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Chronic total occlusion (CTO) is a high-risk factor for stent thrombosis, but little is known about the difference in neointimal healing between CTO and non-CTO lesions regarding implanted stents. We investigated factors affecting neointimal healing after stent implantation for CTO and non-CTO lesions using angioscopy.We retrospectively evaluated 106 stents in 85 consecutive patients between March 2016 and July 2020. Their average age was 68 ± 11 years, and participants (73 male and 12 female) underwent follow-up angiography and angioscopy 1 year after percutaneous coronary intervention (PCI). The stents (n = 106) were divided into three groups according to the lesion status at the previous PCI: CTO (n = 17), acute coronary syndrome (ACS) (n = 35), and stable coronary artery disease without CTO or non-CTO (n = 54).The neointimal stent coverage grade was significantly lower in the CTO and ACS groups than in the non-CTO group (0.4 ± 0.5, 0.9 ± 0.8, and 1.4 ± 0.8, respectively, p 0.001). Thrombi were significantly more frequent in CTO and ACS than in non-CTO (71 %, 51 %, and 15 %, respectively, p 0.001). The yellow grade in CTO was comparable to that in ACS but significantly higher in CTO than in non-CTO (CTO vs. ACS vs. non-CTO 1.5 ± 0.7, 1.4 ± 0.6, and 0.9 ± 0.7, respectively, p = 0.007).Delayed healing occurs in stents implanted for CTO lesions. Longer dual-antithrombotic therapy may be beneficial.

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.

BACKGROUND The development of heart failure is associated with fluid balance, including that of extracellular water (ECW) and intracellular water (ICW). This study determined whether sodium-glucose cotransporter 2 inhibitors affect fluid balance and improve heart failure in patients after acute myocardial infarction. METHODS AND RESULTS EMBODY was a prospective, randomized, double-blinded, placebo-controlled trial of Japanese patients with acute myocardial infarction and type 2 diabetes. Overall, 55 patients who underwent bioelectrical impedance analysis were randomized to receive once daily 10 mg empagliflozin or placebo 2 weeks after acute myocardial infarction onset. We investigated the time course of body fluid balance measured using the bioelectrical impedance analysis device, InBody. The primary end points were changes in body fluid balance from weeks 0 to 24. Changes between baseline and week 24 in the empagliflozin and placebo groups were -0.21 L (P = .127) and +0.40 L (P = .001) in ECW (P = .001) and -0.23 L (P = .264) and +0.74 L (P < .001) in ICW (P < .001), respectively. In a stratified analysis, the rise in ECW and ICW was significantly attenuated in the empagliflozin group in contrast to the placebo group in participants with a body mass index of 25 or higher but not in those with a body mass index of less than 25. CONCLUSIONS Early sodium-glucose cotransporter 2 inhibitor administration may attenuate changes in ECW and ICW.

Objective The coronavirus disease 2019 (COVID-19) pandemic has had a significant impact on global healthcare systems. Some studies have reported the negative impact of COVID-19 on ST-elevation myocardial infarction (STEMI) patients; however, the impact in Japan remains unclear. This study investigated the impact of the COVID-19 pandemic on STEMI patients admitted to an academic tertiary-care center in Tokyo, Japan. Methods In this retrospective, observational, cohort study, we included 398 consecutive patients who were admitted to our institute from January 1, 2018, to March 10, 2021, and compared the incidence of hospitalization, clinical characteristics, time course, management, and outcomes before and after March 11, 2020, the date when the World Health Organization declared COVID-19 a pandemic. Results There was a 10.7% reduction in hospitalization of STEMI patients during the COVID-19 pandemic compared with that in the previous year (117 vs. 131 cases). During the COVID-19 pandemic, the incidence of late presentation was significantly higher (26.5% vs. 12.1%, p

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.

