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Does chronic mitral regurgitation influence Doppler pressure half-time–derived calculation of the mitral valve area in patients with mitral stenosis?
Does chronic mitral regurgitation influence Doppler pressure half-time– derived calculation of the mitral valve area in patients with mitral stenosis? Jagdish C. Mohan, MD,a Samanjoy Mukherjee, MD,a Ashish Kumar, MD,a Ramesh Arora, MD,a Ayan R. Patel, MD, FACC,b and Natesa G. Pandian, MD, FACCb New Delhi, India, and Boston, Mass
Background
In patients with mitral stenosis (MS), Doppler pressure half-time (PHT) may be influenced by hemodynamic variables other than the anatomic mitral valve orifice narrowing. This study was undertaken to assess whether the presence of concomitant mitral regurgitation (MR) affects mitral valve area (MVA) estimation by PHT.
Methods
Consecutive patients (n ⫽ 166) with noncalcific MS, in sinus rhythm, were studied. Group 1 (n ⫽ 106) had no or mild MR, and group 2 (n ⫽ 60) had moderate or severe MR. MVA was assessed by using the PHT method and planimetry.
Results
There was a strong correlation between planimetry and PHT MVA in both groups (group 1: r ⫽ 0.86, P ⬍ .001; group 2: r ⫽ 0.73, P ⬍ .001). However, compared with planimetry MVA, PHT underestimated MVA by ⱖ20% in 18 patients (17%) in group 1 and 21 patients (35%) in group 2 (P ⬍ .01). Overestimation by ⱖ20% occurred in 12 patients (11%) in group 1 and in 7 (12%) in group 2. Group 2 subanalysis (group 2A: moderate MR, n ⫽ 16; group 2B: severe MR, n ⫽ 44) revealed that linear regression weakened with increasing severity of MR (group 2A: r ⫽ 0.824, P ⬍ .001, group 2B: r ⫽ 0.70, P ⬍ .001). PHT underestimation of MVA occurred in 31% and 36% of patients in Groups IIA and IIB, respectively (P ⫽ NS).
Conclusions PHT appears to be reliable for estimating MVA in most patients with MS, even in the presence of MR. However, the presence of significant MR reduces the reliability of PHT-derived MVA, with underestimation of MVA in a significant number of subjects. The severity of MR has a direct impact on PHT-derived MVA. (Am Heart J 2004;148: 703–9.) The severity of mitral stenosis (MS) is assessed by measuring the transmitral pressure gradient and/or the stenotic mitral valve area (MVA). Two-dimensional echocardiographic (2D) planimetry of the mitral valve orifice1 and pressure half-time (PHT)2,3 are the two most commonly used methods to estimate mitral valve orifice area. These two methods have an excellent concordance and, in most cases, can be used interchangeably. However, the accuracy of PHT has been questioned in patients with mitral stenosis in the setting of significant aortic regurgitation,4 sinus tachycardia,5impaired left ventricular compliance,6 im-
From the aDivision of Cardiology, G.B. Pant Hospital, New Delhi, India, and the bCardiovascular Imaging and Hemodynamic Laboratory, Tufts-New England Medical Center, Boston, Mass. Submitted September 25, 2003; accepted December 18, 2003. Reprint requests: Ayan R. Patel, MD, Cardiovascular Imaging and Hemodynamic Laboratory, Tufts-New England Medical Center, 750 Washington St, Box 32, Boston, MA 02111. E-mail: [email protected] 0002-8703/$ - see front matter © 2004, Elsevier Inc. All rights reserved. doi:10.1016/j.ahj.2003.12.043
mediately after mitral valvuloplasty,7 and during pregnancy.8 Furthermore, the impact of mitral regurgitation (MR) on the reliability of PHT-derived MVA has not been fully resolved. It has been suggested that concomitant MR does not change PHT,2,9 –11 but existing data are limited and involve small numbers of patients, often in the setting of atrial fibrillation. In addition, most of the patients included in these studies had mild to moderate MR. The effect of significant MR on mitral valve resistance is therefore not clearly understood. There is evidence that the PHT is dependent not only on MVA but also on net atrioventricular compliance and peak transmitral gradient,12 which are both likely to be affected by the presence of moderate or severe MR. Many patients with MS first present clinically during periods of hemodynamic stress, such as pregnancy, or at a very young age with juvenile MS. These patients frequently undergo percutaneous transvenous mitral commissurotomy, despite the presence of significant concomitant MR, to delay surgery. Accurate assessment of severity of MS in these patients is critical. In
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Table I. Baseline characteristics, groups I and II
Mean age (y) Body surface area (m2) Male:female Heart rate (bpm) Mitral valve score Cardiac output (L/min) Estimated pulmonary artery systolic pressure (mm Hg) Mean transmitral gradient (mm Hg) Peak transmitral gradient (mm Hg) 2D-MVA (cm2) PHT-MVA (cm2) 2D-MVA ⬍1.0 cm2 (No.) Left ventricular fractional shortening (%)
Group 1 (n ⴝ 106)
Group 2 (n ⴝ 60)
P value
27 ⫾ 0.8 1.41 ⫾ 0.02 33:73 78 ⫾ 1.5 6.83 ⫾ 0.02 3.72 ⫾ 0.1 49 ⫾ 3 11 ⫾ 0.6 17 ⫾ 0.7 1.18 ⫾ 0.04 1.14 ⫾ 0.04 46 29.8 ⫾ 0.07
28 ⫾ 1.3 1.49 ⫾ 0.02 22:38 80 ⫾ 2 7.05 ⫾ 0.15 4.07 ⫾ 0.21 47 ⫾ 1.7 12.6 ⫾ 1.2 20 ⫾ 2 1.61 ⫾ 0.08 1.44 ⫾ 0.05 9 28.9 ⫾ 0.08
.34 .0028 .578 .46 .23 .07 .53 .11 .025 ⬍.0001 ⬍.0001 ⬍.01 .45
2D-MVA, 2-Dimensional echocardiographic mitral valve area; PHT-MVA, pressure half-time mitral valve area.
