Publications by authors named "Yoshio Kobayashi"

513 Publications

Inhibition of Interleukin-21 prolongs the survival through the promotion of wound healing after myocardial infarction.

J Mol Cell Cardiol 2021 Jun 15. Epub 2021 Jun 15.

Department of Allergy and Clinical Immunology, Graduate School of Medicine, Japan. Electronic address:

Ly6C macrophages promote scar formation and prevent early infarct expansion after myocardial infarction (MI). Although CD4 T cells influence the regulation of Ly6C macrophages after MI, the mechanism remains largely unknown. Based on the hypothesis that some molecule(s) secreted by CD4 T cells act on Ly6C macrophages, we searched for candidate molecules by focusing on cytokine receptors expressed on Ly6C macrophages. Comparing the transcriptome between Ly6C macrophages and Ly6C macrophages harvested from the infarcted heart, we found that Ly6C macrophages highly expressed the receptor for interleukin (IL)-21, a pleiotropic cytokine which is produced by several types of CD4 T cells, compared with Ly6C macrophages. Indeed, CD4 T cells harvested from the infarcted heart produce IL-21 upon stimulation. Importantly, the survival rate and cardiac function after MI were significantly improved in IL-21-deficient (il21) mice compared with those in wild-type (WT) mice. Transcriptome analysis of infarcted heart tissue from WT mice and il21 mice at 5 days after MI demonstrated that inflammation is persistent in WT mice compared with il21 mice. Consistent with the transcriptome analysis, the number of neutrophils and matrix metalloproteinase (MMP)-9 expression were significantly decreased, whereas the number of Ly6C macrophages and MMP-12 expression were significantly increased in il21 mice. In addition, collagen deposition and the number of myofibroblasts in the infarcted area were significantly increased in il21 mice. Consistently, IL-21 enhanced the apoptosis of Ly6C macrophages. Finally, administration of neutralizing IL-21 receptor Fc protein increased the number of Ly6C macrophages in the infarcted heart and improved the survival and cardiac function after MI. Thus, IL-21 decreases the survival after MI, possibly through the delay of wound healing by inducing the apoptosis of Ly6C macrophages.
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http://dx.doi.org/10.1016/j.yjmcc.2021.06.006DOI Listing
June 2021

Pathophysiological background and prognosis of common atrial flutter in non-elderly patients: Comparison to Atrial Fibrillation.

J Cardiol 2021 Jun 14. Epub 2021 Jun 14.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.

Background: It is unclear whether there is any difference in the background and prognosis between non-elderly patients who undergo catheter ablation of atrial fibrillation (AF) and common atrial flutter (CAFL).

Purpose: To investigate the difference between the patient background of both CAFL and AF in the non-elderly.

Methods: In 526 consecutive patients who underwent catheter ablation of clinical paroxysmal/persistent CAFL or AF in our hospital, we enrolled only patients under 60 years old. Cases harboring both AFL and AF were excluded. We analyzed the patient characteristics, echocardiographic findings, electrocardiographic (ECG) abnormalities during sinus rhythm, and clinical course after ablation.

Results: In total, 196 patients (Cohort 1: 142 males, 156 AF cases) were analyzed. AFL patients were younger than AF patients (47.4 ± 10.6 vs. 50.2 ± 6.4years, p = 0.031) and organic heart disease (OHD) was significantly more common in AFL patients than AF patients (42.5% vs. 11.5%, p<0.001). In 161 patients excluding OHD (Cohort 2), ECG abnormalities were more frequent in AFL than in AF patients (78.3% vs. 39.1%, p = 0.001). There were no significant differences in all-cause death, onset of heart failure, and cerebral strokes. On the other hand, the number of cases that required a pacemaker was significantly higher in the CAFL group than AF group (0.0% vs. 26.1%, p-value <0.001). These results suggested that CAFL may reflect occurrence of any atrial myocardial damage, even if it does not lead to heart failure.

Conclusions: Our present study suggested that CAFL may be associated with a broader atrial myocardial disorder in non-elderly patients.
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http://dx.doi.org/10.1016/j.jjcc.2021.05.008DOI Listing
June 2021

Prognostic Impact of Branch Vessel Involvement on Computed Tomography versus Clinical Presentation of Malperfusion in Patients With Type a Acute Aortic Dissection.

Am J Cardiol 2021 Jun 10. Epub 2021 Jun 10.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.

