Echocardiographic Assessment of Mitral Stenosis Orifice Area: A Comparison of a Novel Three-Dimensional Method Versus Conventional Techniques : Anesthesia & Analgesia

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Perioperative Echocardiography and Cardiovascular Education: Original Clinical Research Report

Echocardiographic Assessment of Mitral Stenosis Orifice Area: A Comparison of a Novel Three-Dimensional Method Versus Conventional Techniques

Karamnov, Sergey MD; Burbano-Vera, Nelson MD; Huang, Chuan-Chin ScD; Fox, John A. MD; Shernan, Stanton K. MD

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Anesthesia & Analgesia 125(3):p 774-780, September 2017. | DOI: 10.1213/ANE.0000000000002223
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Mitral stenosis (MS) is the most common valvular complication of rheumatic fever, a devastating disease highly prevalent in developing countries.1–4 In Europe, rheumatic MS accounts for 9.5% of left-sided valvular heart disease,5 while senile calcific MS and mitral annular calcification remain a persistent pathological disorder in the United States.6 The treatment of MS may be directed towards medical management, percutaneous balloon dilation, or surgical intervention.7 Triaging patients with MS to the correct treatment involves a determination of its progression, which is usually based on multiple parameters including clinical symptoms and the degree of stenosis commonly defined by a comprehensive echocardiographic examination.

Current published guidelines recommend the use of both qualitative and quantitative echocardiographic measures of MS severity, including transvalvular pressure gradients and mitral valve (MV) orifice area.8 A comprehensive echocardiographic evaluation of MS commonly includes two-dimensional (2D) echocardiography using anatomic and functional methods. However, the complex three-dimensional (3D) structure of the MV apparatus poses challenges to the accurate measurement of its orifice area by 2D imaging modalities. 2D planimetry is frequently used to define the anatomic MV orifice, but is based on geometric assumptions that the MV orifice is a flat 2D structure. Doppler echocardiographic techniques including the continuity equation, pressure half-time (PHT), and proximal isovelocity surface area (PISA) can also be used to calculate functional MV area, but have limitations as well.9,10 While 3D echocardiographic techniques including 3D planimetry may enable an improved delineation of the complex, asymmetric anatomic area of both normal and stenotic MVs, current reported techniques are still vulnerable to certain geometric assumptions.11,12

In this study, we hypothesized that the assessment of rheumatic MS severity using a novel 3D echocardiographic method, which minimizes geometric assumptions, would yield significantly different values of MV orifice area compared with 3D planimetry and both conventional 2D anatomic and functional methods.

METHODS

Study Population

T1
Table.:
Patient Demographic Data

Retrospective data were collected as part of an institutional review board–approved protocol with a waiver of consent. Twenty-six adult cardiac surgery patients with at least moderate preoperatively defined rheumatic MS who underwent MV replacement at the Brigham and Women’s Hospital were identified (Table). Patients with either absent or technically inadequate 3D transesophageal echocardiographic (TEE) studies and those with persistent atrial fibrillation or significant aortic valve insufficiency were excluded. All patients in the study group had greater than mild mitral insufficiency.

Intraoperative 3D TEE Data

Intraoperative 3D TEE images were obtained retrospectively from a departmental database consisting of routinely performed 2D and 3D TEE examinations. All images were acquired prior to surgical correction of MS by National Board of Echocardiography–certified providers using matrix-array probes (X7-2t; IE33; Philips Healthcare, Inc, Andover, MA). All 3D measurements were obtained from full volume data sets of the mitral apparatus, reconstructed from 6 consecutive heartbeat subvolumes, which were gated to the electrocardiogram while mechanical ventilation was transiently held to prevent stitching artifacts.13 All video clips used for both 2D and 3D analyses were acquired within a brief period of time to minimize changes associated with intraoperative hemodynamic volatility. Postprocessing grayscale gain settings were standardized and maintained at 50% levels for all measurements.