this study, 2D planimetry-derived MVA and the PHTderived MVA were compared with regard to their concordance and accuracy in a consecutive series of MS patients with and without significant MR. The accuracy of 2D planimetry-derived MVA is well established and has been validated with anatomic measurements and was therefore used as the gold standard to determine MVA in this study.9,10,13
Methods Study patients One hundred sixty-six consecutive patients (male, 57; female, 109) with MS in sinus rhythm were studied by Doppler and 2D echocardiography over a period of 1 year. Patients were excluded from the study if they were not in sinus rhythm or if they had (1) baseline heart rate ⬎120 beats/min, (2) calcified mitral valve, (3) associated moderate or severe aortic valve disease, (4) prior mitral commissurotomy in the preceding 6 months, (6) estimated right ventricular systolic pressure ⬎75 mm Hg with right ventricular dilatation, or (7) a suboptimal acoustic window. The study patients ranged in age from 12 to 55 years (mean, 27 ⫾ 2 years; 7 patients ⬎40 years of age). Eleven patients had undergone percutaneous transvenous mitral commissurotomy in the past (more than 1 year before the index study). Written informed consent was obtained from each patient or from his or her guardian in the case of minors (n ⫽ 17).
Echocardiographic examination Two-dimensional echocardiograms were recorded at rest, using a CFM 800 (VingMed Sound A/S, Horten, Norway) interfaced with a 3.25/2.5-MHz annular array transducer and SONOS 5500 (Hewlett Packard, Andover, Mass) with an S4 ultraband transducer. The electrocardiogram was obtained simultaneously in all patients, and heart rate was calculated from the R-R intervals. The entire examination was recorded on 0.5-inch VHS videotape. For the assessment of intraobserver variability, 10 patients were scanned by the same ob-
server at baseline and 24 hours later. As described previously,14 patients underwent a complete echocardiographic examination including transthoracic imaging, pulsed wave Doppler, continuous wave Doppler, and color flow mapping. The examination consisted of (1) 2D measurements to obtain left ventricular outflow tract (LVOT) diameter, planimetry of the directly observed mitral valve orifice area, and mitral valve score; (2) pulsed Doppler interrogation of the LVOT to acquire LVOT velocity-time integral; and (3) continuous wave Doppler examination of the mitral orifice in the apical 4-chamber view to obtain diastolic filling period, peak and mean transmitral pressure gradients, transmitral velocity-time integral, and PHT. Two-dimensional echocardiographic planimetry of the mitral valve orifice area was performed in the parasternal short-axis view, using the most appropriate site1 by an experienced observer. MVA by PHT method was determined by means of the continuous wave Doppler spectrum of the transmitral flow.2 Mitral valve morphologic score was obtained in all patients.15 Cardiac output was calculated as the product of the (LVOT velocity-time integral) ⫻ (0.785) ⫻ (LVOT diameter)2 ⫻ (heart rate).16 Mitral regurgitation was quantified by the color Doppler and continuous wave Doppler interrogation of the regurgitant jet in 2 orthogonal views (mild MR: mean color flow jet area in the left atrium ⬍4 cm2, jet area/left atrial area ⬍20% and width of vena contracta ⬍3 mm; moderate MR: holosystolic dense continuous wave Doppler spectrum with color jet area 4 to 8 cm2, jet area/left atrial area 20% to 40%, and width of vena contracta 3 to 6 mm; severe MR: holosystolic dense continuous wave Doppler spectrum with jet area ⬎8 cm2, jet area/left atrial area ⬎40% and width of vena contracta ⬎6 mm). At least 5 consecutive measurements of MVA were averaged for each patient.
Analysis of data MVA values by 2D and by the PHT were compared with regard to absolute values, percent difference, and category of severity of MS. The patients were divided into 2 groups, based on the presence or absence of significant MR. Patients
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Figure 1
A, Correlation between pressure half-time– derived mitral valve area and planimetry mitral valve area in group 1. B, Bland-Altman analysis of mean difference (⫾2 SD) between the two methods in group 1. MVA, Mitral valve area; PHT, pressure half-time; 2D, 2-dimensional echocardiographic planimetry.
in group 1 had absent or mild MR and group 2 patients had moderate or severe MR.
Statistical analysis Continuous data are presented as mean value ⫾ SEM unless otherwise indicated. Group 1 and group 2 characteristics were compared by using the unpaired t test for continuous variables and 2 analysis for nominal variables. Differences were considered significant at a value of P ⬍ .05. Linear regression analysis was used to determine the correlation between PHT and planimetry MVA in both groups, and regression coefficient and standard error of estimate were obtained.
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Figure 2
A, Correlation between pressure half-time– derived mitral valve area and planimetry mitral valve area in group 2. B, Bland-Altman analysis of mean difference (⫾2 SD) between the two methods in group 2. MVA, Mitral valve area; PHT, pressure half-time; 2D, 2-dimensional echocardiographic planimetry.
The degree of agreement between both methods in the two groups was examined by using Bland-Altman analysis (Sigmastat, version 2.03).17
Results One hundred nine female and 57 male patients (mean age, 27 ⫾ 2 years; range, 12 to 55 years old) were studied. Of these, 55 patients had severe MS (MVA ⬍1.0 cm2) and 111 had mild-moderate MS (MVA > 1.0 cm2) by planimetry. Patients were divided into 2 groups, based on the presence and severity of MR. Group 1 (n ⫽ 106) had absent or mild MR and group 2 (n ⫽ 60) had moderate or severe MR. Severe mitral
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Figure 3
Bland-Altman analysis of mean difference ⫾2 SD between the two methods in group 2A. MVA, Mitral valve area; PHT, pressure halftime; 2D, 2-dimensional echocardiographic planimetry.