Type A acute aortic dissection (AAD) is a life-threatening disease. The use of contrast-enhanced computed tomography (CT) for diagnosing AAD has increased, and CT can provide pathophysiologic information on dissection such as intramural hematoma (IMH), longitudinal extent of dissection, and branch vessel involvement. However, the prognostic impact of these CT findings is poorly investigated. This multicenter registry included 703 patients with type A AAD. The longitudinal extent of dissection and IMH was determined on CT. Branch vessel involvement was defined as dissection extended into coronary, cerebral, and visceral arteries on CT. The evidence of malperfusion was defined based on clinical presentations. The primary endpoint was in-hospital death. Of 703 patients, 126 (18%) died during hospitalization. Based on contrast-enhanced CT findings, longitudinal extent of dissection was not associated with in-hospital death, while patients with IMH had lower in-hospital mortality than those without (13% vs 22%, p = 0.004). Coronary, cerebral, and visceral artery involvement on CT was found in 6%, 55%, and 32%. In patients with coronary artery involvement, 90% had clinical coronary malperfusion, while only 25% and 21% of patients with cerebral and visceral artery involvement had clinical evidence of corresponding organ malperfusion. Multivariable analysis showed evidence of malperfusion as a significant factor associated with in-hospital mortality. In conclusions, branch vessel involvement on CT was not always associated with end-organ malperfusion in patients with type A AAD, especially in cerebral and visceral arteries. Clinical evidence of malperfusion was significantly associated with in-hospital mortality beyond branch vessel involvement on CT.
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http://dx.doi.org/10.1016/j.amjcard.2021.05.005DOI Listing
June 2021

Serum anti-DIDO1, anti-CPSF2, and anti-FOXJ2 antibodies as predictive risk markers for acute ischemic stroke.

BMC Med 2021 Jun 9;19(1):131. Epub 2021 Jun 9.

Department of Endocrinology, Hematology and Gerontology, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan.

Background: Acute ischemic stroke (AIS) is a serious cause of mortality and disability. AIS is a serious cause of mortality and disability. Early diagnosis of atherosclerosis, which is the major cause of AIS, allows therapeutic intervention before the onset, leading to prevention of AIS.

Methods: Serological identification by cDNA expression cDNA libraries and the protein array method were used for the screening of antigens recognized by serum IgG antibodies in patients with atherosclerosis. Recombinant proteins or synthetic peptides derived from candidate antigens were used as antigens to compare serum IgG levels between healthy donors (HDs) and patients with atherosclerosis-related disease using the amplified luminescent proximity homogeneous assay-linked immunosorbent assay.

Results: The first screening using the protein array method identified death-inducer obliterator 1 (DIDO1), forkhead box J2 (FOXJ2), and cleavage and polyadenylation specificity factor (CPSF2) as the target antigens of serum IgG antibodies in patients with AIS. Then, we prepared various antigens including glutathione S-transferase-fused DIDO1 protein as well as peptides of the amino acids 297-311 of DIDO1, 426-440 of FOXJ2, and 607-621 of CPSF2 to examine serum antibody levels. Compared with HDs, a significant increase in antibody levels of the DIDO1 protein and peptide in patients with AIS, transient ischemic attack (TIA), and chronic kidney disease (CKD) but not in those with acute myocardial infarction and diabetes mellitus (DM). Serum anti-FOXJ2 antibody levels were elevated in most patients with atherosclerosis-related diseases, whereas serum anti-CPSF2 antibody levels were associated with AIS, TIA, and DM. Receiver operating characteristic curves showed that serum DIDO1 antibody levels were highly associated with CKD, and correlation analysis revealed that serum anti-FOXJ2 antibody levels were associated with hypertension. A prospective case-control study on ischemic stroke verified that the serum antibody levels of the DIDO1 protein and DIDO1, FOXJ2, and CPSF2 peptides showed significantly higher odds ratios with a risk of AIS in patients with the highest quartile than in those with the lowest quartile, indicating that these antibody markers are useful as risk factors for AIS.

Conclusions: Serum antibody levels of DIDO1, FOXJ2, and CPSF2 are useful in predicting the onset of atherosclerosis-related AIS caused by kidney failure, hypertension, and DM, respectively.
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http://dx.doi.org/10.1186/s12916-021-02001-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188684PMC
June 2021

Durability of mitral isthmus ablation with and without ethanol infusion in the vein of Marshall.

J Cardiovasc Electrophysiol 2021 May 24. Epub 2021 May 24.

Department of Cardiology, Chiba University Hospital, Chiba, Japan.

Introduction: Ethanol infusion in the vein of Marshall (EIVOM) effectively creates a linear ablation lesion in the mitral isthmus (MI). However, data on the long-term success rates of MI ablation is limited.

