The feasibility of mitral valve device foldoplasty: an in vivo study to evaluate durable retention.

OBJECTIVES: We have previously shown in experimental settings that a leaflet foldoplasty device reduces redundant leaflet area to re-establish mitral valve (MV) coaptation. The current study investigates the in vivo device retention and functional durability following foldoplasty. METHODS: The prototype is of superelastic nitinol formed into a 3-dimensional shape. It is unfolded to engage a specified area of leaflet tissue and then folded to exclude this tissue from the coaptation surface. Design modifications were made and tested in benchtop studies to determine the optimal design for durable retention within the leaflet. To evaluate in vivo performance, posterior leaflet chordae were severed in Yorkshire pigs to produce complete posterior leaflet prolapse and severe mitral regurgitation. Design modifications were then used for MV repair. Five animals that underwent repair using the optimal design were observed for 2 weeks postoperative to evaluate the functional result and implant retention. RESULTS: Device position and orientation were maintained at 2 weeks while preserving the functional MV repair in all 5 animals. Coaptation height was 5.5 ± 1.5 mm, which was not significantly different from a baseline of 4.9 ± 0.8 mm. The degree of leaflet excursion was 41.0 ± 16.0 compared to a baseline of 58.7 ± 27.5. CONCLUSIONS: Device foldoplasty is a new concept for MV repair based on the reduction of redundant leaflet tissue area. This study demonstrates the feasibility of safe maintenance of this repair without early dislodgement or embolization.

Temporal enhancement of 2D color Doppler echocardiography sequences by fragment-based frame reordering and refinement.

PURPOSE: The goal of this study was to develop an algorithm that enhances the temporal resolution of two-dimensional color Doppler echocardiography (2D CDE) by reordering all the acquired frames and filtering out the frames corrupted by out-of-plane motion and arrhythmia. METHODS: The algorithm splits original frame sequence into the fragments based on the correlation with a reference frame. Then, the fragments are aligned temporally and merged into a resulting sequence that has higher temporal resolution. We evaluated the algorithm with 10 animal epicardial 2D CDE datasets of the right ventricle and compared it with the existing approaches in terms of resulting frame rate, image stability and execution time. RESULTS: We identified the optimal combination of alternatives for each step, which resulted in an increase in frame rate from 14 ± 0.87 to 238 ± 93 Hz. The average execution time was 7.23 ± 0.48 s in comparison with 0.009 ± 0.001 s for ECG gating and 1167.37 ± 587.85 s for flow reordering. Our approach demonstrated a significant (p < 0.01) increase in image stability compared with ECG gating and flow reordering. CONCLUSION: This work presents an offline algorithm for temporal enhancement of 2D CDE. Unlike previous frame reordering approaches, it can filter out-of-plane or corrupted frames, increasing the quality of the results, which substantially increases diagnostic value of 2D CDE. It can be used for high-frame-rate intraoperative imaging of intraventricular and valve regurgitant flows and is potentially modifiable for real-time use on ultrasound machines.

An intraoperative test device for aortic valve repair.

OBJECTIVE: Aortic valve repair is currently in transition from surgical improvisation to a reproducible operation and an option for many patients with aortic regurgitation. Our research efforts at improving reproducibility include development of methods for intraoperatively testing and visualizing the valve in its diastolic state. METHODS: We developed a device that can be intraoperatively secured in the transected aorta allowing the aortic root to be pressurized and the closed valve to be inspected endoscopically. Our device includes a chamber that can be pressurized with crystalloid solution and ports for introduction of an endoscope and measuring gauges. We show use of the device in explanted porcine hearts to visualize the aortic valve and to measure leaflet coaptation height in normal valves and in valves that have undergone valve repair procedures. RESULTS: The procedure of introducing and securing the device in the aorta, pressurizing the valve, and endoscopically visualizing the closed valve is done in less than 1 minute. The device easily and reversibly attaches to the aortic root and allows direct inspection of the aortic valve under conditions that mimic diastole. It enables the surgeon to intraoperatively study the valve immediately before repair to determine mechanisms of incompetence and immediately after the repair to assess competence. We also show its use in measuring valve leaflet coaptation height in the diastolic state. CONCLUSIONS: This device enables more relevant prerepair valve assessment and also enables a test of postrepair valve competence under physiological pressures.

