Faculty Profiles - NAKAMURA Kazufumi

MISC - NAKAMURA Kazufumi

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心拍数（共著）

杉山洋樹, 中村一文

日本臨床 74 ( 4 ) 284 - 287 2016

肥大型心筋症と診断されていたミトコンドリア心筋症の1例

小橋宗一郎, 中村一文, 木村朋生, 中川晃志, 西井伸洋, 三好亨, 森田宏, 伊藤浩, 小坂田宗倫, 大郷恵子

日本循環器学会中国地方会(Web) 109th 2016

右冠動脈ステント内閉塞を繰り返した冠動脈肉腫の一例

吉田雅言, 中村一文, 増田善逸, 中川晃志, 麻植浩樹, 赤木達, 吉田賢司, 谷山真規子, 三好亨, 西井伸洋, 渡辺敦之, 森田宏, 伊藤浩

日本循環器学会中国地方会(Web) 108th 2016

卵円孔開存による労作時低酸素血症を合併したEbstein奇形に対し経皮的閉鎖術を施行した一例

川名伸一, 三木崇史, 赤木禎治, 高谷陽一, 麻植浩樹, 中川晃志, 中村一文, 森田宏, 伊藤浩

日本循環器学会中国地方会(Web) 108th 2016

家族性高コレステロール血症を背景としたPolyvascular diseaseに対して血行再建術を施行した1例

原田圭, 戸田洋伸, 赤木達, 中川晃志, 麻植浩樹, 吉田賢司, 谷山真規子, 渡邊敦之, 三好亨, 中村一文, 森田宏, 伊藤浩

日本循環器学会中国地方会(Web) 109th 2016

治療に難渋した壊死性好酸球性心筋炎(一部巨細胞浸潤を伴う)の一例

小出祐嗣, 中村一文, 中川晃志, 麻植浩樹, 三好亨, 西井伸洋, 森田宏, 大澤晋, 笠原真悟, 山中俊明, 伊藤浩

日本循環器学会中国地方会(Web) 108th 2016

血管炎をbaseにした進行性の腎動脈狭窄に対して血管内治療を施行した1例

戸田洋伸, 江尻健太郎, 中川晃志, 渡邊敦之, 三好亨, 西井伸洋, 中村一文, 森田宏, 伊藤浩

日本循環器学会中国地方会(Web) 109th 2016

家族性高コレステロール血症を基礎に持つ,下行大動脈狭窄に対してEVTを行った1例

戸田洋伸, 吉田雅言, 中川晃志, 西井伸洋, 渡邊敦之, 中村一文, 伊藤浩

脈管学(Web) 56 ( supplement ) 2016

治療開始20年後に再発を認めたカテコラミン誘発性多形性心室頻拍の一例

川北祝史, 森田宏, 上岡亮, 津島翔, 橘元見, 中川晃志, 三好亨, 渡辺敦之, 西井伸洋, 中村一文, 伊藤浩

日本循環器学会中国地方会(Web) 108th 2016

左冠動脈主幹部に起始異常を認め物理的圧迫による心筋虚血にて長期間失神を繰り返した若年者の一症例

網岡尚史, 渡辺敦之, 大塚寛昭, 赤木達, 麻植浩樹, 中川晃志, 中村一文, 森田宏, 小谷恭弘, 新井禎彦, 笠原真悟, 佐野俊二, 伊藤浩

日本循環器学会中国地方会(Web) 109th 2016

Incidence and Clinical Significance of Brugada Syndrome Masked by Complete Right Bundle-Branch Block

Tadashi Wada, Satoshi Nagase, Hiroshi Morita, Koji Nakagawa, Nobuhiro Nishii, Kazufumi Nakamura, Kunihisa Kohno, Hiroshi Ito, Kengo F. Kusano, Tohru Ohe

