Computational Investigation of Transmural Differences in Left Ventricular Contractility.

Myocardial contractility of the left ventricle (LV) plays an essential role in maintaining normal pump function. A recent ex vivo experimental study showed that cardiomyocyte force generation varies across the three myocardial layers of the LV wall. However, the in vivo distribution of myocardial contractile force is still unclear. The current study was designed to investigate the in vivo transmural distribution of myocardial contractility using a noninvasive computational approach. For this purpose, four cases with different transmural distributions of maximum isometric tension (Tmax) and/or reference sarcomere length (lR) were tested with animal-specific finite element (FE) models, in combination with magnetic resonance imaging (MRI), pressure catheterization, and numerical optimization. Results of the current study showed that the best fit with in vivo MRI-derived deformation was obtained when Tmax assumed different values in the subendocardium, midmyocardium, and subepicardium with transmurally varying lR. These results are consistent with recent ex vivo experimental studies, which showed that the midmyocardium produces more contractile force than the other transmural layers. The systolic strain calculated from the best-fit FE model was in good agreement with MRI data. Therefore, the proposed noninvasive approach has the capability to predict the transmural distribution of myocardial contractility. Moreover, FE models with a nonuniform distribution of myocardial contractility could provide a better representation of LV function and be used to investigate the effects of transmural changes due to heart disease.

Effects of using the unloaded configuration in predicting the in vivo diastolic properties of the heart.

Computational models are increasingly being used to investigate the mechanical properties of cardiac tissue. While much insight has been gained from these studies, one important limitation associated with computational modeling arises when using in vivo images of the heart to generate the reference state of the model. An unloaded reference configuration is needed to accurately represent the deformation of the heart. However, it is rare for a beating heart to actually reach a zero-pressure state during the cardiac cycle. To overcome this, a computational technique was adapted to determine the unloaded configuration of an in vivo porcine left ventricle (LV). In the current study, in vivo measurements were acquired using magnetic resonance images (MRI) and synchronous pressure catheterization in the LV (N = 5). The overall goal was to quantify the effects of using early-diastolic filling as the reference configuration (common assumption used in modeling) versus using the unloaded reference configuration for predicting the in vivo properties of LV myocardium. This was accomplished by using optimization to minimize the difference between MRI measured and finite element predicted strains and cavity volumes. The results show that when using the unloaded reference configuration, the computational method predicts material properties for LV myocardium that are softer and less anisotropic than when using the early-diastolic filling reference configuration. This indicates that the choice of reference configuration could have a significant impact on capturing the realistic mechanical response of the heart.

Computational Modeling of Healthy Myocardium in Diastole.

In order to better understand the mechanics of the heart and its disorders, engineers increasingly make use of the finite element method (FEM) to investigate healthy and diseased cardiac tissue. However, FEM is only as good as the underlying constitutive model, which remains a major challenge to the biomechanics community. In this study, a recently developed structurally based constitutive model was implemented to model healthy left ventricular myocardium during passive diastolic filling. This model takes into account the orthotropic response of the heart under loading. In-vivo strains were measured from magnetic resonance images (MRI) of porcine hearts, along with synchronous catheterization pressure data, and used for parameter identification of the passive constitutive model. Optimization was performed by minimizing the difference between MRI measured and FE predicted strains and cavity volumes. A similar approach was followed for the parameter identification of a widely used phenomenological constitutive law, which is based on a transversely isotropic material response. Results indicate that the parameter identification with the structurally based constitutive law is more sensitive to the assigned fiber architecture and the fit between the measured and predicted strains is improved with more realistic sheet angles. In addition, the structurally based model is capable of generating a more physiological end-diastolic pressure-volume relationship in the ventricle.

MRI evaluation of injectable hyaluronic acid-based hydrogel therapy to limit ventricular remodeling after myocardial infarction.

