The study of loading mode with in-vitro fatigue testing for mitral annuloplasty ring.

To maintain the physiological dynamics of the mitral annulus, mitral annuloplasty rings (MAR) must be flexible. Enhanced flexibility implies decreased resistance to fatigue and potential for fatigue fracture. This study established new methods to test the flexible fatigue life of MAR in-vitro using numerical analysis; the purpose is that the fatigue test could reflect the real stress distribution in-vivo. Based on the conventional test methods (C1, D1), this paper presents a novel test method (C2, D2). Four testing methods for open-end annuloplasty rings (C1, C2) and closed-end annuloplasty rings (D1, D2) were modelled and their stress distribution calculated by finite element analysis. The mean absolute error (Χ) and the Pearson correlation coefficient (Φ) were used to quantify the difference in stress distribution between the loading modes in-vivo and in-vitro. For closed-end annuloplasty rings, the novel test method (D2) is not obvious better than conventional test methods(D1) in duplicating the stress distribution (ΦD1 = 0.88 vs ΦD2 = 0.92). However, the maximum values of stress in the novel test method are closer to the maximum value of stress under in-vivo loading (ΧD1 = 5.2Mpa vs ΧD2 = 4.4Mpa). For open-end annuloplasty rings, the novel test method(C2) is obviously superior to the conventional test method(C1) in duplicating both the stress distribution and the stress peak values of the in-vivo loading (ΦC1 = 0.22 vs ΦC2 = 0.98; ΧC1 = 59.1Mpa vs ΧC2 = 11.0Mpa). The in-vitro loading methods described in this article more closely approximated in-vivo conditions compared to traditional methods. They are simpler to operate, more efficient and can help manufacturers expedite new product development, assist regulatory agencies with product quality oversight.

A geometry-based finite element tool for evaluating mitral valve biomechanics.

Mitral valve function depends on its complex geometry and tissue health, with alterations in shape and tissue response affecting the long-term restorarion of function. Previous computational frameworks for biomechanical assessment are mostly based on patient-specific geometries; however, these are not flexible enough to yield a variety of models and assess mitral closure for individually tuned morphological parameters or material property representations. This study details the finite element approach implemented in our previously developed toolbox to assess mitral valve biomechanics and showcases its flexibility through the generation and biomechanical evaluation of different models. A healthy valve geometry was generated and its computational predictions for biomechanics validated against data in the literature. Moreover, two mitral valve models including geometric alterations associated with disease were generated and analysed. The healthy mitral valve model yielded biomechanical predictions in terms of valve closure dynamics, leaflet stresses and papillary muscle and chordae forces comparable to previous computational and experimental studies. Mitral valve function was compromised in geometries representing disease, expressed by the presence of regurgitating areas, elevated stress on the leaflets and unbalanced subvalvular apparatus forces. This showcases the flexibility of the toolbox concerning the generation of a range of mitral valve models with varying geometric definitions and material properties and the evaluation of their biomechanics.

Fluid-structure interaction and structural simulation of high acceleration effects on surgical repaired human mitral valve biomechanics.

Mitral valve dynamics depend on force stability in the mitral leaflets, the mitral annulus, the chordae tendineae, and the papillary muscles. In chordal rupture conditions, the proper function of the valve disrupts, causing mitral regurgitation, the most prevalent valvular disease. In this study, Structural and FSI frameworks were employed to study valve dynamics in healthy, pathologic, and repaired states. Anisotropic, non-linear, hyper-elastic material properties applied to tissues of the valve while the first-order Ogden model reflected the best compatibility with the empirical data. Hemodynamic blood pressure of the cardiovascular system is applied on the leaflets as uniform loads varying by time, and exposure to high acceleration loads imposed on models. Immersed boundary method used for simulation of fluid in a cardiac cycle. In comparison between healthy and pathologic models, stress values and chordal tensions are increased, by nearly threefold and twofold, respectively. Stress concentration on leaflets is reduced by 75% after performing a successful surgical repair on the pathological model. Crash acceleration loads led to more significant stress and chordae tension on models, by 27% and 23%, respectively. It is concluded that a more sophisticated model could lead to a better understanding of human heart valve biomechanics in various conditions. If a preoperative plan is developed based on these modeling methods, the requirement for multiple successive repairs would be eliminated, operative times are shortened, and patient outcomes are improved.

