Quantitative Assessment of Mitral Regurgitation

How Best to Do It

Image Acquisition for VCW

A modified parasternal long-axis view is best to image the VC with the transducer laterally translated or angulated, if necessary, to allow complete visualization of the MR jet (3). Although apical transthoracic echocardiography (TTE) acquisitions with the transducer perpendicular to the mitral coaptation plane can be used, this is generally not recommended because of limitations in lateral spatial resolution. A 2-chamber view should not be used because this view is oriented parallel to the line of leaflet coaptation and may exaggerate the MR severity when the MR jet is asymmetrical, with the longer axis occurring through the coaptation line. The transducer should be adjusted as necessary to obtain the largest MR jet size. The focus should be moved to the valve, and the depth and sector width should be minimized to focus on the valve. The color sector should be as narrow as possible to maximize lateral and temporal resolution (3). An aliasing velocity of 50 to 70 cm/s should be used, with the color Doppler gain set just below the threshold for noise. Ideally, the proximal flow convergence region (PFCR), the VC, and the downstream expansion of the MR jet should be included in the acquisition (Fig. 1).

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Figure 1

VCW Measurement

(A) Color-suppressed parasternal long-axis image and (B) the mitral regurgitation (MR) jet with the vena contracta width (VCW) measurement are shown. (C) Calculation of the vena contracta area using a circle assumption. EROA = effective regurgitant orifice area; PFCR = proximal flow convergence region.

VCW measurements can also be performed using transesophageal echocardiography (TEE) at a midesophageal level with an image acquired perpendicular to the mitral commissural plane (≈120°) with image optimization as for TTE. Because of the proximity to the mitral valve, multiplanar capabilities, and higher resolution, VCW measurements with TEE are more accurate than those with TTE (3).

How to Measure the VCW

After image quality is determined to be adequate, each systolic frame should be examined to identify the frame with the largest and best visualized VC. The largest VC can occur at different points in the cardiac cycle depending on the underlying etiology of MR. The image should be zoomed prior to measurement. The VCW is the narrowest dimension of the neck between the PFCR and flow expansion in the atrium just distal to the mitral valve (Fig. 1B). It should be measured from one end of the color jet to the other end perpendicular to the MR jet (Fig. 1B). In the context of multiple MR jets, individual VCWs are not additive; however, the cross-sectional area calculated using a shape assumption (Fig. 1C) can be additive.

Image Acquisition for Vena Contracta Area

The first step in image acquisition for vena contracta area (VCA) is to ensure good-quality electrocardiogram tracing for triggering. The transthoracic transducer position or the TEE plane that provides the best 2-dimensional (2D) view of the mitral valve and the MR jet should be the starting point for the 3-dimensional (3D) acquisition. With TTE (Online Fig. 1), either parasternal or apical TTE transducer positions can be used; most studies describing this technique have used apical images (8–11). Before 3D acquisition, the 2D image should be optimized as described previously, with inclusion of the PFCR, VC, and at least one-third of the downstream jet in the image. During 3D acquisition, gain and compression settings should be in the midrange (50 to 60 units) (12). The spatial and temporal resolution of the 3D acquisition can be maximized by adjusting the acquisition sector (minimal lateral width and elevation height to cover the mitral valve) and the color Doppler sector (small as possible) and by increasing the number of heart beats over which the acquisition is obtained (i.e., using electrocardiogram-gated acquisition). A full-volume acquisition is then obtained. Newer ultrasound systems will allow real-time optimization of the 3D color Doppler in live 3D mode or single heart-beat full-volume mode, but the acquisition should still be gated. End-expiratory breath-hold is desirable for gated acquisitions, and all 3D volumes should be checked perpendicular to the ultrasound sweep plane to ensure that stitching artifacts are absent (Fig. 2H). Several different 3D volumes using different transducer positions or TEE imaging planes should be obtained to ensure that good-quality data are available for post-processing.