In the modern US cardiovascular intensive care unit (CICU), the incidence of non-cardiovascular disorders has increased and non-cardiovascular disorders are associated with an increase in morbidity and mortality. In Japan, however, data regarding the association between non-cardiovascular disorders and outcomes in the CICU are limited.This study examined 490 consecutive admissions to a closed CICU at the Nippon Medical School Hospital from January to December 2017. Characteristics, diagnoses, treatments, and outcomes of admitted patients were identified.The most common primary diagnosis was acute coronary syndrome (50.4%), followed by acute heart failure (20.0%), arrhythmia (6.7%), and non-cardiovascular diseases (3.7%). The mortality rate and median length of stay (LOS) in the CICU were 4.7% and 4 (interquartile range, 2-8) days, respectively. Of all patients, 42.2% (n = 207) developed non-cardiovascular complications such as acute respiratory failure, acute kidney injury, or sepsis during CICU stay. Multivariate logistic regression analysis revealed that acute respiratory failure and sepsis were significantly associated with mortality in the CICU (odds ratio, 11.014 and 25.678, respectively; both p0.05). The multiple linear regression analysis showed that acute kidney injury was significantly associated with LOS in the CICU (β=0.144, p = 0.002).Approximately half of patients admitted to the CICU had non-cardiovascular disorders including non-cardiovascular disease and non-cardiovascular complications, which were significantly associated with mortality and LOS in the CICU.

Introduction Plasma volume status (PVS), a parameter of the discrepancy between actual plasma volume (PV) and ideal PV, has been recently evaluated as a prognostic marker in patients with heart failure. This subgroup analysis of the EMBODY trial was designed to determine whether a sodium-glucose cotransporter 2 (SGLT2) inhibitor affects the alleviation of heart failure and improvement of PVS in patients after acute myocardial infarction (AMI) with congestive heart failure (CHF). Methods The EMBODY trial was a prospective, multicenter, randomized, double-blind, placebo-controlled trial to identify the effect of an SGLT2 inhibitor on cardiac sympathetic hyperactivity in patients with AMI and type 2 diabetes mellitus (T2DM) in Japan. In total, 105 patients were randomized (1:1) to receive 10 mg empagliflozin or a placebo (once daily), 2 weeks after the onset of AMI. In this subanalysis, we investigated the time-course of PVS at baseline and weeks 4, 12, and 24. Results Overall, 96 patients were included in the subgroup analysis set (age 64.3 ± 10.9 years, 80.2% men; 46 in the empagliflozin group and 50 in the placebo group). Body weight and PVS decreased in the empagliflozin group compared with the placebo group at 24 weeks (− 2.2 vs. + 0.1 kg, P

Gastrointestinal (GI) bleeding worsens the outcomes of critically ill patients in the intensive care unit (ICU). Owing to a lack of corresponding data, we aimed to investigate whether GI bleeding during cardiovascular-ICU (C-ICU) admission in acute cardiovascular (CV) disease patients is a risk factor for subsequent CV events. Totally, 492 consecutive C-ICU patients (40.9% acute coronary syndrome, 22.8% heart failure) were grouped into GI bleeding (n = 27; 12 upper GI and 15 lower GI) and non-GI bleeding (n = 465) groups. Thirty-nine patients died or developed CV events during hospitalization, and 453 were followed up from the date of C-ICU discharge to evaluate subsequent major adverse CV events. The GI bleeding group had a higher Acute Physiology and Chronic Health Evaluation II score (20.2 ± 8.2 vs. 15.1 ± 6.8, p

Cyclophosphamide (CY)-induced cardiotoxicity involves rare lethal complications. We previously reported the cardiac events of 811 allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients; 12 out of 811 recipients (1.5%) developed fatal heart failure. The mortality rate was also very high (91.6%, 11/12). CY dose (200 mg/kg or more) was reported as the independent risk factor. The main disease in patients treated with 200 mg/kg or more of CY was severe aplastic anemia (AA). Therefore, we reduced the dose of CY during conditioning for AA (from 200 to 100 mg/kg), and then we analyzed the clinical features of 294 patients who received a total dose of at least 100 mg/kg of CY. We also compared the clinical features between the current study and our previous study. The proportion of patients treated with at least 200 mg/kg of CY was reduced from 4.2% to 0%. However, CY-induced heart failure occurred in four of the 294 patients (1.4%), which was similar to the finding reported in our previous study (1.5%). Two of these four patients received a post-transplant CY (PTCy) regimen (CY 100 mg/kg). All four patients were treated in the cardiac intensive care unit (C-ICU), and two patients survived. In summary, even the CY dose of 120 mg/kg or less would cause cardiotoxicity. We should also carefully monitor patients treated with PTCy, considering the possibility of CY-induced cardiotoxicity. Early diagnosis and ICU management have contributed to improved outcomes.

