Publications by authors named "Hirotsugu Yamada"

234 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

[Development of Photocatalysts-Coated Polyethylene Terephthalate Film for Degradation and Elimination of Chemotherapy Drugs].

Gan To Kagaku Ryoho 2021 Jul;48(7):933-937

Dept. of Pharmacy, Gifu University Hospital.

Prolonged exposure to anticancer drugs can lead to health damage in medical professionals as well as in patients and their families, and can be a serious issue. The risk of occupational acute exposure to anticancer drugs in medical professionals has largely been reduced following the establishment of guidelines for safe handling of hazardous drugs. However, the problem of pollution associated with residual anticancer drugs attached to the surface of floors and walls in the prescription laboratory, treatment room and the lavatory remains unsolved. We have recently developed a polyethylene terephthalate(PET) film coated with photocatalysts such as titanium dioxide and tungsten oxide. In the present study, the ability of the PET film to degrade anticancer drugs was tested by dripping anticancer drug solution on to the surface of the film followed by irradiation with LED light. The contents of several anticancer drugs, including 5-fluorouracil, cyclophosphamide, and cisplatin, were greatly reduced after 24 hr irradiation. Therefore, the present photocatalysts-coated PET film may become a useful tool to reduce the risk for exposure to hazardous agents including anticancer drugs.
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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

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

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

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

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

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

Practical guidance for echocardiography for cancer therapeutics-related cardiac dysfunction.

J Echocardiogr 2021 03 7;19(1):1-20. Epub 2020 Nov 7.

Well-Aging Kyobashi Cardiovascular Clinic, Tokyo, Japan.

The prognosis of patients with cancer has improved due to an early diagnosis of cancer and advances in cancer treatment. There are emerging reports on cardiotoxicity in cancer treatment and on cardiovascular disease in cancer patients, from which cardiovascular disease has been recognized as a common cause of death among cancer survivors. This situation has led to the need for a medical system in which oncologists and cardiologists work together to treat patients. With the growing importance of onco-cardiology, the role of echocardiography in cancer care is rapidly expanding, but at present, the practice of echocardiography in clinical settings varies from institution to institution, and is empirical with no established systematic guidance. In view of these circumstances, we thought that brief guidance for clinical application was necessary and have therefore developed this guidance, although evidence in this field is still insufficient.
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http://dx.doi.org/10.1007/s12574-020-00502-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932955PMC
March 2021

Cardiogenic cerebral embolism caused by a severe hypoglycemic attack : a case report.

J Med Invest 2020 ;67(3.4):362-364

Department of Neurosurgery, Kawasaki medical school hopsptal, Okayama, Japan.

The direct relationship between a hypoglycemic attack and cerebral infarction remains unknown. It has been reported that a hypoglycemic attack can result in takotsubo syndrome, leading to cerebral infarction. We report a case of a cardiogenic cerebral embolism caused by a hypoglycemic attack, with additional literature review. A 71-year-old woman was admitted to our hospital in a semi-comatose state due to a severe hypoglycemic attack ; she developed hemiplegia one day after admission. Magnetic resonance imaging revealed cerebral infarction in the area supplied by the left middle cerebral artery. Takotsubo syndrome was suspected based on echocardiography. We diagnosed cerebral embolism due to takotsubo syndrome, caused by the hypoglycemic attack. J. Med. Invest. 67 : 362-364, August, 2020.
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http://dx.doi.org/10.2152/jmi.67.362DOI Listing
January 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

Review of the efforts of the Japanese Society of Echocardiography for coronavirus disease 2019 (COVID-19) during the initial outbreak in Japan.

J Echocardiogr 2020 12 5;18(4):226-233. Epub 2020 Sep 5.

Saiseikai Senri Hospital, Osaka, Japan.

Under the coronavirus disease 2019 (COVID-19) pandemic, the Japanese Society of Echocardiography (JSE) has been working to protect medical staff involved in echocardiographic examinations and to prevent secondary infections caused by the examinations since mid-March 2020. This review aims to describe the footprint of the JSE's responses, focusing on the 3 months in which the initial outbreak of COVID-19 pandemic occurred in Japan. We summarized the six parts as follows: (1) the initial actions for COVID-19 of JSE, (2) JSE's actions for infection control-associated echocardiographic examinations, (3) statements from the American Society of Echocardiography during the COVID-19 pandemic and their Japanese translation by JSE, (4) making videos for explaining the practice of echocardiography during the COVID-19 pandemic, (5) attempts with the JSE members' opinions by the communication platform and surveys, and (6) efforts of final statement during the initial spread of COVID-19. We look forward that this review will help daily practices associated with echocardiography under the COVID-19 pandemic and in the future event of an unknown infectious disease pandemic.
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http://dx.doi.org/10.1007/s12574-020-00487-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7474571PMC
December 2020

Epicardial adipose tissue volume is not a simple marker of coronary artery disease.

