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Background Cardiac rupture (CR) is a catastrophic complication of acute myocardial infarction. Primary percutaneous coronary intervention (pPCI) reduces the incidence of CR. This study aimed to investigate the clinical risk factors and characteristics of CR after pPCI. Methods This was a retrospective, case-control, multicenter study. We enrolled 2444 consecutive patients with ST-elevation myocardial infarction (STEMI) who had undergone pPCI between 2009 and 2015; 33 patients experienced CR (1.35%): 19 were assigned as early CR (≤72 h) and 14 as late CR (>72 h). The 132 controls were randomly selected from the 2411 STEMI patients without CR, by matching institutions at a 1:4 ratio. Results : Multivariate logistic regression revealed that female sex, acute hyperglycemia, thrombocytopenia (platelets 1, and post-PCI TIMI 1 and thrombocytopenia were strongly associated with late CR. Early CR occurred more frequently between 12:00 and 21:00 h, whereas the peak incidence of late CR was bimodal between 6:00–12:00 and 21:00–24:00 h. Conclusions In STEMI patients after pPCI, acute hyperglycemia and thrombocytopenia are new risk factors for early and late CR, respectively. Clinical risk factors and time of occurrence of early and late CR may differ in the PCI era.

Aims Cardiac ischaemia/reperfusion (I/R) injury remains a critical issue in the therapeutic management of ischaemic heart failure. Although mild hypothermia has a protective effect on cardiac I/R injury, more rapid and safe methods that can obtain similar results to hypothermia therapy are required. 2‐Methyl‐2‐thiazoline (2MT), an innate fear inducer, causes mild hypothermia resulting in resistance to critical hypoxia in cutaneous or cerebral I/R injury. The aim of this study is to demonstrate the protective effect of systemically administered 2MT on cardiac I/R injury and to elucidate the mechanism underlying this effect. Methods and results A single subcutaneous injection of 2MT (50 mg/kg) was given prior to reperfusion of the I/R injured 10 week‐old male mouse heart and its efficacy was evaluated 24 h after the ligation of the left anterior descending coronary artery. 2MT preserved left ventricular systolic function following I/R injury (ejection fraction, %: control 37.9 ± 6.7, 2MT 54.1 ± 6.4, P

Impairment of pancreatic β cells is a principal driver of the development of diabetes. Restoring normal insulin release from the β cells depends on the ATP produced by the intracellular mitochondria. In maintaining mitochondrial function, the tumor suppressor p53 has emerged as a novel regulator of metabolic homeostasis and participates in adaptations to nutritional changes. In this study, we used orotic acid, an intermediate in the pathway for de novo synthesis of the pyrimidine nucleotide, to reduce genotoxicity. Administration of orotic acid reduced p53 activation of MIN6 β cells and subsequently reduced β cell death in the db/db mouse. Orotic acid intake helped to maintain the islet size, number of β cells, and protected insulin secretion in the db/db mouse. In conclusion, orotic acid treatment maintained β cell function and reduced cell death, and may therefore, be a future therapeutic strategy for the prevention and treatment of diabetes.

Purpose:Transcatheter aortic valve replacement (TAVR) can rapidly improve cardiac sympathetic nervous function (CSNF) within 2 weeks in patients with aortic stenosis (AS). However, it remains unclear whether such short-term improvements will be sustained thereafter. The present study aimed to investigate the mid-term (i.e., 6–12 months) effects of TAVR on CSNF in patients with severe AS using 123I-meta-iodobenzylguanidine (MIBG) imaging.Methods:Patients with severe AS who were scheduled to undergo TAVR between October 2017 and June 2019 were enrolled in this single-centre, prospective, observational study. MIBG imaging was performed at baseline, within 2 weeks after TAVR, and at 6–12 months post-TAVR to evaluate the heart–mediastinum ratio (H/M) and washout rate (WR). Differences between each MIBG parameter at three time points were analysed, and factors involved in the long-term improvement in the late H/M were investigated. Results:Of 183 consecutive patients, 75 (19 men; median age: 86 years) were evaluated. The late H/M significantly improved within 2 weeks after TAVR (P=0.041) and further improved over 6–12 months after TAVR (P=0.041). The WR rapidly improved immediately after TAVR (P=0.003) but remained unchanged at 6–12 months (P=0.827). Multivariate analysis revealed that the baseline mean aortic valve pressure gradient (mPG) was an independent predictor of mid-term improvement in the late H/M (>0.1) (adjusted odds ratio: 0.035; 95% confidence interval: 0.004–0.070; P=0.037). Patients with a high baseline mPG (≥58 mmHg) exhibited a significantly greater increase in the late H/M than those with a low baseline mPG (P=0.029).Conclusions:CSNF, as denoted by the late H/M, demonstrated sustained improvement from within 2 weeks after TAVR until 6–12 months later. Such improvement was related to baseline hemodynamic AS severity.

Purpose To report the endovascular treatment for acute progressive and very-late-onset multiple segmental small-artery stenoses in transplanted kidney parenchyma presenting with rapidly deteriorating renal function and refractory hypertension in a 65-year-old man. Case report Nineteen years ago, the patient received a living renal transplant via end-to-end anastomosis of the right internal iliac artery for kidney failure caused by chronic glomerulonephritis. His transplant renal function (creatinine: 0.9 mg/dL) and blood pressure were stable for 18 years. Then rapid worsening of renal function (creatinine: 2.5 mg/dL) and refractory hypertension occurred. Magnetic resonance angiography and renal angiography showed multiple small segmental artery stenoses in the transplanted kidney. At the 1-month follow-up consultation, total occlusion of 2 branches traversing the inferior pole of the kidney was observed, revealing acute progression of artery stenosis. Balloon angioplasty was successfully performed on those branches; renal function improved (creatinine: 1.3 mg/dL), and blood pressure was sufficiently controlled. Conclusions This is a rare case that revealed very-late-onset multiple segmental renal artery stenoses with acute progression in the transplant kidney. Even multiple small segmental artery stenoses can reduce transplant renal function in the chronic phase and progress rapidly. Early percutaneous transluminal angioplasty may thus be feasible and important for preventing graft loss.