Background: Bioresorbable vascular grafts (BVGs) can transform biologically into active blood vessels and represent an alternative to traditional synthetic conduits, which are prone to complications such as infection and thrombosis. Although platelet-derived growth factors and c-Kit positive cells play an important role in smooth muscle cell (SMC) migration and proliferation in vascular injury, atherosclerosis, or allograft, their roles in the vascular remodeling process of an arterial BVG remains unknown. Thus, we assessed the neottisue formation on arterial BVG remodeling by administrating imatinib, which is both a platelet-derived growth factor receptor kinase inhibitor and c-Kit receptor kinase inhibitor, in a murine model. Methods: BVGs were composed of an inner poly(L-lactic-co-ε-caprolactone) copolymer sponge layer and an outer electrospun poly(L-lactic acid) nanofiber layer, which were implanted into the infrarenal abdominal aortas of C57BL/6 mice. After graft implantation, saline or 100 mg/kg of imatinib was administrated intraperitoneally daily for 2 weeks (n = 20 per group). Five mice in each group were scheduled to be humanely killed at 3 weeks and 15 at 8 weeks, and BVGs were explanted for histologic assessments. Results: Graft patency during the 8-week observational period was not significantly different between groups (control, 86.7% vs imatinib, 80.0%; P > .999). Neotissue formation consisting of endothelialization, smooth muscle proliferation, and deposition of collagen and elastin was not observed in either group at 3 weeks. Similar endothelialization was achieved in both groups at 8 weeks, but thickness and percent area of neotissue formation were significantly higher in the control group than in the imatinib group, (thickness, 30.1 ± 7.2 μm vs 19.6 ± 4.5 μm [P = .001]; percent area, 9.8 ± 2.7% vs 6.8 ± 1.8% [P = .005]). Furthermore, SMC layer and deposition of collagen and elastin were better organized at 8 weeks in the control group compared with the imatinib group. The thickness of SMC layer and collagen fiber area were significantly greater at 8 weeks in the control group than in the imatinib group (P < .001 and P = .026, respectively). Because there was no difference in the inner diameter of explanted BVGs (831.7 ± 63.4 μm vs 841.8 ± 41.9 μm; P = .689), neotissue formation was thought to advance toward the outer portion of the BVG with degradation of the polymer scaffold. Conclusions: Imatinib attenuates neotissue formation during vascular remodeling in arterial bioresorbable vascular grafts (BVGs) by inhibiting SMC layer formation and extracellular matrix deposition. : Clinical Relevance: This study demonstrated that imatinib attenuated neotissue formation during vascular remodeling in arterial Bioresorbable vascular graft (BVG) by inhibiting smooth muscle cell formation and extracellular matrix deposition. In addition, as imatinib did not modify the inner diameter of BVG, neotissue advanced circumferentially toward the outer portion of the neovessel. Currently, BVGs have not yet been clinically applied to the arterial circulation. The results of this study are helpful for the design of BVG that can achieve an optimal balance between polymer degradation and neotissue formation.

Pericardiocentesis is an essential procedure for the diagnosis and treatment of pericardial effusions. The purpose of this study was to evaluate the feasibility and safety of a subxiphoid anterior approach using fluoroscopy aided by a sagittal axis chest computed tomography (CT) view in comparison with an ultrasound-guided apical approach in patients with chronic pericardial effusion.Among 72 consecutive patients (68.8 ± 14.4 years old, 52 males) with hemodynamically stable chronic pericardial effusions, a total of 85 procedures were retrospectively analyzed. We divided them into two groups according to the site of the approach for the pericardiocentesis.A subxiphoid anterior approach (n = 53) was performed guided by fluoroscopy. The sagittal axis view of the chest CT was constructed to determine the puncture angle and direction for the subxiphoid anterior approach. An apical approach (n = 32) was performed by ultrasound guidance. The success rates of the anterior and apical approaches were 98.1% and 93.8%, respectively. There were two cases with cardiac perforations in the apical approach group, while no cases developed perforations in the subxiphoid anterior approach group.The subxiphoid anterior approach for pericardiocentesis was feasible and safe for managing chronic pericardial effusions. A reconstruction of the sagittal axis view of the chest CT imaging was helpful to identify the direction and depth to access the pericardial space from the subxiphoid puncture site before the pericardiocentesis using the lateral fluoroscopic view.

