Publications by authors named "Youichi Kobayashi"

107 Publications

Clinical predictors for bradycardia and supraventricular tachycardia necessitating therapy in patients with unexplained syncope monitored by insertable cardiac monitor.

Clin Cardiol 2021 May 16;44(5):683-691. Epub 2021 Mar 16.

Division of Cardiology, Department of Medicine, Showa University, Tokyo, Japan.

Background: Insertable cardiac monitors (ICMs) improve diagnostic yield in patients with unexplained syncope. The most of cardiac syncope is arrhythmic causes include paroxysmal bradycardia and supraventricular tachycardia (SVT) in patients with unexplained syncope receiving ICM. Predictors for bradycardia and SVT that necessitate therapy in patients with unexplained syncope are not well known.

Hypothesis: This study aimed to investigate predictors of bradycardia and SVT necessitating therapy in patients with unexplained syncope receiving ICMs.

Methods: We retrospectively reviewed medical records of consecutive patients who received ICMs to monitor unexplained syncope. We performed Cox's stepwise logistic regression analysis to identify significant independent predictors for bradycardia and SVT.

Results: One hundred thirty-two patients received ICMs to monitor unexplained syncope. During the 17-month follow-up period, 19 patients (14%) needed pacemaker therapy for bradycardia; 8 patients (6%) received catheter ablation for SVT. The total estimated diagnostic rates were 34% and 48% at 1 and 2 years, respectively. Stepwise logistic regression analysis indicated that syncope during effort (odds ratio [OR] = 3.41; 95% confidence interval [CI], 1.21 to 9.6; p = .02) was an independent predictor for bradycardia. Palpitation before syncope (OR = 9.46; 95% CI, 1.78 to 50.10; p = .008) and history of atrial fibrillation (OR = 10.1; 95% CI, 1.96 to 52.45; p = .006) were identified as significant independent predictors for SVT.

Conclusion: Syncope during effort, and palpitations or history of atrial fibrillation were independent predictors for bradycardia and for SVT. ICMs are useful devices for diagnosing unexplained syncope.
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http://dx.doi.org/10.1002/clc.23594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119800PMC
May 2021

Efficacy and safety of early initiation of eplerenone treatment in patients with acute heart failure (EARLIER trial): a multicenter, randomized, double-blind, placebo-controlled trial.

Eur Heart J Cardiovasc Pharmacother 2020 Nov 11. Epub 2020 Nov 11.

Division of Cardiology, Osaka General Medical Center, Osaka, Japan.

Aims: A mineralocorticoid receptor antagonist (MRA) is effective in patients with chronic heart failure; however, the effects of the early initiation of an MRA in patients with acute heart failure (AHF) have not been elucidated.

Methods And Results: In this multicenter, randomized, double-blind, placebo-controlled, parallel-group study, we focused on the safety and effectiveness of the treatment with eplerenone, a selective MRA in 300 patients with AHF, that is, 149 in the eplerenone group and 151 in the placebo group in 27 Japanese institutions. The key inclusion criteria were (1) patients aged 20 years or older and (2) those with left ventricular ejection fraction of ≤ 40%. The primary outcome was a composite of cardiac death or first re-hospitalization due to cardiovascular disease within 6 months. The mean age of the participants was 66.8 years, 27.3% were women, and the median levels of brain natriuretic peptide were 376.0 pg/mL. The incidences of the primary outcome were 19.5% in the eplerenone group and 17.2% in the placebo group (hazard ratio (HR): 1.09, 95% confidence interval (CI): 0.642-1.855). In prespecified secondary outcomes, HR for the composite endpoint, cardiovascular death, or first re-hospitalization due to heart failure (HF) within 6 months was 0.55 (95% CI: 0.213 to 1.434). The safety profile for eplerenone was as expected.

Conclusion: The early initiation of eplerenone in patients with AHF could safely be utilized. The reduction of the incidence of a composite of cardiovascular death or first re-hospitalization for cardiovascular diseases by eplerenone is inconclusive because of inadequate power.
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http://dx.doi.org/10.1093/ehjcvp/pvaa132DOI Listing
November 2020

Dapagliflozin Influences Ventricular Hemodynamics and Exercise-Induced Pulmonary Hypertension in Type 2 Diabetes Patients - A Randomized Controlled Trial.

Circ J 2020 09 12;84(10):1807-1817. Epub 2020 Sep 12.

Department of Medicine, Division of Cardiology, Showa University School of Medicine.

Background: This prospective randomized multicenter open-label trial evaluated whether sodium-glucose cotransporter-2 inhibitor (SGLT2-i) improves left ventricular (LV) pump function and suppresses elevation of LV filling pressure (LVFP) and right ventricular systolic pressure (RVSP) during exercise in type 2 diabetes mellitus (T2DM) patients.Methods and Results:Based on HbA1c and LV ejection fraction, 78 patients with poorly controlled T2DM were randomly assigned to D-group (dapagliflozin 5 mg/day add-on) or C-group (conventional therapy add-on). Physical examination, home and office blood pressure examination, blood tests, and echocardiography at rest and during ergometer exercise were performed at baseline and at 1.5 and 6 months after treatment. The primary endpoint was defined as the change in RVSP (mmHg) between baseline and 6-month follow up. The secondary endpoints were changes in LVFP (ratio), stroke volume index (SVi; mL/m), and cardiac index (CI; L/min/m). Both RVSP and LVFP during exercise significantly decreased from baseline to 6 months after starting treatment in the D-group (P<0.001). No changes to either parameter was observed in the C-group. The SVi and CI did not improve in either group. Both home and office blood pressure significantly decreased in the D-group. Decreases in HbA1c were somewhat greater in the C-group.

Conclusions: Dapagliflozin significantly improved RVSP and LVFP during exercise in patients with T2DM and cardiovascular risk, which may contribute to favorable effects on heart failure.
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http://dx.doi.org/10.1253/circj.CJ-20-0341DOI Listing
September 2020

Caesarean Section of Multifetal Pregnancy.

Surg J (N Y) 2020 Jul 16;6(Suppl 2):S92-S97. Epub 2020 Jun 16.

Department of Obstetrics and Gynecology, Kyorin University School of Medicine, Mitaka City, Tokyo, Japan.

