Three-dimensional echocardiographic imaging of secondary mitral valve regurgitation Raluca Dulgheru1, Paaladinesh Thavendiranathan2, Khalil Fattouch, Mani Vannan, Patrizio Lancellotti1 1 GIGA Cardiovascular Sciences, Heart Valve Clinic, University of Liège, Department of Cardiology, University Hospital Sart Tilman, Liège, Belgium , 2Peter Munk Cardiac Center, University Health Network, Toronto General Hospital, University of Toronto, Toronto, Canada Keywords: secondary mitral, three dimensional echocardiographic, mitral valve morphology. 1 Abstract Many hypotheses regarding the mechanism of secondary mitral regurgitation (SMR) have been made from 2D echocardiographic observations. Some have been confirmed and further developed with the help of 3D echocardiography (1;2). 3D echocardiography, and especially 3D transesophageal echocardiography (TEE), has much to offer in the evaluation of SMR, in addition to 2D echocardiography. First, it offers important information regarding MV geometry, giving insights into the mechanisms involved in the genesis of SMR in each patient. Second, it can improve the accuracy of MR quantification (3;4). Third, it can play an important role in the planning of surgery or percutaneous intervention. Identifying the principal mechanism responsible for SMR, from several potential mechanisms, in each individual patient, is very important, especially when contemplating MV repair. Knowing which mechanism is most involved in SMR genesis and what are the possible solutions to counterbalance and correct it may allow better tailoring of the surgical technique potentially leading to better outcomes. Data acquisition Over the past few years, 3D transthoracic echocardiography (TTE) has overcome many of its initial limitations. However, the quality of the 3D data is still highly dependent on the acoustic window in each patient. When comprehensive and complex analyses of the MV morphology and function are needed, the technique that is able to provide most of the answers, and thus the most frequently used, is 3D TEE. With 3D TEE several techniques for data acquisition are available: 2 Simultaneous Multiplane Mode or Biplane Mode – enables visualization of the MV in two independent 2D planes simultaneously in real time (Figure 1). The first image, usually displayed on the left side of the screen, is a reference image, such as mid-esophageal four or five chamber view. The second image, displayed on the right side of the screen, is a 2D image of the MV taken from a plane rotated 30 to 150 degrees (as chosen by the user) from the reference plane. Color flow Doppler can be added to the analysis in both planes. Real Time 3D acquisition or Live 3D – enables a real-time display of a 30 x 60 degrees pyramidal volume of the MV. It has the disadvantage of not being able to display the entire MV valve apparatus. However, due to the high temporal resolution, it is the modality of choice for guiding interventions on the MV. Rapid switch between “en face” and ventricular view of the MV leaflets can be performed according to the clinical question to be answered. Advances to live 3D now allow increase of the real time display to as high as a 90 x 90 degree sector; however, this comes at the cost of reduced temporal resolution. Focused Wide Sector or 3D Zoom – enables a real time, focused, wide-sector view of the MV apparatus with good spatial resolution and satisfactory temporal resolution (Figure 2). The temporal resolution can be improved by using a “stitched” 3D acquisition over 4-6 heart beats with some vendors. Live 3D Zoom is probably the most important 3D imaging modality for MV morphology assessment by 3D TEE. It is the modality of choice when analyzing valvular morphology in SMR patients. Care should be taken to optimize the spatial and temporal resolution of the acquired images. The acquisition should be started 3 from the mid esophageal bi-commissural view with the sector width adjusted to cover the entire commissure and the elevational plane adjusted to cover the antero-posterior aspect of the MV. The height of the volume sector should also be adjusted to cover the entire mitral annulus, leaflets (both in systole and diastole) and subvalvular apparatus. The key to an optimal temporal and spatial resolution is to set the elevational plane as narrow as possible. Care should be taken to include in the acquired volume some of the landmarks surrounding the MV, such as the aortic valve and the left atrial appendage. This will allow the correct recognition of each MV leaflet and a correct orientation of the MV as seen from the atrial perspective (Supplemental material Movie 1) or ventricular perspective (Supplemental