Hemodynamics with mechanical circulatory support devices using a cardiogenic shock model.

Mechanical circulatory support (MCS) devices, including veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and Impella, have been widely used for patients with cardiogenic shock (CS). However, hemodynamics with each device and combination therapy is not thoroughly understood. We aimed to elucidate the hemodynamics with MCS using a pulsatile flow model. Hemodynamics with Impella CP, VA-ECMO, and a combination of Impella CP and VA-ECMO were assessed based on the pressure and flow under support with each device and the pressure-volume loop of the ventricle model. The Impella CP device with CS status resulted in an increase in aortic pressure and a decrease in end-diastolic volume and end-diastolic pressure (EDP). VA-ECMO support resulted in increased afterload, leading to a significant increase in aortic pressure with an increase in end-systolic volume and EDP and decreasing venous reservoir pressure. The combination of Impella CP and VA-ECMO led to left ventricular unloading, regardless of increase in afterload. Hemodynamic support with Impella and VA-ECMO should be a promising combination for patients with severe CS.

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

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

Estimation Failure Risk by 0.5-mm Differences in Autologous Hamstring Graft Diameter in Anterior Cruciate Ligament Reconstruction: A Meta-analysis.

BACKGROUND: Because grafts are made in 0.5-mm increments clinically for anterior cruciate ligament (ACL) reconstruction, it is important to clarify how the failure rate decreases as the diameter increases. Moreover, it is important to know whether even a slight increase in the graft diameter decreases the risk of failure. HYPOTHESIS: The risk of failure decreases significantly with each 0.5-mm increase in hamstring graft diameter. STUDY DESIGN: Meta-analysis; Level of evidence, 4. METHODS: The systematic review and meta-analysis have estimated the diameter-specific failure risk for each 0.5-mm increase in ACL reconstruction using autologous hamstring grafts. We searched for studies describing the relationship between graft diameter and failure rate published before December 1, 2021, in leading databases, such as PubMed, EMBASE, Cochrane Library, and Web of Science, according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We included studies using single-bundle autologous hamstring grafts to investigate the relationship between failure rate and graft diameter of 0.5-mm intervals with >1-year follow-up. Then, we calculated the failure risk caused by 0.5-mm differences in autologous hamstring graft diameter. Assuming Poisson distribution for the statistical model, we employed an extended linear mixed-effects model in the meta-analyses. RESULTS: Five studies containing 19,333 cases were eligible. The meta-analysis revealed that the estimated value of the coefficient of diameter in the Poisson model was -0.2357 with a 95% CI of -0.2743 to -0.1971 (P < .0001). With every 1.0-mm increase in diameter, the failure rate decreased by 0.79 (0.76-0.82) times. In contrast, the failure rate increased by 1.27 (1.22-1.32) times for each 1.0-mm decrease in diameter. The failure rate significantly decreased with each 0.5-mm increase in graft diameter in the range of <7.0 to >9.0 mm from 3.63% to 1.79%. CONCLUSION: The risk of failure decreased correspondingly with each 0.5-mm increase in graft diameter in the range of <7.0 to >9.0 mm. Failure is multifactorial; however, increasing the graft diameter as much as possible to match each patient's anatomic space without overstuffing is an effective precaution that surgeons can take to reduce failures.

Predicting Intracardiac Thrombus Formation in the Left Atrial Appendage Using Machine Learning and CT Images.

This paper proposes a comprehensive method for estimating thrombus formation factors in the left atrial appendage (LAA). First, using 3D CT (Computer Tomography) image data as input, classification of thrombus presence/absence is learned using 3D ResNet. Besides, 3D Grad-CAM is applied to the prediction results to visualize regions of interest in thrombus formation. Second, features are extracted based on the visualization of regions of interest. Using the extracted features and numerical data obtained from the hospital as input, a regression analysis is performed to predict the presence/absence of thrombus using LightGBM. Visualization of regions of interest using 3D ResNet and 3D Grad-CAM shows that the right inferior pulmonary vein and the LAA were particularly correlated with thrombus formation. Estimation of important factors for thrombus formation using LightGBM shows that the LAA ostium area has the greatest influence on thrombus formation.Clinical Relevance-This paper shows the factors that contribute to thrombus formation in the LAA from the viewpoint of three-dimensional structure. In addition, the features considered important in thrombus formation were identified by comparing a variety of features.

Difference in tissue temperature change between two cryoballoons.