Planned caesarean delivery (CD) did not significantly decrease or increase the risk of fetal or neonatal death or serious neonatal morbidity in twin pregnancy between 32 and 38 weeks of gestation, with the first twin in the vertex presentation. As prevalence rises for the second twin, emergency CD is necessary for delivery of the second twin after vaginal delivery of the first twin. Waiting after 38 weeks' gestation essentially requires close fetal and maternal surveillance to identify if those pregnancies may benefit to extend a gestational period. It is important to construct a system in which an emergency CD can be performed anytime. The caesarean section does not change in even multifetal pregnancy. Each step after laparotomy has few tips: (1) because the uterus strongly leans to the right, image the uterine rotation. To avoid thick vessels on the uterine lateral wall, perform long -shaped incision using a scissor. 2) Ensure not to rupture the membrane of the second twin before delivery of the first twin. (3) Check the presentation of the second twin before rupture of that fetus's membrane. The second twin tends to change the presentation. If the upper uterine segment will clamp down and entrap the second twin, a vertical uterine incision is performed without hesitation. Women with multifetal pregnancy are at increased risk of postpartum hemorrhage (PPH). Mainly PPH is caused by uterine atony. Oxytocin should be prepared before starting the CD. All bleeding may not be recognized in the operation field. Do not lose the timing of blood transfusion.
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http://dx.doi.org/10.1055/s-0040-1712924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396478PMC
July 2020

Idiopathic basal crux ventricular arrhythmias with left bundle branch block and superior axis: A comparison with inferior-septal valvular arrhythmias.

J Cardiovasc Electrophysiol 2019 10 22;30(10):1914-1922. Epub 2019 Aug 22.

Division of Cardiology, Showa University School of Medicine, Tokyo, Japan.

Introduction: Left bundle branch block (LBBB) with superior axis is common in patients with idiopathic-ventricular arrhythmia (VA) originating from the tricuspid annulus (TA) and rarely from the cardiac basal crux and mitral annulus (MA). We described the electrocardiography and electrophysiological findings of idiopathic-VA presenting with LBBB and superior axis.

Methods And Results: We described 42 idiopathic-VA patients who had an LBBB and superior axis; 15 basal crux-VA, 17 TA-VA, and 10 MA-VA. No patient had a structural heart disease. Among patients with idiopathic-VA referred for ablation, we investigated the electrocardiogram and clinical characteristics of basal crux-VA as compared with other LBBB and superior axis-VA. The left ventricular ejection fraction with MA-VA was significantly lower in comparison with basal crux-VA (P = .01). All patients had a positive R wave in lead I and aVL. The maximum deflection index with basal crux-VA was significantly higher in comparison with TA-VA or MA-VA (P = .01). Patients with basal crux-VA presented with QS wave in lead II more frequently as compared with TA-VA or MA-VA (P = .001). All MA-VA patients had Rs wave in V6, and basal crux-VA, and TA-VA patients had a monophasic R wave or Rs wave in V6. Basal crux-VA patients underwent ablation in the middle cardiac vein (MCV) or coronary sinus (success rate: 94%, recurrence rate: 6%).

Conclusions: We could distinguish basal crux-VA, TA-VA, and MA-VA, using a combination of clinical and electrocardiographic findings. These findings might be useful for counseling patients about an ablation strategy. Ablation via the MCV is effective for eliminating basal crux-VA.
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http://dx.doi.org/10.1111/jce.14103DOI Listing
October 2019

J-Wave Elevation in the Inferior Leads Predicts Lethal Ventricular Arrhythmia Initiated by Premature Ventricular Contractions With Right Bundle Branch Block and Superior Axis.

Circ J 2019 08 8;83(9):1851-1859. Epub 2019 Aug 8.

Division of Cardiology, Department of Medicine, Showa University School of Medicine.

Background: Lethal ventricular arrhythmia (VA) can be initiated by idiopathic premature ventricular contractions (PVCs) originating from the left ventricular (LV) inferior wall. Furthermore, J-wave elevation in the inferior leads on ECG is sometimes associated with lethal VA. However, the relationship between these PVCs and J-wave elevation in patients with lethal VA is unclear, so we investigated it in the present study.Methods and Results:We studied 32 consecutive patients who underwent radiofrequency (RF) ablation of idiopathic PVCs with right bundle branch block (RBBB) and superior axis. Thee PVCs were originating from the inferior wall of the LV. Lethal VA was defined as ventricular fibrillation (VF) or ventricular tachycardia (VT) with loss of consciousness (LOC). Among 32 patients, 3 had VF and 2 had VT with LOC. Other 27 had non-lethal VA. Baseline clinical characteristics were not significantly difference between lethal and non-lethal VA. The ratio of J-wave elevation in lethal VA was significantly higher as compared with non-lethal VA (100% vs. 11.1%, P<0.0001). Furthermore, no patients with J-wave elevation in the inferior leads had recurrence of lethal VA after RF ablation of the PVCs.

Conclusions: We speculate that J-wave elevation in the inferior leads might be a predictor of lethal VA initiated by PVCs with RBBB and superior axis. RF ablation of these PVCs was a useful method of treating lethal VA.
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http://dx.doi.org/10.1253/circj.CJ-19-0021DOI Listing
August 2019

Association left ventricular lead and ventricular arrhythmias after upgrade to cardiac resynchronization therapy in patients with implantable cardioverter defibrillators.

Clin Cardiol 2019 Jul 13;42(7):670-677. Epub 2019 May 13.

Division of Cardiology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan.

Background: There are some controversial reports related to the pro-arrhythmic or anti-arrhythmic potential of cardiac resynchronization therapy (CRT) and little is known about the relationship between ventricular arrhythmia (VA) and left ventricular (LV)-lead threshold.

Hypothesis: Upgrade CRT is anti-arrhythmic effect of VA with implantable cardioverter-defibrillator (ICD) patients and has a relationship with the incident of VA and LV-lead threshold.

Methods: Among 384 patients with the implantation of CRT-defibrillator (CRT-D), 102 patients underwent an upgrade from ICD to CRT-D. We divided patients into three groups; anti-arrhythmic effect after upgrade (n = 22), pro-arrhythmic effect (n = 14), and unchanging-VA events (n = 66). The VA event was determined by device reports. We described the electrocardiography parameters, LV-lead characteristics, and clinical outcomes.

Results: Before upgrade, the numbers of VA were 305 episodes and the numbers of ICD therapy were 157 episodes. While after upgrade, the numbers of VA were 193 episodes and the number of ICD therapy were 74 episodes. Ventricular tachycardia cycle length (VT-CL) after upgrade was significantly slower as compared to those with before upgrade. Pro-arrhythmic group was significantly higher with delta LV-lead threshold (after 1 month-baseline) as compared to those with anti-arrhythmic group (0.74 vs -0.21 V). Furthermore, pro-arrhythmic group was significantly bigger with delta VT-CL (after 3 months-before 3 months) as compared to those with anti-arrhythmic group (P = .03).

Conclusions: We described upgrade-CRT was associated with reduction of VA, ICD therapies and VT-CL. While 14 patients had a pro-arrhythmic effect and LV lead threshold might be associated with VA-incidents.
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http://dx.doi.org/10.1002/clc.23192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6605005PMC
July 2019

Thrombomodulin can predict the incidence of second events in patients with acute coronary syndrome: Single-center, retrospective cohort study.

J Cardiol 2018 12 7;72(6):494-500. Epub 2018 Jun 7.

Division of Cardiology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan.