Comparative anatomy of the mitral valve in four species (human, ovine, porcine and canine): A pre-clinical perspective.

This study aimed to provide comparative anatomical data on the mitral valve and to substantiate the choice between large species for pre-clinical testing of cardiac devices. Different anatomical parameters of the anterior and posterior leaflets, chordae and papillary muscles were measured to characterize the anatomy of the mitral valve in 10 individuals for each four species. Ratios were calculated and used to circumvent the interspecies variations of body and heart size and weight. The results underline many relevant anatomical similarities and differences between man and the three animal species. We confirm that the porcine species is a better model based on anatomical measurements. But many parameters should be considered depending on the shape, size and purpose of the device. The mitral and aortic valve are closer than in man leading to potential damage of the aortic valve by a mitral device. The ovine mitral annulus is more flattened and would sustain more mechanical forces on a round-shaped stent. The anterior and posterior leaflets have comparable height in the animal species leading to more space for implantation. The porcine valve has more chordae allowing less space around the valve for a transcatheter stent. Our observations introduce new comparative data in the perspective of the choice of a large animal model for pre-clinical testing of mitral devices. They are very helpful for all cardiologists, surgeons or engineers who need to understand the reasons for success or failure of a device and to have key elements of discussion.

Mitral annular dynamics are influenced by left ventricular load and contractility in an acute animal model.

The purpose of this study was to investigate the effects of loading conditions and left ventricular (LV) contractility on mitral annular dynamics. In 10 anesthetized pigs, eight piezoelectric transducers were implanted equidistantly around the mitral annulus. High-fidelity catheters measured left ventricular pressures and the slope of the end-systolic pressure-volume relationship (Ees ) determined LV contractility. Adjustments of pre- and afterload were done by constriction of the inferior caval vein and occlusion of the descending aorta. Mitral annulus area indexed to body surface area (MAAi ), annular circularity index (ACI), and non-planarity angle (NPA) were calculated by computational analysis. MAAi was more dynamic in response to loading interventions than ACI and NPA. However, MAAi maximal cyclical reduction (-Δr) and average deformational velocity (- v ¯ $$ \overline{v} $$ ) did not change accordingly (p = 0.31 and p = 0.22). Reduced Ees was associated to attenuation in MAAi -Δr and MAAi - v ¯ $$ \overline{v} $$ (r2 = 0.744; p = 0.001 and r2 = 0.467; p = 0.029). In conclusion, increased cardiac load and reduced LV contractility may cause deterioration of mitral annular dynamics, likely impairing coaptation and increasing susceptibility to valvular incompetence.

Generic framework for quantifying the influence of the mitral valve on ventricular blood flow.

Blood flow within the left ventricle provides important information regarding cardiac function in health and disease. The mitral valve strongly influences the formation of flow structures and there exist various approaches for the representation of the valve in numerical models of left ventricular blood flow. However, a systematic comparison of the various mitral valve models is missing, making a priori decisions considering the overall model's context of use impossible. Within this study, a benchmark setup to compare the influence of mitral valve modeling strategies on intraventricular flow features was developed. Then, five mitral valve models of increasing complexity: no modeling, static wall, 2D and 3D porous medium with time-dependent porosity, and one-way fluid-structure interaction (FSI) were compared with each other. The flow features velocity, kinetic energy, transmitral pressure drop, vortex formation, flow asymmetry as well as computational cost and ease-of-implementation were evaluated. The one-way FSI approach provides the highest level of flow detail, which is accompanied by the highest numerical costs and challenges with the implementation. As an alternative, the porous medium approach with the expansion including time-dependent porosity provides good results with up to 10% deviations in the flow features (except the transmitral pressure drop) in comparison to the FSI model and only a fraction (11%) of numerical costs. However, jet propagation speed is highly underestimated by all alternative approaches to the FSI model. Taken together, our benchmark setup allows a quantitative comparison of various mitral valve modeling approaches and is provided to the scientific community for further testing and expansion.

