Faculty Profiles - NAKAMURA Kazufumi

Papers - NAKAMURA Kazufumi

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Liver transplantation in a patient with hereditary haemorrhagic telangiectasia and pulmonary hypertension

Kentaro Ejiri, Satoshi Akagi, Kazufumi Nakamura, Naofumi Amioka, Keishi Ichikawa, Takahito Yagi, Hiroshi Ito

Pulmonary Circulation 9 ( 4 ) 2019.10

Language：English Publishing type：Research paper (scientific journal) Publisher：SAGE Publications Ltd

Hereditary haemorrhagic telangiectasia or Rendu-Osler-Weber syndrome is a systemic vascular disease with autosomal dominant inheritance, mucocutaneous telangiectasia, and repeated nasal bleeding due to vascular abnormalities. Hereditary haemorrhagic telangiectasia may occasionally lead to complications, including arteriovenous malformations and pulmonary hypertension. We present a case of a 52-year-old female patient with hereditary haemorrhagic telangiectasia who was referred to our hospital for treatment of pulmonary hypertension. She had been diagnosed with hereditary haemorrhagic telangiectasia during adolescence and was being followed up. Six months prior to presentation, she had undergone coil embolization for pulmonary haemorrhage due to pulmonary arteriovenous malformations. She was in World Health Organization functional class IV, with a mean of pulmonary arterial pressure of 38 mmHg, a pulmonary capillary wedge pressure of 10 mmHg, and a right atrial pressure of 22 mmHg. A contrast-enhanced computed tomography angiography showed large arteriovenous malformations in the liver. Right heart catheterization revealed an increase in oxygen saturation in the inferior vena cava between the supra- and infra-hepatic veins, low pulmonary vascular resistance, and high right atrial pressure. Hence, she was diagnosed with hereditary haemorrhagic telangiectasia with pulmonary hypertension due to major arteriovenous shunt resulting from arteriovenous malformations in the liver. Therefore, we considered liver transplantation as an essential treatment option. She underwent cadaveric liver transplantation after a year resulting in dramatic haemodynamic improvement to World Health Organization functional class I. Liver transplantation is a promising treatment in patients with hereditary haemorrhagic telangiectasia and pulmonary hypertension resulting from arteriovenous shunt caused by arteriovenous malformations in the liver.

DOI： 10.1177/2045894019896677

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遺残坐骨動脈瘤に対しステントグラフト(VIABAHN)を用いて治療した一例 Reviewed

大塚寛昭, 戸田洋伸, 江尻健太郎, 杜徳尚, 三好亨, 中村一文, 伊藤浩

日本心血管インターベンション治療学会抄録集 28回 [MP34 - 006] 2019.9

A Low Critical Event Rate Despite a High Abnormal Event Rate in Patients with Cardiac Implantable Electric Devices Followed Up by Remote Monitoring.

Yoshimasa Morimoto, Nobuhiro Nishii, Saori Tsukuda, Satoshi Kawada, Masakazu Miyamoto, Akihito Miyoshi, Koji Nakagawa, Atsuyuki Watanabe, Kazufumi Nakamura, Hiroshi Morita, Hiroshi Ito

Internal medicine (Tokyo, Japan) 58 ( 16 ) 2333 - 2340 2019.8

Language：English Publishing type：Research paper (scientific journal)

Objective Remote monitoring (RM) of cardiac implantable electric devices (CIEDs) has been advocated as a healthcare standard. However, expert consensus statements suggest that all patients require annual face-to-face follow-up consultations at outpatient clinics even if RM reveals no episodes. The objective of this study was to determine the critical event rate after CIED implantation through RM. Methods This multicenter, retrospective, cohort study evaluated patients with pacemakers (PMs), implantable cardioverter defibrillators (ICDs), or cardiac resynchronization therapy defibrillator (CRT-Ds) and analyzed whether or not the data drawn from RM included abnormal or critical events. Patients A total of 1,849 CIED patients in 12 hospitals who were followed up by the RM center in Okayama University Hospital were included in this study. Results During the mean follow-up period of 774.9 days, 16,560 transmissions were analyzed, of which 11,040 (66.7%) were abnormal events and only 676 (4.1%) were critical events. The critical event rate in the PM group was significantly lower than that in the ICD or CRT-D groups (0.9% vs. 5.0% or 5.9%, p<0.001). A multivariate analysis revealed that ICD, CRT-D, and a low ejection fraction were independently associated with critical events. In patients with ICD, the independent risk factors for a critical event were old age, low ejection fraction, Brugada syndrome, dilated phase hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy. Conclusion Although abnormal events were observed in two-thirds of the transmitted RM data, the critical event rate was <1% in patients with a PM, which was lower in comparison to the rates in patients with ICDs or CRT-Ds. A low ejection fraction was an independent predictor of critical events.

