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.

Prevalence, Predictors, and Outcomes of Pulmonary Hypertension in CKD.

Pulmonary hypertension (PH) is associated with poor outcomes in the dialysis and general populations, but its effect in CKD is unclear. We evaluated the prevalence and predictors of PH measures and their associations with long-term clinical outcomes in patients with nondialysis-dependent CKD. Chronic Renal Insufficiency Cohort (CRIC) Study participants who had Doppler echocardiography performed were considered for inclusion. PH was defined as the presence of estimated pulmonary artery systolic pressure (PASP) >35 mmHg and/or tricuspid regurgitant velocity (TRV) >2.5 m/s. Associations between PH, PASP, and TRV and cardiovascular events, renal events, and all-cause mortality were examined using Cox proportional hazards models. Of 2959 eligible participants, 21% (n=625) had PH, with higher rates among those with lower levels of kidney function. In the multivariate model, older age, anemia, lower left ventricular ejection fraction, and presence of left ventricular hypertrophy were associated with greater odds of having PH. After adjusting for relevant confounding variables, PH was independently associated with higher risk for death (hazard ratio, 1.38; 95% confidence interval, 1.10 to 1.72) and cardiovascular events (hazard ratio, 1.23; 95% confidence interval, 1.00 to 1.52) but not renal events. Similarly, TRV and PASP were associated with death and cardiovascular events but not renal events. In this study of patients with CKD and preserved left ventricular systolic function, we report a high prevalence of PH. PH and higher TRV and PASP (echocardiographic measures of PH) are associated with adverse outcomes in CKD. Future studies may explain the mechanisms that underlie these findings.

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.

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).

Mitral valve tenting index for assessment of subvalvular remodeling.

BACKGROUND: Ischemic mitral regurgitation results from a variable combination of annular dilatation and remodeling of the subvalvular apparatus. Current surgical techniques effectively treat annular dilatation, but methods for addressing subvalvular remodeling have not been standardized. An effective technique for determining the extent of subvalvular remodeling could improve surgical results by identifying patients who are unlikely to benefit from annuloplasty alone. METHODS: A well-characterized ovine model of ischemic mitral regurgitation was used. Real-time three-dimensional echocardiography was performed on each animal at baseline and at 1 hour and 8 weeks after infarction. Multiple valvular geometric measurements were calculated at each time point. RESULTS: Immediate and long-term changes in mitral valvular geometry were observed. Annular height-to-commissural width ratio decreased from 20.0% +/- 1.6% to 11.2% +/- 0.9% 1 hour after infarction (p < 0.001) and to 9.4% +/- 0.4% 8 weeks after infarction (p < 0.001), whereas mitral annular area increased from 8.1 +/- 0.3 cm2 to 9.2 +/- 0.4 cm2 (p < 0.05) and then to 10.5 +/- 0.6 cm2 (p < 0.05). Maximum mitral valve tenting area increased from 49.7 +/- 5.1 mm2 to 58.6 +/- 4.2 mm2 (p < 0.05) and then to 106.4 +/- 3.9 mm2 (p < 0.001), whereas mitral valve tenting volume increased from 679.0 +/- 75.5 mm3 to 828.6 +/- 102.4 mm3 (p = 0.050) and then to 1530.5 +/- 97.8 mm3 (p < 0.001). The mitral valve tenting index increased from 0.83 +/- 0.08 mm to 0.88 +/- 0.08 mm (p > 0.05) and then to 1.46 +/- 0.08 mm (p < 0.001). CONCLUSIONS: We have described a technique that uses real-time three-dimensional echocardiography to perform a comprehensive assessment of leaflet tethering on the entire mitral valve. Our methodology is not influenced by viewing plane selection, regional tenting asymmetry, or annular dilatation and therefore represents a potentially useful, clinically relevant, and consistent measure of subvalvular remodeling.

Description of regional mitral annular nonplanarity in healthy human subjects: a novel methodology.

OBJECTIVE: Finite-element analysis demonstrates that the nonplanar shape of the mitral annulus diminishes mitral leaflet stress. It has therefore been postulated that repair with annuloplasty rings that maintain the nonplanar shape of the annulus could increase repair durability. Although the global nonplanarity of the mitral annulus has been adequately characterized, design of such a ring requires a quantitative description of regional annular geometry. By using real-time 3-dimensional echocardiography in conjunction with available image processing software, we developed a methodology for describing regional annular geometry and applied it to the characterization of the normal human mitral annulus. METHODS: Five healthy volunteers underwent mitral valve imaging with real-time 3-dimensional echocardiography. Regional annular height was calculated at 36 evenly spaced intervals. RESULTS: Maximal annular height/commissural width ratio was found to occur at the midpoint of the anterior annulus in all cases. These values averaged 26% +/- 3.1%, whereas those for the midposterior annulus averaged 18% +/- 3.0%. The average commissural width was 35.2 +/- 6.0 mm. Although substantial spatial heterogeneity was observed, regional annular height at a given rotational position was highly conserved among subjects when normalized to commissural width. CONCLUSIONS: These quantitative imaging and analytic techniques demonstrate that the normal human mitral annulus is regionally heterogeneous in its nonplanarity, and they establish a means of describing annular geometry at a regional level. With wider application, these techniques may be used both to characterize pathologic annular geometry and to optimize the design of mitral valve annuloplasty devices.

Regional and global patterns of annular remodeling in ischemic mitral regurgitation.

BACKGROUND: The mammalian mitral annulus is saddle shaped. Experimental studies have shown that loss of saddle shape occurs in ischemic mitral regurgitation. However, neither the temporal pattern of global annular remodeling nor the geometric pattern of regional annular remodeling has been described. We sought to characterize these changes using real-time three-dimensional echocardiography in an ovine model. METHODS: Ten sheep underwent real-time three-dimensional echocardiography at baseline and 1 hour and 8 weeks after posterobasal myocardial infarction. Multiple mitral annular geometric indexes were measured at each time point to assess regional and global annular remodeling. RESULTS: One hour after infarction, global annular height decreased from 5.8 +/- 0.5 mm to 4.0 +/- 0.4 mm (p < 0.001) while intercommissural width increased from 29.0 +/- 1.3 mm to 35.7 +/- 1.7 mm (p = 0.023), resulting in a decrease in the global annular height to commissural width ratio from 20.0% +/- 1.6% to 11.2% +/- 0.9% (p < 0.001). Eight weeks after infarction, global annular height decreased to 3.9 +/- 0.2 mm (p < 0.05) while intercommissural width increased to 40.7 +/- 1.5 mm (p < 0.001), resulting in an additional decrease in the global annular height to commissural width ratio to 9.4% +/- 0.4% (p < 0.001). Although annular remodeling involved the entire mitral annulus, there was regional heterogeneity in its extent. CONCLUSIONS: Significant global annular flattening and dilatation occur during the development of ischemic mitral regurgitation in an ovine model. Regional annular remodeling is heterogeneous and is not limited the posterior commissure or the posterior annulus.

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.