material Movie 2) Full Volume Gated Acquisition – enables optimal spatial and temporal resolution. This modality has the largest acquisition sector available (a volume size of 75 x 75 degrees) that allows imaging of the MV apparatus and of the left ventricle in the same volume (Figure 3). It requires ECG gating. This type of acquisition may be very important in SMR when assessing the relationship between MV apparatus, chords, and distortion and LV with regional or global remodeling. When used as a multi-beat stitched acquisition it has also a higher temporal resolution, necessary when analyzing patterns of leaflet motion, such as in SMR. However, because the acquisition modality involves stitching together several smaller pyramidal volumes, each of them acquired during one cardiac cycle, this type of acquisition is predisposed to stitching artifacts especially in patients with irregular heart rhythms. Even in patients with regular heart rhythms stitching 4 artifacts can often occur due to difficulties with breath-holding in a semiconscious patient during TEE. Therefore care should be taken to look through the acquired data set to save images with minimal or no stitching artifacts to ensure accurate analysis. Full Volume Color Flow Doppler (Supplemental material Movie 3) – this technique is similar to the full volume gated acquisition with color Doppler on. With this method the full volume with color Doppler is constructed by stitching together multiple narrow pyramidal sets, each acquired during a single cardiac cycle (Figure 4). Inadequate breath-holding and irregular heart rhythm can lead to stitching artifacts. With TTE this technique is highly dependent on transthoracic image quality, being less suitable in patients with poor apical acoustic windows. With TEE image quality is adequate but acquisition might be hampered by stitching artifacts related to inadequate breath-holding. Real-time 3D color Doppler acquisition and 3D zoom mode with color Doppler on are also available techniques with 3D TEE. Mitral Valve Morphology Assessment by 3D echocardiography 3D echocardiography offers both qualitative and quantitative information in the evaluation of mitral valve morphology in patients with SMR. 3D TEE provides, undoubtedly, the best morphological details of the mitral valve. However, in patients with good acoustic windows, 3D TTE is able to provide satisfactory information regarding MV morphology and function (Figure 5, 6). 5 Through the “en face” view, 3D echocardiography allows direct examination of the atrial surface of the mitral leaflets, coaptation line, and commissures throughout the cardiac cycle (Figure 2). This view provides a qualitative inspection of the mitral valve geometry, as seen from the atrial perspective, also known as the “surgeon’s view” (Figure 2, Figure 5, Panel D; Figure 6, Supplemental material, Movie 1). In SMR, due to the tethering of the leaflets, the geometry of the valve can be markedly changed. The MV usually has a funnel shape, with the lowest points of the funnel at the level of the coaptation line (Figure 6). In normal MVs the coaptation line normally describes a slightly upward concavity as seen from the atrial side, but in SMR, it becomes even more concave (symmetric tethering) or completely changes its shape pointing towards the LV cavity (asymmetric tethering). This simple qualitative assessment of MV geometry from the “en face” view by 3D echocardiography providing a quick insight into the mechanism of SMR, helping the clinician to distinguish between symmetrical or asymmetrical tethering pattern (Supplemental material, Movie 1). In some cases of severe SMR, an orifice, representing the anatomic regurgitant orifice area (AROA), can be visualized from the atrial perspective of the valve, and planimetry of this orifice can be made using multi-planar reformat of the 3D data or with some vendors directly from the 3D image. Care should be taken to adequately set the gain and line density on each 3D echo machine during the acquisition to eliminate dropouts that might lead to overestimation of the regurgitant orifice by planimetry. 