A cyclical tensile testing apparatus was developed to obtain data on the durability of TF in securing artificial chordae (ePTFE suture) over time by simulating the forces exerted on mitral chordae in a beating heart. The testing apparatus consisted of a stationary lower plate and a mobile upper plate that oscillated at a rate of 80 cycles/min (Fig. 5). Because the native anterior chordae tendineae strut is under approximately 0.071 to 0.177 kilogram-force (kgf) during the cardiac cycle,13 extension springs with loads ranging from 0.045 to 0.467 kgf were selected to mimic chordae tension during the normal cardiac cycle. A total of 100 artificial chords, each with a CV-5 ePTFE suture affixed to the mobile upper plate spring and a CV-4 ePTFE suture affixed to the stationary lower plate spring, were secured at a length of 17 mm with the Coaxial TF. This length was consistent with average native mitral chordae, which range from 14.3 to 19.4 mm.14
The apparatus was submersed in normal saline solution, and the chords were tested over time for cycling periods of 1, 3, 7, 30, 60, and 180 days. After completion of each cycling period, chords were removed from the apparatus and underwent pull-apart force testing. A set of 20 chord samples that had not undergone cyclical tensile testing (control group, day 0) were also subjected to a similar evaluation. Pull-apart force data from the control group (20 samples) were compared with data from the short-duration group (40 samples from the 1-, 3-, and 7-day sets) and the long-duration group (60 samples from the 30-, 60-, and 180-day sets) to evaluate durability of the chord samples over time.
The Mitral Chordae Tendineae Replacement Procedure
The MV chordae tendineae replacement procedure as described hereafter was performed using various surgical models throughout the study.
The left atrium was opened via an incision in the left atrial appendage. One to three mitral chordae attached to the anterior leaflet were resected to create an approximately 1-cm segment of flail leaflet, which resulted in a significant regurgitant jet upon saline testing. The steps for repair of the MV prolapse by implantation of artificial chordae tendineae are described hereafter:
- A pledgeted CV-4 ePTFE suture was placed into the head of the papillary muscle using the PMSD.
- A nonpledgeted CV-5 ePTFE suture was placed using a needle driver into the edge of the flail leaflet corresponding to the resected native mitral chordae.
- The CV-4 and CV-5 ePTFE sutures were threaded coaxially using a bidirectional snare through a TF within the Coaxial suture fastener device.
- The device was guided down into the left ventricle over the CV-4 suture and seated firmly onto the head of the papillary muscle.
- The left ventricle was then distended using the integrated saline infusion feature of the device.
- The CV-5 ePTFE suture was tightened until proper coaptation of the mitral leaflets is observed and the MV becomes competent.
- The device lever was squeezed, crimping the TF and securing the ePTFE suture at the desired length while simultaneously cutting excess suture tails.
Benchtop, Human Cadaver, and Live Animal Models
Automated MV chordae tendineae replacements were evaluated in three porcine and nine ovine ex vivo hearts to test proof of concept before conducting studies in a live animal model. This procedure was also performed in two human cadavers via a minimally invasive right thoracotomy approach to evaluate operative angles and device feasibility through limited-access incisions.
A live animal protocol was approved by the University of Rochester's Institutional Animal Care and Use Committee in accordance with the United States Public Health Service Policy on Humane Care and Use of Laboratory Animals.
Eight healthy, adult male Dorset sheep obtained from a local farmer and housed at the institution's Association for Assessment and Accreditation Laboratory Animal Care–accredited National Institutes of Health-assured facility were operated on. Body weights ranged from 48.5 to 58.4 kg. Sheep were premedicated with 4 mg/kg of ketamine intravenous (IV), 0.4 mg/kg of midazolam IV, and 0.004 mg/kg of glycopyrrolate IV. After induction with 2 to 4 mg/kg of propofol, sheep were intubated with an appropriately sized endotracheal tube and anesthesia was maintained with 1% to 2% isoflurane in 100% oxygen. An arterial and central venous catheter was placed in the dorsalis pedis artery and external jugular vein, respectively. Before incision, sheep were administered 22 mg/kg of cefazolin, 5000 U of heparin subcutaneously, and 3 mg/kg of carprofen.
Animals were positioned in the right lateral decubitus position, and the left chest was entered via a 5- to 6-cm muscle-sparing left thoracotomy incision in the fifth intercostal space. The left lung was retracted, and the pericardial sac was incised anterior to the phrenic nerve. For cardiopulmonary bypass (CPB), an 18-French Fem-Flex II arterial cannula (Edwards Lifesciences Corp, Irvine, CA USA) was placed into the descending aorta and a 24-French DLP Single Stage Venous Cannula (Medtronic, Inc, Minneapolis, MN USA) was placed into the main pulmonary artery directed toward the pulmonic valve. An initial dose of heparin (250 U/kg) was given before initiation of CPB and 5000 to 10,000 U of heparin boluses were repeated as needed to maintain an activated clotting time of 480 seconds or greater. Hemodilution was minimized with the use of retrograde autologous priming.
