Bioabsorbable arterial grafts can potentially improve patency and neovessel formation; however, their application in clinical settings has not been realized. In this study, we developed bioabsorbable ...gradient sheets based on silk fibroin (SF) and polyvinyl alcohol (PVA) with a core–shell nanofibrous structure. This gradient sheet was expected to promote vascular remodeling while we maintained its physical properties and a gradual degrading process from the luminal surface. ESP was conducted at various flow rates for SF and PVA to achieve the multilayer gradient structure. Furthermore, the elasticity of the gradient sheet could be increased by increasing the PVA flow rate; however, this reduced the tensile strength of the core–shell fibers. Notably, the physical properties of the gradient sheet did not degrade even after 7 days of immersion in a phosphate buffer saline solution, which indicates that the structure could maintain its structural integrity while resisting arterial pressure. In vitro experiments revealed that the number of endothelial cells attached to the SF/PVA sheet was notably higher than that on the cell‐culture dish. The gradient sheets were implanted in rat abdominal aortas and explanted after 14 days to confirm acute‐phase patency and vascular remodeling. The gradient sheets constructed with SF composed of polyurethane and PVA improved the ease of handling of the material, and these sheets resulted in a favorable vascular remodeling outcome. Our results strongly suggest that the SF/PVA‐based gradient sheets described in this study can serve as a novel design for bioabsorbable arterial grafts upon further modifications.
Background:Alcohol septal ablation (ASA) is a treatment option in patients with drug-refractory symptomatic hypertrophic obstructive cardiomyopathy (HOCM). In many patients, right bundle branch block ...(RBBB) develops during ASA because septal branches supply the right bundle branch. However, the clinical significance of procedural RBBB is uncertain.Methods and Results:We retrospectively reviewed 184 consecutive patients with HOCM who underwent ASA. We excluded 40 patients with pre-existing RBBB (n=10), prior pacemaker implantation (n=15), mid-ventricular obstruction type (n=10), and those lost to follow-up (n=5), leaving 144 patients for analysis. Patients were divided into 2 groups according to the development (n=95) or not (n=49) of procedural RBBB. ASA conferred significant decreases in the left ventricular pressure gradient (LVPG) in both the RBBB and no-RBBB group (from 74±48 to 27±27 mmHg P<0.001 and from 75±45 to 31±33 mmHg P<0.001, respectively). None of the RBBB patients developed further conduction system disturbances. The percentage reduction in LVPG at 1 year after the procedure was significantly greater in the RBBB than no-RBBB group (66±24% vs. 49±45%; P=0.035). Procedural RBBB was not associated with pacemaker implantation after ASA, but was associated with reduction in repeat ASA (odds ratio 0.34; 95% confidence interval 0.13–0.92; P=0.045).Conclusions:Although RBBB frequently occurs during the ASA procedure, it does not adversely affect clinical outcomes.
A 77-year-old female presented with loss of consciousness, blood pressure of 90/60 mmHg, and heart rate of 47 bpm. At admission, highly sensitive Trop-T and lactate were elevated, and an ...electrocardiogram revealed an infero-posterior ST elevation myocardial infarction. Echocardiography revealed a depressed left ventricular ejection fraction with abnormal wall motion in the infero-posterior region and hyperkinetic apical movement along with severe mitral regurgitation (MR). Coronary angiography showed a hypoplastic right coronary artery, 100% thrombotic occlusion of the dominant left circumflex (LCx) artery, and 75% stenosis in the left anterior descending (LAD) artery. Substantial hemodynamic improvement with the reduction of acute ischemic MR was achieved by the initiation of an Impella 2.5, which is a transvalvular axial flow pump, and successful percutaneous coronary intervention (PCI) was conducted with stents to the LCx. The patient was weaned off the Impella 2.5 in 5 days, received staged PCI to LAD, and was later discharged after completion of the staged PCI to LAD.
