The main finding of this study was that compared with the MRvol using EROA by RT3DE multiplied by the TVIMR, the MRvol was overestimated significantly by the 2D TTE QPDA4C method previously recommended [2, 4]. The overestimates were caused by the circular geometric assumption of the MA, which led to the CSA A4C and corresponding SVMA being overestimated. In our study, assumption of a ellipse geometry of MA, MRvol calculated by QPDA4C+A2C showed better correlation (r = 0.905, P < 0.0001) and had no significant difference (mean difference = 1.7 ml, P = 0.0844) with MRvol by RT3DE.
MRvol by QPD is simple in theory. Stroke volume (SV) at aortic valve or MV is derived as the product of CSA and VTI of flow at the LVOT or MA. In the absence of MR, SV determinations at LVOT and MA are equal. In the presence of MR, without any intracardiac shunt, the flow through MA is larger than through the LVOT. The difference between the two represents the MRvol [12]. For MRvol by QPD method, it is very important to accurately evaluate the CSAMA and CSALVOT. The calculation method of CSALVOT is nearly consistent (CSALVOT =πd2/4, where d was the diameter of the LVOT in the PLAX view) [2,4,9]. However, the calculation method of CSAMA is controversial [5]. The MA diameter was measured in the A4C view and the CSAMA was derived as 0.785 d2 (where d is the MA diameter in A4C) assuming that the MA is circular geometry as previously recommended [4,9]. However, previous studies have been demonstrated that the MA has a saddle-shaped contour [13] and the CSA of the MA are oval, with the major and minor diameter [5,14,15]. Ren et al [5] studied geometric errors of the MA by RT3DE. They found that the MA geometry was oval in the 3D en face views with a significant difference between the major and minor diameters. The 2D diameters of the MAA4C was significantly different from both the major and minor diameters. Assuming that the MA was circular geometry, the CSA of the MAA4C by 2D TTE overestimated the CSA compared with RT3DE [5]. In our study, the QPD-MAPLAX and QPD-MAA4C overestimated the MRvol (mean difference = 22.5 ml, P < 0.0001;mean difference = 10.4 ml, P < 0.0001) and QPD-MAA2C underestimated the MRvol (mean difference = 5.5 ml, P = 0.0002) compared with the MRvol by RT3DE. A possible reason is that the 2D MAPLAX and MAA4C diameters may approach the 3D major diameters, and the MAA2C may be close to the 3D minor diameters as previous findings [5,16]. Based on the assumption of circular geometry, the monoplanar measurements of MA diameter and false geometric assumption are crucial factors of error using the 2D TTE QPD method. This error is important because the MA diameter is squared to derive the CSAMA in the geometric circular assumption formula, which result in an overestimation of the CSAPLAX and CSAA4C and an underestimation of the CSAA2C. Because of these, the corresponding SVMA calculated by CSAPLAX or CSAA4C is overestimated, and the corresponding SVMA calculated by CSAA2C is underestimated. Consequently, the QPD-MAPLAX and QPD-MAA4C overestimated the MRvol and QPD-MAA2C underestimated the MRvol, which may cause over- or underestimation of MR severity. In our present study, compared with MRvol by RT3DE, MR severity using QPD-MAPLAX and QPD-MAA4C were overestimated in 23 (26.1%) patients and in 12 (13.6%) patients, respectively, and MR severity using QPD-MAA2C was underestimated in 7 (10.2%) patients.
Based on that the MA is oval with the major and minor diameters previously demonstrated [5,14,15]. In this study, assuming that the MA was ellipse geometry, there was no significant difference of MRvol (mean difference = 1.7 ml, P = 0.0844) between the QPD-MAA4C+A2C and the RT3DE. This is because the MAA4C diameters may approach the 3D major diameters, and the MAA2C may be close to the 3D minor diameters. The CSAMA calculated by 2D MAA2C and MAA4C diameters using ellipse geometric assumption formula (CSAMA = 0.785 × a × b) may be closer to the real CASMA, which led to an accurate evaluation of corresponding SVMA and MRvol by QPD-MAA4C+A2C and may more accurately assess MR severity. In our present study, although MR severity using QPD-MAA4C+A2C was slightly overestimated in 3 (3.4%) patients, Chi-squared revealed no significant difference (P = 0.724). Since the MAPLAX diameter was larger than the MAA4C (3.0 ± 0.4 vs 2.9 ± 0.4, P < 0.001),which resulted in the fact that the CSAPLAX+A2C was larger than the CSAA4C+A2C, the corresponding MRvol by QPD-MAPLAX+A2C was overestimated (mean difference = 6.8 ml, P = 0.0002) compared with the RT3DE. As for the overestimation of MRvol (mean difference = 15.2 ml, P < 0.0001) by QPD-MAPLAX+A4C, this could be related to the fact that the MAA4C diameter was larger than the MAA2C (2.9 ± 0.4 vs 2.7 ± 0.3, P < 0.001),which led to an overestimation of the corresponding CSA PLAX+A4C and SVMA, thus overestimating the MRvol. The smaller difference of the result between the MRvol by QPD-MAA4C+A2C and RT3DE was probably because the MA has an elliptic shape with a saddle-shaped 3D structure, and there are dynamic changes in its shape and position in different diseases during the cardiac cycle [17-20].