Background: Plasma levels of atherothrombosis-related markers such as endothelial biomarkers have been reported to predict the risk of first acute coronary syndrome (ACS) events. Percutaneous coronary intervention (PCI) by balloon angioplasty and stenting established as a treatment for ACS enabled early discharge and early clinic care. The procedure of PCI, however, may itself be associated with arterial injury with endothelial dysfunction. The clinical significance of those biomarkers for second events in patients after PCI has not yet been completely understood to identify patients who need strict follow-up.

Methods: After the exclusion of 100 patients (60 deaths during hospitalization, 40 severe renal failure), 400 ACS patients (291 males, 71.1±13.0 years) who had undergone successful PCI followed by biomarker assessment within the first postoperative hour were enrolled. We evaluated atherothrombosis-related biomarkers: thrombomodulin (TM), C-reactive protein (CRP), and D-dimer, prothrombin fragment F1+2, and plasminogen activator inhibitor-1, other than those assessed by routine biochemical tests. The outcome after PCI in ACS patients was assessed by the incidence of major adverse cardiovascular events (MACEs).

Results: MACEs occurred in 112 patients during the follow-up period (813.9±474.8 days). As in previous reports, patients with MACEs showed decreased left ventricular ejection fraction (LVEF) by echocardiography, elevated brain natriuretic peptide and HbA1c than patients without MACEs. Not only these markers but also TM were significantly associated with MACEs in multivariate analysis. There were no significant correlations between MACEs and CRP. The association between TM and MACEs was especially high (odds ratio 2.73) and unaffected by the stage of cardiac (≤40, 40
Conclusions: TM is independently associated with MACEs and may be predictive of second events in patients after PCI for ACS. ACS patients with high TM value need strict follow up.
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http://dx.doi.org/10.1016/j.jjcc.2018.05.006DOI Listing
December 2018

Modulation of sympathetic preganglionic neuron activity via adrenergic receptors.

Hypertens Res 2018 Jul 10;41(7):499-505. Epub 2018 May 10.

Division of Cardiology, Department of Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan.

The sympathetic preganglionic neurons (SPNs) play a key role in the sympathetic nervous system. Previous reports have suggested that norepinephrine (NE) directly affects SPNs via both inhibitory hyperpolarization interactions mediated by α2 receptors and excitatory depolarization interactions mediated by α1 receptors. It remains poorly understood, however, whether the excitability of SPNs can be inhibited indirectly (presynaptically) as well as directly (postsynaptically). We intracellularly recorded 41 SPNs using the whole-cell patch-clamp technique in spinal cord slice preparations of neonatal rats. We examined the effects of NE or dexmedetomidine hydrochloride (Dxm) (α2-adrenergic receptor agonist) on SPNs by analyzing the excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs). EPSPs were dominant in 15 SPNs (EPSP-SPNs) and IPSPs were dominant in 7 SPNs (IPSP-SPNs) at baseline. We were unable to analyze the postsynaptic potentials in the other 19 SPNs, due to high frequency of action potential firings (firing-SPNs). At baseline, the membrane potentials and resistances of each type of SPN were similar. NE (1  μM) gradually depolarized the EPSP-SPNs and IPSP-SPNs (P   < 0.001) and NE significantly increased the EPSP frequency of the EPSP-SPNs (P   < 0.05). Dxm (10  nM) after application of NE decreased the EPSP frequency of the EPSP-SPNs (P  <  0.001) and the EPSP voltage and IPSP voltage of the IPSP-SPNs (P  <  0.05). In 5 of the 19 firing-SPNs, NE induced membrane hyperpolarization (P   < 0.05) and completely inhibited firings. Dxm had no effect in these neurons. The SPNs received inhibitory modulation through α2-adrenergic receptors. Some SPNs can be directly inhibited via effects independent of the α2 receptors.
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http://dx.doi.org/10.1038/s41440-018-0049-xDOI Listing
July 2018

Small dense low-density lipoprotein cholesterol is a promising biomarker for secondary prevention in older men with stable coronary artery disease.

Geriatr Gerontol Int 2018 Jun 7;18(6):965-972. Epub 2018 Mar 7.

The Department of Medicine, Division of Cardiology, Showa University School of Medicine, Tokyo, Japan.

Aim: The study objective was to investigate whether small dense low-density lipoprotein cholesterol (sdLDL-C) is superior to low-density lipoprotein cholesterol (LDL-C) and other biomarkers to predict future cardiovascular events (CE) in secondary prevention.

Methods: sdLDL-C measured by a homogeneous assay, remnant lipoprotein cholesterol, LDL particle diameter and other biomarkers were compared in 345 men aged ≥65 years with stable coronary artery disease. Baseline LDL-C was 100.5 ± 30.1 mg/dL. CE including cardiovascular death, onset of acute coronary syndrome, need for arterial revascularization, hospitalization for heart failure, surgery procedure for cardiovascular disease and hospitalization for stroke were monitored for 5 years.

Results: CE occurred in 96 patients during the study period. LDL-C, sdLDL-C non-high-density lipoprotein cholesterol, apolipoprotein B, remnant lipoprotein cholesterol, glucose, glycated hemoglobin and brain natriuretic peptide were significantly higher; LDL particle diameter and apolipoprotein A-1 were significantly lower in patients with than in those without CE. Age-adjusted Cox regression analysis showed that sdLDL-C per 10 mg/dL, but not LDL-C, was significantly associated with CE (HR 1.206, 95% CI 1.006-1.446). A significant association of sdLDL-C and incident CE was observed in statin users (HR 1.252, 95% CI 1.017-1.540), diabetes patients (HR 1.219, 95% CI 1.018-1.460), patients without diabetes (HR 1.257, 95% CI 1.019-1.551) and patients with hypertriglyceridemia (HR 1. 376, 95% CI 1.070-1.770).

Conclusions: sdLDL-C was the most effective predictor of residual risk of future CE in stable coronary artery disease patients using statins and in high-risk coronary artery disease patients with diabetes or hypertriglyceridemia. Geriatr Gerontol Int 2018; 18: 965-972.
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http://dx.doi.org/10.1111/ggi.13287DOI Listing
June 2018

Neopterin Counters Vascular Inflammation and Atherosclerosis.

J Am Heart Assoc 2018 02 2;7(3). Epub 2018 Feb 2.

Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.

Background: Neopterin, a metabolite of GTP, is produced by activated macrophages and is abundantly expressed within atherosclerotic lesions in human aorta and carotid and coronary arteries. We aimed to clarify the influence of neopterin on both vascular inflammation and atherosclerosis, as neither effect had been fully assessed.