Injectable biomaterials are an attractive therapy to attenuate left ventricular (LV) remodeling after myocardial infarction (MI). Although studies have shown that injectable hydrogels improve cardiac structure and function in vivo, temporal changes in infarct material properties after treatment have not been assessed. Emerging imaging and modeling techniques now allow for serial, non-invasive estimation of infarct material properties. Specifically, cine magnetic resonance imaging (MRI) assesses global LV structure and function, late-gadolinium enhancement (LGE) MRI enables visualization of infarcted tissue to quantify infarct expansion, and spatial modulation of magnetization (SPAMM) tagging provides passive wall motion assessment as a measure of tissue strain, which can all be used to evaluate infarct properties when combined with finite element (FE) models. In this work, we investigated the temporal effects of degradable hyaluronic acid (HA) hydrogels on global LV remodeling, infarct thinning and expansion, and infarct stiffness in a porcine infarct model for 12 weeks post-MI using MRI and FE modeling. Hydrogel treatment led to decreased LV volumes, improved ejection fraction, and increased wall thickness when compared to controls. FE model simulations demonstrated that hydrogel therapy increased infarct stiffness for 12 weeks post-MI. Thus, evaluation of myocardial tissue properties through MRI and FE modeling provides insight into the influence of injectable hydrogel therapies on myocardial structure and function post-MI.

Temporal Changes in Infarct Material Properties: An In Vivo Assessment Using Magnetic Resonance Imaging and Finite Element Simulations.

BACKGROUND: Infarct expansion initiates and sustains adverse left ventricular (LV) remodeling after myocardial infarction (MI) and is influenced by temporal changes in infarct material properties. Data from ex vivo biaxial extension testing support this hypothesis; however, infarct material properties have never been measured in vivo. The goal of the current study was to serially quantify the in vivo material properties and fiber orientation of infarcted myocardium over a 12-week period in a porcine model of MI. METHODS: A combination of magnetic resonance imaging (MRI), catheterization, finite element modeling, and numeric optimization was used to analyze posterolateral MI. Specifically, properties were determined by minimizing the difference between in vivo strains and volume calculated from MRI and strains and volume predicted by finite element modeling. RESULTS: In 1 week after MI, the infarct region was found to be approximately 20 times stiffer than normal diastolic myocardium. Over the course of 12 weeks, the infarct region became progressively less stiff as the LV dilated and ejection fraction decreased. The infarct thinned by nearly half during the remodeling period, and infarct fiber angles became more circumferentially oriented. CONCLUSIONS: The results reported here are consistent with previously described ex vivo biaxial extension studies of infarct material properties and the circumferential change of collagen orientation in posterolateral infarcts. The current study represents a significant advance in that the method used allows for the serial assessment of an individual infarct in vivo over time and avoids the inherent limitations related to the testing of excised tissues.

The Influence of Mitral Annuloplasty on Left Ventricular Flow Dynamics.

BACKGROUND: Mitral valve (MV) repair using annuloplasty rings is the preferred method of treatment for MV regurgitation, but the impact of annuloplasty ring placement on left ventricular intraventricular flow has not been studied. METHODS: Annuloplasty rings of varying sizes were placed in 5 healthy sheep (intercommissural ring sizes were 24, 26, 28, 30, and 32 mm), and three-dimensional phase contrast magnetic resonance imaging (4D flow MRI) was performed before and 1 week after ring placement. RESULTS: Normal diastolic flow consisted of diastolic intraventricular vortices that naturally unwound during systole. Postsurgical intraventricular flow was highly disturbed in all sheep, and the disturbance was greatest for undersized rings. Ring size was highly correlated with the diastolic inflow angle (Pearson's r = -0.62, p < 0.1, 95% confidence interval: -0.92 to 0.14). There was a mean angle increase of mean diastolic inflow angle increase of 12.3 degrees (< 30 mm, p < 0.01, 95% confidence interval: 4.8 to 19.6) for rings less than 30 mm. There was an inverse relationship between peak velocity and annuloplasty ring area (Pearson's r = -0.80, p < 0.05, 95% confidence interval: -0.96 to -0.2). Transmitral pressure gradients increased significantly from baseline 0.73 ± 0.18 mm Hg to after annuloplasty 2.31 ± 1.04 mm Hg (p < 0.05). CONCLUSIONS: Mitral valve annuloplasty ring placement disturbs normal left ventricular intraventricular flow patterns, and the degree of disturbance is closely associated with annuloplasty ring size.

Development of off-pump mitral valve replacement in a porcine model.

