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.

[Supra-annular Mitral Valve Replacement Using a Composite Valve for an Infant with Acute Rupture of Chordae Tendineae].

Acute rupture of the chordae tendineae of the mitral valve could lead to severe mitral regurgitation and circulatory collapse in infants. Mitral valve replacement may be often challenging because of the valve-annulus size mismatch in small infants when mitral valve repair cannot be accomplished. We present an infant with acute massive rupture of the chordae tendineae of the mitral valve who successfully underwent supra-annular mitral valve replacement using the short composite valve of an expanded polytetrafluoroethylene( ePTFE) graft and a mechanical valve. His mechanical valve has been functioning without complications such as thrombosis and pulmonary venous obstruction for 20 months after surgery. This technique could be helpful even infants with acute rupture of the chordae tendineae of the mitral valve whose left atrium may not be dilated.

A tissue-silicone integrated simulator for right ventricular pulsatile circulation with severe functional tricuspid regurgitation.

There is a great demand for development of a functional tricuspid regurgitation (FTR) model for accelerating development and preclinical study of tricuspid interventional repair devices. This study aimed to develop a severe FTR model by creating a tissue-silicone integrated right ventricular pulsatile circulatory simulator. The simulator incorporates the porcine tricuspid annulus, valve leaflets, chordae tendineae, papillary muscles, and right ventricular wall as one continuous piece of tissue, thereby preserving essential anatomical relationships of the tricuspid valve (TV) complex. We dilated the TV annulus with collagenolytic enzymes under applying stepwise dilation, and successfully achieved a severe FTR model with a regurgitant volume of 45 ± 9 mL/beat and a flow jet area of 15.8 ± 2.3 cm2 (n = 6). Compared to a normal model, the severe FTR model exhibited a larger annular circumference (133.1 ± 8.2 mm vs. 115.7 ± 5.5 mm; p = 0.009) and lower coaptation height (6.6 ± 1.0 mm vs. 17.7 ± 1.3 mm; p = 0.003). Following the De-Vega annular augmentation procedure to the severe FTR model, a significant reduction in regurgitant volume and flow jet area were observed. This severe FTR model may open new avenues for the development and evaluation of transcatheter TV devices.

Biomechanical engineering analysis of neochordae length's impact on chordal forces in mitral repair.

OBJECTIVES: Artificial neochordae implantation is commonly used for mitral valve (MV) repair. However, neochordae length estimation can be difficult to perform. The objective was to assess the impact of neochordae length changes on MV haemodynamics and neochordal forces. METHODS: Porcine MVs (n = 6) were implanted in an ex vivo left heart simulator. MV prolapse (MVP) was generated by excising at least 2 native primary chordae supporting the P2 segments from each papillary muscle. Two neochordae anchored on each papillary muscle were placed with 1 tied to the native chord length (exact length) and the other tied with variable lengths from 2× to 0.5× of the native length (variable length). Haemodynamics, neochordal forces and echocardiography data were collected. RESULTS: Neochord implantation repair successfully eliminated mitral regurgitation with repaired regurgitant fractions of approximately 4% regardless of neochord length (P < 0.01). Leaflet coaptation height also significantly improved to a minimum height of 1.3 cm compared with that of MVP (0.9 ± 0.4 cm, P < 0.05). Peak and average forces on exact length neochordae increased as variable length neochordae lengths increased. Peak and average forces on the variable length neochordae increased with shortened lengths. Overall, chordal forces appeared to vary more drastically in variable length neochordae compared with exact length neochordae. CONCLUSIONS: MV regurgitation was eliminated with neochordal repair, regardless of the neochord length. However, chordal forces varied significantly with different neochord lengths, with a preferentially greater impact on the variable length neochord. Further validation studies may be performed before translating to clinical practices.

Severe tricuspid regurgitation with chordae tendinae rupture in CABG surgery.

A 58-year-old male patient was admitted with chest pain and was diagnosed with coronary heart disease. He was scheduled for coronary artery bypass grafting (CABG) under cardiopulmonary bypass (CPB). Intraoperative real-time transesophageal echocardiography (TEE) showed that the tricuspid valves were well-aligned and subtle regurgitation. Real-time TEE after separation from CPB showed severe tricuspid regurgitation and prolapsed chordae tendineae. The tricuspid chordae tendineae rupture due to a right atrial venous return cannula. The use of negative pressure to improve venous drainage during CPB may result in the tricuspid valve being adsorbed to the cannula, increasing the likelihood of injury to the tricuspid valve.