Methods And Results: Our cohort consisted of 560 patients with nonparoxysmal atrial fibrillation (AF) who underwent an initial MI ablation. Ablations were performed by only radiofrequency (RF) in 384 (RF group) or by RF and EIVOM in 176 (EIVOM/RF group) patients; 5 ml anhydrous ethanol was used to perform EIVOM in advance of RF. Following EIVOM, RF pulses were delivered to the lateral MI line. Bidirectional MI block was fully achieved in 353/384 (92%) (First 318, Re-do 35) patinents in the RF group and 171/176 (97%) (First 128, Re-do 43) patients in the EIVOM/RF group (p = .09 in the first, p = .10 in the re-do ablation cases). In cases with complete MI line block, recurrent AF or atrial tachycardia was observed in 130/353 (37%) patients in the RF group and in 64/171 (37%) patients in the EIVOM/RF group (log-rank p = .12 in the first, and p = .30 in the re-do ablation cases). Of the total 560 patients, 123 proceeded to the subsequent ablation session. Reconduction across MI line block was observed in 39/80 (49%) patients in the RF group and 25/43 (58%) patients in the EIVOM/RF group (p = .32).

Conclusion: EIVOM effectively ensures MI line block; however, the reconduction rate was similar between the two groups.
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http://dx.doi.org/10.1111/jce.15107DOI Listing
May 2021

Ethnic comparison in takotsubo syndrome: novel insights from the International Takotsubo Registry.

Clin Res Cardiol 2021 May 19. Epub 2021 May 19.

Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.

Background: Ethnic disparities have been reported in cardiovascular disease. However, ethnic disparities in takotsubo syndrome (TTS) remain elusive. This study assessed differences in clinical characteristics between Japanese and European TTS patients and determined the impact of ethnicity on in-hospital outcomes.

Methods: TTS patients in Japan were enrolled from 10 hospitals and TTS patients in Europe were enrolled from 32 hospitals participating in the International Takotsubo Registry. Clinical characteristics and in-hospital outcomes were compared between Japanese and European patients.

Results: A total of 503 Japanese and 1670 European patients were included. Japanese patients were older (72.6 ± 11.4 years vs. 68.0 ± 12.0 years; p < 0.001) and more likely to be male (18.5 vs. 8.4%; p < 0.001) than European TTS patients. Physical triggering factors were more common (45.5 vs. 32.0%; p < 0.001), and emotional triggers less common (17.5 vs. 31.5%; p < 0.001), in Japanese patients than in European patients. Japanese patients were more likely to experience cardiogenic shock during the acute phase (15.5 vs. 9.0%; p < 0.001) and had a higher in-hospital mortality (8.2 vs. 3.2%; p < 0.001). However, ethnicity itself did not appear to have an impact on in-hospital mortality. Machine learning approach revealed that the presence of physical stressors was the most important prognostic factor in both Japanese and European TTS patients.

Conclusion: Differences in clinical characteristics and in-hospital outcomes between Japanese and European TTS patients exist. Ethnicity does not impact the outcome in TTS patients. The worse in-hospital outcome in Japanese patients, is mainly driven by the higher prevalence of physical triggers.

Trial Registration: URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT01947621.
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http://dx.doi.org/10.1007/s00392-021-01857-4DOI Listing
May 2021

Association between early intensive care or coronary care unit admission and post-discharge performance of activities of daily living in patients with acute decompensated heart failure.

PLoS One 2021 10;16(5):e0251505. Epub 2021 May 10.

Department of Healthcare Management Research Center, Chiba University Hospital, Chiba, Japan.

The management of acute decompensated heart failure often requires intensive care. However, the effects of early intensive care unit/coronary care unit admission on activities of daily living (ADL) in acute decompensated heart failure patients have not been precisely evaluated. Thus, we retrospectively assessed the association between early intensive care unit admission and post-discharge ADL performance in these patients. Acute decompensated heart failure patients (New York Heart Association I-III) admitted on emergency between April 1, 2014, and December 31, 2018, were selected from the Diagnosis Procedure Combination database and divided into intensive care unit/coronary care unit (ICU) and general ward (GW) groups according to the hospitalization type on admission day 1. The propensity score was calculated to create matched cohorts where admission style (intensive care unit/coronary care unit admission) was independent of measured baseline confounding factors, including ADL at admission. The primary outcome was ADL performance level at discharge (post-ADL) defined according to the Barthel index. Secondary outcomes included length of stay and total hospitalization cost (expense). Overall, 12231 patients were eligible, and propensity score matching created 2985 pairs. After matching, post-ADL was significantly higher in the ICU group than in the GW group [mean (standard deviation), GW vs. ICU: 71.5 (35.3) vs. 78.2 (31.2) points, P<0.001; mean difference: 6.7 (95% confidence interval, 5.1-8.4) points]. After matching, length of stay was significantly shorter and expenses were significantly higher in the ICU group than in the GW group. Stratified analysis showed that the patients with low ADL at admission (Barthel index score <60) were the most benefited from early intensive care unit/coronary care unit admission. Thus, early intensive care unit/coronary care unit admission was associated with improved post-ADL in patients with emergency acute decompensated heart failure admission.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251505PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109822PMC
May 2021

Impact of CADILLAC and GRACE risk scores on short- and long-term clinical outcomes in patients with acute myocardial infarction.

