Publications by authors named "Takeshi Ijichi"

25 Publications

  • Page 1 of 1

Antiplatelet Effect of Single Antiplatelet Therapy With Prasugrel and Oral Anticoagulation After Stent Implantation in a Rabbit Arteriovenous Shunt Model.

Circ Rep 2021 Sep 7;3(9):504-510. Epub 2021 Aug 7.

Department of Cardiology, Kindai University Faculty of Medicine Osaka-Sayama Japan.

Antiplatelet therapy following stent implantation in patients requiring oral anticoagulation (OAC) is controversial because triple therapy (i.e., dual antiplatelet therapy [DAPT] with OAC) is associated with a high risk of bleeding. In this study, 21 rabbits were divided into 5 groups: prasugrel and warfarin (Prasugrel+OAC group); aspirin and warfarin (Aspirin+OAC group); prasugrel, aspirin, and warfarin group (Triple group); prasugrel and aspirin (Conventional DAPT group); and no medication (Control group). The treated groups were administered medication for 1 week. An arteriovenous shunt loop was established from the rabbit carotid artery to the jugular vein and 2 bare metal stents were deployed in a silicone tube. After 1 h of circulation, the volume of thrombi was evaluated quantitatively by measuring the amount of protein. Bleeding time was measured at the same time. The volume of the thrombus (amount of protein) around stent struts was lowest in the Triple group, followed by the Prasugrel+OAC and Conventional DAPT groups, and was highest in the Control group. Bleeding time was the longest in the Triple group, followed by the Aspirin+OAC, Prasugrel+OAC, Conventional DAPT, and Control groups. This study suggests that prasugrel with OAC may be a feasible antithrombotic regimen following stent implantation in patients who require OAC therapy.
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http://dx.doi.org/10.1253/circrep.CR-21-0084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423619PMC
September 2021

Impact of exercise capacity on the long-term incidence of atrial arrhythmias in heart failure.

Sci Rep 2021 09 21;11(1):18705. Epub 2021 Sep 21.

Department of Cardiology, Tokai University, Shimokasuya 143, Isehara, Kanagawa, #259-1193, Japan.

We sought to demonstrate the impact of improved peak exercise oxygen consumption (V̇O) during maximal exercise testing after cardiac rehabilitation (CR) on the incidence of arrhythmias in patients with heart failure (HF). The present study comprised of 220 patients with HF, and peak V̇O was examined at 2 and 5 months after CR. Of the 220 patients, 110 (50%) had a low peak V̇O of < 14 mL/min/kg at 2 months. The peak V̇O improved in 86 of these 110 (78%) patients at 5 months after CR. During a median follow-up of 6 years, the patients with improvement in peak V̇O, compared to those without peak V̇O improvement, had a lower rate of mortality (4% vs. 29%, log-rank, P < 0.001) and HF hospitalization (6 vs. 17%, log-rank, P = 0.044) and a lower incidence of new-onset atrial arrhythmias (9 vs. 27%, log-rank, P = 0.013), with no difference in the incidence of ventricular arrhythmias between groups (1 vs. 4%, log-rank, P = 0.309). The majority of deaths in the patients without an improved peak V̇O were because of cardiovascular events (73%), particularly progressive HF (55%). Early detection and management of atrial arrhythmias may improve outcomes in patients without peak V̇O improvement after CR.
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http://dx.doi.org/10.1038/s41598-021-98172-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455607PMC
September 2021

Exosomally derived Y RNA fragment alleviates hypertrophic cardiomyopathy in transgenic mice.

Mol Ther Nucleic Acids 2021 Jun 20;24:951-960. Epub 2021 Apr 20.

Smidt Heart Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA.

Cardiosphere-derived cell exosomes (CDC) and YF1, a CDC-derived non-coding RNA, elicit therapeutic bioactivity in models of myocardial infarction and hypertensive hypertrophy. Here we tested the hypothesis that YF1, a 56-nucleotide Y RNA fragment, could alleviate cardiomyocyte hypertrophy, inflammation, and fibrosis associated with hypertrophic cardiomyopathy (HCM) in transgenic mice harboring a clinically relevant mutation in cardiac troponin I (cTnI). By quantitative PCR, YF1 was detectable in bone marrow, spleen, liver, and heart 30 min after intravenous (i.v.) infusion. For efficacy studies, mice were randomly allocated to receive i.v. YF1 or vehicle, monitored for ambulatory and cardiac function, and sacrificed at 4 weeks. YF1 (but not vehicle) improved ambulation and reduced cardiac hypertrophy and fibrosis. In parallel, peripheral mobilization of neutrophils and proinflammatory monocytes was decreased, and fewer macrophages infiltrated the heart. RNA-sequencing of macrophages revealed that YF1 confers substantive and broad changes in gene expression, modulating pathways associated with immunological disease and inflammatory responses. Together, these data demonstrate that YF1 can reverse hypertrophic and fibrotic signaling pathways associated with HCM, while improving function, raising the prospect that YF1 may be a viable novel therapeutic candidate for HCM.
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http://dx.doi.org/10.1016/j.omtn.2021.04.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141670PMC
June 2021

Late neointimal volume reduction is observed following biodegradable polymer-based drug eluting stent in porcine model.

Int J Cardiol Heart Vasc 2021 Jun 11;34:100792. Epub 2021 May 11.

Department of Cardiology, Tokai University, School of Medicine, Kanagawa, Japan.