Methods And Results: We investigated neopterin expression in coronary artery lesions and plasma from patients with coronary artery disease. We assessed the atheroprotective effects of neopterin in vitro using human aortic endothelial cells, human monocyte-derived macrophages, and human aortic smooth muscle cells. In vivo experiments included a study of aortic lesions in apolipoprotein E-deficient mice. Neopterin expression in coronary artery lesions and plasma was markedly increased in patients with versus without coronary artery disease. In human aortic endothelial cells, neopterin reduced proliferation and TNF-α (tumor necrosis factor α)-induced upregulation of MCP-1 (monocyte chemotactic protein 1), ICAM-1 (intercellular adhesion molecule 1), and VCAM-1 (vascular cell adhesion molecule 1). Neopterin attenuated TNF-α-induced monocyte adhesion to human aortic endothelial cells and the inflammatory macrophage phenotype via NF-κB (nuclear factor-κB) downregulation. Neopterin suppressed oxidized low-density lipoprotein-induced foam cell formation associated with CD36 downregulation and upregulation of ATP-binding cassette transporters A1 and G1 in human monocyte-derived macrophages. In human aortic smooth muscle cells, neopterin suppressed angiotensin II-induced migration and proliferation via c-Src/Raf-1/ERK1/2 downregulation without inducing apoptosis. Exogenous neopterin administration and endogenous neopterin attenuation with its neutralizing antibody for 4 weeks retarded and promoted, respectively, the development of aortic atherosclerotic lesions in apolipoprotein E-deficient mice.

Conclusions: Our results indicate that neopterin prevents both vascular inflammation and atherosclerosis and may be induced to counteract the progression of atherosclerotic lesions. Consequently, neopterin could be of use as a novel therapeutic target for atherosclerotic cardiovascular diseases.
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http://dx.doi.org/10.1161/JAHA.117.007359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850243PMC
February 2018

Catestatin Prevents Macrophage-Driven Atherosclerosis but Not Arterial Injury-Induced Neointimal Hyperplasia.

Thromb Haemost 2018 01 5;118(1):182-194. Epub 2018 Jan 5.

Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.

Catestatin, a catecholamine-release inhibitory peptide, has multiple cardiovascular activities. Conflicting results have been recently reported by increased or decreased plasma levels of catestatin in patients with coronary artery disease (CAD). However, there have been no previous reports regarding the effects of catestatin on arteriosclerosis. This study evaluated the vasoprotective effects of catestatin on human macrophages, human aortic smooth muscle cells (HASMCs) and human umbilical vein endothelial cells (HUVECs) in vitro, and aortic atherosclerosis and wire injury-induced femoral artery neointimal hyperplasia in apolipoprotein E-deficient (ApoE) mice fed with a high-cholesterol diet. Histological expression of catestatin in coronary artery lesions and its plasma level were compared between CAD and non-CAD patients. Catestatin was abundantly expressed in cultured human monocytes, macrophages, HASMCs and HUVECs. Catestatin significantly suppressed lipopolysaccharide-induced upregulation of tumour necrosis factor-α, vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in HUVECs. Catestatin significantly suppressed inflammatory responses and oxidized low-density lipoprotein-induced foam cell formation associated with acyl-CoA:cholesterol acyltransferase-1 downregulation and ATP-binding cassette transporter A1 upregulation in human macrophages. Catestatin significantly suppressed migration, proliferation and collagen-1 expression without inducing apoptosis, and increased elastin and fibronectin expression in HASMCs. Administration of catestatin into ApoE mice significantly retarded entire aortic atherosclerotic lesions with declined contents of macrophages, SMCs and collagen fibres in atheromatous plaques, but not the femoral artery injury-induced neointimal hyperplasia. In CAD patients, catestatin levels were significantly decreased in plasma but increased in coronary atheromatous plaques. This study provided the first evidence that catestatin could prevent macrophage-driven atherosclerosis, but not SMC-derived neointimal hyperplasia after vascular injury.
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http://dx.doi.org/10.1160/TH17-05-0349DOI Listing
January 2018

Effects of Cardiac Rehabilitation on High-Density Lipoprotein-mediated Cholesterol Efflux Capacity and Paraoxonase-1 Activity in Patients with Acute Coronary Syndrome.

J Atheroscler Thromb 2018 Feb 30;25(2):153-169. Epub 2017 Aug 30.

Division of Cardiology, Department of Medicine, Showa University School of Medicine.

Aims: We evaluated whether exercised-based cardiac rehabilitation (CR) can ameliorate the HDL function, i.e., cholesterol efflux capacity (CEC) and paraoxonase-1 activity in patients with acute coronary syndrome (ACS).

Methods: This study is a retrospective analysis of stored serum from patients with ACS following successful percutaneous coronary intervention. The CEC, measured by a cell-based ex vivo assay using apolipoprotein B-depleted serum and H-cholesterol labeled macrophages and arylesterase activity (AREA) at the onset or early phase of ACS, and the follow-up periods were compared between 69 patients who completed the five-month outpatient CR program (CR group) and 15 patients who did not participate and/or dropped out from CR program (non-CR group).

Results: Apolipoprotein A-I (apoA-I) and CEC significantly increased by 4.0% and 9.4%, respectively, in the CR group, whereas HDL-cholesterol and AREA were not changed during the follow-up periods in both groups. Among CR patients, the CEC significantly increased, irrespective of the different statin treatment, while HDL-cholesterol and apoA-I significantly increased in patients treated with rosuvastatin or pitavastatin. Although CEC and AREA were significantly correlated each other, there is a discordance between CEC and AREA for their correlations with other biomarkers. Both CEC and AREA were significantly correlated with apoA-I rather than HDL-cholesterol. Changes in CEC and those in AREA were significantly correlated with those in apoA-I (rho=0.328, p=0.002, and rho=0.428, p<0.0001, respectively) greater than those in HDL-cholesterol (rho=0.312, p= 0.0042,and rho=0.343, p=0.003, respectively).

Conclusions: CR can improve HDL function, and it is beneficial for secondary prevention.
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http://dx.doi.org/10.5551/jat.41095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5827085PMC
February 2018

Performance of Leadless Pacemaker in Japanese Patients vs. Rest of the World - Results From a Global Clinical Trial.

Circ J 2017 Oct 30;81(11):1589-1595. Epub 2017 May 30.

Department of Cardiology, Showa University Hospital.

Background: A global study designed to demonstrate the safety and efficacy of a transcatheter pacing system included 38 Japanese patients enrolled at 4 sites. Subgroup analysis to evaluate the performance of the leadless intracardiac transcatheter pacing system in Japanese patients was performed.Methods and Results:Safety and efficacy outcomes, patient and implant procedure characteristics, and patient and physician acceptability from the Japanese population were compared with those from outside Japan. Differences in patient characteristics, implant procedure characteristics and patient acceptability were observed. There were no major complications in Japanese patients and pacing thresholds remained low and stable throughout follow-up. There were no observable differences between Japanese patients and patients from outside Japan in the freedom from major complication rate at 12-months post-implant (100.0% vs. 95.7%, P=0.211) or physician acceptability.

