Intraoperative post-annuloplasty three-dimensional valve analysis does not predict recurrent ischemic mitral regurgitation.

BACKGROUND: High ischemic mitral regurgitation (IMR) recurrence rates continue to plague IMR repair with undersized ring annuloplasty. We have previously shown that pre-repair three-dimensional echocardiography (3DE) analysis is highly predictive of IMR recurrence. The objective of this study was to determine the quantitative change in 3DE annular and leaflet tethering parameters immediately after repair and to determine if intraoperative post-repair 3DE parameters would be able to predict IMR recurrence 6 months after repair. METHODS: Intraoperative pre- and post-repair transesophageal real-time 3DE was performed in 35 patients undergoing undersized ring annuloplasty for IMR. An advanced modeling algorhythm was used to assess 3D annular geometry and regional leaflet tethering. IMR recurrence (≥ grade 2) was assessed with transthoracic echocardiography 6 months after repair. RESULTS: Annuloplasty significantly reduced septolateral diameter, commissural width, annular area, and tethering volume and significantly increased all segmental tethering angles (except A2). Intraoperative post-repair annular geometry and leaflet tethering did not differ significantly between patients with recurrent IMR (n = 9) and patients with non-recurrent IMR (n = 26). No intraoperative post-repair predictors of IMR recurrence could be identified. CONCLUSIONS: Undersized ring annuloplasty changes mitral geometry acutely, exacerbates leaflet tethering, and generally fixes IMR acutely, but it does not always fix the delicate underlying chronic problem of continued left ventricular dilatation and remodeling. This may explain why pre-repair 3D valve geometry (which reflects chronic left ventricular remodeling) is highly predictive of recurrent IMR, whereas immediate post-repair 3D valve geometry (which does not completely reflect chronic left ventricular remodeling anymore) is not.

The value of preoperative 3-dimensional over 2-dimensional valve analysis in predicting recurrent ischemic mitral regurgitation after mitral annuloplasty.

OBJECTIVES: Repair for ischemic mitral regurgitation with undersized annuloplasty is characterized by high recurrence rates. We sought to determine the value of pre-repair 3-dimensional echocardiography over 2-dimensional echocardiography in predicting recurrence at 6 months. METHODS: Intraoperative transesophageal 2-dimensional echocardiography and 3-dimensional echocardiography were performed in 50 patients undergoing undersized annuloplasty for ischemic mitral regurgitation. Two-dimensional echocardiography annular diameter and tethering parameters were measured in the apical 2- and 4-chamber views. A customized protocol was used to assess 3-dimensional annular geometry and regional leaflet tethering. Recurrence (grade ≥2) was assessed with 2-dimensional transthoracic echocardiography at 6 months. RESULTS: Preoperative 2- and 3-dimensional annular geometry were similar in all patients with ischemic mitral regurgitation. Preoperative 2- and 3-dimensional leaflet tethering were significantly higher in patients with recurrence (n = 13) when compared with patients without recurrence (n = 37). Multivariate logistic regression revealed preoperative 2-dimensional echocardiography posterior tethering angle as an independent predictor of recurrence with an optimal cutoff value of 32.0° (area under the curve, 0.81; 95% confidence interval, 0.68-0.95; P = .002) and preoperative 3-dimensional echocardiography P3 tethering angle as an independent predictor of recurrence with an optimal cutoff value of 29.9° (area under the curve, 0.92; 95% confidence interval, 0.84-1.00; P < .001). The predictive value of the 3-dimensional geometric multivariate model can be augmented by adding basal aneurysm/dyskinesis (area under the curve, 0.94; 95% confidence interval, 0.87-1.00; P < .001). CONCLUSIONS: Preoperative 3-dimensional echocardiography P3 tethering angle is a stronger predictor of ischemic mitral regurgitation recurrence after annuloplasty than preoperative 2-dimensional echocardiography posterior tethering angle, which is highly influenced by viewing plane. In patients with a preoperative P3 tethering angle of 29.9° or larger (especially when combined with basal aneurysm/dyskinesis), chordal-sparing valve replacement should be strongly considered.