DOI： 10.2169/internalmedicine.1905-18

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Prognosis after lead extraction in patients with cardiac implantable electronic devices infection: Comparison of lead-related infective endocarditis with pocket infection in a Japanese single-center experience.

Nobuhiro Nishii, Yoshimasa Morimoto, Akihito Miyoshi, Saori Tsukuda, Masakazu Miyamoto, Satoshi Kawada, Koji Nakagawa, Atsuyuki Watanabe, Kazufumi Nakamura, Hiroshi Morita, Hiroshi Morimatsu, Nobuchika Kusano, Shingo Kasahara, Morio Shoda, Hiroshi Ito

Journal of arrhythmia 35 ( 4 ) 654 - 663 2019.8

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The increase in the use of cardiac implantable electronic devices (CIEDs) has been associated with an increase in CIED-related infections. Transvenous lead extraction is safe and effective for patients with CIED-related infections; however, the mortality rate in these patients is high. The prognosis after transvenous lead extraction in Japanese patients, especially those with lead-related infective endocarditis, has not been evaluated. Then, the purpose of this study is to clarify the prognosis after transvenous lead extraction in Japanese patients with CIED-related infections at a single Japanese center. METHODS: A total of 107 patients who underwent transvenous lead extraction were retrospectively reviewed. The patients were divided into a lead-related infective endocarditis group (n = 32) and a pocket infection group (n = 75). Procedure success rate and prognosis after lead extraction were evaluated between the two groups. RESULTS: Procedure success rate was not significantly different between the groups. There were no deaths associated with the procedure or with infection. The survival rate was not significantly different at 1 year or at a median of 816 days (lead-related infective endocarditis vs pocket infection; 93.7% vs 94.7%, P = 1.000; 78.1% vs 81.3%, P = 0.791) Time to reimplantation and duration of hospital stay and antibiotics therapy were significantly longer for patients with lead-related infective endocarditis. CONCLUSION: In this study, the prognosis for patients with lead-related infective endocarditis after transvenous lead extraction was favorable. Thus, extraction should be strongly recommended, even if the general condition of the patient is poor.

DOI： 10.1002/joa3.12164

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Combination of Renal Angioplasty and Angiotensin-converting-enzyme Inhibitor Can Reduce Proteinuria in Patients with Bilateral Renal Artery Disease. Reviewed

Hironobu Toda, Haruhito Uchida, Kazufumi Nakamura, Hidemi Takeuchi, Masaru Kinomura, Koji Nakagawa, Atsuyuki Watanabe, Toru Miyoshi, Nobuhiro Nishii, Hiroshi Morita, Jun Wada, Hiroshi Ito

Internal medicine (Tokyo, Japan) 58 ( 13 ) 1917 - 1922 2019.7

Language：English Publishing type：Research paper (scientific journal)

Recent large clinical trials failed to show clear benefits of percutaneous transluminal renal angioplasty (PTRA) as compared with medical therapy on patients with renal artery stenosis. It was also reported that proteinuria is an adverse prognostic factor after PTRA, and PTRA is less effective in patients with overt proteinuria. From the renoprotective point of view, to reduce proteinuria after PTRA is an important therapeutic goal in patients with renal artery stenosis with overt proteinuria. We hereby describe two patients successfully treated by combination therapy with PTRA and administration of angiotensin-converting enzyme (ACE) inhibitor for bilateral renal artery disease with overt proteinuria.