Traction mechanical characterization of porcine mitral valve annulus.

The Mitral Annulus (MA) is an anisotropic, fibrous, flexible and dynamical structure. While MA dynamics are well documented, its passive mechanical properties remain poorly investigated to complete the design of adequate prostheses. Mechanical properties in traction on four sections of the MA (aortic, left, posterior and right segments) were assessed using a traction test system with a 30 N load cell and pulling jaws for sample fixation. Samples were submitted to a 1.5 N pre-load, 10 pre-conditioning cycles. Three strain rates were tested (5 %/min, 7 %/min and 13 %/min), the first two up to 10 % strain and the last until rupture. High-resolution diffusion-MRI provided microstructural mapping of fractional anisotropy and mean diffusion within muscle and collagen fibres. Ten MA from porcine hearts were excised resulting in 40 tested samples, out of which 28 were frozen prior to testing. Freezing samples significantly increased Young Moduli for all strain rates. No significant differences were found between Young Moduli at different strain rates (fresh samples 2.4 ± 1.1 MPa, 3.8 ± 2.2 MPa and 3.1 ± 1.8 MPa for increasing strain rates in fresh samples), while significant differences were found when comparing aortic with posterior and posterior with lateral (p < 0.012). Aortic segments deformed the most (24.1 ± 9.4 %) while lateral segments endured the highest stress (>0.3 MPa), corresponding to higher collagen fraction (0.46) and fractional anisotropy. Passive machinal properties differed between aortic and lateral segments of the MA. The process of freezing samples altered their mechanical properties. Underlying microstructural differences could be linked to changes in strain response.

Cardiac Structure and Function in Adults with Down Syndrome.

Various factors may alter the risk for cardiovascular disease in adults with Down syndrome (Ds), yet few studies have examined differences in cardiac physiology in this population. Previous research suggested lower systolic and diastolic function, but inconsistent methodologies and younger samples warrant research in adults with Ds. Our aim is to compare the cardiac structure and function of adults with Ds to age- and sex-matched adults without Ds. Echocardiography was used to assess systolic function, diastolic function, and cardiac structure in n = 19 adults (Ds n = 9, control n = 10). Regarding cardiac structure, adults with Ds had increased left ventricular posterior wall thickness at end-systole compared to adults without Ds (p = 0.007). Regarding systolic and diastolic function, adults with Ds were found to have lower septal peak systolic annular velocity (S') (p = 0.026), lower lateral and septal mitral annular early diastolic velocity (E') (p = 0.007 and p = 0.025, respectively), lower lateral peak mitral annular late diastolic velocity (A') (p = 0.027), and higher lateral and septal mitral annular early systolic velocity to diastolic velocity ratios (E/e') (p = 0.001 and p = 0.001, respectively). Differences in both cardiac structure and function were found when comparing adults with Ds to matched adults without Ds. Most of the differences were indicative of worse diastolic function.

Ex vivo experimental characterizations for understanding the interrelationship between tissue mechanics and collagen microstructure of porcine mitral valve leaflets.