J Cardiol 2021 May 1. Epub 2021 May 1.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.

Background: Recent guidelines recommend risk stratification using objective scoring systems in patients with acute coronary syndrome. In this context, the CADILLAC (Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications) and GRACE (Global Registry of Acute Coronary Events) risk scores were both originally established to predict short-term mortality. However, their impact on short- and long-term clinical outcomes in a contemporary cohort of patients with acute myocardial infarction (MI) is unclear.

Methods: This bi-center registry included 809 patients with acute MI undergoing primary percutaneous coronary intervention. Patients were divided into three groups according to the pre-defined thresholds and tertiles of the CADILLAC and GRACE scores. The study endpoints included all-cause death and major adverse cardiovascular events (MACE) during the index hospitalization and after discharge.

Results: Of 809 patients, 323 (39.9%) and 255 (31.5%) had high CADILLAC and GRACE risk scores. During the index hospitalization, 61 (7.5%) patients died and 262 (32.4%) had MACE. Both CADILLAC and GRACE risk scores were associated with in-hospital mortality and MACE rates. After discharge, out of 683 patients with available follow-up information who survived to discharge, 42 (6.1%) died and 123 (18.0%) had MACE during the median follow-up period of 632 days. Significantly higher incidence of MACE in higher CADILLAC and GRACE risk scores was observed in a stepwise manner.

Conclusion: Both CADILLAC and GRACE risk scores were predictive for short- and long-term mortality and MACE rates in a contemporary cohort of acute MI patients undergoing primary percutaneous coronary intervention.
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http://dx.doi.org/10.1016/j.jjcc.2021.04.005DOI Listing
May 2021

Layered coronary plaque associated with coronary vasospasm.

Cardiovasc Interv Ther 2021 Apr 23. Epub 2021 Apr 23.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8677, Japan.

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http://dx.doi.org/10.1007/s12928-021-00780-9DOI Listing
April 2021

Visible bigeminal pulses with tortuous common carotid artery.

BMJ Case Rep 2021 Apr 19;14(4). Epub 2021 Apr 19.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.

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http://dx.doi.org/10.1136/bcr-2021-242990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057545PMC
April 2021

Stabilization of Size-Controlled BaTiO Nanocubes via Precise Solvothermal Crystal Growth and Their Anomalous Surface Compositional Reconstruction.

ACS Omega 2021 Apr 30;6(14):9410-9425. Epub 2021 Mar 30.

The Institute of Scientific and Industrial Research, Osaka University, 8-1, Mihogaoka, Ibaraki 567-0047, Osaka, Japan.

Crystal growth of barium titanate (BaTiO) using a wet chemical reaction was investigated at various temperatures. BaTiO nanoparticles were obtained at an energy-efficient temperature of 80 °C. However, BaTiO nanocubes with a preferred size and shape could be synthesized using a solvothermal method at 200 °C via a reaction involving titanium tetraisopropoxide [(CH)CHO]Ti for nucleation and fine titanium oxide (TiO) nanoparticles for crystal growth. The BaTiO nanocubes showed a high degree of dispersion without the use of dispersants or surfactants. The morphology of BaTiO was found to depend on the reaction medium. The size of the BaTiO particles obtained using water as the reaction medium was the largest among the particles synthesized using various reaction media. In the case of alcohol reaction media, the BaTiO particle size increased in the order methanol, ethanol, 1-propanol, 1-butanol, and 1-pentanol. Furthermore, BaTiO powder obtained using alcohol reaction media resulted in cubic shapes as opposed to the round shapes obtained when water was used as the medium. We found that the optimal condition for the synthesis of BaTiO nanocubes involved the use of 1-butanol as the reaction medium, resulting in an average particle size of 52 nm, which is the average distance of the cubes measured diagonally from corner to corner, and gives an average side length of 37 nm, and a tetragonal crystal system as evidenced by the powder X-ray diffraction pattern obtained using high-energy synchrotron X-rays. The origin of the spontaneous polarization of the BaTiO tetragonal crystal structure was clarified by a pair distribution function analysis. In addition, surface reconstruction of BaTiO nanocubes led to an outermost surface comprising two layers of Ti columns.
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http://dx.doi.org/10.1021/acsomega.0c05878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047730PMC
April 2021

Short Coaptation Length is a Predictor of Recurrent Mitral Regurgitation After Mitral Valve Plasty.

Heart Lung Circ 2021 Apr 15. Epub 2021 Apr 15.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.