BACKGROUND: Cryoballoon ablation, especially Arctic Front Advance Pro (AFA-Pro) (Medtronic, Minneapolis, Minnesota, USA), has been widely recognised as a standard approach to atrial fibrillation (AF). Recently, Boston Scientific has released a novel cryoballoon system (POLARx). Despite comparable acute clinical outcomes of these two cryoballoons, the recent study reported a higher complication rate, especially for phrenic nerve palsy, with POLARx. However, their impact on biological tissue remains unclear. OBJECTIVE: The purpose of our study is to evaluate temperature change of biological tissue during cryoablation of each cryoballoon using a porcine experimental model. METHOD: A tissue-based pulmonary vein model was constructed from porcine myocardial tissue and placed on a stage designed to simulate pulmonary vein anatomy and venous flow. Controlled cryoablations of AFA-Pro and POLARx were performed in this model to evaluate the tissue temperature. A temperature sensor was set behind the muscle and cryoballoon ablation was performed after confirming the occlusion of pulmonary vein with cryoballoon. RESULTS: The mean tissue nadir temperature during cryoablation with AFA-Pro was -41.5°C±4.9°C, while the mean tissue nadir temperature during cryoablation with POLARx was -58.4°C±5.9°C (p<0.001). The mean balloon nadir temperature during cryoablation with AFA-Pro was -54.6°C±2.6°C and the mean balloon nadir temperature during cryoablation with POLARx was -64.7°C±3.8°C (p<0.001). CONCLUSION: POLARx could freeze the biological tissue more strongly than AFA-Pro.

Repairable ex vivo model of functional and degenerative mitral regurgitation.

OBJECTIVES: Transcatheter mitral valve repair is an emerging alternative to the surgical repair. This technology requires preclinical studies to assess efficacy in mitigating mitral regurgitation (MR). However, ex vivo MR models are not established. We developed 2 novel repairable models, functional and degenerative, which can quantitatively assess regurgitation and effect of intervention. METHODS: We used porcine mitral valves and a pulsatile flow circulation system. In the functional MR model, the annulus was immersed in 0.1% collagenase solution and dilated using 3D-printed dilators. To control the regurgitation grade, the sizes of the dilator and silicone sheet in which the valve was sutured to were adjusted. Chordae of P2 were severed in the degenerative model, and the number of severed chordae was adjusted to control the regurgitation grade. Models were repaired using the edge-to-edge or artificial chordae technique. RESULTS: The mean regurgitant fraction of the moderate-severe functional and degenerative models were 47.9% [standard deviation (SD): 2.2%] and 58.5% (SD: 8.0%), which were significantly reduced to 28.7% (SD: 4.4%) (P < 0.001) and 26.0% (SD: 4.4%) (P < 0.001) after the valve repair procedures. Severe functional model had a mean regurgitant fraction of 59.4% (SD: 6.0%). CONCLUSIONS: Both functional and degenerative models could produce sufficient MR levels that meet the interventional indication criteria. The repairable models are valuable in evaluating the efficacy of valve repair procedures and devices. The ability to control the amount of regurgitation enhances the versatility and reliability of these models. These reproducible models could expedite the development of novel devices.

Importance of optimal rewiring guided by 3-dimensional optical frequency domain imaging during double-kissing culotte stenting demonstrated through a novel bench model.

The usefulness of optical frequency domain imaging (OFDI) guidance on two-stenting at left main bifurcation has not been evaluated. Here, we used a novel bench model to investigate whether pre-defined optimal rewiring with OFDI-guidance decreases acute incomplete stent apposition (ISA) at the left main bifurcation segment. A novel bench simulation system was developed to simulate the foreshortening and overlapping of daughter vessels as well as left main bifurcation motion under fluoroscopy. Double-kissing (DK) culotte stenting was performed using the novel bench model under fluoroscopy with or without OFDI-guidance. In the OFDI-guidance group, if the guidewire did not pass through the pre-defined optimal cell according to the 3-dimensional OFDI, additional attempts of rewiring into the jailed side branch were performed. The success rate of optimal jailed side branch rewiring after implantation of the first and second stent under OFDI-guidance was significantly higher than that under only angio-guidance. After completion of the DK-culotte stenting, the incidence and volume of ISA at the bifurcation segment in the OFDI-guidance group was significantly lower than that in the angio-guidance group. Online 3-dimensional OFDI-guided DK-culotte stenting according to a pre-defined optimal rewiring point might be superior to only angio-guided rewiring for reducing ISA at the bifurcation.