Preoperative Three-Dimensional Valve Analysis Predicts Recurrent Ischemic Mitral Regurgitation After Mitral Annuloplasty.

BACKGROUND: Valve repair for ischemic mitral regurgitation (IMR) with undersized annuloplasty rings is characterized by high IMR recurrence rates. Patient-specific preoperative imaging-based risk stratification for recurrent IMR would optimize results. We sought to determine if prerepair three-dimensional (3D) echocardiography combined with a novel valve-modeling algorithm would be predictive of IMR recurrence 6 months after repair. METHODS: Intraoperative transesophageal real-time 3D echocardiography was performed in 50 patients undergoing undersized ring annuloplasty for IMR and in 21 patients with normal mitral valves. A customized image analysis protocol was used to assess 3D annular geometry and regional leaflet tethering. IMR recurrence (≥ grade 2) was assessed with two-dimensional transthoracic echocardiography 6 months after repair. RESULTS: Preoperative annular geometry was similar in all IMR patients, and preoperative leaflet tethering was significantly higher in patients with recurrent IMR (n=13) than in patients in whom IMR did not recur (n=37) (tethering index: 3.91 ± 1.01 vs 2.90 ± 1.17, p = 0.008; tethering angles of A3: 23.5° ± 8.9° vs 14.4° ± 11.4°, p = 0.012; P2: 44.4° ± 8.8° vs 28.2° ± 17.0°, p = 0.002; and P3: 35.2° ± 6.0° vs. 18.6° ± 12.7°, p < 0.001). Multivariate logistic regression analysis revealed the preoperative P3 tethering angle as an independent predictor of IMR recurrence with an optimal cutoff value of 29.9° (area under the curve, 0.92; 95% confidence interval, 0.84 to 1.00; p < 0.001). CONCLUSIONS: 3D echocardiography combined with valve modeling is predictive of recurrent IMR. Preoperative regional leaflet tethering of segment P3 is a strong independent predictor of IMR recurrence after undersized ring annuloplasty. In patients with a preoperative P3 tethering angle of 29.9° or larger, chordal-sparing valve replacement rather than valve repair should be strongly considered.

Posterior leaflet augmentation in ischemic mitral regurgitation increases leaflet coaptation and mobility.

BACKGROUND: Restoring leaflet coaptation is the primary objective in repair of ischemic mitral regurgitation (IMR). The common practice of placing an undersized annuloplasty ring partially achieves this goal by correcting annular dilation; however, annular reduction has been demonstrated to exacerbate posterior leaflet tethering. Using a sheep model of IMR, we tested the hypothesis that posterior leaflet augmentation (PLA) combined with standard annuloplasty sizing increases leaflet coaptation more effectively than undersized annuloplasty alone. METHODS: Eight weeks after posterobasal myocardial infarction, 15 sheep with 2+ or greater IMR underwent annuloplasty with either a 24-mm annuloplasty ring (24-mm group, n = 5), 30-mm ring (30-mm group, n = 5), or 30-mm ring with concomitant augmentation of the posterior leaflet (PLA group, n = 5). Using three-dimensional echocardiography, postrepair coaptation zone and posterior leaflet mobility were assessed. RESULTS: Leaflet coaptation length after repair was greater in the PLA group (4.1 ± 0.3 mm) and the 24-mm group (3.8 ± 0.5 mm) as compared with the 30-mm group (2.7 ± 0.6 mm, p < 0.01). Leaflet coaptation area was significantly greater in the PLA group (121.5 ± 6.6 mm(2)) as compared with the 30-mm group (77.5 ± 17.0 mm(2)) or the 24-mm group (92.5 ± 17.9 mm(2), p < 0.01). Posterior leaflet mobility was significantly greater in the PLA group as compared with the 30-mm group or the 24-mm group. CONCLUSIONS: Posterior leaflet augmentation combined with standard-sized annuloplasty enhances leaflet coaptation more effectively than either standard-sized annuloplasty or undersized annuloplasty alone. Increased leaflet coaptation after PLA provides redundancy to IMR repair, and may decrease incidence of both recurrent IMR and mitral stenosis.