Background: High coronary thrombus burden has been associated with unfavorable outcomes in patients with ST-segment elevation myocardial infarction (STEMI), the optimal management of which has not yet been established. Methods: We assessed the adjunctive catheter-directed thrombolysis (CDT) during primary percutaneous coronary intervention (PCI) in patients with STEMI and high thrombus burden. CDT was defined as intracoronary infusion of tissue plasminogen activator (t-PA; monteplase). Results: Among the 1849 consecutive patients with STEMI, 263 had high thrombus burden. Moreover, 41 patients received t-PA (CDT group), whereas 222 did not receive it (non-CDT group). No significant differences in bleeding complications and in-hospital and long-term mortalities were observed (9.8% vs. 7.2%, p = 0.53; 7.3% vs. 2.3%, p = 0.11; and 12.6% vs. 17.5%, p = 0.84, CDT vs. non-CDT). In patients who underwent antecedent aspiration thrombectomy during PCI (75.6% CDT group and 87.4% non-CDT group), thrombolysis in myocardial infarction grade 2 or 3 flow rate after thrombectomy was significantly lower in the CDT group than in the non-CDT group (32.2% vs. 61.0%, p < 0.01). However, the final rates improved without significant difference (90.3% vs. 97.4%, p = 0.14). Conclusions: Adjunctive CDT appears to be tolerated and feasible for high thrombus burden. Particularly, it may be an option in cases with failed aspiration thrombectomy.

Background: High coronary thrombus burden has been associated with unfavorable outcomes in patients with ST-segment elevation myocardial infarction (STEMI), the optimal management of which has not yet to be established. Methods: We evaluated the safety and efficacy of adjunctive catheter-directed thrombolysis (CDT) during primary percutaneous coronary intervention (PCI) in patients with STEMI and high thrombus burden. Results: Among the 1,849 consecutive patients with STEMI, 263 had high thrombus burden. Moreover, 41 patients received intracoronary infusion of tissue plasminogen activator during primary PCI (CDT group), whereas 222 did not receive (non-CDT group). No significant differences in bleeding complications and in-hospital and long-term mortalities were observed (9.8% vs. 7.2%, p=0.53; 7.3% vs. 2.3%, p=0.11; and 12.6% vs. 17.5%, p=0.84, CDT vs. non-CDT). In patients who underwent antecedent aspiration thrombectomy during PCI (75.6%; CDT group and 87.4%; non-CDT group), thrombolysis in myocardial infarction grade 2 or 3 flow rate after thrombectomy was significantly lower in the CDT group than in the non-CDT group (32.2% vs. 61.0%, p

Electrospinning is commonly used to generate polymeric scaffolds for tissue engineering. Using this approach, we developed a small-diameter tissue engineered vascular graft (TEVG) composed of poly-e-caprolactone-co- l -lactic acid (PCLA) fibers and longitudinally assessed its performance within both the venous and arterial circulations of immunodeficient (SCID/bg) mice. Based on in vitro analysis demonstrating complete loss of graft strength by 12 weeks, we evaluated neovessel formation in vivo over 6-, 12- and 24-week periods. Mid-term observations indicated physiologic graft function, characterized by 100% patency and luminal matching with adjoining native vessel in both the venous and arterial circulations. An active and robust remodeling process was characterized by a confluent endothelial cell monolayer, macrophage infiltrate, and extracellular matrix deposition and remodeling. Long-term follow-up of venous TEVGs at 24 weeks revealed viable neovessel formation beyond graft degradation when implanted in this high flow, low-pressure environment. Arterial TEVGs experienced catastrophic graft failure due to aneurysmal dilatation and rupture after 14 weeks. Scaffold parameters such as porosity, fiber diameter, and degradation rate informed a previously described computational model of vascular growth and remodeling, and simulations predicted the gross differential performance of the venous and arterial TEVGs over the 24-week time course. Taken together, these results highlight the requirement for in vivo implantation studies to extend past the critical time period of polymer degradation, the importance of differential neotissue deposition relative to the mechanical (pressure) environment, and further support the utility of predictive modeling in the design, use, and evaluation of TEVGs in vivo. Statement of Significance Herein, we apply a biodegradable electrospun vascular graft to the arterial and venous circulations of the mouse and follow recipients beyond the point of polymer degradation. While venous implants formed viable neovessels, arterial grafts experienced catastrophic rupture due to aneurysmal dilation. We then inform a previously developed computational model of tissue engineered vascular graft growth and remodeling with parameters specific to the electrospun scaffolds utilized in this study. Remarkably, model simulations predict the differential performance of the venous and arterial constructs over 24 weeks. We conclude that computational simulations should inform the rational selection of scaffold parameters to fabricate tissue engineered vascular grafts that must be followed in vivo over time courses extending beyond polymer degradation.