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Figure 2

VCA Measurement With Multiplanar Reformat of the 3D TEE Data

(A and B) Systolic 2-dimensional planes created from the volume data (F). (C and D) MR jet with the B-mode turned off to better delineate the VC. (E) Short-axis (en face) view of the vena contracta area (VCA) with planimetry showing an area of 0.60 cm² (consistent with severe MR). (F) Volume data. (G) Multiple parallel en face views of the VCA (parallel dotted lines in C and D) that can be used to choose the best image for planimetry. (H) Illustration of stitching artifact. Abbreviation as in Figure 1.

How to Measure VCA

Using 2D long-axis images (systolic phase) that are automatically generated from the 3D volume by post-processing software (Figs. 2A and 2B, green and red boxes), the longitudinal planes (red and green lines) are adjusted to bisect the regurgitant jet in both images. Each systolic frame is then examined to identify the frame in which the MR jet is the largest and best visualized—the timing of this may vary, depending on the etiology of MR (13,14). Once this systolic frame is identified, the short-axis plane (Figs. 2A and 2B, blue line) is moved up and down orthogonal to the regurgitant jet and tilted (in the jet direction) until the cross-sectional area of the VC can be visualized (Fig. 2E, blue box). VCA is the narrowest cross-sectional area of the color Doppler jet at valve coaptation level or just within the left atrium. Adjacent systolic frames are re-examined in the short-axis plane to identify the largest VCA in systole while the short-axis plane (blue line) is still at the VC. The en face image should then be viewed on full screen and magnified for direct planimetry of the color flow signal (Fig. 2E) (11). An example of this measurement using TTE is provided in the Online Appendix (Online Fig. 1).

Several steps may help better delineate the axial location of measurement and improve reproducibility. Removal of the B-mode image (Figs. 2C and 2D) allows examination of the long-axis color Doppler alone to more easily identify the narrowest neck of the color jet. The B-mode can then be turned back on to confirm location relative to the site of valve coaptation. Reformatting the 3D volume (Fig. 2F) to obtain an en face view of the VCA can be a guide to the shape of the expected VCA in the short-axis plane (Fig. 2E). Automatically generated multislice planes parallel to the initial user-defined plane (blue plane) may allow selection of the best VCA to planimeter (Fig. 2G).

Image Acquisition for RVol and RF

Mitral inflow SV is obtained from apical 4-chamber (or optionally 2-chamber) cine-loops. The depth should be minimized and the sector-width reduced to focus on the mitral valve and left ventricle (LV). The image should be centered on the mitral annulus in zoom mode and the focus moved to the annulus (Figs. 4A and 4B). The 4-chamber view should not include any part of the left ventricular outflow tract (LVOT), and the atrium and ventricle should not be foreshortened. The cine-loop should consist of at least 2 cardiac cycles to allow choice of the best cycle for analysis. Inflow velocities are measured using pulsed-wave Doppler with a 1- to 3-mm sample placed at the mitral annulus in the exact plane in which the annular diameter is measured. Data for 3 to 5 beats in sinus rhythm and 5 to 10 beats in atrial fibrillation should be obtained at a sweep speed of 50 to 100 mm/s (Fig. 4C). Spectral Doppler tracings should be of good quality with adequate gain settings and absence of spectral broadening. Breath-holding will improve the consistency of the obtained pulsed-wave Doppler recording.

Aortic SV requires a zoomed parasternal long-axis cine-loop to measure the LVOT diameter (Fig. 4D), with the depth and focus set to optimize visualization of the LVOT perpendicular to the ultrasound beam. The basal insertion points of the aortic leaflets and the proximal aortic root should be clearly seen in the acquisition (Fig. 4D). At least 2 cardiac cycles should be acquired. The apical 5- or 3-chamber view is then used to place a 3- to 5-mm pulsed-wave sample approximately 5 mm proximal to the aortic valve to measure LVOT flow velocities in the center of the LVOT, at the location where LVOT diameter is measured (Fig. 4E). The closing click of the aortic valve is often seen when the sample volume is correctly positioned (16).