Unidirectional blood flow in the left side of the heart is regulated by the mitral valve. To better understand the mitral valve function, researchers have examined the structural and mechanical properties of the mitral valve leaflets; however, limitations of the previous studies include the use of mechanics- and structure-altering tissue modifications (e.g., optical clearing) that limit the ability to quantify the unique load-dependent reorientation and realignment of the collagen fibers as well as their interrelation with the valve tissue mechanics. Herein, we aimed to circumvent these limitations by utilizing an integrated polarized-light imaging and biaxial testing system for understanding the mechanics-microstructure interrelationship for porcine mitral valve leaflets. We further performed constitutive modeling and evaluated the accuracy of the affine fiber kinematics theory. From the tissue mechanics perspective, the posterior leaflet was more extensible in the radial direction than the anterior leaflet (14.2% difference in radial tissue stretch), while exhibiting smaller collagen and elastin moduli based on the determined constitutive model parameters. From the collagen microstructure's standpoint, the posterior leaflet had smaller increases in optical anisotropy (closely related to the degree of fiber alignment) than the anterior leaflet (32.8±7.7% vs. 50.0±19.7%). Further, the leaflets were found to possess two distinct fiber families - one family oriented along the circumferential tissue direction, and another more disperse family with a 30°-40° offset from the first fiber family. Finally, affine fiber kinematics consistently underpredicted the collagen fiber reorientations Overall, this study improved our understanding of the mitral valve leaflets that is essential for facilitating tissue-emulated valve replacement and cardiac valve modeling frameworks.

Biomechanics of mitral valve leaflets: Second harmonic generation microscopy, biaxial mechanical tests and tissue modeling.

Collagen fibers are the main load carrier in the mitral valve (MV) leaflets. Their orientation and dispersion are an important factor for the mechanical behavior. Most recent studies of collagen fibers in MVs lack either entire thickness study or high transmural resolution. The present study uses second harmonic generation (SHG) microscopy in combination with planar biaxial mechanical tests to better model and examine collagen fibers and mechanical properties of MV leaflets. SHG in combination with tissue clearing enables the collagen fibers to be examined through the entire thickness of the MV leaflets. Planar biaxial mechanical tests, on the other hand, enable the characterization of the mechanical tissue behavior, which is represented by a structural tissue model. Twelve porcine MV leaflets are examined. The SHG recording shows that the mean fiber angle for all samples varies on average by ±12° over the entire thickness and the collagen fiber dispersion changes strongly over the thickness. A constitutive model based on the generalized structure tensor approach is used for the associated tissue characterization. The model represents the tissue with three mechanical parameters plus the mean fiber direction and the dispersion, and predicts the biomechanical response of the leaflets with a good agreement (average r2=0.94). It is found that the collagen structure can be represented by a mean direction and a dispersion with a single family of fibers despite the variation in the collagen fiber direction and the dispersion over the entire thickness of MV leaflets. STATEMENT OF SIGNIFICANCE: Despite its prominent role in the mechanical behavior of mitral valve (MV) leaflets, the collagen structure has not yet been investigated over the entire thickness with high transmural resolution. The present study quantifies the detailed through thickness collagen fiber structure and examines the effects of its variation on MV tissue modeling. This is important because the study evaluates the assumption that the collagen fibers can be modeled with a representative single fiber family despite the variation across the thickness. In addition, the current comprehensive data set paves the way for quantifying the disruption of collagen fibers in myxomatous MV leaflets associated with disrupted collagen fibers.

Mitral valve thickening in acute rheumatic fever as a predictor of late valvar dysfunction.