CIRCULATION JOURNAL 79 ( 12 ) 2568 - + 2015.11

Language：English Publisher：JAPANESE CIRCULATION SOC

Background: Brugada syndrome (BrS)-type electrocardiogram (ECG) is concealed by complete right bundle-branch block (CRBBB) in some cases of BrS. Clinical significance of BrS masked by CRBBB is not well known.
Methods and Results: We reviewed an ECG database of 326 BrS patients who had type 1 ECG with or without pilsicainide. "BrS masked by CRBBB" was defined on ECG as <2-mm elevation of the J point at the time of CRBBB in the right precordial leads, and BrS-type J-point elevation >= 2 mm at the time of normalized QRS complex on relieved CRBBB. We identified 25 BrS patients (7.7%) with persistent (n=12) or intermittent CRBBB (n=13). Relief of CRBBB by pacing was performed in patients with persistent CRBBB. The prevalence of BrS masked by CRBBB was 3.1% (10/326 patients). Three patients had type 1 ECG, and 7 patients had type 2 or 3 ECG on relief of CRBBB. Two of these 10 patients had lethal arrhythmic events during the follow-up period (mean, 86.4+/-57.2 months). There was no prognostic difference between BrS masked by CRBBB and other BrS.
Conclusions: In a small BrS population, CRBBB can completely mask typical BrS-type ECG. BrS masked by CRBBB is associated with the same risk of fatal ventricular tachyarrhythmia as other BrS.

DOI： 10.1253/circj.CJ-15-0618

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Prognostic significance of endothelial dysfunction in patients undergoing percutaneous coronary intervention in the era of drug-eluting stents

Motoki Kubo, Toru Miyoshi, Hiroki Oe, Yuko Ohno, Kazufumi Nakamura, Hiroshi Ito

BMC CARDIOVASCULAR DISORDERS 15 ( 1 ) 102 - 102 2015.9

Language：English Publisher：BIOMED CENTRAL LTD

Background: Endothelial function is a prognostic predictor in patients undergoing percutaneous coronary intervention (PCI). However, in an era with widespread use of drug-eluting stents, the clinical relevance of endothelial dysfunction on restenosis in patients undergoing PCI has not been fully evaluated.
Methods: This study included 80 patients with stable angina pectoris. Flow-mediated dilation (FMD) of the brachial artery was examined 1 week after PCI. Patients were retrospectively followed-up for an average of 21 months after PCI. The primary endpoints included cardiac death, nonfatal myocardial infarction, stroke, coronary revascularization, and critical limb ischemia.
Results: A drug-eluting stent was used in 58 patients and a cardiovascular event was recorded in 34 patients during follow-up. The incidence of all cardiovascular diseases was significantly greater in the low FMD (median FMD <4.2 %) than the high FMD (median FMD >= 4.2 %) group (60 % vs. 25 %, p <0.01). Furthermore, the incidence of coronary revascularization was significantly higher in the low than the high FMD group (p = 0.02), while the incidence of in-stent restenosis did not differ between the two groups. Cox regression analysis showed that low FMD was an independent predictor of cardiovascular events (hazard ratio: 2.77, 95 % confidence interval: 1.23 to 6.19, p = 0.01).
Conclusions: Impaired brachial artery FMD independently predicts long-term cardiovascular events after PCI in the era of drug-eluting stents.

DOI： 10.1186/s12872-015-0096-z

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Enhancement of Spontaneous Activity by HCN4 Overexpression in Mouse Embryonic Stem Cell-Derived Cardiomyocytes - A Possible Biological Pacemaker

Yukihiro Saito, Kazufumi Nakamura, Masashi Yoshida, Hiroki Sugiyama, Tohru Ohe, Junko Kurokawa, Tetsushi Furukawa, Makoto Takano, Satoshi Nagase, Hiroshi Morita, Kengo F. Kusano, Hiroshi Ito