Augmented mitral valve leaflet area decreases leaflet stress: a finite element simulation.

BACKGROUND: Using human mitral valve (MV) models derived from three-dimensional echocardiography, finite element analysis was used to predict mechanical leaflet and chordal stress. Subsequently, valve geometries were altered to examine the effects on stresses of the following: (1) varying coaptation area; (2) varying noncoapted leaflet tissue area; and (3) varying interleaflet coefficient of friction (µ). METHODS: Three human MV models were loaded with a transvalvular pressure of 80 mm Hg using finite element analysis. Initially leaflet coaptation was set to 10%, 50%, or 100% of actual coaptation length to test the influence of coaptation length on stress distribution. Next, leaflet surface areas were augmented by 1% overall and by 2% in the noncoapted "belly" region to test the influence of increased leaflet billowing without changing the gross geometry of the MV. Finally, the coefficient of friction between the coapted leaflets was set to µ = 0, 0.05, or 0.3, to assess the influence of friction on MV function. RESULTS: Leaflet coaptation length did not affect stress distribution in either the coapted or noncoapted leaflet regions; peak leaflet stress was 0.36 ± 0.17 MPa at 100%, 0.35 ± 0.14 MPa at 50%, and 0.35 ± 0.15 MPa at 10% coaptation lengths (p = 0.85). Similarly, coaptation length did not affect peak chordal tension (p = 0.74). Increasing the noncoapted leaflet area decreased the peak valvular stresses by 5 ± 2% (p = 0.02). Varying the coefficient of friction between leaflets did not alter leaflet or chordal stress distribution (p = 0.18). CONCLUSIONS: Redundant MV leaflet tissue reduces mechanical stress on the noncoapted leaflets; the extent of coaptation or frictional interleaflet interaction does not independently influence leaflet stresses. Repair techniques that increase or preserve noncoapted leaflet area may decrease mechanical stresses and thereby enhance repair durability.

Ischemic mitral regurgitation: a quantitative three-dimensional echocardiographic analysis.

BACKGROUND: A comprehensive three-dimensional echocardiography based approach is applied to preoperative mitral valve (MV) analysis in patients with ischemic mitral regurgitation (IMR). This method is used to characterize the heterogeneous nature of the pathologic anatomy associated with IMR. METHODS: Intraoperative real-time three-dimensional transesophageal echocardiograms of 18 patients with IMR (10 with anterior, 8 with inferior infarcts) and 17 patients with normal MV were analyzed. A customized image analysis protocol was used to assess global and regional determinants of annular size and shape, leaflet tethering and curvature, relative papillary muscle anatomy, and anatomic regurgitant orifice area. RESULTS: Both mitral annular area and MV tenting volume were increased in the IMR group as compared with patients with normal MV (mitral annular area=1,065±59 mm2 versus 779±44 mm2, p=0.001; and MV tenting volume=3,413±403 mm3 versus 1,696±200 mm3, p=0.001, respectively). Within the IMR group, patients with anterior infarct had larger annuli (1,168±99 mm2) and greater tenting volumes (4,260±779 mm3 versus 2,735±245 mm3, p=0.06) than the inferior infarct subgroup. Papillary-annular distance was increased in the IMR group relative to normal; these distances were largest in patients with anterior infarcts. Whereas patients with normal MV had very consistent anatomic determinants, annular shape and leaflet tenting distribution in the IMR group were exceedingly variable. Mean anatomic regurgitant orifice area was 25.8±3.0 mm2, and the number of discrete regurgitant orifices varied from 1 to 4. CONCLUSIONS: Application of custom analysis techniques to three-dimensional echocardiography images allows a quantitative and systematic analysis of the MV, and demonstrates the extreme variability in pathologic anatomy that occurs in patients with severe IMR.