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

BACKGROUND Because development of acute coronary syndrome (ACS) worsens the prognosis of patients with coronary artery disease, preventing recurrent ACS is crucial. However, the degree to which secondary prevention treatment goals are achieved in patients with recurrent ACS is unknown. METHODS 214 consecutive ACS patients were classified as having First ACS (n=182) or Recurrent ACS (n=32), and the clinical characteristics of these groups were compared. Fifteen patients died or developed cardiovascular (CV) events during hospitalization, and the remaining 199 patients were followed from the date of hospital discharge to evaluate subsequent CV events. RESULTS Patients in the Recurrent ACS group were older than those in the First ACS group (76.8±10.8 years vs 68.8±13.4 years, p=0.002) and had a higher rate of diabetes mellitus (DM) (65.6% vs 36.8%, p=0.003). The rate of achieving a low-density lipoprotein cholesterol (LDL-C) level of

An inter-arm difference in blood pressure (IADBP) is characteristic of acute aortic dissection (AAD), but the importance of which arm exhibits lower blood pressure (BP) and the mechanism underlying IADBP are not well understood.We identified consecutive patients with chest and/or back pain and suspected acute cardiovascular disease whose BP had been measured in both arms. We retrospectively compared the characteristics of such patients with AAD (n=93) to those without AAD (non-AAD group, n=122). Additionally, we separately compared patients with type A AAD (TAAD group, n=58) or type B AAD (TBAD group, n=35) to the non-AAD group. The characteristics analyzed were patient background and IADBP-related factors, including systolic BP (SBP) in the right arm (R) and left arm (L), and R-L or L-R as IADBP. Computed tomography (CT) findings of AD extending to the brachiocephalic artery (BCA) and/or left subclavian artery (LSCA) were examined in patients with an IADBP.In a comparison of the TAAD group and non-AAD group, the prevalences of R130 mm Hg (38% vs. 19%, p=0.009), L-R15 mm Hg (19% vs. 8%, p=0.047), L-R20 mm Hg (14% vs. 4%, p=0.029) were higher in the TAAD group. Multivariate analysis showed that L-R15 mm Hg with R130 mm Hg was independently associated with TAAD (OR 25.97, 95% CI 2.45-275.67, p=0.007). However, IADBP-related factors were not associated with TBAD. AAD patients with L-R20 mm Hg all had TAAD, and all aortic dissection extended to the BCA just before the right common carotid artery on CT.IADBP was characterized by RL with low R in TAAD but was not associated with TBAD.

Background: Plasma volume status (PVS), a parameter of the discrepancy between actual plasma volume (PV) and ideal PV, has been evaluated recently as a prognostic marker of patients with heart failure. This subgroup analysis of the EMBODY trial was designed to determine whether the sodium-glucose cotransporter 2 (SGLT2) inhibitor affect the improvement of heart failure and PVS in patients after acute myocardial infarction (AMI) with congestive heart failure (CHF). Methods: The EMBODY trial was a prospective, multicenter, randomized, double-blind, placebo-controlled trial to identify the effect of the SGLT2 inhibitor on cardiac sympathetic hyperactivity in patients with AMI and type 2 diabetes mellitus (T2DM) in Japan. A total of one hundred and five patients were randomized (1:1) to receive once-daily 10 mg empagliflozin or placebo 2 weeks after the onset of AMI. In this subanalysis, we investigated the time-course of PVS on baseline, weeks 4, 12 and 24. Results: Overall, 96 patients were included in the subgroup analysis set (64.3±10.9 years, male 80.2%, and 46 in the empagliflozin group and 50 in the placebo group). The empagliflozin group showed significant decreases in body weight, systolic blood pressure, and PVS compared with the placebo group at 24 weeks (-2.2 vs. +0.1 kg, P=0.0007; -6.6 vs. +3.5 mmHg, P=0.003; and -5.1 vs. -0.3%, P=0.0006; respectively). Decreased of PVS, defined as change of PVS < -4.5 % was associated with received empagliflozin (odds ratio, 2.61; 95% confidence interval, 1.11 - 6.15; P=0.028). On the other hand, NT-Pro BNP levels significantly decreased in the empagliflozin group and placebo group (1028.7 to 370.3 pg/ml, P=0.0001 and 1270.6 to 673.7 pg/ml, P=0.006, respectively). Conclusion: Empagliflozin reduced not only body weight but also PVS. These results suggested that early SGLT2 inhibitor administration in patients with AMI, CHF and T2DM could be effective to reduce body weight and PVS.