Feasibility Study of a Novel Transapical Chordal Implantation System in a Porcine Model.

Transapical beating-heart mitral repair with chordal implantation system has been considered as an alternative treatment for degenerative mitral regurgitation. This study aimed to assess the feasibility and safety of the E-Chord system (Med-Zenith Medical, Beijing, China) for transapical beating-heart mitral valve repair in a porcine model. Artificial chordae were transapically implanted on the mitral valves of 12 anesthetized pigs under epicardial echocardiographic guidance and secured outside the left ventricular apex. The study endpoints included procedural success, device durability, and tissue response to the device. The procedural success rate was 100% (12/12). All animals were implanted with E-Chord in the anterior and posterior leaflets, respectively, and survived uneventfully until euthanized as planned. During the 180-day follow-up, no animal had significant mitral valve dysfunction. The gross observation showed no evidence of anchor detachment and chordal rupture, and there was no obvious damage or changes to mitral leaflets. Microscopic evaluation revealed that the endothelialization of anchor and chordae was completed 90 days after implantation and there was no evidence of chordal rupture, thrombosis, or infection during the 180-day follow-up. The E-Chord system was found to be feasible and safe for heart-beating mitral chordal implantation in a porcine model. The findings of this study suggest that the E-Chord system may be a potential alternative for the treatment of degenerative mitral regurgitation in humans.

Feasibility of concomitant exclusion of left atrial appendage during novel transapical off-pump beating heart mitral valve repair.

The AtriClip device enables the safe and reproducible epicardial clipping of the left atrial appendage. Transapical off-pump beating heart mitral valve repair using NeoChord DS100 Artificial Chordae Delivery System has matured and become more standardized. We aim to evaluate the feasibility of combining NeoChord repair and left atrial appendage exclusion in a single procedure through the same minithoracotomy in patients with mitral valve prolapse and atrial fibrillation. From 2018 to 2019, seven patients with severe mitral regurgitation and atrial fibrillation underwent transesophageal echocardiography-guided transapical off-pump mitral valve repair with the novel NeoChord DS 1000 system and concomitant left atrial appendage exclusion using the AtriClip Pro II device. Both procedures were performed via left mini-thoracotomy. The AtriClip device was applied after the NeoChord repair was done. All seven patients had less than moderate mitral regurgitation after the NeoChord repair and successful left atrial appendage occlusion. There were no device or procedure-related complications. Clinical follow-up revealed significant symptomatic improvement, and no cardiovascular complications were reported. Transesophageal echocardiography at 6-12 months post-procedure showed stable left atrial appendage occlusion with no residual flow between the left atrium and the left atrial appendage and a stump of less than 5 mm. Beating heart epicardial clipping of the left atrial appendage using AtriClip concomitant with transapical mitral valve repair using Neochord DS 1000 system is a feasible and safe treatment option in mitral valve prolapse and atrial fibrillation in patients with limited indications. However, its safety needs to be confirmed in a larger series of patients.

Evaluation of a Novel Automated Suturing Technology for Mitral Chordal Implantation: 1-Year Results.

PURPOSE: A new automated expanded polytetrafluoroethylene (ePTFE) suture placement device and a new customized titanium fastener deployment device were clinically evaluated in open and less-invasive mitral valve repair (MVr). DESCRIPTION: Twelve patients were monitored for 1 year after undergoing MVr using the study devices. The study end points included surgical outcomes, operative times, valve repair durability, adverse events, and mortality. EVALUATION: Three patients received 1 ePTFE chord using the study technology, and 9 patients received 2 chords. Mitral regurgitation at 30 days was absent in 8 patients, trace in 2, and mild in 2. At the 1-year follow-up, mitral regurgitation was absent in 7 patients, trace in 2, mild in 2, and moderate in 1. There were no replacement chord failures, reoperations, or death. CONCLUSIONS: The initial outcomes of new automated ePTFE suture placement and titanium fastener deployment devices encourage further clinical evaluations.

Combination of an extremely rare and a common congenital valvular anomalies: Accessory mitral valve chordae from left atrium and bicuspid aortic valve.

Accessory chordae tendineae is an extremely rare anomaly. In this case report, we described a 61-year-old female patient newly diagnosed with the combination of an accessory mitral valve chordae extending from left atrium which is an extremely rare congenital anomaly and a bicuspid aortic valve. In our patient, three-dimensional echocardiography showed incremental value over two-dimensional echocardiography in the assessment of the exact localization and the extend of accessory chordea.