Three-Dimensional Mitral Valve Orifice Area

F1
Figure 1.:
Multiplanar reformatting of the mitral valve, acquired from a three-dimensional (3D) transesophageal echocardiographic (TEE) full volume data set. Upper left, Mid-esophageal mid-commissural TEE equivalent view. Upper right, Mid-esophageal long-axis TEE equivalent view (orthogonal to the upper left panel). Lower left, Short-axis view of the mitral annulus (ie, “surgeon’s view”). The mitral valve annulus is derived from manually designated data points highlighted in green. Lower right, 3D parametric model of the reconstructed mitral valve annulus and leaflets (Qlab 10; MVN; Philips Healthcare, Inc). A indicates anterior leaflet annular attachment; AL, anterolateral commissure; Ao, aortic valve annulus; P, posterior leaflet annular attachment; PM, posteromedial commissure.
F2
Figure 2.:
Manual tracings of mitral valve (MV) leaflets in selected slices shown sequentially from the anterior-lateral (1) to the posterior-medial commissure (8). The slices were acquired from the frame with the largest diastolic orifice opening derived from a 3-dimensional transesophageal echocardiographic full volume data set. The MV orifice in each slice is identified by the gap between the tips of the leaflets highlighted in green (Qlab 10; MVN; Philips Healthcare, Inc).
F3
Figure 3.:
Parametric model of the mitral valve (MV) reconstructed from a three-dimensional transesophageal echocardiographic full volume data set. Similar to the color coding for the parametric model generated using Qlab MVN (Philips Healthcare, Inc), when used to delineated a mitral regurgitant orifice area, the thin yellow line represents the leaflet coaptation line. The highlighted green line represents the perimeter of the mitral valve orifice (3DOA) at the leaflet tips, which is automatically calculated and projected to the forefront (Qlab 10; MVN; Philips Healthcare, Inc). 3DOA indicates 3-dimensional orifice area; A, anterior leaflet annular attachment; AL, anterolateral commissure; Ao, base of right aortic coronary cusp; P, posterior leaflet annular attachment; PM, posteromedial commissure.

3D orifice area (3DOA) was obtained off-line using a novel adaptation of commercially available software (Qlab 10.0; MVN; Philips Healthcare, Inc), which enabled measurement of 3D MV diastolic area independent of geometric assumptions. Each 3DOA was measured from a diastolic 3D parametric model of the MV (Qlab 10.0; MVN; Philips Healthcare, Inc)14 using the frame displaying the largest diastolic MV opening, as determined by 2 independent echocardiographers with significant experience using this software program. 3D data sets were presented off-line in 4 quadrants, including three 2D orthogonal anatomic planes which displayed 2 long-axis views (mid-esophageal long-axis equivalent and mid-esophageal mitral mid-commissural equivalent view) and 1 short-axis view parallel to the plane of the mitral annulus. The fourth quadrant represented a 3D volume-rendered view (Figure 1). 3DOAs were calculated as follows:

  1. Initially, 4 primary perimeter reference points or fiducials at the anterior, posterior, anterolateral, and posteromedial borders of the mitral annulus were manually tagged on the corresponding 2 long-axis orthogonal planes (Figure 1, left and right upper panels).
  2. The remainder of the MV annulus perimeter was then manually outlined by delineating intermediate reference points in 18 radial planes (ie, 36 reference points), which were circumferentially advanced around the long axis (Figure 1, left lower panel).
  3. The mitral leaflets were manually traced (6 trace points per centimeter) without geometric assumptions, along parallel and equidistant 2D long-axis planes from the lateral to medial border of the mitral annulus, while excluding the mitral orifice (Figure 2).
  4. The MV diastolic 3DOA was derived automatically and without geometric assumptions as the area excluded from the color-coded, 3D-rendered leaflet surface representing a topographical map of the mitral leaflets (Figure 3).

3D Planimetry

3D planimetry was measured using multiplanar reformatting on full volume 3D data sets and the same diastolic frame with the largest MV area that was used for the 3DOA analysis. The plane of interest was aligned at the narrowest portion of the funnel-shaped MV orifice (Qlab 10.0; 3DQ; Phillips, Inc) as previously described.11,12

Conventional 2D Methods

MV areas using PHT, PISA, and continuity equation were obtained according to European Association of Echocardiography/American Society of Echocardiography recommendations for echocardiographic assessment of MS.15

Statistical Analysis

Mean values of MV areas measured using the novel 3DOA techniques were compared with corresponding 3D planimetry and conventional 2D values. Two-tailed paired sample t tests were used to evaluate the significance of the differences between mean values. McNemar's exact tests were used to compare the percentage of the patients with severe MS determined by different methods. Bland-Altman plots were also constructed for each pair of compared measurements to examine the patterns of differences. Statistical analysis was performed using the R software (version 3.1.2; R Core Team, Vienna, Austria).16P values after Bonferroni correction are reported.