The development of vascular bioengineering has led to a variety of novel treatment strategies for patients with cardiovascular disease. Notably, combining biodegradable scaffolds with autologous cell ...seeding to create tissue-engineered vascular grafts (TEVG) allows for in situ formation of organized neovascular tissue and we have demonstrated the clinical viability of this technique in patients with congenital heart defects. The role of the scaffold is to provide a temporary 3-dimensional structure for cells, but applying TEVG strategy to the arterial system requires scaffolds that can also endure arterial pressure. Both biodegradable synthetic polymers and extracellular matrix-based natural materials can be used to generate arterial scaffolds that satisfy these requirements. Furthermore, the role of specific cell types in tissue remodeling is crucial and as a result many different cell sources, from matured somatic cells to stem cells, are now used in a variety of arterial TEVG techniques. However, despite great progress in the field over the past decade, clinical effectiveness of small-diameter arterial TEVG (<6mm) has remained elusive. To achieve successful translation of this complex multidisciplinary technology to the clinic, active participation of biologists, engineers, and clinicians is required. (Circ J 2014; 78: 12–19)
Essential thrombocythemia (ET) and polycythemia vera (PV), are common Philadelphia-negative myeloproliferative neoplasms (MPN). Patients with MPN have a high rate of cardiovascular complications and ...often have acquired JAK2V617F and CALR genetic mutations. In this study, we aimed to analyze vascular endothelial function in patients with MPN.We evaluated 27 outpatients, including 10 patients diagnosed with MPN, flow-mediated dilatation (FMD), and nitroglycerin-mediated dilation (NMD), between September 2014 and August 2016. We measured serum adiponectin, which protects vascular endothelial function, and serum asymmetric dimethyl arginine (ADMA), which inhibits the production of adiponectin. The presence or absence of JAK2V617F and CALR mutations was evaluated in patients with MPN.Venous thrombosis was observed more frequently in patients with MPN than in those without. Seven MPN patients were diagnosed with PV, and 3 MPN patients were diagnosed with ET. JAK2V617F and CALR mutations were found in 5 and 3 MPN patients, respectively. FMD was significantly lower in JAK2V617F-positive MPN patients than in JAK2V617F-negative MPN patients, although NMD, adiponectin, and ADMA were similar in both groups. Adiponectin levels were higher and ADMA levels were lower in CALR-positive MPN patients than in CALR-negative MPN patients. There was no difference in FMD and NMD prevalence between the 2 groups. Furthermore, we had 3 representative MPN patients who were complicated with coronary spasm, possibly caused by MPN-related endothelial dysfunction.We found that patients with MPN presented with endothelial dysfunction, which was related to the presence of genetic mutations and was sometimes associated with cardiovascular disease.
We herein report a case of mitochondrial disease with heart and intestinal tract involvement resulting in hemodynamic collapse. A 66-year-old woman was transferred to our hospital because of ...cardiogenic shock. Vasopressors were administered, and a circulatory support device was deployed. However, her hemodynamics did not improve sufficiently, and we detected abdominal compartment syndrome caused by the aggravation of chronic intestinal pseudo-obstruction as a complication. Insertion of a colorectal tube immediately decreased the intra-abdominal pressure, improving the hemodynamics. Finally, we diagnosed her with mitochondrial disease, concluding that the resulting combination of acute heart failure and abdominal compartment syndrome had aggravated the hemodynamics.
Red blood cell (RBC) transfusion therapy is often performed in patients with acute heart failure (AHF) and anemia; however, its impact on subsequent cardiovascular events is unclear. We examined ...whether RBC transfusion influences major adverse cardiovascular events (MACE) after discharge in patients with AHF and anemia.We classified patients with AHF and anemia (nadir hemoglobin level < 10 g/dL) according to whether they received RBC transfusion during hospitalization. The endpoint was MACE (composite of all-cause death, non-fatal acute coronary syndrome/stroke, or heart failure readmission) 180 days after discharge. For survival analysis, we used propensity score matching analysis with the log-rank test. As sensitivity analysis, we performed inverse probability weighting analysis and multivariable Cox regression analysis.Among 448 patients with AHF and anemia (median age, 81 years; male, 55%), 155 received RBC transfusion and 293 did not. The transfused patients had worse clinical features than the non-transfused patients, with lower levels of nadir hemoglobin and serum albumin and a lower estimated glomerular filtration rate. In the propensity-matched cohort of 87 pairs, there was no significant difference in the MACE-free survival rate between the 2 groups (transfused, 73.8% vs. non-transfused, 65.3%; P = 0.317). This result was consistent in the inverse probability weighting analysis (transfused, 76.0% vs. non-transfused, 68.7%; P = 0.512), and RBC transfusion was not significantly associated with post-discharge MACE in the multivariable Cox regression analysis (adjusted hazard ratio: 1.468, 95% confidence interval: 0.976-2.207; P = 0.065).In conclusion, this study suggests that RBC transfusions for anemia may not improve clinical outcomes in patients with AHF.