Conclusions: Although some differences in specific baseline characteristics, such as body size and pacing indication, and in implant procedure characteristics, including anticoagulation strategy and hospitalization period, were observed in the Japanese patients, transcatheter pacemaker performance was similar to that in the global trial. (Clinical Trial Registration: ClinicalTrials.gov ID NCT02004873.).
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http://dx.doi.org/10.1253/circj.CJ-17-0259DOI Listing
October 2017

Predictors of Mortality, Rehospitalization for Syncope and Cardiovascular Events in Patients With Cardiovascular Syncope.

Circ J 2017 Sep 25;81(10):1395-1402. Epub 2017 May 25.

Division of Cardiology, Department of Medicine, Showa University.

Background: Predictors of poor outcomes remain unknown for cardiovascular syncope patients after discharge.Methods and Results:We reviewed the medical records of consecutive patients admitted to hospital with cardiovascular syncope. We then performed Cox stepwise logistic regression analysis to identify significant independent factors for death, rehospitalization for syncope, and cardiovascular events. The study group was 206 patients with cardiovascular syncope. Of them, bradycardia was diagnosed in 50%, tachycardia in 27%, and structural disease in 23%. During a 1-year follow-up period, 18 (8%) and 45 (23%) patients, respectively, were rehospitalized for syncope or a cardiovascular event, and 10 (4%) died. Independent predictors of cardiovascular events were systolic blood pressure <100 mmHg (odds ratio [OR] 3.25; 95%confidence interval [CI] 1.41-7.51, P=0.006) and implantation of a pacemaker (OR 0.19; 95% CI 0.05-0.51, P=0.0005) (inverse association). Drug-induced syncope (OR 4.57; 95% CI 1.54-12.8, P=0.007) was an independent risk factor for rehospitalization. Finally, a history of congestive heart failure (OR 11.0; 95% CI 2.78-54.7, P=0.0006) and systolic blood pressure <100 mmHg (OR 5.40; 95% CI 1.30-22.7, P=0.02) were identified as significant independent prognostic factors for death.

Conclusions: Drug-induced syncope, hypotension, no indication for a pacemaker, and a history of congestive heart failure are risk factors post-discharge for patients with cardiovascular syncope and careful follow-up of these patients for at least 1 year is recommended.
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http://dx.doi.org/10.1253/circj.CJ-16-1296DOI Listing
September 2017

Potent Vasoconstrictor Kisspeptin-10 Induces Atherosclerotic Plaque Progression and Instability: Reversal by its Receptor GPR54 Antagonist.

J Am Heart Assoc 2017 Apr 14;6(4). Epub 2017 Apr 14.

Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.

Background: Kisspeptin-10 (KP-10), a potent vasoconstrictor and inhibitor of angiogenesis, and its receptor, GPR54, have currently received much attention in relation to pre-eclampsia. However, it still remains unknown whether KP-10 could affect atherogenesis.

Methods And Results: We evaluated the effects of KP-10 on human umbilical vein endothelial cells, human monocyte-derived macrophages, human aortic smooth muscle cells in vitro, and atherosclerotic lesions in apolipoprotein E-deficient (ApoE) mice in vivo. KP-10 significantly increased the adhesion of human monocytes to human umbilical vein endothelial cells, which was significantly inhibited by pretreatment with P234, a GPR54 antagonist. KP-10 stimulated mRNA expression of tumor necrosis factor-α, interleukin-6, monocyte chemotactic protein-1, intercellular adhesion molecule-1, vascular adhesion molecule-1, and E-selectin in human umbilical vein endothelial cells. KP-10 significantly enhanced oxidized low-density lipoprotein-induced foam cell formation associated with upregulation of CD36 and acyl-CoA:cholesterol acyltransferase-1 in human monocyte-derived macrophages. In human aortic smooth muscle cells, KP-10 significantly suppressed angiotensin II-induced migration and proliferation, but enhanced apoptosis and activities of matrix metalloproteinase (MMP)-2 and MMP-9 by upregulation of extracellular signal-regulated kinase 1 and 2, p38, Bcl-2-associated X protein, and caspase-3. Four-week-infusion of KP-10 into ApoE mice significantly accelerated the development of aortic atherosclerotic lesions with increased monocyte/macrophage infiltration and vascular inflammation as well as decreased intraplaque vascular smooth muscle cells contents. Proatherosclerotic effects of endogenous and exogenous KP-10 were completely canceled by P234 infusion in ApoE mice.

Conclusions: Our results suggest that KP-10 may contribute to accelerate the progression and instability of atheromatous plaques, leading to plaque rupture. The GPR54 antagonist may be useful for prevention and treatment of atherosclerosis. Thus, the KP-10/GPR54 system may serve as a novel therapeutic target for atherosclerotic diseases.
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http://dx.doi.org/10.1161/JAHA.117.005790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5533042PMC
April 2017

Immediate discontinuation of ablation during pulmonary vein isolation remarkably decreases the incidence of esophageal thermal lesions even when using steerable sheaths.

J Arrhythm 2017 Feb 3;33(1):23-27. Epub 2016 Jun 3.

Department of Cardiology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan.

Background: Left atrial-esophageal fistulas (LAEFs) are serious complications with high mortality after atrial fibrillation radiofrequency ablation (AFRA). Decreasing the incidence of esophageal thermal lesions (EsoTLs) that may lead to LAEFs is important. The aim of this study was to suppress EsoTL development and determine the appropriate alarm setting for a temperature-monitoring probe by using steerable sheath (STS) methods.

Methods: We enrolled 82 consecutive patients (mean, 61.9±11.7 years; 75.6% men) who underwent AFRA, including pulmonary vein isolation for symptomatic, drug-refractory atrial fibrillation with esophageal temperature monitoring by using STS between January 2011 and April 2014. All patients underwent upper gastrointestinal endoscopy (UGE) 1-3 days after AFRA. The timing of ablation discontinuation in the first 17 patients was determined by each physician during AFRA (only monitoring group, OM). In the next 65 patients, physicians were to immediately discontinue ablation when an alarm set at 39 °C went off (instruction group, INS). We compared two groups with respect to the incidence of EsoTLs.

Results: Among the 82 patients, 5 (6.1%) had EsoTLs after AFRA. EsoTLs occurred in 3 of 17 patients (17.6%) and 2 of 65 patients (3.1%) in the OM and INS groups, respectively. The incidence of EsoTLs in the INS group was significantly lower than that in the OM group (=0.0254). EsoTL did not occur at maximal temperature less than 39 °C, measured by using esophageal temperature-monitoring probe.

Conclusions: Immediate discontinuation of ablation during pulmonary vein isolation remarkably decreased the incidence of EsoTLs, even when using STS.
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http://dx.doi.org/10.1016/j.joa.2016.05.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5300859PMC
February 2017

HotBalloon Ablation of the Pulmonary Veins for Paroxysmal AF: A Multicenter Randomized Trial in Japan.

