Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
Advance online publication
Showing 1-50 articles out of 91 articles from Advance online publication
  • Keiichi Hirono, Yukiko Hata, Makoto Nakazawa, Nobuo Momoi, Tohru Tsuji ...
    Type: ORIGINAL ARTICLE
    Subject Area: Myocardial Disease
    Article ID: CJ-18-0470
    Published: 2018
    [Advance publication] Released: August 18, 2018
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    Background: Left ventricular non-compaction (LVNC) is a cardiomyopathy morphologically characterized by 2-layered myocardium and numerous prominent trabeculations, and is often associated with dilated cardiomyopathy (DCM). Variants in the gene encoding tafazzin (TAZ) may change mitochondrial function and cause dysfunction of many organs, but they also contribute to the DCM phenotype in LVNC, and the clinical and echocardiographic features of children with this phenotype are poorly understood.

    Methods and Results: We enrolled 92 DCM phenotype LVNC patients and performed next-generation sequencing to identify the genetic etiology. Ten TAZ variants were identified in 15 male patients (16.3%) of the 92 patients, including 3 novel missense substitutions. The patients with TAZ variants had a higher frequency of early onset of disease (92.3% vs. 62.3%, P=0.0182), positive family history (73.3% vs. 20.8%, P=0.0001), and higher LV posterior wall thickness Z-score (8.55±2.60 vs. 5.81±2.56, P=0.0103) than those without TAZ variants, although the mortality of both groups was similar.

    Conclusions: This study provides new insight into the impact of DCM phenotype LVNC and emphasizes the clinical advantages available for LVNC patients with TAZ variants.

  • Julie A Damp, Zolt Arany, James D Fett, Lori Blauwet, Uri Elkayam
    Type: LETTER TO THE EDITOR
    Article ID: CJ-17-0624
    Published: 2018
    [Advance publication] Released: August 17, 2018
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  • Yoshiyuki Hattori
    Type: LETTER TO THE EDITOR
    Article ID: CJ-18-0287
    Published: 2018
    [Advance publication] Released: August 16, 2018
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  • Masahide Harada, Masayuki Koshikawa, Yuji Motoike, Tomohide Ichikawa, ...
    Type: ORIGINAL ARTICLE
    Subject Area: Arrhythmia/Electrophysiology
    Article ID: CJ-18-0398
    Published: 2018
    [Advance publication] Released: August 11, 2018
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    Background:In atrial fibrillation (AF) patients, the effect of direct oral anticoagulant (DOACs) therapy on the incidence of left atrial appendage thrombus (LAT) remains poorly investigated. This study examined the prevalence and risk factors of LAT in AF patients on DOACs undergoing catheter ablation, and sought an anticoagulation strategy for LAT.

    Methods and Results:In 407 AF patients on DOACs, transesophageal echocardiography (TEE) was performed 1 day before ablation. If patients had LAT, initial DOACs were switched to dabigatran (300 mg) or warfarin based on their renal function; TEE was repeated after treatment for ≥4 weeks. LAT was detected in 18 patients (4.4%). The prevalence of persistent AF and low-dose treatment/inappropriate dose reduction of DOACs, CHADS2/CHA2DS2-VASc scores, serum N-terminal pro-brain natriuretic peptide levels, and LA dimension/LA volume index significantly increased in patients with LAT vs. those without LAT. AF rhythm on TEE and spontaneous echo contrast also increased in patients with LAT; LA appendage flow velocity decreased. In the multivariate analysis, persistent AF and inappropriately reduced DOAC dose were risk factors for LAT. On repeat TEE, LAT had disappeared in 13 of 16 patients treated with dabigatran and in 2 of 2 patients treated with warfarin.

    Conclusions:DOACs still carry a finite risk of LAT in AF patients. Inappropriately reduced DOAC dose should be avoided to minimize the thromboembolic risk. Regular-dose dabigatran may have therapeutic efficacy against LAT.