Anatomical Mitral Valve Repair: Mathematical Prediction of Artificial Chordae Length in Para-Commissural Regions.

To develop a mathematical formula for calculating the length of ruptured mitral valve chordae (with a view to surgically replacing them with artificial chordae) when rupture occurs at scallop A1, A3, P1, or P3. We studied human cadaver hearts collected by the Faculty of Medicine at Amiens Picardy University Hospital. The donors' mean age standard deviation age at death was 79 ± 10. After weighing and dissection, we counted the number of para-commissural chordae per scallop and measured their length with a digital calliper. A total of 31 human cadaver hearts (14 from females and 17 from males) were analyzed. The mean lengths of scallops A1, A2, A3, P1, P2, and P3 were 17.45, 19.42, 17.58, 13.32, 14.52, and 13.26 mm, respectively. A linear regression gave the following mathematical equations: A1 = 0.96 × A2- - 1.3 (R: 0.99; P < 0.001); A3 = 0.9 × A2 + 0.17 (R: 0.95; P < 0.01); P1 = 0.87 × P2 +0.74 (R: 0.89; P < 0.001), and P3 = 0.91 × P2 - 0.01 (R: 0.87; P < 0.0001). When the patient's anatomy prevents manual measurements of the chordae during mitral valve repair surgery, the mathematical formulae derived here can be used to predict the length of the chordae on A1, A3, P1, and P3 from the length of the chordae on A2 and P2. The mitral chordae can therefore be replaced with prostheses with a great degree of precision.

Parameters of the mitral apparatus in patients with ischemic and nonischemic dilated cardiomyopathy.

The mitral valve apparatus is a complex structure consisting of several coordinating components: the annulus, two leaflets, the chordae tendineae, and the papillary muscles. Due to the intricate interplay between the mitral valve and the left ventricle, a disease of the latter may influence the normal function of the former. As a consequence, valve insufficiency may arise despite the absence of organic valve disease. This is designated as functional or secondary mitral regurgitation, and it arises from a series of distortions to the valve components. This narrative review describes the normal anatomy and the pathophysiology behind the mitral valve changes in ischemic and non-ischemic dilated cardiomyopathies. It also explains the value of a complete multiparametric assessment of this structure. Not only must an assessment include quantitative measures of regurgitation, but also various anatomical parameters from the mitral apparatus and left ventricle, since they carry prognostic value and are predictors of mitral valve repair success and durability.

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.

Structural properties in ruptured mitral chordae tendineae measured by synchrotron-based X-ray phase computed tomography.

The link between the structural properties and the rupturing of chordae tendineae in the mitral valve complex is still unclear. Synchrotron-radiation-based X-ray phase computed tomography (SR-XPCT) imaging is an innovative way to quantitatively analyze three-dimensional morphology. XPCT has been employed in this study to evaluate the chordae tendineae from patients with mitral regurgitation and to analyze structural changes in the ruptured chordae tendineae in patients with this condition. Six ruptured mitral chordae tendineae were obtained during surgical repairs for mitral regurgitation and were fixed with formalin. In addition, 12 healthy chordae tendineae were obtained from autopsies. Employing XPCT (effective pixel size, 3.5 µm; density resolution, 1 mg cm-3), the density of the chordae tendineae in each sample was measured. The specimens were subsequently analyzed pathologically. The mean age was 70.2 ± 3.0 in the rupture group and 67.2 ± 14.1 years old in the control group (p = 0.4927). All scans of chorda tendineae with SR-XPCT were performed successfully. The mean densities were 1.029 ± 0.004 in the rupture group and 1.085 ± 0.015 g cm-3 in the control group (p < 0.0001). Density based on SR-XPCT in the ruptured mitral chordae tendineae was significantly lower compared with the healthy chorda tendinea. Histological examination revealed a change in the components of the connective tissues in ruptured chorda tendinea, in accordance with the low density measured by SR-XPCT. SR-XPCT made it possible to measure tissue density in mitral chordae tendineae. Low density in mitral chordae tendineae is associated with a greater fragility in ruptured mitral chordae tendineae.

Neochordae implantation versus leaflet resection in mitral valve posterior leaflet prolapse and dilated left ventricle: a propensity score matching comparison with long-term follow-up.