Biaxial tensile testing system for measuring mechanical properties of both sides of biological tissues.

The aortic wall exhibits a unique elastic behavior, periodically expanding in aortic diameter by approximately 10% during heartbeats. This elastic behavior of the aortic wall relies on the distinct yet interacting mechanical properties of its three layers: intima, media, and adventitia. Aortic aneurysms develop as a result of multifactorial remodeling influenced by mechanical vulnerability of the aortic wall. Therefore, investigating the mechanical response of the aneurysmal wall, in conjunction with changes in microstructural parameters on both the intimal and adventitial sides, may offer valuable insights into the mechanisms of aortic aneurysm development or rupture. This study aimed to develop a biaxial tensile testing system to measure the mechanical properties of both sides of the tissue to gain insights concerning the interactions in anisotropic layered tissue. The biaxial tensile test set-up consisted of four motors, four cameras, four load cells, and a toggle switch. Porcine ascending aortas were chosen as the test subject. Graphite particles with diameters of approximately 5-11 [µm] were randomly applied to both sides of the aorta. Strain measurements were obtained using the stereo digital-image correlation method. Because stretching a rectangular specimen with a thread inevitably concentrates and localizes stress, to reduce this effect the specimen's shape was investigated using finite element analysis. The finite element analysis showed that a cross-shaped specimen with diagonally cut edges would be suitable. Therefore, we prepared specimens with this novel shape. This test system showed that mechanical response of the aortic tissue was significantly different between the intimal and adventitial side in the high-strain range, due to the disruption of collagen fibers. The adventitia side exhibited a smaller elastic modulus than the intimal side, accompanied by disruption of collagen fibers in the adventitia, which were more pronounced in the longitudinal direction. In contrast, in the mid-strain range, the elastic modulus did not differ between the intimal and adventitial sides, irrespective of longitudinal or circumferential direction, and collagen fibers were not disrupted but elongated. A biaxial tensile test system, which measures the mechanical properties of both sides of biological tissues and the shape of the specimen for reducing the concentration of stress at the chuck region, was developed in this study. The biaxial tensile testing system developed here is useful for better understanding the influences of mechanical loads and tissue degeneration on anisotropic, layered biological tissues.

A survey on the usage of decellularized tissues in orthopaedic clinical trials.

Orthopaedic surgery requires grafts with sufficient mechanical strength. For this purpose, decellularized tissue is an available option that lacks the complications of autologous tissue. However, it is not widely used in orthopaedic surgeries. This study investigated clinical trials of the use of decellularized tissue grafts in orthopaedic surgery. Using the ClinicalTrials.gov (CTG) and the International Clinical Trials Registry Platform (ICTRP) databases, we comprehensively surveyed clinical trials of decellularized tissue use in orthopaedic surgeries registered before 1 September 2022. We evaluated the clinical results, tissue processing methods, and commercial availability of the identified products using academic literature databases and manufacturers' websites. We initially identified 4,402 clinical trials, 27 of which were eligible for inclusion and analysis, including nine shoulder surgery trials, eight knee surgery trials, two ankle surgery trials, two hand surgery trials, and six peripheral nerve graft trials. Nine of the trials were completed. We identified only one product that will be commercially available for use in knee surgery with significant mechanical load resistance. Peracetic acid and gamma irradiation were frequently used for sterilization. Despite the demand for decellularized tissue, few decellularized tissue products are currently commercially available, particularly for the knee joint. To be viable in orthopaedic surgery, decellularized tissue must exhibit biocompatibility and mechanical strength, and these requirements are challenging for the clinical application of decellularized tissue. However, the variety of available decellularized products has recently increased. Therefore, decellularized grafts may become a promising option in orthopaedic surgery.

Performance evaluation methods for improvements at post-market of artificial intelligence/machine learning-based computer-aided detection/diagnosis/triage in the United States.