Background: The BP-SES has an abluminally applied biodegradable polymer that is fully resorbed after 3-4 months but may have longer-lasting effects. The aim of this study was to determine the long-term vascular response to the novel Ultimaster™ sirolimus-eluting stent (BP-SES).

Methods: BP-SESs, everolimus-eluting stents (DP-EESs), and bare metal stents were implanted in 22 coronary arteries of 15 mini-swine. All animals underwent optical frequent domain imaging (OFDI) to assess neointimal volume and quality at either 1 (n = 7) or 3 (n = 8) months and at 9 (n = 15) months and were euthanized at 9 months. Stents were subsequently histologically investigated to analyze the vascular response and maturity of neointimal tissue according to cell density.

Results: OFDI revealed greater regression in neointimal volume from 3 to 9 months with BP-SESs than with DP-EESs (-0.6 ± 0.5 mm vs. 0.00 ± 0.4 mm,  = 0.07). Although there was no significant difference between BP-SESs and DP-EESs in the inflammation score (BMS, BP-SES, and DP-EES: 0.1 ± 0.1, 0.3 ± 0.4, and 0.4 ± 0.4, respectively;  < 0.0001) in histological analysis, BP-SESs showed slightly greater maturity than DP-EESs (1.8 ± 0.3, 1.7 ± 0.3, and 1.6 ± 0.3,  = 0.09).

Conclusions: While both BP-SESs and DP-EESs showed minimal inflammatory responses at 9 months, BP-SESs showed a trend for greater neointimal maturity and regression, which may be related to earlier completion of the vascular response.
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http://dx.doi.org/10.1016/j.ijcha.2021.100792DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134975PMC
June 2021

Formation of Calcified Nodule as a Cause of Early In-Stent Restenosis in Patients Undergoing Dialysis.

J Am Heart Assoc 2020 10 23;9(19):e016595. Epub 2020 Sep 23.

Department of Cardiology Kindai University Osaka Japan.

Background Dialysis is an independent risk factor for in-stent restenosis (ISR) after stent implantation in coronary arteries. However, the characteristics of ISR in patients undergoing dialysis remain unclear, as there are no histological studies evaluating the causes of this condition. The aim of the present study was to investigate the causes of ISR between patients who are undergoing dialysis and those who are not by evaluating tissues obtained from ISR lesions using directional coronary atherectomy. Methods and Results A total of 29 ISR lesions from 29 patients included in a multicenter directional coronary atherectomy registry of 128 patients were selected for analysis and divided into a dialysis group (n=8) and a nondialysis group (n=21). Histopathological evaluation demonstrated that an in-stent calcified nodule was a major histological characteristic of ISR lesions in the dialysis group and the prevalence of an in-stent calcified nodule was significantly higher in the dialysis group compared with the nondialysis group (75% versus 5%, respectively; <0.01). On the other hand, the prevalence of an in-stent lipid-rich plaque was significantly lower in the dialysis group compared with the nondialysis group (0% versus 43%, respectively; =0.03). In all cases with an in-stent calcified nodule, the underlying calcification before stent implantation was moderate to severe. When tissue characteristics were stratified according to duration post-stent implantation, an in-stent calcified nodule in the dialysis group was mainly observed within 1 year after stent implantation. Conclusions In-stent calcified nodules are a common cause of ISR in patients undergoing dialysis and are observed within 1 year after stent implantation, suggesting different causes of ISR between patients undergoing dialysis and those who are not.
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http://dx.doi.org/10.1161/JAHA.120.016595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792410PMC
October 2020

Comparisons of early vascular reactions in biodegradable and durable polymer-based drug-eluting stents in the porcine coronary artery.

PLoS One 2019 10;14(1):e0209841. Epub 2019 Jan 10.

Department of Cardiology, Tokai University School of Medicine, Kanagawa, Japan.

Current drug-eluting stents have abluminal polymer coating; however, thrombus formation in these compared with that in uniformly coated stents remains controversial. We evaluated thrombus formation and early endothelialization after using abluminal biodegradable polymer-coated sirolimus- (BP-SES), and everolimus-eluting stents (BP-EES) versus a durable polymer-coated everolimus-eluting stent (DP-EES) in an in vivo setting. BP-SES, BP-EES, and DP-EES (n = 6 each) were implanted in coronary arteries of 12 mini-pigs that were then sacrificed after 7 and 10 days. Stents were stained with hematoxylin and eosin, and a combined Verhoeff and Masson trichrome stain. Areas of fibrin deposition were digitally detected and measured with off-line morphometric software. Stents were investigated for re-endothelialization by transmission electron microscopy. At 7 days, histological analysis revealed the lowest area of fibrin deposition in BP-SES (BP-SES vs. BP-EES vs. DP-EES; 0.10 ± 0.06 mm2 vs. 0.15 ± 0.07 mm2 vs. 0.19 ± 0.06 mm2, p = 0.0004). At 10 days, the area of fibrin deposition was significantly greater in DP-EES (0.13 ± 0.04 mm2 vs. 0.14 ± 0.05 mm2 vs. 0.19 ± 0.08 mm2, p = 0.007). Endothelial cells in BP-SES demonstrated a significantly greater number of tight junctions than those in DP-EES according to by transmission electron microscopy for both days (p<0.05). Various parameters, including an inflammatory reaction and neointimal formation, were comparable among the groups at 7 and 10 days. An abluminal biodegradable polymer-coated SES showed the least fibrin deposition and greatest endothelial cell recovery at an early stage following implantation in the coronary arteries of mini-pigs.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0209841PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328177PMC
September 2019

Targeting extracellular vesicles to injured tissue using membrane cloaking and surface display.