Power Calculation

In previous work on MV area assessment in patients with MS,17 the comparison between 2D and 3D methods demonstrated an average difference of approximately 1 SD. Therefore, we conducted a power analysis for an effect size of 1 SD when comparing 2D and 3D methods for the assessment of MS. A power analysis using G*Power 3.1 software18 showed that to detect an effect size of 1 SD with a probability of type I error of .05 and power of .95, a sample of 16 patients would be required.

This article adheres to the applicable EQUATOR guidelines.

RESULTS

F4
Figure 4.:
Differences between mitral valve area derived by 3-dimensional orifice area (3DOA) versus 3-dimensional planimetry (3DP) and conventional echocardiographic methods. A, Absolute differences between means of mitral valve areas derived by 3DOA versus the 4 comparative methods. B, Box plots demonstrating the distribution of differences of mitral valve areas acquired by 3DOA versus the 4 comparative methods. CE indicates continuity equation; PHT, pressure half-time; PISA, proximal isovelocity surface area.
F5
Figure 5.:
Bland-Altman plots comparing mitral valve area derived by three-dimensional mitral valve orifice area (3DOA) with conventional methods. 3DP indicates 3-dimensional planimetry; CE, continuity equation; PHT, pressure half-time; PISA, proximal isovelocity surface area.
F6
Figure 6.:
Percentage of patients with severe mitral stenosis diagnosed by 3-dimensional mitral valve orifice area (3DOA) and conventional echocardiographic methods. 3DP indicates three-dimensional planimetry; CE, continuity equation; PHT, pressure half-time; PISA, proximal isovelocity surface area.

MV areas derived by PHT, PISA, continuity equation, 3D planimetry, and 3DOA (mean value ± SD) were 1.12 ± 0.27, 1.03 ± 0.27, 1.16 ± 0.35, 0.97 ± 0.25, and 0.76 ± 0.21 cm2, respectively. Areas obtained from the 3DOA method were significantly smaller compared to areas derived from PHT (mean difference, 0.35 cm2; 95% confidence interval [CI], 0.17–0.52 cm2, P < .0001), PISA (mean difference, 0.28 cm2; 95% CI, 0.11–0.44 cm2, P = .0002), continuity equation (mean difference, 0.43 cm2; 95% CI, 0.13–0.73 cm2, P = .0015), and 3D planimetry (mean difference, 0.19 cm2; 95% CI, 0.11–0.27 cm2, P < .0001; Figure 4). These significant mean differences are further illustrated by Bland-Altman plots (Figure 5), which demonstrate that there is no systematic pattern of variation in these differences depending on the size of measured area (ie, the dispersion of differences around their mean is similar all along the horizontal axis of each plot). MV orifice areas derived using the 3DOA technique also identified a significantly greater percentage of patients with severe MS defined as a valve area <1.0 cm2 (88%)15 compared to values obtained using PHT (31%, P = .006), PISA (42%, P = .01), and continuity equation (39%, P = .017) techniques, but not in comparison to 3D planimetry (62%, P = .165; Figure 6). To minimize the potential for echocardiographer-dependent bias, all measures of MV area were obtained by 2 independent investigators in a subset of 10 randomly selected patients. All measurements had excellent intraobserver and interobserver variability (Pearson correlation coefficient ≥ 0.80 and ≥ 0.85, respectively).

DISCUSSION

The relationship between mitral apparatus anatomy, functional geometry, and transvalvular flow is highly complex and remains an important area of continued investigation for both normal and pathophysiological conditions. The normal 3D saddle shape of the MV annulus, leaflets, and orifice along with the complex structure of the subvalvular apparatus and dynamic nature of their behavior during the cardiac cycle pose difficulties for precise evaluation of its geometry and function. Inflammatory processes observed in rheumatic heart disease and calcific degeneration of the MV significantly distort valve architecture even further, which raises additional challenges for precise valve assessment. Consequently, conventional 2D echocardiographic measures of MV orifice area, which are susceptible to geometric assumptions may not accurately represent the 3D geometry of this complex structure. Using 3D TEE data sets, we now demonstrate in cardiac surgical patients, with at least moderate preoperative rheumatic MS, that the 3D MV orifice is significantly smaller (over 30%) than measurements made using conventional 2D echocardiographic techniques. Furthermore, our results suggest that measuring the stenotic mitral orifice using 3D TEE data sets may result in the identification of a significantly higher comparative incidence of severe MS diagnoses.

