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Original Article, Introduction: In recent years, rather than surgically replacing the aortic valve, transcatheter aortic valve implantation (TAVI) has been performed. This study aimed to evaluate the morphological dynamic changes in the aortic annulus and sinotubular junction (STJ) using 4D-computed tomography (CT) voxel tracking in TAVI candidates. Methods: We enrolled 75 consecutive patients with aortic stenosis (AS) and 42 controls who underwent cardiac CT. Scans were performed using spiral acquisition with retrospective electrocardiogram-gated image reconstruction. We used motion coherence image processing, which performs deformable registration to track all voxels throughout multiple phases and interpolates images between phases to generate new phases. Using voxel tracking technology, we constructed a time-area curve and time-circumference length curve for the aortic annulus and STJ, respectively. From these curves, we determined the peak and nadir values of the area and circumference length during one cardiac cycle. Results: There was no significant difference between the AS and control groups regarding the area size, but the circumference length was significantly greater in the AS group than in the controls (p < 0.001). The phase with the largest area was significantly slower in the AS group than in the controls (p = 0.005). In both groups, the changes in area and circumference length were greater in the aortic annulus than in the STJ (p < 0.001). Conclusions: Dilatability during the cardiac cycle is different between the aortic annulus and the STJ. Additionally, the phase during which the aortic annulus area is maximum occurs later than normal in patients with AS.

Background: The comparative tolerability, efficacy, and safety of bisoprolol and carvedilol have not been established in Japanese patients with heart failure and reduced ejection fraction (HFrEF). Methods and Results: The CIBIS-J trial is a multicenter, open-label, non-inferiority randomized controlled trial of bisoprolol vs. carvedilol in 217 patients with HFrEF (EF

Background Relapses frequently occur in giant cell arteritis (GCA), and long-term glucocorticoid therapy is required. The identification of associated factors with poor treatment outcomes is important to decide the treatment algorithm of GCA. Methods We enrolled 139 newly diagnosed GCA patients treated with glucocorticoids between 2007 and 2014 in a retrospective, multi-center registry. Patients were diagnosed with temporal artery biopsy, 1990 American College of Rheumatology classification criteria, or large vessel lesions (LVLs) detected by imaging based on the modified classification criteria. Poor treatment outcomes (non-achievement of clinical remission by week 24 or relapse during 52 weeks) were evaluated. Clinical remission was defined as the absence of clinical signs and symptoms in cranial and large vessel areas, polymyalgia rheumatica (PMR), and elevation of C-reactive protein (CRP) levels. A patient was determined to have a relapse if he/she had either one of the signs and symptoms that newly appeared or worsened after achieving clinical remission. Re-elevation of CRP without clinical manifestations was considered as a relapse if other causes such as infection were excluded and the treatment was intensified. Associated factors with poor treatment outcomes were analyzed by using the Cox proportional hazard model. Results Cranial lesions, PMR, and LVLs were detected in 77.7%, 41.7%, and 52.5% of the enrolled patients, respectively. Treatment outcomes were evaluated in 119 newly diagnosed patients who were observed for 24 weeks or longer. The mean initial dose of prednisolone was 0.76 mg/kg/day, and 29.4% received any concomitant immunosuppressive drugs at baseline. Overall, 41 (34.5%) of the 119 patients had poor treatment outcomes; 13 did not achieve clinical remission by week 24, and 28 had a relapse after achieving clinical remission. Cumulative rates of the events of poor treatment outcomes in patients with and without LVLs were 47.5% and 17.7%, respectively. A multivariable model showed the presence of LVLs at baseline was significantly associated with poor treatment outcomes (adjusted hazard ratio [HR] 3.54, 95% CI 1.52–8.24, p = 0.003). Cranial lesions and PMR did not increase the risk of poor treatment outcomes. Conclusion The initial treatment intensity in the treatment algorithm of GCA could be determined based upon the presence or absence of LVLs detected by imaging at baseline.

Additional file 1: Table S1. Participation rate and dropout rate according to road distance and required time.