Computer-aided detection (CADe), computer-aided diagnosis (CADx), and computer-aided simple triage (CAST), which incorporate artificial intelligence (AI) and machine learning (ML), are continually undergoing post-market improvement. Therefore, understanding the evaluation and approval process of improved products is important. This study intended to conduct a comprehensive survey of AI/ML-based CAD products approved by the U.S. Food and Drug Administration (FDA) that had been improved post-market to gain insights into the efficacy and safety required for market approval. A survey of the product code database published by the FDA identified eight products that were improved post-market. The methods used to evaluate the performance of improvements were analysed, and post-market improvements were approved with retrospective data. Reader study testing (RT) or software standalone testing (SA) procedures were conducted retrospectively. Six RT procedures were conducted because of modifications to the intended use. An average of 17.3 readers (minimum 14, maximum 24) participated, and the area under the curve (AUC) was considered the primary endpoint. The addition of study learning data that did not change the intended use and changes in the analysis algorithm were evaluated by SA. The average sensitivity, specificity, and AUC were 93% (minimum 91.1, maximum 97), 89.6% (minimum 85.9, maximum 96), and 0.96 (minimum 0.96, maximum 0.97), respectively. The average interval between applications was 348 days (minimum -18, maximum 975), which showed that the improvements were implemented within approximately one year. This is the first comprehensive study on AI/ML-based CAD products that have been improved post-market to elucidate evaluation points for post-market improvements. The findings will be informative for the industry and academia in developing and improving AI/ML-based CAD.

Comprehensive Analysis of Clinical Studies and Regulations of Therapeutic Applications in the United States and Japan.

BACKGROUND: Digital therapeutics (DTx), the provision of treatment through mobile devices such as smartphones, have attracted great interest as a new medical modality. However, the number of authorized therapeutic applications in the US and Japan is low. Understanding the obstacles in obtaining regulatory authorizations will be the key in promoting timely development of therapeutic applications. Thus, we conducted a comprehensive analysis of the clinical study designs of therapeutic applications authorized in the US and Japan. METHODS: Data on authorized therapeutic applications and the regulations involved were collated from the databases of the Food and Drug Administration (USA), Ministry of Health, Labour and Welfare (Japan), and Pharmaceuticals and Medical Devices Agency (Japan). RESULTS: Most therapeutic applications authorized targeted neuropsychiatric disorders and used cognitive behavioral therapy (CBT)-based treatments. All the involved clinical trials were randomized-controlled studies. Various types of controls-such as standard care, sham application, digital control, and therapies delivered by healthcare providers-were used. Both subjective and objective indices were acceptable as the primary endpoints. Long-term efficacy was evaluated, and all adverse events were assessed comprehensively. The setting up of controls and the need to study long-term efficacy depend heavily on the applications functionality and the target disease characteristics. CONCLUSIONS: This study reveals the points to be considered in planning clinical studies and regulatory strategies for authorizing therapeutic applications. Therapeutic applications can provide new therapy and have potential to solve unmet clinical needs. Our findings shed a light on efficient development and rapid commercialization of therapeutic applications.

Comparison of hemodynamics and root configurations between remodeling and reimplantation methods for valve-sparing aortic root replacement: a pulsatile flow study.

PURPOSE: To compare the characteristics of reimplantation (RI) using grafts with sinuses and remodeling (RM) with/without external suture annuloplasty using a pulsatile flow simulator. METHODS: Porcine aortic roots were obtained from an abattoir, and six models of RM and RI with sinuses were prepared. External suture annuloplasty (ESA) was performed in the RM models to decrease the root diameter to 22 mm (RM-AP22) and 18 mm (RM-AP18). Valve models were tested at mean pulsatile flow and aortic pressure of 5.0 L/min and 120/80 (100) mmHg, respectively, at 70 beats/min. The forward flow, regurgitation, leakage, backflow rates, valve-closing time, and mean and peak pressure gradient (p-PG) were evaluated. Root configurations were examined using micro-computed tomography (micro-CT). RESULTS: The backflow rate was larger in the RM models than in the RI models (RI: 8.56% ± 0.38% vs. RM: 12.64% ± 0.79%; p < 0.01). The RM-AP and RI models were comparable in terms of the forward flow, regurgitation, backflow rates, p-PG, and valve-closing time. The analysis using a micro-CT showed a larger dilatation of the sinus of the Valsalva in the RM groups than in the RI group (Valsalva: RI, 26.55 ± 0.40 mm vs. RM-AP22, 31.22 ± 0.55 mm [p < 0.05]; RM-AP18, 31.05 ± 0.85 mm [p < 0.05]). CONCLUSIONS: RM with ESA and RI with neo-sinuses showed comparable hemodynamics. ESA to RM reduced regurgitation.

Systematic analysis of the test design and performance of AI/ML-based medical devices approved for triage/detection/diagnosis in the USA and Japan.