Several treatment options are currently available to manage significant MS, including medical management, percutaneous balloon commissurotomy, and surgical correction. The choice of treatment is based on multiple parameters, including an echocardiographic assessment of MS severity. According to the American Heart Association/American College of Cardiology Valvular Heart Disease Guidelines, MV surgery should be considered for patients with MS and a valve orifice area ≤1.5 cm2, along with clinical parameters.8 In these settings, precise estimation of the MV orifice area is crucial, as it may directly impact a patient’s management.

Echocardiography is a useful instrument for evaluating MV anatomy and function in order to facilitate clinical decision-making. However, conventional echocardiographic methods that rely on 2D assessment of the mitral apparatus have significant limitations. For example, 2D planimetry is an anatomic method based on an assumption that the MV orifice is relatively flat and consequently does not take its complex 3D geometry into consideration. 2D planimetry is also significantly dependent on the selection and orthogonal alignment of the correct plane to the true MV orifice for accurate measurements, since oblique orientation can lead to an overestimation of the MV opening.17 Pressure half-time is a 2D method for calculating functional MV area based on the time to the atrioventricular pressure difference decay. However, PHT can be vulnerable to inaccuracies associated with preexisting left ventricular diastolic dysfunction, aortic regurgitation, and combined MS and mitral regurgitation9,19–21 due to the concurrent impact of these disorders on the time to pressure equilibration. The PISA technique is another method for calculating the functional MV orifice area in patients with MS, which relies on the assumption that the geometry of the flow convergence area on the left atrial side of the transvalvular flow is geometrically symmetrical and in the shape of a hemisphere. However, the PISA geometry for the effective regurgitant area in patients with functional mitral regurgitation and for the stenotic mitral inflow area in those with MS is highly variable and asymmetric.22,23 The continuity equation method can also pose limitations. In the absence of uninterrupted forward flow as in cases of mitral regurgitation or aortic regurgitation, the continuity equation method can produce unreliable results.15 Thus, despite being commonly utilized, conventional 2D methods for the evaluation of MS have important constraints that need to be taken into consideration when the derived data is used to guide clinical decision-making.

The imperfection of existing conventional methods serves as an incentive to develop new diagnostic tools for the precise evaluation of mitral apparatus anatomy including novel adaptations of 3D echocardiography. For example, Sebag et al17 assessed MV area in patients with MS using transthoracic echocardiography and 3D-guided biplane imaging. In their study, 2D short-axis images of the MV orifice were derived from 3D pyramidal volume data sets obtained with a matrix-array transducer. These investigators further demonstrated that their 3D method–derived MV areas were significantly smaller than those obtained by 2D transthoracic echocardiography without 3D navigation. While still assuming that the MV orifice has fundamental 2D geometrical characteristics, the results of this study nonetheless showed that 3D echocardiographic navigation may yet provide benefit for the precise estimation of the orifice area. In another study, Schlosshan et al11 evaluated MS using a novel 3D planimetry method. Multiplanar reconstruction of the MV derived from a 3D echocardiographic data set was used to identify the diastolic opening in patients with rheumatic MS. In this study, the MV opening areas derived by 3D planimetry were significantly smaller than those obtained by conventional 2D methods. The technology used by their group still used a 2D acquired plane from the 3D data set, which therefore did not enable comprehensive consideration of the 3D geometry of the MV orifice. Consequently, any technique that ultimately uses 2D images or planes cannot take into consideration the full extent of 3D geometry of the mitral apparatus since the normal, postrepaired, and especially the diseased MV orifice associated with severely distorted calcified structures is asymmetric. Thus, our results demonstrating significantly smaller 3DOAs in patients with MS compared to those measured by conventional methods should not necessarily be unexpected, but nonetheless have not been previously demonstrated with an echocardiographic technique that accounts for the complex 3D geometry of the MV orifice in this patient population.