J Am Coll Cardiol 2016 Dec;68(25):2747-2757

Division of Cardiovascular Medicine, University of Tsukuba, Tsukuba, Japan.

Background: Point-by-point catheter ablation is an established treatment for drug-refractory paroxysmal atrial fibrillation (PAF). However, it is time consuming, requires excellent technique to achieve complete pulmonary vein (PV) isolation, and is associated with severe complications.

Objectives: The purpose of this study was to evaluate the safety and effectiveness of a HotBalloon ablation (HBA) compared with antiarrhythmic drug therapy (ADT) for the treatment of PAF.

Methods: A prospective multicenter randomized controlled study was conducted in Japan. Patients with symptomatic PAF refractory to antiarrhythmic drugs (Class I to IV) were randomized to HBA or ADT at a 2:1 ratio and assessed for effectiveness in a comparable 9-month follow-up period.

Results: A total of 100 patients in the HBA group and 43 patients in the ADT group received treatment at 17 sites. HBA procedure produced acute complete PV isolation in 98.0% (392 of 400) of the PVs and in 93.0% (93 of 100) of patients in the HBA group. The chronic success rates after the 9-month effective evaluation period were 59.0% in the HBA group (n = 100) and 4.7% in the ADT group (n = 43; p < 0.001). The incidence of major complications was 11.2% (15 of 134 patients). The incidences of PV stenosis (>70%) and transient phrenic nerve injury were 5.2% and 3.7%, respectively. The mean fluoroscopy time was 49.4 ± 26.6 min (n = 134), and the mean procedure duration was 113.9 ± 31.9 min (n = 133).

Conclusions: This study demonstrates the superiority of HBA compared with ADT for treatment of patients with PAF, and a favorable safety profile.
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http://dx.doi.org/10.1016/j.jacc.2016.10.037DOI Listing
December 2016

Increased Coagulation With Aging: Importance of Homocysteine and Vitamin B12 - Reply.

Circ J 2017 Jan 16;81(2):269. Epub 2016 Dec 16.

Division of Cardiology, Department of Medicine, Showa University School of Medicine.

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http://dx.doi.org/10.1253/circj.CJ-16-1187DOI Listing
January 2017

Atheroprotective Effects of Tumor Necrosis Factor-Stimulated Gene-6.

JACC Basic Transl Sci 2016 Oct 31;1(6):494-509. Epub 2016 Oct 31.

Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.

Tumor necrosis factor-stimulated gene-6 (TSG-6), an anti-inflammatory protein, was shown to be localized in the neointima of injury-induced rat arteries. However, the modulatory effect of TSG-6 on atherogenesis has not yet been reported. We aimed to evaluate the atheroprotective effects of TSG-6 on human endothelial cells (HECs), human monocyte-derived macrophages (HMDMs), human aortic smooth muscle cells (HASMCs) in vitro, and aortic lesions in apolipoprotein E-deficient mice, along with expression levels of TSG-6 in coronary lesions and plasma from patients with coronary artery disease (CAD). TSG-6 was abundantly expressed in HECs, HMDMs, and HASMCs in vitro. TSG-6 significantly suppressed cell proliferation and lipopolysaccharide-induced up-regulation of monocyte chemotactic protein-1, intercellular adhesion molecule-1, and vascular adhesion molecule-1 in HECs. TSG-6 significantly suppressed inflammatory M1 phenotype and suppressed oxidized low-density lipoprotein-induced foam cell formation associated with down-regulation of CD36 and acyl-CoA:cholesterol acyltransferase-1 in HMDMs. In HASMCs, TSG-6 significantly suppressed migration and proliferation, but increased collagen-1 and -3 expressions. Four-week infusion of TSG-6 into apolipoprotein E-deficient mice significantly retarded the development of aortic atherosclerotic lesions with decreased vascular inflammation, monocyte/macrophage, and SMC contents and increased collagen fibers. In addition, it decreased peritoneal M1 macrophages with down-regulation of inflammatory molecules and lowered plasma total cholesterol levels. In patients with CAD, plasma TSG-6 levels were significantly increased, and TSG-6 was highly expressed in the fibrous cap within coronary atherosclerotic plaques. These results suggest that TSG-6 contributes to the prevention and stability of atherosclerotic plaques. Thus, TSG-6 may serve as a novel therapeutic target for CAD.
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http://dx.doi.org/10.1016/j.jacbts.2016.07.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113406PMC
October 2016

Effects of Aging on the Coagulation Fibrinolytic System in Outpatients of the Cardiovascular Department.

Circ J 2016 Sep 29;80(10):2133-40. Epub 2016 Aug 29.

Division of Cardiology, Department of Medicine, Showa University School of Medicine.

Background: Although clinical trials demonstrate that the elderly with atrial fibrillation have risks of thrombosis and bleeding, the relationship between aging and coagulation fibrinolytic system in "real-world" cardiology outpatients is uncertain.

Methods and results: We retrospectively evaluated 773 patients (mean age: 58 years; 52% men; Asian ethnicity). To thoroughly investigate markers of coagulation and fibrinolysis, we simultaneously measured levels of D-dimer, prothrombin-fragment1+2 (F1+2), plasmin-α2 plasmin inhibitor complex (PIC), and thrombomodulin (TM). There were correlations between aging and levels of F1+2, D-dimer, PIC, and TM (R=0.61, 0.57, 0.49, and 0.30, respectively). We compared 3 age groups, which were defined as the Y group (<64 years), M group (65-74 years), and the O group (>75 years). Levels of markers were higher in older individuals (D-dimer: 1.0±0.8 vs. 0.8±0.8 vs. 0.6±0.4 μg/ml, F1+2: 281.8±151.3 vs. 224.6±107.1 vs. 155.5±90.0 pmol/L, PIC: 0.9±0.3 vs. 0.8±0.3 vs. 0.6±0.5 μg/ml, and TM: 2.9±0.8 vs. 2.7±0.7 vs. 2.5±0.7FU/ml). We performed logistic regression analysis to determine F1+2 and PIC levels. Multivariate analysis revealed that aging was the most important determinant of high F1+2 and PIC levels.

Conclusions: Hypercoagulable states develop with advancing age in "real-world" cardiology outpatients. (Circ J 2016; 80: 2133-2140).
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http://dx.doi.org/10.1253/circj.CJ-16-0530DOI Listing
September 2016

Pulmonary vein obstruction after catheter ablation in a patient with partial anomalous pulmonary vein connection.

J Cardiol Cases 2016 Sep 26;14(3):78-81. Epub 2016 May 26.

Department of Cardiology, Showa University, Japan.