BACKGROUND: Rheumatic heart disease (RHD) complicating acute rheumatic fever (ARF) remains an important health problem in developing countries. No definitive diagnostic test for ARF exists and the role of Doppler echocardiography (DEC) for long-term prognostic evaluation following ARF is not well established. OBJECTIVE: To investigate the prognostic value of DEC in patients with ARF as a predictor of chronic valve dysfunction. METHODS: Prospectively enrolled patients with clinical ARF had a DEC performed soon after diagnosis and repeated at 1, 3, 6 and 12 months and thereafter at every 1-2 years. We defined chronic valve dysfunction by ≥ 3 of the following: increased valve thickening, commissure fusion, subvalvular thickening, reduced leaflet mobility, non-trivial mitral and/or aortic regurgitation. We performed univariate analysis and developed multivariate logistic regression models to identify variables that may influence evolution to RHD. p <0.05 was considered significant. RESULTS: We evaluated 70(57% men) patients, 10.8±5.6 years-old during the ARF episode and followed for 95±26 months. Chronic valve dysfunction was identified in 36(51.4%) which fulfilled criteria for RHD and 10(27.8%) of them died or underwent valve surgery. Univariate analysis showed that mitral valve thickening and presence of mitral regurgitation at baseline DEC, were associated with RHD(p<0.01). Multivariate logistic regression showed that only mitral valve thickness either as a continuous (Odds-Ratio:5.8;95%CI:1.7-19.7) or as a categorical variable (Odds-Ratio:4.04;95%CI:1.06-15.3) was an independent predictor of chronic valve dysfunction. CONCLUSIONS: Mitral leaflets thickening documented at the time of diagnosis of ARF is a consistent prognostic marker for the subsequent evolution to RHD.

Effect of Neprilysin Inhibition for Ischemic Mitral Regurgitation after Myocardial Injury.

Angiotensin receptor neprilysin inhibitor (ARNI) treatment reduces functional mitral regurgitation (MR) to a greater extent than angiotensin receptor blocker (ARB) treatment alone, but the mechanism is unclear. We evaluated the mechanisms of how ARNI has an effect on functional MR. After inducing functional MR by left circumflex coronary artery occlusion, male Sprague Dawley rats (n = 31) were randomly assigned to receive the ARNI LCZ696, the ARB valsartan, or corn oil only (MR control). Excised mitral leaflets and left ventricle (LV) were analyzed, and valvular endothelial cells were evaluated focusing on molecular changes. LCZ696 significantly attenuated LV dilatation after 6 weeks when compared with the control group (LV end-diastolic volume, 461.3 ± 13.8 µL versus 525.1 ± 23.6 µL; p < 0.05), while valsartan did not (471.2 ± 8.9 µL; p > 0.05 to control). Histopathological analysis of mitral leaflets showed that LCZ696 strongly reduced fibrotic thickness compared to the control group (28.2 ± 2.7 µm vs. 48.8 ± 7.5 µm; p < 0.05). Transforming growth factor-ß and downstream phosphorylated extracellular-signal regulated kinase were also significantly lower in the LCZ696 group. Consequently, excessive endothelial-to-mesenchymal transition (EndoMT) was mitigated in the LCZ696 group compared to the control group and leaflet area was higher (11%) in the LCZ696 group than in the valsartan group. Finally, the MR extent was significantly lower in the LCZ696 group and functional improvement was observed. In conclusion, neprilysin inhibitor has positive effects on LV reverse remodeling and also attenuates fibrosis in MV leaflets and restores adaptive growth by directly modulating EndoMT.

Left atrial minimal volume: association with diastolic dysfunction and heart failure in patients in sinus rhythm or atrial fibrillation with preserved ejection fraction.

BACKGROUND: Evidence of diastolic dysfunction (DD) required for the diagnosis of heart failure with preserved ejection fraction (HFpEF) is elusive in atrial fibrillation (AF). Left ventricular (LV) and left atrial (LA) speckle-tracking echocardiography (STE) may provide rhythm independent indications of DD. We aimed to find common LV/LA myocardial mechanics parameters to demonstrate DD, using STE in patients with AF. METHODS: 176 echocardiographic assessments of patients were studied retrospectively by STE. 109 patients with history of AF were divided in three groups: sinus with normal diastolic function (n = 32, ND), sinus with DD (n = 35, DD) and patients with AF during echocardiography (n = 42). These assessments were compared to 67 normal controls. Demographic, clinical, echocardiographic and myocardial mechanic characteristics were obtained. RESULTS: The patients with DD in sinus rhythm and patients with AF were similar in age, mostly women, and had cardiovascular risk factors as well as higher dyspnea prevalence compared to either controls or patients with ND. In the AF group, LV ejection fraction (LVEF) (p = 0.008), global longitudinal strain and LA emptying were lower (p < 0.001), whereas LA volumes were larger (p < 0.001) compared to the other groups. In a multivariable analysis of patients in sinus rhythm, LA minimal volume indexed to body surface area (Vmin-I) was found to be the single significant factor associated with DD (AUC 83%). In all study patients, Vmin-I correlated with dyspnea (AUC 80%) and pulmonary hypertension (AUC 90%). CONCLUSIONS: Vmin-I may be used to identify DD and assist in the diagnosis of HFpEF in patients with AF.