Authors:
Hirotsugu Yamada

Int J Cardiol 2021 01 1;322:45. Epub 2020 Sep 1.

Department of Community Medicine for Cardiology, Tokushima University Graduate School of Biomedical Sciences, 2-50-1 Kuramoto, Tokushima, Japan. Electronic address:

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http://dx.doi.org/10.1016/j.ijcard.2020.08.096DOI Listing
January 2021

Inhibition of S1P Receptor 2 Attenuates Endothelial Dysfunction and Inhibits Atherogenesis in Apolipoprotein E-Deficient Mice.

J Atheroscler Thromb 2021 Jun 2;28(6):630-642. Epub 2020 Sep 2.

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

Aim: The bioactive lipid, sphingosine-1-phosphate (S1P), has various roles in the physiology and pathophysiology of many diseases. There are five S1P receptors; however, the role of each S1P receptor in atherogenesis is still obscure. Here we investigated the contribution of S1P receptor 2 (S1P2) to atherogenesis by using a specific S1P2 antagonist, ONO-5430514, in apolipoprotein E-deficient (Apoe ) mice.

Methods: Apoe mice fed with a western-type diet (WTD) received ONO-5430514 (30 mg/kg/day) or vehicle. To examine the effect on atherogenesis, Sudan IV staining, histological analysis, qPCR, and vascular reactivity assay was performed. Human umbilical vein endothelial cells (HUVEC) were used for in vitro experiments.

Results: WTD-fed Apoe mice had significantly higher S1P2 expression in the aorta compared with wild-type mice. S1P2 antagonist treatment for 20 weeks reduced atherosclerotic lesion development (p<0.05). S1P2 antagonist treatment for 8 weeks ameliorated endothelial dysfunction (p<0.05) accompanied with significant reduction of lipid deposition, macrophage accumulation, and inflammatory molecule expression in the aorta compared with vehicle. S1P2 antagonist attenuated the phosphorylation of JNK in the abdominal aorta compared with vehicle (p<0.05). In HUVEC, S1P promoted inflammatory molecule expression such as MCP-1 and VCAM-1 (p<0.001), which was attenuated by S1P2 antagonist or a JNK inhibitor (p<0.01). S1P2 antagonist also inhibited S1P-induced JNK phosphorylation in HUVEC (p<0.05).

Conclusions: Our results suggested that an S1P2 antagonist attenuates endothelial dysfunction and prevents atherogenesis. S1P2, which promotes inflammatory activation of endothelial cells, might be a therapeutic target for atherosclerosis.
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http://dx.doi.org/10.5551/jat.54916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219539PMC
June 2021

Association between Sarcopenia/Lower Muscle Mass and Short-Term Regression of Deep Vein Thrombosis Using Direct Oral Anticoagulants.

Int Heart J 2020 Jul 18;61(4):787-794. Epub 2020 Jul 18.

Department of Cardiovascular Medicine, Tokushima University Hospital.

Advanced age, obesity, and muscle weakness are independent factors in the onset of deep vein thrombosis (DVT). Recently, an association between sarcopenia and DVT has been reported. We hypothesized that sarcopenia related factors, observed by ultrasonography, are associated with the regression effect on the thrombus following anticoagulation therapy. The present study focused on gastrocnemius muscle (GCM) thickness and the GCM's internal echogenic brightness. We examined the association with DVT regression following direct oral anticoagulants (DOACs) treatment.The prospective cohort study period was between October 2017 and August 2018. We enrolled 46 patients diagnosed with DVT by ultrasonography, who were aged >60 years old and treated with DOACs. Sarcopenia was evaluated using the Asian Working Group for Sarcopenia flowchart. The average DOACs treatment period was 94 days, and 29 patients exhibited thrombus regression. On univariate logistic regression analysis, sarcopenia, average GCM diameter index, and gastrocnemius integrated backscatter index were significantly associated with thrombus regression. In a multivariate model, only the average GCM diameter index correlated with thrombus regression.The average GCM diameter index is associated with DVT regression treated with DOACs. Considering the GCM diameter during DVT treatment can be a marker to make a decision for the treatment of DVT.
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http://dx.doi.org/10.1536/ihj.20-032DOI Listing
July 2020

Clinically Feasible and Accurate View Classification of Echocardiographic Images Using Deep Learning.

