Patient-Specific Quantitative In-Vivo Assessment of Human Mitral Valve Leaflet Strain Before and After MitraClip Repair.

PURPOSE: Mitral regurgitation (MR) is a highly prevalent and deadly cardiac disease characterized by improper mitral valve (MV) leaflet coaptation. Among the plethora of available treatment strategies, the MitraClip is an especially safe option, but optimizing its long-term efficacy remains an urgent challenge. METHODS: We applied our noninvasive image-based strain computation pipeline [1] to intraoperative transesophageal echocardiography datasets taken from ten patients undergoing MitraClip repair, spanning a range of MR etiologies and MitraClip configurations. We then analyzed MV leaflet strains before and after MitraClip implementation to develop a better understanding of (1) the pre-operative state of human regurgitant MV, and (2) the MitraClip's impact on the MV leaflet deformations. RESULTS: The MV pre-operative strain fields were highly variable, underscoring both the heterogeneity of the MR in the patient population and the need for patient-specific treatment approaches. Similarly, there were no consistent overall post-operative strain patterns, although the average A2 segment radial strain difference between pre- and post-operative states was consistently positive. In contrast, the post-operative strain fields were better correlated to their respective pre-operative strain fields than to the inter-patient post-operative strain fields. This quantitative result implies that the patient specific pre-operative state of the MV guides its post-operative deformation, which suggests that the post-operative state can be predicted using pre-operative data-derived modelling alone. CONCLUSIONS: The pre-operative MV leaflet strain patterns varied considerably across the range of MR disease states and after MitraClip repair. Despite large inter-patient heterogeneity, the post-operative deformation appears principally dictated by the pre-operative deformation state. This novel finding suggests that though the variation in MR functional state and MitraClip-induced deformation were substantial, the post-operative state can be predicted from the pre-operative data alone. This study suggests that, with use of larger patient cohort and corresponding long-term outcomes, quantitative predictive factors of MitraClip durability can be identified.

Quantitative in vivo assessment of human mitral valve coaptation area after undersized ring annuloplasty repair for ischemic mitral regurgitation.

Objectives: Long-term outcomes of mitral valve repair procedures to correct ischemic mitral regurgitation remain unpredictable, due to an incomplete understanding of the disease process and the inability to reliably quantify the coaptation zone using echocardiography. Our objective was to quantify patient-specific mitral valve coaptation behavior from clinical echocardiographic images obtained before and after repair to assess coaptation restoration and its relationship with long-term repair durability. Methods: To circumvent the limitations of clinical imaging, we applied a simulation-based shape-matching technique that allowed high-fidelity reconstructions of the complete mitral valve in the systolic configuration. We then applied this method to an extant database of human regurgitant mitral valves before and after undersized ring annuloplasty to quantify the effect of the repair on mitral valve coaptation geometry. Results: Our method was able to successfully resolve the coaptation zone into distinct contacting and redundant regions. Results indicated that in patients whose regurgitation recurred 6 months postrepair, both the contacting and redundant regions were larger immediately postrepair compared with patients with no recurrence (P < .05), even when normalized to account for generally larger recurrent valves. Conclusions: Although increasing leaflet coaptation area is an intuitively obvious way to improve long-term repair durability, this study has implied that this may not be a reliable target for mitral valve repair. This study underscores the importance of a rigorous understanding of the consequences of repair techniques on mitral valve behavior, as well as a patient-specific approach to ischemic mitral regurgitation treatment within the context of mitral valve and left ventricle function.

In vivo assessment of mitral valve leaflet remodelling following myocardial infarction.