Figure 4
Bland-Altman analysis of mean difference ⫾2 SD between the two methods in group 2B. MVA, Mitral valve area; PHT, pressure halftime; 2D, 2-dimensional echocardiographic planimetry.
Table II. Baseline characteristics, groups 2A and 2B
Mean age (y) Body surface area (m2) Male/female Heart rate (beats/min) Mitral valve score Cardiac output (L/min) Estimated pulmonary artery systolic pressure (mm Hg) Mean transmitral gradient (mm Hg) Peak transmitral gradient (mm Hg) 2D-MVA (cm2) PHT-MVA (cm2) MVA ⬍1.0 cm2 (No.) Left ventricular fractional shortening (%)
Group 2A (n ⴝ 16)
Group 2B (n ⴝ 44)
P value
25 ⫾ 0.8 1.48 ⫾ 0.03 6:10 78 ⫾ 1.5 6.8 ⫾ 0.02 3.78 ⫾ 0.1 44 ⫾ 3 11.3 ⫾ 0.6 19 ⫾ 0.9 1.44 ⫾ 0.07 1.46 ⫾ 0.04 4 29.2 ⫾ 1.3
31 ⫾ 1.0 1.48 ⫾ 0.04 16:28 81 ⫾ 2 7.2 ⫾ 0.15 3.92 ⫾ 0.2 54 ⫾ 3.4 13.2 ⫾ 1.6 23 ⫾ 2 1.65 ⫾ 0.12 1.42 ⫾ 0.05 5 31.0 ⫾ 1.4
.12 .16 .67 .48 .29 .17 .043 .19 .025 ⬍.0001 ⬍.0001 .1 .57
2D-MVA, 2-Dimensional echocardiographic mitral valve area; PHT-MVA, pressure half-time mitral valve area.
stenosis was present in 46 patients in group 1 and in 9 patients in group 2 (P ⬍ .01). Patients in group 1 had smaller body surface area, smaller baseline MVA, and lesser peak transmitral gradient compared with patients in group 2. Other baseline parameters were similar in the two groups (Table I). There was a strong correlation between the two methods of MVA measurement in group 1 (group 1: r ⫽ 0.86, P ⬍ .001, SEE ⫽ 0.21 cm2, y ⫽ 0.84X ⫹ 0.10). Mean bias (2D MVA-PHT MVA) was 0.035 ⫾ 0.02 cm2, and limits of agreement ranged from – 0.40 to 0.47 cm2 (Figure 1). Patients in group 2 had a weaker correlation between the two methods, with wider standard error of estimate (SEE): (r ⫽ 0.73, P ⬍
.001, SEE ⫽ 0.26 cm2, y ⫽ 0.41X ⫹ 0.78). Mean bias in group 2 was 0.17 ⫾ 0.06 cm2, with limits of agreement ranging from ⫺0.78 to 1.12 cm2 (Figure 2). A PHT-derived area overestimation by ⱖ20% occurred in 12 patients (11%) in group 1 and in 7 patients (12%) in group 2. An underestimation by ⱖ20% occurred in 18 patients (17%) in group 1 and in 21 (35%) in group 2 (P ⬍ .01). The percentage of patients in each group whose category of mitral stenosis severity changed by PHT assessment was also calculated. Mild MS was defined as MVA ⱖ1.5 cm2, moderate as MVA between 1 and 1.5 cm2, and severe was defined as MVA ⬍ 1 cm2. Nine patients (all in group 2) had a change in category of severity when MVA was assessed by PHT method
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Figure 5
Example of underestimation of mitral valve area by pressure half-time method in a patient with combined mitral stenosis and regurgitation. MR, Mitral regurgitation; MVA, mitral valve area.
(mild changed to moderate in 7 subjects, and moderate to severe in 2). Subanalysis of group 2 (group 2A ⫽ moderate MR, n ⫽ 16; group 2B ⫽ severe MR, n ⫽ 44) revealed that linear regression weakened with increasing severity of MR (group 2A: r ⫽ 0.824, P ⬍ .001, SEE ⫽ 0.20 cm2, y ⫽ 0.5X ⫹ 0.61; group 2B: r ⫽ 0.70, P ⬍ .001, SEE ⫽ 0.29 cm2, y ⫽ 0.39X ⫹ 0.83). The clinical characteristics of groups IIA and IIB are shown in Table II. Underestimation of MVA by PHT occurred in 31% and 36% of patients in groups IIA and IIB, respectively (P ⫽ NS); however, the number of subjects in these subgroups was relatively small. Mean bias and limits of agreement in group 2A were 0.16 ⫾ 0.08 cm2 and ⫺0.52 cm2 to 0.84 cm2, respectively, whereas in group 2B, these were 0.17 ⫾ 0.08 cm2 and ⫺0.87 to 1.21 cm2 respectively (Figure 3 and Figure 4). There was a good correlation between peak transmitral gradient and the PHT in group 1 (r ⫽ ⫺0.51, P ⬍ .0001), but only a modest correlation in group 2 (r ⫽ ⫺0.25, P ⬍ .05). Figure 5 shows a representative example of significant underestimation of MVA by the PHT method in presence of MR.