J Nanobiotechnology 2018 Aug 30;16(1):61. Epub 2018 Aug 30.

Smidt Heart Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Davis Building, Los Angeles, CA, 90048, USA.

Background: Extracellular vesicles (EVs) and exosomes are nano-sized, membrane-bound vesicles shed by most eukaryotic cells studied to date. EVs play key signaling roles in cellular development, cancer metastasis, immune modulation and tissue regeneration. Attempts to modify exosomes to increase their targeting efficiency to specific tissue types are still in their infancy. Here we describe an EV membrane anchoring platform termed "cloaking" to directly embed tissue-specific antibodies or homing peptides on EV membrane surfaces ex vivo for enhanced vesicle uptake in cells of interest. The cloaking system consists of three components: DMPE phospholipid membrane anchor, polyethylene glycol spacer and a conjugated streptavidin platform molecule, to which any biotinylated molecule can be coupled for EV decoration.

Results: We demonstrate the utility of membrane surface engineering and biodistribution tracking with this technology along with targeting EVs for enhanced uptake in cardiac fibroblasts, myoblasts and ischemic myocardium using combinations of fluorescent tags, tissue-targeting antibodies and homing peptide surface cloaks. We compare cloaking to a complementary approach, surface display, in which parental cells are engineered to secrete EVs with fusion surface targeting proteins.

Conclusions: EV targeting can be enhanced both by cloaking and by surface display; the former entails chemical modification of preformed EVs, while the latter requires genetic modification of the parent cells. Reduction to practice of the cloaking approach, using several different EV surface modifications to target distinct cells and tissues, supports the notion of cloaking as a platform technology.
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http://dx.doi.org/10.1186/s12951-018-0388-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6116387PMC
August 2018

Angiotensin II-Induced End-Organ Damage in Mice Is Attenuated by Human Exosomes and by an Exosomal Y RNA Fragment.

Hypertension 2018 08 4;72(2):370-380. Epub 2018 Jun 4.

From the Smidt Heart Institute (L.C., W.L., T.I., A.K.E., J.V., E.M.)

Hypertension often leads to cardiovascular disease and kidney dysfunction. Exosomes secreted from cardiosphere-derived cells (CDC-exo) and their most abundant small RNA constituent, the Y RNA fragment EV-YF1, exert therapeutic benefits after myocardial infarction. Here, we investigated the effects of CDC-exo and EV-YF1, each administered individually, in a model of cardiac hypertrophy and kidney injury induced by chronic infusion of Ang (angiotensin) II. After 2 weeks of Ang II, multiple doses of CDC-exo or EV-YF1 were administered retro-orbitally. Ang II infusion induced an elevation in systolic blood pressure that was not affected by CDC-exo or EV-YF1. Echocardiography confirmed that Ang II infusion led to cardiac hypertrophy. CDC-exo and EV-YF1 both attenuated cardiac hypertrophy and reduced cardiac inflammation and fibrosis. In addition, both CDC-exo and EV-YF1 improved kidney function and diminished renal inflammation and fibrosis. The beneficial effects of CDC-exo and EV-YF1 were associated with changes in the expression of the anti-inflammatory cytokine IL (interleukin)-10 in plasma, heart, spleen, and kidney. In summary, infusions of CDC-exo or EV-YF1 attenuated cardiac hypertrophy and renal injury induced by Ang II infusion, without affecting blood pressure, in association with altered IL-10 expression. Exosomes and their defined noncoding RNA contents may represent potential new therapeutic approaches for hypertension-associated cardiovascular and renal damage.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.118.11239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6043385PMC
August 2018

Tissue characterization with depth-resolved attenuation coefficient and backscatter term in intravascular optical coherence tomography images.

J Biomed Opt 2017 Sep;22(9):1-16

Leiden University Medical Center, Division of Imaging Processing, Department of Radiology, Leiden, The Netherlands.

An important application of intravascular optical coherence tomography (IVOCT) for atherosclerotic tissue analysis is using it to estimate attenuation and backscatter coefficients. This work aims at exploring the potential of the attenuation coefficient, a proposed backscatter term, and image intensities in distinguishing different atherosclerotic tissue types with a robust implementation of depth-resolved (DR) approach. Therefore, the DR model is introduced to estimate the attenuation coefficient and further extended to estimate the backscatter-related term in IVOCT images, such that values can be estimated per pixel without predefining any delineation for the estimation. In order to exclude noisy regions with a weak signal, an automated algorithm is implemented to determine the cut-off border in IVOCT images. The attenuation coefficient, backscatter term, and the image intensity are further analyzed in regions of interest, which have been delineated referring to their pathology counterparts. Local statistical values were reported and their distributions were further compared with a two-sample t-test to evaluate the potential for distinguishing six types of tissues. Results show that the IVOCT intensity, DR attenuation coefficient, and backscatter term extracted with the reported implementation are complementary to each other on characterizing six tissue types: mixed, calcification, fibrous, lipid-rich, macrophages, and necrotic core.
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http://dx.doi.org/10.1117/1.JBO.22.9.096004DOI Listing
September 2017

Comparison of the endothelial coverage in everolimus and zotarolimus-eluting stents in normal, atherosclerotic, and bifurcation rabbit iliac arteries.

