Publications by authors named "Masataka Sata"

466 Publications

How to standardize the measurement of left ventricular ejection fraction.

J Med Ultrason (2001) 2021 Jul 28. Epub 2021 Jul 28.

Department of Cardiovascular Medicine, Tokushima University Hospital, 2-50-1 Kuramoto, Tokushima, Japan.

Despite recent advances in imaging for myocardial deformation, left ventricular ejection fraction (LVEF) is still the most important index for systolic function in daily practice. Its role in multiple fields (e.g., valvular heart disease, myocardial infarction, cancer therapy-related cardiac dysfunction) has been a mainstay in guidelines. In addition, assessment of LVEF is vital to clinical decision-making in patients with heart failure. However, notable limitations to LVEF include poor inter-observer reproducibility dependent on observer skill, poor acoustic windows, and variations in measurement techniques. To solve these problems, methods for standardization of LVEF by sharing reference images among observers and artificial intelligence for accurate measurements have been developed. In this review, we focus on the standardization of LVEF using reference images and automated LVEF using artificial intelligence.
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http://dx.doi.org/10.1007/s10396-021-01116-zDOI Listing
July 2021

Emerging Roles of the Innate Immune System Regulated by DNA Sensors in the Development of Vascular and Metabolic Diseases.

J Atheroscler Thromb 2021 Jul 12. Epub 2021 Jul 12.

Department of Cardiovascular Medicine, Tokushima University Graduate School of Biomedical Sciences.

Sterile chronic inflammation causes cardiometabolic disorders; however, the mechanisms are not fully understood. Previous studies have demonstrated the degradation of cells/tissues in the vasculature and metabolic organs in lifestyle-associated diseases, such as diabetes and hyperlipidemia, suggesting the release and/or accumulation of nucleic acids from damaged cells. DNA is indispensable for life; however, DNA fragments, especially those from pathogens, strongly induce inflammation by the activation of DNA sensors. Growing evidence suggests that DNA-sensing mechanisms, which are normally involved in self-defense against pathogens as the innate immune system, are associated with the progression of inflammatory diseases in response to endogenous DNA fragments. There are several types of DNA sensors in our bodies. Toll-like receptor 9 (TLR9)-one of the most studied DNA sensors-recognizes DNA fragments in endosome. In addition, stimulator of interferon genes (STING), which has recently been extensively investigated, recognizes cyclic GMP-AMP (cGAMP) generated from DNA fragments in the cytosol. Both TLR9 and STING are known to play pivotal roles in host defense as the innate immune system. However, recent studies have indicated that the activation of these DNA sensors in immune cells, such as macrophages, promotes inflammation leading to the development of vascular and metabolic diseases associated with lifestyle. In this review, we discuss recent advances in determining the roles of DNA sensors in these disease contexts. Revealing a novel mechanism of sterile chronic inflammation regulated by DNA sensors might facilitate clinical interventions for these health conditions.
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http://dx.doi.org/10.5551/jat.RV17059DOI Listing
July 2021

Evaluation of the input site and characteristics of the antegrade fast pathway based on three-dimensional bi-atrial stimulus-ventricle mapping.

J Interv Card Electrophysiol 2021 Jul 7. Epub 2021 Jul 7.

Department of Cardiology, Tokushima University Hospital, 3-18-15 Kuramoto-cho, Tokushima City, Tokushima, 770-8501, Japan.

Purpose: Previous studies examined the right atrial (RA) input site of the antegrade fast pathway (AFp) (AFpI). However, the left atrial (LA) input to the atrioventricular (AV) node has not been extensively evaluated. In this study, we created three-dimensional (3-D) bi-atrial stimulus-ventricle (St-V) maps and analyzed the input site and characteristics of the AFp in both the RA and LA.

Methods: Forty-four patients diagnosed with atrial fibrillation or WPW syndrome were included in this study. Three-dimensional bi-atrial St-V mapping was performed using an electroanatomical mapping system. Sites exhibiting the minimal St-V interval (MinSt-V) were defined as AFpIs and were classified into seven segments, four in the RA (F, S, M, and I) and three in the LA (M1, M2, and M3). By combining the MinSt-V in the RA and LA, the AFpIs were classified into three types: RA, LA, and bi-atrial (BA) types. The clinical and electrophysiological characteristics were compared.

Results: AFpIs were most frequently observed at site S in the RA (34%) and M2 in the LA (50%), and the BA type was the most common (57%). AFpIs in the LA were recognized in 75% of the patients. There were no clinical or electrophysiological indicators for predicting AFpI sites.

Conclusions: Three-dimensional bi-atrial St-V maps could classify AFpIs in both the RA and LA. AFpIs in the LA were frequently recognized. There were no significant clinical or electrophysiological indicators for predicting AFpI sites, and 3-D bi-atrial St-V mapping was the only method to reveal the precise AFp input site.
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http://dx.doi.org/10.1007/s10840-021-01026-7DOI Listing
July 2021

STING, a cytosolic DNA sensor, plays a critical role in atherogenesis: a link between innate immunity and chronic inflammation caused by lifestyle-related diseases.

Eur Heart J 2021 Jul 6. Epub 2021 Jul 6.

Department of Cardiovascular Medicine, Tokushima University Graduate School of Biomedical Sciences, 3-18-15, Kuramoto-Cho, Tokushima 770-8503, Japan.

Aims : Lifestyle-related diseases promote atherosclerosis, a chronic inflammatory disease; however, the molecular mechanism remains largely unknown. Endogenous DNA fragments released under over-nutrient condition provoke sterile inflammation through the recognition by DNA sensors. Here, we investigated the role of stimulator of interferon genes (STING), a cytosolic DNA sensor, in atherogenesis.