These measurements can also be obtained with TEE using midesophageal views for the mitral annular and LVOT dimensions (0 and 120°) and mitral inflow pulsed-wave Doppler (0 or 90°). A transgastric view is needed to obtain the LVOT Doppler measurements.

How to Calculate RVol and RF

With the 4-chamber cine-loop (Fig. 4A), the mitral annular diameter is measured at the base of the leaflets during early diastole to mid-diastole, 1 frame after the leaflets begin to close after passive filling (16). Using this diameter, the cross-sectional area of the mitral annulus can be calculated using π(D/2)², assuming that the annulus is circular (3). Alternatively, the annular measurements from the 2- and 4-chamber views can be used to calculate the area using an ellipse assumption (π[D/2 for 2 chamber] × [D/2 for 4 chamber]). The brightest edge of the pulsed-wave Doppler (modal velocities) should then be traced to obtain a VTI (Fig. 4C). Mitral inflow SV (mitral valve cross-sectional area × mitral inflow VTI) is measured from averaging annular and Doppler measurements over multiple cardiac cycles. LV SV obtained by the biplane Simpson method can be used as a surrogate for mitral inflow SV (17) in the absence of other sources of variability in SV measurement such as ventricular septal defect (VSD) and aortic regurgitation.

For the aortic SV, LVOT diameter measurements should be taken from inner edge to inner edge using a zoomed image (Fig. 4D). Although the largest diameter from 3 to 5 repeated measurements is often used (16), an average of the measurements may be more robust. The LVOT pulsed-wave Doppler should be traced for multiple heart beats with the considerations described for the mitral valve. The aortic SV (ml) = LVOT cross-sectional area (πr²) × LVOT VTI.

This method of MR assessment is challenging technically, and operator experience is important to ensure reproducibility. Centers that are successful with this method first use the technique to ensure that calculations of mitral inflow and aortic outflow SV match in patients without mitral or aortic valve disease or VSD before applying it to patients with MR. Assumptions about circular geometry of the mitral valve and LVOT can add to further errors in MR quantification.

Image Acquisition and Measurement of RVol and RF

MR RVol can be measured using the difference in LV SV obtained from a 3D acquisition of the LV (difference between LV end-diastolic and systolic volumes) and aortic SV measured using the 2D method (described previously) or 3D method (described in the next section). High-volume–rate 3D full-volume acquisition (>30 volumes/s) from an apical window, without stitching artifact and dropouts, should be used to measure LV SV. This method is only valid in the absence of other sources of variability in SV measurement such as VSD and aortic regurgitation.

Mitral RVol and RF can also be calculated with 3DE using the VCA (described previously) or PISA technique (described in the next section).

Potential Novel Method for RVol and RF Quantification

A novel method used to calculate RVol and RF is to obtain 3D color Doppler acquisitions at the mitral and aortic valves and use both the color Doppler velocity data and area to calculate SV at each orifice (Fig. 5) (18). Although this technique has been validated using 2DE (19), 3D studies have shown accuracy in separate measurement of mitral and aortic SV (20,21), with only preliminary data on MR quantification (22). Only a brief description of this technique is provided; previous publications have provided further acquisition details (18,20,21).

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Figure 5

3-Dimensional Color Doppler Used to Quantify Mitral Inflow and Aortic Outflow Stroke Volumes

(A to C) Patient without MR. The mitral inflow stroke volumes (SVs) range from 80.0 to 77.1 ml depending on the RR interval; similarly, the aortic SVs range from 72.1 to 75.0 ml. On average (average of 3 beats), there is minimal difference between the inflow and outflow SVs. (D to F) Patient with mild MR. On average, there is 17 ml of mitral regurgitant volume. Abbreviation as in Figure 1.

A full-volume 3D acquisition of the LV including the mitral and aortic valve with color Doppler sector covering both valves in the same volume or acquired as 2 separate volumes depending on the temporal resolution (minimum volume rate >10/s) is needed (Fig. 5). Color Doppler settings should be adjusted to avoid color bleeding into B-mode, and the Nyquist limit should be maximized. Breath-holding is required for gated acquisition. Custom software is necessary for the quantification of SV using user-defined planes at the valves (20,21). The ability to measure mitral inflow and aortic outflow SV with a single 3D acquisition in an automated manner (18) may encourage the use of this method for MR quantification (22).