Takayasu arteritis (TAK) is classified as large-vessel vasculitis caused by inflammation. It is often difficult to identify on clinical examination, and (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) plays an indispensable role in diagnosing TAK by detecting the location and grade of the inflammatory lesions. The clinical utility of (18)F-FDG PET has been established by clinical evidence, and (18)F-FDG PET was added to the Japanese national health insurance listing in April 2018. In TAK, (18)F-FDG uptake shows typical findings and is easily distinguished, except from physiological uptake. Particularly, the clinical significance of (18)F-FDG PET is that can present not only with stenosis but also without stenosis in the arteries, which means that therapeutic intervention is possible before irreversible stenosis develops in the arteries. Additionally, (18)F-FDG PET has superior diagnostic accuracy because it allows quantitative analysis using the maximum standardized uptake value. The analysis is used for the assessment of disease activity of TAK and can be utilized for therapeutic intervention in case of repeating remission during the follow-up term.

Additional file 1. Supplementary tables.

We have previously reported that hypertrophic stimuli induce the expression of cyclinD1 and CDK4 in cardiomyocytes, and that overexpression of cyclin D1 and CDK4 causes hypertrophic change. Recently, it is reported that pTEFb (CDK9 and cyclinT) is involved in cardiac hypertrophy through phosphorylation of the RNA polymerase Ⅱ C-terminal domain (pol Ⅱ CTD), promoting transcript elongation by Pol Ⅱ. We assessed the hypothesis that cyclinD1/CDK4 induce hypertrophy through phosphorylation of pol Ⅱ CTD in cultured neonatal rat cardiomyocytes. In this study, we examined whether the overexpression of cyclinD1/CDK4 induces hypertrophy by using［3H］ leucine incorpolation assay. CyclinD1/CDK4 overexpression increased the rate of protein synthesis by 1.55 fold, compared to those in LacZ-overexpressed cells. Further, we assayed the rate of RNA synthesis by［3H］uridine incorpolation. Results showed that CyclinD1/CDK4 cells increased the rate of RNA synthesis compared to the control cells (1.57 fold).Finally, we examined whether phophorylation of pol Ⅱ CTD is involved in cyclinD1/CDK4-induced hypertrophy. DRB, a chemical antagonist of pol Ⅱ CTD phosphorylation, decreased the rate of incorporation of［3H］leucine and uridine in cyclinD1/CDK4 cells. These data altogether suggest that cyclinD1/CDK4 activates Pol Ⅱ transcription through inducing CTD phosphorylation and is involved in cardiac hypertrophy.

Heart transplantation has been broadly performed in humans. However, occurrence of acute and chronic rejection has not yet been resolved. Several inflammatory factors, such as cytokines and adhesion molecules, enhance the rejection. The graft arterial disease (GAD), which is a type of chronic rejection, is characterized by intimal thickening comprised of proliferative smooth muscle cells. Specific treatments that target the attenuation of acute rejection and GAD formation have not been well studied in cardiac transplantation. Recent progress in the nucleic acid drugs, such as antisense oligodeoxynucleotides (ODNs) to regulate the transcription of disease-related genes, has important roles in therapeutic applications. Transfection of cis-element double-stranded DNA, named as “decoy,” has been also reported to be a useful nucleic acid drug. This decoy strategy has been not only a useful method for the experimental studies of gene regulation but also a novel clinical strategy. In this paper, we reviewed the experimental results of NF-κB, E2F, AP-1, and STAT-1 decoy and other ODNs using the experimental heart transplant models.

Tea polyphenols known as catechins are key components with many biological functions, including anti-inflammatory, antioxidative, and anticarcinogenic effects. These effects are induced by the suppression of several inflammatory factors including nuclear factor-kappa B (NF- 𝜅 B). While these characteristics of catechins have been well documented, actions of catechins as mediators on inflammation-related cardiovascular diseases have not yet been well investigated. In this article, we reviewed recent papers to reveal the anti-inflammatory effects of catechins in cardiovascular diseases. In our laboratory, we performed oral administration of catechins into murine and rat models of cardiac transplantation, myocarditis, myocardial ischemia, and atherosclerosis to reveal the effects of catechins on the inflammation-induced ventricular and arterial remodeling. From our results, catechins are potent agents for the treatment and prevention of inflammation-related cardiovascular diseases because they are critically involved in the suppression of proinflammatory signaling pathways.

Background Recent epidemiologic evidence suggests that periodontal infection may increase the risk of atherosclerosis and acute thromboembolic events. The present study investigated the contribution of the major periodontal pathogen, Actinobacillus actinomycetemcomitans (A.a.), on myocardial inflammation and injury after ischaemia-reperfusion (I/R). Methods and Results Male C57Bl/6J mice were subjected to 30 min of coronary ligation, followed by 7 days of reperfusion. Either live A.a. (10 8 CFU) or saline was administered intravenously for 2 days before surgery. A.a.-challenged mice showed significantly larger infarction (53%±6%) compared with control mice (36%±3%) (p Conclusion Taken together, these data demonstrate that systemic challenge with A. Actinomycetemcomitans, a major periodontal pathogen, may exacerbate myocardial ischaemia/reperfusion injury.