Cardiovasc Interv Ther 2018 Jan 7;33(1):55-61. Epub 2016 Nov 7.

Department of Cardiology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.

The aim of this study is to evaluate differences in stent endothelial coverage among the second generation of drug-eluting stents. Incomplete stent coverage is one of the major causes of late stent thrombosis. Rabbits fed a normal diet received an everolimus (Xience Prime; EES) and a zotarolimus-eluting stent (Resolute Integrity; R-ZES) in each iliac artery, followed by sacrifice at 14 and 28 days after stent implantation. In addition, a group of atherosclerotic rabbits similarly received EES and R-ZES, and were sacrificed at 28 days. The extent of stent endothelial coverage was assessed by scanning electron microscopy. To evaluate endothelial coverage after bifurcation stenting, rabbits received EES and R-ZES placed with culotte stenting at the iliac bifurcation, followed by sacrifice at 14 and 28 days. In rabbits fed a normal diet, the percent uncovered strut area 14 days after stent implantation was significantly higher in R-ZES than in EES (10.1% (IQR 9.8-15.5) vs. 3.0% (IQR 1.5-9.7), p = 0.03), whereas it was not significantly different at 28-days (3.9% (IQR 0.8-10.3) vs. 1.0% (IQR 0.0-2.8), p = 0.2). In rabbits with induced atheroma, R-ZES also showed less endothelial coverage 28 days after stent implantation (5.3% (IQR 2.2-9.9) vs. 1.1% (IQR 0-6.2), p = 0.03). In the culotte stenting model, the percent uncovered strut area of the proximal overlapped segment was significantly higher in R-ZES at 14 days (15.8% (IQR 14.3-17.7) vs. 8.8% (IQR 8.3-9.8), p = 0.03) and 28 days (9.9% (IQR 4.1-13.9) vs. 2.5% (IQR 1.6-6.7), p = 0.04) after stent implantation. The carina area also showed a better coverage in EES compared with R-ZES. EES showed a better stent endothelial coverage compared with R-ZES after stent implantation in the early phase in normals, in arteries with lipid rich plaque, and in bifurcation stented sites.
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http://dx.doi.org/10.1007/s12928-016-0437-6DOI Listing
January 2018

Comparison of Vascular Responses Following New-Generation Biodegradable and Durable Polymer-Based Drug-Eluting Stent Implantation in an Atherosclerotic Rabbit Iliac Artery Model.

J Am Heart Assoc 2016 10 19;5(10). Epub 2016 Oct 19.

Department of Cardiology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.

Background: Incomplete endothelialization is the primary substrate of late stent thrombosis; however, recent reports have revealed that abnormal vascular responses are also responsible for the occurrence of late stent failure. The aim of the current study was to assess vascular response following deployment of biodegradable polymer-based Synergy (Boston Scientific) and Nobori (Terumo) drug-eluting stents and the durable polymer-based Resolute Integrity stent (Medtronic) in an atherosclerotic rabbit iliac artery model.

Methods And Results: A total of 24 rabbits were fed an atherogenic diet, and then a balloon injury was used to induce atheroma formation. Synergy, Nobori, and Resolute Integrity stents were randomly implanted in iliac arteries. Animals were euthanized at 28 days for scanning electron microscopic evaluation and at 90 days for histological analysis. The percentage of uncovered strut area at 28 days was lowest with Synergy, followed by Resolute Integrity, and was significantly higher with Nobori stents (Synergy 1.1±2.2%, Resolute Integrity 2.0±3.9%, Nobori 4.6±3.0%; P<0.001). At 90 days, inflammation score was lowest for Synergy (0.27±0.45), followed by Nobori (0.62±0.59), and was highest for Resolute Integrity (0.89±0.46, P<0.001). Foamy macrophage infiltration within neointima (ie, neoatherosclerosis) was significantly less with Synergy (0.62±0.82) compared with Nobori (0.85±0.74) and Resolute Integrity (1.39±1.32; P=0.034).

Conclusions: The biodegradable polymer-coated thin-strut Synergy drug-eluting stent showed the fastest stent strut neointimal coverage and the lowest incidence of neoatherosclerosis in the current animal model.
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http://dx.doi.org/10.1161/JAHA.116.003803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5121480PMC
October 2016

Treat-to-target lipid control is effective but highlighted poor prognosis without indication of statin following percutaneous coronary intervention.

Cardiovasc Interv Ther 2017 Oct 18;32(4):358-364. Epub 2016 Aug 18.

Division of Cardiology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1143, Japan.