Each year, more than 40,000 people undergo mitral valve (MV) repair surgery domestically to treat regurgitation caused by myocardial infarction (MI). Although continual MV tissue remodelling following repair is believed to be a major contributor to regurgitation recurrence, the effects of the post-MI state on MV remodelling remain poorly understood. This lack of understanding limits our ability to predict the remodelling of the MV both post-MI and post-surgery to facilitate surgical planning. As a necessary first step, the present study was undertaken to noninvasively quantify the effects of MI on MV remodelling in terms of leaflet geometry and deformation. MI was induced in eight adult Dorset sheep, and real-time three-dimensional echocardiographic (rt-3DE) scans were collected pre-MI as well as at 0, 4, and 8 weeks post-MI. A previously validated image-based morphing pipeline was used to register corresponding open- and closed-state scans and extract local in-plane strains throughout the leaflet surface at systole. We determined that MI induced permanent changes in leaflet dimensions in the diastolic configuration, which increased with time to 4 weeks, then stabilised. MI substantially affected the systolic shape of the MV, and the range of stretch experienced by the MV leaflet at peak systole was substantially reduced when referred to the current time-point. Interestingly, when we referred the leaflet strains to the pre-MI configuration, the systolic strains remained very similar throughout the post-MI period. Overall, we observed that post-MI ventricular remodeling induced permanent changes in the MV leaflet shape. This predominantly affected the MV's diastolic configuration, leading in turn to a significant decrease in the range of stretch experienced by the leaflet when referenced to the current diastolic configuration. These findings are consistent with our previous work that demonstrated increased plastic (i.e. non-recoverable) leaflet deformations post-MI, that was completely accounted for by the associated changes in collagen fiber structure. Moreover, we demonstrated through noninvasive methods that the state of the MV leaflet can elucidate the progression and extent of MV adaptation following MI and is thus highly relevant to the design of current and novel patient specific minimally invasive surgical repair strategies.

Dynamic Volumetric Assessment of the Aortic Root: The Influence of Bicuspid Aortic Valve Competence.

BACKGROUND: Aortic root evaluation is conventionally based on 2-dimensional measurements at a single phase of the cardiac cycle. This work presents an image analysis method for assessing dynamic 3-dimensional changes in the aortic root of minimally calcified bicuspid aortic valves (BAVs) with and without moderate to severe aortic regurgitation. METHODS: The aortic root was segmented over the full cardiac cycle in 3-dimensional transesophageal echocardiographic images acquired from 19 patients with minimally calcified BAVs and from 16 patients with physiologically normal tricuspid aortic valves (TAVs). The size and dynamics of the aortic root were assessed using the following image-derived measurements: absolute mean root volume and mean area at the level of the ventriculoaortic junction, sinuses of Valsalva, and sinotubular junction, as well as normalized root volume change and normalized area change of the ventriculoaortic junction, sinuses of Valsalva, and sinotubular junction over the cardiac cycle. RESULTS: Normalized volume change over the cardiac cycle was significantly greater in BAV roots with moderate to severe regurgitation than in normal TAV roots and in BAV roots with no or mild regurgitation. Aortic root dynamics were most significantly different at the mid-level of the sinuses of Valsalva in BAVs with moderate to severe regurgitation than in competent TAVs and BAVs. CONCLUSIONS: Echocardiographic reconstruction of the aortic root demonstrates significant differences in dynamics of BAV roots with moderate to severe regurgitation relative to physiologically normal TAVs and competent BAVs. This finding may have implications for risk of future dilatation, dissection, or rupture, which warrant further investigation.

Assessment of myocardial injury after reperfused infarction by T1ρ cardiovascular magnetic resonance.