  • Koki Nakanishi, Masao Daimon
    Type: EDITORIAL
    Article ID: CJ-18-0836
    Published: 2018
    [Advance publication] Released: August 11, 2018
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  • Tomoya Yamashita, Tomohiro Hayashi, Tokiko Tabata, Ken-ichi Hirata
    Type: EDITORIAL
    Article ID: CJ-18-0844
    Published: 2018
    [Advance publication] Released: August 11, 2018
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  • Naokata Sumitomo, Reizo Baba, Shozaburo Doi, Takashi Higaki, Hitoshi H ...
    Type: JCS GUIDELINES
    Article ID: CJ-66-0153
    Published: 2018
    [Advance publication] Released: August 11, 2018
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  • Yoshiro Onoue, Yasuhiro Izumiya, Shinsuke Hanatani, Toshifumi Ishida, ...
    Type: ORIGINAL ARTICLE
    Subject Area: Vascular Biology and Vascular Medicine
    Article ID: CJ-18-0135
    Published: 2018
    [Advance publication] Released: August 10, 2018
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    Background:Resistance exercise has beneficial effects for patients with peripheral arterial diseases. The hypothesis that muscle growth promotes angiogenesis by interacting with neighboring cells in ischemic lesions was assessed.

    Methods and Results:Skeletal muscle-specific inducible Akt1 transgenic (Akt1-TG) mice that induce growth of functional skeletal muscles as a model of resistance training were used. Proteomics analysis identified significant upregulation of heme oxigenase-1 (HO-1) in muscle tissue in Akt1-TG mice compared with control mice. Blood flow recovery after hindlimb ischemia was significantly increased in Akt1-TG mice compared with control mice. Enhanced blood flow and capillary density in Akt1-TG mice were completely abolished by the HO-1 inhibitor, Tin-mesoporphyrin. Immunohistochemistry showed that HO-1 expression was not increased in muscle cells, but it was increased in macrophages and endothelial cells. Consistent with these findings, blood flow recovery after hindlimb ischemia was similar between control mice and skeletal muscle-specific HO-1-knockout mice. Adenoviral-mediated overexpression of Akt1 did not increase HO-1 protein expression in C2C12 myotubes; however, the conditioned medium from Akt1-overexpressing C2C12 myotubes increased HO-1 expression in endothelial cells. Cytokine array demonstrated that a panel of cytokine secretion was upregulated in Akt1-overexpressing C2C12 cells, suggesting paracrine interaction between muscle cells and endothelial cells and macrophages.

    Conclusions:Akt1-mediated muscle growth improves blood flow recovery after hindlimb ischemia by enhancing HO-1 expression in neighboring cells.

  • Kazuya Kobayashi, Ken Suzuki
    Type: REVIEW
    Article ID: CJ-18-0786
    Published: 2018
    [Advance publication] Released: August 09, 2018
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    Transplantation of stem/progenitor cells is a promising, emerging treatment for heart failure (HF) in the modern era. Mesenchymal stem/stromal cells (MSCs) are considered as one of the most promising cell sources for this purpose, because of their powerful secretion of reparative factors and immunomodulatory ability. To date, various sources of MSCs have been examined for the treatment of HF in preclinical or clinical studies, including adult tissues (bone marrow and adipose tissue), perinatal tissues (umbilical cord and amnion), and pluripotent stem cells (induced pluripotent stem cells and embryonic stem cells). Adult tissue-derived MSCs have been more extensively examined. Previous clinical trials have suggested the safety and feasibility of these MSCs in HF treatment, but their therapeutic effects remain arguable. Perinatal tissue-derived MSCs have the advantages of removing the necessity of invasiveness biopsy and of mass production. An increasing number of clinical studies (albeit early stage) have been conducted. Pluripotent stem cell-derived MSCs may be another promising source because of their mass-production ability underpinned by their unlimited expansion with consistent quality. However, the risk of tumorigenicity restricts their clinical application. In this review, we summarize the current information available from preclinical and clinical studies, highlighting the advantages and disadvantages of each MSC type. This will provide an insight into consideration of the best MSC source for the treatment of HF.