Aims In patients with aortic valve stenosis (AS), cardiac sympathetic nervous (CSN) dysfunction and its improvement after transcatheter aortic valve replacement (TAVR) have been reported. The prognostic impact of CSN function remains unclear. This study investigated the prognostic value of cardiac 123I‐metaiodobenzylguanidine (MIBG) imaging for predicting cardiac events after TAVR. Methods and results This single‐centre prospective observational study enrolled patients with AS between July 2017 and May 2019. MIBG scintigraphy was performed before and soon after TAVR to evaluate the late heart–mediastinum ratio (L‐H/M). Patients were classified into three pairs of groups based on the baseline and post‐TAVR L‐H/M (≥2.0 or

Background: Obesity is reportedly associated with the incidence of atrial fibrillation (AF), but the patterns of age-specific associations between body mass index (BMI) and the risk of AF are unknown. Methods and Results: We analyzed 10,921 Japanese men without AF from a cohort of employees undergoing annual health examinations. During a follow-up period of 5.0±3.8 years, the incidence of AF was 118 (2.18/1,000 person-years). Using a multivariable Cox regression analysis, high BMI was associated with a risk of AF (hazard ratio; 1.07 by 1 unit change of BMI, 95% confidence interval [CI] 1.00–1.13, P=0.05) overall, and the effect of BMI on AF incidence changed with age (P for interaction=0.08); with subjects aged

Background Transcatheter aortic valve replacement (TAVR) is a viable treatment option for managing aortic prosthetic valve dysfunction. Although the transfemoral approach is the most commonly used and preferred treatment strategy for TAVR, complex vascular access, such as aortic aneurysm, severe tortuosity, and shaggy aorta, is challenging. Case summary An 87-year-old man, who underwent surgical aortic valve replacement for aortic stenosis using a 21-mm Carpentier-Edwards Perimount Valve, presented with New York Heart Association functional Class III dyspnoea. He was diagnosed as having severe symptomatic structural valve deterioration of a bioprosthetic aortic valve. Computed tomography revealed a tortuous and shaggy descending aorta with a saccular aneurysm in the aortic arch. Simultaneous transfemoral valve-in-valve TAVR and Zone 2 thoracic endovascular aortic repair (TEVAR) with debranching were successfully performed using a 22-Fr 65-cm sheath. Although the patient developed paraplegia due to transient spinal cord ischaemia associated with TEVAR, he fully recovered with vasopressor therapy. Discussion To the best of our knowledge, this is the first report on simultaneous successful ‘valve-in-valve’ TAVR and debranching TEVAR using the transfemoral approach. This case demonstrated the feasibility of single-stage transfemoral TAVR and TEVAR in a high-risk patient with multicomponent disease.

Jugular venous pressure (JVP) has been established for the assessment of central venous pressure in patients with heart failure (HF), but data are limited regarding the response of JVP to exercise because of its complicated methods. Simplifying the estimation of JVP may be applied in such situations. JVP was assessed before and after the 6-minute walk test (6MWT) in 81 patients with HF using a simple method by which the JVP was considered high when the internal jugular venous pulsation on the right side was visually identified above the right clavicle in the sitting position. The primary outcome was a composite of cardiovascular death and hospitalization for worsening HF. None of the patients exhibited high JVP before the 6MWT and 11 patients (14%) had a high JVP after. The 6MWT distances were lower in patients with a high JVP after the 6MWT (338 ± 114 m) than those in patients without a high JVP (417 ± 78 m, p = 0.04). During a follow-up period of 13.4 ± 6.9 months, 11 patients died and 8 patients were hospitalized for worsening HF. The incidence of adverse cardiac events was higher in patients with a high JVP after the 6MWT (64%) than in patients without a high JVP after (64% vs 17%; hazard ratio, 7.52; 95% confidence interval, 2.69 to 20.83; p

Background The combination of a bioresorbable scaffold and antiproliferative drugs is a promising treatment for peripheral artery disease. The novel paclitaxel-eluting peripheral Igaki-Tamai stent (PTX-ITS) has the same backbone design as the drug-free peripheral Igaki-Tamai stent and a paclitaxel coating. Arterial responses to the PTX-ITS and ITS using optical coherence tomography (OCT) and histological analysis in a porcine iliac artery model were compared.Methods and Results:In total, 6 PTX-ITSs and 6 ITSs implanted in porcine iliac arteries were evaluated. Quantitative measurements of the scaffold, lumen, neointimal areas, and percent area stenosis were performed using OCT at 1 and 3 months. Histological evaluations (PTX-ITS [n=5], ITS [n=4]) were performed following euthanasia at 3 months. Injury, inflammation, endothelialization, and fibrin scores were measured. Baseline angiographic characteristics were similar in both groups. The ITS group showed significantly smaller scaffold areas than the PTX-ITS group at 1 month (18.50±3.62 mm2vs. 23.54±3.64 mm2; P=0.037) and 3 months (15.82±2.57 mm2vs. 21.67±3.57 mm2; P=0.009). Percent area stenosis was significantly lower in the PTX-ITS group at 3 months (28.70±7.24% vs. 40.36±7.07%; P=0.018). Histological evaluations revealed similar low-grade inflammatory reactions for both scaffolds. Conclusions PTX-ITSs showed significantly better suppression of late scaffold shrinkage and lower in-scaffold stenosis for up to 3 months. Additionally, PTX-ITSs exhibited high biocompatibility, which is comparable to ITSs.

A 50-year-old man presented with general fatigue on exertion. Investigations revealed tachycardia-induced cardiomyopathy induced by Wolff-Parkinson-White syndrome and atrial fibrillation. He was successfully treated with catheter ablation. Cardiac magnetic resonance imaging revealed that delayed enhancement throughout the left ventricle disappeared within 2 months after ablation. (Level of Difficulty: Beginner.), Graphical abstract, A 50-year-old man presented with general fatigue on exertion. Investigations revealed tachycardia-induced cardiomyopathy caused by Wolff-Parkinson-White…

An early diastolic flow from the left ventricular apex to the base can be shown in patients with hypertrophic cardiomyopathy (HCM). This tiny flow or a diastolic paradoxic jet flow is important to detect on echocardiography because of its association with cardiovascular adverse events. We report an asymptomatic 44-year-old man with mid-ventricular obstructive HCM, in which a diastolic paradoxic jet flow was observed not only in the left ventricle but also in the right ventricle. The diastolic paradoxic jet flow in the right ventricle started approximately 110 ms after the onset of the second heart sound, lasted for almost 95 ms, and disappeared in coincidence with the third heart sound; the onset was later and the duration was similar, compared with the diastolic paradoxic jet flow in the left ventricle. He had been doing well without any medication for months and later lost to follow-up. J Med Cases. 2020;11(3):57-60 doi: https://doi.org/10.14740/jmc3210

Hypertrophic cardiomyopathy (HCM) can involve the right ventricle (RV), although RV hypertrophy usually exists with left ventricular (LV) hypertrophy and the severity of hypertrophy is milder in the RV than in the LV. We report a case of isolated extreme RV hypertrophy with a maximum RV wall thickness of 40 mm. A 72-year-old man presented with an abnormal electrocardiogram and isolated hypertrophy of the RV apex was found on echocardiography. A diagnosis of HCM was made based on myocardial features on multiple imaging modalities such as the similar myocardial characteristics to LV hypertrophy and systolic thickening. The isolated hypertrophy of the RV apex exhibited partial calcification, which was surrounded by hypoperfused areas of the myocardium on multidetector computed tomography.