BACKGROUND: The evolution of T1ρ and of other endogenous contrast methods (T2, T1) in the first month after reperfused myocardial infarction (MI) is uncertain. We conducted a study of reperfused MI in pigs to serially monitor T1ρ, T2 and T1 relaxation, scar size and transmurality at 1 and 4 weeks post-MI. METHODS: Ten Yorkshire swine underwent 90 min of occlusion of the circumflex artery and reperfusion. T1ρ, T2 and native T1 maps and late gadolinium enhanced (LGE) cardiovascular magnetic resonance (CMR) data were collected at 1 week (n = 10) and 4 weeks (n = 5). Semi-automatic FWHM (full width half maximum) thresholding was used to assess scar size and transmurality and compared to histology. Relaxation times and contrast-to-noise ratio were compared in healthy and remote myocardium at 1 and 4 weeks. Linear regression and Bland-Altman was performed to compare infarct size and transmurality. RESULTS: Relaxation time differences between infarcted and remote myocardial tissue were ∆T1 (infarct-remote) = 421.3 ± 108.8 (1 week) and 480.0 ± 33.2 ms (4 week), ∆T1ρ = 68.1 ± 11.6 and 74.3 ± 14.2, and ∆T2 = 51.0 ± 10.1 and 59.2 ± 11.4 ms. Contrast-to-noise ratio was CNRT1 = 7.0 ± 3.5 (1 week) and 6.9 ± 2.4 (4 week), CNRT1ρ = 12.0 ± 6.2 and 12.3 ± 3.2, and CNRT2 = 8.0 ± 3.6 and 10.3 ± 5.8. Infarct size was not significantly different for T1ρ, T1 and T2 compared to LGE (p = 0.14) and significantly decreased from 1 to 4 weeks (p < 0.01). Individual infarct size changes were ∆T1ρ = -3.8%, ∆T1 = -3.5% and ∆LGE = -2.8% from 1 - 4 weeks, but there was no observed change in infarct size for T2 or histologically. CONCLUSIONS: T1ρ was highly correlated with alterations left ventricle (LV) pathology at 1 and 4 weeks post-MI and therefore it may be a useful method endogenous contrast imaging of infarction.

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.

An inverse modeling approach for stress estimation in mitral valve anterior leaflet valvuloplasty for in-vivo valvular biomaterial assessment.

Estimation of regional tissue stresses in the functioning heart valve remains an important goal in our understanding of normal valve function and in developing novel engineered tissue strategies for valvular repair and replacement. Methods to accurately estimate regional tissue stresses are thus needed for this purpose, and in particular to develop accurate, statistically informed means to validate computational models of valve function. Moreover, there exists no currently accepted method to evaluate engineered heart valve tissues and replacement heart valve biomaterials undergoing valvular stresses in blood contact. While we have utilized mitral valve anterior leaflet valvuloplasty as an experimental approach to address this limitation, robust computational techniques to estimate implant stresses are required. In the present study, we developed a novel numerical analysis approach for estimation of the in-vivo stresses of the central region of the mitral valve anterior leaflet (MVAL) delimited by a sonocrystal transducer array. The in-vivo material properties of the MVAL were simulated using an inverse FE modeling approach based on three pseudo-hyperelastic constitutive models: the neo-Hookean, exponential-type isotropic, and full collagen-fiber mapped transversely isotropic models. A series of numerical replications with varying structural configurations were developed by incorporating measured statistical variations in MVAL local preferred fiber directions and fiber splay. These model replications were then used to investigate how known variations in the valve tissue microstructure influence the estimated ROI stresses and its variation at each time point during a cardiac cycle. Simulations were also able to include estimates of the variation in tissue stresses for an individual specimen dataset over the cardiac cycle. Of the three material models, the transversely anisotropic model produced the most accurate results, with ROI averaged stresses at the fully-loaded state of 432.6±46.5 kPa and 241.4±40.5 kPa in the radial and circumferential directions, respectively. We conclude that the present approach can provide robust instantaneous mean and variation estimates of tissue stresses of the central regions of the MVAL.

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.

A model of ischemic mitral regurgitation in pigs with three-dimensional echocardiographic assessment.