Methods And Results : Apolipoprotein E-deficient (Apoe-/-) mice fed a western-type diet (WTD), a hypercholesterolaemic mouse model, showed higher STING expression and markers for DNA damage such as γH2AX, p53, and single-stranded DNA (ssDNA) accumulation in macrophages in the aorta compared with wild-type (WT) mice. The level of cGAMP, a STING agonist, in the aorta was higher in Apoe-/- mice. Genetic deletion of Sting in Apoe-/- mice reduced atherosclerotic lesions in the aortic arch, lipid, and macrophage accumulation in plaques, and inflammatory molecule expression in the aorta compared with the control. Pharmacological blockade of STING using a specific inhibitor, C-176, ameliorated atherogenesis in Apoe-/- mice. In contrast, bone marrow-specific STING expression in Apoe-/- mice stimulated atherogenesis. Expression or deletion of STING did not affect metabolic parameters and blood pressure. In vitro studies revealed that STING activation by cGAMP or mitochondrial DNA accelerated inflammatory molecule expression (e.g. TNF-α or IFN-β) in mouse and human macrophages. Activation of nuclear factor-κB and TANK binding kinase 1 was involved in STING-associated vascular inflammation and macrophage activation. Furthermore, human atherosclerotic lesions in the carotid arteries expressed STING and cGAMP.

Conclusion : Stimulator of interferon genes stimulates pro-inflammatory activation of macrophages, leading to the development of atherosclerosis. Stimulator of interferon genes signalling may serve as a potential therapeutic target for atherosclerosis.
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http://dx.doi.org/10.1093/eurheartj/ehab249DOI Listing
July 2021

Clinical Utility of Overlap Time for Incomplete Relaxation to Predict Cardiac Events in Heart Failure.

J Card Fail 2021 Jun 12. Epub 2021 Jun 12.

Department of Cardiovascular Medicine, Tokushima University Hospital.

Background: The overlap time of transmitral flow can be a novel marker of subclinical left ventricular dysfunction for predicting adverse events in heart failure (HF). We aimed to (1) investigate the role of overlap time of the E-A wave in association with clinical parameters and (2) evaluate whether the overlap time could add prognostic information with respect to other conventional clinical prognosticators in HF.

Methods: We prospectively evaluated 153 patients hospitalized with HF (mean age 68 ± 15 years; 63% male). The primary endpoint was readmission following HF or cardiac death.

Results: During a median period of 25 months, 43 patients were readmitted or died. Overlap time appeared to be associated with worse outcomes. After adjustment for readmission scores and ratios of diastolic filling period and cardiac cycle length in a Cox proportional-hazards model, overlap time was associated with event-free survival, independent of elevated left atrial pressure based on guidelines. When overlap time was added to the model based on clinical variables and elevated left atrial pressure, the C-statistic significantly improved from 0.70 (95% CI: 0.63-0.77) to 0.77 (95% CI: 0.69-0.83, compared) (P = 0.035).

Conclusion: This preliminary study suggested that prolonged overlap time may have potential for predicting readmission and cardiac mortality risk assessment in patients with HF.
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http://dx.doi.org/10.1016/j.cardfail.2021.05.018DOI Listing
June 2021

Predictive value of left atrial function for latent paroxysmal atrial fibrillation as the cause of embolic stroke of undetermined source.

J Cardiol 2021 Jun 9. Epub 2021 Jun 9.

Department of Cardiovascular Medicine, Tokushima University Hospital, Tokushima, Japan.

Background: In patients with embolic stroke of undetermined source (ESUS), paroxysmal atrial fibrillation (AF) is often diagnosed, however, the risk of paroxysmal AF in ESUS has not been well described. Several studies have suggested a linkage between left atrial (LA) functional parameters and risk of AF in stroke patients. The aim of this study was to assess the role of LA functional parameters as predictors of latent paroxysmal AF in ESUS on admission.

Methods: Between January 2015 and December 2019, consecutive stroke patients with suspected ESUS at admission were prospectively included in this study. They were under hospital electrocardiographic monitoring for detection of new-onset AF. Various echocardiographic parameters including left atrial strain were assessed for association with new-onset AF.

Results: We gathered 1082 consecutive patients with ischemic stroke. After exclusions, 121 patients with suspected ESUS at admission formed the study cohort. New-onset AF was detected in 46 (38%) patients during hospital electrocardiographic monitoring (median follow-up: 18 days). LA pump and reservoir strains were significantly and independently associated with new-onset AF. Receiver operating characteristic analysis for the association with new-onset AF showed that the areas under the curve (AUCs) of clinical parameters plus one of each strain (LA pump strain: AUC: 0.86±0.04 and LA reservoir strain: AUC: 0.76±0.05) models were significantly better than plus LA volume index (AUC: 0.68±0.04, compared p-values <0.05).

Conclusions: LA strain was significantly associated with new development of AF. Patients with impaired LA function at admission should be carefully monitored to find AF.
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http://dx.doi.org/10.1016/j.jjcc.2021.05.005DOI Listing
June 2021

Acute Hospital Mortality of Venous Thromboembolism in Patients With Cancer From Registry Data.

J Am Heart Assoc 2021 Jun 22;10(11):e019373. Epub 2021 May 22.

Department of Cardiovascular Medicine Tokushima University Hospital Tokushima Japan.