Background: The purpose of this study was to investigate the effect of angiotensin II type 1-receptor antagonist telmisartan on ventricular remodeling in post-infarcted myocardium of rat. Methods: Myocardial infarction (MI) was produced by ligation of the left anterior coronary artery. Telmisartan at 1mg/kg/day was given orally 24 hours after MI. At 4 weeks after MI, we analyzed the difference of cardiac function by Doppler echocardiography, serum BNP concentration, cardiac fibrosis, and metalloproteinase (MMP) activation in non-infarcted myocardial region between the control (MI only) and the telmisartan-treated group. Results: Treatment with telmisartan improved the survival rate significantly compared to the control group. Improved left ventricular (LV) remodeling and dysfunction, as indicated by the smaller LV cavity and heart/body weight ratio, greater fractional shortening and E/A ratio, lower serum BNP concentration, were observed in the telmisartan-treated rats. Although the infarct size was similar in both groups, non-infarcted wall was thinner in telmisartan-treated hearts accompanied by the reduction of cardiac myocyte hypertrophy. Furthermore, cardiac fibrotic change and MMP2, 9 activations, detected by gelatin zymograhy, were inhibited remarkably by treatment with telmisartan. Conclusion: Telmisartan, angiotensin II type 1-receptor antagonist, prevented the adverse cardiac remodeling through the reduction of cardiac hypertrophic change and fibrosis.

Objective: CC chemokine receptor-1 (CCR-1) is bound to CC chemokine and is expressed on T lymphocytes. We examined the role of CCR1 in myocarditis using CCR1 antagonist, BX471. Methods: Lewis rats were immunized with cardiac myosin to establish experimental autoimmune myocarditis (EAM) on day 0. Rats were administered subcutaneously with CCR-1 antagonist from day 0 (group BX0) or from day 14 (group BX14) daily and were sacrificed on day 21 (each group: n = 6). Results: We confirmed the expression of CCR1 in heart inflammatory cells using immunohistochemical study. Myocarditis-affected areas in the treated groups were lower than controls. Cardiac function in the treated group improved. (group BX0 or group BX14 vs controls: area ratio; 1.0 ± 1.1%vs51.8 ± 8.3% or 11.8 ± 2.9%vs52.4 ± 9.3%, FS; 46.7 ± 3.6%vs20.8 ± 2.6% or 39.4 ± 4.1%vs22.0 ± 5.9%, respectively P

ObjectivesThe aim of this study was to investigate whether the maximum standardized uptake value (max SUV) of 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) provides a quantitative indication of disease activity in Takayasu arteritis (TA) cases.BackgroundThe clinical value of FDG-PET for assessing TA has been investigated. Clinical evaluation of disease activity is often difficult, because most patients develop recurrent inflammation while receiving corticosteroid treatment.MethodsThirty-nine TA patients underwent FDG-PET/CT at Tokyo Medical and Dental University from 2006 to 2010 (35 women and 4 men; median age, 30 years). Disease activity was defined according to National Institutes of Health criteria. Biomarkers including C-reactive protein and erythrocyte sedimentation rate were measured. Forty subjects without vasculitis served as control subjects.ResultsThe max SUV was significantly higher in active than in inactive cases and control subjects (active [n = 27], median value, 2.7 vs. inactive [n = 12], 1.9; control [n = 40], 1.8; p < 0.001 each). Given a max SUV cutoff of 2.1, sensitivity for active-phase TA was 92.6%, specificity 91.7%, positive predictive value 96.2%, and negative predictive value 84.6%. In receiver-operating characteristic curves comparison, max SUV was superior to C-reactive protein (p < 0.05) and erythrocyte sedimentation rate (p < 0.05). Max SUV was significantly higher in relapsing on treatment cases (n = 17) than in stable on treatment cases (n = 12) (median value, 2.6 vs. 1.9; p < 0.001).ConclusionsFDG-PET/CT is useful for detection of active inflammation not only in patients with active TA before treatment but also in relapsing patients receiving immunosuppressive agents. The max SUV is useful for assessing subtle activity of TA with high sensitivity.