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Transcatheter therapies are emerging for functional mitral regurgitation (FMR) treatment, however there is lack of pathological models for their preclinical assessment. We investigated the applicability of deer hearts for this purpose.8 whole deer hearts were housed in a pulsatile flow bench. At baseline, all mitral valves featured normal coaptation. The pathological state was induced by 60-minutes intraventricular constant pressurization. It caused mitral annulus dilation (antero-posterior diameter increase from 31.8 ± 5.6 mm to 39.5 ± 4.9 mm, p = 0.001), leaflets tethering (maximal tenting height increase from 7.3 ± 2.5 mm to 12.7 ± 3.4 mm, p < 0.001) and left ventricular diameter increase (from 67.8 ± 7.5 mm to 79.4 ± 6.5 mm, p = 0.004). These geometrical reconfigurations led to restricted mitral valve leaflets motion and leaflet coaptation loss. Preliminary feasibility assessment of two FMR treatments was performed in the developed model.Deer hearts showed ability to dilate under constant pressurization and have potential to be used for realistic preclinical research of novel FMR therapies. Graphical abstract figure legend: Deer heart mitral valve fiberscopic and echocardiographic images in peak systole at baseline and after inducing the pathological conditions representing functional mitral regurgitation. In the pathological conditions lack of coaptation between the leaflets, enlargement of the antero-posterior distance (red dashed line) and the left ventricular diameter (orange dashed line) were observed.

Prosthetic mechanical valves are the elective choice in mitral valve (MV) replacement, because of their reliability and easiness of implantation. However, these prostheses can suffer from complications, the major one being prosthetic mitral valve thrombosis (PMVT). In these cases, transthoracic doppler echocardiogram (TDE) is the standard diagnostic workup for diagnosis of valve malfunction. The American Society of Echocardiography (ASE) indicates the possible TDE-derived indexes, which can help in identifying insurgence of MV replacement complications. Unfortunately, in some cases, it is not possible to detect PMVT based on these criteria. In these cases, we speak of Doppler silent thrombosis and only more accurate and invasive analyses, such as fluoroscopy, allow for a correct diagnosis. In this work, computational fluid dynamic models were implemented to simulate valve fluid dynamics in different clinical scenarios in order to improve the reliability of PMVT diagnosis based on TDE. In detail, seven mechanical valve configurations, associated to different potential thrombotic conditions (symmetric and asymmetric stenosis), were designed and tested using five pathologic transmitral velocity profile, extracted from real TDE images; to obtain the flow rate profiles, each TDE velocity profile was scaled to yield a mean flow rate (MFR) of 4, 5 and 6 L/min, respectively. As a result, 105 (7 × 5 × 3) synthetic cases, accounting for different velocity profiles, MFRs and valve configurations, were simulated. TDE-derived indexes were calculated according to the ASE guidelines that were extracted. Advanced statistical methods were applied to propose a new diagnostic algorithm for detecting PMVT. Our results showed that there isn't any significant difference between symmetric and asymmetric stenosis, probe location and flow rate waveform and confirmed that the single modality diagnostic is not able to predict thrombosis in a relevant number of cases, referable to mild and mild-severe stenosis cases. To overcome the problem, a novel multi-parametric discrete score based on the designed diagnostic algorithm was attained and tested; the percentage of stenosis (POS) was predicted with an accuracy rate of 90.5%. Even more interestingly, the error rate of 9.5% is related to four false positive cases corresponding to mild stenosis (POS = 15%) which were erroneously classified as mild-severe stenosis. No false negatives were obtained. Our results suggest that a reliable estimation must take into account the mean flow rate as well as the transmitral velocity profile in order to provide a correct diagnosis., (Copyright © 2019 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Patient-specific finite element (FE) models can assess the impact of mitral valve (MV) repair on the complex MV anatomy and function. However, FE excessive time requirements hamper their use for surgical planning; mass-spring models (MSMs) represent a more approximate approach but can provide almost real-time simulations. On this basis, we implemented MSMs of three healthy MVs from cardiac magnetic resonance (cMR) imaging to simulate the systolic MV closure, including the in vivo papillary muscles and annular kinematics, and the anisotropic and non-linear mechanical response of MV tissues. To test MSM reliability we compared the systolic peak configurations computed by MSMs and FE: mismatches by less than twice the in-plane cMR image resolution were detected over 75% of the leaflets' surface, independently of the MSM mesh refinement and of the specific MV anatomy. Data on MSMs time-efficiency and data from the comparison of MSMs vs. FE models suggest that MSM could represent a suitable trade-off between almost real-time simulations and reliability when computing MV systolic configuration, with the potential to be used in a clinical setting either as a support to the decisional process or as a virtual training tool., (Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.)

