Judkins MP, Gosselin AJ, Killip T. Complications of coronary arteriography from the Collaborative Study of Coronary Artery Surgery (CASS). Circulation. 1979;59:1105-1112.[Abstract/Free Full Text]
    
32. Lopez JF, Hanson S, Orchard RC, Tan L. Quantification of mitral valvular incompetence. Cathet Cardiovasc Diagn. 1985;11:139-152.[Medline] [Order article via Infotrieve]
    
33. Sandler H, Dodge HT, Hay RE, Rackley CE. Quantitation of valvular insufficiency in man by angiocardiography. Am Heart J. 1963;65:501-513.[Medline] [Order article via Infotrieve]
    
34. Pu M, Vandervoort PM, Griffin BP, Stewart WJ, Rodriguez L, Cosgrove DM, Thomas JD. Assessment of mitral regurgitant severity using quantitative Doppler transesophageal echocardiography: comparison with angiography. J Am Coll Cardiol. 1996;27(suppl A):349A. Abstract.
    
35. Mego DM, Nottestad SY, McClure JW, Rubal BR. Validation of a new Doppler-echocardiographic method for quantifying mitral regurgitation. J Am Soc Echocardiogr. 1995;8:897-903.[Medline] [Order article via Infotrieve]
    
36. Schwammenthal E, Chen C, Benning F, Block M, Breithardt G, Levine RA. Dynamics of mitral regurgitant flow and orifice area: physiologic application of the proximal flow convergence method: clinical data and experimental testing. Circulation. 1994;90:307-322.[Abstract/Free Full Text]
    
37. Chen C, Koschyk D, Brockhoff C, Heik S, Hamm C, Bleifeld W, Kupper W. Noninvasive estimation of regurgitant flow rate and volume in patients with mitral regurgitation by Doppler color mapping of accelerating flow field. J Am Coll Cardiol. 1993;21:374-383.[Abstract]
    
38. Rodriguez L, Anconina J, Flachskampf FA, Weyman AE, Levine RA, Thomas JD. Impact of finite orifice size on proximal flow convergence: implications for Doppler quantification of valvular regurgitation. Circ Res. 1992;70:923-930.[Abstract/Free Full Text]
    
39. Salerno DM, Wang K, Goldenberg IF, Van Tassel RA. The impact of selection bias on measurement of noninvasive test accuracy. Am J Cardiol. 1993;72:223-225. Editorial.[Medline] [Order article via Infotrieve]
    
40. Miller MG, Miller LS, Fireman B, Black SB. Variation in practice for discretionary admissions: impact on estimates of quality of hospital care. JAMA. 1994;271:1493-1498.[Abstract]
    
41. Zhang Y, Ihlen H, Myhre E, Levorstad K, Nitter-Hauge S. Quantification of mitral regurgitation by Doppler echocardiography. Eur Heart J. 1987;8(suppl C):59-62.
    
42. Tribouilloy C, Shen WF, Slama MA, Dufosse H, Choquet D, Marek A, Lesbre JP. Non-invasive measurement of the regurgitant fraction by pulse Doppler echocardiography in isolated pure mitral regurgitation. Br Heart J. 1991;66:290-294.[Abstract/Free Full Text]
    
43. Borgenhagen DM, Serur JR, Gorlin R, Adams D, Sonnenblick EH. The effects of left ventricular load and contractility on mitral regurgitant orifice size and flow in the dog. Circulation. 1977;56:106-113.[Abstract/Free Full Text]
    
44. Geffers H, Stauch M. Assessment of regurgitation fractions by radionuclide ventriculography. Z Kardiol. 1979;68:491-496.[Medline] [Order article via Infotrieve]
    
45. Viana MA. Bayesian small-sample estimation of misclassified multinomial data. Biometrics. 1994;50:237-243.[Medline] [Order article via Infotrieve]
    

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