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In minimally invasive endovascular procedures, surgeons rely on catheters with low dexterity and high aspect ratios to reach an anatomical target. However, the environment inside the beating heart presents a combination of challenges unique to few anatomic locations, making it difficult for interventional tools to maneuver dexterously and apply substantial forces on an intracardiac target. We demonstrate a millimeter-scale soft robotic platform that can deploy and self-stabilize at the entrance to the heart, and guide existing interventional tools toward a target site. In two exemplar intracardiac procedures within the right atrium, the robotic platform provides enough dexterity to reach multiple anatomical targets, enough stability to maintain constant contact on motile targets, and enough mechanical leverage to generate newton-level forces. Because the device addresses ongoing challenges in minimally invasive intracardiac intervention, it may enable the further development of catheter-based interventions.

Severe diaphragm dysfunction can lead to respiratory failure and to the need for permanent mechanical ventilation. Yet permanent tethering to a mechanical ventilator through the mouth or via tracheostomy can hinder a patient's speech, swallowing ability and mobility. Here we show, in a porcine model of varied respiratory insufficiency, that a contractile soft robotic actuator implanted above the diaphragm augments its motion during inspiration. Synchronized actuation of the diaphragm-assist implant with the native respiratory effort increased tidal volumes and maintained ventilation flow rates within the normal range. Robotic implants that intervene at the diaphragm rather than at the upper airway and that augment physiological metrics of ventilation may restore respiratory performance without sacrificing quality of life., (© 2022. The Author(s).)

Atypical fibroxanthoma (AFX) is a rare skin tumor characterized by a combination of a «malignant» morphological features and non-aggressive clinical course. Diagnosing AFX is challenging due to histological «diversity» and heterogeneous immunophenotype. The presented review describes the history and evolution of AFX as a nosological form of cancer, its histogenetic origin, pathogenesis and biological potential. The clinical, morphological, immunohistochemical, molecular cytogenetic characteristics and histological subtypes of the tumor as well as differential diagnosis have been presented in detail.

Purpose: In clinical practice, many patients with right heart failure (RHF) have elevated pulmonary artery pressures and increased afterload on the right ventricle (RV). In this study, we evaluated the feasibility of RV augmentation using a soft robotic right ventricular assist device (SRVAD), in cases of increased RV afterload., Methods: In nine Yorkshire swine of 65-80 kg, a pulmonary artery band was placed to cause RHF and maintained in place to simulate an ongoing elevated afterload on the RV. The SRVAD was actuated in synchrony with the ventricle to augment native RV output for up to one hour. Hemodynamic parameters during SRVAD actuation were compared to baseline and RHF levels., Results: Median RV cardiac index (CI) was 1.43 (IQR, 1.37-1.80) L/min/m 2 and 1.26 (IQR 1.05-1.57) L/min/m 2 at first and second baseline. Upon PA banding RV CI fell to a median of 0.79 (IQR 0.63-1.04) L/min/m 2 . Device actuation improved RV CI to a median of 0.87 (IQR 0.78-1.01), 0.85 (IQR 0.64-1.59) and 1.11 (IQR 0.67-1.48) L/min/m 2 at 5 min (p = 0.114), 30 min (p = 0.013) and 60 (p = 0.033) minutes respectively. Statistical GEE analysis showed that lower grade of tricuspid regurgitation at time of RHF (p = 0.046), a lower diastolic pressure at RHF (p = 0.019) and lower mean arterial pressure at RHF (p = 0.024) were significantly associated with higher SRVAD effectiveness., Conclusions: Short-term augmentation of RV function using SRVAD is feasible even in cases of elevated RV afterload. Moderate or severe tricuspid regurgitation were associated with reduced device effectiveness., (© 2021. The Author(s).)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Patients suffering from heart failure often require circulatory support using ventricular assist devices (VADs). However, most existing VADs provide nonpulsatile flow, involve direct contact between the blood flow and the device's lumen and moving components, and require a driveline to connect to an external power source. These design features often lead to complications such as gastrointestinal bleeding, device thrombosis, and driveline infections. Here, a concept of magnetically active cardiac patches (MACPs) that can potentially function as non-blood contacting, untethered pulsatile VADs inside a magnetic actuationsystem is reported. The MACPs, which are composed of permanent magnets and 3D-printed patches, are attached to the epicardial surfaces, thus avoiding direct contact with the blood flow. They provide powerful actuation assisting native heart pumping inside a magnetic actuation system. In ex vivo experiments on a healthy pig's heart, it is shown that the ventricular ejection fractions are as high as 37% in the left ventricle and 63% in the right ventricle. Non-blood contacting, untethered VADs can eliminate the risk of serious complications associated with existing devices, and provide an alternative solution for myocardial training and therapy for patients with heart failure., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Left ventricular failure is strongly associated with secondary mitral valve regurgitation. Implantable soft robotic devices are an emerging technology that enables augmentation of a native function of a target tissue. We demonstrate the ability of a novel soft robotic ventricular assist device to dynamically augment left ventricular contraction, provide native pulsatile flow, simultaneously reshape the mitral valve apparatus, and eliminate the associated regurgitation in an Short-term large animal model of acute left ventricular systolic dysfunction., (© 2020 The Authors.)