Background The prognosis of patients with cancer-venous thromboembolism (VTE) is not well known because of a lack of registry data. Moreover, there is also no knowledge on how specific types are related to prognosis. We sought to evaluate the clinical characteristics and outcomes of patients with cancer-associated VTE, compared with a matched cohort without cancer using real-world registry data of VTE. Methods and Results This study was based on the Diagnosis Procedure Combination database in the JROAD-DPC (Japanese Registry of All Cardiac and Vascular Diseases and the Diagnosis Procedure Combination). Of 5 106 151 total patients included in JROAD-DPC, we identified 49 580 patients who were first hospitalized with VTE from April 2012 to March 2017. Propensity score was estimated with a logistic regression model, with cancer as the dependent variable and 18 clinically relevant covariates. After propensity matching, there were 25 148 patients with VTE with or without cancer. On propensity score-matched analysis with 25 148 patients with VTE, patients with cancer had higher total in-hospital mortality within 7 days (1.3% versus 1.1%, odds ratio [OR], 1.66; 95% CI, 1.31-2.11; <0.0001), 14 days (2.5% versus 1.5%, OR, 2.07; 95% CI, 1.72-2.49; <0.0001), and 30 days (4.8% versus 2.0%, OR, 2.85; 95% CI, 2.45-3.31; <0.0001). On analysis for each type of cancer, in-hospital mortality in 11 types of cancer was significantly high, especially pancreas (OR, 12.96; 95% CI, 6.41-26.20), biliary tract (OR, 8.67; 95% CI, 3.00-25.03), and liver (OR, 7.31; 95% CI, 3.05-17.50). Conclusions Patients with cancer had a higher in-hospital acute mortality for VTE than those without cancer, especially in pancreatic, biliary tract, and liver cancers.
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http://dx.doi.org/10.1161/JAHA.120.019373DOI Listing
June 2021

Congenital Hypogonadotropic Hypogonadism with Early-Onset Coronary Artery Disease.

J Med Invest 2021 ;68(1.2):189-191

Department of Cardiovascular Medicine, Tokushima University Hospital, Tokushima, Japan.

The patient with congenital hypogonadotropic hypogonadism (HH) shows low serum levels of androgen, which is a group of sex hormones including testosterone, caused by the decreased gonadotropin release in the hypothalamus. Recent reports showed androgens exert protective effects against insulin resistance or atherosclerotic diseases, such as diabetes mellitus or coronary artery disease. However, whether the juvenile hypogonadism affects the diabetes or cardiovascular disease is unclear. We report a case of a middle-aged man with congenital HH who had severe coronary artery disease complicated with metabolic disorders. J. Med. Invest. 68 : 189-191, February, 2021.
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http://dx.doi.org/10.2152/jmi.68.189DOI Listing
January 2021

Infective Endocarditis from Furuncle with Meningitis Complication Caused by Methicillin-resistant Staphylococcus aureus.

Intern Med 2021 Apr 19. Epub 2021 Apr 19.

Department of Cardiovascular Medicine, Tokushima University Graduate School of Biomedical Sciences, Japan.

Infective endocarditis (IE) may be acquired in the community as community-acquired (CA) IE or in the healthcare setting. In Japan, cases of CA-methicillin-resistant Staphylococcus aureus (MRSA) infection as skin infection have been increasing. CA-MRSA strains, including the USA300 clone, have higher pathogenicity and are more destructive to tissue than healthcare-associated MRSA strains because of the toxins they produce, including arginine-catabolic mobile element (ACME) and Panton-Valentine leukocidin (PVL). However, only a few IE cases induced by USA300 have been reported. We herein report a 64-year-old man who developed CA-IE from a furuncle caused by USA300 MRSA producing PVL and ACME, which resulted in complications of meningitis.
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http://dx.doi.org/10.2169/internalmedicine.6902-20DOI Listing
April 2021

Left Atrial Strain Associated with Functional Recovery in Patients Receiving Optimal Treatment for Heart Failure.

J Am Soc Echocardiogr 2021 Apr 20. Epub 2021 Apr 20.

Department of Cardiovascular Medicine, Tokushima University Hospital, Tokushima, Japan.

Background: Heart failure with recovered ejection fraction (HFrecEF) has been reported in several previous studies to have a better prognosis than heart failure with reduced ejection fraction (HFrEF). However, the factors associated with HFrecEF have not been identified. The aim of this study was to test the hypothesis that left atrial (LA) strain could help identify patients with recovered ejection fraction (EF) among those with heart failure (HF) with low EF on admission.

Methods: One hundred consecutive patients hospitalized for the first time for new-onset HF were enrolled. Patients were clinically diagnosed with HFrEF on admission (left ventricular EF < 40%) and received optimal treatment for HF. Twenty-eight patients improved to HFrecEF during 6 months of follow-up.

Results: Regarding clinical background, there were significantly more women and a lower rate of atrial fibrillation in the HFrecEF group than in the HFrEF group. In a multivariate logistic regression analysis, LA strain was an independent predictor of HFrecEF, even after adjustment for gender and left ventricular EF (odds ratio: 4.06; 95% CI: 2.04-8.07; P < .001). A cutoff value of 10.8% for LA strain showed high sensitivity (96%) and specificity (82%) in identifying HFrecEF in patients with HF presenting with low EF on admission. During a follow-up period of 24 ± 13 months, 31 patients (31%) had cardiovascular death or readmission for HF. Patients with reduced LA strain (<10.8%) had significantly shorter event-free survival than those with preserved LA strain (P = .02).