Depression is an independent risk factor for cardiovascular disease (CVD). We have previously shown that repeated social defeat (RSD) exaggerates atherosclerosis development by enhancing neutrophil extracellular trap (NET) formation. In this study, we investigated the impact of RSD on arterial thrombosis. Eight-week-old male wild-type mice (C57BL/6J) were exposed to RSD by housing with larger CD-1 mice in a shared home cage. They were subjected to vigorous physical contact daily for 10 consecutive days. After confirming depression-like behaviors, mice underwent FeCl3-induced carotid arterial injury and were analyzed after 3 h. Although the volume of thrombi was comparable between the two groups, fibrin(ogen)-positive areas were significantly increased in defeated mice, in which Ly-6G-positive cells were appreciably co-localized with Cit-H3-positive staining. Treatment with DNase I completely diminished exaggerated fibrin-rich clot formation in defeated mice. Flow cytometric analysis showed that neutrophil CD11b expression before FeCl3 application was significantly higher in defeated mice than in control mice. In vitro NET formation induced by activated platelets was significantly augmented in defeated mice, which was substantially inhibited by anti-CD11b antibody treatment. Our findings demonstrate that RSD enhances fibrin-rich clot formation after arterial injury by enhancing NET formation, suggesting that NET can be a new therapeutic target in depression-related CVD.

Background Atrial fibrillation (AF) is associated with increased risks of stroke and heart failure. AF risk prediction can facilitate the efficient deployment of diagnosis or interventions to prevent AF. Purpose We sought to assess the combination prediction value of Holter electrocardiogram (Holter ECG) and the CHARGE-AF score (Cohorts for Aging and Research in Genomic Epidemiology-AF) for the new-onset of AF in a single center study. We also investigated the association between clinical findings and the new-onset of cerebral cardiovascular events. Methods From January 2008 and May 2014, 1246 patients with aged≥20 undergoing Holter ECG for palpitations, dizziness, or syncope were recruited. Among them, 350 patients were enrolled in this study after exclusion of 1) AF history at the time of inspection or before, 2) post cardiac device implantation, 3) follow-up duration Results During the 5.9-year follow-up, 40 patients (11.4%) developed AF incidence. Multivariate cox regression analysis revealed that CHARGE-AF score (hazard ratio [HR]: 1.59, 95% confidence interval (95% CI): 1.13–2.26, P Conclusion CHARGE-AF score has higher predictive power of both the new incident AF and cerebral cardiovascular events. The combination of CHARGE-AF score and SVEs≥1000 beats/day in Holter ECG can demonstrate the additional effect of prediction ability for the new incident AF, but not for cerebral cardiovascular events. Funding Acknowledgement Type of funding sources: None.

Background and purpose Arrhythmias such as atrial fibrillation (AF) is often associated with depression, with vague anxiety about symptom and the risk of serious complication such as stroke or heart failure. In the geriatric population, geriatric depression often occurs with an increase of physical illness and has substantial costly and quality of life implications for functionality and life satisfaction. However, few studies have investigated relationship between geriatric depression and Quality of Life (QoL), and arrhythmia symptoms (palpitation, dyspnea and chest discomfort). Method Between November 2019 and October 2020, elderly people (≥65 years) who participated in the AF awareness symposium were enrolled in this study. They were divided into 4 groups according to the presence or absence of chest symptom and AF, and were examined geriatric depression by Geriatric depression scale (GDS)-15 and Quality of Life (QoL) by the 12-item Short- Form Health Survey (SF-12) including physical and mental health status. Results Of the 1511 subjects, 1364 were analyzed after excluding 147 with missing values. Among them, 911 were in the non-AF group without symptom (Group A), 43 in the AF group without symptom (group B), 323 in the non-AF group with symptom (group C), and 87 in the AF group with symptom (group D). Geriatric depression rates (defined as GDS-15 ≥10) were 2.7% in non-symptomatic group (2.7% in A [n=25] and 2.3% in B [n=1]) and 7.8% in symptomatic group (7.4% in C [n=24] and 9.2% in D [n=8]). (P The mean values of physical and mental health status in SF-12 were 48.5 (±7.9) and 56.7 (±6.8) in A, 44.6 (±10.7) and 57.3 (±7.3) in B, 45.0 (±9.9) and 53.8 (±7.7) in C, and 43.4 (±10.8) and 54.8 (±8.6) in D, respectively. Physical health status in SF-12 was associated with group C (C vs A: estimate −2.95 [CI: −4.03, −1.87], p Conclusion Older adults with arrhythmia symptoms were more likely to have geriatric depression and low QoL, especially those with symptomatic AF, with a geriatric depressive complication rate of 9.2%. Further studies are needed to investigate whether improving physical health status can improve QoL and geriatric depression. Funding Acknowledgement Type of funding sources: None.

Author's summary We experienced the case of a 61-year-old man who had recurrent infective endocarditis following transcatheter edge-to-edge mitral valve repair using the MitraClip system. Infective endocarditis after MitraClip implantation is a serious complication with high mortality. Early surgical intervention should be considered even in cases of high surgical risk.

A 74-year-old man who had a history of paroxysmal atrial fibrillation, visited the emergency department because of syncope. An electrocardiogram showed atrial fibrillation with slow ventricular response and long pauses. A permanent pacemaker was implanted under oral anticoagulation. Two screw-in leads were positioned at the right atrial appendage and the right ventricular apex. Seven hours after the implantation, he collapsed with hypotension due to cardiac tamponade. Vital signs improved after urgent pericardial drainage, but blood was continuously drained from the pericardial catheter. Due to uncontrollable cardiac tamponade, surgical repair was indicated. We found neither of the leads perforated the myocardium, but there was intermittent bleeding from a pin hole injury in the atrial wall site of the right coronary artery. Redness was observed in the right atrial appendage, but there was no bleeding point. We supposed that the screw tip of the atrial lead might have perforated the atrial appendage, but was retracted spontaneously afterwards. The pin hole was closed with a patch and the postoperative course was uneventful. This is a rare case of cardiac tamponade due to the injury of the coronary artery by a screw-in lead positioned at the right atrial appendage.

A 51-year-old man, who had a history of open heart surgery for corrected transposition of great arteries, presented with palpitation due to atrial tachycardia. A propagation map using three-dimensional electroanatomical mapping (CARTO3) showed atrial flutter and underwent linear ablation successfully. This case highlights the difficulty of diagnosis before mapping following a complicated cardiac operation and the usefulness of three-dimensional mapping.