The complex motion of the beating heart is accomplished by the spatial arrangement of contracting cardiomyocytes with varying orientation across the transmural layers, which is difficult to imitate in organic or synthetic models. High-fidelity testing of intracardiac devices requires anthropomorphic, dynamic cardiac models that represent this complex motion while maintaining the intricate anatomical structures inside the heart. In this work, we introduce a biorobotic hybrid heart that preserves organic intracardiac structures and mimics cardiac motion by replicating the cardiac myofiber architecture of the left ventricle. The heart model is composed of organic endocardial tissue from a preserved explanted heart with intact intracardiac structures and an active synthetic myocardium that drives the motion of the heart. Inspired by the helical ventricular myocardial band theory, we used diffusion tensor magnetic resonance imaging and tractography of an unraveled organic myocardial band to guide the design of individual soft robotic actuators in a synthetic myocardial band. The active soft tissue mimic was adhered to the organic endocardial tissue in a helical fashion using a custom-designed adhesive to form a flexible, conformable, and watertight organosynthetic interface. The resulting biorobotic hybrid heart simulates the contractile motion of the native heart, compared with in vivo and in silico heart models. In summary, we demonstrate a unique approach fabricating a biomimetic heart model with faithful representation of cardiac motion and endocardial tissue anatomy. These innovations represent important advances toward the unmet need for a high-fidelity in vitro cardiac simulator for preclinical testing of intracardiac devices., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

The paper presents a case of biphasic (dedifferentiated) osteosarcoma arising primarily on the lung, which has not previously encountered in the literature. It provides a detailed description of its clinical, instrumental, and morphological pattern. It also analyzes the literature on the study of primary pulmonary osteosarcoma and extraskeletal osteosarcoma with high-grade transformation. This clinical case is a clear example of classic biphasic sarcoma interpreted in the context of the phenomenon of biphasic tumors. Their most important aspects (terminology, morphology, biological behavior, and a mechanism of dedifferentiation) are highlighted; the key characteristics of biphasic sarcomas are listed.

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.

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., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

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.

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 β from rats with lipopolysaccharide-induced hypercytokinemia.

The present study aimed to present a workflow algorithm for automatic processing of 2D echocardiography images. The workflow was based on several sequential steps. For each step, we compared different approaches. Epicardial 2D echocardiography datasets were acquired during various open-chest beating-heart surgical procedures in three porcine hearts. We proposed a metric called the global index that is a weighted average of several accuracy coefficients, indices and the mean processing time. This metric allows the estimation of the speed and accuracy for processing each image. The global index ranges from 0 to 1, which facilitates comparison between different approaches. The second step involved comparison among filtering, sharpening and segmentation techniques. During the noise reduction step, we compared the median filter, total variation filter, bilateral filter, curvature flow filter, non-local means filter and mean shift filter. To clarify the endocardium borders of the right heart, we used the linear sharpen. Lastly, we applied watershed segmentation, clusterisation, region-growing, morphological segmentation, image foresting segmentation and isoline delineation. We assessed all the techniques and identified the most appropriate workflow for echocardiography image segmentation of the right heart. For successful processing and segmentation of echocardiography images with minimal error, we found that the workflow should include the total variation filter/bilateral filter, linear sharpen technique, isoline delineation/region-growing segmentation and morphological post-processing. We presented an efficient and accurate workflow for the precise diagnosis of cardiovascular diseases. We introduced the global index metric for image pre-processing and segmentation estimation.