  • Yuichiro Hirata, Hiroki Aoki, Takahiro Shojima, Kazuyoshi Takagi, Tohr ...
    Type: ORIGINAL ARTICLE
    Subject Area: Aortic Disease
    Article ID: CJ-17-1465
    Published: 2018
    [Advance publication] Released: August 08, 2018
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    Background:Dilatation of the ascending aorta affects those patients with bicuspid aortic valve (BAV), even after valvular surgery, possibly due to tissue fragility. The goal of the study was the molecular characterization of aorta with BAV compared to that with normal tricuspid aortic valve (TAV).

    Methods and Results: The subjects were patients who underwent surgery for aortic valve stenosis in 2013 and 2014. Nine patients with BAV and 13 with TAV were examined. There was no difference in the clinical characteristics or grade of aortic valve stenosis, but the diameters of the ascending aorta were significantly higher in the BAV group. The ascending aortic specimens were subjected to transcriptome analyses, which revealed the changes in receptor tyrosine kinase (RTK) pathway-related genes between TAV and BAV samples. Immunohistochemical study revealed higher staining of phosphorylated AKT (pAKT) in the media of the ascending aorta in the BAV group, regardless of the size of ascending aorta, whereas total AKT did not show such a difference. Immunofluorescence staining revealed the AKT activation was mainly in the medial vascular smooth muscle cells.

    Conclusions:The results showed that the RTK-AKT pathway in the medial layer of the ascending aorta is activated in aortae with BAV. Activation of this pathway may be associated with fragility and dilatation of the ascending aorta with BAV.

  • Gianluca Di Bella, Fausto Pizzino
    Type: LETTER TO THE EDITOR
    Article ID: CJ-17-1392
    Published: 2018
    [Advance publication] Released: August 07, 2018
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  • Hiroshi Morita
    Type: EDITORIAL
    Article ID: CJ-18-0810
    Published: 2018
    [Advance publication] Released: August 07, 2018
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  • Hideki Ishii, Toyoaki Murohara
    Type: EDITORIAL
    Article ID: CJ-18-0811
    Published: 2018
    [Advance publication] Released: August 07, 2018
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  • Seitaro Oda
    Type: AUTHOR’S REPLY
    Article ID: CJ-18-0816
    Published: 2018
    [Advance publication] Released: August 07, 2018
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  • Kenzaburo Nakajima, Takeshi Aiba, Takeru Makiyama, Suguru Nishiuchi, S ...
    Type: ORIGINAL ARTICLE
    Subject Area: Arrhythmia/Electrophysiology
    Article ID: CJ-18-0339
    Published: 2018
    [Advance publication] Released: August 04, 2018
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    Background:Mutation in the lamin A/C gene (LMNA) is associated with several cardiac phenotypes, such as cardiac conduction disorders (CCD), atrial arrhythmia (AA), malignant ventricular arrhythmia (MVA) and left ventricular dysfunction (LVD), leading to sudden cardiac death (SCD) and/or end-stage heart failure. We investigated how these phenotypes are associated with each other and which of them are most important for total mortality.

    Methods and Results:A multicenter registry included 110 LMNA mutation carriers (age, 43±15 years, male: 62%) from 60 families. After genetic diagnosis of LMNA mutation (missense: 27%, non-missense: 73%), patients or subjects were followed to evaluate the manifestations of their phenotypes and the risk of total mortality; 90 patients could be followed (median: 5 [0–35] years). Prevalence of the 4 clinical phenotypes was significantly increased during follow-up. Among these phenotypes, AA was significantly associated with MVA. CCD was significantly associated with LVD. LVD, meanwhile, was significantly associated with CCD and MVA. Male sex was significantly associated with MVA. Furthermore, during follow-up, 17 patients died: 12 end-stage heart failure, 4 SCD and 1 stroke. LVD was the only independent predictor for all-cause death (OR: 41.7, 95% CI: 4.1–422.3; P=0.0016).