Conclusions: LA strain is a useful indicator for predicting HFrecEF and should be considered as a routine measurement in patients with HFrEF on admission.
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http://dx.doi.org/10.1016/j.echo.2021.03.016DOI Listing
April 2021

Regional Variations of Insulin Secretion and Insulin Sensitivity in Japanese Participants With Normal Glucose Tolerance.

Front Nutr 2021 22;8:632422. Epub 2021 Mar 22.

Department of Diabetes, Endocrinology and Metabolism, School of Medicine, Fukushima Medical University, Fukushima, Japan.

Regional differences in dietary patterns in Asian countries might affect the balance of insulin response and sensitivity. However, this notion is yet to be validated. To clarify the regional differences in the insulin response and sensitivity and their relationship to nutrients, we compared the insulin secretory response during an oral glucose tolerance test in Japanese participants. This observational retrospective cohort study analyzed the data from participants with normal glucose tolerance (NGT) from four distinct areas of Japan with regard to the food environment: Fukushima, Nagano, Tokushima, and Okinawa based on data available in the Japanese National Health Insurance database. Although the glucose levels were comparable among the four regions, the insulin responses were significantly different among the regions. This difference was observed even within the same BMI category. The plot between the insulin sensitivity index (Matsuda index) and insulin/glucose or the insulinogenic index showed hyperbolic relationships with variations in regions. The indices of insulin secretion correlated positively with fat intake and negatively with the intake of fish, carbohydrate calories, and dietary fiber. We found that significant regional differences in insulin response and insulin sensitivity in Japanese participants and that nutritional factors may be linked to these differences independently of body size/adiposity. Insulin response and insulin sensitivity can vary among adult individuals, even within the same race and the same country, and are likely affected by environmental/lifestyle factors as well as genetic traits.
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http://dx.doi.org/10.3389/fnut.2021.632422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019818PMC
March 2021

Frontiers of inflammatory disease research: inflammation in cardiovascular-cerebral diseases.

Inflamm Regen 2021 Mar 29;41(1):10. Epub 2021 Mar 29.

Department of Cardiovascular Medicine, Tokushima University Graduate School of Biomedical Sciences, 3-18-15, Kuramoto-Cho, Tokushima, 770-8503, Japan.

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http://dx.doi.org/10.1186/s41232-021-00160-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008555PMC
March 2021

Pemafibrate, A Novel Selective Peroxisome Proliferator-Activated Receptor α Modulator, Reduces Plasma Eicosanoid Levels and Ameliorates Endothelial Dysfunction in Diabetic Mice.

J Atheroscler Thromb 2021 Mar 27. Epub 2021 Mar 27.

Department of Cardiovascular Medicine, Tokushima University Graduate School of Biomedical Sciences.

Aims: Various pathological processes related to diabetes cause endothelial dysfunction. Eicosanoids derived from arachidonic acid (AA) have roles in vascular regulation. Fibrates have recently been shown to attenuate vascular complications in diabetics. Here we examined the effects of pemafibrate, a selective peroxisome proliferator-activated receptor α modulator, on plasma eicosanoid levels and endothelial function in diabetic mice.

Methods: Diabetes was induced in 7-week-old male wild-type mice by a single injection of streptozotocin (150 mg/kg). Pemafibrate (0.3 mg/kg/day) was administered orally for 3 weeks. Untreated mice received vehicle. Circulating levels of eicosanoids and free fatty acids were measured using both gas and liquid chromatography-mass spectrometry. Endothelium-dependent and endothelium-independent vascular responses to acetylcholine and sodium nitroprusside, respectively, were analyzed.

Results: Pemafibrate reduced both triglyceride and non-high-density lipoprotein -cholesterol levels (P<0.01), without affecting body weight. It also decreased circulating levels of AA (P<0.001), thromboxane B (P<0.001), prostaglandin E, leukotriene B (P<0.05), and 5-hydroxyeicosatetraenoic acid (P<0.001), all of which were elevated by the induction of diabetes. In contrast, the plasma levels of 15-deoxy-Δ-prostaglandin J, which declined following diabetes induction, remained unaffected by pemafibrate treatment. In diabetic mice, pemafibrate decreased palmitic acid (PA) and stearic acid concentrations (P<0.05). Diabetes induction impaired endothelial function, whereas pemafibrate ameliorated it (P<0.001). The results of ex vivo experiments indicated that eicosanoids or PA impaired endothelial function.

Conclusion: Pemafibrate diminished the levels of vasoconstrictive eicosanoids and free fatty acids accompanied by a reduction of triglyceride. These effects may be associated with the improvement of endothelial function by pemafibrate in diabetic mice.
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http://dx.doi.org/10.5551/jat.61101DOI Listing
March 2021

Long-chain monounsaturated fatty acids improve endothelial function with altering microbial flora.

Transl Res 2021 Mar 26. Epub 2021 Mar 26.