Quantitative mitral valve modeling using real-time three-dimensional echocardiography: technique and repeatability.

BACKGROUND: Real-time three-dimensional (3D) echocardiography has the ability to construct quantitative models of the mitral valve (MV). Imaging and modeling algorithms rely on operator interpretation of raw images and may be subject to observer-dependent variability. We describe a comprehensive analysis technique to generate high-resolution 3D MV models and examine interoperator and intraoperator repeatability in humans. METHODS: Patients with normal MVs were imaged using intraoperative transesophageal real-time 3D echocardiography. The annulus and leaflets were manually segmented using a TomTec Echo-View workstation. The resultant annular and leaflet point cloud was used to generate fully quantitative 3D MV models using custom Matlab algorithms. Eight images were subjected to analysis by two independent observers. Two sequential images were acquired for 6 patients and analyzed by the same observer. Each pair of annular tracings was compared with respect to conventional variables and by calculating the mean absolute distance between paired renderings. To compare leaflets, MV models were aligned so as to minimize their sum of squares difference, and their mean absolute difference was measured. RESULTS: Mean absolute annular and leaflet distance was 2.4±0.8 and 0.6±0.2 mm for the interobserver and 1.5±0.6 and 0.5±0.2 mm for the intraobserver comparisons, respectively. There was less than 10% variation in annular variables between comparisons. CONCLUSIONS: These techniques generate high-resolution, quantitative 3D models of the MV and can be used consistently to image the human MV with very small interoperator and intraoperator variability. These data lay the framework for reliable and comprehensive noninvasive modeling of the normal and diseased MV.

A novel approach to in vivo mitral valve stress analysis.

Three-dimensional (3-D) echocardiography allows the generation of anatomically correct and time-resolved geometric mitral valve (MV) models. However, as imaged in vivo, the MV assumes its systolic geometric configuration only when loaded. Customarily, finite element analysis (FEA) is used to predict material stress and strain fields rendered by applying a load on an initially unloaded model. Therefore, this study endeavors to provide a framework for the application of in vivo MV geometry and FEA to MV physiology, pathophysiology, and surgical repair. We hypothesize that in vivo MV geometry can be reasonably used as a surrogate for the unloaded valve in computational (FEA) simulations, yielding reasonable and meaningful stress and strain magnitudes and distributions. Three experiments were undertaken to demonstrate that the MV leaflets are relatively nondeformed during systolic loading: 1) leaflet strain in vivo was measured using sonomicrometry in an ovine model, 2) hybrid models of normal human MVs as constructed using transesophageal real-time 3-D echocardiography (rt-3DE) were repeatedly loaded using FEA, and 3) serial rt-3DE images of normal human MVs were used to construct models at end diastole and end isovolumic contraction to detect any deformation during isovolumic contraction. The average linear strain associated with isovolumic contraction was 0.02 ± 0.01, measured in vivo with sonomicrometry. Repeated loading of the hybrid normal human MV demonstrated little change in stress or geometry: peak von Mises stress changed by <4% at all locations on the anterior and posterior leaflets. Finally, the in vivo human MV deformed minimally during isovolumic contraction, as measured by the mean absolute difference calculated over the surfaces of both leaflets between serial MV models: 0.53 ± 0.19 mm. FEA modeling of MV models derived from in vivo high-resolution truly 3-D imaging is reasonable and useful for stress prediction in MV pathologies and repairs.

Dermal filler injection: a novel approach for limiting infarct expansion.