    Conclusions:Several cardiac phenotypes were age-dependently increased in LMNA mutation carriers, suggesting that ICD or CRT-D could suppress SCD after middle age; however, LVD leading to end-stage heart failure was the only independent predictor for total mortality.

  • Yasuo Okumura, Katsuaki Yokoyama, Naoya Matsumoto, Eizo Tachibana, Kei ...
    Type: ORIGINAL ARTICLE
    Subject Area: Arrhythmia/Electrophysiology
    Article ID: CJ-18-0535
    Published: 2018
    [Advance publication] Released: August 04, 2018
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    Background:Although direct oral anticoagulants (DOACs) are widely used in Japanese patients with atrial fibrillation (AF), large-scale investigations into their use, with suitable follow-up times and rates, are lacking.

    Methods and Results:The SAKURA AF Registry is a prospective multicenter registry created to investigate therapeutic outcomes of oral anticoagulant (OAC) use in Japanese AF patients. We conducted a study involving 3,237 enrollees from 63 institutions in the Tokyo area being treated with any of 4 DOACs (n=1,676) or warfarin (n=1,561) and followed-up for a median of 39.3 months (range 28.5–43.6 months). Analyses of 1- and 2-year follow-up data available for 3,157 (97.5%) and 2,952 (91.2%) patients, respectively, showed no significant differences in rates of stroke or systemic embolism (SE), major bleeding, and all-cause mortality for DOAC vs. warfarin users (1.2 vs. 1.8%/year, 0.5 vs. 1.2%/year, and 2.1 vs. 1.7%/year, respectively). Under propensity score matching, the incidence of stroke or SE (P=0.679) and all-cause death (P=0.864) remained equivalent, but the incidence of major bleeding was significantly lower (P=0.014) among DOAC than warfarin users.

    Conclusions:A high follow-up rate allowed us to obtain reliable data on the status of OAC use and therapeutic outcomes among AF patients in Japan. Warfarin and DOACs appear to yield equivalent 3-year stroke and all-cause mortality rates, but DOACs appear to reduce the risk of major bleeding.

  • Toyoaki Murohara
    Type: MESSAGE FROM THE EDITOR-IN-CHIEF
    Article ID: CJ-66-0155
    Published: 2018
    [Advance publication] Released: August 03, 2018
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  • Tomoki Ochiai, Sung-Han Yoon, Rahul Sharma, Masaki Miyasaka, Takahiro ...
    Type: ORIGINAL ARTICLE
    Subject Area: Valvular Heart Disease
    Article ID: CJ-18-0157
    Published: 2018
    [Advance publication] Released: August 02, 2018
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    Background:Transcatheter aortic valve-in-valve (VIV) replacement within failed bioprosthetic surgical aortic valves is a feasible therapeutic option. However, data comparing the hemodynamic and clinical outcomes of VIV replacement with supra-annular self-expanding and balloon-expandable transcatheter heart valves (THV) are limited.

    Methods and Results: Outcomes of 40 and 95 patients treated with supra-annular self-expanding and balloon-expandable THV, respectively, were compared after propensity score matching, which yielded 37 pairs of patients with similar baseline characteristics. Hemodynamic and clinical outcomes were analyzed. Postprocedural mean gradient was significantly lower in the self-expanding THV group than in the balloon-expandable THV group (12.1±6.1 mmHg vs. 19.0±7.3 mmHg, P<0.001). The incidence of at least mild postprocedural aortic regurgitation (AR) was comparable between the self-expanding and balloon-expandable THV groups (21.6% vs. 10.8%, P=0.39). In the self-expanding THV group, the new-generation THV showed a trend towards a lower incidence of at least mild AR compared with the early-generation THV (12.5% vs. 38.5%, P=0.07). A similar trend was observed in the balloon-expandable THV group (4.2% vs. 23.1%, P=0.08). There was no significant difference between the self-expanding and balloon-expandable THV groups in the cumulative 2-year all-cause mortality rates (22.4% vs. 43.4%, log-rank P=0.26).