The clinical translation of regenerative therapy for the diseased heart, whether in the form of cells, macromolecules or small molecules, is hampered by several factors: the poor retention and short biological half-life of the therapeutic agent, the adverse side effects from systemic delivery, and difficulties with the administration of multiple doses. Here, we report the development and application of a therapeutic epicardial device that enables sustained and repeated administration of small molecules, macromolecules and cells directly to the epicardium via a polymer-based reservoir connected to a subcutaneous port. In a myocardial infarct rodent model, we show that repeated administration of cells over a four-week period using the epicardial reservoir provided functional benefits in ejection fraction, fractional shortening and stroke work, compared to a single injection of cells and to no treatment. The pre-clinical use of the therapeutic epicardial reservoir as a research model may enable insights into regenerative cardiac therapy, and assist the development of experimental therapies towards clinical use.

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.

Previous soft robotic ventricular assist devices have generally targeted biventricular heart failure and have not engaged the interventricular septum that plays a critical role in blood ejection from the ventricle. We propose implantable soft robotic devices to augment cardiac function in isolated left or right heart failure by applying rhythmic loading to either ventricle. Our devices anchor to the interventricular septum and apply forces to the free wall of the ventricle to cause approximation of the septum and free wall in systole and assist with recoil in diastole. Physiological sensing of the native hemodynamics enables organ-in-the-loop control of these robotic implants for fully autonomous augmentation of heart function. The devices are implanted on the beating heart under echocardiography guidance. We demonstrate the concept on both the right and the left ventricles through in vivo studies in a porcine model. Different heart failure models were used to demonstrate device function across a spectrum of hemodynamic conditions associated with right and left heart failure. These acute in vivo studies demonstrate recovery of blood flow and pressure from the baseline heart failure conditions. Significant reductions in diastolic ventricle pressure were also observed, demonstrating improved filling of the ventricles during diastole, which enables sustainable cardiac output., (Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

We introduce an implantable intracardiac soft robotic right ventricular ejection device (RVED) for dynamic approximation of the right ventricular (RV) free wall and the interventricular septum (IVS) in synchrony with the cardiac cycle to augment blood ejection in right heart failure (RHF). The RVED is designed for safe and effective intracardiac operation and consists of an anchoring system deployed across the IVS, an RV free wall anchor, and a pneumatic artificial muscle linear actuator that spans the RV chamber between the two anchors. Using a ventricular simulator and a custom controller, we characterized ventricular volume ejection, linear approximation against different loads and the effect of varying device actuation periods on volume ejection. The RVED was then tested in vivo in adult pigs (n = 5). First, we successfully deployed the device into the beating heart under 3D echocardiography guidance (n = 4). Next, we performed a feasibility study to evaluate the device's ability to augment RV ejection in an experimental model of RHF (n = 1). RVED actuation augmented RV ejection during RHF; while further chronic animal studies will provide details about the efficacy of this support device. These results demonstrate successful design and implementation of the RVED and its deployment into the beating heart. This soft robotic ejection device has potential to serve as a rapidly deployable system for mechanical circulatory assistance in RHF.

Soft robotic devices have significant potential for medical device applications that warrant safe synergistic interaction with humans. This article describes the optimization of an implantable soft robotic system for heart failure whereby soft actuators wrapped around the ventricles are programmed to contract and relax in synchrony with the beating heart. Elastic elements integrated into the soft actuators provide recoiling function so as to aid refilling during the diastolic phase of the cardiac cycle. Improved synchronization with the biological system is achieved by incorporating the native ventricular pressure into the control system to trigger assistance and synchronize the device with the heart. A three-state electro-pneumatic valve configuration allows the actuators to contract at different rates to vary contraction patterns. An in vivo study was performed to test three hypotheses relating to mechanical coupling and temporal synchronization of the actuators and heart. First, that adhesion of the actuators to the ventricles improves cardiac output. Second, that there is a contraction-relaxation ratio of the actuators which generates optimal cardiac output. Third, that the rate of actuator contraction is a factor in cardiac output.