Discussion This study addresses the accuracy of the Doppler PHT method for assessing MS complicated by MR. This is the first study including such a large number of patients with MS and concomitant significant MR in sinus rhythm. There was a high degree of concordance between Doppler and 2D-echocardiography in patients with MS and absent or mild MR. We observed a significant underestimation of mitral valve area by the PHT method in 35% of patients with moderate or severe MR. Correlation, standard error of estimate, and agreement between 2D-MVA and PHT-MVA worsened with increasing severity of regurgitation. However, only 9 patients (all in group 2) had a change in category of severity when MVA was measured by PHT method. These findings address a clinically important question regarding the accuracy of PHT method in the setting of mixed stenotic and regurgitant mitral valve disease. Although PHT appears to be reliable in most patients with mixed mitral valve disease, PHT underestimates MVA in a considerable number of patients with significant MR. These observations support the importance of adjunctive use of the 2D
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planimetry method in patients with mixed mitral valve disease.
Previous studies There are limited data reported in the literature regarding the effect of MR on PHT assessment of MVA. Hatle et al2 studied 12 patients with combined mitral stenosis and regurgitation, of whom 7 had simultaneous Doppler and cardiac catheterization studies. There was a good correlation between PHT and MVA derived by Gorlin equation in these 7 patients, but the severity of MR in this study was not specified. Furthermore, calculation of MVA by the Gorlin formula may result in underestimation of the valve orifice area in the presence of MR, since the forward cardiac output used in the valve area formula fails to account for the regurgitant fraction that contributes to the total transmitral diastolic flow.18 Other investigators have reported a good correlation between PHT MVA and 2D MVA in small groups of patients with MS and MR, but these studies either predominantly included patients with mild or moderate regurgitation or did not specifically assess the effect of severe MR.9 –11,13 In the current study, we observed that there was an acceptable correlation and standard error of estimate between PHT and planimetry MVA in patients with MS and mild MR but that this correlation weakens with increasing severity of MR. Inclusion of a majority of patients with mild or moderate regurgitation in previous studies2,9 –11 may have limited the effect of MR on the PHT MVA. We observed a strong inverse correlation between PHT and peak transmitral gradient in group 1 patients but only a modest correlation in group 2 patients, suggesting that MR alters the relation between the initial pressure gradient and PHT. The rate of decay of the transmitral gradient and hence the PHT varies inversely with the mitral valve orifice area and varies directly with the left atrial compliance and the square root of the peak transmitral gradient.6 The use of PHT remains valid in a majority of patients with significant MR, possibly because the initial pressure gradient and chamber compliance change in opposite direction.11However, in a significant number of patients, left atrial compliance change may predominate and alter the relation between mitral valve orifice area and the PHT.
Limitations The use of 2D planimetry mitral valve orifice area as the gold standard may be seen as a limitation. However, planimetry measurement of MVA by 2D echocardiography correlates closely with anatomic MVA.10In addition, previous studies9,10,13 have shown that the Doppler PHT method and 2D valve area are closely correlated, with acceptable standard error of estimate. Assessment of the severity of MR by Doppler tech-
niques may also introduce errors, particularly in patients with eccentric regurgitant jets. Although quantitative assessment of regurgitant volume was not used, the semiquantitative methods used for the assessment of regurgitation in this study are widely used in clinical practice. In addition, we used strict criteria to grade MR, using multiple parameters to minimize potential errors. Four patients in each group had sinus tachycardia (heart rate, 100 to 119 beats/min), which can result in overestimation of valve area by the Doppler PHT method. When the data were reanalyzed with these few patients excluded, the results of the current study remained unchanged.
Conclusions This study demonstrates that the presence of significant MR reduces the accuracy of Doppler PHT-derived MVA, with significant underestimation in approximately one third of patients. These data support the concomitant use of the 2D planimetry method for mitral valve area determination when there is coexistent mitral stenosis and regurgitation.
References 1. Martin RP, Rakowskai H, Kleiman JH, et al. Reliability and reproducibility of two dimensional echocardiographic measurement of the stenotic mitral valve orifice area. Am J Cardiol 1979;43: 560 – 8. 2. Hatle L, Angelsen B, Tromsdal A. Non-invasive assessment of atrioventricular pressure half-time by Doppler ultrasound. Circulation 1979;60:1096 –104. 3. Libanoff AJ, Rodbard S. Atrioventricular pressure half-time: measure of mitral valve orifice area. Circulation 1968;38:144 –50. 4. Flaschkampf FA, Weyman AE, Gillam L, et al. Aortic regurgitation shortens Doppler pressure half time in mitral stenosis: clinical evidence: in vitro stimulation and theoretical analysis. J Am Coll Cardiol 1990;16:396 – 404. 5. Voelker W, Regele H, Dittmann M, et al. Effect of heart rate on transmitral flow velocity profile and Doppler measurement in mitral valve area in patients with mitral stenosis. Eur Heart J 1992;13: 152–9. 6. Karp K, Teien D, Bjerle P, et al. Reassessment of valve area determination by pressure half time method: impact of left ventricular stiffness and peak diastolic pressure difference. J Am Coll Cardiol 1989;13:594 –9. 7. Thomas JD, Wilkins GT, Choong CYP, et al. Inaccuracy of mitral pressure half-time immediately after percutaneous mitral valvotomy: dependence on transmitral gradient and left atrial and ventricular compliance. Circulation 1988;78:980 –93. 8. Bryg RJ, Gordon PR, Kudesia VS, et al. Effect of pregnancy on pressure gradient in mitral stenosis. Am J Cardiol 1989;63:384– 6. 9. Bryg RJ, Williams GA, Labowitz AJ, et al. Effect of atrial fibrillation and mitral regurgitation on calculated mitral valve area in mitral stenosis. Am J Cardiol 1986;57:634 – 8. 10. Faletra F, Pezzano A Jr, Fusco R, et al. Measurement of mitral valve area in mitral stenosis: four echocardiographic methods compared with direct measurement of anatomic orifices. J Am Coll Cardiol 1996;28:1190 –7.