Biomolecules 2020 04 25;10(5). Epub 2020 Apr 25.

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

A proper echocardiographic study requires several video clips recorded from different acquisition angles for observation of the complex cardiac anatomy. However, these video clips are not necessarily labeled in a database. Identification of the acquired view becomes the first step of analyzing an echocardiogram. Currently, there is no consensus whether the mislabeled samples can be used to create a feasible clinical prediction model of ejection fraction (EF). The aim of this study was to test two types of input methods for the classification of images, and to test the accuracy of the prediction model for EF in a learning database containing mislabeled images that were not checked by observers. We enrolled 340 patients with five standard views (long axis, short axis, 3-chamber view, 4-chamber view and 2-chamber view) and 10 images in a cycle, used for training a convolutional neural network to classify views (total 17,000 labeled images). All DICOM images were rigidly registered and rescaled into a reference image to fit the size of echocardiographic images. We employed 5-fold cross validation to examine model performance. We tested models trained by two types of data, averaged images and 10 selected images. Our best model (from 10 selected images) classified video views with 98.1% overall test accuracy in the independent cohort. In our view classification model, 1.9% of the images were mislabeled. To determine if this 98.1% accuracy was acceptable for creating the clinical prediction model using echocardiographic data, we tested the prediction model for EF using learning data with a 1.9% error rate. The accuracy of the prediction model for EF was warranted, even with training data containing 1.9% mislabeled images. The CNN algorithm can classify images into five standard views in a clinical setting. Our results suggest that this approach may provide a clinically feasible accuracy level of view classification for the analysis of echocardiographic data.
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http://dx.doi.org/10.3390/biom10050665DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277840PMC
April 2020

Febuxostat does not delay progression of carotid atherosclerosis in patients with asymptomatic hyperuricemia: A randomized, controlled trial.

PLoS Med 2020 04 22;17(4):e1003095. Epub 2020 Apr 22.

Department of Cardiovascular Medicine, Saga University, Saga, Japan.

Background: An elevated level of serum uric acid (SUA) is associated with an increased risk of cardiovascular disease. Pharmacological intervention with urate-lowering agents, such as the conventional purine analogue xanthine oxidase (XO) inhibitor, allopurinol, has been used widely for a long period of time in clinical practice to reduce SUA levels. Febuxostat, a novel non-purine selective inhibitor of XO, has higher potency for inhibition of XO activity and greater urate-lowering efficacy than conventional allopurinol. However, clinical evidence regarding the effects of febuxostat on atherosclerosis is lacking. The purpose of the study was to test whether treatment with febuxostat delays carotid intima-media thickness (IMT) progression in patients with asymptomatic hyperuricemia.