BACKGROUND: Early infarct expansion after coronary occlusion compromises contractile function in perfused myocardial regions and promotes adverse long-term left ventricular (LV) remodeling. We hypothesized that injection of a tissue-expanding dermal filler material into a myocardial infarction (MI) would attenuate infarct expansion and limit LV remodeling. METHODS: Fifteen sheep were subjected to an anteroapical MI involving approximately 20% of the LV followed by the injection of 1.3 mL of a calcium hydroxyapatite-based dermal filler into the infarct. Real-time three-dimensional echocardiography was performed at baseline, 30 minutes after MI, and 15 minutes after injection to assess infarct expansion. Sixteen additional sheep were subjected to the same infarction and followed echocardiographically and hemodynamically for 4 weeks after MI to assess chronic remodeling. Eight animals had injection with dermal filler as described above immediately after MI, and 8 animals were injected with an equal amount of saline solution. RESULTS: All animals exhibited infarct expansion soon after coronary occlusion. The regional ejection fraction of the apex became negative after infarction, consistent with systolic dyskinesia. Injection of the dermal filler converted the apical wall motion from dyskinetic to akinetic and resulted immediately in significant decreases in global, regional, and segmental LV volumes. Chronically, relative to saline control, dermal filler injection significantly reduced LV end-systolic volume (62.2 +/- 3.6 mL versus 44.5 +/- 3.9 mL; p < 0.05) and improved global ejection fraction (0.295 +/- 0.016 versus 0.373 +/- 0.017; p < 0.05) at 4 weeks after infarction. CONCLUSIONS: Injection of an acellular dermal filler into an MI immediately after coronary occlusion reduces early infarct expansion and limits chronic LV remodeling.

A methodology for assessing human mitral leaflet curvature using real-time 3-dimensional echocardiography.

OBJECTIVES: Using 3-dimensional echocardiography in conjunction with novel geometric modeling and rendering techniques, we have developed a high-resolution, quantitative, 3-dimensional methodology for imaging the human mitral valve. Leaflet and annular geometry are important determinants of mitral valve stress. Repair techniques that optimize valvular geometry will reduce stress and potentially increase repair durability. The development of such procedures will require image-processing methodologies that provide a quantitative description of 3-dimensional valvular geometry. METHODS: Ten healthy adult subjects underwent mitral valve imaging with real-time 3-dimensional echocardiography. By using specially designed image analysis software, multiple valvular geometric parameters, including 2- and 3-dimensional leaflet curvature, leaflet surface area, annular height, intercommissural width, septolateral annular diameter, and annular area were determined for each subject. Image-rendering techniques that allow for the clear and concise presentation of this detailed information are also presented. RESULTS: Although 3-dimensional annular and leaflet geometry were found to be highly conserved between healthy human subjects in general, substantial intrasubject and intersubject regional geometric heterogeneity was observed in the midposterior leaflet, the region most commonly involved in leaflet flail in subjects with myxomatous disease. CONCLUSIONS: The image-processing and graphic-rendering techniques that we have developed can be used to provide a complete description of 3-dimensional mitral valve geometry in human subjects. Widespread application of these techniques to healthy subjects and patients with mitral valve disease will provide insight into the geometric basis of both valvular pathology and repair durability.

The influence of annuloplasty ring geometry on mitral leaflet curvature.

BACKGROUND: The effect of mitral leaflet curvature on stress reduction is an important mechanism in optimizing valve function. We hypothesize that annuloplasty ring shape could directly influence leaflet curvature and, potentially, repair durability. We describe an echocardiographically based methodology for quantifying mitral valve geometry and its application to the characterization of ovine mitral valve geometry before and after implantation of an annuloplasty ring. METHODS: Multiple mitral annular and leaflet geometric variables were calculated for 8 naïve adult male sheep using real-time three-dimensional echocardiographic images. These indexes were recalculated after annuloplasty using a 30-mm Carpentier-Edward Physio ring (n = 4; Edwards Lifesciences, Irvine, CA) or a 30-mm saddle ring (n = 4). RESULTS: After implantation of the Physio ring, the annular height to commissural width ratio (AHCWR) decreased from 19.4% +/- 2.3% to 11.1% +/- 2.5% (p = 0.06). After implantation of the saddle ring, AHCWR increased from 19.6% +/- 1.3% to 24.3% +/- 1.3% (p < 0.05). Statistically significant increases in three-dimensional Gaussian curvature occurred after implantation within six defined leaflet regions (A1 to A3, P1 to P3) of the saddle ring but only within the P1 and P3 leaflet regions with the Physio ring. CONCLUSIONS: Annuloplasty ring shape affects leaflet curvature. Implantation of a saddle ring reflecting normal human annular geometry augmented ovine annular nonplanarity and increased three-dimensional leaflet curvature across the entire mitral valve surface. The Physio ring decreased annular nonplanarity and increased leaflet curvature only across limited regions of the posterior leaflet. These findings confirm the hypothesis that ring design influences leaflet curvature.