Senescent vascular cells are detected in atherosclerotic lesion, and its involvement in the development of atherosclerosis has been revealed; however, whether and the mechanism by which endothelial cell (EC) senescence is causally implicated in atherosclerosis remains unclear. We here investigate a role of EC senescence in atherosclerosis by utilizing EC-specific progeroid mice that overexpress the dominant negative form of telomeric repeat-binding factor 2 under the control of the Tie2 or vascular endothelial cadherin promoter. EC-specific progeria accelerated atherosclerosis in mice with target deletion of ApoE. Mechanistically, senescent ECs were markedly sensitive for inflammation-mediated VCAM-1 induction, leading to enhanced monocyte adhesion. Inhibition of NF-κB signaling abolished the enhanced inflammatory responses in senescent ECs, while NF-κB nuclear translocation in response to TNF-α were similar between young and senescent ECs. We found a higher association of VCAM-1 gene with active histone H3 trimethylated on lysine 4, leading to increased NF-κB accessibility in senescent ECs. Our data revealed that EC cellular senescence causes endothelial hyper-inflammability through epigenetic alteration, which consequently accelerates atherosclerosis. Therefore, EC senescence is a promising therapeutic target for the prevention and/or treatment of atherosclerotic disease in elderly population.

Cisplatin is a commonly used anticancer drug, but nephrotoxicity is a dose-limiting adverse effect. Recent experimental and clinical observations have demonstrated that multiple injections of cisplatin induce the transition to chronic kidney disease; however, the underlying mechanisms remain unclear. We found that multiple injections of higher doses of cisplatin in a shorter interval affected the severity of kidney injury, causing kidney fibrosis to develop at a later time point. An additional injection of cisplatin during the recovery period after a prior injury, when proximal tubule epithelia are actively proliferating, induced substantial tubular injury by inducing more severe DNA damage than that induced by a single injection. Lineage tracing analysis of proximal tubular epithelia demonstrated that the tubular epithelia that underwent multiple rounds of cell division after multiple injections of cisplatin existed at the chronic phase, and these populations often expressed vcam1 + , suggesting the induction of proinflammatory failed-repair tubular epithelia. Our study revealed that as cisplatin exerts cytotoxic effects on actively proliferating cells, additional cisplatin injections before the completion of tubular repair exacerbates kidney injury through cumulative DNA damage. Appropriate both the setting of dosage and dosing intervals, with careful monitoring, are essential to prevent nephrotoxicity of repeated cisplatin treatment in cancer patients.

A 58-year-old woman with a history of multi-origin atrial tachycardia and limb-girdle muscular dystrophy was treated for presyncope caused by pauses in atrial rhythm. A dual-chamber pacemaker was implanted. The low-voltage area extended broadly, but 10-V pacing could not capture the large right atrium, including the right atrial appendage, except the coronary sinus ostium. The atrial lead was screwed in using a steerable stylet. A ventricular lead was placed in the right ventricular apex. Atrial pacing at the coronary sinus was required to treat the pauses in the atrial rhythm.

The effects of transcatheter aortic valve replacement (TAVR) on cardiac sympathetic nervous (CSN) function have not been fully explored. This study aimed to investigate the early (within 2 weeks) effects of TAVR on CSN function in patients with severe aortic valve stenosis (AS) using 123I-metaiodobenzylguanidine (MIBG) scintigraphy. Of 143 consecutive patients who were scheduled to undergo TAVR, 67 (18 men; median age 86 years) were evaluated in this single-centre prospective observational study. MIBG scintigraphy was performed at baseline and 3–14 days after the TAVR procedure to evaluate the heart–mediastinum ratio (H/M) and washout rate (WR). Differences between baseline and post-TAVR MIBG parameters were analysed. MIBG parameter changes were compared with echocardiographic parameters. Furthermore, factors involved in the improvement in MIBG parameters were investigated. All patients successfully underwent TAVR with improved echocardiographic parameters, including aortic valve area (AVA; 0.6 cm2 vs. 1.6 cm2), peak velocity (4.5 m/s vs. 2.0 m/s), mean pressure gradient (50 mmHg vs. 9 mmHg), and left ventricular ejection fraction (56% vs. 62%) (all p 3%). Female sex, Clinical Frailty Scale score ≤ 5, baseline estimated glomerular filtration rate, and baseline AVA were predictors of improvement in delayed H/M (> 0.1). Baseline AVA and E/E′ were independent predictors of improvement in both WR and delayed H/M. The CSN function was impaired in patients with AS, as assessed using MIBG scintigraphy. WR and delayed H/M improved immediately after TAVR. Improvement in CSN function may be related to echocardiographic AS severity at baseline before TAVR.

A 61-year-old Japanese man with IgG4-related autoimmune pancreatitis developed a mass in the right atrium (RA) and a mass lesion surrounding the left anterior descending coronary artery. We performed an intracardiac echo catheter-guided percutaneous biopsy of the RA mass, and histologically diagnosed it as IgG4-related disease. Oral corticosteroid therapy gradually downsized the mass lesions. We encountered a very rare case with mass lesions in the cardiovascular system of the IgG4-related disease that were able to be diagnosed using an intracardiac echo-guided biopsy.

Background Many patients with collagen disease (CD), particularly scleroderma (SSc), develop critical limb ischemia (CLI), which leads to limb amputation. However, conventional therapies, including revascularization via surgical bypass, showed poor outcomes in CLI patients with CD. Many CLI patients with SSc showed poor responses to combination therapies including intravenous iloprost, PDE-5 inhibitors, and bosentan. Therefore, new methods of improving the peripheral circulation for limb salvage are required. This study was a subanalysis of the long-term clinical outcomes after autologous bone marrow-derived mononuclear cells (BM-MNC) in CLI patients with SSc. Methods and Results: We assessed no-option CLI patients with CD who underwent BM-MNC implantation at 10 institutes; 69 patients (39 with SSc-related diseases (SSc group) and 30 with other CDs (non-SSc group)), were included. The median follow-up duration was 36.5 months. The 10-year overall survival rate was 59.1% in the SSc group and 82.4% in the non-SSc group. The 10-year major amputation-free rates were 97.4% and 82.6%, respectively. The number of major or minor amputations in the SSc group trended to be less than that in the non-SSc group. Significant improvements in visual analog scale scores were observed in both groups. Conclusions The BM-MNC implantation may be feasible in no-option CLI patients with CD. In the SSc group, limb salvage rate tended to be higher than in the non-SSc group.

A 61-year-old man with essential thrombocythemia (ET) presented with acute myocardial infarction (AMI) and underwent primary percutaneous coronary intervention. After stent deployment from the left main (LM) to the left anterior descending artery, intravascular ultrasound revealed thrombi formation in the whole stent. Two days later, optical frequency domain imaging confirmed stent malapposition and thrombi remaining in only the LM. The stent malapposition and ET might have contributed to this phenomenon. He underwent an additional stent expansion and aggressive anti-thrombotic regimen. AMI complicated with ET carries increased risks of in-stent thrombi formation and requires careful revascularization and aggressive pharmacotherapy.