The development of computer-aided detection (CAD) using artificial intelligence (AI) and machine learning (ML) is rapidly evolving. Submission of AI/ML-based CAD devices for regulatory approval requires information about clinical trial design and performance criteria, but the requirements vary between countries. This study compares the requirements for AI/ML-based CAD devices approved by the US Food and Drug Administration (FDA) and the Pharmaceuticals and Medical Devices Agency (PMDA) in Japan. A list of 45 FDA-approved and 12 PMDA-approved AI/ML-based CAD devices was compiled. In the USA, devices classified as computer-aided simple triage were approved based on standalone software testing, whereas devices classified as computer-aided detection/diagnosis were approved based on reader study testing. In Japan, however, there was no clear distinction between evaluation methods according to the category. In the USA, a prospective randomized controlled trial was conducted for AI/ML-based CAD devices used for the detection of colorectal polyps, whereas in Japan, such devices were approved based on standalone software testing. This study indicated that the different viewpoints of AI/ML-based CAD in the two countries influenced the selection of different evaluation methods. This study's findings may be useful for defining a unified global development and approval standard for AI/ML-based CAD.

Gap distribution mapping to visualize regions associated with type 1 endoleak in a fenestrated thoracic stent graft.

OBJECTIVES: Our goal was to analyse the relationships between aortic surface irregularity and a type 1 endoleak (T1EL) after a thoracic endovascular repair using the Najuta fenestrated stent graft. METHODS: The patients who were treated using the Najuta stent graft for an intact aortic arch aneurysm at the Saitama Cardiovascular and Respiratory Center between June 2013 and June 2017 were analysed retrospectively. The primary end point was the occurrence of a T1EL. The gap between a virtual aorta and the patient's aortic wall at the stent graft fixation was calculated over the whole circumference at 1 mm intervals, and gap distribution mapping was performed. The rate of freedom from a T1EL was estimated using the Kaplan-Meier method and compared between the patients with or without a continuously malapposed region of >1 mm from the branches to the aneurysm. RESULTS: Twenty-one patients were analysed. During the mean follow-up period of 21.7 months, 4 patients were confirmed to have T1ELs. Three of the T1Els were detected during the perioperative period and occurred through a fenestration. The remaining patient had a T1EL 2 years postoperatively. The gap distribution mapping confirmed the presence of a continuously malapposed region of >1 mm from the cervical branch to the aneurysm postoperatively in 4 patients with T1ELs. Patients who had a continuously malapposed region of >1 mm showed a statistically lower T1EL rate than those without (p < 0.001). Malapposed regions defined using the gap distribution mapping were consistent with flow channels through T1EL fenestrations detected using the perioperative computed tomography data. CONCLUSIONS: The gap distribution mapping could be useful to predict the occurrence of T1ELs in patients with the Najuta stent graft.

Time-series biological responses toward decellularized bovine tendon graft and autograft for 52 consecutive weeks after rat anterior cruciate ligament reconstruction.

There is an essential demand for developing biocompatible grafts for knee anterior cruciate ligament reconstruction (ACLR). This study investigated cell infiltration into decellularized bovine tendon xenografts using a rat knee ACLR model. Twelve-week-old Sprague-Dawley rats were used. At weeks 1, 2, 4, 8, 16, 26, and 52 (each period, n = 6) after ACLR, rats receiving decellularized bovine tendon (group D, n = 42) or autologous tendon (group A, n = 42) as grafts underwent peritibial bone tunnel bone mineral density (BMD), histological, and immunohistological assessments. BMD increased over time in both the groups until week 16 and then remained unchanged without exhibiting significant differences between the groups. Initially, cellularity in group D was lower than that in group A; however, by weeks 4-8, both the groups were comparable to the native anterior cruciate ligament group and cellularity remained unchanged until week 52. Initially, group A had more M1 macrophages, indicating inflammation, whereas group D had more M2 macrophages, indicating tissue regeneration. Nonetheless, the M1 and M2 macrophage counts of both the groups were comparable at most times. This study revealed the excellent recellularization and tendon-bone integration abilities of decellularized tendons using a cross-species model.

Biodesign program introduction in Japan: promotion of entrepreneurship and viewpoints of education on medical technology innovation.

