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.

Chordal force profile after neochordal repair of anterior mitral valve prolapse: An ex vivo study.

Objective: This study aimed to biomechanically evaluate the force profiles on the anterior primary and secondary chordae after neochord repair for anterior valve prolapse with varied degrees of residual mitral regurgitation using an ex vivo heart simulator. Methods: The experiment used 8 healthy porcine mitral valves. Chordal forces were measured using fiber Bragg grating sensors on primary and secondary chordae from A2 segments. The anterior valve prolapse model was generated by excising 2 primary chordae at the A2 segment. Neochord repair was performed with 2 pairs of neochords. Varying neochord lengths simulated postrepair residual mitral regurgitation with regurgitant fraction at >30% (moderate), 10% to 30% (mild), and <10% (perfect repair). Results: Regurgitant fractions of baseline, moderate, mild, and perfect repair were 4.7% ± 0.8%, 35.8% ± 2.1%, 19.8% ± 2.0%, and 6.0% ± 0.7%, respectively (P < .001). Moderate had a greater peak force of the anterior primary chordae (0.43 ± 0.06 N) than those of baseline (0.19 ± 0.04 N; P = .011), mild (0.23 ± 0.05 N; P = .041), and perfect repair (0.21 ± 0.03 N; P = .006). In addition, moderate had a greater peak force of the anterior secondary chordae (1.67 ± 0.17 N) than those of baseline (0.64 ± 0.13 N; P = .003), mild (0.84 ± 0.24 N; P = .019), and perfect repair (0.68 ± 0.14 N; P = .001). No significant differences in peak and average forces on both primary and secondary anterior chordae were observed between the baseline and perfect repair as well as the mild and perfect repair. Conclusions: Moderate residual mitral regurgitation after neochord repair was associated with increased anterior primary and secondary chordae forces in our ex vivo anterior valve prolapse model. This difference in chordal force profile may influence long-term repair durability, providing biomechanical evidence in support of obtaining minimal regurgitation when repairing mitral anterior valve prolapse.

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.

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.

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.

Ex vivo biomechanical analysis of the Ross procedure using the modified inclusion technique in a 3-dimensionally printed left heart simulator.

OBJECTIVE: The inclusion technique was developed to reinforce the pulmonary autograft to prevent dilation after the Ross procedure. Anticommissural plication (ACP), a modification technique, can reduce graft size and create neosinuses. The objective was to evaluate pulmonary valve biomechanics using the inclusion technique in the Ross procedure with and without ACP. METHODS: Seven porcine and 5 human pulmonary autografts were harvested from hearts obtained from a meat abattoir and from heart transplant recipients and donors, respectively. Five additional porcine autografts without reinforcement were used as controls. The Ross procedure was performed using the inclusion technique with a straight polyethylene terephthalate graft. The same specimens were tested both with and without ACP. Hemodynamic parameter data, echocardiography, and high-speed videography were collected via the ex vivo heart simulator. RESULTS: Porcine autograft regurgitation was significantly lower after the use of inclusion technique compared with controls (P < .01). ACP compared with non-ACP in both porcine and human pulmonary autografts was associated with lower leaflet rapid opening velocity (3.9 ± 2.4 cm/sec vs 5.9 ± 2.4 cm/sec; P = .03; 3.5 ± 0.9 cm/sec vs 4.4 ± 1.0 cm/sec; P = .01), rapid closing velocity (1.9 ± 1.6 cm/sec vs 3.1 ± 2.0 cm/sec; P = .01; 1.8 ± 0.7 cm/sec vs 2.2 ± 0.3 cm/sec; P = .13), relative rapid opening force (4.6 ± 3.0 vs 7.7 ± 5.2; P = .03; 3.0 ± 0.6 vs 4.0 ± 2.1; P = .30), and relative rapid closing force (2.5 ± 3.4 vs 5.9 ± 2.3; P = .17; 1.4 ± 1.3 vs 2.3 ± 0.6; P = .25). CONCLUSIONS: The Ross procedure using the inclusion technique demonstrated excellent hemodynamic parameter results. The ACP technique was associated with more favorable leaflet biomechanics. In vivo validation should be performed to allow direct translation to clinical practice.

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.

A novel accelerated fatigue testing system for pulsatile applications of cardiac devices using widely translatable cam and linkage-based mechanisms.