BackgroundTreatment options for inoperable chronic thromboembolic pulmonary hypertension (CTEPH) remain limited. Selexipag, an oral selective IP prostacyclin receptor agonist approved for pulmonary arterial hypertension, is a potential treatment option for CTEPH.MethodsIn this multicentre, randomised, double-blind, placebo-controlled study, 78 Japanese patients with inoperable CTEPH or persistent/recurrent pulmonary hypertension after pulmonary endarterectomy and/or balloon pulmonary angioplasty were randomly assigned to receive placebo or selexipag. The primary end-point was the change in pulmonary vascular resistance (PVR) from baseline to week 20. Secondary end-points were changes in other haemodynamic parameters: 6-min walk distance (6MWD), Borg dyspnoea scale score, World Health Organization (WHO) functional class, EuroQol five-dimension five-level tool and N-terminal pro-brain natriuretic peptide.ResultsThe change in PVR was −98.2±111.3 dyn·s·cm−5 and −4.6±163.6 dyn·s·cm−5 in the selexipag and placebo groups, respectively (mean difference −93.5 dyn·s·cm−5; 95% CI −156.8 to −30.3; p=0.006). The changes in cardiac index (pConclusionSelexipag significantly improved PVR and other haemodynamic variables in patients with CTEPH, although exercise capacity remained unchanged. Further large-scale investigation is necessary to prove the role of selexipag in CTEPH.

Heart failure is frequently accompanied by kidney failure and co-incidence of these organ failures worsens the mortality in patients with heart failure. Recent clinical observations revealed that increased kidney venous pressure, rather than decreased cardiac output, causes the deterioration of kidney function in patients with heart failure. However, the underlying pathophysiology is unknown. Here, we found that decreased blood flow velocity in peritubular capillaries by kidney congestion and upregulation of endothelial nuclear factor-κB (NF-κB) signaling synergistically exacerbate kidney injury. We generated a novel mouse model with unilateral kidney congestion by constriction of the inferior vena cava between kidney veins. Intravital imaging highlighted the notable dilatation of peritubular capillaries and decreased kidney blood flow velocity in the congestive kidney. Damage after ischemia reperfusion injury was exacerbated in the congestive kidney and accumulation of polymorphonuclear leukocytes within peritubular capillaries was noted at the acute phase after injury. Similar results were obtained in vitro, in which polymorphonuclear leukocytes adhesion on activated endothelial cells was decreased in flow velocity-dependent manner but cancelled by inhibition of NF-κB signaling. Pharmacological inhibition of NF-κB for the mice subjected by both kidney congestion and ischemia reperfusion injury ameliorated the accumulation of polymorphonuclear leukocytes and subsequent exacerbation of kidney injury. Thus, our study demonstrates the importance of decreased blood flow velocity accompanying activated NF-κB signaling in aggravation of kidney injury. Hence, inhibition of NF-κB signaling may be a therapeutic candidate for the vicious cycle between heart and kidney failure with increased kidney venous pressure.

Background: Hypertension in patients with atrial fibrillation (AF) is a known independent risk factor for stroke. The Complete blood pressure (BP) monitor (Omron Healthcare, Kyoto, Japan) was developed as the first BP monitor with electrocardiogram (ECG) capability in a single device to simultaneously monitor ECG and BP readings. This study investigated whether the Complete can accurately differentiate sinus rhythm (SR) from AF during BP measurement. Methods and Results: Fifty-six consecutive patients with persistent AF admitted for catheter ablation were enrolled in the study (mean age 65.8 years; 83.9% male). In all patients, 12-lead ECGs and simultaneous Complete recordings were acquired before and after ablation. The Complete interpretations were compared with physician-reviewed ECGs, whereas Complete recordings were reviewed by cardiologists in a blinded manner and compared with ECG interpretations. Sensitivity, specificity, and κ coefficient were also determined. In all, 164 Complete and ECG recordings were simultaneously acquired from the 56 patients. After excluding unclassified recordings, the Complete automated algorithm performed well, with 100% sensitivity, 86% specificity, and a κ coefficient of 0.87 compared with physician-interpreted ECGs. Physician-interpreted Complete recordings performed well, with 99% sensitivity, 85% specificity, and a κ coefficient of 0.85 compared with physician-interpreted ECGs. Conclusions: The Complete, which combines BP and ECG monitoring, can accurately differentiate SR from AF during BP measurement.

Background: Patients with thromboangiitis obliterans (TAO) can develop critical limb-threatening ischemia (CLTI) and require limb amputation. Smoking cessation and exercise therapy are recommended as standard treatments, and revascularization by bypass surgery or endovascular therapy (EVT) is required for patients with CLTI. However, there are many cases in which revascularization is difficult because of vascular characteristics, and the patency rate after revascularization remains unsatisfactory. Therapeutic angiogenesis using bone marrow-derived mononuclear cell (BM-MNC) implantation is used clinically, with many trials demonstrating long-term efficacy and safety of the technique in patients with CLTI, especially that caused by TAO. To expand the use of BM-MNCs implantation in clinical practice, further evidence is required in patients with CLTI caused by TAO. Methods and Results: This trial is a multicenter, prospective, non-randomized interventional trial of an Advanced Medicine B treatment approach. We aim to enroll 25 patients aged 20-80 years with Fontaine classification Stage III or IV, who will undergo BM-MNC implantation. The primary endpoint is the improvement in skin perfusion pressure of the target limb 180 days after BM-MNC implantation, whereas secondary endpoints are improvements in rest pain or ulcer size. We will also investigate rates of major or minor amputation, survival, and adverse events during follow-up. Conclusions: BM-MNC implantation is expected to be an efficacious and feasible treatment for patients with CLTI caused by TAO.

Self-expanding prostheses for transcatheter aortic valve replacement (TAVR), which can be recaptured, provide us the option of repositioning for a more accurate placement. We report a very rare case in which the recapture of CoreValve Evolut R (Medtronic, Minneapolis, Minnesota) to correct the implantation depth during the deployment could not be achieved. We planned TAVR with a 23 mm Evolut R prosthesis for a 92-year-old female with severe aortic stenosis and tightly bent thoracic aorta. During the first deployment attempt, the implantation depth was greater than we expected at 2/3 deployment. They tried to recapture and reposition the prosthesis, but the prosthesis was not re-sheathed into the capsule of the delivery system. The prosthesis could not be recaptured despite a repeat attempt, and they were forced to deploy the device as it was. The prosthesis was deployed very carefully and implanted successfully without a pop-up into the ascending aorta. At a later date, this situation was replicated in vitro and was found that the distal segment of the capsule became deformed, increasing the resistance to rotating the grip handle.

BACKGROUND: The associations between body mass index (BMI) and incidence of atrial fibrillation (AF) in young men are scarce, especially in Asian countries, given the differences in BMI between Asians and Western populations.Methods and Results:This study analyzed 17,865 middle-aged Japanese men without AF from a cohort of employees undergoing annual health examinations. AF incidence was evaluated during a follow-up period (median 4.0 years, interquartile range 2.0-7.1 years). Among young men aged 30-49 years, AF incidence was 0.64/1,000 person-years, whereas it was 2.54/1,000 and 7.60/1,000 person-years among men aged 50-59 and ≥60 years, respectively. Multivariable Cox regression analysis among young men revealed age (hazard ratio [HR] 3.28 by 10-years' increase, 95% confidence interval [CI] 1.72-6.25, PCONCLUSIONS: AF incidence displays a reverse J-shaped relationship with BMI in young men, but a linear association in men aged ≥50 years. The paradoxical relationship seen in young men only may reflect atrial electrical or structural abnormalities.