Our novel adaptation of commercially available software designed specifically to evaluate the mitral apparatus independent of geometrical assumptions allows for comprehensive consideration of the 3D geometry of the MV orifice in patients with MS. The use of 3D echocardiographic full volume acquisitions preserves spatial resolution to enable precise leaflet delineation and the creation of an accurately reconstructed parametric model of the mitral apparatus. To minimize the chance of potential bias in delineating the MV orifice, postprocessing gain was standardized at the 50% level to achieve uniformity between 3D planimetry and 3DOA methods. Our technique also allowed for optimal temporal resolution to assure accurate selection of the desired frame within the cardiac cycle. The same diastolic frame was chosen for both 3D methods in each individual study to eliminate the risk of evaluating the orifice area at different stages of cardiac cycle. Thus, all efforts were made to optimize and standardize the technical aspects of 3D echocardiography image acquisition and display prior to the creation of the parametric model from which the measurement of the mitral orifice was obtained.

Certain study limitations warrant further discussion. First, the definition of the separation between leaflets and calcified subvalvular apparatus is performed manually and carries the potential for human error. As previously noted, postprocessing gain was standardized at the 50% level to achieve uniformity and minimize bias between data sets and patients. Second, our patient population demonstrated stenotic features of the MV that were more consistent with rheumatic heart disease rather than calcific degeneration according to standard echocardiographic criteria.15 Consequently, our findings may at least in theory be limited to patients with rheumatic heart disease. Third, all measurements in our study were obtained offline from data sets acquired using intraoperative echocardiographic techniques. Consequently, a conventional non-echocardiographic “gold standard” such as MRI was not included to validate our results due to the retrospective study design. While magnetic resonance imaging might be considered the ultimate “gold standard” for assessing MV orifice area, its inclusion in the echocardiographic literature is actually not common. Furthermore, MV area acquired by echocardiographic techniques has the advantage of enabling additional data sets to be obtained using other comparative echocardiographic techniques within a brief period of time. Thus, inaccurate comparisons due to differences in hemodynamics that could influence MRI measurements and would need to be obtained at a different time can be avoided. Fourth, despite our results, which are potentially consistent with a higher incidence of severe MS diagnosed by 3DOA compared to conventional methods, current American Heart Association/American College of Cardiology guidelines for management of MS are based on valve orifice area obtained by conventional 2D methods. Nonetheless, it should be recognized from even subjective assessment of the 3D images that the complex geometry of the mitral apparatus includes significant asymmetry along the variable height of the orifice periphery, which remains in continuity with the funnel shape created by the leaflets extending into the left ventricle. The inability of any single 2D plane to account for this asymmetry is responsible for its vulnerability to geometric assumptions of the stenotic MV orifice and, at least to a notable extent, the associated differences in the values between 2D and 3D techniques in our study. Finally, while significantly smaller MV orifice areas were demonstrated using the 3DOA method compared to all the other techniques, the inability to identify a statistically significant higher percentage of patients with severe MS using the 3DOA method compared to the 3D planimetry technique may in part be due to the relatively small number of patients, all of whom had a perioperative diagnosis of at least moderate rheumatic MS. Thus, in the absence of longitudinal studies validating 3D-derived measurements in a larger sample of patients with a wider spectrum of MS severity, the clinical relevance of our results has yet to be determined.

In conclusion, the MV orifice area derived by novel 3D echocardiographic methods for the assessment of MS highlights the significant asymmetrical geometry of this complex structure. Novel 3DOA measures of the MV orifice area in patients with MS are significantly smaller than the values obtained by conventional methods and may be consistent with a higher incidence of severe MS compared to 2D techniques. Further investigation is warranted to validate and determine the clinical relevance of 3D echocardiographic techniques used to measure MV area in patients with MS.

DISCLOSURES

Name: Sergey Karamnov, MD.

Contribution: This author helped with study design, data collection, data analysis, and manuscript preparation.

Conflicts of Interest: None.

Name: Nelson Burbano-Vera, MD.

Contribution: This author helped with data collection, data analysis, and manuscript preparation.

Conflicts of Interest: None.

Name: Chuan-Chin Huang, ScD.

Contribution: This author helped with data analysis and manuscript preparation.

Conflicts of Interest: None.

Name: John A. Fox, MD.

Contribution: This author helped with data collection, data analysis, and manuscript preparation.

Conflicts of Interest: None.

Name: Stanton K. Shernan, MD.

Contribution: This author helpd with study design, data collection, data analysis, and manuscript preparation.

Conflicts of Interest: Philips Healthcare, Inc: Other/Educator.

This manuscript was handled by: Nikolaos J. Skubas, MD, DSc, FACC, FASE.

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