Baseline MV competence was confirmed with epicardial echocardiography and/or saline testing before commencement of the procedure. In planned survivor sheep, myocardial protection was achieved by inducing fibrillatory arrest and moderate hypothermia (25°C), because cardioplegia was not used. In addition, intermittent aortic cross-clamping was performed for up to 20 minutes during the MV chordae replacement to decrease back bleeding and to improve visualization. Carbon dioxide insufflation was also used to reduce the risk of air emboli.
After institution of CPB and aortic cross-clamping, MV chordae replacements were performed. After completion of the procedure, the left atrium was closed and the heart was defibrillated. Sheep were weaned from CPB, and epicardial echocardiography was then performed to evaluate success of the repair.
At reoperation, sheep were induced and intubated in the same manner as the initial procedure. Transthoracic echocardiography was performed before the reoperative procedure to evaluate the integrity of the MV repair and general heart function.
Sheep were positioned in right lateral decubitus, and the site of the previous left thoracotomy incision was reopened to expose the heart. Epicardial echocardiography was performed to confirm integrity of the repairs. Subsequently, the animals were euthanized and the hearts were harvested. Careful dissection of these hearts was performed to evaluate healing and endothelialization of the chords. The hearts were then fixed in formalin, sectioned, and embedded in paraffin. Specimens of the MV, chord, and papillary muscle were then sent to histology for further analysis.
Assessment of MV Function
Transthoracic and epicardial echocardiography was performed by an independent, certified, cardiac-trained anesthesiologist who was blinded to both the study method and device. Mitral regurgitation (MR) was quantified subjectively, given the lack of postoperative regurgitation. Preoperative mitral assessment was quantified by the presence/lack of flail chordae and left atrial regurgitant volume. Pulmonary vein assessment for flow reversal could not be performed.
A total of 10 devices were used to create 120 ePTFE samples secured by a TF (12 samples per device) for cycle testing. Tensile testing for a total of more than 440 million cycles indicated no degradation of TF pull-apart forces over cycling periods of up to 3 months (Table 1). Average TF pull-apart forces did not significantly differ between either the control group [mean ± standard deviation (SD), 0.645 ± 0.093 kgf), the short-duration group (mean ± SD, 0.698 ± 0.091 kgf), or the long-duration group (mean ± SD, 0.696 ± 0.114 kgf; P = 0.13). All TF pull-apart forces were greater than 0.5 kgf (range, 0.505–0.912 kgf), approximately 10 times the force that a typical native mitral chord is subjected to during the cardiac cycle.
Benchtop, Human Cadaver, and Live Animal Models
Benchtop tissue testing aided in iterative device refinement and proof of concept before studies in a live animal model. Successful MV chordae replacements were completed in all 12 ex vivo hearts (3 porcine, 9 ovine) with an average of 1.5 chordae per heart to restore mitral competence. Minimally invasive MV chordae replacements were also successfully completed in two cadavers with the placement of one or two ePTFE artificial chordae. Repairs in the cadaver model confirmed feasibility of this technology for use in human minimally invasive MV repairs.
Restoration of mitral competence using the Coaxial suture fastener device was successfully achieved in all eight sheep. An average of 1.25 ePTFE chordae (range, 1–3 chordae) were placed in vivo to restore MV competence. The first four sheep were considered nonsurvivor animals and used to test device proof of concept and to refine the surgical ovine model and postoperative recovery protocols. The latter four sheep were survived for approximately 6 months to evaluate healing and durability of the repairs.
The average survival time for the four long-term survival sheep was 6.5 months. Despite an uneventful postoperative course, one sheep died at 6.5 months, before the scheduled reoperation from undetermined causes at necropsy.
Transthoracic and epicardial echocardiography on the three remaining sheep showed trace MR in two sheep and no MR in one sheep (Fig. 6). Gross and histopathologic evaluation of the harvested hearts revealed appropriate healing responses with two thirds to near complete endothelialization of the artificial chordae components (ePTFE sutures, Teflon pledget, and TF; Fig. 7). There was no evidence of any local trauma induced by the implanted TF on nearby adjacent structures (native chordae, papillary muscle, cardiac endothelium). In addition, no associated thrombus was visualized nor did embolization of the TF or chordae occur.