OBJECTIVES: Uncorrected severe mitral regurgitation (MR) due to posterior prolapse leads to left ventricular dilatation. At this stage, mitral valve repair becomes mandatory to avoid permanent myocardial injury. However, which technique among neochoardae implantation and leaflet resection provides the best results in this scenario remains unknown. METHODS: We selected 332 patients with left ventricular dilatation and severe degenerative MR due to posterior leaflet (PL) prolapse who underwent neochoardae implantation (85 patients) or PL resection (247 patients) at our institution between 2008 and 2020. A propensity score matching analysis was carried on to decrease the differences at baseline. RESULTS: Matching yielded 85 neochordae implantations and 85 PL resections. At 10 years, freedom from cardiac death and freedom from mitral valve reoperation were 92.6 ± 6.1% vs 97.8 ± 2.1% and 97.7 ± 2.2% vs 95 ± 3% in the neochordae group and in the PL resection group, respectively. The MR ≥2+ recurrence rate was 23.9 ± 10% in the neochordae group and 20.8 ± 5.8% in the PL resection group (P = 0.834) at 10 years. At the last follow-up, the neochordae group showed a higher reduction of left ventricular end-diastolic diameter (44 vs 48 mm; P = 0.001) and a better ejection fraction (60% vs 55%; P < 0.001) compared to PL resection group. CONCLUSIONS: In this subgroup of patients, both neochordae implantation and leaflet resection provide excellent durability of the repair in the long term. Neochordae implantation might have a better effect on dilated left ventricle.

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.

A Computational Pipeline for Patient-Specific Prediction of the Postoperative Mitral Valve Functional State.

While mitral valve (MV) repair remains the preferred clinical option for mitral regurgitation (MR) treatment, long-term outcomes remain suboptimal and difficult to predict. Furthermore, pre-operative optimization is complicated by the heterogeneity of MR presentations and the multiplicity of potential repair configurations. In the present work, we established a patient-specific MV computational pipeline based strictly on standard-of-care pre-operative imaging data to quantitatively predict the post-repair MV functional state. First, we established human mitral valve chordae tendinae (MVCT) geometric characteristics obtained from five CT-imaged excised human hearts. From these data, we developed a finite-element model of the full patient-specific MV apparatus that included MVCT papillary muscle origins obtained from both the in vitro study and the pre-operative three-dimensional echocardiography images. To functionally tune the patient-specific MV mechanical behavior, we simulated pre-operative MV closure and iteratively updated the leaflet and MVCT prestrains to minimize the mismatch between the simulated and target end-systolic geometries. Using the resultant fully calibrated MV model, we simulated undersized ring annuloplasty (URA) by defining the annular geometry directly from the ring geometry. In three human cases, the postoperative geometries were predicted to 1 mm of the target, and the MV leaflet strain fields demonstrated close agreement with noninvasive strain estimation technique targets. Interestingly, our model predicted increased posterior leaflet tethering after URA in two recurrent patients, which is the likely driver of long-term MV repair failure. In summary, the present pipeline was able to predict postoperative outcomes from pre-operative clinical data alone. This approach can thus lay the foundation for optimal tailored surgical planning for more durable repair, as well as development of mitral valve digital twins.

Anatomical and biometric study of the mitral valve apparatus: application in valve repair surgery.

OBJECTIVE: Most mitral valve repair techniques provide excellent surgical results by removing regurgitation, but all of these techniques simultaneously reduce posterior valve mobility. A comprehensive biometric study of the mitral valve apparatus will provide landmarks that would help improve this posterior valve mobility. MATERIALS AND METHODS: Thirty one (31) human hearts have been studied, from 14 women and 17 men. The characteristics of the studied sample were analyzed descriptively. The difference in means of the variables between women and men were tested using a Student t test. Correlations between the different measures were determined by simple regression analysis. Mean values are shown with ± 1 standard deviation and the limit of significance was set at 0.05. RESULTS: The mean weight of the hearts was 275.3 ± 2.4 g. The anteroposterior diameter of the mitral annulus was 29.3 ± 1.22 mm, the intertrigonal distance was 25.2 ± 3.50 mm and the anterior leaflet to posterior leaflet ratio was 1.9 ± 0.10, the length of the chordae A2 = 19.4 ± 1.15 mm and P2 = 14.5 ± 0.85 mm. The length of the anterior papillary muscle averaged 30.9 ± 7.20 mm and that of the posterior one 30.0 ± 8.75 mm. The comparison of the different values measured between women and men showed no statistically significant difference (p > 0.05). There was no correlation between these different measured values (p > 0.05). CONCLUSION: A perfect knowledge of anatomy and biometry is therefore essential to offer alternative techniques that reproduce the real anatomy and physiology with a complete reconstruction of the mitral valve.