Mitraclip ® implantation is widely used as a valid alternative to conventional open-chest surgery in high-risk patients with severe mitral valve (MV) regurgitation. Although effective in reducing mitral regurgitation (MR) in the majority of cases, the clip implantation produces a double-orifice area that can result in altered MV biomechanics, particularly in term of hemodynamics and mechanical stress distribution on the leaflets. In this scenario, we combined the consistency of in vitro experimental platforms with the versatility of numerical simulations to investigate clip impact on MV functioning. The fluid dynamic determinants of the procedure were experimentally investigated under different working conditions (from 40bpm to 100bpm of simulated heart rate) on six swine hearts; subsequently, fluid dynamic data served as realistic boundary conditions in a computational framework able to quantitatively assess the post-procedural MV biomechanics. The finite element model of a human mitral valve featuring an isolated posterior leaflet prolapse was reconstructed from cardiac magnetic resonance. A complete as well as a marginal, sub-optimal grasping of the leaflets were finally simulated. The clipping procedure resulted in a properly coapting valve from the geometrical perspective in all the simulated configurations. Symmetrical complete grasping resulted in symmetrical distribution of the mechanical stress, while uncomplete asymmetrical grasping resulted in higher stress distribution, particularly on the prolapsing leaflet. This work pinpointed that the mechanical stress distribution following the clipping procedure is dependent on the cardiac hemodynamics and has a correlation with the proper execution of the grasping procedure, requiring accurate evaluation prior to clip delivery., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objectives: Intraoperative assessment of the proper neochordal length during mitral plasty may be complex sometimes. Patient-specific finite element models were used to elucidate the biomechanical drawbacks underlying an apparently correct mitral repair for isolated posterior prolapse., Methods: Preoperative patient-specific models were derived from cardiac magnetic resonance images; integrated with intraoperative surgical details to assess the location and extent of the prolapsing region, including the number and type of diseased chordae; and complemented by the biomechanical properties of mitral leaflets, chordae tendineae, and artificial neochordae. We investigated postoperative mitral valve biomechanics in a wide spectrum of different techniques (single neochorda, double neochordae, and preconfigured neochordal loop), all reestablishing adequate valvular competence, but differing in suboptimal millimetric expanded polytetrafluoroethylene suture lengths in a range of ±2 mm, compared with the corresponding "ideal repair.", Results: Despite the absence of residual regurgitation, alterations in chordal forces and leaflet stresses arose simulating suboptimal repairs; alterations were increasingly relevant as more complex prolapse anatomies were considered and were worst when simulating single neochorda implantation. Multiple chordae implantations were less sensitive to errors in neochordal length tuning, but associated postoperative biomechanics were hampered when asymmetric configurations were reproduced. Computational outcomes were consistent with the presence and entity of recurrent mitral regurgitation at midterm follow-up of simulated patients., Conclusions: Suboptimal suture length tuning significantly alters chordal forces and leaflet stresses, which may be key parameters in determining the long-term outcome of the repair. The comparison of the different simulated techniques suggests possible criteria for the selection and implementation of neochordae implantation techniques., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Mitral regurgitation is the most prevalent heart valve disease in the western population. When severe, it requires surgical treatment, repair being the preferred option. The edge-to-edge repair technique treats mitral regurgitation by suturing the leaflets together and creating a double-orifice valve. Due to its relative simplicity and versatility, it has become progressively more widespread. Recently, its percutaneous version has become feasible, and has raised interest thanks to the positive results of the Mitraclip(®) device. Edge-to-edge features and evolution have stimulated debate and multidisciplinary research by both clinicians and engineers. After providing an overview of representative studies in the field, here we propose a novel computational approach to the most recent percutaneous evolution of the edge-to-edge technique. Image-based structural finite element models of three mitral valves affected by posterior prolapse were derived from cine-cardiac magnetic resonance imaging. The models accounted for the patient-specific 3D geometry of the valve, including leaflet compound curvature pattern, patient-specific motion of annulus and papillary muscles, and hyperelastic and anisotropic mechanical properties of tissues. The biomechanics of the three valves throughout the entire cardiac cycle was simulated before and after Mitraclip(®) implantation, assessing the biomechanical impact of the procedure. For all three simulated MVs, Mitraclip(®) implantation significantly improved systolic leaflets coaptation, without inducing major alterations in systolic peak stresses. Diastolic orifice area was decreased, by up to 58.9%, and leaflets diastolic stresses became comparable, although lower, to systolic ones. Despite established knowledge on the edge-to-edge surgical repair, latest technological advances make its percutanoues implementation a challenging field of research. The modeling approach herein proposed may be expanded to analyze clinical scenarios that are currently critical for Mitraclip(®) implantation, helping the search for possible solutions.