DOI： 10.2169/internalmedicine.2076-18

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Inhibitory Effects of Tofogliflozin on Cardiac Hypertrophy in Dahl Salt-Sensitive and Salt-Resistant Rats Fed a High-Fat Diet.

Tomonari Kimura, Kazufumi Nakamura, Toru Miyoshi, Masashi Yoshida, Kaoru Akazawa, Yukihiro Saito, Satoshi Akagi, Yuko Ohno, Megumi Kondo, Daiji Miura, Jun Wada, Hiroshi Ito

International heart journal 60 ( 3 ) 728 - 735 2019.5

Language：English Publishing type：Research paper (scientific journal)

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are drugs for diabetes and might prevent heart failure. In this study, we investigated the effects of tofogliflozin, an SGLT2 inhibitor, on cardiac hypertrophy and metabolism in hypertensive rats fed a high-fat diet. Dahl salt-sensitive (DS) rats, hypertensive model rats, and Dahl salt-resistant (DR) rats, non-hypertensive model rats, were fed a high-salt and high-fat diet containing tofogliflozin (0.005%) for 9 weeks to examine the effects of this drug on cardiac hypertrophy and metabolism. Tofogliflozin tended to suppress a rise of the systolic blood pressure, relative to the control, throughout the treatment period in both DR and DS rats, and significantly suppress a rise of the systolic blood pressure, relative to the control, at the 9th week in DS rats. Tofogliflozin reduced cardiac hypertrophy (heart weight/body weight) not only in DS rats but also in DR rats. Histological analysis showed that tofogliflozin significantly decreased cardiomyocyte hypertrophy and perivascular fibrosis in both DS and DR rats. Tofogliflozin significantly decreased the expression levels of genes related to cardiac hypertrophy (encoding for natriuretic peptides A and B and interleukin-6), and to cardiac fibrosis (encoding for transforming growth factor-β1 and collagen type IV), in DS rats. Recent studies have shown that hypertrophied and failing hearts shift to oxidizing ketone bodies as a significant fuel source. We also performed metabolome analysis for ventricular myocardial tissue. Tofogliflozin reduced 3-hydroxybutyrate, a ketone body, and significantly decreased the expression levels of β-hydroxybutyrate dehydrogenase 1 and 3-oxoacid CoA-transferase, which are related to ketone oxidization. In conclusion, tofogliflozin ameliorated cardiac hypertrophy and fibrosis along with reduction of ketone usage in myocardial tissue.

DOI： 10.1536/ihj.18-392

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The optimal amount of salt intake. International journal

Kazufumi Nakamura, Toru Miyoshi

Hypertension research : official journal of the Japanese Society of Hypertension 42 ( 5 ) 752 - 753 2019.5

Successful radiofrequency catheter ablation of a premature ventricular contraction triggering ventricular fibrillation in a patient with short QT syndrome. International journal

Yoshimasa Morimoto, Atsuyuki Watanabe, Hiroshi Morita, Nobuhiro Nishii, Kazufumi Nakamura, Hiroshi Ito

HeartRhythm case reports 5 ( 5 ) 262 - 265 2019.5

CLI診療(循環器内科医に求められる役割について) Reviewed

大塚寛昭, 戸田洋伸, 江尻健太郎, 三好亨, 中村一文, 森田宏, 伊藤浩

日本下肢救済・足病学会誌 11 ( 1 ) 58 - 58 2019.4

Radiofrequency catheter ablation prior to percutaneous coronary intervention in patients with atrial fibrillation coexisting with stable coronary artery disease: a single-center pilot study.