Department of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan; Diabetes Therapeutics and Research Centre, Tokushima University, Tokushima, Japan. Electronic address:

Fish oil-derived long-chain monounsaturated fatty acids (LCMUFAs) with a carbon chain length longer than 18 units ameliorate cardiovascular risk in mice. In this study, we investigated whether LCMUFAs could improve endothelial functions in mice and humans. In a double-blind, randomized, placebo-controlled, parallel-group, multi-center study, healthy subjects were randomly assigned to either an LCMUFA oil (saury oil) or a control oil (olive and tuna oils) group. Sixty subjects were enrolled and administrated each oil for 4 weeks. For the animal study, ApoE mice were fed a Western diet supplemented with 3% of either gadoleic acid (C20:1) or cetoleic acid (C22:1) for 12 weeks. Participants from the LCMUFA group showed improvements in endothelial function and a lower trimethylamine-N-oxide level, which is a predictor of coronary artery disease. C20:1 and C22:1 oils significantly improved atherosclerotic lesions and plasma levels of several inflammatory cytokines, including IL-6 and TNF-α. These beneficial effects were consistent with an improvement in the gut microbiota environment, as evident from the decreased ratio of Firmicutes and/ or Bacteroidetes, increase in the abundance of Akkermansia, and upregulation of short-chain fatty acid (SCFA)-induced glucagon-like peptide-1 (GLP-1) expression and serum GLP-1 level. These data suggest that LCMUFAs alter the microbiota environment that stimulate the production of SCFAs, resulting in the induction of GLP-1 secretion. Fish oil-derived long-chain monounsaturated fatty acids might thus help to protect against cardiovascular disease.
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http://dx.doi.org/10.1016/j.trsl.2021.03.016DOI Listing
March 2021

Activated Factor X Signaling Pathway via Protease-Activated Receptor 2 Is a Novel Therapeutic Target for Preventing Atrial Fibrillation.

Circ J 2021 Jul 20;85(8):1383-1391. Epub 2021 Mar 20.

Department of Cardiovascular Medicine, Tokushima University Graduate School of Biomedical Sciences.

Background: Activated factor X (FXa), which contributes to chronic inflammation via protease-activated receptor 2 (PAR2), might play an important role in atrial fibrillation (AF) arrhythmogenesis. This study aimed to assess whether PAR2 signaling contributes to AF arrhythmogenesis and whether rivaroxaban ameliorates atrial inflammation and prevents AF.Methods and Results:In Study 1, PAR2 deficient (PAR2-/-) and wild-type mice were infused with angiotensin II (Ang II) or a vehicle via an osmotic minipump for 2 weeks. In Study 2, spontaneously hypertensive rats (SHRs) were treated with rivaroxaban, warfarin, or vehicle for 2 weeks after 8 h of right atrial rapid pacing. The AF inducibility and atrial remodeling in both studies were examined. Ang II-treated PAR2-/- mice had a lower incidence of AF and less mRNA expression of collagen1 and collagen3 in the atrium compared to wild-type mice treated with Ang II. Rivaroxaban significantly reduced AF inducibility compared with warfarin or vehicle. In SHRs treated with a vehicle, rapid atrial pacing promoted gene expression of inflammatory and fibrosis-related biomarkers in the atrium. Rivaroxaban, but not warfarin, significantly reduced expression levels of these genes.

Conclusions: The FXa-PAR2 signaling pathway might contribute to AF arrhythmogenesis associated with atrial inflammation. A direct FXa inhibitor, rivaroxaban, could prevent atrial inflammation and reduce AF inducibility, probably by inhibiting the pro-inflammatory activation.
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http://dx.doi.org/10.1253/circj.CJ-20-1006DOI Listing
July 2021

Diastolic Mitral Regurgitation on Color M-Mode Echocardiography in a Patient With Complete Atrioventricular Block.

Circ Rep 2020 Feb 20;2(3):207-208. Epub 2020 Feb 20.

Department of Cardiovascular Medicine, Tokushima University Hospital Tokushima Japan.

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http://dx.doi.org/10.1253/circrep.CR-20-0002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921352PMC
February 2020

Sirt7 Deficiency Attenuates Neointimal Formation Following Vascular Injury by Modulating Vascular Smooth Muscle Cell Proliferation.

Circ J 2021 Mar 5. Epub 2021 Mar 5.

Department of Cardiovascular Medicine, Faculty of Life Sciences, Kumamoto University.

Background: Sirt7 is a recently identified sirtuin and has important roles in various pathological conditions, including cancer progression and metabolic disorders. It has previously been reported that Sirt7 is a key molecule in acute myocardial wound healing and pressure overload-induced cardiac hypertrophy. In this study, the role of Sirt7 in neointimal formation after vascular injury is investigated.Methods and Results:Systemic (Sirt7) and smooth muscle cell-specific Sirt7-deficient mice were subjected to femoral artery wire injury. Primary vascular smooth muscle cells (VSMCs) were isolated from the aorta of wild type (WT) and Sirt7mice and their capacity for cell proliferation and migration was compared. Sirt7 expression was increased in vascular tissue at the sites of injury. Sirt7mice demonstrated significant reduction in neointimal formation compared to WT mice. In vitro, Sirt7 deficiency attenuated the proliferation of serum-induced VSMCs. Serum stimulation-induced upregulation of cyclins and cyclin-dependent-kinase 2 (CDK2) was significantly attenuated in VSMCs of Sirt7compared with WT mice. These changes were accompanied by enhanced expression of the microRNA 290-295 cluster, the translational negative regulator of CDK2, in VSMCs of Sirt7mice. It was confirmed that smooth muscle cell-specific Sirt7-deficient mice showed significant reduction in neointima compared with control mice.

Conclusions: Sirt7 deficiency attenuates neointimal formation after vascular injury. Given the predominant role in vascular neointimal formation, Sirt7 is a potentially suitable target for treatment of vascular diseases.
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http://dx.doi.org/10.1253/circj.CJ-20-0936DOI Listing
March 2021

Antegrade slow pathway mapping of typical atrioventricular nodal reentrant tachycardia based on direct slow pathway capture.

J Arrhythm 2021 Feb 24;37(1):128-139. Epub 2020 Dec 24.