PURPOSE: We describe our initial experience with on-bypass and off-bypass (off-pump) mitral valve replacement with the modified version of our novel catheter-based sutureless mitral valve (SMV) technology, which was developed to atraumatically anchor and seal in the mitral position. DESCRIPTION: The SMV is a self-expanding device consisting of a custom designed nitinol framework and a pericardial leaflet valve mechanism. For the current studies, our original device was modified (SMV2) to reduce the delivery profile and to allow for controlled deployment while still maintaining the key principles necessary for atraumatic anchoring and sealing in the mitral valve position. EVALUATION: Ten Yorkshire pigs underwent successful SMV2 device implantation through a left atriotomy (on-pump, n = 6; off-pump, n = 4). Echocardiography and angiography revealed excellent left ventricular systolic function, no significant perivalvular leak, no mitral valve stenosis, no left ventricular outflow tract obstruction, and no aortic valve insufficiency. Postmortem examination demonstrated that the SMV2 devices were anchored securely. CONCLUSIONS: This study demonstrates the feasibility and short-term success of off-pump mitral valve replacement using a novel, catheter-based device in a porcine model.

Regional myocardial three-dimensional principal strains during postinfarction remodeling.

BACKGROUND: The purpose of this study was to quantify myocardial three-dimensional (3D) principal strains as the left ventricle (LV) remodels after myocardial infarction (MI). Serial quantification of myocardial strains is important for understanding the mechanical response of the LV to MI. Principal strains convert the 3D LV wall-based strain matrix with three normal and three shear elements, to a matrix with three nonzero normal elements, thereby eliminating the shear elements, which are difficult to physically interpret. METHODS: The study was designed to measure principal strains of the remote, border zone, and infarct regions in a porcine model of post-MI LV remodeling. Magnetic resonance imaging was used to measure function and strain at baseline, 1 week, and 4 weeks after infarct. Principal strain was measured using 3D acquisition and the optical flow method for displacement tracking. RESULTS: Principal strains were altered as the LV remodeled. Maximum principal strain magnitude decreased in all regions, including the noninfarcted remote, while maximum principal strain angles rotated away from the radial direction in the border zone and infarct. Minimum principal strain magnitude followed a similar pattern; however, strain angles were altered in all regions. Evolution of principal strains correlated with adverse LV remodeling. CONCLUSIONS: Using a state-of-the-art imaging and optical flow method technique, 3D principal strains can be measured serially after MI in pigs. Results are consistent with progressive infarct stretching as well as with decreased contractile function in the border zone and remote myocardial regions.

Estimating passive mechanical properties in a myocardial infarction using MRI and finite element simulations.

Myocardial infarction (MI) triggers a series of maladaptive events that lead to structural and functional changes in the left ventricle. It is crucial to better understand the progression of adverse remodeling, in order to develop effective treatment. In addition, being able to assess changes in vivo would be a powerful tool in the clinic. The goal of the current study is to quantify the in vivo material properties of infarcted and remote myocardium 1 week after MI, as well as the orientation of collagen fibers in the infarct. This will be accomplished by using a combination of magnetic resonance imaging (MRI), catheterization, finite element modeling, and numerical optimization to analyze a porcine model ([Formula: see text]) of posterolateral myocardial infarction. Specifically, properties will be determined by minimizing the difference between in vivo strains and volume calculated from MRI and finite element model predicted strains and volume. The results indicate that the infarct region is stiffer than the remote region and that the infarct collagen fibers become more circumferentially oriented 1 week post-MI. These findings are consistent with previous studies, which employed ex vivo techniques. The proposed methodology will ultimately provide a means of predicting remote and infarct mechanical properties in vivo at any time point post-MI.

Injectable microsphere gel progressively improves global ventricular function, regional contractile strain, and mitral regurgitation after myocardial infarction.