Antibody-modified conduits for highly selective cytokine elimination from blood.

Cytokines play an important role in dysregulated immune responses to infection, pancreatitis, ischemia/reperfusion injury, burns, hemorrhage, cardiopulmonary bypass, trauma, and many other diseases. Moreover, the imbalance between inflammatory and antiinflammatory cytokines can have deleterious effects. Here, we demonstrated highly selective blood-filtering devices - antibody-modified conduits (AMCs) - that selectively eliminate multiple specific deleterious cytokines in vitro. AMCs functionalized with antibodies against human vascular endothelial growth factor A or tumor necrosis factor α (TNF-α) selectively eliminated the target cytokines from human blood in vitro and maintained them in reduced states even in the face of ongoing infusion at supraphysiologic rates. We characterized the variables that determine AMC performance, using anti-human TNF-α AMCs to eliminate recombinant human TNF-α. Finally, we demonstrated selective cytokine elimination in vivo by filtering interleukin 1 ß from rats with lipopolysaccharide-induced hypercytokinemia.

Towards Alternative Approaches for Coupling of a Soft Robotic Sleeve to the Heart.

Efficient coupling of soft robotic cardiac assist devices to the external surface of the heart is crucial to augment cardiac function and represents a hurdle to translation of this technology. In this work, we compare various fixation strategies for local and global coupling of a direct cardiac compression sleeve to the heart. For basal fixation, we find that a sutured Velcro band adheres the strongest to the epicardium. Next, we demonstrate that a mesh-based sleeve coupled to the myocardium improves function in an acute porcine heart failure model. Then, we analyze the biological integration of global interface material candidates (medical mesh and silicone) in a healthy and infarcted murine model and show that a mesh interface yields superior mechanical coupling via pull-off force, histology, and microcomputed tomography. These results can inform the design of a therapeutic approach where a mesh-based soft robotic DCC is implanted, allowed to biologically integrate with the epicardium, and actuated for active assistance at a later timepoint. This strategy may result in more efficient coupling of extracardiac sleeves to heart tissue, and lead to increased augmentation of heart function in end-stage heart failure patients.

A leaflet plication clip is an effective surgical template for mitral valve foldoplasty.

OBJECTIVES: During mitral valve repair using the foldoplasty technique, correct judgement of the necessary dimensions and orientation of the leaflet fold is a critical but challenging step that can affect the chances of successful repair. In this study, we investigated whether a leaflet plication clip can be used to guide suture foldoplasty for posterior leaflet prolapse of the mitral valve. METHODS: Complete posterior leaflet prolapse was created in both in vivo and ex vivo pig hearts by severing the chordae supporting the middle scallop. A plication clip was applied to perform leaflet foldoplasty. Sutures were then placed using the clip as a template and the clip was removed. Leaflet width after flail creation, clip application and suture placement was determined in an ex vivo test. In vivo repair and evaluation was then performed in 7 pigs to determine the repair efficacy under normal physiological loading, at 1 and 6 h after recovery from cardiopulmonary bypass. RESULTS: Leaflet width after suture placement was comparable to the clip alone (7.0 ± 1.4 vs 9.0 ± 1.6) and both were significantly less than the flail width 15.7± 2.5 mm. In vivo, average coaptation height following repair was restored to 4.7 ± 1.4 mm and 4.2 ± 1.3 mm at 1 and 6 h, respectively, after recovery compared with the baseline height of 5.5 ± 0.9 mm. Mitral regurgitation was reduced from moderate-severe to mild or less, and addition of a De-Vega annuloplasty in the last 3 animals abolished residual leaks to trivial or none. CONCLUSIONS: Application of the adjustable leaflet plication clip facilitated accurate determination of the correct position, width, height and orientation of the foldoplasty. Any necessary clip repositioning was made prior to the placement of sutures avoiding the need to redo the sutures. This approach could potentially help improve the ease and reproducibility of the foldoplasty repair.

Management of Systemic Right Ventricular Failure in Patients With Congenitally Corrected Transposition of the Great Arteries.

