Valvular disease is the most prevalent structural heart disease among adults and its burden is growing along with the increase in life expectancy.1 Mitral regurgitation (MR) is the second most frequent valvular disease, after aortic stenosis. Its natural history is very variable and highly dependent on the presence of symptoms. However, even in asymptomatic patients, the prognosis of severe MR is reserved. In addition to symptoms, age, atrial fibrillation, severity of MR, left atrial or ventricular dilatation, pulmonary hypertension, and compromised left or right ventricular function are all predictors of poor outcome.2,3
According to current guidelines, patients with symptomatic organic MR, and also asymptomatic patients with left ventricular dysfunction, atrial fibrillation, or significant pulmonary hypertension (>50 mmHg), should be referred for surgery.3 As for cases of ischemic MR, surgical treatment should be the choice in the presence of moderate to severe MR and a clinical indication for coronary artery bypass grafting.
Recent studies have shown that, amongst patients with severe MR and an indication for intervention, those selected for earlier surgery have improved survival.4 On the other hand, the possibility of mitral valve repair imposes an additional assignment on the accurate imagiologic evaluation of MR.5
Echocardiography is the preferred diagnostic test for assessing the presence and severity of heart valve disease, as well as its underlying etiology and severity.3 In the last decades, this has conventionally been performed by 2D evaluation through integration of color, pulsed-wave, and continuous-wave Doppler findings, providing data on anatomic and functional valve assessment.3 Recently, 3D echocardiography has shown its advantages in anatomic valve evaluation and 4D echocardiography is presenting volume color flow in realtime as a new methodology for the assessment of the severity of valvular pathology.
Limitations of the 2D Evaluation
Using color and Doppler techniques, several parameters have traditionally been available to determine MR severity, including jet/left atrial (LA) area ratio, vena contracta (VC) width, effective regurgitant orifice area (EROA) by proximal isovelocity surface area (PISA), and regurgitant volume by Doppler volumetric methods.5 However, all these methods present significant and well-recognized limitations and there is no single parameter allowing the correct grading of lesion severity alone; consequently, an integrated approach is mandatory.3
An extensive description of 2D echocardiography limitations is beyond the scope of this article, but a few points will be remembered. Both 2D color flow imaging and jet/LA area ratio, despite providing simple estimates of regurgitation severity, are easily confounded by variable hemodynamics and gain settings.5 Given this limitation, color flow imaging should only be used for MR diagnosis and not for its quantification.6
The width of the VC, which is defined as the narrowest cross-sectional area of the jet, reflects the regurgitant orifice area and the regurgitant volume.7 Nevertheless, this is true only for circular regurgitant orifices. Recent studies concluded that in most functional MR cases, the VC is elongated along the semilunar-shaped line of the incomplete mitral leaflet closure, making it impossible to rely on this parameter to assess the severity of such lesions.8
Effective regurgitant orifice area (EROA) calculation by the PISA formula requires the measurement of PISA radius, which is normally performed on the apical four-chamber view, using the vertical radius and ignoring the horizontal length.5,6 This assumes a hemispheric shape of proximal isovelocity; therefore, it can only be applied to circular regurgitant lesions.8 However, it was recently shown that the true PISA is generally more hemi-elliptical than hemispherical, and that an erroneous assumption of spherical PISA underestimates the severity of MR (see Figure 1).9
This is even more significant in those cases of functional MR.9,10 Despite attempts to introduce corrections to the PISA formula, differences in orifice shape, size, and leaflet angle made strict formulae always inaccurate in the presence of non-circular lesions.9,11,12 To minimize the effect of this limitation, cut-off values for severity grading are different in functional versus organic MR (≥0.2 cm2 versus ≥0.4 cm2, respectively).6,13
Quantitative Doppler methods, based on the difference between mitral and aortic stroke volume, are time-consuming, present several constraints at the time of measuring left ventricular outflow tract or mitral annulus diameter, and are of limited value in patients with combined regurgitant lesions.14 Therefore, they are not routinely recommended as a first-line method for quantifying MR severity.6
Thus, even using the recommended methods, 2D quantification of MR remains suboptimal, time-consuming, and dependent on the sonographer’s expertise, leading to continuous research of newer and more accurate quantification techniques.