Methods And Findings: The study was a multicenter, prospective, randomized, open-label, blinded-endpoint clinical trial undertaken at 48 sites throughout Japan between May 2014 and August 2018. Adults with both asymptomatic hyperuricemia (SUA >7.0 mg/dL) and maximum IMT of the common carotid artery (CCA) ≥1.1 mm at screening were allocated equally using a central web system to receive either dose-titrated febuxostat (10-60 mg daily) or as a control-arm, non-pharmacological lifestyle modification for hyperuricemia, such as a healthy diet and exercise therapy. Of the 514 enrolled participants, 31 were excluded from the analysis, with the remaining 483 people (mean age 69.1 years [standard deviation 10.4 years], female 19.7%) included in the primary analysis (febuxostat group, 239; control group, 244), based on a modified intention-to-treat principal. The carotid IMT images were recorded by a single sonographer at each site and read in a treatment-blinded manner by a single analyzer at a central core laboratory. The primary endpoint was the percentage change from baseline to 24 months in mean IMT of the CCA, determined by analysis of covariance using the allocation adjustment factors (age, gender, history of type 2 diabetes, baseline SUA, and baseline maximum IMT of the CCA) as the covariates. Key secondary endpoints included changes in other carotid ultrasonographic parameters and SUA and the incidence of clinical events. The mean values (± standard deviation) of CCA-IMT were 0.825 mm ± 0.173 mm in the febuxostat group and 0.832 mm ± 0.175 mm in the control group (mean between-group difference [febuxostat - control], -0.007 mm [95% confidence interval (CI) -0.039 mm to 0.024 mm; P = 0.65]) at baseline; 0.832 mm ± 0.182 mm in the febuxostat group and 0.848 mm ± 0.176 mm in the control group (mean between-group difference, -0.016 mm [95% CI -0.051 mm to 0.019 mm; P = 0.37]) at 24 months. Compared with the control group, febuxostat had no significant effect on the primary endpoint (mean percentage change 1.2% [95% CI -0.6% to 3.0%] in the febuxostat group (n = 207) versus 1.4% [95% CI -0.5% to 3.3%] in the control group (n = 193); mean between-group difference, -0.2% [95% CI -2.3% to 1.9%; P = 0.83]). Febuxostat also had no effect on the other carotid ultrasonographic parameters. The mean baseline values of SUA were comparable between the two groups (febuxostat, 7.76 mg/dL ± 0.98 mg/dL versus control, 7.73 mg/dL ± 1.04 mg/dL; mean between-group difference, 0.03 mg/dL [95% CI -0.15 mg/dL to 0.21 mg/dL; P = 0.75]). The mean value of SUA at 24 months was significantly lower in the febuxostat group than in the control group (febuxostat, 4.66 mg/dL ± 1.27 mg/dL versus control, 7.28 mg/dL ± 1.27 mg/dL; mean between-group difference, -2.62 mg/dL [95% CI -2.86 mg/dL to -2.38 mg/dL; P < 0.001]). Episodes of gout arthritis occurred only in the control group (4 patients [1.6%]). There were three deaths in the febuxostat group and seven in the control group during follow-up. A limitation of the study was the study design, as it was not a placebo-controlled trial, had a relatively small sample size and a short intervention period, and only enrolled Japanese patients with asymptomatic hyperuricemia.

Conclusions: In Japanese patients with asymptomatic hyperuricemia, 24 months of febuxostat treatment did not delay carotid atherosclerosis progression, compared with non-pharmacological care. These findings do not support the use of febuxostat for delaying carotid atherosclerosis in this population.

Trial Registration: University Hospital Medical Information Network Clinical Trial Registry UMIN000012911.
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http://dx.doi.org/10.1371/journal.pmed.1003095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176100PMC
April 2020

Atherosclerotic Coronary Plaque Is Associated With Adventitial Vasa Vasorum and Local Inflammation in Adjacent Epicardial Adipose Tissue in Fresh Cadavers.

Circ J 2020 04 10;84(5):769-775. Epub 2020 Apr 10.

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

Background: The coronary adventitia has recently attracted attention as a source of inflammation because it harbors nutrient blood vessels, termed the vasa vasorum (VV). This study assessed the link between local inflammation in adjacent epicardial adipose tissue (EAT) and coronary arterial atherosclerosis in fresh cadavers.Methods and Results:Lesion characteristics in the left anterior descending coronary artery of 10 fresh cadaveric hearts were evaluated using integrated backscatter intravascular ultrasound (IB-IVUS), and the density of the VV and levels of inflammatory molecules from the adjacent EAT were measured for each of the assessed lesions. The lesions were divided into lipid-rich, lipid-moderate, and lipid-poor groups according to percentage lipid volume assessed by IB-IVUS. Higher expression of inflammatory molecules (i.e., vascular endothelial growth factor A [VEGFA] andVEGFB) was observed in adjacent EAT of lipid-rich (n=11) than in lipid-poor (n=11) lesions (7.99±3.37 vs. 0.45±0.85 arbitrary units [AU], respectively, forVEGFA; 0.27±0.15 vs. 0.11±0.07 AU, respectively, forVEGFB; P<0.05). The density of adventitial VV was greater in lipid-rich than lipid-poor lesions (1.50±0.58% vs. 0.88±0.23%; P<0.05).

Conclusions: Lipid-rich coronary plaques are associated with adventitial VV and local inflammation in adjacent EAT in fresh cadavers. This study suggests that local inflammation of EAT is associated with coronary plaque progression via the VV.
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http://dx.doi.org/10.1253/circj.CJ-19-0914DOI Listing
April 2020
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