Aim: The post-endovascular treatment outcomes of thrombotic lesions remain unclear. This study aimed to investigate the effects of thrombotic lesions on post-endovascular treatment outcomes in patients with non-acute aortoiliac total occlusions. Methods: This subanalysis of a multicenter prospective observational registry study included patients from 64 institutions in Japan between April 2014 and April 2016. A total of 346 patients (394 limbs; median age, 72 years), including 186 men, underwent endovascular treatment for non-acute aortoiliac total occlusions and were included. The patients were classified as having thrombotic or non-thrombotic lesions. The primary (1-year primary patency rate) and secondary (1-year overall survival rate) endpoints were evaluated. Results: Thrombotic lesions were identified in 18.5% (64/346) of the patients. The 1-year primary patency (85.9% versus 95.4%, log-rank p ＜.001) and overall survival (90.6% versus 97.9%, log-rank p =.003) rates were significantly lower in the thrombotic group than in the non-thrombotic group. Thrombotic lesions had significant effects on the post-endovascular treatment outcomes, with adjusted hazard ratios of 3.91 (95% confidence interval, 1.64–9.34, p =.002) for primary patency and 4.93 (95% confidence interval, 1.59–15.3, p =.006) for all-cause mortality. Conclusions: Thrombotic lesions were associated with 1-year restenosis and all-cause mortality after endovascular treatment for non-acute aortoiliac total occlusions. Endovascular treatment strategies should be carefully planned for patients with thrombotic lesions.

Background While developments in oncology have lengthened survival in patients with cancer, such patients often develop cardiovascular diseases. Thus, percutaneous coronary intervention (PCI) is frequently undertaken in them. Although stent thrombosis remains a fatal complication in stent-based PCI, worldwide consensus panels tend to recommend shorter duration of dual-antiplatelet therapy. This is based on its clinical efficacy that has resulted from technological innovation. However, there is insufficient discussion on the risk of stent thrombosis in cancer patients with coronary artery disease, especially in those undergoing chemotherapeutic regimens that have a risk for thrombosis, such as regimens with the anti-vascular endothelial growth factor. Presented here is a case of early stent thrombosis that occurred in a cancer patient on regorafenib, despite the administration of triple antithrombotic therapy. Case presentation A 66-year-old Japanese male patient received regorafenib for metastatic colorectal carcinoma and apixaban for deep vein thrombosis. Coronary angiography revealed severe stenosis in the proximal left anterior descending artery. A sirolimus-eluting stent was implanted, without malapposition and under-expansion, under intravascular ultrasound guidance while administering a triple antithrombotic therapy (aspirin: 100 mg/day, prasugrel: 3.75 mg/day, and apixaban: 5 mg/day). However, he was admitted to the hospital for exacerbation of heart failure 1 month after PCI. Coronary angiography revealed contrastive defects in the previous stent. Optical frequency domain imaging confirmed stent thrombosis. PCI was successfully performed with perfusion balloon long-inflation. Antithrombotic therapy was enhanced (aspirin: 100 mg/day, ticagrelor: 120 mg/day, and apixaban: 10 mg/day) and regorafenib was discontinued permanently. While ischemic events did not occur thereafter, the patient died due to metastatic carcinoma progression. Conclusions This case suggests that anti-vascular endothelial growth factor might contribute to early stent thrombosis, despite triple antithrombotic therapy. Further discussion is needed on the surveillance and management of cancer patients with coronary artery disease receiving chemotherapy, which carries a risk of thrombosis.

Glomerulopathy with fibronectin deposits (GFND) is a rare hereditary kidney disease with autosomal dominant inheritance. A 21-year-old woman who had been diagnosed with GFND 10 years ago was admitted for investigation of a rapid decline in her renal function, hemolytic anemia, and cardiac dysfunction. A renal biopsy showed GFND accompanied by extraglomerular vascular lesions. Comprehensive treatments against hypertension and anemia improved the renal function. Although there have been few reports of vascular lesions in GFND, we suspect that endothelial hyperpermeability resulting from hypertension caused the fibronectin deposition and narrowing of the extraglomerular vascular lumens, thereby accelerating hypertension and inducing hemolytic anemia.

BACKGROUND Paclitaxel-coated balloon angioplasty for de-novo coronary artery lesions causes late lumen enlargement (LLE), however, the mechanisms and predictors of LLE have not been elucidated. METHODS AND RESULTS We retrospectively analyzed 91 consecutive patients with 95 de-novo coronary lesions, who underwent paclitaxel-coated balloon angioplasty without stenting from August 2018 to July 2019 as well as follow-up coronary angiography and optical coherence tomography (OCT). The mean follow-up duration was 8.2 ± 2.9 months. The target lesion revascularization rate was 7.3%. OCT demonstrated LLE in 50.5% of lesions. The lesions with LLE had a higher incidence of vessel enlargement (76.6 vs. 29.2%, p

Background and Objective: Depression is an independent risk factor of cardiovascular disease and significantly associated with the prevalence of abdominal aortic aneurysm (AAA). We investigated the impact of repeated social defeat (RSD) on AAA formation. Methods and Results: Eight-week-old male WT mice were exposed to RSD by housing with a larger CD-1 mouse in a shared cage. They were subjected to vigorous physical contact daily for 10 consecutive days. Control mice were housed in the same cage without physical contact. After social interaction test to confirm depressive-like behaviors, mice underwent application of 0.5M calcium chloride (CaCl 2 ) on the infrarenal aorta. At one-week, maximum diameter and circumference of external elastic membrane were comparable between the two groups. The number of F-4/80 and MMP-9-positive cells in immunofluorescent images were also comparable. Consistently, fluorescent image taken by IVIS revealed no difference in MMP activity, suggesting that acute inflammatory response was comparable between the two groups. In contrast, at two weeks, maximum diameter and circumference of external elastic membrane were significantly increased in defeated mice ( p < 0.01). Intriguingly, periaortic fibrotic area in aneurysmal portion was markedly decreased in defeated mice (12.5х10 3 μm 2 vs. 3.7х10 3 μm 2 , Control vs. Defeat, p < 0.01). Consistently, accumulation of α-SMA-positive cells in adventitia of aneurysmal portion was much lesser in defeated mice (876 cells/mm 2 vs. 319 cells/mm 2 , Control vs. Defeat, p < 0.05), whereas those in tunica media of non-aneurysmal portion did not show any difference between the two groups. LPS-induced iNOS gene and protein expressions in bone marrow-derived macrophages (BMDMs) were significantly decreased in defeated mice, whereas the TGF-β-induced phosphorylation of Smad2 and ERK1/2 in primary cultured aortic VSMCs were comparable between the two groups. Conclusions: Our findings demonstrate that RSD enhances AAA expansion by suppressing the periaortic fibrosis following inflammatory response, and suggest that decreased NO production from accumulated macrophages contributes to the reduced VSMCs proliferation and collagen deposition.