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11. Fredman CS, Pearson AC, Labowitz AJ, et al. Comparison of hemodynamic pressure half-time method and Gorlin formula with Doppler and echocardiographic determinations of mitral valve area in patients with combined mitral stenosis and regurgitation. Am Heart J 1990;119:121–9. 12. Braverman AC, Thomas JD, Lee RT. Doppler echocardiographic estimation of mitral valve area during changing hemodynamic conditions. Am J Cardiol 1991;68:1485–90. 13. Nakatani S, Masuyama T, Kodama K, et al. Value and limitation of Doppler echocardiography in the quantification of stenotic mitral valve area: comparison of the pressure half-time and the continuity equation. Circulation 1988;77:78 – 85. 14. Mohan JC, Patel AR, Passey R, et al. Is the mitral valve area flowdependent in mitral stenosis? A dobutamine stress echocardio-
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graphic study. J Am Coll Cardiol 2002;40:1809 –15. 15. Wilkins GT, Weyman AE, Abascal VM, et al. Percutaneous balloon dilatation of the mitral valve: an analysis of echocardiographic variables related to outcome and the mechanism of dilatation. Br Heart J 1988;60:299 –308. 16. Lewis JF, Kuo LC, Nelson JG, et al. Pulsed Doppler echocardiographic determination of stroke volume and cardiac output: clinical validation of two new methods using the apical window. Circulation 1984;70:425–31. 17. Bland JM, Altman DG. Statistical methods for assessing agreement between methods of clinical measurement. Lancet 1986;2:307–10. 18. Gorlin R, Gorlin SG. Hydraulic formula for calculation of the area of mitral valve, other cardiac valves, and central circulation shunts. Am Heart J 1951;41:1–29.
Background
In patients with mitral stenosis (MS), Doppler pressure half-time (PHT) may be influenced by hemodynamic variables other than the anatomic mitral valve orifice narrowing. This study was undertaken to assess whether the presence of concomitant mitral regurgitation (MR) affects mitral valve area (MVA) estimation by PHT.
Methods
Consecutive patients (n ⫽ 166) with noncalcific MS, in sinus rhythm, were studied. Group 1 (n ⫽ 106) had no or mild MR, and group 2 (n ⫽ 60) had moderate or severe MR. MVA was assessed by using the PHT method and planimetry.
Results
There was a strong correlation between planimetry and PHT MVA in both groups (group 1: r ⫽ 0.86, P ⬍ .001; group 2: r ⫽ 0.73, P ⬍ .001). However, compared with planimetry MVA, PHT underestimated MVA by ⱖ20% in 18 patients (17%) in group 1 and 21 patients (35%) in group 2 (P ⬍ .01). Overestimation by ⱖ20% occurred in 12 patients (11%) in group 1 and in 7 (12%) in group 2. Group 2 subanalysis (group 2A: moderate MR, n ⫽ 16; group 2B: severe MR, n ⫽ 44) revealed that linear regression weakened with increasing severity of MR (group 2A: r ⫽ 0.824, P ⬍ .001, group 2B: r ⫽ 0.70, P ⬍ .001). PHT underestimation of MVA occurred in 31% and 36% of patients in Groups IIA and IIB, respectively (P ⫽ NS).
Conclusions PHT appears to be reliable for estimating MVA in most patients with MS, even in the presence of MR. However, the presence of significant MR reduces the reliability of PHT-derived MVA, with underestimation of MVA in a significant number of subjects. The severity of MR has a direct impact on PHT-derived MVA. (Am Heart J 2004;148: 703–9.) The severity of mitral stenosis (MS) is assessed by measuring the transmitral pressure gradient and/or the stenotic mitral valve area (MVA). Two-dimensional echocardiographic (2D) planimetry of the mitral valve orifice1 and pressure half-time (PHT)2,3 are the two most commonly used methods to estimate mitral valve orifice area. These two methods have an excellent concordance and, in most cases, can be used interchangeably. However, the accuracy of PHT has been questioned in patients with mitral stenosis in the setting of significant aortic regurgitation,4 sinus tachycardia,5impaired left ventricular compliance,6 im-
From the aDivision of Cardiology, G.B. Pant Hospital, New Delhi, India, and the bCardiovascular Imaging and Hemodynamic Laboratory, Tufts-New England Medical Center, Boston, Mass. Submitted September 25, 2003; accepted December 18, 2003. Reprint requests: Ayan R. Patel, MD, Cardiovascular Imaging and Hemodynamic Laboratory, Tufts-New England Medical Center, 750 Washington St, Box 32, Boston, MA 02111. E-mail: [email protected] 0002-8703/$ - see front matter © 2004, Elsevier Inc. All rights reserved. doi:10.1016/j.ahj.2003.12.043
mediately after mitral valvuloplasty,7 and during pregnancy.8 Furthermore, the impact of mitral regurgitation (MR) on the reliability of PHT-derived MVA has not been fully resolved. It has been suggested that concomitant MR does not change PHT,2,9 –11 but existing data are limited and involve small numbers of patients, often in the setting of atrial fibrillation. In addition, most of the patients included in these studies had mild to moderate MR. The effect of significant MR on mitral valve resistance is therefore not clearly understood. There is evidence that the PHT is dependent not only on MVA but also on net atrioventricular compliance and peak transmitral gradient,12 which are both likely to be affected by the presence of moderate or severe MR. Many patients with MS first present clinically during periods of hemodynamic stress, such as pregnancy, or at a very young age with juvenile MS. These patients frequently undergo percutaneous transvenous mitral commissurotomy, despite the presence of significant concomitant MR, to delay surgery. Accurate assessment of severity of MS in these patients is critical. In
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704 Mohan et al
Table I. Baseline characteristics, groups I and II
Mean age (y) Body surface area (m2) Male:female Heart rate (bpm) Mitral valve score Cardiac output (L/min) Estimated pulmonary artery systolic pressure (mm Hg) Mean transmitral gradient (mm Hg) Peak transmitral gradient (mm Hg) 2D-MVA (cm2) PHT-MVA (cm2) 2D-MVA ⬍1.0 cm2 (No.) Left ventricular fractional shortening (%)
Group 1 (n ⴝ 106)
Group 2 (n ⴝ 60)
P value
27 ⫾ 0.8 1.41 ⫾ 0.02 33:73 78 ⫾ 1.5 6.83 ⫾ 0.02 3.72 ⫾ 0.1 49 ⫾ 3 11 ⫾ 0.6 17 ⫾ 0.7 1.18 ⫾ 0.04 1.14 ⫾ 0.04 46 29.8 ⫾ 0.07
28 ⫾ 1.3 1.49 ⫾ 0.02 22:38 80 ⫾ 2 7.05 ⫾ 0.15 4.07 ⫾ 0.21 47 ⫾ 1.7 12.6 ⫾ 1.2 20 ⫾ 2 1.61 ⫾ 0.08 1.44 ⫾ 0.05 9 28.9 ⫾ 0.08
.34 .0028 .578 .46 .23 .07 .53 .11 .025 ⬍.0001 ⬍.0001 ⬍.01 .45
2D-MVA, 2-Dimensional echocardiographic mitral valve area; PHT-MVA, pressure half-time mitral valve area.