A reduction of low-density lipoprotein cholesterol (LDL-C) is important for the secondary prevention of coronary artery disease. We performed secondary prevention in 632 consecutive patients, including 315 with acute coronary syndrome, who underwent percutaneous coronary intervention according to current treat-to-target lipid-lowering guidelines to achieve LDL-C <100 mg/dL. We retrospectively analyzed 2-year all-cause mortality. The average LDL-C level was reduced from 114 ± 36 mg/dL at baseline to 94 ± 25 mg/dL at follow-up; 61 % of patients achieved the guideline target. Statin was not prescribed for 42 (6.6 %) patients, with reasons mainly due to a low baseline LDL-C level, however, renal failure, an older age, stable coronary artery disease and having a female gender were also related factors. At the end of follow-up (average 2.0 ± 0.9 years), 90 % of patients were on statins and showed a lower 2-year mortality rate than those not on statins (3.3 vs. 20.5 %, p < 0.001). In contrast, achieving LDL-C target levels did not impact mortality (4.9 vs. 4.8 %, p = 0.99). Propensity score matching analysis revealed statin use to be a predictor of better survival (p = 0.009) after adjusting for a baseline difference between statin and no statin groups. A multivariable Cox proportional hazard showed that age (HR = 1.12, 95 % CI 1.03-1.22) and statin use (HR = 0.14, 95 % CI 0.008-0.77) were predictors of survival. Statin use was a significant predictor of improved mortality rates under treat-to-target guidelines. However, it also highlighted a poor prognosis in patients without an indication for statins.
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http://dx.doi.org/10.1007/s12928-016-0419-8DOI Listing
October 2017

Transcatheter closure of atrial septal defect protects from pulmonary edema: septal occluder device gradually reduces LR shunt.

Heart Vessels 2017 Jan 17;32(1):101-104. Epub 2016 Jun 17.

Department of Cardiology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.

A 56-year-old woman was diagnosed as atrial septal defect (ASD) with pulmonary hypertension; pulmonary blood flow/systemic blood flow (Qp/Qs) of 2.3, pulmonary artery pressure (PAP) of 71/23(39) mmHg and diastolic dysfunction of left ventricle. PAP was improved after medical therapy; therefore, transcatheter ASD closure was performed. Seven days later, left-sided heart failure occurred, however, the improvement of Qp/Qs (1.7) and PAP of 51/21(32) was confirmed. Diuretic therapy was introduced which led to further decrease of PAP 40/12(25) and Qp/Qs (1.1). Because of gradual decrease of Qp/Qs, this patient appeared to be protected from acute pulmonary edema.
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http://dx.doi.org/10.1007/s00380-016-0863-5DOI Listing
January 2017

Impact of a single universal guiding catheter on door-to-balloon time in primary transradial coronary intervention for ST segment elevation myocardial infarction.

Cardiovasc Interv Ther 2017 Apr 28;32(2):114-119. Epub 2016 Apr 28.

Department of Cardiology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, 259-1193, Kanagawa, Japan.

The purpose of this study is to determine reduction of door-to-balloon (D2B) time using a single universal guiding catheter (Ikari-Left catheter) in transradial approach. In this procedure, we can skip a total of five steps compared with a conventional procedure (two catheter insertions, two catheter removals, and one catheter engagement). Reducing total ischemic time is important to achieving a better outcome in primary percutaneous coronary intervention (PCI) for ST segment elevation myocardial infarction (STEMI). We retrospectively compared 30 consecutive STEMI patients who underwent transradial primary PCI with a single guiding catheter (IL group) with 30 consecutive patients with conventional transradial primary PCI. Patients with cardiogenic shock, heart failure, or need for intra-aortic balloon pumping support before primary PCI were excluded. Baseline characteristics were not different between the two groups. The D2B time was significantly shorter in the IL group (55 ± 16 vs. 63 ± 17 min, respectively; p = 0.01). Puncture-to-balloon time was also significantly shorter in the IL group (15 ± 11 min vs. 25 ± 11 min, respectively; p = 0.001). The total number of diagnostic and guiding catheters was significantly less in IL group (1 (IQR 1-1) vs. 3 (IQR 3-3), respectively; p < 0.0001). Primary PCI with a single universal guiding catheter reduced D2B time by skipping several procedural steps, and reduced the total number of catheters needed. This technique could reduce patient mortality as well as total medical cost.
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http://dx.doi.org/10.1007/s12928-016-0395-zDOI Listing
April 2017

[Introduction and PDCA-Management of a Liaison-Clinical Pathway with Cancer Patients after a Curative Operation].

Gan To Kagaku Ryoho 2015 Oct;42(10):1197-201

Dept. of Surgery, Osaka Saiseikai Izuo Hospital.

Our hospital was appointed as an Osaka designated cancer care hospital in April 2012. At that time, we introduced the same liaison-clinical pathway with cancer patients after a curative operation in all of Osaka. Based on the management of the plan-do-check-act cycle, we found problems in the clinical pathway. These problems included the following: the clinical pathway was not known, was complicated, was troubling for patients, and not well understood by doctors. To solve these problems, we planned and carried out the following five measures. The first was public information, followed by practice processes, informed consent, patient referral documents, and clinical pathway investigation reports. We were able to promote the use of the liaison-clinical pathway by constantly improving these measures.
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October 2015

Simultaneous Intravascular Ultrasound Usage Overcomes Misinterpretation When Evaluating Lipid-Rich Plaques With Optical Frequency Domain Imaging--Ex Vivo Study.

Circ J 2015 21;79(12):2641-7. Epub 2015 Oct 21.

Department of Cardiology, Tokai University School of Medicine.

Background: The aim of this study was to investigate the accuracy of optical frequency domain imaging (OFDI) in lipid-rich plaque detection and determine the causes of "misinterpretation," and evaluate whether these limitations can be overcome with intravascular ultrasound (IVUS) using ex-vivo human coronaries.