Satoshi Kawada, Atsuyuki Watanabe, Yoshimasa Morimoto, Koji Nakagawa, Nobuhiro Nishii, Kazufumi Nakamura, Hiroshi Morita, Hiroshi Ito

Heart and vessels 34 ( 4 ) 632 - 640 2019.4

Language：English Publishing type：Research paper (scientific journal)

Atrial fibrillation (AF) frequently coexists with cardiovascular disease (CAD) in a clinical setting. However, the optimum therapy for AF patients who have concomitant CAD is unclear. We retrospectively examined the efficacy and safety of radiofrequency catheter ablation (RFCA) prior to percutaneous coronary intervention (PCI) in patients with AF who had concomitant stable CAD. Between January 2014 and December 2015, a total 264 patients (179 men; mean age, 65.5 ± 10.1 years) who were referred to undergo a first RFCA procedure were reviewed in this study. Of the 264 patients, 41 (15.5%) had stable CAD detected by multi-detector computed tomography before RFCA. Thirty-seven patients who had AF with stable CAD were divided into two treatment arms: (1) RFCA prior to PCI (n = 13) and (2) PCI prior to RFCA (n = 24) [four patients excluded because of left main coronary artery disease (LMCA) or triple vessel disease (TVD)]. The median follow-up was 14 (IQR 8-19) months. There was no significant difference in AF recurrence rate after the procedure between the RFCA first group and PCI first group (P = 0.515). No symptomatic cardiovascular events occurred the during follow-up period. The PCI first group had a significantly longer duration of triple therapy (188.5 ± 167 days vs 5.6 ± 24.5 days, P = 0.01) and all of the four bleeding events occurred during triple therapy (P = 0.01). The results of this single-center pilot study suggested that prior RFCA in patients with AF coexisting with CAD could have fewer serious bleeding events than prior PCI.

DOI： 10.1007/s00380-018-1280-8

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Improvement of lung function and pulmonary hypertension after pulmonary aneurysm repair: case series

Satoshi Akagi, Kentaro Ejiri, Shingo Kasahara, Kazufumi Nakamura, Hiroshi Ito

Pulmonary Circulation 9 ( 1 ) 2019.1

Language：English Publishing type：Research paper (scientific journal) Publisher：SAGE Publications Ltd

Pulmonary artery aneurysms (PAA) can be complicated with pulmonary arterial hypertension (PAH), causing sudden death due to PA rupture and dissection. Because treatment with PAH-targeted drugs does not always prevent PAA progression, prophylactic surgical repair of the PAA seems a promising alternative. However, although it avoids rupture and dissection of the PAs, additional benefits have not been forthcoming. We therefore present two patients with co-existing PAH and a PAA who underwent surgical repair of the aneurysm. Following the surgery, their lung function and pulmonary hypertension improved. Optimal treatment of PAA remains uncertain, however, with no clear guidelines regarding the best therapeutic approach. This case series provides physicians with reasons to repair PAA surgically in patients with PAH.

DOI： 10.1177/2045894019831217

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Japanese Antibacterial Drug Management for Cardiac Sarcoidosis (J-ACNES): A multicenter, open-label, randomized, controlled study. Reviewed

Kohei Ishibashi, Yoshinobu Eishi, Nobuhiro Tahara, Masanori Asakura, Naka Sakamoto, Kazufumi Nakamura, Yoichi Takaya, Tomohisa Nakamura, Yoshikazu Yazaki, Tetsuo Yamaguchi, Koko Asakura, Toshihisa Anzai, Teruo Noguchi, Satoshi Yasuda, Fumio Terasaki, Toshimitsu Hamasaki, Kengo Kusano

Journal of arrhythmia 34 ( 5 ) 520 - 526 2018.10

Language：English Publishing type：Research paper (scientific journal)