Fluid-structure interaction in a fully coupled three-dimensional mitral-atrium-pulmonary model.

This paper aims to investigate detailed mechanical interactions between the pulmonary haemodynamics and left heart function in pathophysiological situations (e.g. atrial fibrillation and acute mitral regurgitation). This is achieved by developing a complex computational framework for a coupled pulmonary circulation, left atrium and mitral valve model. The left atrium and mitral valve are modelled with physiologically realistic three-dimensional geometries, fibre-reinforced hyperelastic materials and fluid-structure interaction, and the pulmonary vessels are modelled as one-dimensional network ended with structured trees, with specified vessel geometries and wall material properties. This new coupled model reveals some interesting results which could be of diagnostic values. For example, the wave propagation through the pulmonary vasculature can lead to different arrival times for the second systolic flow wave (S2 wave) among the pulmonary veins, forming vortex rings inside the left atrium. In the case of acute mitral regurgitation, the left atrium experiences an increased energy dissipation and pressure elevation. The pulmonary veins can experience increased wave intensities, reversal flow during systole and increased early-diastolic flow wave (D wave), which in turn causes an additional flow wave across the mitral valve (L wave), as well as a reversal flow at the left atrial appendage orifice. In the case of atrial fibrillation, we show that the loss of active contraction is associated with a slower flow inside the left atrial appendage and disappearances of the late-diastole atrial reversal wave (AR wave) and the first systolic wave (S1 wave) in pulmonary veins. The haemodynamic changes along the pulmonary vessel trees on different scales from microscopic vessels to the main pulmonary artery can all be captured in this model. The work promises a potential in quantifying disease progression and medical treatments of various pulmonary diseases such as the pulmonary hypertension due to a left heart dysfunction.

Multimodal cardiovascular model for hemodynamic analysis: Simulation study on mitral valve disorders.

Valvular heart diseases are a prevalent cause of cardiovascular morbidity and mortality worldwide, affecting a wide spectrum of the population. In-silico modeling of the cardiovascular system has recently gained recognition as a useful tool in cardiovascular research and clinical applications. Here, we present an in-silico cardiac computational model to analyze the effect and severity of valvular disease on general hemodynamic parameters. We propose a multimodal and multiscale cardiovascular model to simulate and understand the progression of valvular disease associated with the mitral valve. The developed model integrates cardiac electrophysiology with hemodynamic modeling, thus giving a broader and holistic understanding of the effect of disease progression on various parameters like ejection fraction, cardiac output, blood pressure, etc., to assess the severity of mitral valve disorders, naming Mitral Stenosis and Mitral Regurgitation. The model mimics an adult cardiovascular system, comprising a four-chambered heart with systemic, pulmonic circulation. The simulation of the model output comprises regulated pressure, volume, and flow for each heart chamber, valve dynamics, and Photoplethysmogram signal for normal physiological as well as pathological conditions due to mitral valve disorders. The generated physiological parameters are in agreement with published data. Additionally, we have related the simulated left atrium and ventricle dimensions, with the enlargement and hypertrophy in the cardiac chambers of patients with mitral valve disorders, using their Electrocardiogram available in Physionet PTBI dataset. The model also helps to create 'what if' scenarios and relevant analysis to study the effect in different hemodynamic parameters for stress or exercise like conditions.