It is estimated that more than 150 million people worldwide may be affected by MR, and approximately 5% to 10% of these patients progress to its most severe form. Left untreated, MR results in gradual worsening of left ventricular function, pulmonary hypertension, and an increased risk of developing atrial fibrillation, with annual mortality rates ranging between 6% and 7%.15 Surgical repair of the valve to restore competency historically involved complete excision of the mitral leaflets and subvalvular apparatus with implantation of a prosthetic valve. However, a greater understanding of this complex disease and advancements in surgical technique has led to a gradual trend toward MV repair as opposed to valve replacement.2
The technical challenges associated with MV repair have been present since its inception, with difficulties in using ePTFE chordae to accurately replace diseased native chordae being an ever-present concern among many surgeons.11 It has been shown by Reimink et al16 that even minor errors in replacement, chordae length can have significant consequences on chordal tension, with a 10% increase in chordal length resulting in close to a twofold increase in chordae tension. This finding stresses the importance of reliable and consistent securing of ePTFE chordae at the correct length. With more than 30 different techniques described in the literature to facilitate artificial chordae implantation,17 there is currently no consensus as to the optimal approach for this critical component of the MV repair.
The technology described in this study addresses several concerns that have been presented in the literature regarding artificial chordae implantation. First, the integrated saline feature of the Coaxial suture fastener device provides real-time feedback because the surgeon can visualize mitral leaflet coaptation while adjusting chordae length. This could greatly facilitate accurate chordae length determination, obviating the need for preoperative assessment of length using echocardiography, intraoperative calipers, and repeated length measurements and readjustments using temporary knots, clips, or tourniquets for temporary chordae fixation. The use of TF in lieu of hand-tied knots has also been shown to be a stronger and more reliable method of securing suture,12 and its use for securing artificial chordae has been shown in this study to allow for immediate suture fixation at the desired length, eliminating the risk of inadvertent knot migration and obviating the need for multiple slip knots. In addition, the use of this technology allows the artificial chordae to be secured using techniques that keep the knot away from the leading edge of the MV, because the TF is secured at the apex of the papillary muscle and is not in direct contact with the mitral leaflets, which may lead to less leaflet trauma.
We are of the opinion that the ability to both simplify the process of measuring artificial chordae length and increase surgeon accuracy in performing such measurements, using this technology, may reduce errors in chordae sizing and potentially decrease operative times. It is also important to note that the implantation of a TF within the left ventricle for securing artificial chordae did not, to the best of our knowledge, cause any local injury or result in any adverse consequences to the animals being studied, despite its close proximity to nearby critical structures. Near-complete endothelialization of the artificial chordae and TF were observed in all three sheep during the reoperations, which suggests that such a procedure, if performed in human subjects, would be safe and encourages further investigation.
Another advantage of this automated system is its applicability in minimally invasive cardiac surgery and its ability to facilitate MV repairs through the left atrial appendage, as demonstrated by the successful use of the Coaxial TF and the PMSD via thoracotomies in human cadavers and in the animal model. The PMSD was designed to remotely place pledgeted ePTFE sutures into the head of the papillary muscle, which can be difficult using a needle driver through a limited-access approach. In this study, the Coaxial suture fastener device and PMSD performed as intended without difficulty. Furthermore, no complications occurred related to their use.
A significant limitation encountered in the animal study was the condition of the native MV leaflets. As a result of using sheep without baseline MR, the MV leaflets were very thin and fragile and may have been predisposed to inadvertent tearing with the use of artificial chordae and this technology. Such attenuated leaflets should not be an issue when placing artificial chordae in patients with chronic MR because the diseased leaflets are typically thickened and fibrotic. In addition, only three sheep were available for long-term follow-up, and further testing is required to fully establish the efficacy of this technology for the repair of MR secondary to MV prolapse. Furthermore, the results obtained from this study in sheep may not be fully generalizable to human use, and additional clinical testing will be required to determine its complete safety profile and feasibility for use in human subjects.
In conclusion, the implementation of this system may decrease the complexity of artificial chordae implantation and increase the adoption of MV chordae tendineae replacements as a technique for MV repair. The data from this study may suggest a more robust repair if this system was to be applied for use in humans. The potential benefits from its application could result in standardization and simplification of what was previously a complex procedure, resulting in decreased operative times that ultimately may lead to an improvement in patient outcomes.
The devices evaluated in this study remain investigational and are not for commercial use nor approved by the Food and Drug Administration for any purpose.
The authors thank Dr Louis DiVincenti, Dr Devang Joshi, Dr Leon Metlay, Robin Westcott, Anthony Ryan, Sherry Steinmetz, and Dale Martin for their contribution to this study.