In recent decades, significant progress has been made in the diagnosis and management of congenitally corrected transposition of the great arteries (ccTGA). Nevertheless, gradual dysfunction and failure of the right ventricle (RV) in the systemic circulation remain the main contributors to mortality and disability for patients with ccTGA, especially after adolescence. Anatomic repair of ccTGA effectively resolves the problem of failure of the systemic RV and has good early and midterm results. However, this strategy is applicable primarily in infants and children up to their teens and has associated risks and limitations, and new challenges can arise in the late postoperative period. Patients with ccTGA manifesting progressive systemic RV dysfunction beyond adolescence represent the major challenge. Several palliative options such as cardiac resynchronization therapy, tricuspid valve repair or replacement, pulmonary artery banding, and implantation of an assist device into the systemic RV can be used to improve functional status and to delay the progression of ventricular dysfunction in patients who are not suitable for anatomic correction of ccTGA. For adult patients with severe systemic RV failure, heart transplantation currently remains the only long-term lifesaving procedure, although donor organ availability remains one of the most limiting factors in this type of therapy. This review focuses on current surgical and medical strategies and interventional options for the prevention and management of systemic RV failure in adults and children with ccTGA.

Cardioscopic Tool-delivery Instrument for Beating-heart Surgery.

This paper describes an instrument that provides solutions to two open challenges in beating-heart intracardiac surgery - providing high-fidelity imaging of tool-tissue contact and controlling tool penetration into tissue over the cardiac cycle. Tool delivery is illustrated in the context of tissue removal for which these challenges equate to visualization of the tissue as it is being removed and to control of cutting depth. Cardioscopic imaging is provided by a camera and illumination system encased in an optical window. When the optical window is pressed against tissue, it displaces the blood between the camera and tissue allowing clear visualization. Control of cutting depth is achieved via precise extension of the cutting tool from a port in the optical window. Successful tool use is demonstrated in ex vivo and in vivo experiments.

Concentric Tube Robot Design and Optimization Based on Task and Anatomical Constraints.

Concentric tube robots are catheter-sized continuum robots that are well suited for minimally invasive surgery inside confined body cavities. These robots are constructed from sets of pre-curved superelastic tubes and are capable of assuming complex 3D curves. The family of 3D curves that the robot can assume depends on the number, curvatures, lengths and stiffnesses of the tubes in its tube set. The robot design problem involves solving for a tube set that will produce the family of curves necessary to perform a surgical procedure. At a minimum, these curves must enable the robot to smoothly extend into the body and to manipulate tools over the desired surgical workspace while respecting anatomical constraints. This paper introduces an optimization framework that utilizes procedureor patient-specific image-based anatomical models along with surgical workspace requirements to generate robot tube set designs. The algorithm searches for designs that minimize robot length and curvature and for which all paths required for the procedure consist of stable robot configurations. Two mechanics-based kinematic models are used. Initial designs are sought using a model assuming torsional rigidity. These designs are then refined using a torsionally-compliant model. The approach is illustrated with clinically relevant examples from neurosurgery and intracardiac surgery.

A light-reflecting balloon catheter for atraumatic tissue defect repair.

A congenital or iatrogenic tissue defect often requires closure by open surgery or metallic components that can erode tissue. Biodegradable, hydrophobic light-activated adhesives represent an attractive alternative to sutures, but lack a specifically designed minimally invasive delivery tool, which limits their clinical translation. We developed a multifunctional, catheter-based technology with no implantable rigid components that functions by unfolding an adhesive-loaded elastic patch and deploying a double-balloon design to stabilize and apply pressure to the patch against the tissue defect site. The device uses a fiber-optic system and reflective metallic coating to uniformly disperse ultraviolet light for adhesive activation. Using this device, we demonstrate closure on the distal side of a defect in porcine abdominal wall, stomach, and heart tissue ex vivo. The catheter was further evaluated as a potential tool for tissue closure in vivo in rat heart and abdomen and as a perventricular tool for closure of a challenging cardiac septal defect in a large animal (porcine) model. Patches attached to the heart and abdominal wall with the device showed similar inflammatory response as sutures, with 100% small animal survival, indicating safety. In the large animal model, a ventricular septal defect in a beating heart was reduced to <1.6 mm. This new therapeutic platform has utility in a range of clinical scenarios that warrant minimally invasive and atraumatic repair of hard-to-reach defects.