A 75-year-old man with symptomatic atrial fibrillation was referred to our hospital for catheter ablation. Preprocedural echocardiogram showed mild-moderate degree mitral regurgitation (MR) and mild tricuspid regurgitation (TR) with transvalvular peak gradient (TVPG) of 27 mmHg. The complete isolation of the pulmonary veins was performed by radiofrequency ablation, and the patient was kept in sinus rhythm after the procedure. However, the exertional dyspnea had gradually developed one year after the procedure. Echocardiogram showed severe TR with TVPG 60 mmHg. MDCT showed partial anomalous pulmonary vein connection (PAPVC) of the left upper pulmonary vein and the occlusion of left lower pulmonary vein ostium: pulmonary venous flow of the left upper lung was drained into the brachiocephalic vein. The patient underwent surgical correction of PAPVC and annuloplasty of the mitral and tricuspid valve. Although it is unclear whether there is direct causal relationship between PAPVC and PV obstruction, anatomical evaluation of PVs is important in patients undergoing catheter ablation. < Partial anomalous pulmonary vein connection (PAPVC) is rare and often asymptomatic in adults. In the present case, pulmonary vein obstruction occurred after radiofrequency catheter ablation in a patient with PAPVC. Although pulmonary venous flow from only left upper lobe drained into the brachiocephalic vein before ablation, occlusion of the left lower pulmonary vein resulted in right heart failure one year after ablation.>.
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http://dx.doi.org/10.1016/j.jccase.2016.04.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282881PMC
September 2016

Waon Therapy for Managing Chronic Heart Failure - Results From a Multicenter Prospective Randomized WAON-CHF Study.

Circ J 2016 18;80(4):827-34. Epub 2016 Mar 18.

Waon Therapy Research Institute.

Background: Waon therapy improves heart failure (HF) symptoms, but further evidence in patients with advanced HF remains uncertain.

Methods and results: In 19 institutes, we prospectively enrolled hospitalized patients with advanced HF, who had plasma levels of B-type natriuretic peptide (BNP) >500 pg/ml on admission and BNP >300 pg/ml regardless of more than 1 week of medical therapy. Enrolled patients were randomized into Waon therapy or control groups. Waon therapy was performed once daily for 10 days with a far infrared-ray dry sauna maintained at 60℃ for 15 min, followed by bed rest for 30 min covered with a blanket. The primary endpoint was the ratio of BNP before and after treatment. In total, 76 Waon therapy and 73 control patients (mean age 66 years, men 61%, mean plasma BNP 777 pg/ml) were studied. The groups differed only in body mass index and the frequency of diabetes. The plasma BNP, NYHA classification, 6-min walk distance (6MWD), and cardiothoracic ratio significantly improved only in the Waon therapy group. Improvements in NYHA classification, 6MWD, and cardiothoracic ratio were significant in the Waon therapy group, although the change in plasma BNP did not reach statistical significance. No serious adverse events were observed in either group.

Conclusions: Waon therapy, a holistic soothing warmth therapy, showed clinical advantages in safety and efficacy among patients with advanced HF.
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http://dx.doi.org/10.1253/circj.CJ-16-0051DOI Listing
December 2016

Dataset of calcified plaque condition in the stenotic coronary artery lesion obtained using multidetector computed tomography to indicate the addition of rotational atherectomy during percutaneous coronary intervention.

Data Brief 2016 Jun 27;7:376-80. Epub 2016 Feb 27.

Division of Cardiology, Department of Medicine, Showa University School of Medicine, Japan.

Our data shows the regional coronary artery calcium scores (lesion CAC) on multidetector computed tomography (MDCT) and the cross-section imaging on MDCT angiography (CTA) in the target lesion of the patients with stable angina pectoris who were scheduled for percutaneous coronary intervention (PCI). CAC and CTA data were measured using a 128-slice scanner (Somatom Definition AS+; Siemens Medical Solutions, Forchheim, Germany) before PCI. CAC was measured in a non-contrast-enhanced scan and was quantified using the Calcium Score module of SYNAPSE VINCENT software (Fujifilm Co. Tokyo, Japan) and expressed in Agatston units. CTA were then continued with a contrast-enhanced ECG gating to measure the severity of the calcified plaque condition. We present that both CAC and CTA data are used as a benchmark to consider the addition of rotational atherectomy during PCI to severely calcified plaque lesions.
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http://dx.doi.org/10.1016/j.dib.2016.02.052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4781927PMC
June 2016

Beneficial Effects of Exercise-Based Cardiac Rehabilitation on High-Density Lipoprotein-Mediated Cholesterol Efflux Capacity in Patients with Acute Coronary Syndrome.

J Atheroscler Thromb 2016 Jul 5;23(7):865-77. Epub 2016 Mar 5.

The Department of Medicine, Division of Cardiology, Showa University School of Medicine.

Aim: Recent studies reported that low high-density lipoprotein (HDL)-mediated cholesterol efflux capacity rather than low HDL cholesterol (HDL-C) is strongly associated with the increased risk for coronary artery disease. It remains unclear whether exercised-based cardiac rehabilitation (CR) can increase HDL cholesterol efflux capacity.

Method: This study is a retrospective analysis of stored serum from patients with acute coronary syndrome (ACS) who participated in outpatient CR program following successful percutaneous coronary intervention. We employed a cell-based cholesterol efflux system including the incubation of (3)H-cholesterol labeled macrophages with apolipoprotein B-depleted serum at the onset or early phase of ACS and at 6-month follow-up periods in 57 male and 11 female patients with ACS. Cardiopulmonary exercise tests were performed at the beginning and end of CR program.

Result: Fifty-seven patients completed the CR program. Compared with patients who dropped out from CR program (non-CR group), CR participants showed marked amelioration in serum lipid levels, increased efflux capacity, and improved exercise capacity. Spearman's rank correlation coefficient analysis revealed that the percent increases of efflux capacity were significantly associated with the percent increases in HDL-C (ρ=0.598, p<0.0001) and apolipoprotein A1 (ρ=0.508, p<0.0001), whereas no association between increases in efflux capacity and increases in cardiopulmonary fitness was observed. Increases in cholesterol efflux capacity were not seen in patients who continued smoking and those who did not achieve all risk factor targets and higher exercise tolerance.

Conclusion: CR can markedly increase both HDL-C and HDL cholesterol efflux capacity. These results suggest that CR is a very useful therapy for reverse cholesterol transport and secondary prevention.
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http://dx.doi.org/10.5551/jat.34454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399273PMC
July 2016

Regional calcified plaque score evaluated by multidetector computed tomography for predicting the addition of rotational atherectomy during percutaneous coronary intervention.

J Cardiovasc Comput Tomogr 2016 May-Jun;10(3):221-8. Epub 2016 Jan 13.

Division of Cardiology, Department of Medicine, Showa University School of Medicine, Japan.

Background: Rotational atherectomy (rotablation) has been proposed as a potentially superior strategy for percutaneous coronary intervention (PCI) in complex and severely calcified lesions.

Objectives: We hypothesized that a per-lesion coronary artery calcium score determined by multidetector computed tomography (MDCT) would be useful for predicting the requriement for rotablation during PCI.