CMR

Mitral RVol and RF can be obtained with CMR using direct and indirect methods. Indirect methods include measurement of the difference between: 1) LV SV by planimetry of short-axis cine images and aortic SV using PC imaging; 2) LV and RV SVs by planimetry; or 3) mitral inflow and aortic outflow SVs by using PC imaging. The direct method uses short-axis PC imaging at the level of the mitral valve with through-plane phase encoding to directly measure RVol.

Image Acquisition

How to Measure RVol and RF by CMR

PC Analysis

The PC acquisition provides magnitude and phase images (Fig. 6). Regions of interest (ROIs) over the area of flow can either be drawn on the magnitude image and transferred to the phase image or drawn directly on the phase image. For mitral inflow SV quantification, an ROI encompassing only the mitral inflow orifice should be carefully drawn through all acquired systolic frames (Figs. 6C to 6F). This ensures that the mitral inflow measurement is not contaminated by other flows. Although this is done in a semi-automated manner, it can be time intensive and subject to interobserver variability. Once all ROIs are drawn, mitral inflow SV is automatically computed using velocity data in the phase image and the ROI (Fig. 6G). Similarly for the aortic SV, an ROI is drawn encompassing the inner edge of the aortic wall (Figs. 6H and 6I). This is less subjective because the aortic wall is usually well defined, allowing automated propagation of the ROI from one image with subsequent minor adjustments of each frame if needed. With these data, the MR RVol can be calculated as the difference between the mitral inflow (Fig. 6G) and aortic outflow SVs (Fig. 6J) by PC imaging or as the difference between LV SV by planimetry and aortic SV by PC data. RF is the RVol divided by the mitral inflow SV or the LV planimetry SV.

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Figure 6

Mitral Inflow and Aortic Outflow SV Quantification With Through-Plane PC Imaging

(A) Magnitude image. (B) Systolic phase-contrast (PC) image. (C to F) Representative diastolic PC images with manual planimetry (red) of the inflow orifices. (G) Time-volume curve illustrating the mitral inflow SV. (H) Ascending aorta magnitude image. (I) 2 representative phase images with planimetry of the aorta during systole. (J) Outflow time-volume curve from illustrating aortic SV. In this case with concomitant aortic regurgitation, both forward and reverse volume curves are shown. LV = left ventricle; RV = right ventricle; other abbreviation as in Figure 5.

If the PC images are used for the direct quantification of RVol, an ROI should be drawn on each systolic frame to encompass the regurgitant flow on the phase images (Online Fig. 5). Integration of flow through systole over this ROI results in computation of RVol.

Image Acquisition and Analysis

Current CT technology does not allow flow measurements across the valves. However, one study has illustrated RVol and RF measurement using LV and RV contouring similar to that described for CMR (30). This technique requires a retrospectively gated cardiac acquisition with multiphase reconstruction followed by either semiautomated calculation of LV and RV SV or calculation of ventricular SV using reconstructed short-axis slices to perform endocardial contouring identical to CMR. Despite the feasibility of this method, CCT is still limited by temporal resolution and the need for retrospectively gated acquisition, which increases radiation exposure. In addition, the LV/RV SV method is only valid in the absence of concomitant valvular disease or intracardiac shunting. This technique should therefore be the last resort for MR severity quantification.

Image Acquisition for PISA

The PFCR should be imaged from an apical view (TTE) or the midesophageal view (TEE). The optimal PFCR is usually seen in either the 4- or 3-chamber view. First, the mitral valve should be centered in the image with the sector optimized by width and depth to ensure the highest possible temporal and spatial resolution (Fig. 7). The color sector is adjusted to include the mitral valve, a portion of the ventricle, and base of the atrium. Aliasing velocity should be adjusted either by baseline-shifting the color in the direction of the MR to 30 to 40 cm/s or by lowering the Nyquist limit to optimize visualization of the PFCR (31). The color Doppler variance map should be turned off (usually the default with most software). The cine-loop is then reviewed frame-by-frame during systole to identify the largest PFCR where the first isovelocity shell is clearly visualized. A continuous wave (CW) Doppler cursor is then aligned parallel to MR flow to obtain the peak velocity of the MR (Vmax, cm/s) and the MR VTI (VTI_MR, cm), with velocity measurements taken from the outer border of the envelope (Fig. 7C) (16).

