2D Transthoracic Echocardiographic Assessment

Two-dimensional transthoracic echocardiography was performed by experienced sonographers according to a standardized echocardiographic protocol using an iE33 ultrasound system (Philips Medical Systems, Andover, MA) with an S5-1 probe.

Doppler color flow mapping was used to evaluate the direction of the MR jets. The primary direction of the MR jets was classified as central or eccentric. Asymmetric or symmetric tethering patterns were determined by asymmetric or symmetric coaptation of the mitral leaflets and the direction of the MR jet. Specifically, asymmetric tethering pattern was defined by (1) asymmetric coaptation (predominant posterior tethering of both leaflets, with the distal anterior leaflet, less restricted, sliding up toward the midlevel of the posterior leaflet, creating a “pseudoprolapse” or “hockey stick configuration”) and (2) an eccentric, posteriorly directed MR jet consistent with the asymmetric coaptation. Symmetric tethering pattern was defined by (1) symmetric coaptation (symmetric and predominant apical tethering of both leaflets into the left ventricle) and (2) a central MR jet consistent with the symmetric coaptation. Tethering patterns were assessed on apical four-chamber and long-axis views as well as the parasternal long-axis view at midsystole ( Figure 1 ).

Schematic representation of mitral leaflet tethering patterns in IMR. (A) Symmetric tethering pattern with symmetric coaptation. (D) Asymmetric tethering pattern with asymmetric coaptation, forming a “pseudoprolapse” or “hockey stick configuration” appearance. An example is shown of a symmetric tethering pattern with a central mitral regurgitant jet by transthoracic echocardiography (B) and by TEE (C) . An example is shown of an asymmetric tethering pattern with an eccentric regurgitant jet by transthoracic echocardiography (E) and by TEE (F) .

Color flow Doppler images of the MR jet were acquired at a Nyquist limit of 50 to 60 cm/sec and a color gain that just eliminated random color speckle from nonmoving regions. Quantification of MR was performed as recommended by the American Society of Echocardiography using an integrative method, including measurement of vena contracta (VC) width, effective regurgitant orifice area (EROA), and the ratio of mitral regurgitant jet area to left atrial area. VC width was measured as the narrowest width of the proximal jet measured from a magnified parasternal long-axis view. EROA was calculated using the proximal isovelocity surface area (PISA) method from apical views, using the formula EROA = 2π × R _PISA ² × V _aliasing / V _max , where R _PISA is the maximal PISA radius (centimeters), V _aliasing is the aliasing velocity of the proximal flow convergence (centimeters per second), and V _max is the maximal velocity of the continuous-wave Doppler MR signal (centimeters per second). Jet area/left atrial area ratio was calculated as the ratio of MR jet area to left atrial area, averaged from apical four-chamber and two-chamber views. Severe MR was defined by the presence of at least two of three color Doppler methods categorizing MR severity as severe by American Society of Echocardiography–recommended thresholds.

LV end-diastolic volume (EDV) and end-systolic volume (ESV) were measured using the biplane Simpson’s rule. Ejection fraction (EF) was calculated as (EDV − ESV)/EDV. Regional wall motion was scored using a 16-segment model on a five-point grading scale (1 = normal, 2 = hypokinetic, 3 = akinetic, 4 = dyskinetic, 5 =aneurysmal). A wall motion score index was calculated as the average value of the analyzed segments.

3D Transesophageal Echocardiographic Acquisition and Analysis

TEE was performed by using a fully sampled matrix transducer (X7-2t). The transducer was positioned at the midesophageal four-chamber view. To avoid stitching artifacts, special care was taken to stabilize the probe during data acquisition. The acquisition was electrocardiographically gated, with sector settings optimized for resolution. Either full volume or zoom-mode acquisition of the entire mitral valve and aortic valve was used. Three-dimensional data sets were analyzed using the commercial software MVQ (Mitral Valve Quantification, QLAB version 8.0; Philips Medical Systems) according to the software manufacturer’s recommended method. The aortic annulus, mitral annulus, mitral leaflets, and papillary muscles were manually traced at midsystole. Briefly, four key reference points indicating the orientation of the mitral annulus (anterior, posterior, anterolateral, and posteromedial points) were marked on two cut planes representing the three-chamber view and an orthogonal plane. The mitral annulus was then outlined by marking a total of 16 annular points at the leaflet insertion on eight equiangular image planes intersecting at the center of the mitral annulus. To delineate the leaflet geometry and coaptation points, mitral leaflets were traced in a set of 17 equidistant parallel long-axis planes. The anterior and posterior papillary muscle tips were identified by comparing the adjacent long-axis planes. Finally, QLAB was used to reconstruct the mitral valve apparatus ( Figure 2 ), generating parameters representing 3D geometry, including mitral annular intercommissural (CC) diameter, anteroposterior diameter, height, circumference, 2D projection area, aortic-mitral angle, anterior leaflet tethering angle, posterior leaflet tethering angle, tenting volume, tenting height, and leaflet closure areas. Leaflet closure areas were the areas of leaflets involved in coaptation, defined as the closed leaflet surface between the left ventricle and the left atrium in midsystole. Leaflet closure area was the summation of anterior mitral leaflet closure area and posterior mitral leaflet closure area. The following calculations were also made: (1) the ratio of mitral annular height to CC diameter, representing the degree of saddle shape ; (2) the ratio of posterior to anterior leaflet tethering angle, representing a measure of the tethering pattern (the higher the ratio, the more asymmetric the pattern); (3) the ratio of anterior to posterior leaflet closure area, representing the position of the coaptation line; and (4) the ratio of VC width or EROA to tenting volume or tenting height, representing MR severity relative to tenting volume or tenting height.

Volumetric data set of the mitral valve obtained by 3D TEE. The mitral annulus, mitral leaflets, points of coaptation, and papillary muscle (PM) tips are manually traced at midsystole (A,B) . The anterior mitral leaflet (AML) or posterior mitral leaflet (PML) angle is measured as the angle between the annular plane and a line that joins the coaptation point and anterior or posterior annulus (B) . The mitral leaflets and points of coaptation are traced in multiple parallel planes from commissure to commissure. Tracing markers outline the annular shape and coaptation line (C) . QLAB MVQ software reconstructs a 3D model of the entire mitral valve with a schematic demonstration (D) .

To assess the reproducibility of the measurements of mitral valve geometry by 3D TEE, 15 patients were randomly selected. To evaluate interobserver variability, two independent observers measured the mitral valve geometry using the same 3D data sets. To test intraobserver variability, measurements were repeated 3 months later by the same observer.