Large Animal Translational Validation of 3 Mitral Valve Repair Operations for Mitral Regurgitation Using a Mitral Valve Prolapse Model: A Comprehensive In Vivo Biomechanical Engineering Analysis.

BACKGROUND: Various mitral repair techniques have been described. Though these repair techniques can be highly effective when performed correctly in suitable patients, limited quantitative biomechanical data are available. Validation and thorough biomechanical evaluation of these repair techniques from translational large animal in vivo studies in a standardized, translatable fashion are lacking. We sought to evaluate and validate biomechanical differences among different mitral repair techniques and further optimize repair operations using a large animal mitral valve prolapse model. METHODS: Male Dorset sheep (n=20) had P2 chordae severed to create the mitral valve prolapse model. Fiber Bragg grating force sensors were implanted to measure chordal forces. Ten sheep underwent 3 randomized, paired mitral valve repair operations: neochord repair, nonresectional leaflet remodeling, and triangular resection. The other 10 sheep underwent neochord repair with 2, 4, and 6 neochordae. Data were collected at baseline, mitral valve prolapse, and after each repair. RESULTS: All mitral repair techniques successfully eliminated regurgitation. Compared with mitral valve prolapse (0.54±0.18 N), repair using neochord (0.37±0.20 N; P=0.02) and remodeling techniques (0.30±0.15 N; P=0.001) reduced secondary chordae peak force. Neochord repair further decreased primary chordae peak force (0.21±0.14 N) to baseline levels (0.20±0.17 N; P=0.83), and was associated with lower primary chordae peak force compared with the remodeling (0.34±0.18 N; P=0.02) and triangular resectional techniques (0.36±0.27 N; P=0.03). Specifically, repair using 2 neochordae resulted in higher peak primary chordal forces (0.28±0.21 N) compared with those using 4 (0.22±0.16 N; P=0.02) or 6 neochordae (0.19±0.16 N; P=0.002). No difference in peak primary chordal forces was observed between 4 and 6 neochordae (P=0.05). Peak forces on the neochordae were the lowest using 6 neochordae (0.09±0.11 N) compared with those of 4 neochordae (0.15±0.14 N; P=0.01) and 2 neochordae (0.29±0.18 N; P=0.001). CONCLUSIONS: Significant biomechanical differences were observed underlying different mitral repair techniques in a translational large animal model. Neochord repair was associated with the lowest primary chordae peak force compared to the remodeling and triangular resectional techniques. Additionally, neochord repair using at least 4 neochordae was associated with lower chordal forces on the primary chordae and the neochordae. This study provided key insights about mitral valve repair optimization and may further improve repair durability.

A 3D-Printed Externally Adjustable Symmetrically Extensible (EASE) Aortic Annuloplasty Ring for Root Repair and Aortic Valve Regurgitation.

PURPOSE: The valve-sparing aortic root replacement (VSARR) procedure was developed to preserve the aortic valve apparatus to replace aneurysmal aortic roots with synthetic grafts and to eliminate associated aortic regurgitation (AR). However, residual post-repair AR is not uncommon and has been found to be associated with recurrent AR and future reoperation. METHODS: We designed and manufactured a 3D-printed, external adjustable symmetrically extensible (EASE) aortic annuloplasty ring that can symmetrically reduce the aortic annulus diameter via a radial constriction, compliant mechanism. An ex vivo porcine VSARR model with annular dilation and AR was developed (n = 4) and used for hemodynamic, echocardiography, and high-speed videography data collection. RESULTS: After ring annuloplasty repair using the EASE aortic ring, the regurgitant fraction decreased from 23.6 ± 6.9% from the VSARR model to 7.4 ± 5.6% (p = 0.05), which was similar to that measured from baseline with a regurgitant fraction of 10.2 ± 3.9% (p = 0.34). The leaflet coaptation height after annuloplasty repair also significantly increased from that measured in VSARR model (0.4 ± 0.1 cm) to 0.9 ± 0.1 cm (p = 0.0004), a level similar to that measured in baseline (1.1 ± 0.1 cm, p = 0.28). CONCLUSION: Using an ex vivo VSARR model, the EASE ring successfully reduced AR by reducing the annular diameter and improving leaflet coaptation. With its broad applicability and ease of use, this device has the potential to have a significant impact on patients suffering worldwide from AR due to root aneurysms.