BACKGROUND: There is continued need for therapies which reverse or abate the remodeling process after myocardial infarction (MI). In this study, we evaluate the longitudinal effects of calcium hydroxyapatite microsphere gel on regional strain, global ventricular function, and mitral regurgitation (MR) in a porcine MI model. METHODS: Twenty-five Yorkshire swine were enrolled. Five were dedicated weight-matched controls. Twenty underwent posterolateral infarction by direct ligation of the circumflex artery and its branches. Infarcted animals were randomly divided into the following 4 groups: 1-week treatment; 1-week control; 4-week treatment; and 4-week control. After infarction, animals received either twenty 150 µL calcium hydroxyapatite gel or saline injections within the infarct. At their respective time points, echocardiograms, cardiac magnetic resonance imaging, and tissue were collected for evaluation of MR, regional and global left ventricular function, wall thickness, and collagen content. RESULTS: Global and regional left ventricular functions were depressed in all infarcted subjects at 1 week compared with healthy controls. By 4-weeks post-infarction, global function had significantly improved in the calcium hydroxyapatite group compared with infarcted controls (ejection fraction 0.485 ± 0.019 vs 0.38 ± 0.017, p < 0.01). Similarly, regional borderzone radial contractile strain (16.3% ± 1.5% vs 11.2% ± 1.5%, p = 0.04), MR grade (0.4 ± 0.2 vs 1.2 ± 0.2, p = 0.04), and infarct thickness (7.8 ± 0.5 mm vs 4.5 ± 0.2 mm, p < 0.01) were improved at this time point in the treatment group compared with infarct controls. CONCLUSIONS: Calcium hydroxyapatite injection after MI progressively improves global left ventricular function, borderzone function, and mitral regurgitation. Using novel biomaterials to augment infarct material properties is a viable alternative in the current management of heart failure.

Three-dimensional ultrasound-derived physical mitral valve modeling.

PURPOSE: Advances in mitral valve repair and adoption have been partly attributed to improvements in echocardiographic imaging technology. To educate and guide repair surgery further, we have developed a methodology for fast production of physical models of the valve using novel three-dimensional (3D) echocardiographic imaging software in combination with stereolithographic printing. DESCRIPTION: Quantitative virtual mitral valve shape models were developed from 3D transesophageal echocardiographic images using software based on semiautomated image segmentation and continuous medial representation algorithms. These quantitative virtual shape models were then used as input to a commercially available stereolithographic printer to generate a physical model of the each valve at end systole and end diastole. EVALUATION: Physical models of normal and diseased valves (ischemic mitral regurgitation and myxomatous degeneration) were constructed. There was good correspondence between the virtual shape models and physical models. CONCLUSIONS: It was feasible to create a physical model of mitral valve geometry under normal, ischemic, and myxomatous valve conditions using 3D printing of 3D echocardiographic data. Printed valves have the potential to guide surgical therapy for mitral valve disease.

Targeted injection of a biocomposite material alters macrophage and fibroblast phenotype and function following myocardial infarction: relation to left ventricular remodeling.

A treatment target for progressive left ventricular (LV) remodeling prevention following myocardial infarction (MI) is to affect structural changes directly within the MI region. One approach is through targeted injection of biocomposite materials, such as calcium hydroxyapatite microspheres (CHAM), into the MI region. In this study, the effects of CHAM injections upon key cell types responsible for the MI remodeling process, the macrophage and fibroblast, were examined. MI was induced in adult pigs before randomization to CHAM injections (20 targeted 0.1-ml injections within MI region) or saline. At 7 or 21 days post-MI (n = 6/time point per group), cardiac magnetic resonance imaging was performed, followed by macrophage and fibroblast isolation. Isolated macrophage profiles for monocyte chemotactic macrophage inflammatory protein-1 as measured by real-time polymerase chain reaction increased at 7 days post-MI in the CHAM group compared with MI only (16.3 ± 6.6 versus 1.7 ± 0.6 cycle times values, P < 0.05), and were similar by 21 days post-MI. Temporal changes in fibroblast function and smooth muscle actin (SMA) expression relative to referent control (n = 5) occurred with MI. CHAM induced increases in fibroblast proliferation, migration, and SMA expression-indicative of fibroblast transformation. By 21 days, CHAM reduced LV dilation (diastolic volume: 75 ± 2 versus 97 ± 4 ml) and increased function (ejection fraction: 48 ± 2% versus 38 ± 2%) compared with MI only (both P < 0.05). This study identified that effects on macrophage and fibroblast differentiation occurred with injection of biocomposite material within the MI, which translated into reduced adverse LV remodeling. These unique findings demonstrate that biomaterial injections impart biologic effects upon the MI remodeling process over any biophysical effects.

Real-time magnetic resonance imaging technique for determining left ventricle pressure-volume loops.