Methods and results: The OFDI images and corresponding 218 histological segments were evaluated. Segments with a poor signal and diffuse borders on OFDI, classified as lipid-rich plaques, were compared with the histological segments and IVUS images. Using histological images as the gold standard, the sensitivity, specificity, positive predictive value, and negative predictive value of OFDI for the detection of lipid-rich plaques were 93%, 93%, 85%, and 97%, respectively. The causes of false-positive diagnosis of lipid-rich plaque (11 segments) were superficial macrophage infiltration causing signal attenuation (8/11 segments, 73%) and tangential signal dropout of light (3/11 segments, 27%), whereas the cause of false-negative diagnosis was thickening of the fibrous cap (5 segments, 100%). Simultaneous IVUS helped to correct the misinterpretation of OFDI results and improved the diagnostic accuracy; the sensitivity, specificity, positive predictive value, and negative predictive value of OFDI with adjunct use of IVUS were 96%, 99%, 99%, and 98%, respectively.

Conclusions: OFDI occasionally over- or underestimates the existence of lipid-rich plaques, which may be overcome with adjunctive usage of IVUS.
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http://dx.doi.org/10.1253/circj.CJ-15-0490DOI Listing
September 2016

Evaluation of coronary arterial calcification - Ex-vivo assessment by optical frequency domain imaging.

Atherosclerosis 2015 Nov 7;243(1):242-7. Epub 2015 Sep 7.

Tokai University School of Medicine, Kanagawa, 259-1193, Japan.

Aims: The purpose of this study was to determine the diagnostic ability of optical frequency domain imaging (OFDI) to carry out quantitative and qualitative evaluation of coronary calcification in comparing with ex vivo human autopsy heart specimens.

Methods: Analysis was carried out in 25 coronary artery specimen obtained from 16 cadavers that were imaged ex-vivo imaging by OFDI and intravascular ultrasound (IVUS). Of 235 cross-sections obtained for histologic evaluation, 149 were classified as showing calcified plaques, and in this group a comparison between histology versus co-registered images by OFDI and IVUS was performed.

Results: Maximum thickness of calcification measured by OFDI was well correlated with histology (rs = 0.70, p < 0.0001) whereas IVUS was not useful for quantitative analysis because of the presence of acoustic shadows occurring behind calcifications. Furthermore qualitative evaluation could be carried out using OFDI, for calcifications with vague or invisible outer borders by OFDI had lipid contents (lipid pool or histologic necrotic core) more frequently as compared to those with a clear outer border (79% vs. 24%, p < 0.0001). We also found that calcified nodules, a well-recognized thrombogenic substrate, demonstrated atypical appearance in OFDI, showing irregular surfaces with high attenuation.

Conclusion: OFDI demonstrated a greater ability than IVUS to provide quantitative and qualitative evaluation of coronary arterial calcification. Precise recognition of calcified plaque morphology by OFDI may serve to determine the treatment strategy of patients having atherosclerotic coronary disease.
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http://dx.doi.org/10.1016/j.atherosclerosis.2015.09.002DOI Listing
November 2015

The Efficacy and Feasibility of Chronic Total Occlusion by Transradial Intervention: A Japanese Single-Center Retrospective Study.

J Invasive Cardiol 2015 Sep;27(9):E177-81

Department of Cardiology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.

Objectives: To evaluate transradial intervention (TRI) for chronic total occlusion (CTO).

Background: Although TRI has been applied to more complex lesions in percutaneous coronary intervention, efficacy and feasibility of TRI versus transfemoral intervention (TFI) for CTO have not yet been determined.

Methods: We retrospectively analyzed 207 CTO lesions in 195 patients in a single center between January 2008 and December 2011. Patients were divided into four groups according to procedures: TRI (135 lesions in 124 patients); TFI (40 lesions in 39 patients); TRI/TFI (20 lesions in 20 patients); and TFI/TFI (12 lesions in 12 patients). Antegrade approach was used in TRI and TFI, but antegrade plus retrograde approach was used in TRI/TFI and TFI/TFI.

Results: Although there were no differences in patient characteristics, complex CTO lesions such as blunt-type entry and retry lesions were frequently observed in the TFI/TFI group. Average sheath size was 5.7 Fr for TRI and 6.6 Fr for TFI. Fluoroscopy time was significantly longer for the antegrade plus retrograde approach. Procedure success rates were not statistically different: 82.2% in TRI, 72.5% in TFI, 75.0% in TRI/TFI, and 75.0% in TFI/TFI groups. There was no death, myocardial infarction, or stroke at 30 days in any groups. Two femoral cases and no radial cases had access-site complications. Access-site crossover from radial to femoral was conducted in 4 cases.

Conclusion: More than one-half of CTO lesions can be treated with high success and low complication rates by TRI if the lesions are carefully selected.
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September 2015

Coronary angiographic characteristics that influence fractional flow reserve.

Circ J 2015 30;79(4):802-7. Epub 2015 Jan 30.

Department of Cardiology, Tokai University Hospital.

Background: Percutaneous coronary intervention (PCI) guided with fractional flow reserve (FFR) has been shown to improve clinical outcome. Although coronary angiography is the standard method for PCI guidance, the visual severity of stenosis is not always correlated with functional severity, suggesting that there are additional angiographic factors that affect functional ischemia.