BACKGROUND AND AIM OF THE STUDY: Ischemic mitral regurgitation (IMR), the incidence of which is increasing, results from annular and subvalvular remodeling after myocardial infarction (MI). Although a sheep model of IMR has been used extensively over the past two decades, the ventricular, coronary and leaflet anatomy in sheep is significantly different from that in humans. In contrast, pigs are more similar to humans with regard to these parameters, and therefore may serve as a better animal to test emerging new technologies designed to treat IMR. METHODS: Twenty-nine pigs (body weight 30-35 kg) underwent left thoracotomy and ligation of the mid main circumflex and distal right posterior descending coronary arteries to create a posterolateral MI. Of these pigs, 18 were used for acute data acquisition, while 11 surviving animals in the chronic group were assessed at eight weeks after MI. Real-time three-dimensional echocardiography was performed at baseline, and at 30 min and eight weeks after MI, to assess geometric changes in the mitral annulus, mitral leaflets and left ventricle. RESULTS: Compared to baseline, the MR grade was increased significantly at eight weeks (0.7 + 0.5 versus 2.0 +/- 1.2), together with a significant decrease in left ventricular ejection fraction (40.3 +/- 6.6% versus 25.8 +/- 7.7%). Significant increases were also noted at eight weeks in the commissural width (30.1 +/- 3.2 mm versus 35.1 +/- 2.9 mm) and septolateral diameter (25.0 +/- 2.0 mm versus 33.8 +/- 5.9 mm), with a resultant increase in mitral annular area (596 +/- 85 versus 931 +/- 181 mm3) and a decrease in the annular height to commissural width ratio (15.7 +/- 2.6% versus 13.7 +/- 1.9%). The mitral valve tenting volume was also increased significantly (1577 +/- 645 versus 2440 +/- 755 mm3). The distance between the papillary muscle tips at baseline and at eight weeks was increased significantly (23.9 +/- 2.5 versus 30.9 +/- 5.2 mm), as was the distance between the posterior papillary muscle tip and the posterior commissure (20.9 +/- 2.7 versus 24.1 +/- 2.8 mm). CONCLUSION: The surgical model described here reliably replicates the changes seen in humans with IMR. Hence, this model can be used for further studies of the pathophysiology of IMR, and of any novel interventions in this challenging clinical area.

Dynamic 3-dimensional echocardiographic assessment of mitral annular geometry in patients with functional mitral regurgitation.

BACKGROUND: Mitral valve (MV) annular dynamics have been well described in animal models of functional mitral regurgitation (FMR). Despite this, little if any data exist regarding the dynamic MV annular geometry in humans with FMR. In the current study we hypothesized that 3-dimensional (3D) echocardiography, in conjunction with commercially available software, could be used to quantify the dynamic changes in MV annular geometry associated with FMR. METHODS: Intraoperative 3D transesophageal echocardiographic data obtained from 34 patients with FMR and 15 controls undergoing cardiac operations were dynamically analyzed for differences in mitral annular geometry with TomTec 4D MV Assessment 2.0 software (TomTec Imaging Systems GmbH, Munich, Germany). RESULTS: In patients with FMR, the mean mitral annular area (14.6 cm(2) versus 9.6 cm(2)), circumference (14.1 cm versus 11.4 cm), anteroposterior (4.0 cm versus 3.0 cm) and anterolateral-posteromedial (4.3 cm versus 3.6 cm) diameters, tenting volume (6.2 mm(3) versus 3.5 mm(3)) and nonplanarity angle (NPA) (154 degrees ± 15 versus 136 degrees ± 11) were greater at all points during systole compared with controls (p < 0.01). Vertical mitral annular displacement (5.8 mm versus 8.3 mm) was reduced in FMR compared with controls (p < 0.01). CONCLUSIONS: There are significant differences in dynamic mitral annular geometry between patients with FMR and those without. We were able to analyze these changes in a clinically feasible fashion. Ready availability of this information has the potential to aid comprehensive quantification of mitral annular function and possibly assist in both clinical decision making and annuloplasty ring selection.

Dynamic assessment of mitral annular force profile in an ovine model.