Aortic root movement correlation with the function of the left ventricle.

Echocardiographic assessment of systolic and diastolic function of the heart is often limited by image quality. However, the aortic root is well visualized in most patients. We hypothesize that the aortic root motion may correlate with the systolic and diastolic function of the left ventricle of the heart. Data obtained from 101 healthy volunteers (mean age 46.6 ± 12.4) was used in the study. The data contained sequences of standard two-dimensional (2D) echocardiographic B-mode (brightness mode, classical ultrasound grayscale presentation) images corresponding to single cardiac cycles. They also included sets of standard echocardiographic Doppler parameters of the left ventricular systolic and diastolic function. For each B-mode image sequence, the aortic root was tracked with use of a correlation tracking algorithm and systolic and diastolic values of traveled distances and velocities were determined. The aortic root motion parameters were correlated with the standard Doppler parameters used for the assessment of LV function. The aortic root diastolic distance (ARDD) mean value was 1.66 ± 0.26 cm and showed significant, moderate correlation (r up to 0.59, p < 0.0001) with selected left ventricular diastolic Doppler parameters. The aortic root maximal diastolic velocity (ARDV) was 10.8 ± 2.4 cm/s and also correlated (r up to 0.51, p < 0.0001) with some left ventricular diastolic Doppler parameters. The aortic root systolic distance (ARSD) was 1.63 ± 0.19 cm and showed no significant moderate correlation (all r values < 0.40). The aortic root maximal systolic velocity (ARSV) was 9.2 ± 1.6 cm/s and correlated in moderate range only with peak systolic velocity of medial mitral annulus (r = 0.44, p < 0.0001). Based on these results, we conclude, that in healthy subjects, aortic root motion parameters correlate significantly with established measurements of left ventricular function. Aortic root motion parameters can be especially useful in patients with low ultrasound image quality precluding usage of typical LV function parameters.

Validation of estimating left ventricular ejection fraction by mitral annular displacement derived from speckle-tracking echocardiography: A neglected method for evaluating left ventricular systolic function.

PURPOSE: The echocardiographic measurement of left ventricular (LV) ejection fraction (EF) is dependent on professional experience and adequate visualization. Tissue motion of mitral annular displacement (TMAD) can be easily assessed using speckle-tracking echocardiography (STE), even in patients with poor acoustic windows. Therefore, this study aimed to assess whether left ventricular ejection fraction (LVEF) can be estimated using STE-derived TMAD when LVEF is not available. METHODS: Four-hundred fifty-six outpatients were enrolled after excluding the patients whose LVEF measurements remained challenging or TMAD value could be confounded. An optimized regression model for LVEF-TMAD was developed in the derivation set (n = 287), and its reliability was verified in the validation set (n = 123) and regional wall motion abnormalities (RWMA) set (n = 46). RESULTS: In the derivation set, the power models had the highest F-value. Therefore, the power equations were chosen to estimate LVEF by TMAD in the validation set. There was a near-zero bias and a narrow range between the observed and estimated LVEF. The highest intra-class correlation coefficient was found between the observed and the estimated LVEF by normalized TMAD at the midpoint of mitral annular (nTMADmid). Moreover, there were no significant differences between the observed and the estimated LVEF in the RWMA set. CONCLUSION: The LVEF can be estimated with STE-derived TMAD, even for patients with RWMA, and nTMADmid may be the optimal parameter.

Energy loss associated with in-vitro modeling of mitral annular calcification.