this study, 2D planimetry-derived MVA and the PHTderived MVA were compared with regard to their concordance and accuracy in a consecutive series of MS patients with and without significant MR. The accuracy of 2D planimetry-derived MVA is well established and has been validated with anatomic measurements and was therefore used as the gold standard to determine MVA in this study.9,10,13
Methods Study patients One hundred sixty-six consecutive patients (male, 57; female, 109) with MS in sinus rhythm were studied by Doppler and 2D echocardiography over a period of 1 year. Patients were excluded from the study if they were not in sinus rhythm or if they had (1) baseline heart rate ⬎120 beats/min, (2) calcified mitral valve, (3) associated moderate or severe aortic valve disease, (4) prior mitral commissurotomy in the preceding 6 months, (6) estimated right ventricular systolic pressure ⬎75 mm Hg with right ventricular dilatation, or (7) a suboptimal acoustic window. The study patients ranged in age from 12 to 55 years (mean, 27 ⫾ 2 years; 7 patients ⬎40 years of age). Eleven patients had undergone percutaneous transvenous mitral commissurotomy in the past (more than 1 year before the index study). Written informed consent was obtained from each patient or from his or her guardian in the case of minors (n ⫽ 17).
Echocardiographic examination Two-dimensional echocardiograms were recorded at rest, using a CFM 800 (VingMed Sound A/S, Horten, Norway) interfaced with a 3.25/2.5-MHz annular array transducer and SONOS 5500 (Hewlett Packard, Andover, Mass) with an S4 ultraband transducer. The electrocardiogram was obtained simultaneously in all patients, and heart rate was calculated from the R-R intervals. The entire examination was recorded on 0.5-inch VHS videotape. For the assessment of intraobserver variability, 10 patients were scanned by the same ob-
server at baseline and 24 hours later. As described previously,14 patients underwent a complete echocardiographic examination including transthoracic imaging, pulsed wave Doppler, continuous wave Doppler, and color flow mapping. The examination consisted of (1) 2D measurements to obtain left ventricular outflow tract (LVOT) diameter, planimetry of the directly observed mitral valve orifice area, and mitral valve score; (2) pulsed Doppler interrogation of the LVOT to acquire LVOT velocity-time integral; and (3) continuous wave Doppler examination of the mitral orifice in the apical 4-chamber view to obtain diastolic filling period, peak and mean transmitral pressure gradients, transmitral velocity-time integral, and PHT. Two-dimensional echocardiographic planimetry of the mitral valve orifice area was performed in the parasternal short-axis view, using the most appropriate site1 by an experienced observer. MVA by PHT method was determined by means of the continuous wave Doppler spectrum of the transmitral flow.2 Mitral valve morphologic score was obtained in all patients.15 Cardiac output was calculated as the product of the (LVOT velocity-time integral) ⫻ (0.785) ⫻ (LVOT diameter)2 ⫻ (heart rate).16 Mitral regurgitation was quantified by the color Doppler and continuous wave Doppler interrogation of the regurgitant jet in 2 orthogonal views (mild MR: mean color flow jet area in the left atrium ⬍4 cm2, jet area/left atrial area ⬍20% and width of vena contracta ⬍3 mm; moderate MR: holosystolic dense continuous wave Doppler spectrum with color jet area 4 to 8 cm2, jet area/left atrial area 20% to 40%, and width of vena contracta 3 to 6 mm; severe MR: holosystolic dense continuous wave Doppler spectrum with jet area ⬎8 cm2, jet area/left atrial area ⬎40% and width of vena contracta ⬎6 mm). At least 5 consecutive measurements of MVA were averaged for each patient.
Analysis of data MVA values by 2D and by the PHT were compared with regard to absolute values, percent difference, and category of severity of MS. The patients were divided into 2 groups, based on the presence or absence of significant MR. Patients
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Figure 1
A, Correlation between pressure half-time– derived mitral valve area and planimetry mitral valve area in group 1. B, Bland-Altman analysis of mean difference (⫾2 SD) between the two methods in group 1. MVA, Mitral valve area; PHT, pressure half-time; 2D, 2-dimensional echocardiographic planimetry.
in group 1 had absent or mild MR and group 2 patients had moderate or severe MR.