Fatigue testing of mechanical components is important for designing safe implantable medical prosthetics, and accelerated systems can be used to increase the speed of evaluation. We developed a platform for accelerated testing of linear force applications of cardiac devices, called the Fatigue Acceleration System Tester (FAST). FAST operates using a core translation mechanism, converting motor-driven rotary motion to linear actuation. The advantages of using this mechanism include 40x rate increases with largely 3D-printed components, versatility based on modular design paradigms, and accessible manufacturability with 3D-printable forms, enabling access for small and large research laboratories alike. FAST has been crucial in informing our designs for continuing device development. Over two fatigue cycle courses of 52 and 110 days, the motor cycled at rotational frequencies up to 1500 rpm, 43 times faster than those experienced in a typical heart and equating to approximate life cycles of five and ten years, respectively. In designing FAST, our goal was to accessibly bring a strong mechanical basis to study the long-term effects of repeated loading, and we present a design that can be applied across many industries to not only evaluate fatigue performance, but also generate any cycling linear motion.

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.

Ex vivo biomechanical analysis of flexible versus rigid annuloplasty rings in mitral valves using a novel annular dilation system.

BACKGROUND: Mitral annuloplasty rings restore annular dimensions to increase leaflet coaptation, serving a fundamental component in mitral valve repair. However, biomechanical evaluations of annuloplasty rings are lacking. We aim to biomechanically analyze flexible and rigid annuloplasty rings using an ex vivo mitral annular dilation model. METHODS: Juvenile porcine mitral valves (n = 4) with intercommissural distance of 28 mm were dilated to intercommissural distances of 40 mm using a 3D-printed dilator and were sewn to an elastic mount. Fiber bragg grating sensors were anchored to native chordae to measure chordal forces. The valves were repaired using size 28 rigid and flexible annuloplasty rings in a random order. Hemodynamic data, echocardiography, and chordal force measurements were collected. RESULTS: Mitral annular dilation resulted in decreased leaflet coaptation height and increased mitral regurgitation fraction. Both the flexible and rigid annuloplasty rings effectively increased leaflet coaptation height compared to that post dilation. Rigid ring annuloplasty repair significantly decreased the mitral regurgitation fraction. Flexible annuloplasty ring repair reduced the chordal rate of change of force (7.1 ± 4.4 N/s versus 8.6 ± 5.9 N/s, p = 0.02) and peak force (0.6 ± 0.5 N versus 0.7 ± 0.6 N, p = 0.01) compared to that from post dilation. Rigid annuloplasty ring repair was associated with higher chordal rate of change of force (9.8 ± 5.8 N/s, p = 0.0001) and peak force (0.7 ± 0.5 N, p = 0.01) compared to that after flexible ring annuloplasty repair. CONCLUSIONS: Both rigid and flexible annuloplasty rings are effective in increasing mitral leaflet coaptation height. Although the rigid annuloplasty ring was associated with slightly higher chordal stress compared to that of the flexible annuloplasty ring, it was more effective in mitral regurgitation reduction. This study may help direct the design of an optimal annuloplasty ring to further improve patient outcomes.

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.

Ex Vivo Model of Ischemic Mitral Regurgitation and Analysis of Adjunctive Papillary Muscle Repair.

Ischemic mitral regurgitation (IMR) is particularly challenging to repair with lasting durability due to the complex valvular and subvalvular pathologies resulting from left ventricular dysfunction. Ex vivo simulation is uniquely suited to quantitatively analyze the repair biomechanics, but advancements are needed to model the nuanced IMR disease state. Here we present a novel IMR model featuring a dilation device with precise dilatation control that preserves annular elasticity to enable accurate ex vivo analysis of surgical repair. Coupled with augmented papillary muscle head positioning, the enhanced heart simulator system successfully modeled IMR pre- and post-surgical intervention and enabled the analysis of adjunctive subvalvular papillary muscle repair to alleviate regurgitation recurrence. The model resulted in an increase in regurgitant fraction: 11.6 ± 1.7% to 36.1 ± 4.4% (p < 0.001). Adjunctive papillary muscle head fusion was analyzed relative to a simple restrictive ring annuloplasty repair and, while both repairs successfully eliminated regurgitation initially, the addition of the adjunctive subvalvular repair reduced regurgitation recurrence: 30.4 ± 5.7% vs. 12.5 ± 2.6% (p = 0.002). Ultimately, this system demonstrates the success of adjunctive papillary muscle head fusion in repairing IMR as well as provides a platform to optimize surgical techniques for increased repair durability.