Biomechanics and clinical outcomes of various conduit configurations in valve sparing aortic root replacement.

Background: Several conduit configurations, such as straight graft (SG), Valsalva graft (VG), anticommissural plication (ACP), and the Stanford modification (SMOD) technique, have been described for the valve-sparing aortic root replacement (VSARR) procedure. Prior ex vivo studies have evaluated the impact of conduit configurations on root biomechanics, but the mock coronary artery circuits used could not replicate the physical properties of native coronary arteries. Moreover, the individual leaflet's biomechanics, including the fluttering phenomenon, were unclear. Methods: Porcine aortic roots with coronary arteries were explanted (n=5) and underwent VSARR using SG, VG, ACP, and SMOD for evaluation in an ex vivo left heart flow loop simulator. Additionally, 762 patients who underwent VSARR from 1993 through 2022 at our center were retrospectively reviewed. Analysis of variance was performed to evaluate differences between different conduit configurations, with post hoc Tukey's correction for pairwise testing. Results: SG demonstrated lower rapid leaflet opening velocity compared with VG (P=0.001) and SMOD (P=0.045) in the left coronary cusp (LCC), lower rapid leaflet closing velocity compared with VG (P=0.04) in the right coronary cusp (RCC), and lower relative opening force compared with ACP (P=0.04) in the RCC. The flutter frequency was lower in baseline compared with VG (P=0.02) and in VG compared with ACP (P=0.03) in the LCC. Left coronary artery mean flow was higher in SG compared with SMOD (P=0.02) and ACP (P=0.05). Clinically, operations using SG compared with sinus-containing graft was associated with shorter aortic cross-clamp and cardiopulmonary bypass time (P<0.001, <0.001). Conclusions: SG demonstrated hemodynamics and biomechanics most closely recapitulating those from the native root with significantly shorter intraoperative times compared with repair using sinus-containing graft. Future in vivo validation studies as well as correlation with comprehensive, comparative clinical study outcomes may provide additional invaluable insights regarding strategies to further enhance repair durability.

An analytical, mathematical annuloplasty ring curvature model for planning of valve-in-ring transcatheter mitral valve replacement.

Objectives: An increasing number of high-risk patients with previous mitral valve annuloplasty require transcatheter mitral valve replacement due to recurrent regurgitation. Annulus dilation with a transcatheter balloon is often performed before valve-in-ring transcatheter mitral valve replacement, which is believed to reduce misalignment and paravalvular leakage, yet little evidence exists to support this practice. Our objective was to generate intuitive annuloplasty ring analyses for improved valve-in-ring transcatheter mitral valve replacement planning. Methods: We generated a mathematical model that calculates image-tracked differential ring curvature to build quantifications for improved planning for valve-in-ring procedures. Carpentier-Edwards Physio M24 and M30 (n = 2 each), Physio II M24 and M26 (n = 3 each), LivaNova AnnuloFlex M26 (n = 2), and Edwards Geoform M28 (n = 2) rings were tested with a 30-mm Toray Inoue balloon inflated to maximum rated pressures. Results: Curvature variance reduces with larger ring sizes, indicating that larger rings are initially more circular than smaller ones. Evaluated semi-rigid and rigid rings showed little to no difference between pre- and post-dilation states. Annuloflex rings (flexible band) showed a postdilation variance reduction of 32.83% (P < .001) followed by an increase after 10 minutes of relaxation that was still reduced by 19.62% relative to the initial state (P < .001). Conclusions: We discovered that balloon dilation does not significantly deform evaluated semi-rigid or rigid rings at maximum rated balloon pressures. This may mean that dilation for these conditions before valve-in-ring transcatheter mitral valve replacement is unnecessary. Our mathematical approach creates a foundation for extended classification of this practice, providing meaningful quantification of ring geometry.

Biomechanical analysis of novel leaflet geometries for bioprosthetic valves.