Background: Long-term predictors of recurrent mitral regurgitation (MR) after mitral valve plasty (MVP) remain to be elucidated. This study sought to determine the prognostic factors of recurrent MR during long-term follow-up after MVP, by analysing findings of three-dimensional transoesophageal echocardiography (TEE) conducted after MVP.

Methods: This study analysed 207 patients who underwent MVP for A2 and/or P2 prolapse and received TEE before discharge. Recurrent MR was defined as moderate or worse regurgitation detected by annual transthoracic echocardiography.

Results: During a median follow-up period of 49 months after MVP, 18 patients experienced recurrent MR and six patients needed reoperation. In the recurrent group, 16 of 18 patients showed less than moderate MR before discharge. Patients in the recurrent group underwent repair for worse MR (effective orifice area, 54±19 vs 44±16 mm; p=0.01) and had shorter A2-P2 coaptation length (5.3±1.4 vs 7.3±1.5 mm; p<0.001) after MVP compared with the non-recurrent group. Cox proportional hazards regression analysis identified the A2-P2 coaptation length as significant risk of recurrent MR (coaptation length increase: HR, 0.44; 95% CI, 0.32-0.59; p<0.0001). The receiver operator characteristics curve demonstrated that a coaptation length of <5.6 mm had 78% sensitivity and 89% specificity for predicting recurrent MR.

Conclusion: Coaptation length measured by post-MVP TEE predicted the tendency of recurrent MR. Patients with short coaptation length should be carefully monitored, even when residual MR is less than moderate after MVP.
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http://dx.doi.org/10.1016/j.hlc.2021.03.269DOI Listing
April 2021

Academic Research Consortium Definition of High Bleeding Risk in Clinical Practice - Validation and Beyond.

Circ J 2021 May 15;85(6):806-807. Epub 2021 Apr 15.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine.

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http://dx.doi.org/10.1253/circj.CJ-21-0192DOI Listing
May 2021

Impact of in-hospital blood pressure variability on clinical outcomes in patients with symptomatic peripheral arterial disease.

Hypertens Res 2021 Apr 13. Epub 2021 Apr 13.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.

Various types of blood pressure (BP) variability have been recognized as risk factors for future cardiovascular events. However, the prognostic impact of in-hospital BP variability in patients with symptomatic peripheral arterial disease (PAD) has not yet been thoroughly investigated. A total of 386 patients with PAD who underwent endovascular therapy in two hospitals were retrospectively included. BP variability was assessed by the coefficient of variation (CV) of systolic BP measured during hospitalization by trained nurses. The primary endpoint was a composite of major adverse cardiovascular events (cardiovascular death, acute coronary syndrome, stroke, and hospitalization for heart failure) and major adverse limb events (major amputation, acute limb ischemia, and surgical limb revascularization). The mean systolic BP and the CV of systolic BP during hospitalization were 130.8 ± 15.7 mmHg and 11.2 ± 4.1%, respectively. During the median follow-up period of 22 months, 80 patients (21%) reached the primary endpoint. Receiver operating characteristic curve analysis showed that the CV of systolic BP significantly predicted major adverse cardiovascular and limb events (area under the curve 0.60, best cutoff value 9.8, P = 0.01). Using the best cutoff value, patients with high BP variability (n = 242) had a higher risk of clinical events than those with low BP variability (n = 144) (26% vs. 12%, P < 0.001). Multivariable analysis indicated that the CV of systolic BP, age, hemodialysis, and atrial fibrillation were associated with the primary endpoint. In conclusion, greater in-hospital systolic BP variability was associated with major adverse cardiovascular and limb events in patients with symptomatic PAD undergoing endovascular therapy.
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http://dx.doi.org/10.1038/s41440-021-00648-8DOI Listing
April 2021

Development of X-ray contrast agents using single nanometer-sized gold nanoparticles and lactoferrin complex and their application in vascular imaging.

Colloids Surf B Biointerfaces 2021 Jul 1;203:111732. Epub 2021 Apr 1.

Department of Medical Physics, Graduate School of Medicine, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan; International Center for Synchrotron Radiation InnovationSmart (SRIS), Tohoku University, 2-1-1, Katahira, Aoba-ku, Sendai 980-8577, Japan. Electronic address:

The technology to accurately image the morphology of tumor vessels with X-ray contrast agents is important to clarify mechanisms underlying tumor progression and evaluate the efficacy of chemotherapy. However, in clinical practice, iodine-based contrast agents present problems such as short blood retention owing to a high clearance ability and insufficient X-ray absorption capacity when compared with other high atomic number elements. To resolve these issues, gold nanoparticles (AuNPs), with a high atomic number, have attracted a great deal of attention as contrast agents for angiography, and have been employed in small animal models. Herein, we developed novel contrast agents using AuNPs and captured changes in tumor vessel morphology with time using X-ray computed tomography (CT). First, glutathione-supported single nanometer-sized AuNPs (sAu/GSH) (diameter, 2.2 nm) were fabricated using tetrakis(hydroxymethyl)phosphonium chloride as a reducing agent. The sAu/GSH particles were intravenously injected into mice, remained in vessels for a few minutes, and were then excreted by the kidneys after 24 h, similar to the commercial contrast agent iopamidol. Next, the Au/GSH and lactoferrin (sAu/GSH-LF) (long axis size, 17.3 nm) complex was produced by adding lactoferrin to the sAu/GSH solution under the influence of a condensing agent. On intravenously administering sAu/GSH-LF to mice, the blood retention time was 1-3 h, which was considerably longer than that observed with iopamidol and sAu/GSH. Moreover, we succeeded in imaging morphological changes in identical tumor vessels for several days using X-ray CT with sAu/GSH-LF.
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http://dx.doi.org/10.1016/j.colsurfb.2021.111732DOI Listing
July 2021

Periorbital ecchymosis and shoulder pad sign in transthyretin amyloidosis.

BMJ Case Rep 2021 Apr 7;14(4). Epub 2021 Apr 7.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.

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http://dx.doi.org/10.1136/bcr-2021-242614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8031027PMC
April 2021

Austrian syndrome associated with mitral paravalvular pneumococcal abscess.

QJM 2021 Mar 25. Epub 2021 Mar 25.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

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http://dx.doi.org/10.1093/qjmed/hcab064DOI Listing
March 2021

Clinical implications and debates on the ISCHEMIA trial.

Cardiol Rev 2021 Mar 19. Epub 2021 Mar 19.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan Department of Cardiovascular Medicine, Gifu Heart Center, Gifu, Japan.

The ISCHEMIA was eagerly awaited study in the field of ischemic heart disease. Following the presentation and publication of ISCHEMIA, multiple opinions and viewpoints get complicated. The ongoing debates have been including the relevance of coronary revascularization, non-invasive diagnostic methods, and invasive ischemic testing in patients with stable ischemic heart disease (SIHD). Prior to ISCHEMIA, observational studies indicated the potential of coronary revascularization for improving clinical outcomes, while the randomized COURAGE trial did not support the plausible concept. Although the FAME 2 trial implied the superiority of percutaneous coronary intervention over medical therapy alone, the clinical relevance of coronary revascularization to improve outcomes and quality of life has been questioned. As a consequence, the ISCHEMIA trial did not demonstrate clear benefits in reducing clinical events but showed antianginal effects of revascularization. This landmark trial also suggested the difficulties of non-invasive ischemia testing rather than computed tomography angiography. Despite the complex results, the ISCHEMIA trial may simplify the clinical indications of coronary revascularization in patients with SIHD. Future publications from the ISCHEMIA trial and debates on the results will sharpen our thinking and understanding.
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http://dx.doi.org/10.1097/CRD.0000000000000389DOI Listing
March 2021

Deep learning-based intravascular ultrasound segmentation for the assessment of coronary artery disease.

Int J Cardiol 2021 06 16;333:55-59. Epub 2021 Mar 16.

Division of Cardiovascular Medicine, Stanford University School of Medicine and Stanford Cardiovascular Institute, Stanford, CA, USA. Electronic address:

Background: Accurate segmentation of the coronary arteries with intravascular ultrasound (IVUS) is important to optimize coronary stent implantation. Recently, deep learning (DL) methods have been proposed to develop automatic IVUS segmentation. However, most of those have been limited to segmenting the lumen and vessel (i.e. lumen-intima and media-adventitia borders), not applied to segmenting stent dimension. Hence, this study aimed to develop a DL method for automatic IVUS segmentation of stent area in addition to lumen and vessel area.

Methods: This study included a total of 45,449 images from 1576 IVUS pullback runs. The datasets were randomly split into training, validation, and test datasets (0.7:0.15:0.15). After developing the DL-based system to segment IVUS images using the training and validation datasets, we evaluated the performance through the independent test dataset.

Results: The DL-based segmentation correlated well with the expert-analyzed segmentation with a mean intersection over union (± standard deviation) of 0.80 ± 0.20, correlation coefficient of 0.98 (95% confidence intervals: 0.98 to 0.98), 0.96 (0.95 to 0.96), and 0.96 (0.96 to 0.96) for lumen, vessel, and stent area, and the mean difference (± standard deviation) of 0.02 ± 0.57, -0.44 ± 1.56 and - 0.17 ± 0.74 mm for lumen, vessel and stent area, respectively.