BACKGROUND: Limited knowledge exists regarding the forces that act on devices implanted in the mitral annulus. Determining the peak magnitudes, directions, rates, variation throughout the cardiac cycle, and change with left ventricular pressure (LVP) will aid in device development and evaluation. METHODS: Novel transducers with the ability to measure forces in the septal-lateral and transverse directions were implanted in six healthy ovine subjects. Forces were measured for cardiac cycles reaching a peak LVP of 90, 125, 150, 175, and 200 mm Hg. RESULTS: The septal-lateral force was observed to significantly increase from 3.9 ± 0.8 N (90) to 5.2 ± 1.0 N (125) p < 0.001, 5.9 ± 0.9 N (150) p < 0.001, 6.4 ± 1.2 N (175) p < 0.001, and 6.7 ± 1.5 N (200 mm Hg) p < 0.001. Similarly, the transverse force was seen to increase from 2.6 ± 0.6 N (90) to 3.8 ± 1.0 N (125) p < 0.01, 4.6 ± 1.3 N (150) p < 0.001, 4.3 ± 1.2 N (175) p < 0.001, and 3.5 ± 0.7 N (200 mm Hg) p < 0.05. In comparison, the septal-lateral force was significantly greater than the transverse force at 90 (p < 0.05), 125 (p < 0.05), 175 (p < 0.001), and 200 mm Hg (p < 0.0005). CONCLUSIONS: Annular forces and their variations with LVP through the cardiac cycle are described. The results demonstrate differences in force magnitude and rate for increasing levels of LVP between the septal-lateral and transverse directions. These directional differences have strong implications in the development of future mitral devices.

Graft selection for aortic root replacement in complex active endocarditis: does it matter?

BACKGROUND: Endocarditis affecting the aortic valve, with abscess formation and root destruction, remains a challenge to treat. Aortic root homografts have been advocated because of a perceived lower risk of infective complications than with other root replacement grafts. However, the theoretical advantage of homografts has not been re-evaluated in the modern era. This report is based on an examination of our results for all aortic root replacements in complex, active endocarditis affecting the aortic valve. METHODS: From 2000 to 2010, 134 patients (70.9% male; mean age 58.3±14.8 years) at our institution underwent aortic root replacement for active endocarditis. Ninety of the patients (67.2%) had a previously implanted prosthetic aortic valve. Our findings for these patients included one or more of the following: abscess (n=110, 82.1%), valve vegetation (n=98, 73.1%), and pseudoaneurysm or rupture or both (n=62, 46.3%). We retrospectively reviewed data for the patients from hospital records and the social security data base. RESULTS: A mechanical composite graft (MC) was used in 43 of the patients (32.1%), a non-homograft biologic valve conduit (BC) in 55 patients (41.0%), and a homograft (HG) valve in 36 patients (26.9%). There was no significant difference among the groups in the incidence of major complications or in-hospital mortality. During a mean follow-up of 32.1±29.4 months, the rates of readmission, reinfection, and reoperation were similar for the three groups. The mean 5-year survival in the study was 58±9% for the MC group, 62±7% for the BC group, and 58 ± 9% for the HG group, respectively (p=0.48). CONCLUSIONS: Aortic root replacement in the presence of complex active infection is associated with significant morbidity and mortality. We report that the rates of major complications and late mortality were similar among MC, BC, and HG groups in our study.

In vivo fluorometric assessment of cyclosporine on mitochondrial function during myocardial ischemia and reperfusion.

BACKGROUND: Cyclosporine A (CsA) limits myocardial reperfusion injury and preserves mitochondrial integrity, but its influence on mitochondrial function has not been described in vivo. Auto-fluorescence of mitochondrial nicotinamide adenine dinucleotide and flavin adenine dinucleotide correlate with mitochondrial dysfunction. We hypothesized that CsA limits mitochondrial dysfunction and that fluorometry can quantify this influence. METHODS: Seventeen rabbits were studied: untreated (UnT, n = 7), CsA preinfarction (CsAp, n = 6), and CsA on reperfusion (CsAr, n = 4). Animals underwent 30 minutes of myocardial ischemia and 3 hours reperfusion. Infarct size was determined by staining. Nicotinamide adenine dinucleotide and flavin adenine dinucleotide fluorescence was continually measured in the risk area. The redox ratio was calculated [flavin adenine dinucleotide(f)/(flavin adenine dinucleotide(f) + nicotinamide adenine dinucleotide(f))]. Electron microscopy evaluated mitochondria morphology. RESULTS: The infarct size by group was 39.1% +/- 1.7% in CsAp, 39.1% +/- 1.7% in CsAr, and 53.4% +/- 1.9% in UnT (p < 0.001). During ischemia, the CsAp group demonstrated less hypoxic reduction, with the redox ratio decreasing to 75.6% +/- 4.1% of baseline. The UnT and CsAr groups deceased to 67.1% +/- 4.0% and 67.2% +/- 3.6%, respectively (p < 0.005). During reperfusion the UnT group redox ratio increased to 1.59 +/- 0.04 times baseline. This increase was blunted in the CsAp (1.17 +/- 0.04, p = 0.026) and CsAr (1.35 +/- 0.02, p = 0.056) groups. Electron microscopy revealed reduced mitochondrial disruption in CsAp (19.7% +/- 7.6%) and CsAr (18.1% +/- 7.1%) rabbits compared with UnT (53.3% +/- 12.5%). CONCLUSIONS: Fluorometric spectroscopy can be used in vivo to quantitatively assess the time course of CsA's influence on the mitochondrial dysfunction associated with myocardial ischemia and reperfusion.

