Shinji Miyamoto

Objective: While heart transplantation primarily relies on donors after brain death, the use of donors after circulatory death is increasing to address donor shortages. Although favourable outcomes with donation after circulatory death (DCD) have been reported, its safety in patients bridged with durable mechanical circulatory support (MCS) remains uncertain. Design: Using the United Network for Organ Sharing database, we identified adult recipients supported with durable MCS who underwent isolated primary heart transplantation between 2019 and 2023. Outcomes were compared between recipients of hearts from donors after brain death and donors after circulatory death. Results: Among 14 881 heart transplants, 3681 patients were supported with durable MCS, comprising 3374 (91.7%) recipients from donors after brain death and 307 (8.3%) from donors after circulatory death. Compared with recipients of hearts from donors after brain death, those receiving hearts from donors after circulatory death were more often male, had higher body mass index, lower ABO blood group compatibility, fewer pretransplant infections, less extracorporeal membrane oxygenation use, longer ischaemic times (3.5 vs 5.5 hours, P < .05), and shorter waitlist times (404.4 vs 336.9, P < .05). Survival was similar between groups (90.9% vs 93.2% at 6 months, 89.0% vs 90.2% at 1 year; P = .946). Cause of death and other adverse events were also comparable. Conclusions: Utilizing DCD donors significantly reduces waitlist duration for patients with durable MCS. Although early post-transplant survival was statistically stable, definitive conclusions regarding survival equivalence involve several limitations. Further larger comparative studies with comprehensive donor characteristics are strictly required to evaluate the safety profile of DCD hearts in this high-risk recipient population.

Objectives: Aortic valve neocuspidization (AVNeo) has gained widespread recognition in clinical practice; however, multicentre data describing its mid-term functional durability in real-world populations remain limited. This study aimed to evaluate the clinical and echocardiographic outcomes of AVNeo in a large multicentre cohort with extended follow-up. Methods: This retrospective multicentre study included 672 patients who underwent AVNeo at 16 institutions. The study population was characterized by advanced age, small body size, and a substantial burden of comorbidities. Mid-term outcomes included overall survival, freedom from reoperation, and longitudinal echocardiographic performance assessed from discharge through mid-term follow-up. Survival analyses were performed using the Kaplan–Meier method, and temporal echocardiographic changes were evaluated using linear mixed-effects models accounting for repeated measurements and center-level clustering. Results: Early postoperative outcomes demonstrated acceptable procedural safety, with a 30-day mortality of 3.0%. Echocardiographic assessment showed functional optimization during the first postoperative year, while effective orifice area remained stable. Beyond 1 year, transvalvular gradients, peak velocity, valve area, and ventricular function remained stable up to 7 years after surgery. Estimated overall survival was 91.7% at 1 year and 79.5% at 5 years, while freedom from reoperation remained high at 99.4% at 1 year and 96.5% at 5 years. Conclusions: In this large multicentre real-world cohort, AVNeo demonstrated stable mid-term valve performance without evidence of clinically significant progressive deterioration. These findings support the durability and reproducibility of AVNeo in routine clinical practice.

A 51-year-old female patient presented with abdominal distension. Computed tomography revealed a right ovarian tumor suspicious for clinical stage IC ovarian cancer, along with a considerable inferior vena cava (IVC) thrombus extending to the Th2 level, accompanied by a deep vein thrombus and a peripheral left pulmonary embolism (PE). Preoperative IVC filter placement was deemed unfavorable due to the short distance between the renal vein and the thrombus. On the second day of hospitalization, ovarian tumor extraction, thrombectomy, and IVC filter placement were performed. Pathology of the excised tumor revealed endometrioid carcinoma. Postoperatively, anticoagulation therapy with edoxaban 30 mg/day resulted in improvement of the deep vein thrombus and PE. The concomitant adnexal resection and thrombectomy rendered the safe placement of an IVC filter feasible despite the preoperative placement being unfeasible. Open thrombectomy remains a valid treatment strategy despite advances in endovascular therapy.

This study investigated the long-term patency of regenerative Biotube grafts and discusses their feasibility as an alternative to autologous vein grafts for peripheral artery disease. Six Biotubes with a diameter of 4 mm were autologously fabricated in recipients using in vivo tissue engineering (in-body tissue architecture) technology and implanted as carotid artery bypass grafts in a goat model. All six grafts remained patent at 6 months despite exceeding 10 cm in length, demonstrating their biocompatibility and durability. Histological analysis revealed neointima formation, endothelialization, and minimal inflammation. However, in one goat, a graft developed stenosis, while another showed dilatation. These findings demonstrate the use of Biotubes as a viable option for peripheral vascular reconstruction as tissue-engineered vascular grafts. However, further optimization is needed to address emerging issues with their use, such as stenosis and aneurysm formation, to improve long-term patency.