Methods And Results: To evaluate angiographic predictors of positive FFR in stenotic lesions, angiographic characteristics of 260 consecutive patients (362 lesions) who underwent FFR testing from April 2009 to September 2012 were analyzed. A scoring system (STABLED score) using these predictors was developed and compared with quantitative coronary angiography (QCA). %Diameter stenosis >50% (OR, 8.43; P<0.0001), tandem lesion (OR, 4.00; P<0.0001), true bifurcation (OR, 2.42; P=0.028), lesion length >20 mm (OR, 5.40; P=0.0002), and distance from ostium <20 mm (OR, 1.94; P=0.028) were determined as independent predictors of positive FFR. Area under the ROC curve for probability of positive FFR using the STABLED score (Stenosis 2 points, TAndem lesion 1 point, Bifurcation 1 point, LEsion length 1 point, Distance from ostium 1 point) was 0.85, higher than that for QCA stenosis alone (0.76). STABLED score ≥3 had 72.3% sensitivity and 83.6% specificity for predicting positive FFR, and PPV was 76.7%.

Conclusions: Specific angiographic features are applicable for predicting functional ischemia. STABLED score correlates well with FFR.
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http://dx.doi.org/10.1253/circj.CJ-14-0931DOI Listing
December 2015

Comparison of vascular response between durable and biodegradable polymer-based drug-eluting stents in a porcine coronary artery model.

EuroIntervention 2014 Oct;10(6):717-23

Department of Cardiology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.

Aims: Biodegradable polymer-based drug-eluting stents are thought to be safer than durable polymer-based stents. However, the long-term vascular response remains unclear. The aim of this study was to compare the biocompatibility of durable polymer-based sirolimus-eluting (SES) and everolimus-eluting (EES) stents with biodegradable polymer-based biolimus-eluting (BES) stents in a porcine coronary model. Stents were implanted in porcine coronaries. Acetylcholine challenge tests and optical coherence tomography (OCT) examination were performed at one month. Animals were sacrificed at three and six months (n=6 each), and the stents were analysed histologically. At one month, acetylcholine challenge tests revealed a trend towards greatest vasoconstriction in SES, less in BES, and least in EES, but the differences were not significant. OCT analysis demonstrated the highest incidence of uncovered struts in SES, followed by BES, while EES showed almost complete strut coverage (41.7±27.0%, 24.5±23.8%, 0.4±0.8%, respectively; p=0.004). Upon histological analysis at three months, SES showed a significantly higher inflammatory score than BES and EES (2.9±1.4, 0.8±0.9, 0.5±0.4, respectively; p=0.001), and this was maintained at six months (1.6±1.5, 0.3±0.3, 0.4±0.6, respectively; p=0.049). While SES showed an increased inflammatory reaction, EES and BES showed minimal inflammation. These results indicate that the late inflammatory reaction does not necessarily depend on degradability of the polymer, if the combination of the drug, metal, and polymer is biocompatible.
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http://dx.doi.org/10.4244/EIJV10I6A124DOI Listing
October 2014

Optical coherence tomography and histopathology assessment after implantation of first- and second-generation drug-eluting stents in a porcine coronary model.

Circ J 2014 27;78(11):2665-73. Epub 2014 Sep 27.

Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine.

Background: This study directly compared optical coherence tomography (OCT) and histopathology for the assessment of vascular response to first- and second-generation drug-eluting stents. METHODS AND RESULTS: Sirolimus-, everolimus-, and biolimus-eluting stents (SES, EES, and BES, respectively) were randomly implanted into the coronary arteries of 12 porcine. OCT was conducted after implantation: at 1, 3, and 6 months; histopathology was assessed at 3 and 6 months. At 1-month OCT, EES had the highest neointimal area (NA) and lowest neointimal unevenness score (NUS). At 6 months, NA and NUS were equivalent among the stent types. ∆NA from 1 to 6 months was lowest for EES, and ∆NA correlated with the histopathological inflammation score at 6 months, which was highest for SES (P<0.001). The mean signal intensity (MSI) and the attenuation were different for the stent types at 3 months, and were associated with inflammation score. Moderate diagnostic efficiency for measuring MSI was found, with an optimal cut-off of 6.88 predicting a high (≥grade 3) inflammation score.

Conclusions: EES had the greatest uniformity and the least neointimal proliferation and were associated with less persistent inflammation. OCT provides accurate morphometric data; furthermore, quantitative measurement of the optical properties may help assess histological inflammation, which was more predominantly associated with SES than with EES and BES.
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http://dx.doi.org/10.1253/circj.cj-14-0315DOI Listing
June 2015

Comparison of in vivo longitudinal strength and conformability following stent implantation in rabbit iliac artery.

J Invasive Cardiol 2014 Feb;26(2):64-9

Tokai University School of Medicine, Cardiology, 143 Shimokasuya, Isehara, Kanagawa 2591193, Japan.

Objectives: The aim of this study was to determine the in vivo longitudinal strength and conformability of various stent platforms following stent implantation in rabbit iliac arteries.

Background: Recently, longitudinal coronary stent deformation has been highlighted and bench tests have demonstrated differences in longitudinal strength among various stent platforms. However, this has not been investigated in an in vivo setting. This is of interest because there may be a trade-off between longitudinal strength and conformability.

Methods: We evaluated 4 types of commercially available stents: Multi-Link 8 (Abbott Vascular); Omega (Boston Scientific); Integrity (Medtronic); and Nobori (Terumo Corporation). To investigate the longitudinal strength, constant axial force was applied to the stent edge by a guiding catheter after deployment in a rabbit iliac artery. The amount of longitudinal stent deformation was calculated by measuring stent length. In order to evaluate conformability, stents were deployed crossing over the iliac bifurcation and the bifurcation angles were measured before and after stent implantation. If the change in the angle was small, the stent was considered to be more conformable.