The Stanford Biodesign program was first introduced in Japan in 2015 at three national universities to develop medical technology innovation and its talent. This study aimed to (1) show the outcomes of leadership talent development, (2) indicate the educational results of the program, and (3) objectively analyze the ways in which the program executed in Japan, effectively promoted entrepreneurship orientation and the origination of new businesses. The latter is especially relevant as Japan has low entrepreneurial awareness and new business entry rates compared to the United States and Europe. Herein, fellows were subjected to questionnaires, interviews, and a survey based on academic papers, extant literature, and treatises issued by the Nihon Biodesign Gakkai (Academic Society of Japan Biodesign). Overall program performance showed notable results, despite indicating a need to improve business-related programs and team learning which is greatly influenced by Japanese culture. An externship program, planned and developed in Japan, was most inspiring and served to expose participants to role models. Comparing Japan Biodesign education elements to factors of general entrepreneurship promotion in Japan, sampled and organized from relevant White Papers, proved its educational effectiveness in entrepreneurship promotion from an objective viewpoint. Within the 4-year timeframe, the results indicated that leadership talent was indeed developed. Medical device innovation should progress through the stages of establishing new ventures, followed by contriving medical devices with novel, impactful value. This study revealed that Japan Biodesign education provides a platform for achieving these goals, despite the challenging Japanese new business environment.

Latest outcomes of transcatheter left atrial appendage closure devices and direct oral anticoagulant therapy in patients with atrial fibrillation over the past 5 years: a systematic review and meta-analysis.

Left atrial appendage closure (LAAC) are emerging treatment for patients with atrial fibrillation (AF). However, data on the safety, efficacy, and medications for LAAC devices in patients with AF are lacking. We aimed to investigate the incidence of all-cause mortality, stroke, and major bleeding in AF patients with LAAC devices and DOACs. Moreover, we aimed to investigate the incidence rate of device-related thrombus (DRT) and the medications used in the management of AF patients with LAAC devices to gain insights into achieving better outcome. Based on a literature search using PubMed, EMBASE, Cochrane Library, and Web of Science databases between January 2015 and December 2020, eight LAAC device studies that used WATCHMAN and Amulet, and three DOAC studies that used rivaroxaban, with a total of 24,055 AF patients (LAAC devices, n = 2855; DOAC, n = 21,200), were included. A random-effects model was used to incorporate heterogeneity among studies. The pooled incidence of events per person-years were as follows: all-cause mortality, 0.06 (95% confidence interval [CI] 0.02-0.10) for WATCHMAN, 0.04 (95% CI 0.00-0.14) for Amulet, and 0.03 (95% CI 0.01-0.04) for rivaroxaban; stroke; 0.02 (95% CI 0.00-0.04) for WATCHMAN, 0 for Amulet, and 0.01 (95% CI 0.01-0.02) for rivaroxaban; major bleeding, 0.04 (95% CI 0.02-0.06) for WATCHMAN, 0.02 (95% CI 0.00-0.06) for Amulet, and 0.02 (95% CI 0.01-0.03) for rivaroxaban. The incidence rate of DRT was 2.3%, and complications were reported in 9%. The incidence of all-cause mortality, stroke, and major bleeding were similar between LAAC devices and DOACs. The rate of complications was acceptable, and those of DRT were lower than the average incidence reported in previous studies. However, further follow-up is needed. Concomitant anticoagulant and antiplatelet therapies should be further evaluated to find the optimal regimen for AF patients with LAAC devices.

Perfusable vascular tree like construction in 3D cell-dense tissues using artificial vascular bed.

Perfusable vascular structures in cell-dense tissues are essential for fabricating functional three-dimensional (3D) tissues in vitro. However, it is challenging to introduce functional vascular networks observable as vascular tree, finely spaced at intervals of tens of micrometers as in living tissues, into a 3D cell-dense tissue. Herein, we propose a method for introducing numerous vascular networks that can be perfused with blood into 3D tissues constructed by cell sheet engineering. We devise an artificial vascular bed using a hydrogel that is barely deformed by cells, enabling perfusion of the culture medium directly beneath the cell sheets. Triple-layered cell sheets with an endothelial cell network prepared by fibroblast co-culture are transplanted onto the vascular bed and subjected to perfusion culture. We demonstrate that numerous vascular networks are formed with luminal structures in the cell sheets and can be perfused with India ink or blood after a five-day perfusion culture. Histological analysis also demonstrates that perfusable vascular structures are constructed at least 100 µm intervals uniformly and densely within the tissues. The results suggest that our perfusion culture method enhances vascularization within the 3D cell-dense tissues and enables the introduction of functional vasculature macroscopically observable as vascular tree in vitro. In conclusion, this technology can be used to fabricate functional tissues and organs for regenerative therapies and in vitro experimental models.