Effect of reperfusion on left ventricular regional remodeling strains after myocardial infarction.

BACKGROUND: Reperfusion therapy for myocardial infarction is currently the most effective means for limiting early and late mortality. We sought to elucidate how reperfusion influences remodeling strains in the infarct, borderzone, and remote myocardial regions. Understanding the effects of reperfusion on regional remodeling will help to evaluate and optimize emerging treatments for patients who do not achieve effective reperfusion after myocardial infarction. METHODS: An ovine infarct model (n = 13) was used to assess the effect of 1 hour of ischemia followed by reperfusion on regional and global myocardial geometry, function, and perfusion using sonomicrometry, echocardiography, and microspheres. Thirteen additional animals were assessed chronically (8 weeks) with echocardiography and postmortem analysis after either reperfusion (n = 5) or untreated infarction (n = 8). RESULTS: During ischemia the area at risk thinned, stretched, and became dyskinetic. The normally perfused borderzone also stretched, and contraction decreased by 40% during ischemia. Reperfusion increased area at risk wall thickness and reduced area at risk stretching but did not restore contractile function. Borderzone stretching was reduced and contractile function improved by reperfusion. Contractile function of remote regions was also improved with reperfusion. Ventricular dilatation after ischemia was reversed within 180 minutes of reperfusion. Chronically, reperfusion significantly improved global remodeling when compared with nonreperfused controls. Reperfused animals had thicker infarcts and akinetic rather than dyskinetic apical segments. CONCLUSIONS: Reperfusion acutely increases area at risk wall thickness, reduces area at risk and borderzone stretching, and improves borderzone and remote function. Reperfusion increases mature scar thickness and improves chronic global remodeling. These beneficial effects of reperfusion result primarily from reduced infarct expansion (stretching).

Quantitative description of mitral valve geometry using real-time three-dimensional echocardiography.

OBJECTIVES: : Leaflet and annular geometry are important determinants of mitral valve (MV) stress. Repair techniques which optimize valvular geometry will reduce stress and potentially increase repair durability. The development of such procedures will require image processing methodologies that provide a quantitative description of three-dimensional valvular geometry. Using three-dimensional echocardiography in conjunction with novel geometric modeling and rendering techniques, we have developed a high-resolution, quantitative, three-dimensional methodology for imaging the human MV. METHODS: : Five normal adults underwent MV imaging using real-time three-dimensional echocardiography. Using specially designed image analysis software, multiple valvular geometric parameters, including the magnitude and orientation of leaflet curvature, leaflet surface area, annular height, intercommissural width, septolateral annular diameter, and annular area were determined for each subject. Image rendering techniques that allow for the clear and concise presentation of this detailed information are also presented. RESULTS: : Although three-dimensional annular and leaflet geometry were found to be highly conserved among normal human subjects, substantial regional variation in leaflet geometry was observed. Interestingly, leaflet geometric heterogeneity was most pronounced in the midposterior leaflet, the region most commonly involved in leaflet flail in subjects with myxomatous disease. CONCLUSIONS: : The image processing and graphical rendering techniques that we have developed can be used to provide a complete description of three-dimensional MV geometry in human subjects. Widespread application of these techniques to normal subjects and patients with MV disease will provide insight into the geometric basis of both valvular pathology and repair durability.