Objectives: Finite element modeling was adopted to quantitatively compare, for the first time and on a patient-specific basis, the biomechanical effects of a broad spectrum of different neochordal implantation techniques for the repair of isolated posterior mitral leaflet prolapse., Methods: Cardiac magnetic resonance images were acquired from 4 patients undergoing surgery. A patient-specific 3-dimensional model of the mitral apparatus and the motion of the annulus and papillary muscles were reconstructed. The location and extent of the prolapsing region were confirmed by intraoperative findings, and the mechanical properties of the mitral leaflets, chordae tendineae and expanded polytetrafluoroethylene neochordae were included. Mitral systolic biomechanics was simulated under preoperative conditions and after 5 different neochordal procedures: single neochorda, double neochorda, standard neochordal loop with 3 neochordae of the same length and 2 premeasured loops with 1 common neochordal loop and 3 different branched neochordae arising from it, alternatively one third and two thirds of the entire length., Results: The best repair in terms of biomechanics was achieved with a specific neochordal technique in the single patient, according to the location of the prolapsing region. However, all techniques achieved a slight reduction in papillary muscle forces and tension relief in intact native chordae proximal to the prolapsing region. Multiple neochordae implantation improved the repositioning of the prolapsing region below the annular plane and better redistributed mechanical stresses on the leaflet., Conclusions: Although applied on a small cohort of patients, systematic biomechanical differences were noticed between neochordal techniques, potentially affecting their short- to long-term clinical outcomes. This study opens the way to patient-specific optimization of neochordal techniques., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

The anterior mitral leaflet (AML) is a thin membrane that withstands high left ventricular (LV) pressure pulses 100,000 times per day. The presence of contractile cells determines AML in vivo stiffness and complex geometry. Until recently, mitral valve finite element (FE) models have neglected both of these aspects. In this study we assess their effect on AML strains and stresses, hypothesizing that these will differ significantly from those reported in literature. Radiopaque markers were sewn on the LV, the mitral annulus, and AML in sheep hearts, and their four-dimensional coordinates obtained with biplane video fluoroscopy. Employing in vivo data from three representative hearts, AML FE models were created from the marker coordinates at the end of isovolumic relaxation assumed as the unloaded reference state. AML function was simulated backward through systole, applying the measured trans-mitral pressure on AML LV surface and marker displacements on AML boundaries. Simulated AML displacements and curvatures were consistent with in vivo measurements, confirming model accuracy. AML circumferential strains were mostly tensile (1-3%), despite being compressive (-1%) near the commissures. Radial strains were compressive in the belly (-1 to -0.2%), and tensile (2-8%) near the free edge. These results differ significantly from those of previous FE models. They reflect the synergy of high tissue stiffness, which limits tensile circumferential strains, and initial compound curvature, which forces LV pressure to compress AML radially. The obtained AML shape may play a role not only in preventing mitral regurgitation, but also in optimizing LV outflow fluid dynamics., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Purpose: We developed a new pulsatile hydrodynamic simulator for the in vitro testing of mitral valve (MV) samples. The required specifications included a 3D positioning system for the papillary muscles (PMs) that is accurate and simple to manage; measurement of the force exerted by the chordae tendineae on the PMs; and the possibility to visually inspect the MV for kinematic analysis., Methods: An atrial/ventricular chamber system was developed. The ventricular chamber housed a tri-axial actuator system that was aligned to a morphometric Cartesian frame, allowing for PM positioning even while tests are running. Each PM holder had an embedded load cell for force measurement. The atrial chamber was designed so as to permit MV visual inspection, maintaining a non-disturbed flow at the sample inlet. The setup was subjected to trials with fresh porcine MVs. Flow and pressure difference across the MVs and PM forces were measured in different MV configurations, with different PM spatial dislocations. High speed video recordings were acquired., Results: The positioning accuracy was assessed. Tests with MVs showed good usability, even by the non-engineering personnel. The effects of PM displacement on valve function (valve competence and PM forces) was consistent with previously published data, thus confirming the general soundness of the design principles., Conclusions: The developed simulator is a promising instrument for performing MV in vitro tests in a precise, well-repeatable manner. The ability to completely adjust the PM position while a test is running boosts the simulator's potential for detailed investigations of the pathological and surgically treated MV.

Functional mitral regurgitation (FMR) is usually treated through annuloplasty, i.e., the restriction of the mitral annulus by implanting an undersized prosthetic ring. We conceived a steady-state fluid-dynamic mock simulator that allows for controlling the main mechanic determinants of FMR: transmitral pressure and papillary muscle (PM) apical and lateral dislocation. We used our system to compare the FMR-specific Geoform ring with the general purpose Physio ring in the treatment of FMR. Each ring was implanted on 10 excised fresh porcine valves. Different transmitral pressures (40, 80, 120, 140, and 160 mm Hg) and symmetrical PM apical displacements (2.5-15 mm, step 2.5 mm) were imposed with submillimetric precision. In each configuration, the regurgitant flow through the valve was measured. For PM apical displacement ≥7.5 mm, the regurgitant flow was lower (p < 0.05) with the Geoform ring than with the Physio ring. Differences and their statistical significance increased as PM displacement or transmitral pressure increased. Regression analysis showed that this outcome did not depend on the morphology of the valves. The adopted approach proved itself simple and reliable and allowed to highlight the differences between the two examined annuloplasty devices in countering the two main determinants of FMR: high apical PM dislocation and transvalvular pressure.