Methods: MDCT was performed in patients with stable angina pectoris who were scheduled for first PCI. In 116 consecutive subjects (168 target lesions) with successful PCI, MDCT and quantitative coronary angiography (QCA) data were retrospectively evaluated regarding their ability to predict rotablation.

Results: PCI without rotablation was performed in 105 patients (154 lesions), and rotablation was added in 11 patients (14 lesions). Patients with rotablation had significantly higher SYNTAX scores (p = 0.007) and total calcium scores (p < 0.001) than those without rotablation. Per-lesion, a lesion length ≥20 mm and diameter stenosis ≥74% on QCA as well as a per-lesion calcium score ≥453 and calcification arc ≥270 in MDCT predicted rotablation. After adjustment for potential confounding variables, a high per-lesion calcium score was an independent predictor of rotablation (odds ratio 31.3, 95% confidence interval 2.8-345, p = 0.005, sensitivity 93% and specificity 88%).

Conclusion: The extent of target lesion calcification in MDCT, a simple marker of calcified plaque, is useful for predicting the need for rotablation during PCI.
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http://dx.doi.org/10.1016/j.jcct.2016.01.004DOI Listing
April 2017

Counteractive effects of omentin-1 against atherogenesis†.

Cardiovasc Res 2016 May 19;110(1):118-28. Epub 2016 Jan 19.

Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji-City, Tokyo 192-0393, Japan

Aims: Omentin-1, a novel adipocytokine expressed in visceral fat tissue, is negatively correlated with obesity, insulin resistance, and stable coronary artery disease (CAD). However, there have been no previous reports regarding the effects of omentin-1 on atherogenesis.

Methods And Results: This study was performed to evaluate the atheroprotective effects of omentin-1 on human monocyte-derived macrophages, human aortic smooth muscle cells (HASMCs) in vitro, and aortic lesions in Apoe(-/-) mice in vivo. The histological expression of omentin-1 in coronary artery lesions and epicardial adipose tissues and its plasma levels were compared between CAD and non-CAD patients. Omentin-1 was abundantly expressed in human umbilical vein endothelial cells, macrophages, HASMCs, and human coronary artery SMCs in vitro. Omentin-1 promoted anti-inflammatory M2 phenotype during differentiation of human monocytes into macrophages. Omentin-1 suppressed oxidized low-density lipoprotein-induced foam cell formation associated with down-regulation of CD36, scavenger receptor class A, and acyl-CoA:cholesterol acyltransferase-1 and up-regulation of neutral cholesterol ester hydrolase in human macrophages. Omentin-1 suppressed angiotensin II-induced migration and platelet-derived growth factor-BB-induced proliferation, and collagen-1 and -3 expression in HASMCs. Four-week infusion of omentin-1 into Apoe(-/-) mice retarded the development of aortic atherosclerotic lesions with reduced contents of monocytes/macrophages, SMCs, and collagen fibres along with peritoneal M2-activated macrophages with inflammasome down-regulation and lowered plasma total cholesterol levels. Omentin-1 levels were markedly reduced in coronary endothelium and epicardial fat but increased in plasma and atheromatous plaques (macrophages/SMCs) in CAD patients compared with non-CAD patients.

Conclusion: This study provided the first evidence that omentin-1 may serve as a novel therapeutic target for atherosclerosis and CAD.
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http://dx.doi.org/10.1093/cvr/cvw016DOI Listing
May 2016

Effects of Phase II Comprehensive Cardiac Rehabilitation on Coronary Plaque Volume After Acute Coronary Syndrome.

Int Heart J 2015 9;56(6):597-604. Epub 2015 Nov 9.

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

The present study aimed to determine the effects of phase II (PII) comprehensive cardiac rehabilitation (CR) on coronary plaque volume in patients after acute coronary syndrome (ACS).We assigned 46 patients with ACS who had undergone standard phase I CR into groups who proceeded with PII-CR (PII-CR; n = 21) and those who did not (non-PII-CR; n = 25). We then measured anthropometric parameters and daily physical activity using a pedometer for up to 60 days. The isokinetic strength of the knee extensor and flexor muscles and exercise tolerance were tested and non-culprit lesions were analyzed using volumetric intravascular ultrasound at baseline and 6 months later.Baseline characteristics did not significantly differ between the two groups and exercise tolerance was significantly improved in both. Waist size and fat weight were significantly decreased, and muscle strength was significantly increased in the PII-CR group but not in the non-PII-CR group. The percent change in plaque volume (primary endpoint) did not differ significantly between the two groups. The percent change in plaque volume was significantly and negatively correlated with daily physical activity.Although risk factors, muscle strength, and exercise tolerance were improved by PII-CR, plaque regression did not differ significantly between the two study groups. A significant correlation between percent change in coronary plaque volume and physical activity was observed. A comprehensive phase II-CR, including frequent supervised exercise sessions and a program encouraging an increase in daily physical activity, may reduce plaque volume in patients after ACS (UMIN000006038).
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http://dx.doi.org/10.1536/ihj.15-049DOI Listing
March 2016

Recurrence of atrial fibrillation within three months after pulmonary vein isolation for patients with paroxysmal atrial fibrillation: Analysis using external loop recorder with auto-trigger function.

J Arrhythm 2015 Apr 20;31(2):88-93. Epub 2014 Sep 20.

Division of Cardiology, Department of Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.

Background: Pulmonary vein isolation (PVI) via catheter ablation has been shown to be a highly effective treatment option for patients with symptomatic paroxysmal atrial fibrillation (AF). The recurrence of AF within 3 months after PVI is not considered to be the result of ablation procedure failure, because early recurrence of AF is not always associated with late recurrence. We examined the usefulness of an external loop recorder with an auto-trigger function (ELR-AUTO) for the detection of atrial fibrillation following PVI to characterize early recurrence and to determine the implications of AF occurrence within 3 months after PVI.

Methods: Fifty-three consecutive symptomatic patients with paroxysmal AF (age 61.6±12.6 years, 77% male) who underwent PVI and were fitted with ELR-AUTO for 7±2.0 days within 3 months after PVI were enrolled in this study.

Results: Of the 33 (62.2%) patients who did not have AF recurrence within 3 months after PVI, only 1 patient experienced AF recurrence at 12 months. Seven (35%) of the 20 patients who experienced AF within 3 months of PVI experienced symptomatic AF recurrence at 12 months. The sensitivity, specificity, positive predictive value, and negative predictive value of early AF recurrence for late recurrence were 87.5%, 71.1%, 35.0%, and 96.9%, respectively.

Conclusions: AF recurrence measured by ELR-AUTO within 3 months after PVI can predict the late recurrence of AF. Freedom from AF in the first 3 months following ablation significantly predicts long-term AF freedom. ELR-AUTO is useful for the detection of symptomatic and asymptomatic AF.
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http://dx.doi.org/10.1016/j.joa.2014.08.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4550125PMC
April 2015
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