6 After this initial on-line qualitative assessment of MV morphology, all necessary 3D datasets of the MV apparatus are acquired. This will enable later off line analysis, and a more quantitative assessment of MV morphology in SMR patients. Each of the possible mechanisms involved in SMR are carefully inspected while performing the off-line analysis of the acquired data to measure: mitral annulus size and shape, mitral annulus dynamics (change in shape between diastole and systole), MV leaflet surface area computation, and subvalvular apparatus geometry and its relative position to the MV annular plane. Mitral annular geometry in SMR For a more comprehensive analysis of MV morphology in SMR, off line reconstruction of the MV leaflets and annulus is possible from the 3D data sets with the help of various commercial software applications available on the market (Figure 7). Mitral annulus anteroposterior diameter, the inter-commissural diameter, the perimeter of the mitral annulus, the length of each annular segment (anterior annulus length vs. posterior annulus length), the height of the annulus, i.e. the distance between the highest and the lowest points on the annulus, can be measured during each frame of the cardiac cycle to characterize mitral annular morphology and its dynamic properties in patients with SMR. Many of these measurements can be obtained without any geometric assumptions. Studies that analyzed MV annular morphology, by 3D echocardiography, have shown that annular perimeter and area are increased, and that the annulus is less elliptical and more flattened in patients with SMR as compared to normal subjects (5;6). These studies have also 7 shown that the degree of mitral annular deformation in ischemic SMR is more pronounced following anterior MI than inferior MI (7). An attenuation of the sphincter function of the mitral annulus, i.e. the annular area change between diastole and systole, has been described as one of the mechanisms that contribute to SMR (8). The annular sphincter function is decreased in these patients (9), while in normal subjects annular contraction is around 25% (10). 3D echocardiography has also proven that in healthy individuals, caudal displacement of the mitral annulus occurs during systole and is more accentuated in the posterior region, while in patients with SMR, this displacement is reduced, most notably in the posterior region (11). Mitral leaflet morphology in SMR Optimal coaptation of the MV leaflets throughout systole requires perfect match between MV leaflet’s surface and the MV orifice. SMR is characterized by suboptimal leaflet coaptation related to increased MV leaflets tethering. Through 3D reconstruction of the MV the measurement of mitral leaflets surface area, mitral leaflets coaptation area (CA), coaptation height (CH), and coaptation index (CI) is possible. Mitral leaflets surface computation (Figure 8) form 3D data sets, using dedicated software has helped us understand that mitral valve leaflets are not inert structures, and that they are capable of adapting dynamically to maintain adequate coaptation. This was first elegantly shown using 3D echocardiographic studies in animal models where this dynamic enlargement of the leaflets was shown to increase mitral valve coaptation surface, explaining at least in part, why in some cases with significant leaflets tethering, SMR may be only mild in severity (12). This adaptive remodeling of the leaflets was felt to be a response to the chronic mechanical stress exerted by leaflet tethering (12). 8 This finding was confirmed by another “in vivo” study which demonstrated that despite increased leaflet size to compensate for the increased mitral leaflet tethering, coaptation can be significantly decreased in patients with LV remodeling and significant SMR as compared to patients without significant SMR and similar degrees of LV remodeling. In this study, all indexes of coaptation, as assessed by 3D TEE (CA, CI and coaptation length) were related to SMR severity (13). CA was defined as the difference between total leaflet area (MV leaflet surface measured at the onset of mitral leaflet closure) and closed leaflet area in mid-systole (MV leaflet surface measured form the mid-systolic frame). Since it has been demonstrated that mitral leaflets stretch during systole (14), leading thus to an underestimation of the coaptation area, another parameter, namely the CI, was calculated to account for the “dynamic” increase in mitral leaflets surface during systole. The CI was defined as the ratio of CA to total leaflet area and multiplied by 100. CI was also associated with the SMR severity in this study (13). In addition, the tenting volume, which is the volume encompassed between the surface of the MV leaflets and the mitral annulus plane in mid-systole, can be calculated from the 3D datasets with a dedicated software (Figure 9). The software is able to reconstruct the tenting volume shape and render it in its 3D shape. A simple eyeball examination of the tenting volume shape gives valuable hints regarding the pattern of tethering on the MV leaflets. Asymmetric tethering usually exhibits a tenting volume shape deformed toward the most tethered segment of the leaflet, pointing