Finite element modeling represents an established method for the comprehension of the mitral function and for the simulation of interesting clinical scenarios. However, current models still do not include all the key aspects of the real system. We implemented a new structural finite element model that considers (i) an accurate morphological description of the valve, (ii) a description of the tissues' mechanical properties that accounts for anisotropy and nonlinearity, and (iii) dynamic boundary conditions that mimic annulus and papillary muscles' contraction. The influence of such contraction on valve biomechanics was assessed by comparing the computed results with the ones obtained through an auxiliary model with fixed annulus and papillary muscles. At the systolic peak, the leaflets' maximum principal stress contour showed peak values in the anterior leaflet at the strut chordae insertion zone (300 kPa) and near the annulus (200-250 kPa), while much lower values were detected in the posterior leaflet. Both leaflets underwent larger tensile strains in the longitudinal direction, while in the circumferential one the anterior leaflet experienced nominal tensile strains up to 18% and the posterior one experienced compressive strains up to 23% associated with the folding of commissures and paracommissures, consistently with tissue redundancy. The force exerted by papillary muscles at the systolic peak was equal to 4.11 N, mainly borne by marginal chordae (76% of the force). Local reaction forces up to 45 mN were calculated on the annulus, leading to tensions of 89 N/m and 54 N/m for its anterior and posterior tracts, respectively. The comparison with the results of the auxiliary model showed that annular contraction mainly affects the leaflets' circumferential strains. When it was suppressed, no more compressive strains could be observed and peak strain values were located in the belly of the anterior leaflet. Computational results agree to a great extent with experimental data from literature. They provided insight into some of the features characterizing normal mitral function, such as annular contraction and leaflets' tissue anisotropy and nonlinearity. Some of the computed results may be useful in the design of surgical devices and techniques. In particular, forces applied on the annulus by the surrounding tissues could be considered as an indication for annular prostheses design.

In the current scientific literature, particular attention is dedicated to the study of the mitral valve and to comprehension of the mechanisms that lead to its normal function, as well as those that trigger possible pathological conditions. One of the adopted approaches consists of computational modelling, which allows quantitative analysis of the mechanical behaviour of the valve by means of continuum mechanics theory and numerical techniques. However, none of the currently available models realistically accounts for all of the aspects that characterize the function of the mitral valve. Here, a new computational model of the mitral valve has been developed from in vivo data, as a first step towards the development of patient-specific models for the evaluation of annuloplasty procedures. A structural finite-element model of the mitral valve has been developed to account for all of the main valvular substructures. In particular, it includes the real geometry and the movement of the annulus and papillary muscles, reconstructed from four-dimensional ultrasound data from a healthy human subject, and a realistic description of the complex mechanical properties of mitral tissues. Preliminary simulations allowed mitral valve closure to be realistically mimicked and the role of annulus and papillary muscle dynamics to be quantified.

Background: Functional mitral regurgitation (FMR) is the inability of mitral leaflets to coapt due to a combination of functional and geometrical factors. Valve competence is commonly restored by undersized annuloplasty, reducing the native annulus anteroposterior dimension. In case of severe FMR, this solution may be inadequate. The use of rings specific for the correction of FMR may lead to better results., Methods: The performance of the Geoform ring, a recently designed FMR-specific prosthesis, was compared with that of a standard Physio annuloplasty ring. Finite element modeling was used to simulate dilated cardiomyopathy-related FMR and compare, at the systolic peak, the valve's pathologic condition with the postoperative scenario corresponding to both devices. Three degrees of the pathology were simulated by progressively displacing papillary muscles apically, up to 5 mm. Three ring sizes were modeled., Results: Regurgitant area, coaptation length, and stresses acting on valve structures were assessed. When the use of the Geoform was modeled, coaptation length was always longer than 7 mm. In the most unfavorable case, the regurgitant area reduction was 74% with respect to baseline, and leaflets stresses were reduced by 20% when undersizing was simulated. When Physio ring implantation was simulated, coaptation length maximum extent was equal to 4.3 mm, the maximum regurgitant area reduction was equal to 60%, and leaflet stress reduction was observed., Conclusions: Disease-specific prostheses may allow for restoration of valve competence even for significant degrees of leaflets tethering and avoid the need for aggressive undersizing, thus leading to more durable results.