The Emerging 4D Evaluation
The first 3D images of the heart were obtained by Dekker et al. in 1974.15 During the next two decades, 3D imaging required an arduous offline reconstruction of acquired 2D images, synchronized with the electrocardiogram and respiratory motion. This led to a pseudo-real-time imaging, requiring a long processing time, with use restricted to research laboratories.
Afterwards, the advance of matrix transducers enabled the acquisition of real-time images without the need for offline reconstruction, providing appropriate visualization of valvular morphology and quantification of chamber size and ventricular function. This was the step for 3D echocardiography to enter daily clinical practice. However, the image quality, besides being strongly dependent on the intrinsic quality of the ultrasound, was the result of the number of 2D images used in the reconstruction and of the ability to limit motion artifacts with adequate electrocardiographic and respiratory gating.16 These limitations are particularly relevant in color flow analysis, presenting the main constraints on the daily clinical use of 3D color.
However, even with these restrictions, 3D echo was able to circumvent some of the limitations of the 2D valve evaluation and several studies have reported on its important aspects. Realtime 3D transthoracic (TT) and/or transesophageal (TE) echocardiography provides a comprehensive visualization of each of the different components of the mitral valve apparatus and is probably the method of choice when available.17
Its excellent and precise anatomic representation of the mitral valve make real-time 3D very useful in the evaluation of the extent of commissural fusion in rheumatic MR, the quantification of leaflet involvement in degenerative myxomatous disease, the detection of chordal rupture and concomitant annular dilatation, the measurement of the annular ring size, and mitral valve segmentation, with precise localization of the prolapsing scallops.6,18 In fact, Gutierrez-Chico et al. compared segmental analysis of mitral prolapse performed with TT 3D echocardiography and with TE 2D echocardiography, and found similar accuracy using both techniques.19
Along with the detailed representation of mitral valve components, real-time 3D allows the generation of images which reflect typical ‘surgeon’s eye’ views, facilitating the dialogue between the surgeon and the echocardiographer.6,18
The ability to demonstrate color information in 3D was first shown in patients with MR using data acquired with a gated sequential rotational TE echocardiographic approach and processed offline. This showed the direction of the jet and its 3D extent and geometry. Afterwards, a better correlation between 3D (versus 2D) findings and those from angiography was reported, especially in the presence of eccentric jets.20 With further software development, 3D reconstructions of color flow with gray-scale anatomy subsequently permitted better delineation of the jet origin, which was particularly relevant in patients with periprosthetic regurgitation, providing a better understanding of the mechanism of regurgitation.21
The use of 3D color flow volumetric imaging, by fully sampled matrix array probes, allowed direct assessment of the regurgitant flow, as well as of the size and shape of the regurgitant orifice, obviating the geometric assumptions applied by 2D echocardiography and leading to a more accurate assessment of the VC, PISA, and jet volume. These new 3D volumetric images provided the visualization and measurement of the narrowest portion of the jets in two orthogonal views, leading to the conclusion that the VC area was more oval than circular.21 Similarly, Matsumura et al. evaluated functional MR by 3D, finding that the PISA is curved and elongated, rather than round, probably explaining the underestimation of functional MR severity by 2D PISA methods.22 Other studies compared these 3D-derived data with the 2D findings and showed that, when using a hemispheric model, 2D PISA underestimates flow rates and regurgitant volumes by as much as 35 % in in vitro models and 44 % in live patients.23,24
Also, 3D echo allows an innovative method of anatomical EROA measurement, which represents a direct, rather than hemodynamically derived, approach to estimating MR severity.25 It involves manual cropping of the image plane perpendicularly orientated to the jet direction as far as the narrowest cross-sectional area of the jet.8 Then, the regurgitation orifice can be measured by manual planimetry of the color Doppler signal, tilting the image in an ‘en face’ view and selecting the systolic frame with the most relevant lesion size.8
Several authors have already demonstrated a close agreement between 3D VC area measurements and the 2D flow convergence width method.24,26,27 Additionally, Marsan et al. found an excellent correlation between 3D anatomic EROA-derived regurgitant volume and the recently proposed reference method for mitral regurgitant volume quantification, cardiac magnetic resonance.28
Nevertheless, 3D color Doppler used in recent years remains suboptimal: it still requires several heartbeats to acquire an image of interest, the color sector size is narrow, the balance between color and gray-scale remains difficult, the acoustic sampling rate is suboptimal, volume rates are restricted, and quantitative software is lacking, which makes it of limited clinical applicability.