Adhesion to wet and dynamic surfaces, including biological tissues, is important in many fields but has proven to be extremely challenging. Existing adhesives are cytotoxic, adhere weakly to tissues, or cannot be used in wet environments. We report a bioinspired design for adhesives consisting of two layers: an adhesive surface and a dissipative matrix. The former adheres to the substrate by electrostatic interactions, covalent bonds, and physical interpenetration. The latter amplifies energy dissipation through hysteresis. The two layers synergistically lead to higher adhesion energies on wet surfaces as compared with those of existing adhesives. Adhesion occurs within minutes, independent of blood exposure and compatible with in vivo dynamic movements. This family of adhesives may be useful in many areas of application, including tissue adhesives, wound dressings, and tissue repair., (Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

There is much interest in form-fitting, low-modulus, implantable devices or soft robots that can mimic or assist in complex biological functions such as the contraction of heart muscle. We present a soft robotic sleeve that is implanted around the heart and actively compresses and twists to act as a cardiac ventricular assist device. The sleeve does not contact blood, obviating the need for anticoagulation therapy or blood thinners, and reduces complications with current ventricular assist devices, such as clotting and infection. Our approach used a biologically inspired design to orient individual contracting elements or actuators in a layered helical and circumferential fashion, mimicking the orientation of the outer two muscle layers of the mammalian heart. The resulting implantable soft robot mimicked the form and function of the native heart, with a stiffness value of the same order of magnitude as that of the heart tissue. We demonstrated feasibility of this soft sleeve device for supporting heart function in a porcine model of acute heart failure. The soft robotic sleeve can be customized to patient-specific needs and may have the potential to act as a bridge to transplant for patients with heart failure., (Copyright © 2017, American Association for the Advancement of Science.)

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 anatomic 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 in order to accommodate tissue growth. By using mathematical modeling and ex vivo experiments using harvested swine hearts, we demonstrate the predictability and tunability of the behavior 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., Competing Interests: Competing interests E.N.F., Y.L., E.D.O., N.V.V., D.P., P.E.H., H.Y., V.A., J.M.K., P.J.d.N. have a provisional patent application entitled ‘Autonomously Growing Implantable Device’ (USSN 62/295,768).

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., (© 2016 American Heart Association, Inc.)

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.

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., (Copyright © 2015, American Association for the Advancement of Science.)

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.

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/β-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/β-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., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

A class of soft actuated materials that can achieve lifelike motion is presented. By embedding pneumatic actuators in a soft material inspired by a biological muscle fibril architecture, and developing a simple finite element simulation of the same, tunable biomimetic motion can be achieved with fully soft structures, exemplified here by an active left ventricle simulator., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

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., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

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.

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., (Copyright © 2010 Elsevier B.V. All rights reserved.)

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 cm(2)) 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.

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.

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.

The congenital bicuspid aortic valve (BAV) is associated with increased leaflet calcification, ascending aortic dilatation, aortic stenosis (AS) and regurgitation (AR). Although underlying genetic factors have been primarily implicated for these complications, the altered mechanical environment of BAVs could potentially accelerate these pathologies. The objective of the current study is to characterize BAV hemodynamics in an in vitro system. Two BAV models of varying stenosis and jet eccentricity and a trileaflet AV (TAV) were constructed from excised porcine AVs. Particle Image Velocimetry (PIV) experiments were conducted at physiological flow and pressure conditions to characterize fluid velocity fields in the aorta and sinus regions, and ensemble averaged Reynolds shear stress and 2D turbulent kinetic energy were calculated for all models. The dynamics of the BAV and TAV models matched the characteristics of these valves which are observed clinically. The eccentric and stenotic BAV showed the strongest systolic jet (V = 4.2 m/s), which impinged on the aortic wall on the non-fused leaflet side, causing a strong vortex in the non-fused leaflet sinus. The magnitudes of TKE and Reynolds stresses in both BAV models were almost twice as large as comparable values for TAV, and these maximum values were primarily concentrated around the central jet through the valve orifice. The in vitro model described here enables detailed characterization of BAV flow characteristics, which is currently challenging in clinical practice. This model can prove to be useful in studying the effects of altered BAV geometry on fluid dynamics in the valve and ascending aorta. These altered flows can be potentially linked to increased calcific responses from the valve endothelium in stenotic and eccentric BAVs, independent of concomitant genetic factors.