PLOS ONE 10 ( 9 ) e0138193-e0138193 2015.9

Language：English Publisher：PUBLIC LIBRARY SCIENCE

Background
Establishment of a biological pacemaker is expected to solve the persisting problems of a mechanical pacemaker including the problems of battery life and electromagnetic interference. Enhancement of the funny current (If) flowing through hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and attenuation of the inward rectifier K+ current (I-K1) flowing through inward rectifier potassium (K-ir) channels are essential for generation of a biological pacemaker. Therefore, we generated HCN4-overexpressing mouse embryonic stem cells (mESCs) and induced cardiomyocytes that originally show poor I-K1 currents, and we investigated whether the HCN4-overexpressing mESC-derived cardiomyocytes (mESC-CMs) function as a biological pacemaker in vitro.
Methods and Results
The rabbit Hcn4 gene was transfected into mESCs, and stable clones were selected. mESC-CMs were generated via embryoid bodies and purified under serum/glucose-free and lactate-supplemented conditions. Approximately 90% of the purified cells were troponin I-positive by immunostaining. In mESC-CMs, expression level of the Kcnj2 gene encoding K(ir)2.1, which is essential for generation of I-K1 currents that are responsible for stabilizing the resting membrane potential, was lower than that in an adult mouse ventricle. HCN4-overexpressing mESC-CMs expressed about a 3-times higher level of the Hcn4 gene than did non-overexpressing mESC-CMs. Expression of the Cacna1h gene, which encodes T-type calcium channel and generates diastolic depolarization in the sinoatrial node, was also confirmed. Additionally, genes required for impulse conduction including Connexin40, Connexin43, and Connexin45 genes, which encode connexins forming gap junctions, and the Scn5a gene, which encodes sodium channels, are expressed in the cells. HCN4-overexpressing mESC-CMs showed significantly larger I-f currents and more rapid spontaneous beating than did non-overexpressing mESC-CMs. The beating rate of HCN4-overexpressing mESC-CMs responded to ivabradine, an I-f inhibitor, and to isoproterenol, a beta-adrenergic receptor agonist. Co-culture of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) with aggregates composed of mESC-CMs resulted in synchronized contraction of the cells. The beating rate of hiPSC-CMs co-cultured with aggregates of HCN4-overexpressing mESC-CMs was significantly higher than that of nontreated hiPSC-CMs and that of hiPSC-CMs co-cultured with aggregates of non-overexpressing mESC-CMs.
Conclusions
We generated HCN4-overexpresssing mESC-CMs expressing genes required for impulse conduction, showing rapid spontaneous beating, responding to an I-f inhibitor and beta-adrenergic receptor agonist, and having pacing ability in an in vitro co-culture system with other excitable cells. The results indicated that these cells could be applied to a biological pacemaker.

DOI： 10.1371/journal.pone.0138193

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Impact of Ezetimibe Alone or in Addition to a Statin on Plasma PCSK9 Concentrations in Patients with Type 2 Diabetes and Hypercholesterolemia: A Pilot Study