Comparison of biomaterial delivery vehicles for improving acute retention of stem cells in the infarcted heart.

Cell delivery to the infarcted heart has emerged as a promising therapy, but is limited by very low acute retention and engraftment of cells. The objective of this study was to compare a panel of biomaterials to evaluate if acute retention can be improved with a biomaterial carrier. Cells were quantified post-implantation in a rat myocardial infarct model in five groups (n = 7-8); saline injection (current clinical standard), two injectable hydrogels (alginate, chitosan/ß-glycerophosphate (chitosan/ß-GP)) and two epicardial patches (alginate, collagen). Human mesenchymal stem cells (hMSCs) were delivered to the infarct border zone with each biomaterial. At 24 h, retained cells were quantified by fluorescence. All biomaterials produced superior fluorescence to saline control, with approximately 8- and 14-fold increases with alginate and chitosan/ß-GP injectables, and 47 and 59-fold increases achieved with collagen and alginate patches, respectively. Immunohistochemical analysis qualitatively confirmed these findings. All four biomaterials retained 50-60% of cells that were present immediately following transplantation, compared to 10% for the saline control. In conclusion, all four biomaterials were demonstrated to more efficiently deliver and retain cells when compared to a saline control. Biomaterial-based delivery approaches show promise for future development of efficient in vivo delivery techniques.

A blood-resistant surgical glue for minimally invasive repair of vessels and heart defects.

Currently, there are no clinically approved surgical glues that are nontoxic, bind strongly to tissue, and work well within wet and highly dynamic environments within the body. This is especially relevant to minimally invasive surgery that is increasingly performed to reduce postoperative complications, recovery times, and patient discomfort. We describe the engineering of a bioinspired elastic and biocompatible hydrophobic light-activated adhesive (HLAA) that achieves a strong level of adhesion to wet tissue and is not compromised by preexposure to blood. The HLAA provided an on-demand hemostatic seal, within seconds of light application, when applied to high-pressure large blood vessels and cardiac wall defects in pigs. HLAA-coated patches attached to the interventricular septum in a beating porcine heart and resisted supraphysiologic pressures by remaining attached for 24 hours, which is relevant to intracardiac interventions in humans. The HLAA could be used for many cardiovascular and surgical applications, with immediate application in repair of vascular defects and surgical hemostasis.

Repair of posterior mitral valve prolapse with a novel leaflet plication clip in an animal model.

OBJECTIVE: Recently, there has been increased interest in minimally invasive mitral valve prolapse repair techniques; however, these techniques have limitations. A new technique was developed for treating mitral valve prolapse that uses a novel leaflet plication clip to selectively plicate the prolapsed leaflet segment. The clip's efficacy was tested in an animal model. METHODS: Yorkshire pigs (n = 7) were placed on cardiopulmonary bypass (CPB), and mitral valve prolapse was created by cutting chordae supporting the P2 segment of the posterior leaflet. Animals were weaned off CPB and mitral regurgitation (MR) was assessed echocardiographically. CPB was reinitiated and the plication clip was applied under direct vision to the P2 segment to eliminate the prolapse. The animals survived for 2 hours. Epicardial echocardiography was obtained before and after prolapse creation and 2 hours after clip placement to quantify MR grade and vena contracta area. Posterior leaflet mobility and coaptation height were analyzed before and after clip placement. RESULTS: There were no cases of clip embolization. Median MR grade increased from trivial (0-1.5) to moderate-severe after MR creation (2.5-4+) (P < .05), and decreased to mild after clip placement (0-3+) (P < .05). Vena contracta area tended to increase after cutting the chordae and decrease after clip placement: 0.08 ± 0.10 cm(2) versus 0.21 ± 0.15 cm(2) versus 0.16 ± 0.16 cm(2) (P = .21). The plication clip did not impair leaflet mobility. Coaptation height was restored to baseline: 0.51 ± 0.07 cm versus 0.44 ± 0.18 cm (P = 1.0). CONCLUSIONS: The leaflet plication clip can treat mitral valve prolapse in an animal model, restoring coaptation height without affecting leaflet mobility. This approach is a simple technique that may improve the effectiveness of beating-heart and minimally invasive valve surgery.