Three-dimensional echocardiographic assessment of changes in mitral valve geometry after valve repair.

BACKGROUND: Application of annuloplasty rings during mitral valve (MV) repair has been shown to significantly change the mitral annular geometry. Until recently, a comprehensive two-dimensional echocardiographic evaluation of annular geometric changes was difficult owing to its nonplanar orientation. In this study, an analysis of the three-dimensional intraoperative transesophageal echocardiographic evaluation of the MV annulus is presented before and immediately after repair. METHODS: We performed three-dimensional geometric analysis on 75 patients undergoing MV repair during coronary artery bypass graft surgery for mitral regurgitation or myxomatous mitral valve disease. Geometric analysis of the MV was performed before and immediately after valve repair with full rings and annuloplasty bands. The acquired three-dimensional volumetric data were analyzed in the operating room. Specific measurements included annular diameter, leaflet lengths, the nonplanarity angle, and the circularity index. Before and after repair data were compared. RESULTS: Complete echocardiographic assessment of the MV was feasible in 69 of 75 patients (92%) within 2 to 3 minutes of acquisition. Placement of full rings resulted in an increase in the nonplanarity angle or a less saddle shape of the native mitral annulus (137 +/- 14 versus 146 +/- 14; p = 0.002. By contrast, the nonplanarity angle did not change significantly after placement of partial rings. CONCLUSIONS: Mitral annular nonplanarity can be assessed in the operating room. Application of full annuloplasty rings resulted in the mitral annulus becoming more planar. Partial annuloplasty bands did not significantly change the nonplanarity angle. Neither of the two types of rings restored the native annular planarity.

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.

In vivo biomechanical assessment of triglycidylamine crosslinked pericardium.

While glutaraldehyde crosslinking is most often used to fabricate bioprosthetic heart valves (BHV) using heterograft tissues, it predisposes BHV to calcification and dramatically stiffens the heterograft tissues. Our group previously reported the synthesis and characterization of a novel epoxy-crosslinker, triglycidylamine (TGA). TGA pretreatment of BHV tissues compared to glutaraldehyde results in both calcification resistance in subdermal implants and improved leaflet compliance. In these prior studies, optimal calcification inhibition was noted with the combined use of TGA with mercapto-aminobisphosphonate (MABP). In the present study, we investigated the hypothesis that bovine pericardium cross-linked with TGA-MABP retains these beneficial biomechanical properties in vivo using a novel mitral valve anterior leaflet (MVAL) ovine valvuloplasty model. Bovine pericardial specimens were crosslinked with either glutaraldehyde or TGA-MABP, from which 1cm2 sections were implanted in the ovine MVAL after removal of the original tissue of the same size. An array of four sonomicrometry transducers were implanted on the corners and used to compute the complete in-surface strain tensor cardiac cycle over the cardiac cycle at 0 and 4 weeks. Following explant samples were fixed in formalin for histology studies. At 4 weeks both treatment groups experienced no dimensional changes in the unloaded state, indicating no shrinkage. When fully loaded during peak systolic ejection, TGA-MABP valvuloplasty patches were significantly more compliant, which did not change at 4 weeks. In contrast, the glutaraldehyde areal strain increased significantly by 4 weeks. Estimated implant stresses for both treatment groups, based on previously measured biomechanical properties [Connolly JM, Alferiev I, Clark-Gruel JN, Eidelman N, Sacks M, Palmatory E, et al. Triglycidylamine crosslinking of porcine aortic valve cusps or bovine pericardium results in improved biocompatibility, biomechanics, and calcification resistance: chemical and biological mechanisms. Am J Pathol 2005;166(1):1-13], were 40 and 250 kPa in the circumferential and radial directions, respectively, which are comparable to predicted BHV peak stress levels. We conclude that TGA-MABP crosslinked bovine pericardium, when subjected to in vivo BHV stress levels in a blood-contacting environment, maintains stable functionality.