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., (Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Real-time 3D ultrasound (3DUS) imaging offers improved spatial orientation information relative to 2D ultrasound. However, in order to improve its efficacy in guiding minimally invasive intra-cardiac procedures where real-time visual feedback of an instrument tip location is crucial, 3DUS volume visualization alone is inadequate. This paper presents a set of enhanced visualization functionalities that are able to track the tip of an instrument in slice views at real-time. User study with in vitro porcine heart indicates a speedup of over 30% in task completion time.

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.

We describe a method to increase the frame rate for 3-dimensional ultrasound sequences of periodically moving cardiac structures by reordering the acquired volume series. The frame rate is especially important in studying intracardiac structures such as valve leaflet motion in which valve closing times are on the order of milliseconds. Current commercially available systems for volumetric ultrasound imaging are limited to approximately 10 to 20 volumes per second. Although this frame rate is sufficient for real-time observation of basic cardiac morphology, understanding cardiac dynamics requires faster frame rates. The presented work achieves higher frame rates by sampling over several beats and using a simultaneous electrocardiography signal to accurately place the frame within the cardiac cycle. The proposed method relies on periodicity of the heart motion and that within the temporal regions of highest velocity, the structural motions of interest have the lowest beat-to-beat variability., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Measurement of the shape and motion of the mitral valve annulus has proven useful in a number of applications, including pathology diagnosis and mitral valve modeling. Current methods to delineate the annulus from four-dimensional (4D) ultrasound, however, either require extensive overhead or user-interaction, become inaccurate as they accumulate tracking error, or they do not account for annular shape or motion. This paper presents a new 4D annulus segmentation method to account for these deficiencies. The method builds on a previously published three-dimensional (3D) annulus segmentation algorithm that accurately and robustly segments the mitral annulus in a frame with a closed valve. In the 4D method, a valve state predictor determines when the valve is closed. Subsequently, the 3D annulus segmentation algorithm finds the annulus in those frames. For frames with an open valve, a constrained optical flow algorithm is used to the track the annulus. The only inputs to the algorithm are the selection of one frame with a closed valve and one user-specified point near the valve, neither of which needs to be precise. The accuracy of the tracking method is shown by comparing the tracking results to manual segmentations made by a group of experts, where an average RMS difference of 1.67±0.63mm was found across 30 tracked frames., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Registration of three-dimensional ultrasound (3DUS) volumes is necessary in several applications, such as when stitching volumes to expand the field of view or when stabilizing a temporal sequence of volumes to cancel out motion of the probe or anatomy. Current systems that register 3DUS volumes either use external tracking systems (electromagnetic or optical), which add expense and impose limitations on acquisitions, or are image-based methods that operate offline and are incapable of providing immediate feedback to clinicians. This paper presents a real-time image-based algorithm for rigid registration of 3DUS volumes designed for acquisitions in which small probe displacements occur between frames. Described is a method for feature detection and descriptor formation that takes into account the characteristics of 3DUS imaging. Volumes are registered by determining a correspondence between these features. A global set of features is maintained and integrated into the registration, which limits the accumulation of registration error. The system operates in real-time (i.e. volumes are registered as fast or faster than they are acquired) by using an accelerated framework on a graphics processing unit. The algorithm's parameter selection and performance is analyzed and validated in studies which use both water tank and clinical images. The resulting registration accuracy is comparable to similar feature-based registration methods, but in contrast to these methods, can register 3DUS volumes in real-time., (Copyright © 2011 Elsevier B.V. All rights reserved.)

A novel robotic tool is proposed to enable the surgical removal of tissue from inside the beating heart. The tool is manufactured using a unique metal MEMS process that provides the means to fabricate fully assembled devices that incorporate micron-scale features in a millimeter scale tool. The tool is integrated with a steerable curved concentric tube robot that can enter the heart through the vasculature. Incorporating both irrigation and aspiration, the tissue removal system is capable of extracting substantial amounts of tissue under teleoperated control by first morselizing it and then transporting the debris out of the heart through the lumen of the robot. Tool design and robotic integration are described and ex vivo experimental results are presented.