Statistical analysis Continuous data are presented as mean value ⫾ SEM unless otherwise indicated. Group 1 and group 2 characteristics were compared by using the unpaired t test for continuous variables and 2 analysis for nominal variables. Differences were considered significant at a value of P ⬍ .05. Linear regression analysis was used to determine the correlation between PHT and planimetry MVA in both groups, and regression coefficient and standard error of estimate were obtained.
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Figure 2
A, Correlation between pressure half-time– derived mitral valve area and planimetry mitral valve area in group 2. B, Bland-Altman analysis of mean difference (⫾2 SD) between the two methods in group 2. MVA, Mitral valve area; PHT, pressure half-time; 2D, 2-dimensional echocardiographic planimetry.
The degree of agreement between both methods in the two groups was examined by using Bland-Altman analysis (Sigmastat, version 2.03).17
Results One hundred nine female and 57 male patients (mean age, 27 ⫾ 2 years; range, 12 to 55 years old) were studied. Of these, 55 patients had severe MS (MVA ⬍1.0 cm2) and 111 had mild-moderate MS (MVA > 1.0 cm2) by planimetry. Patients were divided into 2 groups, based on the presence and severity of MR. Group 1 (n ⫽ 106) had absent or mild MR and group 2 (n ⫽ 60) had moderate or severe MR. Severe mitral
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Figure 3
Bland-Altman analysis of mean difference ⫾2 SD between the two methods in group 2A. MVA, Mitral valve area; PHT, pressure halftime; 2D, 2-dimensional echocardiographic planimetry.
Figure 4
Bland-Altman analysis of mean difference ⫾2 SD between the two methods in group 2B. MVA, Mitral valve area; PHT, pressure halftime; 2D, 2-dimensional echocardiographic planimetry.
Table II. Baseline characteristics, groups 2A and 2B
Mean age (y) Body surface area (m2) Male/female Heart rate (beats/min) Mitral valve score Cardiac output (L/min) Estimated pulmonary artery systolic pressure (mm Hg) Mean transmitral gradient (mm Hg) Peak transmitral gradient (mm Hg) 2D-MVA (cm2) PHT-MVA (cm2) MVA ⬍1.0 cm2 (No.) Left ventricular fractional shortening (%)
Group 2A (n ⴝ 16)
Group 2B (n ⴝ 44)
P value
25 ⫾ 0.8 1.48 ⫾ 0.03 6:10 78 ⫾ 1.5 6.8 ⫾ 0.02 3.78 ⫾ 0.1 44 ⫾ 3 11.3 ⫾ 0.6 19 ⫾ 0.9 1.44 ⫾ 0.07 1.46 ⫾ 0.04 4 29.2 ⫾ 1.3
31 ⫾ 1.0 1.48 ⫾ 0.04 16:28 81 ⫾ 2 7.2 ⫾ 0.15 3.92 ⫾ 0.2 54 ⫾ 3.4 13.2 ⫾ 1.6 23 ⫾ 2 1.65 ⫾ 0.12 1.42 ⫾ 0.05 5 31.0 ⫾ 1.4
.12 .16 .67 .48 .29 .17 .043 .19 .025 ⬍.0001 ⬍.0001 .1 .57
2D-MVA, 2-Dimensional echocardiographic mitral valve area; PHT-MVA, pressure half-time mitral valve area.
stenosis was present in 46 patients in group 1 and in 9 patients in group 2 (P ⬍ .01). Patients in group 1 had smaller body surface area, smaller baseline MVA, and lesser peak transmitral gradient compared with patients in group 2. Other baseline parameters were similar in the two groups (Table I). There was a strong correlation between the two methods of MVA measurement in group 1 (group 1: r ⫽ 0.86, P ⬍ .001, SEE ⫽ 0.21 cm2, y ⫽ 0.84X ⫹ 0.10). Mean bias (2D MVA-PHT MVA) was 0.035 ⫾ 0.02 cm2, and limits of agreement ranged from – 0.40 to 0.47 cm2 (Figure 1). Patients in group 2 had a weaker correlation between the two methods, with wider standard error of estimate (SEE): (r ⫽ 0.73, P ⬍
.001, SEE ⫽ 0.26 cm2, y ⫽ 0.41X ⫹ 0.78). Mean bias in group 2 was 0.17 ⫾ 0.06 cm2, with limits of agreement ranging from ⫺0.78 to 1.12 cm2 (Figure 2). A PHT-derived area overestimation by ⱖ20% occurred in 12 patients (11%) in group 1 and in 7 patients (12%) in group 2. An underestimation by ⱖ20% occurred in 18 patients (17%) in group 1 and in 21 (35%) in group 2 (P ⬍ .01). The percentage of patients in each group whose category of mitral stenosis severity changed by PHT assessment was also calculated. Mild MS was defined as MVA ⱖ1.5 cm2, moderate as MVA between 1 and 1.5 cm2, and severe was defined as MVA ⬍ 1 cm2. Nine patients (all in group 2) had a change in category of severity when MVA was assessed by PHT method
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Figure 5
Example of underestimation of mitral valve area by pressure half-time method in a patient with combined mitral stenosis and regurgitation. MR, Mitral regurgitation; MVA, mitral valve area.