out the part of the leaflet that is predominantly stretched. The tenting volume proved to be closely related to SMR severity and a reliable marker of leaflets tethering severity. MV subvalvular apparatus morphology in SMR 9 3D echocardiography allows also a comprehensive evaluation of the MV subvalvular apparatus and its position relative to the mitral annular plane. The distance between each PM tip and a point located in the center of a plane with least deviation of annular hinge point about it, the inter-papillary muscle distance, and the distance between each PM tip and its contralateral or ipsilateral commissure, are all methods that can be used to characterize the pattern of the MV tethering and to estimate its severity in SMR patients. One of the most important parameters that can be evaluated with the use of 3D echocardiography to describe MV apparatus deformation in SMR is the tethering distance. It is the distance measured between the intervalvular fibrosa (the middle anterior part of the MV annulus that extends between the anterior mitral valve leaflet and the aortic valve) and the head of the posteromedial PM at mid-systole. This parameter proved to be a reliable indicator of the severity of distortion of the MV apparatus, and a strong predictor of SMR after MI (2;15). The distance between the head of the anterolateral PM and the intervalvular fibrosa can be also measured. Classically this is named the “lateral tethering distance”, while the distance between the posteromedial PM and the intervalvular fibrosa is referred to as the “medial tethering distance”. The advantage of 3D echocardiography over 2D echocardiography in the measurement of this parameter is the accurate identification of the PMs tips closest to the base of the heart, which lowers the variability of the measurement. SMR Severity Assessment by 3D echocardiography In the current guidelines (16), the quantification of SMR severity is still based on several well validated parameters derived from 2D echocardiography: the vena contracta width (VC) and the PISA method for effective regurgitant orifice area (EROA) and regurgitant volume (RV) 10 estimation. According to current guidelines, SMR is considered severe whenever EROA is > 20 mm² or/and the regurgitant volume (RV) is > 30 mL, as assessed by 2D echocardiography. Using 3D color Doppler echocardiography, several small studies have shown that 2D echocardiography might underestimate the EROA as well as the RV in certain cases of SMR. There are several limitations of the PISA method and VC width, as assessed by 2D echocardiography that should be acknowledged. 3D echocardiography seems to be able to overcome these limitations and improve the accuracy of assessing EROAs and RVs in patients with SMR. In the years to come, paralleling the improvement in 3D echocardiography, a higher availability of this technique in daily clinical practice is expected. Thus, the need for establishing 3D derived cut off values for the parameters used to quantify SMR severity is imperative. The reader should keep in mind that the cut of values for EROA and RV derived from 2D echocardiography and those derived from 3D echocardiography are not interchangeable. In SMR, the regurgitant orifice is usually not circular and is more commonly elliptical in shape. Therefore using the vena contracta width the severity of SMR may be overestimated if measured by 2D echocardiography along the long-axis of the regurgitant orifice (e.g from a 2 chamber view), or underestimated if measured from a plane perpendicular to the regurgitant orifice (e.g. 4 chamber view) (Figure 9). 3D echocardiography can overcome this limitation by being able to provide the area of the vena contracta with no geometric assumptions by direct planimetry in the plane perpendicular to the direction of the regurgitant jet using reconstructed en face view of the 3D regurgitant jet (Figure 10). 3D derived VC area measurement is a method of measuring the effective regurgitant orifice area. 3D derived VC area has been shown to correlate more closely with Doppler-derived EROA than 2D VC width. There are some limitations of this technique that have to be acknowledged. The limited spatial resolution of the reconstructed 11 images may make measurement of VC area particularly challenging in mild to moderate SMR. The choice of the systolic frame for VC area measurement may lead to important interobserver variability because SMR is highly dynamic throughout systole and depending on the chosen frame computed values might be very different between observers. Color bleeding into gray scale and cropping of the regurgitant jet in a nonorthogonal manner can overestimate