Toru Miyoshi, Keigo Nakamura, Masayuki Doi, Hiroshi Ito

AMERICAN JOURNAL OF CARDIOVASCULAR DRUGS 15 ( 3 ) 213 - 219 2015.6

Language：English Publisher：ADIS INT LTD

Background and Aim The increase in proprotein convertase subtilisin/kexin type 9 (PCSK9) leads to low-density lipoprotein (LDL) receptor degradation. Statins significantly reduce LDL-cholesterol levels, but upregulate PCSK9. This study evaluated the effect of ezetimibe monotherapy or ezetimibe in combination with a statin on serum levels of PCSK9 in patients with type 2 diabetes and hypercholesterolemia.
Methods Ezetimibe treatment was given to ten patients with diabetes without statin therapy and ten patients with statin therapy. Plasma levels of PCSK9 were examined at baseline and 24 weeks after treatment.
Results At baseline, PCSK9 concentrations in patients with statin therapy were significantly higher than those in patients without statin use and in control subjects [median (25th-75th percentile) 411 (272-467) and 382 (356-453) ng/mL, respectively, p<0.01]. After ezetimibe treatment for 24 weeks, LDL-cholesterol, triglyceride and remnant-like lipoprotein cholesterol were significantly decreased in both groups. However, PCSK9 concentration did not change compared with baseline measurements in both groups. The percentage change in LDL-cholesterol after ezetimibe therapy for 24 weeks was not correlated with the percentage change in PCSK9 concentration.
Conclusion Ezetimibe may reduce LDL-cholesterol levels without affecting PCSK9 in patients with type 2 diabetes and hypercholesterolemia.

DOI： 10.1007/s40256-015-0119-2

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Nonalcoholic Hepatic Steatosis Is a Strong Predictor of High-Risk Coronary-Artery Plaques as Determined by Multidetector CT

Kazuhiro Osawa, Toru Miyoshi, Kentarou Yamauchi, Yasushi Koyama, Kazufumi Nakamura, Shuhei Sato, Susumu Kanazawa, Hiroshi Ito

PLOS ONE 10 ( 6 ) e0131138-e0131138 2015.6

Language：English Publisher：PUBLIC LIBRARY SCIENCE

Background
Nonalcoholic fatty liver disease is associated with a risk of coronary artery disease (e.g., diabetes mellitus, dyslipidemia, metabolic syndrome). We evaluated whether nonalcoholic hepatic steatosis is associated with high-risk plaques as assessed by multidetector computed tomography (CT).
Methods
This retrospective study involved 414 participants suspected of having coronary artery disease. Nonalcoholic hepatic steatosis was defined as a liver-to-spleen fat ratio of <1.0 and the presence and appropriate characteristics of coronary-artery plaques as assessed by coronary CT angiography. High-risk plaques were identified, as were low-density plaques, positive remodeling, and spotty calcification.
Results
Compared with patients who did not have nonalcoholic hepatic steatosis, patients with nonalcoholic hepatic steatosis had more low-density plaques (21% vs. 44%, p<0.01), positive remodeling (41% vs. 58%, p = 0.01), and spotty calcification (12% vs. 36%, p<0.01). The number of high-risk plaques in patients with nonalcoholic hepatic steatosis was greater than in those without nonalcoholic hepatic steatosis (p<0.01). Patients with nonalcoholic hepatic steatosis were more likely to have high-risk plaques than were those with only an elevated level of visceral adipose tissue (>= 86 cm(2); 35% vs. 16%, p<0.01). Multivariate analyses that included nonalcoholic hepatic steatosis, amount of visceral adipose tissue, and the presence/absence of traditional risk factors demonstrated that nonalcoholic hepatic steatosis was an independent predictor of high-risk plaques (odds ratio: 4.60; 95% confidence interval: 1.94-9.07, p<0.01).
Conclusions
Diagnosis of nonalcoholic hepatic steatosis may be of value when assessing the risk of coronary artery disease.

DOI： 10.1371/journal.pone.0131138

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Comparison of effects of sitagliptin and voglibose on left ventricular diastolic dysfunction in patients with type 2 diabetes: results of the 3D trial

Hiroki Oe, Kazufumi Nakamura, Hajime Kihara, Kenei Shimada, Shota Fukuda, Tsutomu Takagi, Toru Miyoshi, Kumiko Hirata, Junichi Yoshikawa, Hiroshi Ito