Conclusion: This automated DL-based IVUS segmentation of lumen, vessel and stent area showed an excellent agreement with manual segmentation by experts, supporting the feasibility of artificial intelligence-assisted IVUS assessment in patients undergoing coronary stent implantation.
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http://dx.doi.org/10.1016/j.ijcard.2021.03.020DOI Listing
June 2021

Prognostic impact of acute pulmonary triggers in patients with takotsubo syndrome: new insights from the International Takotsubo Registry.

ESC Heart Fail 2021 Jun 13;8(3):1924-1932. Epub 2021 Mar 13.

Department of Cardiology, Charité, Campus Rudolf Virchow, Berlin, Germany.

Aims: Acute pulmonary disorders are known physical triggers of takotsubo syndrome (TTS). This study aimed to investigate prevalence of acute pulmonary triggers in patients with TTS and their impact on outcomes.

Methods And Results: Patients with TTS were enrolled from the International Takotsubo Registry and screened for triggering factors and comorbidities. Patients were categorized into three groups (acute pulmonary trigger, chronic lung disease, and no lung disease) to compare clinical characteristics and outcomes. Of the 1670 included patients with TTS, 123 (7%) were identified with an acute pulmonary trigger, and 194 (12%) had a known history of chronic lung disease. The incidence of cardiogenic shock was highest in patients with an acute pulmonary trigger compared with those with chronic lung disease or without lung disease (17% vs. 10% vs. 9%, P = 0.017). In-hospital mortality was also higher in patients with an acute pulmonary trigger than in the other two groups, although not significantly (5.7% vs. 1.5% vs. 4.2%, P = 0.13). Survival analysis demonstrated that patients with an acute pulmonary trigger had the worst long-term outcome (P = 0.002). The presence of an acute pulmonary trigger was independently associated with worse long-term mortality (hazard ratio 2.12, 95% confidence interval 1.33-3.38; P = 0.002).

Conclusions: The present study demonstrates that TTS is related to acute pulmonary triggers in 7% of all TTS patients, which accounts for 21% of patients with physical triggers. The presence of acute pulmonary trigger is associated with a severe in-hospital course and a worse long-term outcome.
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http://dx.doi.org/10.1002/ehf2.13165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120351PMC
June 2021

Rationale and Design of Therapeutic Angiogenesis by Cell Transplantation Using Adipose-Derived Regenerative Cells in Patients With Critical Limb Ischemia - TACT-ADRC Multicenter Trial.

Circ Rep 2020 Aug 8;2(9):531-535. Epub 2020 Aug 8.

Department of Cardiology, Nagoya University Graduate School of Medicine Nagoya Japan.

Despite the growing knowledge regarding optimal treatments for critical limb ischemia (CLI), there are still a considerable number of patients who have to undergo major limb amputation. Intramuscular injection of autologous adipose-derived regenerative cells (ADRCs) in these patients has shown therapeutic potential in improving tissue ischemia, in both preclinical and initial pilot studies. Here, we present a clinical protocol for ADRCs use in a multicenter trial. The TACT-ADRC multicenter trial is a prospective, interventional, single-arm, open-labeled study at 8 hospitals in Japan, investigating the safety and feasibility of intramuscular injections of ADRCs and testing the hypothesis that this treatment promotes neovascularization and improves major amputation-free survival rates in patients with CLI who have no other treatment option. 40 patients with CLI will be enrolled and followed up from November 2015 to November 2020. Freshly isolated autologous ADRCs will be injected into the target ischemic limbs. Survival rate, adverse events, major limb amputation, ulcer size, 6-min walking distance, numerical rating scale, ankle-brachial pressure index, skin perfusion pressure and digital subtraction angiography will be evaluated at baseline and during 6 months' follow-up. This trial will demonstrate whether implantation of autologous ADRCs is a safe and effective method for therapeutic angiogenesis, resulting in an improvement in major amputation-free survival rates in patients with CLI.
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http://dx.doi.org/10.1253/circrep.CR-20-0055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819646PMC
August 2020

Real-World Safety Profile of Atrial Fibrillation Ablation Using a Second-Generation Cryoballoon in Japan: Insight From a Large Multicenter Observational Study.

JACC Clin Electrophysiol 2021 05 24;7(5):604-613. Epub 2021 Feb 24.

Department of Cardiovascular Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.

Objectives: This study sought to investigate the incidence and characteristics of the real-world safety profile of second-generation cryoballoon ablation (2nd-CBA) in Japan.

Background: Pulmonary vein isolation using second-generation cryoballoons is an accepted atrial fibrillation ablation strategy.

Methods: This multicenter observational study included 4,173 patients with atrial fibrillation (3,807 paroxysmal) who underwent a 2nd-CBA in 18 participating centers. The baseline data and details of all procedure-related complications within 3 months post-procedure in consecutive patients from the first case at each center were retrospectively collected.