Introduction: In patients with aortic valve stenosis (AS), cardiac sympathetic nervous (CSN) dysfunction and its improvement after transcatheter aortic valve replacement (TAVR) have been reported; however, the prognostic impact of CSN function remains unclear. This study investigated the prognostic value of cardiac 123 I-metaiodobenzylguanidine (MIBG) imaging for predicting cardiac events after TAVR. Hypothesis: We hypothesized that the improvement in MIBG parameter with TAVR treatment can be an indicator of better prognosis. Methods: This single-center prospective observational study enrolled patients with AS between July 2017 and May 2019. MIBG scintigraphy was performed before and after TAVR to evaluate the delayed heart-mediastinum ratio (d-H/M). Patients were classified into three pairs of groups based on the baseline and post-TAVR d-H/M (≥2.0 or 0 or ≤0). The study endpoint was the occurrence of major adverse cardiac events (MACE), defined as a composite of all-cause death, non-fatal myocardial infarction, and hospitalization due to heart failure. Results: Among the 187 consecutive patients who underwent TAVR, 107 (27 men; median age: 86 years) were evaluated. Over a median follow-up of 366 days, 15 (14.0%) patients had MACE. The incidence of MACE was significantly low in patients with d-H/M improvement and/or high post-TAVR d-H/M (≥2.0). Baseline d-H/M and frailty were associated with poor response of d-H/M to TAVR treatment. Moreover, post-TAVR d-H/M had significant effects on MACE, with an adjusted hazard ratio of 1.264 (95% confidence interval, 0.034-2.480; p=0.04). Conclusions: Both d-H/M improvement and high post-TAVR d-H/M were associated with better prognosis in patients who underwent TAVR. Cardiac MIBG imaging is useful for predicting cardiac events after TAVR.

Background and Objective: Depression is an independent risk factor of cardiovascular disease (CVD). We have recently shown that repeated social defeat (RSD) exaggerates atherosclerosis development by enhancing neutrophil extracellular traps (NETs) formation. Here, we investigated the impact of RSD on arterial thrombosis. Methods and Results: Eight-week-old male WT mice were exposed to RSD by housing with a larger CD-1 mouse in a shared home cage. They were subjected to vigorous physical contact daily for 10 consecutive days. Control mice were housed in the same gage without physical contact. After social interaction test to confirm depressive-like behaviors, defeated mice (19 of 31) and control mice (12 of 14) were underwent arterial injury at 10 wks of age. A filter paper saturated with 10% FeCl3 was applied on the adventitial surface of left carotid artery for 3 min and analyzed 3 hrs later. The volume of thrombi was comparable between the two groups. However, fibrinogen/fibrin-positive areas in immunofluorescent images significantly increased in defeated mice (48.8% vs. 27.8%, p < 0.01). The number of Ly-6G-positive cells in thrombi was markedly higher in defeated mice (878/mm2 vs. 144/mm2, p < 0.05). Further, Ly-6G-positive cells were co-localized with neutrophil elastase, Cit-H3, and CD42b-positive staining. Percentage of CD42b-positive area in thrombi and in vitro platelets aggregations induced by ADP or collagen were comparable between the two groups. Treatment with DNase I completely diminished the exaggerated fibrin-rich clot formation in defeated mice to an extent similar to that in control mice (22.3% vs. 25.7%, p = ns), although the number of Ly-6G-positive cells in thrombi was not affected. We therefore examined the vulnerability to NETs formation induced by thrombin-activated platelets. Flow cytometric analysis showed that in vitro NETs formation assessed by Cit-H3/MPO double-positive cells was significantly higher in defeated mice (20.7% vs 12.5%, p < 0.01). Conclusions: Our findings demonstrate that RSD enhances fibrin-rich clot formation after arterial injury by enhancing NETs formation via platelet-neutrophil interactions, suggesting that NETosis could be a new therapeutic target in depression-related CVD development.

Background Hyperhomocysteinemia is caused by genetic and environmental factors, which can result in systemic arteriosclerosis and arteriovenous thrombosis including acute coronary syndrome. Thrombus burden in patients with acute coronary syndrome and hyperhomocysteinemia might involve the culprit lesion as compared with those without any coagulopathy. The primary percutaneous coronary intervention with stent implantation had been established as the treatment strategy for patients with acute coronary syndrome. However, in patients with acute coronary syndrome with high thrombus burden or uncontrolled coagulopathy, stent implantation might lead to slow-flow phenomenon or stent thrombosis. Therefore, the treatment strategy in these patients was not established. Case presentation A 49-year-old Japanese man with history of splenic infarction of unknown cause had continued anticoagulant therapy since its diagnosis, but stopped taking the medication several months ago. He presented with sudden-onset chest dorsalgia. Contrast computed tomography showed a small pulmonary embolism and his troponin I level was elevated on initial laboratory test. Coronary angiography revealed a contrast defect caused by a large thrombus from the proximal to mid portion of the left anterior descending artery. Near-infrared spectroscopy–intravascular ultrasonography showed a large amount of thrombus without lipid plaque. Therefore, revascularization was performed using a thrombus-aspiration catheter and intracoronary thrombolysis. In addition, , hyperhomocysteinemia and a deep vein thrombosis occurred. He was diagnosed with acute coronary syndrome complicated with pulmonary embolism and deep vein thrombosis simultaneously induced by hyperhomocysteinemia. After 1 week of antithrombotic therapy, near-infrared spectroscopy–intravascular ultrasonography and optical coherence tomography revealed a decreased thrombus and no significant residual organic stenosis in the left anterior descending artery. He continued conservative therapy with antithrombotic medications including aspirin and warfarin and had no cardiovascular events after discharge. Follow-up coronary angiography and optical coherence tomography at 9 months revealed complete disappearance of the thrombus and no severe stenosis. Conclusions Hyperhomocysteinemia should be considered as a cause of arterial vein thrombosis of unknown cause. The antithrombotic therapy and percutaneous revascularization without stenting based on intravascular imaging might be a safe and effective treatment option in patients with acute coronary syndrome complicated with hyperhomocysteinemia.