CARDIOVASCULAR DIABETOLOGY 14 83 - 83 2015.6

Language：English Publisher：BIOMED CENTRAL LTD

Background: Left ventricular ( LV) diastolic dysfunction is frequently observed in patients with type 2 diabetes. Dipeptidyl peptidase-4 inhibitor ( DPP-4i) attenuates postprandial hyperglycemia ( PPH) and may have cardio-protective effects. It remains unclear whether DPP-4i improves LV diastolic function in patients with type 2 diabetes, and, if so, it is attributable to the attenuation of PPH or to a direct cardiac effect of DPP-4i. We compared the effects of the DPP-4i, sitagliptin, and the alpha-glucosidase inhibitor, voglibose, on LV diastolic function in patients with type 2 diabetes.
Methods: We conducted a prospective, randomized, open-label, multicenter study of 100 diabetic patients with LV diastolic dysfunction. Patients received sitagliptin ( 50 mg/day) or voglibose ( 0.6 mg/day). The primary endpoints were changes in the e' velocity and E/e' ratio from baseline to 24 weeks later. The secondary efficacy measures included HbA1c, GLP-1, lipid profiles, oxidative stress markers and inflammatory markers.
Results: The study was completed with 40 patients in the sitagliptin group and 40 patients in the voglibose group. There were no significant changes in the e' velocity and E/e' ratio from baseline to 24 weeks later in both groups. However, analysis of covariance demonstrated that pioglitazone use is an independent factor associated with changes in the e' and E/e' ratio. Among patients not using pioglitazone, e' increased and the E/e' ratio decreased in both the sitagliptin and voglibose groups. GLP-1 level increased from baseline to 24 weeks later only in the sitagliptin group ( 4.8 +/- 4.7 vs. 7.3 +/- 5.5 pmol/L, p < 0.05). The reductions in HbA1c and body weight were significantly greater in the sitagliptin group than in the voglibose group (-0.7 +/- 0.6 % vs. -0.3 +/- 0.4, p < 0.005; -1.3 +/- 3.2 kg vs. 0.4 +/- 2.8 kg, p < 0.05, respectively). There were no changes in lipid profiles and inflammatory markers in both groups.
Conclusions: Our trial showed that sitagliptin reduces HbA1c levels more greatly than voglibose does, but that neither was associated with improvement in the echocardiographic parameters of LV diastolic function in patients with diabetes.

DOI： 10.1186/s12933-015-0242-z

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Comparison of Outcomes in Patients With Probable Versus Definite Cardiac Sarcoidosis

Yoichi Takaya, Kengo F. Kusano, Kazufumi Nakamura, Hiroshi Ito

AMERICAN JOURNAL OF CARDIOLOGY 115 ( 9 ) 1293 - 1297 2015.5

Language：English Publisher：EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC

Patients with probable cardiac sarcoidosis (CS) who satisfy only clinical cardiac findings for CS are not uncommon. The aim of this study was to compare outcomes between patients with probable CS and those with definite CS treated with steroids. The study population consisted of 101 consecutive patients who satisfied clinical cardiac findings for CS. Patients with definite CS were defined as having histologic or clinical confirmation of CS according to the guidelines and were treated with steroids. Patients with probable CS were defined as having only clinical cardiac findings but not definite CS because of no histologic confirmation or extracardiac sarcoidosis and were not treated with steroids. The end point was major adverse cardiac events. Forty-seven patients had definite CS, and the other 54 had probable CS. Except for serum angiotensin-converting enzyme levels and left ventricular dysfunction, clinical characteristics were similar between the 2 groups. Over a median follow-up period of 15 months, major adverse cardiac events occurred more frequently in patients with probable CS than in those with definite CS (74% vs 53%, p = 0.029). The event-free survival rate was worse in patients with probable CS than in those with definite CS (log-rank test, p = 0.006). Cox proportional-hazards analysis showed that probable CS was an independent predictor of major adverse cardiac events. In conclusion, outcomes were worse in patients with probable CS than in those with definite CS treated with steroids. The initiation of steroid treatment may be considered for patients who satisfy only clinical cardiac findings for CS. (C) 2015 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.amjcard.2015.01.562

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Outcomes in Patients With High-Degree Atrioventricular Block as the Initial Manifestation of Cardiac Sarcoidosis