Percutaneous steerable robotic tool delivery platform and metal microelectromechanical systems device for tissue manipulation and approximation: closure of patent foramen ovale in an animal model.

BACKGROUND: Beating-heart image-guided intracardiac interventions have been evolving rapidly. To extend the domain of catheter-based and transcardiac interventions into reconstructive surgery, a new robotic tool delivery platform and a tissue approximation device have been developed. Initial results using these tools to perform patent foramen ovale closure are described. METHODS AND RESULTS: A robotic tool delivery platform comprising superelastic metal tubes provides the capability of delivering and manipulating tools and devices inside the beating heart. A new device technology is also presented that uses a metal-based microelectromechanical systems-manufacturing process to produce fully assembled and fully functional millimeter-scale tools. As a demonstration of both technologies, patent foramen ovale creation and closure was performed in a swine model. In the first group of animals (n=10), a preliminary study was performed. The procedural technique was validated with a transcardiac hand-held delivery platform and epicardial echocardiography, video-assisted cardioscopy, and fluoroscopy. In the second group (n=9), the procedure was performed percutaneously using the robotic tool delivery platform under epicardial echocardiography and fluoroscopy imaging. All patent foramen ovales were completely closed in the first group. In the second group, the patent foramen ovale was not successfully created in 1 animal, and the defects were completely closed in 6 of the 8 remaining animals. CONCLUSIONS: In contrast to existing robotic catheter technologies, the robotic tool delivery platform uses a combination of stiffness and active steerability along its length to provide the positioning accuracy and force-application capability necessary for tissue manipulation. In combination with a microelectromechanical systems tool technology, it can enable reconstructive procedures inside the beating heart.

Robotic tissue tracking for beating heart mitral valve surgery.

The rapid motion of the heart presents a significant challenge to the surgeon during intracardiac beating heart procedures. We present a 3D ultrasound-guided motion compensation system that assists the surgeon by synchronizing instrument motion with the heart. The system utilizes the fact that certain intracardiac structures, like the mitral valve annulus, have trajectories that are largely constrained to translation along one axis. This allows the development of a real-time 3D ultrasound tissue tracker that we integrate with a 1 degree-of-freedom (DOF) actuated surgical instrument and predictive filter to devise a motion tracking system adapted to mitral valve annuloplasty. In vivo experiments demonstrate that the system provides highly accurate tracking (1.0 mm error) with 70% less error than manual tracking attempts.

Robotics and imaging in congenital heart surgery.

The initial success seen in adult cardiac surgery with the application of available robotic systems has not been realized as broadly in pediatric cardiac surgery. The main obstacles include extended set-up time and complexity of the procedures, as well as the large size of the instruments with respect to the size of the child. Moreover, while the main advantage of robotic systems is the ability to minimize incision size, for intracardiac repairs, cardiopulmonary bypass is still required. Catheter-based interventions, on the other hand, have expanded rapidly in both application as well as the complexity of procedures and lesions being treated. However, despite the development of sophisticated devices, robotic systems to aid catheter procedures have not been commonly applied in children. In this article, we describe new catheter-like robotic delivery platforms, which facilitate safe navigation and enable complex repairs, such as tissue approximation and fixation, and tissue removal, inside the beating heart. Additional features including the tracking of rapidly moving tissue targets and novel imaging approaches are described, along with a discussion of future prospects for steerable robotic systems.

Right ventricular papillary muscle approximation as a novel technique of valve repair for functional tricuspid regurgitation in an ex vivo porcine model.