INTRODUCTION: Study aims were to compare hemodynamics and viscous energy dissipation (VED) in 3D printed mitral valves-one replicating a normal valve and the other a valve with severe mitral annular calcification (MAC). Patients with severe MAC develop transmitral gradients, without the commissural fusion typifying rheumatic mitral stenosis (MS), and may have symptoms similar to classical MS. A proposed mechanism relates to VED due to disturbed blood flow through the diseased valve into the ventricle. METHODS: A silicone model of a normal mitral valve (MV) was created using a transesophageal echocardiography dataset. 3D printed calcium phantoms were incorporated into a second valve model to replicate severe MAC. The synthetic MVs were tested in a left heart duplicator under rest and exercise conditions. Fine particles were suspended in a water/glycerol blood analogue for particle image velocimetry calculation of VED. RESULTS: Catheter mean transmitral gradients were slightly higher in the MAC valve compared to the normal MV, both at rest (3.2 vs. 1.3 mm Hg) and with exercise (5.9 vs. 5.0 mm Hg); Doppler gradients were 2.7 vs. 2.1 mm Hg at rest and 9.9 vs 8.2 mm Hg with exercise. VED was similar between the two valves at rest. During exercise, VED increased to a greater extent for the MAC valve (240%) versus the normal valve (127%). CONCLUSION: MAC MS is associated with slightly increased transmitral gradients but markedly increased VED during exercise. These energy losses may contribute to the exercise intolerance and exertional dyspnea present in MAC patients.

A statistical comparison of reproducibility in current pediatric two-dimensional echocardiographic nomograms.

BACKGROUND: The aim of this study is to compare new pediatric nomograms for clinical parameters from 2D echocardiography. METHODS: 2D pediatric echocardiographic parameters from four recent nomograms were used for statistical analysis. To assess the accuracy of the predictive models from each study, namely multivariate, linear, and nonlinear regression, mean values and 5th and 95th percentiles (µ ± 1.65σ) were calculated. A Z-score calculator was created. RESULTS: Mean values and 5th and 95th percentiles have been provided for a range of BSA (0.15-2.20 m2) for each nomogram assessed in this study. Moreover, plots of Z-scores over the same range of BSA have been generated to assess trends among different studies. For most measurements from the two most recent nomograms, namely Lopez et al. and Cantinotti et al., differences were within a Z-score of 0.5 (Z-score range: 0.001-1.26). Measurements from Sluysmans and Colan and Pettersen et al. were observed to diverge from Lopez et al. at the upper extremities of BSA. Differences among various nomograms emerged at lower extremes of BSA. CONCLUSIONS: The two most recent echocardiographic nomograms were observed to have the most statistically similar ranges of normality. Significant deviations in ranges of normality were observed at extremes of BSA. IMPACT: Echocardiographic nomograms for pediatric age are discordant. Comparison of current pediatric echocardiographic nomograms. A Z-score calculator was created. Clinical relevance of differences among nomograms is highlighted.

Age related extracellular matrix and interstitial cell phenotype in pulmonary valves.

Heart valve disease is a common manifestation of cardiovascular disease and is a significant cause of cardiovascular morbidity and mortality worldwide. The pulmonary valve (PV) is of primary concern because of its involvement in common congenital heart defects, and the PV is usually the site for prosthetic replacement following a Ross operation. Although effects of age on valve matrix components and mechanical properties for aortic and mitral valves have been studied, very little is known about the age-related alterations that occur in the PV. In this study, we isolated PV leaflets from porcine hearts in different age groups (~ 4-6 months, denoted as young versus ~ 2 years, denoted as adult) and studied the effects of age on PV leaflet thickness, extracellular matrix components, and mechanical properties. We also conducted proteomics and RNA sequencing to investigate the global changes of PV leaflets and passage zero PV interstitial cells in their protein and gene levels. We found that the size, thickness, elastic modulus, and ultimate stress in both the radial and circumferential directions and the collagen of PV leaflets increased from young to adult age, while the ultimate strain and amount of glycosaminoglycans decreased when age increased. Young and adult PV had both similar and distinct protein and gene expression patterns that are related to their inherent physiological properties. These findings are important for us to better understand the physiological microenvironments of PV leaflet and valve cells for correctively engineering age-specific heart valve tissues.