(mild changed to moderate in 7 subjects, and moderate to severe in 2). Subanalysis of group 2 (group 2A ⫽ moderate MR, n ⫽ 16; group 2B ⫽ severe MR, n ⫽ 44) revealed that linear regression weakened with increasing severity of MR (group 2A: r ⫽ 0.824, P ⬍ .001, SEE ⫽ 0.20 cm2, y ⫽ 0.5X ⫹ 0.61; group 2B: r ⫽ 0.70, P ⬍ .001, SEE ⫽ 0.29 cm2, y ⫽ 0.39X ⫹ 0.83). The clinical characteristics of groups IIA and IIB are shown in Table II. Underestimation of MVA by PHT occurred in 31% and 36% of patients in groups IIA and IIB, respectively (P ⫽ NS); however, the number of subjects in these subgroups was relatively small. Mean bias and limits of agreement in group 2A were 0.16 ⫾ 0.08 cm2 and ⫺0.52 cm2 to 0.84 cm2, respectively, whereas in group 2B, these were 0.17 ⫾ 0.08 cm2 and ⫺0.87 to 1.21 cm2 respectively (Figure 3 and Figure 4). There was a good correlation between peak transmitral gradient and the PHT in group 1 (r ⫽ ⫺0.51, P ⬍ .0001), but only a modest correlation in group 2 (r ⫽ ⫺0.25, P ⬍ .05). Figure 5 shows a representative example of significant underestimation of MVA by the PHT method in presence of MR.
Discussion This study addresses the accuracy of the Doppler PHT method for assessing MS complicated by MR. This is the first study including such a large number of patients with MS and concomitant significant MR in sinus rhythm. There was a high degree of concordance between Doppler and 2D-echocardiography in patients with MS and absent or mild MR. We observed a significant underestimation of mitral valve area by the PHT method in 35% of patients with moderate or severe MR. Correlation, standard error of estimate, and agreement between 2D-MVA and PHT-MVA worsened with increasing severity of regurgitation. However, only 9 patients (all in group 2) had a change in category of severity when MVA was measured by PHT method. These findings address a clinically important question regarding the accuracy of PHT method in the setting of mixed stenotic and regurgitant mitral valve disease. Although PHT appears to be reliable in most patients with mixed mitral valve disease, PHT underestimates MVA in a considerable number of patients with significant MR. These observations support the importance of adjunctive use of the 2D
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planimetry method in patients with mixed mitral valve disease.
Previous studies There are limited data reported in the literature regarding the effect of MR on PHT assessment of MVA. Hatle et al2 studied 12 patients with combined mitral stenosis and regurgitation, of whom 7 had simultaneous Doppler and cardiac catheterization studies. There was a good correlation between PHT and MVA derived by Gorlin equation in these 7 patients, but the severity of MR in this study was not specified. Furthermore, calculation of MVA by the Gorlin formula may result in underestimation of the valve orifice area in the presence of MR, since the forward cardiac output used in the valve area formula fails to account for the regurgitant fraction that contributes to the total transmitral diastolic flow.18 Other investigators have reported a good correlation between PHT MVA and 2D MVA in small groups of patients with MS and MR, but these studies either predominantly included patients with mild or moderate regurgitation or did not specifically assess the effect of severe MR.9 –11,13 In the current study, we observed that there was an acceptable correlation and standard error of estimate between PHT and planimetry MVA in patients with MS and mild MR but that this correlation weakens with increasing severity of MR. Inclusion of a majority of patients with mild or moderate regurgitation in previous studies2,9 –11 may have limited the effect of MR on the PHT MVA. We observed a strong inverse correlation between PHT and peak transmitral gradient in group 1 patients but only a modest correlation in group 2 patients, suggesting that MR alters the relation between the initial pressure gradient and PHT. The rate of decay of the transmitral gradient and hence the PHT varies inversely with the mitral valve orifice area and varies directly with the left atrial compliance and the square root of the peak transmitral gradient.6 The use of PHT remains valid in a majority of patients with significant MR, possibly because the initial pressure gradient and chamber compliance change in opposite direction.11However, in a significant number of patients, left atrial compliance change may predominate and alter the relation between mitral valve orifice area and the PHT.
Limitations The use of 2D planimetry mitral valve orifice area as the gold standard may be seen as a limitation. However, planimetry measurement of MVA by 2D echocardiography correlates closely with anatomic MVA.10In addition, previous studies9,10,13 have shown that the Doppler PHT method and 2D valve area are closely correlated, with acceptable standard error of estimate. Assessment of the severity of MR by Doppler tech-
niques may also introduce errors, particularly in patients with eccentric regurgitant jets. Although quantitative assessment of regurgitant volume was not used, the semiquantitative methods used for the assessment of regurgitation in this study are widely used in clinical practice. In addition, we used strict criteria to grade MR, using multiple parameters to minimize potential errors. Four patients in each group had sinus tachycardia (heart rate, 100 to 119 beats/min), which can result in overestimation of valve area by the Doppler PHT method. When the data were reanalyzed with these few patients excluded, the results of the current study remained unchanged.
Conclusions This study demonstrates that the presence of significant MR reduces the accuracy of Doppler PHT-derived MVA, with significant underestimation in approximately one third of patients. These data support the concomitant use of the 2D planimetry method for mitral valve area determination when there is coexistent mitral stenosis and regurgitation.
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11. Fredman CS, Pearson AC, Labowitz AJ, et al. Comparison of hemodynamic pressure half-time method and Gorlin formula with Doppler and echocardiographic determinations of mitral valve area in patients with combined mitral stenosis and regurgitation. Am Heart J 1990;119:121–9. 12. Braverman AC, Thomas JD, Lee RT. Doppler echocardiographic estimation of mitral valve area during changing hemodynamic conditions. Am J Cardiol 1991;68:1485–90. 13. Nakatani S, Masuyama T, Kodama K, et al. Value and limitation of Doppler echocardiography in the quantification of stenotic mitral valve area: comparison of the pressure half-time and the continuity equation. Circulation 1988;77:78 – 85. 14. Mohan JC, Patel AR, Passey R, et al. Is the mitral valve area flowdependent in mitral stenosis? A dobutamine stress echocardio-
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