Department of Cardiology Saitama Medical University International Medical Center Hidaka Japan.

Background: Radiofrequency (RF) ablation of typical atrioventricular nodal reentrant tachycardia (tAVNRT) is performed without revealing out the location of antegrade slow pathway (ASp). In this study, we studied a new electrophysiological method of identifying the site of ASp.

Methods: This study included 19 patients. Repeated series of very high-output single extrastimulations (VhoSESts) were delivered at the anatomical slow pathway region during tAVNRT. Tachycardia cycle length (TCL), coupling interval (CI), and return cycle (RC) were measured and the prematurity of VhoSESts [ΔPM (= TCL - CI)] and the prolongation of RCs [ΔPL (= RC - TCL)] were calculated. Pacing sites were classified into two categories: (i) ASp capture sites [DSPC(+) sites], where two different RCs were shown, and ASp non-capture sites [DSPC(-) sites], where only one RC was shown. RF ablation was performed at DSPC(+) sites and/or sites with catheter-induced mechanical trauma (CIMT) to ASp.

Results: DSPC(+) sites were shown in 13 patients (68%). RF ablation was successful in all patients without any degree of atrioventricular block nor recurrence. Total number of RF applications was 1.8 ± 1.1. Minimal distance between successful ablation sites and DSPC(+)/CIMT sites and His bundle (HB) electrogram recording sites was 1.9 ± 0.8 mm and 19.8 ± 6.1 mm, respectively. ΔPL of more than 92.5 ms, ΔPL/TCL of more than 0.286, and ΔPL/ΔPM of more than 1.565 could identify ASp with sensitivity of 100%, 91.1%, and 88.9% and specificity of 92.9%, 97.0%, and 97.6%, respectively.

Conclusions: Sites with ASp capture and CIMT were close to successful ablation sites and could be useful indicators of tAVNRT ablation.
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http://dx.doi.org/10.1002/joa3.12484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896471PMC
February 2021

Deep Learning for Detection of Elevated Pulmonary Artery Wedge Pressure Using Standard Chest X-Ray.

Can J Cardiol 2021 Feb 18. Epub 2021 Feb 18.

Ultrasound Examination Center, Tokushima University Hospital, Tokushima, Japan; Department of Cardiovascular Medicine, Tokushima University Hospital, Tokushima, Japan.

Background: To accurately diagnose and control heart failure (HF), it is important to carry out a simple assessment of elevated pulmonary arterial wedge pressure (PAWP). The aim of this study was to develop and validate an objective method for detecting elevated PAWP by applying deep learning (DL) to a chest x-ray (CXR).

Methods: We enrolled 1013 consecutive patients with a right-heart catheter between October 2009 and February 2020. We developed a convolutional neural network to identify patients with elevated PAWP (> 18 mm Hg) as the actual value of PAWP to be used in the dataset for training. In the prospective validation dataset used to detect elevated PAWP, the area under the receiver operating characteristic curve (AUC) was calculated using the DL model that evaluated the CXR.

Results: In the prospective validation dataset, the AUC of the DL model with CXR was not significantly different from the AUC produced by brain natriuretic peptide (BNP) and the echocardiographic left-ventricular diastolic dysfunction (DD) algorithm (DL model: 0.77 vs BNP: 0.77 vs DD algorithm: 0.70; respectively; P = NS for all comparisons); it was, however, significantly higher than the AUC of the cardiothoracic ratio (DL model vs cardiothoracic ratio [CTR]: 0.66, P = 0.044). The model based on 3 parameters (BNP, DD algorithm, and CTR) was improved by adding the DL model (AUC: from 0.80 to 0.86; P = 0.041).

Conclusions: Applying the DL model based on a CXR (a classical, universal, and low-cost test) is useful for screening for elevated PAWP.
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http://dx.doi.org/10.1016/j.cjca.2021.02.007DOI Listing
February 2021

Cardiac reserve by 6-minute walk stress echocardiography in systemic sclerosis.

Open Heart 2021 02;8(1)

Department of Cardiovascular Medicine, Tokushima University Hospital, Tokushima, Japan.

Objectives: There is a high prevalence of left ventricular diastolic dysfunction (LVDD) in systemic sclerosis (SSc) which is associated with high mortality. Thus, early detection of LVDD could be important in management of SSc. We hypothesised that exercise echocardiography in SSc patients with normal resting haemodynamics may expose early phase LVDD, which could affect its prognosis, defined as cardiovascular death and unplanned hospitalisation for heart failure.

Methods: Between January 2014 and December 2018, we prospectively enrolled 140 patients with SSc who underwent 6-minute walk (6MW) stress echocardiographic studies with normal range of estimated mean pulmonary arterial pressure (mPAP) (<25 mm Hg) and mean pulmonary artery wedge pressure (mPAWP) (<15 mm Hg) at rest. We used ΔmPAP/Δcardiac output (CO) to assess pulmonary vascular reserve and ΔmPAWP/ΔCO to assess LV cardiac reserve between resting and post-6MW.

Results: During a median period of 3.6 years (IQR 2.0-5.1 years), 25 patients (18%) reached the composite outcome. Both ΔmPAP/ΔCO and ΔmPAWP/ΔCO in patients with events were significantly greater than in those without events (8.9±3.8 mm Hg/L/min vs 3.0±1.7 mm Hg/L/min; p=0.002, and 2.2±0.9 mm Hg/L/min vs 0.9±0.5 mm Hg/L/min; p<0.001, respectively). Patients with both impaired LV cardiac reserve (ΔmPAWP/ΔCO>1.4 mm Hg/L/min) and impaired pulmonary vascular reserve (ΔmPAP/ΔCO>3.0 mm Hg/L/min) had worse outcomes compared with those without these abnormalities (p<0.001).