Previous study by Lewis JF observed a high correlation between thermodilution- derived stroke volume and Doppler-determined mitral inflow volume, and did not find significant difference between the use of assumption of a circular geometry of MA from the A4C view and the use of assumption of a ellipse geometry of MA from the A4C and A2C views [21]. However, the study by Rokey R found that the average regurgitant volume by the Doppler method (6.04 ± 3.09 liters/min), assuming that the MA was circular geometry from the A4C view, was slightly higher than that obtained by angiography (5.33 ± 3.48 liters/min), although not significant [22]. Similar results were obtained in study by Enriquez-Sarano M in which the assumption of a circular geometry of MA from the A4C view by the Doppler method mildly overestimated the MA stroke volume and significantly overestimated regurgitant volume [23]. Most of the earlier studies of Doppler method was mainly based on the standard angiographic grading method, which is subjective and influenced by many factors, including catheter position, rhythm disturbances, amount and velocity of dye injected, chamber size, and radiogram penetration [24]. Even the quantitative angiography, which makes use of left ventriculographic stroke volume for mitral valve flow and thermodilution for cardiac output, has conspicuous limitations. The error of cardiac output measurement is between 5% and 10% for thermodilution and between 10% and 15% for angiography, leading to a greater error when they are combined into the MR [24].
Echocardiography is the most commonly method for evaluating MR severity, and the QPD method has been successfully introduced into routine clinical practice for assessment of MR severity [4]. The QPD method is based on accurately evaluating the CSAMA and CSALVOT. The MA diameter was measured in the A4C view and the CSAMA was derived as 0.785 d2 assuming that the MA is circular geometry as previously recommended [4]. Unfortunately, the human left heart and mitral valve do not provide the ideal conditions for the application of assumption of a circular geometry of MA, which eventually diminish the accuracy of assessment of MR severity. Previous studies have been demonstrated that the MA has a saddle-shaped contour and the CSA of the MA are oval [5,13-15]. Therefore, our aim of the present study is to find the appropriate geometric model and the optimal MA diameters combination for traditional 2D TTE through systematic research, so as to measure the MRvol by 2D TTE QPD more accurately. To the best of our knowledge, no clinical studies have assessed the impact different geometric assumption of MA on the assessment of MRvol by QPD. This study showed that the QPD-MAA4C overestimated the MRvol assuming that the MA was circular geometry as previously recommended, and assuming that the MA is ellipse geometry, the MRvol with QPD-MAA4C+A2C correlated well and had good agreement compared with MRvol using EROA by RT3DE multiplied by the VTIMR. The QPD-MAA4C+A2C provided more accurate assessment of MRvol using ellipse assumption of MA than the QPD-MAA4C applying circular assumption previously recommended.
Limitations
First, a limitation of a true gold standard for calculating MRvol was absent in the present study. In this study, the MRvol derived from EROA by RT3DE multiplied by the VTIMR was used as the reference method, which has been documented as an accurate method [6,7], and some studies have used it as reference method [10,25]. However, RT3DE has limited spatial resolution of the reconstructed image, which may lead to biased results [26]. Second, this study did not evaluate the dynamic changes of 3D structure and CSA of the MA in different diseases and cardiac cycles. Third, in this study, the relationship between 3D MA diameters and 2D diameters in different views, as well as the geometry of LVOT were not evaluated, which may add to further errors in calculating MRvol by QPD. Fourth, this present study did not address the significance to stratify the results in primary and secondary MR, and further researches and follow-up data are necessary to explore. Finally, further studies are needed to confirm the results of MRvol by QPD-MAA4C+A2C based on ellipse assumption of MA.