Objectives: Although bioprosthetic valves have excellent hemodynamic properties and can eliminate the need for lifelong anticoagulation therapy, these devices are associated with high rates of reoperation and limited durability. Although there are many distinct bioprosthesis designs, all bioprosthetic valves have historically featured a trileaflet pattern. This in silico study examines the biomechanical effect of modulating the number of leaflets in a bioprosthetic valve. Methods: Bioprosthetic valves with 2 to 6 leaflets were designed in Fusion 360 using quadratic spline geometry. Leaflets were modeled with standard mechanical parameters for fixed bovine pericardial tissue. A mesh of each design was structurally evaluated using finite element analysis software Abaqus CAE. Maximum von Mises stresses during valve closure were assessed for each leaflet geometry in both the aortic and mitral position. Results: Computational analysis demonstrated that increasing the number of leaflets is associated with reduction in leaflet stresses. Compared with the standard trileaflet design, a quadrileaflet pattern reduces leaflet maximum von Mises stresses by 36% in the aortic position and 38% in the mitral position. Maximum stress was inversely proportional to the square of the leaflet quantity. Surface area increased linearly and central leakage increased quadratically with leaflet quantity. Conclusions: A quadrileaflet pattern was found to reduce leaflet stresses while limiting increases in central leakage and surface area. These findings suggest that modulating the number of leaflets can allow for optimization of the current bioprosthetic valve design, which may translate to more durable valve replacement bioprostheses.

The Critical Biomechanics of Aortomitral Angle and Systolic Anterior Motion: Engineering Native Ex Vivo Simulation.

Systolic anterior motion (SAM) of the mitral valve (MV) is a complex pathological phenomenon often occurring as an iatrogenic effect of surgical and transcatheter intervention. While the aortomitral angle has long been linked to SAM, the mechanistic relationship is not well understood. We developed the first ex vivo heart simulator capable of recreating native aortomitral biomechanics, and to generate models of SAM, we performed anterior leaflet augmentation and sequential undersized annuloplasty procedures on porcine aortomitral junctions (n = 6). Hemodynamics and echocardiograms were recorded, and echocardiographic analysis revealed significantly reduced coaptation-septal distances confirming SAM (p = 0.003) and effective manipulation of the aortomitral angle (p < 0.001). Upon increasing the angle in our pathological models, we recorded significant increases (p < 0.05) in both coaptation-septal distance and multiple hemodynamic metrics, such as aortic peak flow and effective orifice area. These results indicate that an increased aortomitral angle is correlated with more efficient hemodynamic performance of the valvular system, presenting a potential, clinically translatable treatment opportunity for reducing the risk and adverse effects of SAM. As the standard of care shifts towards surgical and transcatheter interventions, it is increasingly important to better understand SAM biomechanics, and our advances represent a significant step towards that goal.

A Novel Rheumatic Mitral Valve Disease Model with Ex Vivo Hemodynamic and Biomechanical Validation.

PURPOSE: Rheumatic heart disease is a major cause of mitral valve (MV) dysfunction, particularly in disadvantaged areas and developing countries. There lacks a critical understanding of the disease biomechanics, and as such, the purpose of this study was to generate the first ex vivo porcine model of rheumatic MV disease by simulating the human pathophysiology and hemodynamics. METHODS: Healthy porcine valves were altered with heat treatment, commissural suturing, and cyanoacrylate tissue coating, all of which approximate the pathology of leaflet stiffening and thickening as well as commissural fusion. Hemodynamic data, echocardiography, and high-speed videography were collected in a paired manner for control and model valves (n = 4) in an ex vivo left heart simulator. Valve leaflets were characterized in an Instron tensile testing machine to understand the mechanical changes of the model (n = 18). RESULTS: The model showed significant differences indicative of rheumatic disease: increased regurgitant fractions (p < 0.001), reduced effective orifice areas (p < 0.001), augmented transmitral mean gradients (p < 0.001), and increased leaflet stiffness (p = 0.025). CONCLUSION: This work represents the creation of the first ex vivo model of rheumatic MV disease, bearing close similarity to the human pathophysiology and hemodynamics, and it will be used to extensively study both established and new treatment techniques, benefitting the millions of affected victims.

Biomechanical Engineering Analysis of Pulmonary Valve Leaflet Hemodynamics and Kinematics in the Ross Procedure.