Conclusion: The 6MW stress echocardiography revealed impaired LV cardiac reserve in SSc patients with normal resting haemodynamics. Furthermore, LV cardiac reserve independently associates with clinical worsening in SSc, providing incremental prognostic utility, in addition to pulmonary vascular parameters.
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http://dx.doi.org/10.1136/openhrt-2020-001559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898855PMC
February 2021

Deleterious Effects of Epicardial Adipose Tissue Volume on Global Longitudinal Strain in Patients With Preserved Left Ventricular Ejection Fraction.

Front Cardiovasc Med 2020 15;7:607825. Epub 2021 Jan 15.

Department of Diabetes, Endocrinology and Metabolism, School of Medicine, Fukushima Medical University, Fukushima, Japan.

It is known that epicardial adipose tissue (EAT) volume is linked to cardiac dysfunction. However, it is unclear whether EAT volume (EATV) is closely linked to abnormal LV strain. We examined the relationship between EATV and global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) in patients with preserved LV function. Notably, 180 consecutive subjects (68 ± 12 years; 53% men) underwent 320-slice multi-detector computed tomography coronary angiography and were segregated into coronary artery disease (CAD) (≥1 coronary artery branch stenosis ≥50%) and non-CAD groups. GLS, GCS, and GRS were evaluated by 2-dimensional speckle tracking in patients with preserved left ventricular (LV) ejection fraction (LVEF) ≥50%. First, GLS, but not GRS and GCS, was lower in the high EATV group though the LVEF was comparable to the low EATV group. Frequency of GLS ≤18 was higher in the high EATV group. Second, multiple regression model showed that EATV, age, male sex, and CAD, were determinants of GLS. Third, the cutoff points of EATV were comparable (~116-117 mL) in both groups. The cutoff of EATV ≥116 showed a significant correlation with GLS ≤18 in overall subjects. Increasing EATV was independently associated with global longitudinal strain despite the preserved LVEF and lacking obstructive CAD. Our findings suggest an additional role of EAT on myocardial systolic function by impaired LV longitudinal strain.
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http://dx.doi.org/10.3389/fcvm.2020.607825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843424PMC
January 2021

Association between Vitamin D and Heart Failure Mortality in 10,974 Hospitalized Individuals.

Nutrients 2021 Jan 23;13(2). Epub 2021 Jan 23.

Department of Cardiovascular Medicine, Tokushima University Hospital, Tokushima 770-8503, Japan.

A broad range of chronic conditions, including heart failure (HF), have been associated with vitamin D deficiency. Existing clinical trials involving vitamin D supplementation in chronic HF patients have been inconclusive. We sought to evaluate the outcomes of patients with vitamin D supplementation, compared with a matched cohort using real-world big data of HF hospitalization. This study was based on the Diagnosis Procedure Combination database in the Japanese Registry of All Cardiac and Vascular Datasets (JROAD-DPC). After exclusion criteria, we identified 93,692 patients who were first hospitalized with HF between April 2012 and March 2017 (mean age was 79 ± 12 years, and 52.2% were male). Propensity score (PS) was estimated with logistic regression model, with vitamin D supplementation as the dependent variable and clinically relevant covariates. On PS-matched analysis with 10,974 patients, patients with vitamin D supplementation had lower total in-hospital mortality (6.5 vs. 9.4%, odds ratio: 0.67, < 0.001) and in-hospital mortality within 7 days and 30 days (0.9 vs. 2.5%, OR, 0.34, and 3.8 vs. 6.5%, OR: 0.56, both < 0.001). In the sub-group analysis, mortalities in patients with age < 75, diabetes, dyslipidemia, atrial arrhythmia, cancer, renin-angiotensin system blocker, and β-blocker were not affected by vitamin D supplementation. Patients with vitamin D supplementation had a lower in-hospital mortality for HF than patients without vitamin D supplementation in the propensity matched cohort. The identification of specific clinical characteristics in patients benefitting from vitamin D may be useful for determining targets of future randomized control trials.
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http://dx.doi.org/10.3390/nu13020335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911510PMC
January 2021

Effects of L-/N-Type Calcium Channel Blockers on Angiotensin II-Renin Feedback in Hypertensive Patients.

Int J Hypertens 2020 22;2020:6653851. Epub 2020 Dec 22.

Department of Cardiovascular Medicine, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.

Objectives: Cilnidipine, an L-/N-type calcium channel blocker (CCB), has unique organ-protective properties due to suppression of hyperactivity in the sympathetic nervous system and renin-angiotensin system (RAS). In this study, we hypothesized that cilnidipine might exert a renoprotective effect by suppressing the RAS.

Methods: A total of 25 hypertensive patients receiving a RAS inhibitor were randomly assigned to a cilnidipine ( = 12) or amlodipine ( = 13) group. The effects of cilnidipine on proteinuria and angiotensin II-renin feedback were assessed.

Results: After 6 months of treatment, both systolic and diastolic blood pressures were significantly reduced to a similar extent in both groups. The urine albumin-to-creatinine ratio was significantly lower in the cilnidipine group ( < 0.05) than in the amlodipine group. Amlodipine increased plasma angiotensin I and angiotensin II levels ( < 0.05), whereas cilnidipine did not. Interestingly, the cilnidipine group had a higher ratio of angiotensin-(1-7) (Ang-(1-7)) to angiotensin II in plasma than the amlodipine group ( < 0.05).