The 4D echocardiography technique is the ultimate step in echocardiography evolution and may overcome the main limitations on 2D and classical 3D evaluation of valvular regurgitation. Instantaneous full-volume echocardiography with the ACUSON SC2000TM volume imaging ultrasound system brings an innovative technology based on INFocus coherent imaging and launches a new concept in performing echocardiography.
The entire acquisition is performed in one heartbeat and analyzed in realtime. The transducer (4Z1c) delivers full-field transmit focusing and uses the power of 64 receive beams. This results in improved penetration and high-volume acquisition rates, without stitching artifacts. It provides an instantaneous full volume of the heart in a single heartbeat, in the format of 90° pyramids, without apneas or large electrocardiographic gating. The image acquisition is performed with simultaneous visualization of coronal, sagittal, and transverse planes and allows the acquisition of instantaneous color Doppler images, presented in the format of 60° pyramids, with a frame rate superior to 16 volumes per second, within one heartbeat acquisition (see Figure 2).
With this technology of instantaneous full-volume color Doppler echocardiography, most of the previous 3D limitations are overcome, resulting in a factual realtime image, with a color sector size of 60 x 60° pyramid, good balance between color Doppler and gray-scale, and quantitative software on-cart included.18
Additionally, this software provides a new quantitative method of 3D PISA calculation. After one-heartbeat high-volume-rate color flow acquisition, the analysis is initialized by the operator by setting the location of the jet and valve coaptation point. Afterwards, the operator specifies the desired isovelocity value and the direction of interest (relative to the annulus or valve coaptation line) in such a way that the target isovelocity surface is contained entirely within the acquisition. It is followed by fully automatic segmentation of the valve annulus and isovelocity surface area computation (see Figure 3).
This allows automatic visualization of 3D PISA surface and anatomic EROA, with expected higher accuracy of the subsequent regurgitant volume calculation when compared with the conventional manual tracing methods. Extensive in vitro experiments established the accuracy of this method in measuring surface area, EROA, and regurgitant flow, especially when compared with the calculations obtained from the conventional spherical approximation. Studies regarding in vivo validation of this technique for MR quantification are currently in progress and there is great expectation regarding their results.
From the concept to the main principals of application, which overcome the well-known limitations of 2D and conventional 3D echocardiography, assessment of the new PISA methodology by full-volume color flow quantification of MR promises to be a more precise approach to the assessment of the severity of valvular pathology, capable of changing our way of performing echocardiography.
Conclusions
MR is a common pathology requiring precise evaluation for appropriate clinical decision-making, and the use of 3D echocardiography is overcoming the limitations of 2D echocardiography. A new methodology is being developed to further improve MR quantification: 4D instantaneous full-volume color flow quantitative software, allowing the automatic calculation of the flow convergence area and aiming to provide a more precise and easier approach to the assessment of the severity of valve regurgitation. It is validated in vitro, and further in vivo validation will allow its use in clinical practice.