Objective Autologous grafts are used to repair atherosclerotic cardiovascular diseases; however, many patients lack suitable donor graft tissue. Recently, tissue engineering techniques have emerged ...to make biologically active blood vessels. We applied this technique to produce arterial grafts using established biodegradable materials without cell seeding. The grafts were evaluated in vivo for vessel remodeling during 12 months. Methods Poly( l -lactide-co-ε-caprolactone) scaffolds reinforced by poly(lactic acid) (PLA) fiber were prepared as arterial grafts. Twenty-eight cell-free grafts were implanted as infrarenal aortic interposition grafts in 8-week-old female SCID/Bg mice. Serial ultrasound and micro computed tomography angiography were used to monitor grafts after implantation. Five grafts were harvested for histologic assessments and reverse transcription-quantitative polymerase chain reaction analysis at time points ranging from 4 months to 1 year after implantation. Results Micro computed tomography indicated that most implanted mice displayed aneurysmal changes (three of five mice at 4 months, four of five mice at 8 months, and two of five mice at 12 months). Histologic assessments demonstrated extensive tissue remodeling leading to the development of well-circumscribed neovessels with an endothelial inner lining, a neointima containing smooth muscle cells and elastin, and a collagen-rich extracellular matrix. There were a few observed calcified deposits, located around residual PLA fibers at 12 months after implantation. Macrophage infiltration into the scaffold, as evaluated by F4/80 immunohistochemical staining, remained after 12 months and was focused mostly around residual PLA fibers. Reverse transcription-quantitative polymerase chain reaction analysis revealed that gene expression of Itgam, a marker for macrophages, and of matrix metalloproteinase 9 was higher than in native aorta during the course of 12 months, indicating prolonged inflammation (Itgam at 8 months: 11.75 ± 0.99 vs native aorta, P < .01; matrix metalloproteinase 9 at 4 months: 4.35 ± 3.05 vs native aorta, P < .05). Conclusions In this study, we demonstrated well-organized neotissue of cell-free biodegradable arterial grafts. Although most grafts experienced aneurysmal change, such findings provide insight into the process of tissue-engineered vascular graft remodeling and should allow informed rational design of the next generation of arterial grafts.
Abstract Objective Bioresorbable vascular grafts are biologically active grafts that are entirely reconstituted by host-derived cells through an inflammation-mediated degradation process. ...Calcification is a detrimental condition that can severely affect graft performance. Therefore, prevention of calcification is of great importance to the success of bioresorbable arterial vascular grafts. The objective of this study was to test whether fast-degrading (FD) bioresorbable arterial grafts with high cellular infiltration will inhibit calcification of grafts. Methods We created two versions of bioresorbable arterial vascular grafts, slow-degrading (SD) grafts and FD grafts. Both grafts had the same inner layer composed of a 50:50 poly( l -lactic-co-ε-caprolactone) copolymer scaffold. However, the outer layer of SD grafts was composed of poly( l -lactic acid) nanofiber, whereas the outer layer of FD grafts was composed of a combination of poly( l -lactic acid) and polyglycolic acid nanofiber. Both grafts were implanted in 8- to 10-week-old female mice (n = 15 in the SD group, n = 10 in the FD group) as infrarenal aortic interposition conduits. Animals were observed for 8 weeks. Results von Kossa staining showed calcification in 7 of 12 grafts in the SD group but zero in the FD group ( P < .01, χ2 test). The cell number in the outer layer of FD grafts was significantly higher than in the SD grafts (SD, 0.87 ± 0.65 × 103 /mm2 ; FD, 2.65 ± 1.91 × 103 /mm2 ; P = .02). Conclusions The FD bioresorbable arterial vascular graft with high cellular infiltration into the scaffold inhibited calcification of grafts.
Background: Lower extremity artery disease is strongly associated with morbidity and is typically addressed through revascularization interventions. We assessed the clinical outcomes of patients with ...chronic limb-threatening ischemia (CLTI) without revascularization who did and did not undergo repetitive hyperbaric oxygen therapy (HBOT). Methods: Between April 2002 and March 2017, the records of 58 patients with CLTI (Rutherford classification 4 in 19% and 5 in 81%) were evaluated retrospectively. HBOT was performed at 2.8 atm of oxygen (HBOT group). The control group included those who could not continue HBOT and historical controls. Patients in poor general health or with an indication for revascularization therapy were excluded. We examined major adverse events (MAEs) and limb salvage rates. Independent predictors and risk stratification were analyzed using a multivariate regression analysis. Results: The mean age was 71±13 years. Of all patients, 67% had diabetes and 43% were undergoing hemodialysis. The mean follow-up period was 4.3±0.8 years. The overall survival rate was 84.5% and 81.0% at 1 and 3 years, respectively. The Cox regression analysis indicated that high body mass index (odds ratio OR: 0.86; 95% confidence interval CI: 0.76-0.97; p=0.01), well-nourished (OR: 1.21; 95% CI: 1.01-1.45), and HBOT (OR: 0.05; 95% CI: 0.01-0.26; p<0.001) independently predicted absence of MAEs. For major limb amputation, the ankle-brachial index (OR: 0.2; 95% CI: 0.05-0.86; p=0.03) and HBOT (OR: 0.04; 95% CI: 0.004-0.32; p=0.003) were independent predictors. Conclusions: Repetitive, stand-alone HBOT was associated with MAE-free survival and limb salvage in patients with CLTI.
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