Background and purpose In acute coronary syndrome (ACS) patients, major cardiovascular events during follow-up were equally attributable to recurrence at the site of culprit lesions and to non-culprit lesions, and mostly occurred within one year. Recent studies showed that Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor significantly reduces the risk of cardiovascular events. However, the rigorous effects of PCSK9 inhibitor in patients with ACS, especially for the stabilization of plaque in the non-culprit lesions has not been identified. The purpose of this study was to evaluate the efficacy of a PCSK9 inhibitor for the plaque stabilization in the non-culprit lesion of ACS patients. Methods We retrospectively analyzed the 10 ACS patients (STEMI:5 cases, NSTEMI:1 case, and UAP:4 cases) who had non-culprit lesions and were injected with a PCSK9 inhibitor. We analyzed 11 non-culprit lesions before and after PSCK9 injections by using a near-infrared intravascular ultrasonography (NIRS-IVUS). Results The follow up intervals were 229.4±82.9 days. Major cardiovascular events did not occur in all patients. The serum low-density lipoprotein (LDL) cholesterol levels were significantly decreased form 128±36.7 mg/dl to 26.7±7.4 mg/dl (P Conclusion This study suggested that the plaque morphology can be altered by the aggressive lipid lowering therapy by using a PCSK9 inhibitor, and NIRS-IVUS can detect these plaque stabilizations of non-culprit lesion in ACS patients. The authors have no financial conflicts of interest to disclose concerning the presentation. Figure 1 Funding Acknowledgement Type of funding source: None

Background Transcatheter aortic valve replacement (TAVR) has emerged as an important therapeutic option among intermediate- and high-risk patients with symptomatic severe aortic stenosis. Heart rhythm disorders frequently complicate TAVR, particularly atrial fibrillation (AF), which can affect >40% patients undergoing the procedure. There is wide variation in rates of new-onset AF (NOAF) following TAVR across the initial pivotal randomized trials and observational studies, but burden of AF in each patient is not well known. The aim of this study is to evaluate AF burden detected by continuous patch ECG monitor (WR-100; Fukuda-Denshi, Tokyo,Japan) in patients after TAVR. Method Among KPUM-TAVR cohort, 58 consecutive patients (mean age:85.5±5.5, 44 females) kept recording continuous patch ECG monitor for 14 days after the procedure of TAVR. We excluded 11 patients with ECG indicating AF before procedure (paroxysmal AF 5, persistent AF 6). Finally, 47 eligible patients were selected according to the study criteria. AF was defined as a presence of AF more than 30sec on ECG monitor. The incidence and burden of NOAF was assessed. Results We identified 9 of 47 patients (19.1%) who developed NOAF (94% of transfemoral access patients, 6% of non- transfemoral access patients). Patients developing NOAF and had higher Society of Thoracic Surgeons risk scores (5.9±3.8 vs 9.9±6.3 p=0.0187). AF was first observed from day1 to day13. Despite having a median CHA2DS2-VASc score of 5 (25th and 75th percentile: 5 to 6), only 33% of patients with NOAF were given oral anticoagulation during the follow-up. Conclusion By using continuous patch ECG monitor, NOAF can be identified in 19.1% of patients after TAVR, with wide variety of first onset of AF. Given the clinical significance of post-TAVR AF, additional studies are necessary to describe the optimal management strategy in this high-risk population. Figure 1 Funding Acknowledgement Type of funding source: None

Background and objective Maternal high-fat diet (HFD) has been shown to modulate vascular function and remodeling in adult offspring. Here, we investigated the impact of maternal HFD on abdominal aortic aneurysm (AAA) formation. Methods and results Eight-week-old female wild-type mice (C57BL/6) were fed a HFD or normal diet (ND) one week prior to mating, and the diet was continued throughout gestation and lactation. In eight-week-old male offspring, AAA was induced with the application of 0.5 M calcium chloride (CaCl2) on the infrarenal aorta. Offspring of HFD-fed dams (O-HFD) showed a significant increase in maximum outer diameter of AAA at 1, 4 and 8 weeks after surgery compared with offspring of ND-fed dams (O-ND). The lengths of outer circumference assessed by histological analysis were increased in O-HFD (p Conclusion Our findings demonstrate that maternal HFD accelerates CaCl2-induced AAA expansion, accompanied by the exaggerated accumulation of osteoclast-like macrophages and augmented activity of MMPs. Inhibition of macrophages skewing toward osteoclast-like cells could be a potential therapeutic target for preventing AAA development. Funding Acknowledgement Type of funding source: None

Background Abdominal aortic aneurysm (AAA) is a common and life-threatening vascular disease. The initial phase of AAA progression is vascular inflammation. Inflammation sites present adhesion molecules, such as vascular cell adhesion molecule-1 (VCAM-1) and intracellular cell adhesion molecule-1 (ICAM-1). These molecules play a crucial role in recruiting inflammatory cells to endothelial cells through NF-κB signaling. Endothelial cells express serum deprivation response (SDPR)/Cavin-2 localized in caveolae on the cell membrane. Although Cavin-2 is involved in such as cell proliferation, migration, and signal transduction, the role of Cavin-2 in vascular inflammation in the development of AAA is still unclear. Purpose To assess the influence of Cavin-2 deficiency in AAA development and clarify the role of Cavin-2 in the regulation of inflammatory cell adhesion in endothelial cells. Methods CaCl2-induced AAAs were induced by the periaortic application of 0.5 M CaCl2 in male SDPR-knockout (KO) and wild-type (WT) mice at 8–10 weeks of age. Angiotensin II (Ang II)-induced AAAs were created by 4-week-subcutaneous drug infusion in male ApoE-KO and ApoE/Cavin-2-double KO (DKO) mice at 24 weeks of age. Inflammatory response and cell adhesion were evaluated using human aortic endothelial cells (HAECs) and human monocytes (THP-1 cells). Results Six weeks after CaCl2 treatment, Cavin-2 deficiency significantly attenuated the development of AAAs. Elastin degradation was markedly suppressed and F4/80-positive macrophages infiltration in aortic walls were decreased in Cavin-2-KO mice. Although Ang II infusion for 4 weeks formed AAAs in ApoE KO mice and ApoE/Cavin-2-DKO mice, ApoE/Cavin-2-DKO mice exhibited the suppression of AAA formation independently of blood pressure. Immunohistochemical staining showed VCAM-1 expression on endothelial cells was suppressed in ApoE/Cavin-2-DKO mice. Further, in vitro co-culture experiment, the number of THP-1 cells adhered to TNF-treated SDPR-knockdown HAECs was decreased compared with that to control HAECs. Moreover, mRNA expression of VCAM-1 and ICAM-1 was decreased in TNFα-treated SDPR-knockdown HAECSs. Protein expression of VCAM-1 was also suppressed in TNFα-treated SDPR-knockdown HAECSs. The activity of NF-κB p65, an upstream regulator of VCAM-1 and ICAM-1,tended to be suppressed in TNFα-treated SDPR-knockdown HAECs. Conclusion In this study, we revealed that SDPR/Cavin-2 loss attenuated AAA development with the suppression of elastin degradation and macrophage infiltration. Our findings suggest that SDPR/Cavin-2 in the endothelial cells regulates the expression of adhesion molecules via NF-κB signaling and promotes the adhesion and infiltration of inflammatory cells to the aortic wall. Funding Acknowledgement Type of funding source: None