Autologous-engineered artificial tissues constitute an ideal alternative for radical surgery in terms of natural anticoagulation, self-repair, tissue regeneration, and the possibility of growth. Previously, we focused on the development and practical application of artificial tissues using “in-body tissue architecture (iBTA)”, a technique that uses living bodies as bioreactors. This study aimed to further develop iBTA by fabricating tissues with diverse shapes and evaluating their physical properties. Although the breaking strength increased with tissue thickness, the nominal breaking stress increased with thinner tissues. By carving narrow grooves on the outer periphery of an inner core with narrow grooves, we fabricated approximately 2.2 m long cord-shaped tissues and net-shaped tissues with various designs. By assembling the two inner cores inside the branched stainless-steel pipes, a large graft with branching was successfully fabricated, and its aortic arch replacement was conducted in a donor goat without causing damage. In conclusion, by applying iBTA technology, we have made it possible, for the first time, to create tissues of various shapes and designs that are difficult using existing tissue-engineering techniques. Thicker iBTA-induced tissues exhibited higher rupture strength; however, rupture stress was inversely proportional to thickness. These findings broaden the range of iBTA-induced tissue applications.

This study investigated six-month outcomes of first models of ascending aortic replacement. The molds used to produce the Biotube were implanted subcutaneously in goats. After 2–3 months, the molds were explanted to obtain the Biotubes (inner diameter, 12 mm; wall thickness, 1.5 mm). Next, we performed ascending aortic replacement using the Biotube in five allogenic goats. At 6 months, the animals underwent computed tomography (CT) and histologic evaluation. As a comparison, we performed similar surgeries using glutaraldehyde-fixed autologous pericardial rolls or pig-derived heterogenous Biotubes. At 6 months, CT revealed no aneurysmalization of the Biotube or pseudoaneurysm formation. The histologic evaluation showed development of endothelial cells, smooth muscle cells, and elastic fibers along the Biotube. In the autologous pericardium group, there was no evidence of new cell development, but there was calcification. The histologic changes observed in the heterologous Biotube group were similar to those in the allogenic Biotube group. However, there was inflammatory cell infiltration in some heterologous Biotubes. Based on the above, we could successfully create the world’s first Biotube-based ascending aortic replacement models. The present results indicate that the Biotube may serve as a scaffold for aortic tissue regeneration.

Biotubes are autologous tubular tissues developed within a patient’s body through in-body tissue architecture, and they demonstrate high potential for early clinical application as a vascular replacement. In this pilot study, we used large animals to perform implantation experiments in preparation for preclinical testing of Biotube. The biological response after Biotube implantation was histologically evaluated. The designed Biotubes (length: 50 cm, internal diameter: 4 mm, and wall thickness: 0.85 mm) were obtained by embedding molds on the backs of six goats for a predetermined period (1–5 months). The same goats underwent bypass surgery on the carotid arteries using Biotubes (average length: 12 cm). After implantation, echocardiography was used to periodically monitor patency and blood flow velocity. The maximum observation period was 6 months, and tissue analysis was conducted after graft removal, including the anastomosis. All molds generated Biotubes that exceeded the tensile strength of normal goat carotid arteries, and eight randomly selected Biotubes were implanted. Thrombotic occlusion occurred immediately postoperatively (1 tube) if anticoagulation was insufficient, and two tubes, with insufficient Biotube strength (2 months without aneurysm formation. The spots far from the anastomosis became stenosed within 3 months (3 tubes) when Biotubes had a wide intensity distribution, but the shape of the remaining two tubes remained unchanged for 6 months. The entire length of the bypass region was walled with an αSMA-positive cell layer, and an endothelial cell layer covered most of the lumen at 2 months. Complete endothelial laying of the luminal surface was obtained at 3 months after implantation, and a vascular wall structure similar to that of native blood vessels was formed, which was maintained even at 6 months. The stenosis was indicated to be caused by fibrin adhesion on the luminal surface, migration of repair macrophages, and granulation formation due to the overproliferation of αSMA-positive fibroblasts. We revealed the importance of Biotubes that are homogeneous, demonstrate a tensile strength > 5 N, and are implanted under appropriate antithrombotic conditions to achieve long-term patency of Biotube. Further, we clarified the Biotube regeneration process and the mechanism of stenosis. Finally, we obtained the necessary conditions for a confirmatory implant study planned shortly.