VC area (17). The 2D echocardiography derived PISA method, used to estimate the EROA and RV, assumes that the flow convergence area is hemispheric. As demonstrated by 3D echocardiography, flow convergence area is frequently hemielliptic or more complex in SMR (18). Applying a 2D PISA radius method with a hemispheric assumption in patients with SMR might lead to underestimation of EROA and RV (Figure). Using 3D color Doppler echocardiography the EROA and RV can be calculated more accurately in SMR. Several methods can be applied. The 3D VC area, 3D PISA based EROA (see paragraph below) coupled with the MR velocity time integral (MR-VTI) obtained from the continuous wave Doppler can be used to derive RV. In patients with less than mild aortic regurgitation, the RV calculated with one of the 3D methods or by 2D PISA method, can be combined with the 3D LV stroke volume obtained by automated/semiautomated endocardial tracking algorithms, to derive the RF. In addition, subtraction of the conventional 2D Doppler derived LV outflow tract stroke volume (using LVOT area and PW Doppler) from the 3D LV stroke volume from endocardial contouring is an alternate way to calculate the RV in patients with SMR. With 3D TTE computation of the true 3D proximal isovelocity surface area without any specific geometric assumptions is also possible. Instantaneous “Full Volume” 3D color Doppler echocardiography with the ACUSON SC2000TM volume imaging ultrasound system provides a 12 new technology that allows calculation of EROA and RV applying the same equations used in 2D echocardiography, but with the advantage of PISA being directly measured as a 3D (Figure 11). This approach was validated against “in vitro” phantoms, showing higher accuracy when compared with results obtained from the conventional spherical approximation method (19). One of the limitations of this technique is that PISA measurement is made in one fixed frame, as chosen by the sonographer, thus missing the dynamic character of SMR throughout systole. Interobserver variability may be encountered due to this limitation. However, in the future, instantaneous calculation of the 3D PISA in each frame during systole might become available, as 3D echocardiography techniques are constantly improving. A mean value for EROA and RV calculated frame by frame being probably more close to the real EROA and RV in patients with SMR. Validation studies on large populations of these techniques and outcome studies are also expected. Role of 3D echocardiography in pre-procedural selection of patients and intervention guiding 3D TEE proved to be useful both in the selection of the patients for the percutaneous catheter based edge-to-edge MV repair and for procedure guiding. It should be emphasized that candidates for the percutaneous repair of the MV in severe SMR are only patients in whom the coaptation length of the MV leaflets is higher than 2 mm and coaptation depth lower than 11 mm. Pre-procedural 3D TEE increases the confidence that the selected patient is suitable for such a procedure because it allows measurement of the coaptation length and coaptation depth in multiple image planes, with less chance of “missing” the lowest value of the coaptation length 13 and highest value of coaptation depth that would make the patient unsuitable for the procedure. Guiding of the procedure is also facilitated by 3D TEE because it can optimize the selection of the transseptal puncture site and the steering of the device towards the center of the MV orifice. These aspects will be discussed in another chapter of this book (see “The role of the “edge-toedge” in mitral valve repair” chapter). Figure legend: Figure 1. Biplane Mode (X-plane) acquisition with 3D transoesophageal echocardiography. Left side panel: the reference plane is mid-oesophageal 4 chamber view. Right side panel: 2D image of the mitral valve from a plane rotated 95⁰ from the reference plane. AML- anterior mitral leaflet; PML – posterior mitral leaflet. Figure 2. 3D Zoom acquisition of the mitral valve as seen from the atrial perspective by 3D transoesophageal echocardiography. The image is then rotated in such a way that the aorta is located anteriorly (flipped image indicated by arrow). Ao –aorta. Figure 3. Full Volume Gated Acquisition with 3D transoesophageal echocardiography. Acquisition is done over 4 cardiac cycles that enables a good temporal resolution (32 volumes per second). Figure 4. Full Volume Color Flow Doppler acquisition with 3D transthoracic echocardiography. The full volume color Doppler is reconstructed by stitching together 4 narrow pyramidal sets. Off line analysis enables evaluation of vena contracta area by direct planimetry. Figure 5. 