Eric N. Feins

A Blood-Resistant Surgical Glue for Minimally Invasive Repair of Vessels and Heart Defects

A light-activated, biodegradable adhesive seals cardiovascular defects in the presence of blood flow and could be useful during minimally invasive surgery. Light-Activated Adhesive Seals Tissues An easy way to repair vessels or attach devices to tissues would be welcomed by surgeons. An adhesive, for instance, can reconnect tissue and interface prosthetics, but currently available materials have limitations such as low strength, high toxicity, and most do not function well in wet environments. In response, Lang and colleagues developed a new biomaterial glue that is biocompatible, biodegradable, and easily manipulated. This material, called poly(glycerol sebacate acrylate) (PGSA), when combined with a photoinitiator, creates a solution that the authors called HLAA: hydrophobic light-activated adhesive. The HLAA is a thick gel that can be slathered on a tissue and then cross-linked within seconds by ultraviolet light, which is a unique feature that avoids stitches. The resulting bond is water-tight yet flexible and stays intact in the face of high pressure and flowing blood. The authors first tested their material in rats, showing that the HLAA could be used to attach a polymer patch to the heart and that the HLAA alone could seal up defects in the heart wall, performing as well as sutures. Lang et al. then moved into pigs, whose hearts beat at similar rates to humans (by contrast, rats have much higher heart rates). Lang et al. showed that the light-activated adhesive could attach a patch to the interventricular septum of a pig’s beating heart and that this patch remained in place even under higher than normal heart rates (induced by adrenaline). Additionally, the HLAA alone was able to immediately close up defects in the pig carotid artery without any bleeding complications. The light-responsive adhesive performed well in several different in vivo scenarios, suggesting its broad applicability in the clinic, at least for cardiovascular surgeries and defects. As an added bonus, components of PGSA—namely, glycerol and sebacic acid—exist in the body and are readily metabolized. It is expected that this material could be translated soon to use in people. 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.

Percutaneous Steerable Robotic Tool Delivery Platform and Metal MEMS 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.

Anomalous Aortic Origin of a Coronary Artery: Surgical Repair With Anatomic- and Function-Based Follow-Up

BACKGROUND Anomalous aortic origin of the coronary artery (AAOCA) with an interarterial (IAC) course is an uncommon congenital anomaly. Surgical indications and repair techniques have evolved. We have managed 259 adult patients with AAOCA over 40 years. Our management strategy includes anatomic- and function-based surveillance to select surgical candidates. We reviewed our surgical cohort and analyzed anatomic and functional outcomes. METHODS We queried our heart center databases to obtain the names of all patients with AAOCA managed at our institution between 1974 and 2014. We performed a retrospective chart review. RESULTS Two hundred fifty-nine patients were managed for AAOCA. Sixty-one underwent surgical intervention. Twenty-six with associated coronary atherosclerosis were excluded. Thirty-one who underwent surgical repair were analyzed. Mean age was 42.5 ± 2.7 years. Twenty-four patients (77.4%) had right AAOCA. Six (19.4%) had left AAOCA. One (3.2%) had bilateral coronary anomalies. Repair techniques included 21 unroofing procedures (67.7%), 6 translocations (19.4%), and 4 coronary artery bypass grafting (CABG) procedures (12.9%). Mean follow-up was 3.8 ± 0.8 years. Thirteen patients underwent follow-up anatomic testing with computed tomography. Twelve of these patients had widely patent coronary arteries, and 1 patient had mild coronary artery stenosis. Seventeen patients underwent functional testing. Fifteen of these patients had no evidence of ischemia. One patient had reversible ischemia after CABG, and 1 had subclinical ischemia after unroofing. There was 1 late mortality from endocarditis. CONCLUSIONS Our multidisciplinary program uses a treatment algorithm to select patients with AAOCA for surgical intervention. Only a small subset requires an operation, and we favor unroofing and translocation techniques. With this paradigm, outcomes are excellent, as validated with anatomic- and function-based testing.

A light-reflecting balloon catheter for atraumatic tissue defect repair

A catheter-based technology reflects light to activate a photocurable adhesive for minimally invasive, atraumatic tissue defect closure. Catheter device lights the way to tissue closure Closing small defects in the body typically requires stitching of tissues during surgery. Toward a minimally invasive approach, Roche et al. engineered a balloon catheter with a reflective surface coating that could be used to adhere biodegradable patches to tissues. The device unfolds the patch and its adhesive, delivers ultraviolet (UV) light, and then applies pressure to stabilize the adhesive as the light cures the polymer. The authors demonstrated catheter-mediated application of the photocurable polymer patch in vivo in rat tissue, with minimal inflammation and complete animal survival, as well as in a challenging septal defect in the beating hearts of pigs. The device was also used to seal porcine stomach ulcers and abdominal hernias ex vivo, suggesting versatility of this approach in repairing defects more easily and atraumatically than sutures. 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.