Conclusions: The L-/N-type CCB cilnidipine, but not amlodipine, decreased urinary albumin excretion in hypertensive patients. Cilnidipine also increased the ratio of Ang-(1-7) to angiotensin II in plasma, which might be one factor underlying its beneficial effects.
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http://dx.doi.org/10.1155/2020/6653851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803135PMC
December 2020

An Adult Case of Congenital Extrahepatic Portosystemic Shunt Successfully Treated with Balloon-occluded Retrograde Transvenous Obliteration.

Intern Med 2021 Jun 15;60(12):1839-1845. Epub 2021 Jan 15.

Department of Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, Japan.

A 42-year-old woman visited our hospital due to syncope. Contrast-enhanced CT revealed portosystemic shunt, portal vein hypoplasia, and multiple liver nodules. The histological examination of a liver biopsy specimen exhibited portal vein hypoplasia and revealed that the liver tumor was positive for glutamine synthetase. The patient was therefore diagnosed with congenital extrahepatic portosystemic shunt type II, and with focal nodular hyperplasia (FNH)-like nodules. She had the complication of severe portopulmonary hypertension and underwent complete shunt closure by balloon-occluded retrograde transvenous obliteration (B-RTO). The intrahepatic portal vein was well developed at 1 year after B-RTO, and multiple liver nodules completely regressed. Her pulmonary hypertension also improved.
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http://dx.doi.org/10.2169/internalmedicine.5914-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263181PMC
June 2021

Quantification of Carotid Plaque Histology Using iPlaque Software.

Ultrasound Med Biol 2021 04 3;47(4):928-931. Epub 2021 Jan 3.

Department of Cardiovascular Medicine, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan; Department of Community Medicine for Cardiology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.

The iPlaque software package can use integrated backscatter (IB) values of carotid plaque to extract information on tissue composition. The aim of this study was to evaluate the association between the plaque histologic classification and IB values evaluated by iPlaque. In 49 patients undergoing carotid endarterectomy, IB values of whole carotid plaque were measured using iPlaque from the long-axis ultrasonographic image. Histologic findings of resected plaques were defined using the classification of the American Heart Association. The average IB values were statistically compared with the classification. Plaque samples from 49 patients were categorized into V, VI and VII, (13, 32 and 4 cases, respectively). Both the average and standard deviation of the IB values in each plaque sample significantly differed among the three classifications (p = 0.001). The IB of carotid plaque obtained by iPlaque analysis was associated with its histologic characteristics.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2020.12.002DOI Listing
April 2021

Roles of Epicardial Adipose Tissue in the Pathogenesis of Coronary Atherosclerosis - An Update on Recent Findings.

Circ J 2020 12 1;85(1):2-8. Epub 2020 Dec 1.

Department of Cardiovascular Medicine, Tokushima University Graduate School of Biomedical Sciences.

Adipose tissue serves not only as an energy store or a mechanical cushion, but also as an endocrine organ. Recent evidence revealed that perivascular adipose tissue is involved in vascular homeostasis and pathophysiology of adjacent arteries by producing various adipokines. Epicardial adipose tissue (EAT) is located between the surface of the heart and the visceral layer of the pericardium and surrounds the coronary arteries. Many clinical studies suggest that an increase in EAT volume is associated with coronary artery disease. It has been reported that exercise and some antidiabetic drugs can reduce EAT volume. In this review, we outline recent findings on the roles of EAT in the pathogenesis of coronary atherosclerosis.
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http://dx.doi.org/10.1253/circj.CJ-20-0935DOI Listing
December 2020

Deep learning to predict elevated pulmonary artery pressure in patients with suspected pulmonary hypertension using standard chest X ray.

Sci Rep 2020 11 17;10(1):19311. Epub 2020 Nov 17.

Department of Cardiovascular Medicine, Tokushima University Hospital, 2-50-1 Kuramoto, Tokushima, Japan.

Accurate diagnosis of pulmonary hypertension (PH) is crucial to ensure that patients receive timely treatment. We hypothesized that application of artificial intelligence (AI) to the chest X-ray (CXR) could identify elevated pulmonary artery pressure (PAP) and stratify the risk of heart failure hospitalization with PH. We retrospectively enrolled a total of 900 consecutive patients with suspected PH. We trained a convolutional neural network to identify patients with elevated PAP (> 20 mmHg) as the actual value of PAP. The endpoints in this study were admission or occurrence of heart failure with elevated PAP. In an independent evaluation set for detection of elevated PAP, the area under curve (AUC) by the AI algorithm was significantly higher than the AUC by measurements of CXR images and human observers (0.71 vs. 0.60 and vs. 0.63, all p < 0.05). In patients with AI predicted PH had 2-times the risk of heart failure with PH compared with those without AI predicted PH. This preliminary work suggests that applying AI to the CXR in high risk groups has limited performance when used alone in identifying elevated PAP. We believe that this report can serve as an impetus for a future large study.
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http://dx.doi.org/10.1038/s41598-020-76359-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672097PMC
November 2020

Identifying the extent of oral fluid droplets on echocardiographic machine consoles in COVID-19 era.

J Echocardiogr 2020 12 18;18(4):268-270. Epub 2020 Sep 18.

Department of Cardiovascular Medicine, Tokushima University Hospital, 2-50-1 Kuramoto, Tokushima, Japan.

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http://dx.doi.org/10.1007/s12574-020-00491-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499010PMC
December 2020
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