3D transthoracic echocardiography evaluation in a patient with dilated cardiomyopathy and secondary mitral regurgitation. Apical systolic displacement of the mitral valve leaflets 14 coaptation point as seen from a lateral aspect (Panel A, yellow arrow, the blue dotted line represents the mitral annulus plane). Apical and lateral displacement of the papillary muscles exerting a tethering effect on the mitral leaflets in mid-systole as seen from the ventricular view (Panel B, yellow arrows). For rapid recognition of the anatomic landmarks the ventricular aspect of the mitral valve apparatus is also shown in diastole (Panel C). Funnel shape morphology of the mitral valve as seen from the atrial perspective in the same patient (Surgeon’s view, Panel D). All images are reconstructed from the same 3D pyramidal data set. AML- anterior mitral leaflet; PML- posterior mitral leaflet; Ao- aorta. Figure 6. Surgeon’s view of the mitral valve in a patient with secondary mitral regurgitation (SMR) and idiopathic dilated cardiomyopathy showing the funnel shape of the mitral valve as seen from the atrial perspective (3D transthoracic echocardiography, Panel A). The chosen frame is in mid-systole, tethering on the MV leaflets being maximal (Panel A, yellow arrow indicating mid-systole on the ECG tracing). For easy recognition of the anatomic landmarks the valve is also shown in diastole (Panel B). Ao-aorta; ALC –anterolateral commissure; PMC – posteromedial commissure. Figure 7. Mitral annular reconstruction from 3D transoesopageal datasets with measurement of the antero-posterior diameter of the mitral annulus (green continuous line). Figure 8. Mitral valve morphology reconstruction in a patient with secondary mitral regurgitation from 3D transoesopageal datasets: measurement of the mitral valve tenting volume and height, intercommissural diameter, and anterior and posterior leaflet area. Figure 9. 2D transthoracic evaluation from the parasternal short axis view at the level of the mitral valve in a patient with secondary mitral regurgitation showing the elliptical shape of the 15 vena contracta (VC) of the regurgitant jet (green dotted line). Measurement of VC from the parasternal long axis view (PSLA) would underestimate the severity of the MR (white line) while measurement from the 2-chamber view (2-Ch) would overestimate its severity (black arrow). PSLA- parasternal long axis view; 2-Ch – 2 chamber view. Figure 10. Vena contracta (VC) area measurement by 3D transthoracic echocardiography in a patient with secondary mitral regurgitation and dilated cardiomyopathy. After full volume color Doppler acquisition with the 3D transthoracic probe from the apical window the 3D data set is cropped to derive the area of the vena contracta of the regurgitant jet. Direct planimetry of the vena contracta area is possible (white line enclosed area). The dotted green line represents the orthogonal plane in which the VC area measurement was done. Figure 11. Instantaneous “Full volume” 3D transthoracic echocardiography with the assessment of the effective regurgitant orifice (ERO) area and regurgitant volume of a secondary mitral regurgitation by direct 3D measurement of proximal isovelocity surface area. Supplemental material Movie 1. 3D Zoom mode acquisition of the mitral valve as seen from the atrial perspective (“surgeon’s view) by 3D transoesophageal echocardiography. The displayed image is then rotated in such a way that the aorta is located anteriorly. Supplemental material Movie 1. 3D Zoom mode acquisition of the mitral valve as seen from the ventricular perspective by 3D transoesophageal echocardiography. The displayed image is then rotated in such a way that the anterior mitral leaflet is seen opening in diastole towards the interventricular septum, while the posterior leaflet is almost fixed during the cardiac cycle. 16 Supplemental material Movie 3. Full Volume Color Flow Doppler Gated Acquisition with 3D transoesophageal echocardiography in a patient with ischemic mitral regurgitation and a centrally oriented regurgitation jet, indicative of symmetric tethering pattern. 17 Reference List 1. Otsuji Y, Handschumacher M, Schwammenthal E et al. Insights from three dimensional echocardiography into the mechanism of functional mitral regurgitation. Circulation. 1997;96:1999-2008. 2. Otsuji Y, Hanschumacher MD, Liel-Cohen N et al. Mechanism of ischemic mitral regurgitation with segmental left ventricular dysfunction: three-dimensional echocardiographic studies in models of acute and chronic progressive regurgitation. J Am Coll Cardiol. 2001;37:641-648. 3. 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