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 clips 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.

Creation of Nonischemic Functional Mitral Regurgitation by Annular Dilatation and Nonplanar Modification in a Chronic In Vivo Swine Model

Background— Mechanisms and treatments of nonischemic functional mitral regurgitation (NIMR) are not fully established, in part, because of a lack of proper large animal models. We developed a novel technique of NIMR creation in a swine model by making multiple small incisions in the mitral annulus. Methods and Results— Ex vivo experiments using isolated swine hearts (n=10) showed a 15% increase in annular area (6.8–7.8 cm2) after 16 incisions were made along the posterior mitral annulus of a pressurized left ventricle. In an in vivo swine model (n=7; 46.4±2.2 kg), NIMR was created by making fourteen to twenty-six 2-mm incisions in the atrial aspect of the mitral annulus using a cardioport video-assisted imaging system in the beating heart. Animals were euthanized at 4 weeks (n=4) and 6 weeks (n=3). Three-dimensional (3D) echocardiography was obtained before and immediately after NIMR creation and at euthanasia; vena contracta area, mitral annular dimension, left ventricular volume, and inter-papillary muscle distance were measured. The mitral annular incisions resulted in mild to moderate mitral regurgitation and an increased vena contracta area. NIMR creation altered mitral valve geometry by decreasing mitral annular nonplanarity and increasing annular area, primarily in the anteroposterior dimension. NIMR creation did not significantly change left ventricular volume or inter-papillary muscle distance. Longer follow-up period did not significantly affect these outcomes. Conclusions— NIMR can successfully be created in a beating heart swine model and results in dilatation and 3D changes in mitral annular geometry. This model can enhance the experimental validation of new valve repair devices and techniques.

Fast simulation of mitral annuloplasty for surgical planning

Mitral valve repair is a complex procedure that requires the ability to predict closed valve shape through the examination of an unpressurized, accid valve. These procedures typically include the remodeling of the mitral annulus through the insertion of an annuloplasty ring. While simulations could facilitate the planning of the procedure, traditional finite-element models of mitral annuloplasty are too slow to be clinically feasible and have never been validated in tissue. This work presents a fast method for simulating valve closure post-annuloplasty using a mass-spring tissue model and subject-specific valve geometry. Closed valve shape is predicted in less than one second. The results are validated by implanting an annuloplasty ring in an excised porcine heart and comparing simulated to imaged results. Results indicate that not only can mitral annuloplasty be simulated quickly, but also with submillimeter accuracy.

A growth-accommodating implant for paediatric applications

Medical implants of fixed size cannot accommodate normal tissue growth in children and often require eventual replacement or—in some cases—removal, leading to repeated interventions, increased complication rates and worse outcomes. Implants that can correct anatomical deformities and accommodate tissue growth remain an unmet need. Here, we report the design and use of a growth-accommodating device for paediatric applications that consists of a biodegradable core and a tubular braided sleeve, with inversely related sleeve length and diameter. The biodegradable core constrains the diameter of the sleeve, and gradual core degradation following implantation enables sleeve and overall device elongation to accommodate tissue growth. By means of mathematical modelling and ex vivo experiments using harvested swine hearts, we demonstrate the predictability and tunability of the behaviour of the device for disease- and patient-specific needs. We also used the rat tibia and the piglet heart valve as two models of tissue growth to demonstrate that polymer degradation enables device expansion and growth accommodation in vivo.An implantable device consisting of a biodegradable core and a tubular braided sleeve autonomously elongates to accommodate tissue growth, as shown with prototypes implanted on a rat tibial bone and a piglet heart valve.

Extraanatomic Bypass of a Complex Adult Coarctation

Complex adult coarctations associated with arch hypoplasia and aneurysms require a range of surgical approaches depending upon anatomy. Extraanatomic bypass is an important strategy that enables the surgeon to avoid the risks of extensive dissection/mobilization. Extraanatomic bypass can be accomplished from the ascending to lower descending thoracic aorta via an intrapericardial route lateral to the right atrium and posterior to the inferior vena cava; however, this approach incompletely addresses post-stenotic aneurysmal disease. In the case of complex coarctation with aneurysm, we prefer an alternate approach to exclude the aneurysm, routing the bypass graft anterior to the phrenic nerve to the upper descending thoracic aorta.

A Novel and Successful Repair of a Left Atriogastric Fistula After Esophagectomy

Atriogastric fistulas remain a rare adverse event in patients who undergo esophagectomy with gastric pullthrough. The presentation of an atriogastric fistula ranges from self-limited gastrointestinal bleeding to life-threatening hemorrhage, end-organ dysfunction from septic emboli, or both. These fistulas are associated with significant mortality. Previous reports describe successful repairs of gastrocardiac fistulas with the use of cardiopulmonary bypass. This report describes a patient with a significant burden of cerebral embolic disease, which therefore required a unique approach to fistula repair.