Background: Cardiac sarcoidosis (CS) is a noncaseating granulomatous disease of unknown etiology. Lifelong immunosuppressive therapy, most frequently using corticosteroids, is a standard therapy to control hypersensitivity of immune reactions and prevent inflammation. However, it sometimes causes various systemic adverse effects and requires dose escalation. Thus, additional therapy may be required for the treatment of this disease. Recently, Propionibacterium acnes (P. acnes) was reported as one of the etiologic agents of CS, indicating that antibacterial drugs (ABD) may be effective for the treatment of CS. The objective of this study was to investigate the effect of ABD treatment, in addition to standard corticosteroid therapy, in patients with CS. Methods: The Japanese Antibacterial Drug Management for Cardiac Sarcoidosis (J-ACNES) trial was designed as a prospective, multicenter, randomized, open-label, controlled clinical trial. The patients will be randomized to receive either standard corticosteroid therapy plus ABD therapy (ABD group) or standard corticosteroid therapy (standard group). The primary endpoint is change in the total standardized uptake value at 6 months vs baseline using fluorine-18 fluorodeoxyglucose positron emission tomography and computed tomography. Secondary endpoints include efficacy, prognosis, and safety. Results: The results of this study are currently under investigation. Conclusion: The J-ACNES trial will be the first prospective study assessing the clinical benefit and safety of ABD therapy, in addition to corticosteroid treatment, in patients with CS. Our findings may improve treatment of patients with CS, as additional ABD therapy reduces recurrence of inflammation and elucidates the mechanism of sarcoidosis.

DOI： 10.1002/joa3.12084

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Coral reef aorta一連の病変と考えられた移植腎動脈狭窄に対する血管内治療の1例 Reviewed

戸田洋伸, 大塚寛昭, 江尻健太郎, 内田治仁, 杜徳尚, 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

脈管学 58 ( Suppl. ) S206 - S206 2018.9

Corrigendum to "Serum cystatin C levels are associated with coronary artery calcification in women without chronic kidney disease" [J. Cardiol. 70 (2017) 559-564]. International journal

Hiroyasu Sugiyama, Toru Miyoshi, Kazuhiro Osawa, Takashi Miki, Yuji Koide, Kazufumi Nakamura, Hiroshi Morita, Hiroshi Ito

Journal of cardiology 72 ( 3 ) 267 - 268 2018.9

重度低心機能患者に発症した重症下肢虚血、糖尿病性壊疽に対し集学的治療を行った一例 Reviewed

大塚寛昭, 戸田洋伸, 江尻健太郎, 奥山倫弘, 大澤晋, 山田潔, 三好亨, 中村一文, 伊藤浩

日本下肢救済・足病学会誌 10 ( 1 ) 83 - 83 2018.6

High Baseline Lipoprotein(a) Level as a Risk Factor for Coronary Artery Calcification Progression: Sub-analysis of a Prospective Multicenter Trial.

Jun Ida, Kazuhiko Kotani, Toru Miyoshi, Kazufumi Nakamura, Kunihisa Kohno, Hirohiko Asonuma, Satoru Sakuragi, Masayuki Doi, Takashi Miki, Yasushi Koyama, Hiroshi Ito

Acta medica Okayama 72 ( 3 ) 223 - 230 2018.6

Language：English Publishing type：Research paper (scientific journal)

Lipoprotein(a), or Lp(a), is a low-density lipoprotein-like particle largely independent of known risk factors for, and predictive of, cardiovascular disease (CVD). We investigated the association between baseline Lp(a) levels and the progression of coronary artery calcification (CAC) in patients with hypercholesterolemia undergoing statin therapy. This study was a sub-analysis of a multicenter prospective study that evaluated the annual progression of CAC under intensive and standard pitavastatin treatment with or without eicosapentaenoic acid in patients with an Agatston score of 1 to 999, and hypercholesterolemia treated with statins. We classified the patients into 3 groups according to CAC progression. A total of 147 patients (mean age, 67 years; men, 54%) were analyzed. The proportion of patients with Lp(a) > 30 mg/dL significantly increased as CAC progressed (non-progression; 5.4%, 0<CAC progression ≦100; 7.7%, and CAC progression >100; 23.6%). Logistic regression analysis showed that Lp(a) > 30 mg/dL was an independent predictor of the annual change in Agatston score > 100 (OR: 5.51; 95% CI: 1.28-23.68; p=0.02), even after adjusting for age, sex, hypertension, diabetes mellitus, current smoking, body mass index, and lipid-lowering medications. Baseline Lp(a) >30 mg/dL was a predictor of CAC progression in this population of patients with hypercholesterolemia undergoing statin therapy.

DOI： 10.18926/AMO/56067

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HCN4-Overexpressing Mouse Embryonic Stem Cell-Derived Cardiomyocytes Generate a New Rapid Rhythm in Rats with Bradycardia.