Introduction: Although renoprotective effect of sodium glucose co-transporter-2 (SGLT2) inhibitors has been recognized in the patients with heart failure or type 2 diabetes mellitus (T2DM), this protection has not been fully examined in patients with acute myocardial infarction (AMI). We therefore examined renoprotection of the SGLT2 inhibitor empagliflozin in patients with AMI and T2DM. Methods: The EMBODY trial was a prospective, multicenter, randomized, double-blind, placebo-controlled trial to identify the effect of the SGLT inhibitor on cardiac sympathetic hyperactivity in patients with AMI and T2DM in Japan. One hundred and five patients were randomized (1:1) to receive once-daily 10-mg empagliflozin, or placebo 2 weeks after the onset of AMI. In this sub-analysis, we specifically focused on the time-course of renal function on baseline, weeks 4, 12 and 24. Results: Overall, 96 patients (64±11 y, 78 male) were included in the full analysis set (n = 46 and 50 in empagliflozin and placebo groups, respectively). In the placebo group, estimated glomerular filtration rate (eGFR) decreased from 66.1 at baseline to 62.8 mL/min/1.73m 2 on week 24, (P = 0.02). On the other hand, the empagliflozin group did not worsen it (from 64.6 to 64.4 mL/min/1.73m 2 , P = 0.84). The empagliflozin group exhibited the significant reduction in systolic blood pressure and uric acid level from baseline to week 24 (129.7 mmHg to 123.1 mmHg, P = 0.004, and 5.8 mg/dL to 4.9 mg/dL, P < 0.0001, respectively), whereas the reduction was not significant in the placebo group (123.1 mmHg to 126.2 mmHg, P = 0.19, and 5.7 mg/dL to 5.8 mg/dL, P = 0.82, respectively). The change in eGFR from baseline to 24 weeks was negatively correlated with the changes in uric acid in the placebo group (r=0.685, P2 , the empagliflozin group showed the significant increase in eGFR compared with the placebo group (+1.15 mL/min/1.73m 2 vs, - 6.43 mL/min/1.73m 2 , P=0.008), but not among the other population. Conclusions: Empagliflozin seemed to prevent the progression of renal dysfunction compared with placebo in the patients with AMI and T2DM. This tendency was remarkable when eGFR was 60-90 mL/min/1.73m 2 .

Background Chronic total occlusion (CTO) is thought as a high-risk feature of stent thrombosis, but little is known about the difference in neointimal healing of stents implanted for CTO lesions compared to that of non-CTO lesions. Methods and results A total of 62 stents in consecutive 47 patients (69±11 years, 41 male) who underwent follow-up angiography and angioscopy one year after percutaneous coronary intervention (PCI) between March 2016 and July 2019 were evaluated. The examined stents were divided into 3 groups according to the lesion status at previous PCI: CTO group (n=12), stable coronary artery disease without CTO (non-CTO group, n=30) and acute coronary syndrome (ACS group, n=20). The grade of neointimal stent coverage in CTO group was significantly lower than that of non-CTO group (0.5±0.5 vs 1.4±0.9, p=0.001). The frequency of presence of thrombus was significantly higher in CTO group and ACS group compared to non-CTO group (67%, 50%, and 13%, respectively, p=0.001). The yellow grade in CTO group was equivalent (p=1.00) to that in ACS group and was tented to be higher (p=0.051) compared to non-CTO group (1.3±0.8, 1.5±0.6, and 0.8±0.7, respectively). Conclusion The present study suggested a delayed healing in stents implanted for CTO lesions. Longer dual-antithrombotic therapy maybe beneficial for these patients. Funding Acknowledgement Type of funding source: None

Introduction Protection from lethal ventricular arrhythmias leading to sudden cardiac death is one of the most important problems after myocardial infarction. Cardiac sympathetic hyperactivity is related to poor prognosis and fatal arrhythmias and can be non-invasively assessed with heart rate variability, heart rate turbulence, T-wave alternans, late potentials, and 123I-meta-iodobenzylguanide (123I-MIBG) scintigraphy. Sodium glucose cotransporter 2 (SGLT2) inhibitors potentially reduce sympathetic nervous system activity that is augmented in part due to the stimulatory effect of hyperglycemia. The EMBODY trial is designed to determine whether the suppression of cardiac sympathetic activity induced by the SGLT2 inhibitor is accompanied by protection against adverse cardiovascular outcomes. Methods The EMBODY trial is a prospective, multicenter, randomized, double-blind, placebo-controlled trial in patients with acute MI and type 2 diabetes in Japan. A total of 98 patients will be randomized (1:1) to receive once-daily placebo or empagliflozin, an SGLT2 inhibitor, 10 mg. The primary end point is the change from baseline to 24 weeks in heart rate variability. Secondary end points include the change from baseline for other sudden cardiac death surrogate-markers such as heart rate turbulence, T-wave alternans, late potentials, and 123I-MIBG scintigraphy imaging. Adverse effects will be evaluated throughout the trial period. Planned Outcomes The EMBODY trial will evaluate the potential cardioprotective effect of empagliflozin and will provide additional important new data regarding its preventative effects on sudden cardiac death. Trial Registration Unique Trial Number, UMIN000030158 (https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000034442). Funding Nippon Boehringer Ingelheim and Eli Lilly and Company.