1. Suri RM, Schaff HV, Dearani JA, et al. Survival advantage and improved durability of mitral repair for leaflet prolapse subsets in the current era. Ann Thorac Surg
2. Shuhaiber J, Anderson RJ. Meta-analysis of clinical outcomes following surgical mitral valve repair
or replacement. Eur J Cardiothorac Surg
3. Padala M, Powell SN, Croft LR, Thourani VH, Yoganathan AP, Adams DH. Mitral valve hemodynamics after repair of acute posterior leaflet prolapse: quadrangular resection versus triangular resection versus neochordoplasty. J Thorac Cardiovasc Surg
4. Falk V, Seeburger J, Czesla M, et al. How does the use of polytetrafluoroethylene neochordae for posterior mitral valve prolapse (loop technique) compare with leaflet resection? A prospective randomized trial. J Thorac Cardiovasc Surg
5. Seeburger J, Falk V, Borger MA, et al. Chordae replacement versus resection for repair of isolated posterior mitral leaflet prolapse: à ègalité. Ann Thorac Surg
6. Lange R, Guenther T, Noebauer C, et al. Chordal replacement versus quadrangular resection for repair of isolated posterior mitral leaflet prolapse. Ann Thorac Surg
7. Ibrahim M, Rao C, Savvopoulou M, Casula R, Athanasiou T. Outcomes of mitral valve repair
using artificial chordae. Eur J Cardiothorac Surg
8. Chiappini B, Sanchez A, Noirhomme P, et al. Replacement of chordae tendineae with polytetrafluoroethylene (PTFE) sutures in mitral valve repair
: early and long-term results. J Heart Valve Dis
9. Bortolotti U, Milano AD, Frater RW. Mitral valve repair
with artificial chordae: a review of its history, technical details, long-term results, and pathology. Ann Thorac Surg
10. Phillips MR, Daly RC, Schaff HV, Dearani JA, Mullany CJ, Orszulak TA. Repair of anterior leaflet mitral valve prolapse: chordal replacement versus chordal shortening. Ann Thorac Surg
11. von Oppell UO, Mohr FW. Chordal replacement for both minimally invasive and conventional mitral valve surgery using premeasured Gore-Tex loops. Ann Thorac Surg
12. Lee CY, Sauer JS, Gorea HR, Martellaro AJ, Knight PA. Comparison of strength, consistency, and speed of COR-KNOT versus manually hand-tied knots in an ex vivo minimally invasive model. Innovations
13. Jimenez JH, Soerensen DD, He Z, He S, Yoganathan AP. Effects of a saddle shaped annulus on mitral valve function and chordal force distribution: an in vitro study. Ann Biomed Eng
14. Lam JH, Ranganathan N, Wigle ED, Silver MD. Morphology of the human mitral valve. I. Chordae tendineae: a new classification. Circulation
15. Verma S, Mesana TG. Mitral-valve repair for mitral-valve prolapse. N Engl J Med
16. Reimink MS, Kunzelman KS, Cochran RP. The effect of chordal replacement suture length on function and stresses in repaired mitral valves: a finite element study. J Heart Valve Dis
17. Ibrahim M, Rao C, Athanasiou T. Artificial chordae for degenerative mitral valve disease: critical analysis of current techniques. Interact Cardiovasc Thorac Surg
This experimental study by Lee et al at the University of Rochester examined the efficacy of two new devices: a remote-suturing device for delivery of expanded polytetrafluoroethylene suture to the papillary muscle and a coaxial titanium suture fastener (TF) device with integrated saline infusion for real-time determination of chordae length during fixation. Investigation of this technology was performed in ex vivo porcine, ovine, and in situ cadaver hearts and also in a survivor ovine model. Durability testing of the expanded polytetrafluoroethylene suture secured with TF demonstrated no degradation for 440 million cycles. Mitral valve repairs using this technology were performed in eight sheep; four demonstrated proof of concept and four survived for an average of 6.5 months. At reoperation, echocardiography demonstrated trace to no mitral regurgitation with near complete endothelialization of the TF and artificial chordae.
This is a well-performed experimental study demonstrating the efficacy of these new technologies. The authors are to be congratulated for their careful evaluation employing a logical stepwise approach to test these devices.
The limitations of this study were the small number of animals, the lack of quantification of mitral regurgitation, and the lack of objective histology. Only three sheep were available at chronic follow-up, and further chronic testing will be needed to establish the efficacy of the device.Moreover, findings in a sheep model may not be fully applicable to humans, and device development will likely be needed for clinical application. Finally, the authors have significant conflict of interest because this work was funded by the company, which makes the technology.
However, this is a preliminary study, with a good experimental design and impressive early results.With modification, this technology has great promise to potentially facilitate minimally invasive valve repair.
Mitral valve repair; Minimally invasive cardiac surgery; Artificial chordae tendineae; Titanium fastener; Automated suturing
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