BACKGROUND: Rapid determination of the left ventricular (LV) pressure-volume (PV) relationship as loading conditions are varied is the gold standard for assessment of LV function. Cine magnetic resonance imaging (MRI) does not have sufficient spatiotemporal resolution to assess beat-to-beat changes of the LV PV relationship required to measure the LV end-systolic elastance (EES) or preload-recruitable stroke work (PRSW). Our aim was to investigate real-time MRI and semiautomated LV measurement of LV volume to measure PV relations in large animals under normal and inotropically stressed physiologic conditions. METHODS: We determined that PV relationships could be accurately measured using an image exposure time Tex less than 100 ms and frame rate Tfr less than 50 ms at elevated heart rates (∼140 beats per minute) using a golden angle radial MRI k-space trajectory and active contour segmentation. RESULTS: With an optimized exposure time (Tex=95 ms and frame rate Tfr=2.8 ms), we found that there was no significant difference between cine and real-time MRI at rest in end-diastolic volume, end-systolic volume, ejection fraction, stroke volume, or cardiac output (n=5, p<0.05) at either normal or elevated heart rates. We found EES increased from 1.9±0.7 to 3.1±0.3 mm Hg/mL and PRSW increased from 6.2±1.2 to 9.1±0.9 mm Hg during continuous intravenous dobutamine infusion (n=5, p<0.05). CONCLUSIONS: Real-time MRI can assess LV volumes, EES, and PRSW at baseline and elevated inotropic states.

Local hydrogel release of recombinant TIMP-3 attenuates adverse left ventricular remodeling after experimental myocardial infarction.

An imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) contributes to the left ventricle (LV) remodeling that occurs after myocardial infarction (MI). However, translation of these observations into a clinically relevant, therapeutic strategy remains to be established. The present study investigated targeted TIMP augmentation through regional injection of a degradable hyaluronic acid hydrogel containing recombinant TIMP-3 (rTIMP-3) in a large animal model. MI was induced in pigs by coronary ligation. Animals were then randomized to receive targeted hydrogel/rTIMP-3, hydrogel alone, or saline injection and followed for 14 days. Instrumented pigs with no MI induction served as referent controls. Multimodal imaging (fluoroscopy/echocardiography/magnetic resonance imaging) revealed that LV ejection fraction was improved, LV dilation was reduced, and MI expansion was attenuated in the animals treated with rTIMP-3 compared to all other controls. A marked reduction in proinflammatory cytokines and increased smooth muscle actin content indicative of myofibroblast proliferation occurred in the MI region with hydrogel/rTIMP-3 injections. These results provide the first proof of concept that regional sustained delivery of an MMP inhibitor can effectively interrupt adverse post-MI remodeling.

Minimally invasive delivery of a novel direct epicardial assist device in a porcine heart failure model.

OBJECTIVE: Despite advances in design, modern ventricular assist device placement involves median sternotomy and cardiopulmonary bypass and is associated with infectious/embolic complications. In this study, we examine the feasibility and function of a novel minimally invasive, non-blood-contacting epicardial assist device in a porcine ischemic cardiomyopathy model. METHODS: Feasibility was first tested in an ex vivo thoracoscopic trainer box with slaughterhouse hearts. Five male Yorkshire swine underwent selective ligation of the circumflex artery to create a posterolateral infarct Twelve weeks after infarct, all animals underwent left minithoracotomy. A custom inflatable bladder was positioned over the epicardial surface of the infarct and firmly secured to the surrounding border zone myocardium with polypropylene mesh and minimally invasive mesh tacks. An external gas pulsation system actively inflated and deflated the bladder in synchrony with the cardiac cycle. All animals then underwent cardiac magnetic resonance imaging to assess ventricular function. RESULTS: All subjects successfully underwent off-pump placement of the epicardial assist device via minithoracotomy. Ejection fraction significantly improved from 29.1% ± 4.8% to 39.6% ± 4.23% (P < 0.001) when compared with pretreatment. End-systolic volume decreased (76.6 ± 13.3 mL vs 62.4 ± 12.0 mL, P < 0.001) and stroke volume increased (28.6 ± 3.4 mL vs 37.9 ± 3.1 mL, P < 0.05) when assisted. No change was noted in end-diastolic volume (105.1 ± 11.4 vs 100.3 ± 12.7). On postmortem examination, mesh fixation and device position were excellent in all cases. No adverse events were encountered. CONCLUSIONS: Directed epicardial assistance improves ventricular function in a porcine ischemic cardiomyopathy model and may provide a safe alternative to currently available ventricular assist device therapies. Further, the technique used for device positioning and fixation suggests that an entirely thoracoscopic approach is possible.