Four-dimensional flow magnetic resonance imaging (4D flow MRI) provides the detailed visualization of complex blood flow patterns and the evaluation of energy loss. Turbulent kinetic energy estimation (TKE) is reported to have good correlation with irreversible pressure loss in patients having aortic stenosis or great vessel disease. However, little is known about the usefulness of 4D flow MRI and the significance of TKE value in hypertrophic cardiomyopathy (HCM). Purpose The aims of this study were to investigate the relationship between TKE value and echocardiographic findings, clinical symptoms and evaluate the usefulness of 4D flow MRI to distinguish hypertrophic obstructive cardiomyopathy (HOCM) from non-obstructive HCM (HNCM). Methods From April 2018 to January 2019, 18 hypertrophic obstructive cardiomyopathy (HOCM) and 14 non-obstructive HCM (HNCM) patients underwent 4D flow MRI. We investigated TKE value calculated by 4D flow MRI, echocardiographic findings; left ventricular pressure gradient (LVPG), mitral regurgitation (MR) and clinical symptom. Results HOCM was defined by the 30 mmHg or greater of LVPG (HOCM: 87.7±47.3 mmHg, HNCM; 5.8±7.8 mmHg, p Conclusion Our findings suggest that 4D Flow MRI can effectively evaluate the energy dissipation associated with LV outflow tract obstruction and TKE value is useful for identifying HOCM. TKE value also can be the novel parameter of the severity of HOCM.

Background Thrombolysis has been recommended for high-risk pulmonary embolism (PE) in ESC guidelines, used as a reference in Japan. Recently, indication of thrombolysis for acute PE has been limited with recent guideline revision. Little is known regarding trends of treatment strategy and mortality in high-risk PE patients. Purpose To clarify temporal trends of treatment strategy and short-term outcomes in high-risk PE patients. Methods A retrospective analysis of therapeutic interventions and short-term outcomes was performed for 52 consecutive high-risk PE patients including cardiac arrest. According to timing of ESC guidelines update (2000, 2008 and 2014), patients were divided into four time periods: 1992 to 2000, 2001 to 2008, 2009 to 2014, and 2015 to 2018. Results Mean age and proportion of male were not different over the period. Nosocomial case decreased from 100% to 25% (p Table 1 1992–2000 (n=14) 2001–2008 (n=15) 2009–2014 (n=14) 2015–2018 (n=9) p Age (years) 54±12 59±17 64±13 65±16 0.224 Male 29% 13% 29% 44% 0.269 Any thrombolytic therapy 92% 87% 71% 44% 0.067 Catheter-directed therapy 86% 87% 71% 0% Conclusion The temporal analysis identified a decreased trend in any thrombolytic therapy and IVC filter insertion in high-risk PE. The study also found a decreasing trend in major bleeding.

Background Current commercialized small-diameter arterial grafts have not shown clinical effectiveness due to their poor patency rates. The present study evaluated the feasibility of an arterial bioresorbable vascular graft, which has a porous sponge-type scaffold, as a small-diameter arterial conduit. Methods The grafts were constructed by a 50:50 poly (1-lactic-co-e-caprolactone) copolymer (PLCL) scaffold reinforced by a poly (1-lactic acid) (PLA) nanofiber. The pore size of the PLCL scaffold was adjusted to a small size (12.8 ± 1.85 μm) or a large size (28.5 ± 5.25 μm). We compared the difference in cellular infiltration, followed by tissue remodeling, between the groups. The grafts were implanted in 8- to 10-week-old female mice (n = 15 in each group) as infrarenal aortic interposition conduits. Animals were monitored for 8 weeks and euthanized to evaluate neotissue formation. Results No aneurysmal change or graft rupture was observed in either group. Histologic assessment demonstrated favorable cell infiltration into scaffolds, neointimal formation with endothelialization, smooth muscle cell proliferation, and elastin deposition in both groups. No significant difference was observed between the groups. Immunohistochemical characterization with anti-F4/80 antibody demonstrated that macrophage infiltration into the grafts occurred in both groups. Staining for M1 and M2, which are the two major macrophage phenotypes, showed no significant difference between groups. Conclusions Our novel bioresorbable vascular grafts showed well-organized neointimal formation in the high-pressure arterial circulation environment. The large-pore scaffold did not improve cellular infiltration and neotissue formation compared with the small-pore scaffold.