Results: The Omega stent demonstrated significantly greater longitudinal compression compared with other stents (Omega, 17.4 ± 9.3%; Multi-Link 8, 2.8 ± 2.3%; Integrity, 2.8 ± 1.4%; Nobori, 3.8 ± 3.2%; P=.01), but Omega showed better conformability, as evidenced by the smallest percent change in the bifurcation angle (Omega, 12.7 ± 0.8%; Multi-Link 8, 25.7 ± 2.4%; Integrity, 28.3 ± 1.1%; Nobori, 28.1 ± 6.8%; P=.03).

Conclusion: In this rabbit model, the Omega stent, which has the platform of the Element stent, showed less longitudinal strength but greater conformability compared with the other stent platforms.
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February 2014

Transradial intervention for patients with ST elevation myocardial infarction with or without cardiogenic shock.

Catheter Cardiovasc Interv 2014 Jan 25;83(1):E1-7. Epub 2013 Sep 25.

Division of Cardiology, Tokai University School of Medicine, Isehara, Japan.

Objectives: To compare clinical outcomes between transradial (TRI) and transfemoral intervention (TFI) in primary percutaneous coronary intervention (PCI) in patients with ST elevation myocardial infarction (STEMI) with or without shock.

Background: TRI for STEMI has benefits in TRI high volume centers. However, TRI has not been reported for STEMI with shock even in such centers.

Methods: We retrospectively studied 425 STEMI patients who underwent primary PCI. Patients were divided into four groups according to approach site and presence of cardiogenic shock, including TRI without shock (TR group, n = 273), TRI with shock (TRS group, n = 38), TFI without shock (TF group, n = 71), and TFI with shock (TFS group, n = 43).

Results: PCI success rates were similar among the four groups. The TR group was superior to the TF group in terms of shorter cath lab to first device activation time, and lower access site complications, and 30-day mortality rates (1.1% vs. 11.3%, P < 0.001). In shock patients, cardiopulmonary arrest was commonly observed in both the TRS and TFS groups (42.1% and 51.2%, respectively). The TRS group showed a trend toward a shorter door to first device activation time compared to the TFS group and lower access site complications; however, 30-day mortality rate was 28.9% in TRS and 25.6% in TFS group (P = 0.7).

Conclusions: In TRI high volume center, TRI for STEMI was safe and feasible as a default approach. TRI could be applied to severe shock patients with similar clinical outcome to TFI.
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http://dx.doi.org/10.1002/ccd.24896DOI Listing
January 2014

Transradial coronary angiography with virtual 1 French, sheathless 3 French catheter.

Catheter Cardiovasc Interv 2013 Nov 8;82(5):E676-7. Epub 2013 Aug 8.

Department of Cardiology, Tokai University School of Medicine, Kanagawa, Japan.

Minimizing catheter size can reduce bleeding complications in coronary angiography. We herein report extreme slender "needle size" (19-G) coronary diagnostic catheterization using a new 3-Fr diagnostic catheter by sheathless method. A 58-year-old man having effort angina underwent coronary angiography. The 3-Fr Ikari Left diagnostic catheter, which is equal to 19-G, was inserted smoothly both for left and right coronary arteries by sheathless method. We only needed 4 min to achieve hemostasis with manual compression after catheter withdrawal in this case.
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http://dx.doi.org/10.1002/ccd.24885DOI Listing
November 2013

Feasibility of 6 Fr intra-aortic balloon pumping via the femoral or brachial approach.

J Invasive Cardiol 2012 Dec;24(12):641-4

Department of Cardiology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, 259- 1193, Japan.

Objectives: To demonstrate safety and efficacy of new 6 Fr intra-aortic balloon pumping (IABP) system.

Background: Access-site complications have been reported to increase adverse events following PCI. Some reports have shown access-site complications in conventional 8-Fr compatible IABP system. The new 6 Fr IABP system may reduce the complication rate due to the smaller size.

Methods: We extracted medical records for patients who underwent elective percutaneous coronary intervention under prophylactic 6 Fr or 8 Fr IABP assistance from January 2006 to December 2009 at Tokai University School of Medicine. The clinical outcomes were compared between 6 Fr and 8 Fr or between transfemoral and transbrachial IABP.

Results: A total of 42 cases were extracted, including 20 cases using 6 Fr IABP (47.6%) and 22 cases using 8 Fr IABP (52.4%). The 6 Fr IABP included 15 cases of transbrachial approach (75.0%) and 5 cases of transfemoral approach (25.0%). All cases of 8 Fr IABP were via transfemoral approach. The bedrest time was clearly shorter in the 6 Fr IABP group (75.8 ± 139.8 minutes vs 360.0 ± 104.7 minutes in the 8 Fr IABP group; P<.001). Bedrest time and duration of hospitalization were shorter in the transbrachial IABP group (0.0 ± 0.0 minutes and 1.0 days [interquartile range, 1.0- 2.0 days] vs 288.0 ± 107.3 minutes and 5.0 days in the transfemoral group [interquartile range, 3.0-8.0]; P<.001). Access-site complications were 0% with the 6 Fr system, but 13.6% with the 8 Fr IABP system.

Conclusions: This study demonstrated that the 6 Fr IABP system and its transbrachial application may be feasible because of lower complication rates.
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December 2012
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