Assessment of left ventricular viscoelastic components based on ventricular harmonic behavior.

BACKGROUND: Assessment of left ventricular (LV) function with an emphasis on contractility has been a challenge in cardiac mechanics during the recent decades. The LV function is usually described by the LV pressure-volume (P-V) relationship. Based on this relationship, the ratio of instantaneous pressure to instantaneous volume is an index for LV chamber stiffness. The standard P-V diagrams are easy to interpret but difficult to obtain and require invasive instrumentation for measuring the corresponding volume and pressure data. In the present study, we introduce a technique that can estimate viscoelastic properties, not only the elastic component but also the viscous properties of the LV based on oscillatory behavior of the ventricular chamber and it can be applied non-invasively as well. MATERIALS AND METHODS: The estimation technique is based on modeling the actual long axis displacement of the mitral annulus plane toward the cardiac base as a linear damped oscillator with time-varying coefficients. Elastic deformations resulting from the changes in the ventricular mechanical properties of myocardium are represented as a time-varying spring while the viscous components of the model include a time-varying viscous damper, representing relaxation and the frictional energy loss. To measure the left ventricular axial displacement ten healthy sheep underwent left thoracotomy and sonomicrometry transducers were implanted at the apex and base of the LV. The time-varying parameters of the model were estimated by a standard Recursive Linear Least Squares (RLLS) technique. RESULTS: LV stiffness at end-systole and end-diastole was in the range of 61.86-136 dyne/gxcm and 1.25-21.02 dyne/gxcm, respectively. Univariate linear regression was performed to verify the agreement between the estimated parameters, and the measured values of stiffness. The averaged magnitude of the stiffness and damping coefficients during a complete cardiac cycle were estimated as 58.63+/-12.8 dyne/gxcm and 0 dynexs/gxcm, respectively. CONCLUSION: The results for the estimated elastic coefficients are consistent with the ones obtained from force-displacement diagram. The trend of change in the estimated parameters is also in harmony with the previous studies done using P-V diagram. The only input used in this model is the long axis displacement of the annulus plane, which can also be obtained non-invasively using tissue Doppler or MR imaging.

Border zone geometry increases wall stress after myocardial infarction: contrast echocardiographic assessment.

After myocardial infarction (MI), the border zone expands chronically, causing ventricular dilatation and congestive heart failure (CHF). In an ovine model (n = 4) of anteroapical MI that results in CHF, contrast echocardiography was used to image short-axis left ventricular (LV) cross sections and identify border zone myocardium before and after coronary artery ligation. In the border zone at end systole, the LV endocardial curvature (K) decreased from 0.86 +/- 0.33 cm(-1) at baseline to 0.35 +/- 0.19 cm(-1) at 1 h (P < 0.05), corresponding to a mean decrease of 55%. Also in the border zone, the wall thickness (h) decreased from 1.14 +/- 0.26 cm at baseline to 1.01 +/- 0.25 cm at 1 h (P < 0.05), corresponding to a mean decrease of 11%. By Laplace's law, wall stress is inversely proportional to the product K. h. Therefore, a 55% decrease in K results in a 122% increase in circumferential stress; a 11% decrease in h results in a 12% increase in circumferential stress. These findings indicate that after MI, geometric changes cause increased dynamic wall stress, which likely contributes to border zone expansion and remodeling.