Statistical assessment of normal mitral annular geometry using automated three-dimensional echocardiographic analysis.

BACKGROUND: The basis of mitral annuloplasty ring design has progressed from qualitative surgical intuition to experimental and theoretical analysis of annular geometry with quantitative imaging techniques. In this work, we present an automated three-dimensional (3D) echocardiographic image analysis method that can be used to statistically assess variability in normal mitral annular geometry to support advancement in annuloplasty ring design. METHODS: Three-dimensional patient-specific models of the mitral annulus were automatically generated from 3D echocardiographic images acquired from subjects with normal mitral valve structure and function. Geometric annular measurements including annular circumference, annular height, septolateral diameter, intercommissural width, and the annular height to intercommissural width ratio were automatically calculated. A mean 3D annular contour was computed, and principal component analysis was used to evaluate variability in normal annular shape. RESULTS: The following mean ± standard deviations were obtained from 3D echocardiographic image analysis: annular circumference, 107.0 ± 14.6 mm; annular height, 7.6 ± 2.8 mm; septolateral diameter, 28.5 ± 3.7 mm; intercommissural width, 33.0 ± 5.3 mm; and annular height to intercommissural width ratio, 22.7% ± 6.9%. Principal component analysis indicated that shape variability was primarily related to overall annular size, with more subtle variation in the skewness and height of the anterior annular peak, independent of annular diameter. CONCLUSIONS: Patient-specific 3D echocardiographic-based modeling of the human mitral valve enables statistical analysis of physiologically normal mitral annular geometry. The tool can potentially lead to the development of a new generation of annuloplasty rings that restore the diseased mitral valve annulus back to a truly normal geometry.

Preclinical evaluation of the engineered stem cell chemokine stromal cell-derived factor 1α analog in a translational ovine myocardial infarction model.

RATIONALE: After myocardial infarction, there is an inadequate blood supply to the myocardium, and the surrounding borderzone becomes hypocontractile. OBJECTIVE: To develop a clinically translatable therapy, we hypothesized that in a preclinical ovine model of myocardial infarction, the modified endothelial progenitor stem cell chemokine, engineered stromal cell-derived factor 1α analog (ESA), would induce endothelial progenitor stem cell chemotaxis, limit adverse ventricular remodeling, and preserve borderzone contractility. METHODS AND RESULTS: Thirty-six adult male Dorset sheep underwent permanent ligation of the left anterior descending coronary artery, inducing an anteroapical infarction, and were randomized to borderzone injection of saline (n=18) or ESA (n=18). Ventricular function, geometry, and regional strain were assessed using cardiac MRI and pressure-volume catheter transduction. Bone marrow was harvested for in vitro analysis, and myocardial biopsies were taken for mRNA, protein, and immunohistochemical analysis. ESA induced greater chemotaxis of endothelial progenitor stem cells compared with saline (P<0.01) and was equivalent to recombinant stromal cell-derived factor 1α (P=0.27). Analysis of mRNA expression and protein levels in ESA-treated animals revealed reduced matrix metalloproteinase 2 in the borderzone (P<0.05), with elevated levels of tissue inhibitor of matrix metalloproteinase 1 and elastin in the infarct (P<0.05), whereas immunohistochemical analysis of borderzone myocardium showed increased capillary and arteriolar density in the ESA group (P<0.01). Animals in the ESA treatment group also had significant reductions in infarct size (P<0.01), increased maximal principle strain in the borderzone (P<0.01), and a steeper slope of the end-systolic pressure-volume relationship (P=0.01). CONCLUSIONS: The novel, biomolecularly designed peptide ESA induces chemotaxis of endothelial progenitor stem cells, stimulates neovasculogenesis, limits infarct expansion, and preserves contractility in an ovine model of myocardial infarction.

Regional annular geometry in patients with mitral regurgitation: implications for annuloplasty ring selection.