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Figure 7

EROA and RVol Quantification Using Transesophageal Echocardiography in a Patient With Moderately Severe MR

(A and B) The proximal isovelocity surface area radius is measured from the first aliasing velocity to the leaflet using color compare (A vs. B). (C) Continuous wave Doppler is used to compute the VTI. (D) Illustration of effective regurgitant orifice area (EROA) and regurgitant volume (RVol) calculation. AV = aliasing velocity; other abbreviations as in Figures 1 and 4.

How to Measure EROA, RVol, and RF Using the PISA Technique

In measurement of the radius of the PFCR (Fig. 7), recognition of the outer surface (red-blue interface of first aliasing velocity) is easier than identification of the center of the MR orifice. Use of “color compare/suppress” options or switching the color Doppler on and off can improve accuracy in identifying this point (Figs. 7A and 7B). The EROA is calculated using the continuity principle with the below formula (Fig. 7). RVol can then be calculated as EROA × VTI_MR and RF is RVol/mitral inflow or LV SV (also see the section on RVol and RF measurements above)EROA=2πr2×Aliasin⁡gVelocity(cms)MRVmax(cms)

A simplified formula can be used as a rapid screening tool. With the Nyquist limit at 40 cm/s and the MR peak velocity assumed to be 500 cm/s, then the formula simplifies to EROA = r²/2. This method makes a number of assumptions and should only be used as a screening tool or when CW Doppler is not obtained. A number of important considerations regarding the PISA technique are summarized in the Online Appendix and Online Figure 6. Perhaps most important is that using the largest PFCR may overestimate severity when MR is not pansystolic.

Image Acquisition for PISA Quantification

With TTE, 3D PFCR should be imaged from an apical view, with the best initial transducer position determined by 2D imaging. With TEE, the midesophageal long-axis view from which the MR is best seen should be selected. After 2D image and color optimization, the transducer should be adjusted to place the PFCR at the center of the acquisition volume. Color Doppler baseline shifting can be performed at the time of acquisition or during post-processing, depending on the software. Misalignment artifacts can be avoided by acquisition of the full volume with suspended or shallow respiration or using a single heart beat acquisition (although this is at the cost of reduced temporal resolution). The single beat method is best used to optimize the B-mode and color Doppler in real-time 3D (e.g., to steer the beam to ensure that the MR jet is included in the volume or to change lateral width or elevation height of the volume to include a larger portion of the mitral valve) before subsequent high-resolution acquisition over several cardiac cycles. The acquired volume should be examined to ensure that the complete MR jet was captured and that no artifacts are present. A CW spectrum of the MR jet is necessary to calculate the EROA and RVol.

Image Acquisition for Anatomic Regurgitant Orifice Area Measurement

For planimetry of the anatomic regurgitant orifice area (AROA) using TEE, 2 different acquisitions can be used from the midesophageal position: zoom-mode or full-volume acquisition (12); the only contemporary study used zoom-mode (32). We position the 3D-zoomed image from an optimized 2D view of the mitral valve (e.g., at 120°). With 2 orthogonal views of the mitral valve, the 3D volume sector is planned by adjusting the height of the volume sector to include the mitral valve leaflets in systole and diastole and by lengthening the volume sector to include the entire mitral annulus and at least a portion of the aortic valve for orientation (Online Fig. 7). The size of the 3D volume sector affects the temporal resolution of the acquisition and should be adjusted to obtain a volume rate >10 volumes/s. The line density should be set at medium or high (with each 3D system, the user should first identify the appropriate gain and line density settings in patients without MR to ensure that the acquisition does not have dropouts, particularly at the coaptation lines that may mimic a regurgitant orifice). The 3D volume should then be turned downward (toward the viewer) and rotated to orient the aortic valve in the 12 o'clock position (12) (Online Fig. 7), customarily referred to as the “surgeon's view.” The image should be carefully examined to ensure that no dropouts are present and that the valve is within the acquired volume throughout the cardiac cycle. Alternatively, a full 3D volume (12), including the LV and the mitral valve, can also be used to measure the AROA. However, the need for gated acquisitions predisposes this technique to stitching artifacts. The AROA can also be measured with 3D TTE using zoom or full-volume acquisitions, although the accuracy and feasibility of this method is yet to be described.