The Ross procedure using the inclusion technique with anticommissural plication (ACP) is associated with excellent valve hemodynamics and favorable leaflet kinematics. The objective was to evaluate individual pulmonary cusp's biomechanics and fluttering by including coronary flow in the Ross procedure using an ex vivo three-dimensional-printed heart simulator. Ten porcine and five human pulmonary autografts were harvested from a meat abattoir and heart transplant patients. Five porcine autografts without reinforcement served as controls. The other autografts were prepared using the inclusion technique with and without ACP (ACP and NACP). Hemodynamic and high-speed videography data were measured using the ex vivo heart simulator. Although porcine autografts showed similar leaflet rapid opening and closing mean velocities, human ACP compared to NACP autografts demonstrated lower leaflet rapid opening mean velocity in the right (p = 0.02) and left coronary cusps (p = 0.003). The porcine and human autograft leaflet rapid opening and closing mean velocities were similar in all three cusps. Porcine autografts showed similar leaflet flutter frequencies in the left (p = 0.3) and noncoronary cusps (p = 0.4), but porcine NACP autografts versus controls demonstrated higher leaflet flutter frequency in the right coronary cusp (p = 0.05). The human NACP versus ACP autografts showed higher flutter frequency in the noncoronary cusp (p = 0.02). The leaflet flutter amplitudes were similar in all three cusps in both porcine and human autografts. The ACP compared to NACP autografts in the Ross procedure was associated with more favorable leaflet kinematics. These results may translate to the improved long-term durability of the pulmonary autografts.

Native and Post-Repair Residual Mitral Valve Prolapse Increases Forces Exerted on the Papillary Muscles: A Possible Mechanism for Localized Fibrosis?

BACKGROUND: Recent studies have linked mitral valve prolapse to localized myocardial fibrosis, ventricular arrhythmia, and even sudden cardiac death independent of mitral regurgitation or hemodynamic dysfunction. The primary mechanistic theory is rooted in increased papillary muscle traction and forces due to prolapse, yet no biomechanical evidence exists showing increased forces. Our objective was to evaluate the biomechanical relationship between prolapse and papillary muscle forces, leveraging advances in ex vivo modeling and technologies. We hypothesized that mitral valve prolapse with limited hemodynamic dysfunction leads to significantly higher papillary muscle forces, which could be a possible trigger for cellular and electrophysiological changes in the papillary muscles and adjacent myocardium. METHODS: We developed an ex vivo papillary muscle force transduction and novel neochord length adjustment system capable of modeling targeted prolapse. Using 3 unique ovine models of mitral valve prolapse (bileaflet or posterior leaflet prolapse), we directly measured hemodynamics and forces, comparing physiologic and prolapsing valves. RESULTS: We found that bileaflet prolapse significantly increases papillary muscle forces by 5% to 15% compared with an optimally coapting valve, which are correlated with statistically significant decreases in coaptation length. Moreover, we observed significant changes in the force profiles for prolapsing valves when compared with normal controls. CONCLUSIONS: We discovered that bileaflet prolapse with the absence of hemodynamic dysfunction results in significantly elevated forces and altered dynamics on the papillary muscles. Our work suggests that the sole reduction of mitral regurgitation without addressing reduced coaptation lengths and thus increased leaflet surface area exposed to ventricular pressure gradients (ie, billowing leaflets) is insufficient for an optimal repair.

Quantitative biomechanical optimization of neochordal implantation location on mitral leaflets during valve repair.