OBJECTIVES: Annuloplasty for functional tricuspid regurgitation may sometimes be ineffective because of chamber dilation and valve tethering. This study compared a novel technique, right ventricle (RV)-papillary muscle approximation, with annuloplasty in experimentally-produced tricuspid regurgitation. METHODS: RVs of isolated porcine hearts (n = 10) were statically pressurized, which led to RV dilation and central tricuspid regurgitation. Regurgitant flow was measured with a saline solution-filled column. The head of the anterior papillary muscle was approximated to 4 points on the ventricular septum. Next, a prosthetic ring was implanted, and then RV-papillary muscle approximation was combined. Tricuspid annular dimension, RV geometry, and tricuspid valve tethering were analyzed with 3-dimensional echocardiography. RESULTS: Tricuspid regurgitation (2270 ± 186 mL/min) was reduced by RV-papillary muscle approximation alone (214 ± 45 mL/min; P < .05) more than by annuloplasty alone (724 ± 166 mL/min; P < .05). Combined RV-papillary muscle approximation and annuloplasty resulted in the least regurgitation (80 ± 39 mL/min). RV-papillary muscle approximation reduced tricuspid septolateral diameter (25%; P < .05), and annular area (23%; P < .05), as did annuloplasty. RV-papillary muscle approximation also reduced RV sphericity index (33%; P < .05) and tricuspid tethering height (54%; P < .05), whereas annuloplasty did not. Direction of RV-papillary muscle approximation did not independently affect outcomes. CONCLUSIONS: This ex vivo study suggests that RV-papillary muscle approximation potentially repairs tricuspid regurgitation better than annuloplasty by improving ventricular sphericity and valve tethering as well as annular dimension.

Percutaneous intracardiac beating-heart surgery using metal MEMS tissue approximation tools.

Achieving superior outcomes through the use of robots in medical applications requires an integrated approach to the design of the robot, tooling and the procedure itself. In this paper, this approach is applied to develop a robotic technique for closing abnormal communication between the atria of the heart. The goal is to achieve the efficacy of surgical closure as performed on a stopped, open heart with the reduced risk and trauma of a beating-heart catheter-based procedure. In the proposed approach, a concentric tube robot is used to percutaneously access the right atrium and deploy a tissue approximation device. The device is constructed using a metal microelectromechanical system (MEMS) fabrication process and is designed to both fit the manipulation capabilities of the robot as well as to reproduce the beneficial features of surgical closure by suture. The effectiveness of the approach is demonstrated through ex vivo and in vivo experiments.

A novel cardioport for beating-heart, image-guided intracardiac surgery.

OBJECTIVE: Intracardiac beating-heart procedures require the introduction and exchange of complex instruments and devices. To prevent potential complications such as air embolism and bleeding, a universal cardioport was designed and tested. METHODS: The design consists of a port body and a series of interchangeable sleeves. The port uses a fluid purging system to remove air from the instrument before insertion into the heart, and a valve system minimizes blood loss during instrument changes. RESULTS: The cardioport was tested ex vivo and in vivo in pigs (n = 5). Beating-heart procedures, such as septal defect closure and mitral valve repair, were modeled. Ex vivo trials (n = 150) were performed, and no air emboli were introduced using the port. In comparison, air emboli were detected in 40% to 85% of the cases without the use of the port-based purging system. Port operation revealed excellent ergonomics and minimal blood loss. CONCLUSIONS: A novel cardioport system designed to prevent air entry and blood loss from transcardiac instrument introduction was shown to be an enabling platform for intracardiac beating-heart surgery. The port system improves safety and facilitates further development of complex instruments and devices for transcardiac beating-heart surgery.

Beating-heart mitral valve suture annuloplasty under real-time three-dimensional echocardiography guidance: an ex vivo study.

We are developing an alternative mitral valve suture annuloplasty technique on the beating-heart under real-time three-dimensional echocardiography (RT3DE) guidance. The purpose of this initial study was to evaluate a feasibility of this technique using commercially available suturing devices (Sutur Tek Endo 360-degree, Sutur Tek Inc, North Chelmsford, MA, USA). Isolated porcine hearts (n=10) were mounted in a water-filled tank and attached to an ex vivo pulse simulation device, where varying left ventricle pressures with associated valve motion were generated by pulsatile flow through an apical cannula. The suturing device was inserted through the left atrium. Intra-annular (De Vega type) suture annuloplasty was performed under RT3DE guidance. The procedure was successfully performed in all cases. The diameter of the annulus was effectively reduced (85.5+/-4.2% of original antero-posterior dimension, 86.7+/-6.1% of original transverse dimension). The number of tissue bites was 7.4+/-0.8. The maximum distance between the annulus and sutures placed was 1.1 mm. The total procedure time was 9.4+/-2.4 min. There was no collateral tissue injury in any of the cases. This ex vivo study demonstrates the feasibility of beating-heart mitral valve suture annuloplasty under RT3DE guidance.