Stenosis limits widespread use of tissue-engineered vascular grafts (TEVGs), and bone marrow mononuclear cell (BM-MNC) seeding attenuates this complication. Yet seeding is a multistep process, and the singular effects of each component are unknown. We investigated which components of the clinical seeding protocol confer graft patency and sought to identify the optimal MNC source. Scaffolds composed of polyglycolic acid and ε-caprolactone/ι-lactic acid underwent conditioned media (CM) incubation (n = 25) and syngeneic BM-MNC (n = 9) or peripheral blood (PB)-MNC (n = 20) seeding. TEVGs were implanted for 2 weeks in the mouse IVC. CM incubation and PB-MNC seeding did not increase graft patency compared to control scaffolds prewet with PBS (n = 10), while BM-MNC seeding reduced stenosis by suppressing inflammation and smooth muscle cell, myofibroblast, and pericyte proliferation. IL-1β, IL-6, and TNFα were elevated in the seeded BM-MNC supernatant. Further, BM-MNC seeding reduced platelet activation in a dose-dependent manner, possibly contributing to TEVG patency.

Aim: Surgical management of pediatric extrahepatic portal vein obstruction requires meso-Rex bypass using autologous or synthetic grafts. Tissue-engineered vascular grafts (TEVGs) provide an alternative, but no validated animal models using portal TEVGs exist. Herein, we preclinically assess TEVGs as portal vein bypass grafts. Materials & methods: TEVGs were implanted as portal vein interposition conduits in SCID-beige mice, monitored by ultrasound and micro-computed tomography, and histologically assessed postmortem at 12 months. Results: TEVGs remained patent for 12 months. Histologic analysis demonstrated formation of neovessels that resembled native portal veins, with similar content of smooth muscle cells, collagen type III and elastin. Conclusion: TEVGs are feasible portal vein conduits in a murine model. Further preclinical evaluation of TEVGs may facilitate pediatric clinical translation.

One problem of vascular angiogenesis therapy is the lack of reliable methods for evaluating blood flow in the microcirculation. We aimed to assess whether (99m)Tc-macroaggregated albumin perfusion scintigraphy ((99m)Tc-MAA) predicts quantitated blood flow after therapeutic angiogenesis in patients with peripheral artery disease.Forty-six patients with peripheral artery disease were treated with bone marrow mononuclear cell implantation (BMCI). Before and 4 wk after BMCI, blood flow was evaluated via transcutaneous oxygen tension (TcPO2), ankle-brachial index, intravenous (99m)Tc-tetrofosmin perfusion scintigraphy ((99m)Tc-TF), and intraaortic (99m)Tc-MAA.Four weeks after BMCI, TcPO2 improved significantly (20.4 ± 14.4 to 36.0 ± 20.0 mm Hg, P0.01), but ankle-brachial index did not (0.65 ± 0.30 to 0.76 ± 0.24, P = 0.07). Improvement in (99m)Tc-TF count (0.60 ± 0.23 to 0.77 ± 0.29 count ratio/pixel, P0.01) and (99m)Tc-MAA count (5.21 ± 3.56 to 10.33 ± 7.18 count ratio/pixel, P = 0.02) was observed in the foot region but not the lower limb region, using both methods. When these data were normalized by subtracting the pixel count of the untreated side, the improvements in (99m)Tc-TF count (-0.04 ± 0.26 to 0.08 ± 0.32 count ratio/pixel, P = 0.04) and (99m)Tc-MAA count (1.49 ± 3.64 to 5.59 ± 4.84 count ratio/pixel, P = 0.03) in the foot remained significant. (99m)Tc-MAA indicated that the newly developed arteries were approximately 25 μm in diameter.BMCI induced angiogenesis in the foot, which was detected using (99m)Tc-TF and (99m)Tc-MAA. (99m)Tc-MAA is a useful method to quantitate blood flow, estimate vascular size, and evaluate flow distribution after therapeutic angiogenesis.