How to Measure the PISA

Although several methods for 3D PISA quantification have been described (33–35), no standard method exists. Four quadrants are displayed in the post-processing software (Figs. 8A,8B, 8D, and 8E). The first step is to obtain an optimal view of the MR jet (see VCA section) (Figs. 8A and 8B). The PFCR size can vary throughout systole depending on the etiology of the MR. Although the systolic frame with the largest and best visualized PFCR should be used for analysis, this may overestimate the severity of MR. The color Doppler aliasing velocity is shifted in the direction of the MR jet to between 20 to 40 cm/s. Then the axial (blue) plane is moved to the base of the PFCR (ventricular side of the mitral valve) and adjusted using both of the long-axis views (red and green boxes) to obtain an en face view of the base of the PFCR (Figs. 8C and 8D). This view provides a measure of the length (D1) and width (D2) of the base of the PFCR. With this view, the red or green lines (planes) can be moved along the base of the PFCR (Fig. 8C, red lines) to obtain a long-axis view of the PFCR with the largest vertical radius (34,36). The radius should be measured as described for 2D PISA (Fig. 8F; color can be turned off during post-processing to aid this process). PISA is calculated from the traditional hemisphere formula (2πrz) or the hemiellipse assumption (using the radius, length, and width). Alternatively, the 3D surface area of the PISA can be measured using complex surface reconstruction from multiple 2D measurements (33,35,36), but this is impractical. Recent preliminary work has illustrated a method of automated segmentation of the 3D PFCR without shape assumptions (37). The accuracy of this technique in the clinical setting remains undefined.

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Figure 8

PISA Measured From a 3-Dimensional Full-Volume Color Doppler Acquisition

(A and B) The systolic long-axis views are optimized to visualize the MR jet. The largest systolic proximal isovelocity surface area (PISA) is used to adjust the short-axis plane (blue line) to obtain an en face view of the base of the PISA (C and D). (E) The color Doppler baseline is adjusted to 39.6 cm/s. (F) Multiple orthogonal views can be generated (C and D, red planes) to obtain the largest 2-dimensional PFCR. The radius, length, and width measurements are shown (A and D), and the longest PISA radius is shown (F). Abbreviations as in Figure 1.

How to Measure the AROA

With post-processing software, the 3D volume should first be tilted to visualize the mitral coaptation line from the atrial aspect (Online Fig. 8D). The 2 planes on the 3D image should then be adjusted to place one parallel and the second perpendicular to the commissural line (cutting through the aortic valve), generating an intercommisural and outflow tract view, respectively (Online Figs. 8A and 8B) (32). Using these 2 long-axis views, the 2 planes (blue and red lines) are moved parallel to the assumed location of the MR orifice in each of the systolic frames and then rotated along the assumed regurgitant jet direction to identify the maximal regurgitant orifice (a 2D color Doppler acquisition viewed separately can help with this orientation). The axial plane (blue line) is positioned orthogonal to the 2 previous planes and moved up and down through the coaptation line to identify the smallest regurgitant orifice (Online Fig. 8C). The AROA is zoomed, and planimetry is performed using the area tool to carefully follow the inner border of the leaflets. This same technique can be used if a 3D full-volume data set is used for analysis.

CMR Imaging and CCT

PISA cannot be measured with CMR or CCT, but AROA can be measured directly by both methods.