Yukihiro Saito, Kazufumi Nakamura, Masashi Yoshida, Hiroki Sugiyama, Makoto Takano, Satoshi Nagase, Hiroshi Morita, Kengo F Kusano, Hiroshi Ito

International heart journal 59 ( 3 ) 601 - 606 2018.5

Language：English Publishing type：Research paper (scientific journal)

A biological pacemaker is expected to solve the persisting problems of an artificial cardiac pacemaker including short battery life, lead breaks, infection, and electromagnetic interference. We previously reported HCN4 overexpression enhances pacemaking ability of mouse embryonic stem cell-derived cardiomyocytes (mESC-CMs) in vitro. However, the effect of these cells on bradycardia in vivo has remained unclear. Therefore, we transplanted HCN4-overexpressing mESC-CMs into bradycardia model animals and investigated whether they could function as a biological pacemaker. The rabbit Hcn4 gene was transfected into mouse embryonic stem cells and induced HCN4-overexpressing mESC-CMs. Non-cardiomyocytes were removed under serum/glucose-free and lactate-supplemented conditions. Cardiac balls containing 5 × 103 mESC-CMs were made by using the hanging drop method. One hundred cardiac balls were injected into the left ventricular free wall of complete atrioventricular block (CAVB) model rats. Heart beats were evaluated using an implantable telemetry system 7 to 30 days after cell transplantation. The result showed that ectopic ventricular beats that were faster than the intrinsic escape rhythm were often observed in CAVB model rats transplanted with HCN4-overexpressing mESC-CMs. On the other hand, the rats transplanted with non-overexpressing mESC-CMs showed sporadic single premature ventricular contraction but not sustained ectopic ventricular rhythms. These results indicated that HCN4-overexpressing mESC-CMs produce rapid ectopic ventricular rhythms as a biological pacemaker.

DOI： 10.1536/ihj.17-241

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開胸マッピングにより右室心外膜側に多彩な異常電位を認めた孤発性無症候Brugada症候群の1例

渡邊敦之, 森田宏, 川田哲史, 森本芳正, 橘元見, 中川晃志, 西井伸洋, 中村一文, 伊藤浩, 衛藤弘城, 増田善逸, 佐野俊二

臨床心臓電気生理 41 123 - 126 2018.5

TRPM4 Mutation in Patients With Ventricular Noncompaction and Cardiac Conduction Disease. International journal

Yukihiro Saito, Kazufumi Nakamura, Nobuhiro Nishi, Osamu Igawa, Masashi Yoshida, Toru Miyoshi, Atsuyuki Watanabe, Hiroshi Morita, Hiroshi Ito

Circulation. Genomic and precision medicine 11 ( 5 ) e002103 2018.5

Platypnea-orthodeoxia Syndrome Induced by Multiple Vertebral Compression Fractures and an Atrial Septal Defect.

Ko Harada, Koji Nakagawa, Hiroaki Ohtsuka, Yoichi Takaya, Teiji Akagi, Kazufumi Nakamura, Hiroshi Morita, Hiroshi Ito

Internal medicine (Tokyo, Japan) 57 ( 7 ) 971 - 973 2018.4

Language：English Publishing type：Research paper (scientific journal)

Platypnea-orthodeoxia syndrome (POS) is a rare condition that is characterized by dyspnea and arterial oxygen desaturation, which worsen on standing and which are relieved by recumbency. We treated an 80-year-old woman with an atrial septal defect (ASD) who demonstrated POS following thoracic and lumbar vertebral compression fractures. The surgical closure of the ASD relieved her symptoms. The etiology might have been multiple compression fractures causing kyphosis and aortic distortion producing right atrial compression and increased right-to-left flow through the ASD. POS should be considered in the differential diagnosis of patients who develop dyspnea after vertebral compression fractures. The careful assessment of the patient's history and clinical condition helps in the diagnosis of POS.

DOI： 10.2169/internalmedicine.9904-17

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Papers - NAKAMURA Kazufumi