Surgical repair of the mitral valve is a difficult procedure that is often avoided in favor of less effective valve replacement because of the associated technical challenges facing non-expert surgeons. In the interest of increasing the rate of valve repair, an accurate, interactive surgical simulator for mitral valve repair was developed. With a haptic interface, users can interact with a mechanical model during simulation to aid in the development of a surgical plan and then virtually implement the procedure to assess its efficacy. Sub-millimeter accuracy was achieved in a validation study, and the system was successfully used by a cardiac surgeon to repair three virtual pathological valves.

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., (Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Three-dimensional ultrasound can be an effective imaging modality for image-guided interventions since it enables visualization of both the instruments and the tissue. For robotic applications, its realtime frame rates create the potential for image-based instrument tracking and servoing. These capabilities can enable improved instrument visualization, compensation for tissue motion as well as surgical task automation. Continuum robots, whose shape comprises a smooth curve along their length, are well suited for minimally invasive procedures. Existing techniques for ultrasound tracking, however, are limited to straight, laparoscopic-type instruments and thus are not applicable to continuum robot tracking. Toward the goal of developing tracking algorithms for continuum robots, this paper presents a method for detecting a robot comprised of a single constant curvature in a 3D ultrasound volume. Computational efficiency is achieved by decomposing the six-dimensional circle estimation problem into two sequential three-dimensional estimation problems. Simulation and experiment are used to evaluate the proposed method.

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 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. Experimental results demonstrate device efficacy through manual in-vivo deployment and bench-top robotic deployment.

Background and Aim of the Study: Experimental models of tricuspid valve regurgitation (TR) are used to study novel annuloplasty techniques (including prosthetic rings), and they can also serve as physiologic models to investigate TR pathophysiology. The study aim was to develop an appropriate simple and reproducible experimental model of TR from annular dilatation., Methods: Acute TR was successfully created through multiple small 3- to 5-mm incisions in the annulus using a custom-made optical port with an instrument shaft (the Cardioport) that accepts a standard endoscopic imaging system. The Cardioport was inserted, via a thoracotomy, through the right atrium of seven Yorkshire pigs, and directed towards the tricuspid valve annulus to create the annular incisions. Tricuspid valve anatomy and function were evaluated using 2D and 3D echocardiography. The presence and severity of TR, annulus diameter, and changes in heart rate and atrial pressures after making the annular incisions were documented. To monitor tricuspid annular dilatation and the progression of TR, follow up echocardiography and color Doppler examinations were performed at two and eight weeks postoperatively., Results: The acute onset of TR was well tolerated, and there were no deaths or significant morbidity associated with the procedure. The annular diameter was increased from a preoperative mean of 23.1 +/- 1.7 mm, to 32.2 +/- 2.5 mm at two weeks postoperatively, and to 37.3 +/- 3.6 mm at eight weeks postoperatively. Overall, the TR progressed from mild (grade I) to severe (grade III) in all of the animals., Conclusion: This novel porcine model represents a relatively simple and a reproducible surgical technique for the creation of annular dilatation and TR, and may also serve as a chronic model of the latter condition.

The shape of the mitral valve annulus is used in diagnostic and modeling applications, yet methods to accurately and reproducibly delineate the annulus are limited. This paper presents a mitral annulus segmentation algorithm designed for closed mitral valves which locates the annulus in three-dimensional ultrasound using only a single user-specified point near the center of the valve. The algorithm first constructs a surface at the location of the thin leaflets, and then locates the annulus by finding where the thin leaflet tissue meets the thicker heart wall. The algorithm iterates until convergence metrics are satisfied, resulting in an operator-independent mitral annulus segmentation. The accuracy of the algorithm was assessed from both a diagnostic and surgical standpoint by comparing the algorithm's results to delineations made by a group of experts on clinical ultrasound images of the mitral valve, and to delineations made by an expert with a surgical view of the mitral annulus on excised porcine hearts using an electromagnetically tracked pointer. In the former study, the algorithm was statistically indistinguishable from the best performing expert (p=0.85) and had an average RMS difference of 1.81+/-0.78 mm to the expert average. In the latter, the average RMS difference between the algorithm's annulus and the electromagnetically tracked points across six hearts was 1.19+/-0.17 mm .