Yoichi Takaya, Kengo Fukushima Kusano, Kazufumi Nakamura, Hiroshi Ito

AMERICAN JOURNAL OF CARDIOLOGY 115 ( 4 ) 505 - 509 2015.2

Language：English Publisher：EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC

Although high-degree atrioventricular block (AVB) is a common initial manifestation of cardiac sarcoidosis, little is known about the outcomes. The aim of this study was to assess outcomes in patients with AVB as an initial manifestation of cardiac sarcoidosis compared with those in patients with ventricular tachyarrhytlunia (VT) and/or heart failure (HF). Fifty-three consecutive patients with cardiac sarcoidosis, who had high-degree AVB (n = 22) or VT and/or HF (n = 31), were enrolled. The end point was defined as major adverse cardiac events, including cardiac death, ventricular fibrillation, sustained VT, and hospitalization for HF. Over a median follow-up period of 34 months, the outcomes of major adverse cardiac events were better in patients with high-degree AVB than in those with VT and/or HF (log-rank test, p = 0.046). However, this difference was due mainly to HF hospitalization. The outcomes of fatal cardiac events, including cardiac death, ventricular fibrillation, and sustained VT, were comparable between the 2 groups (log-rank test, p = 0.877). The fatal cardiac events in patients with high-degree AVB were not associated with the initiation of steroid treatment or left ventricular dysfunction. In conclusion, the outcomes of major adverse cardiac events are better in patients with high-degree AVB than in those with VT and/or HF. However, patients with high-degree AVB have a high rate of fatal cardiac events, similar to those with VT and/or HF. An indication for an implantable cardioverter-defibrillator, but not a pacemaker system, can be considered in patients with cardiac sarcoidosis manifested by high-degree AVB. (C) 2015 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.amjcard.2014.11.028

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Remote ischemic preconditioning reduces contrast-induced acute kidney injury in patients with ST-elevation myocardial infarction: A randomized controlled trial

Toshiaki Yamanaka, Yusuke Kawai, Toru Miyoshi, Tsutomu Mima, Kenji Takagaki, Saori Tsukuda, Yukio Kazatani, Kazufumi Nakamura, Hiroshi Ito

INTERNATIONAL JOURNAL OF CARDIOLOGY 178 136 - 141 2015.1

Language：English Publisher：ELSEVIER IRELAND LTD

Background: Contrast medium-induced acute kidney injury (CI-AKI) is a cardiovascular complication after myocardial infarction treated with emergency percutaneous coronary intervention. The aim of this randomized, sham-controlled trial was to evaluate the impact of remote ischemic preconditioning (RIPC) on CI-AKI in patients with ST-elevation myocardial infarction who received emergency primary percutaneous coronary intervention.
Methods and results: Patients with a suspected ST-elevation myocardial infarction were randomly assigned at a 1: 1 ratio to receive percutaneous coronary intervention eitherwith (n = 63) or without (n = 62) RIPC (intermittent arm ischemia through three cycles of 5 min of inflation and 5 min of deflation of a blood pressure cuff). A total of 47 RIPC patients and 47 control patients met all study criteria. The primary endpoint was the incidence of CI-AKI, which was defined as an increase in serum creatinine >0.5 mg/dL or N25% over the baseline value 48-72 h after administration of contrast medium. The incidence of CI-AKI was 10% (n = 5) in the RIPC group and 36% (n = 17) in the control group (p = 0.003). The odds ratio of CI-AKI in patients who received RIPC was 0.18 (95% confidence interval: 0.05-0.64; p = 0.008).
Conclusions: In patients with ST-elevation myocardial infarction, RIPC before percutaneous coronary intervention reduced the incidence of CI-AKI. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.ijcard.2014.10.135

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ナノ粒子を用いたDrug Delivery System(共著）

赤木達, 中村一文

Medical Practice 32 ( 12 ) 2001 - 2003 2015

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