BACKGROUND: The saddle shape of the normal mitral annulus has been quantitatively described by several groups. There is strong evidence that this shape is important to valve function. A more complete understanding of regional annular geometry in diseased valves may provide a more educated approach to annuloplasty ring selection and design. We hypothesized that mitral annular shape is markedly distorted in patients with diseased valves. METHODS: Real-time 3-dimensional echocardiography was performed in 20 patients with normal mitral valves, 10 with ischemic mitral regurgitation, and 20 with myxomatous mitral regurgitation (MMR). Thirty-six annular points were defined to generate a 3-dimensional model of the annulus. Regional annular parameters were measured from these renderings. Left ventricular inner diameter was obtained from 2-dimensional echocardiographic images. RESULTS: Annular geometry was significantly different among the three groups. The annuli were larger in the MMR and in the ischemic mitral regurgitation groups. The annular enlargement was greater and more pervasive in the MMR group. Both diseases were associated with annular flattening, although though the regional distribution of that flattening was different between groups. Left ventricular inner diameter was increased in both groups. However, relative to the Left ventricular inner diameter, the annulus was disproportionately dilated in the MMR group. CONCLUSIONS: Patients with MMR and ischemic mitral regurgitation have enlarged and flattened annuli. In the case of MMR, annular distortions may be the driving factor leading to valve incompetence. These data suggest that the goal of annuloplasty should be the restoration of normal annular saddle shape and that the use of flexible, partial, and flat rings may be ill advised.

In-vivo mitral annuloplasty ring transducer: implications for implantation and annular downsizing.

Mitral annuloplasty has been a keystone to the success of mitral valve repair in functional mitral regurgitation. Understanding the complex interplay between annular-ring stresses and left ventricular function has significant implications for patient-ring selection, repair failure, and patient safety. A step towards assessing these challenges is developing a transducer that can be implanted in the exact method as commercially available rings and can quantify multidirectional ring loading. An annuloplasty ring transducer was developed to measure stresses at eight locations on both the in-plane and out-of-plane surfaces of an annuloplasty ring's titanium core. The transducer was implanted in an ovine subject using 10 sutures at near symmetric locations. At implantation, the ring was observed to undersize the mitral annulus. The flaccid annulus exerted both compressive (-) and tensile stresses (+) on the ring ranging from -3.17 to 5.34 MPa. At baseline hemodynamics, stresses cyclically changed and peaked near mid-systole. Mean changes in cyclic stress from ventricular diastole to mid-systole ranged from -0.61 to 0.46 MPa (in-plane direction) and from -0.49 to 1.13 MPa (out-of-plane direction). Results demonstrate the variability in ring stresses that can be introduced during implantation and the cyclic contraction of the mitral annulus. Ring stresses at implantation were approximately 4 magnitudes larger than the cyclic changes in stress throughout the cardiac cycle. These methods will be extended to ring transducers of differing size and geometry. Upon additional investigation, these data will contribute to improved knowledge of annulus-ring stresses, LV function, and the safer development of mitral repair techniques.

Sutureless mitral valve replacement: initial steps toward a percutaneous procedure.

PURPOSE: Transcatheter mitral valve replacement would represent a major advance in heart valve therapy. Such a device requires a specialized anchoring and sealing technology. This study was designed to test the feasibility of a novel mitral valve replacement device (the sutureless mitral valve [SMV]) designed to anchor and seal in the mitral position without need for sutures. DESCRIPTION: The SMV is a self-expanding device consisting of a custom-designed nitinol framework and a pericardial leaflet valve mechanism. EVALUATION: Ten sheep underwent successful surgical SMV device implantation. All animals underwent cardiac catheterization 6 hours postoperatively. Hemodynamic, angiographic, echocardiographic and necroscopic data were recorded. The mean aortic cross-clamp time was 9.5 ± 3.1 minutes. Echocardiography and angiography revealed excellent left ventricular systolic function, no significant perivalvular leak, no mitral valve stenosis, no left ventricular outflow tract obstruction, and no aortic valve insufficiency. Necropsy demonstrated that the SMV devices were anchored securely. CONCLUSIONS: This study demonstrates the feasibility and short-term success of sutureless mitral valve replacement using a novel SMV device.