Results: Adjunctive ablation after the pulmonary vein isolation was performed in 2,745 (65.8%) patients. Complications associated with the entire procedure were observed in 206 (4.9%) total patients, and in the multivariate analysis, the age (odds ratio: 1.015; 95% confidence interval: 1.001 to 1.030; p = 0.035) and study period were predictors. Air embolisms manifesting as ST-segment elevation and cardiac tamponade requiring drainage occurred in 63 (1.5%) and 15 (0.36%) patients, respectively. Six (0.14%) patients had strokes/transient ischemic attacks, among whom 5 underwent ablation under an interrupted anticoagulation regimen. No atrioesophageal fistulae occurred; however, 10 (0.24%) patients had symptomatic gastric hypomotility. Esophageal temperature monitoring did not reduce the incidence, and the incidence was significantly higher in patients with adjunctive posterior wall isolations or mitral isthmus ablation than those without (p = 0.004). Phrenic nerve injury occurred during the 2nd-CBA in 58 (1.4%) patients; however, all were asymptomatic and recovered within 13 months. One patient died of aspiration pneumonia.

Conclusions: This study had a high safety profile of 2nd-CBA despite including the early experience and high rate of adjunctive ablation. Care should be taken for air embolisms during 2nd-CBA.
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http://dx.doi.org/10.1016/j.jacep.2020.11.016DOI Listing
May 2021

Sore Hand Syndrome.

Am J Med 2021 Feb 21. Epub 2021 Feb 21.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chuo-ku, Chiba, Japan.

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http://dx.doi.org/10.1016/j.amjmed.2021.01.029DOI Listing
February 2021

CO sign after mitral valve plasty and tricuspid annuloplasty.

QJM 2021 Feb 12. Epub 2021 Feb 12.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.

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http://dx.doi.org/10.1093/qjmed/hcab032DOI Listing
February 2021

In-beam Mössbauer spectra of Mn implanted into lithium aluminum hydride.

Appl Radiat Isot 2021 Apr 20;170:109582. Epub 2021 Jan 20.

National Institute of Radiological Sciences, Inage, Chiba, Japan.

In-beam Mössbauer spectra of Mn implanted into LiAlH were measured at different temperatures between 17 and 300 K. The Mössbauer spectrum measured at 17 K showed two sets of doublets, which were assigned to Fe atoms at substitutional sites at Al and Li sites. The Debye temperatures θ for the Fe atoms at Al-substituted and Li-substituted sites were estimated to be 194 K and 117 K, respectively. The assignments were confirmed by density functional theory calculations.
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http://dx.doi.org/10.1016/j.apradiso.2020.109582DOI Listing
April 2021

Anechoic crescent sign.

BMJ Case Rep 2021 Feb 1;14(2). Epub 2021 Feb 1.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.

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http://dx.doi.org/10.1136/bcr-2020-241358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853005PMC
February 2021

Atrial flutter with alternating tachycardia cycle length after atrial fibrillation ablation.

HeartRhythm Case Rep 2021 Jan 23;7(1):34-38. Epub 2020 Oct 23.

Department of Cardiology, Chiba University Hospital, Chiba, Japan.

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http://dx.doi.org/10.1016/j.hrcr.2020.10.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813786PMC
January 2021

Drug-eluting stent thrombosis: current and future perspectives.

Cardiovasc Interv Ther 2021 Apr 13;36(2):158-168. Epub 2021 Jan 13.

Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Over the past 40 years, the safety and efficacy of percutaneous coronary intervention has dramatically improved by overcoming several challenges. The introduction of drug-eluting stent (DES) in particular was a major breakthrough in interventional cardiology. Compared to bare-metal stents, first-generation DES (G1-DES) has dramatically reduced the rates of in-stent restenosis and subsequent target lesion revascularization. However, major safety concerns surrounding stent thrombosis (ST) emerged with G1-DES in clinical practice as a result of the high incidences of death, myocardial infarction, and repeat revascularization associated with ST. To overcome these limitations, second-generation DES (G2-DES) has been developed with an improved stent platform with thinner strut and biocompatible durable or biodegradable polymers. Indeed, G2-DES, when compared with G1-DES, has improved clinical outcomes by reducing the risk of late thrombotic events while maintaining anti-restenotic efficacy, whereas ST still occurs, even with the use of G2-DES. This review gives an overview of pathophysiology, risk factors, and outcomes of ST after DES implantation. Additionally, we discuss the management and prevention of ST.
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http://dx.doi.org/10.1007/s12928-021-00754-xDOI Listing
April 2021

IVUS Tells a Potential of Late Lumen Enlargement After CTO PCI: The Story so Far.

Cardiovasc Revasc Med 2021 Apr 31;25:18-19. Epub 2020 Dec 31.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan. Electronic address:

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http://dx.doi.org/10.1016/j.carrev.2020.12.029DOI Listing
April 2021