Objective: Suture pull-out remains a significant mechanism of long-term neochordal repair failure, as demonstrated by clinical reports on recurrent mitral valve regurgitation and need for reoperation. The objective of this study was to provide a quantitative comparison of suture pull-out forces for various neochordal implantation locations. Methods: Posterior leaflets were excised from fresh porcine mitral valves (n = 54) and fixed between two 3-dimensional-printed plates. Gore-Tex CV-5 sutures (WL Gore & Associates Inc) were placed with distances from the leading edge and widths between anchoring sutures with values of 2 mm, 6 mm, and 10 mm for a total of 9 groups (n = 6 per group). Mechanical testing was performed using a tensile testing machine to evaluate pull-out force of the suture through the mitral valve leaflet. Results: Increasing the suture anchoring width improved failure strength significantly across all leading-edge distances (P < .001). Additionally, increasing the leading-edge distance from 2 mm to 6 mm increased suture pull-out forces significantly across all suture widths (P < .001). For 6-mm and 10-mm widths, increasing the leading-edge distance from 6 mm to 10 mm increased suture pull-out forces by an average of 3.58 ± 0.15 N; in comparison, for leading-edge distances of 6 mm and 10 mm, increasing the suture anchoring width from 6 mm to 10 mm improves the force by an average of 7.09 ± 0.44 N. Conclusions: Increasing suture anchoring width and leading-edge distance improves the suture pull-out force through the mitral leaflet, which may optimize postrepair durability. The results suggest a comparative advantage to increasing suture anchoring width compared with leading-edge distance.

Biomechanical analysis of neochordal repair error from diastolic phase inversion of static left ventricular pressurization.

Objective: Neochordal implantation is a common form of surgical mitral valve (MV) repair. However, neochord length is assessed using static left ventricular pressurization, leading surgeons to evaluate leaflet coaptation and valve competency when the left ventricle is dilating instead of contracting physiologically, referred to as diastolic phase inversion (DPI). We hypothesize that the difference in papillary muscle (PM) positioning between DPI and physiologic systole results in miscalculated neochord lengths, which might affect repair performance. Methods: Porcine MVs (n = 6) were mounted in an ex vivo heart simulator and PMs were affixed to robots that accurately simulate PM motion. Baseline hemodynamic and chordal strain data were collected, after which P2 chordae were severed to simulate posterior leaflet prolapse from chordal rupture and subsequent mitral regurgitation. Neochord implantation was performed in the physiologic and DPI static configurations. Results: Although both repairs successfully reduced mitral regurgitation, the DPI repair resulted in longer neochordae (2.19 ± 0.4 mm; P < .01). Furthermore, the hemodynamic performance was reduced for the DPI repair resulting in higher leakage volume (P = .01) and regurgitant fraction (P < .01). Peak chordal forces were reduced in the physiologic repair (0.57 ± 0.11 N) versus the DPI repair (0.68 ± 0.12 N; P < .01). Conclusions: By leveraging advanced ex vivo technologies, we were able to quantify the effects of static pressurization on neochordal length determination. Our findings suggest that this post-repair assessment might slightly overestimate the neochordal length and that additional marginal shortening of neochordae might positively affect MV repair performance and durability by reducing load on surrounding native chordae.

Biomechanical engineering analysis of an acute papillary muscle rupture disease model using an innovative 3D-printed left heart simulator.

OBJECTIVES: The severity of acute papillary muscle (PM) rupture varies according to the extent and site of the rupture. However, the haemodynamic effects of different rupture variations are still poorly understood. Using a novel ex vivo model, we sought to study acute PM rupture to improve clinical management. METHODS: Using porcine mitral valves (n = 32) mounted within an ex vivo left heart simulator, PM rupture was simulated. The mitral valve was divided into quadrants for analysis according to the PM heads. Acute PM rupture was simulated by incrementally cutting from 1/3 to the total number of chordae arising from 1 PM head of interest. Haemodynamic parameters were measured. RESULTS: Rupture >2/3 of the chordae from 1 given PM head or regurgitation fraction >60% led to markedly deteriorated haemodynamics. Rupture at the anterolateral PM had a stronger negative effect on haemodynamics than rupture at the posteromedial PM. Rupture occurring at the anterior head of the anterolateral PM led to more marked haemodynamic instability than rupture occurring at the other PM heads. CONCLUSIONS: The haemodynamic effects of acute PM rupture vary considerably according to the site and extent of the rupture. Rupture of ≤2/3 of chordae from 1 PM head or rupture at the posteromedial PM lead to less marked haemodynamics effects, suggesting a higher likelihood of tolerating surgery. Rupture at the anterolateral PM, specifically the anterior head, rupture of >2/3 of chordae from 1 PM head or regurgitation fraction >60% led to marked haemodynamic instability, suggesting the potential benefit from bridging strategies prior to surgery.