    Conclusions:The supra-annular self-expanding THV was associated with a lower postprocedural mean gradient compared with balloon-expandable THV in patients undergoing aortic VIV replacement.

  • Masazumi Watanabe, Shinya Takahashi, Hironori Yamaoka, Taijiro Sueda, ...
    Type: ORIGINAL ARTICLE
    Subject Area: Cardiovascular Intervention
    Article ID: CJ-18-0530
    Published: 2018
    [Advance publication] Released: August 02, 2018
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    Background:Recently, the carotid artery has been used as an alternative approach for transcatheter aortic valve implantation (TAVI). The aim of this study was to prove the safety and feasibility of transcarotid (TC) vs. transfemoral (TF) TAVI.

    Methods and Results: This retrospective study enrolled 726 consecutive patients with severe symptomatic aortic stenosis. All patients underwent TC-TAVI or TF-TAVI at Hôpital Haut-Lévèque, Bordeaux Heart University Hospital between September 2012 and October 2017. The TC-TAVI (n=83) and TF-TAVI (n=643) groups were compared statistically. The EuroSCORE II was significantly higher (8.2±6.7 vs. 6.4±5.5; P=0.007) and rates of current smoking, dyslipidemia and peripheral arterial disease were higher in the TC-TAVI than TF-TAVI group. All TC-TAVIs and 9.3% of TF-TAVIs were performed under general anesthesia. Radiation time was significantly shorter in the TC-TAVI than TF-TAVI group (14.5±6.0 vs. 23.0±10.8 min; P<0.001). Postimplant balloon valvuloplasty was performed more frequently in the TF-TAVI than TC-TAVI group (7.2% vs. 19.4%; P=0.006). Postoperative echocardiographic data were similar between the 2 groups, and there were no significant differences in 30-day mortality (8.4% vs. 5.0%; P=0.189) or stroke rate (1.2% vs. 2.6%; P=0.428) between the TF-TAVI and TC-TAVI groups.

    Conclusions:The feasibility and 30-day safety of TC-TAVI and TF-TAVI are similar. When TF-TAVI is not suitable anatomically for a particular patient, TC-TAVI is a preferable alternative.

  • Kentaro Hayashida
    Type: EDITORIAL
    Article ID: CJ-18-0813
    Published: 2018
    [Advance publication] Released: August 02, 2018
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  • Hendrik Drinhaus, Andreas Hohn, Thorsten Annecke
    Type: LETTER TO THE EDITOR
    Article ID: CJ-17-0783
    Published: 2018
    [Advance publication] Released: August 01, 2018
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  • Seungwoo Cha, Jin Joo Park, Sunyoung Kim, Hong-Yup Ahn, Kyungdo Han, Y ...
    Type: ORIGINAL ARTICLE
    Subject Area: Cardiac Rehabilitation
    Article ID: CJ-17-1405
    Published: 2018
    [Advance publication] Released: August 01, 2018
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    Background:Modification of health-related behaviors may improve clinical outcomes after acute myocardial infarction (AMI), but the need for systematic efforts to modify such behaviors and the estimated effect have not been investigated, especially in Asian populations. The aim of the study was to investigate changes in smoking and physical activity after AMI and their associations with death and recurrent revascularization.

    Methods and Results:Using the Korean National Insurance Health Service database, we included 13,452 patients with AMI in 2011, who were stable until 1.5 years on average after onset. Patients were grouped according to their smoking status and physical activity before and after AMI. After AMI, 44.6% of smokers continued smoking and only 11.0% of inactive patients increased their physical activity to a sufficient level. The ‘smoker/smoker’ group and ‘non-smoker/smoker’ group showed higher mortality (hazard ratio (HR): 1.566, 95% confidence interval (CI): 1.192–2.035; HR: 1.785, 95% CI: 1.061–2.815, respectively). On the other hand, the ‘active/active’ group and ‘inactive/active’ group showed less mortality (HR: 0.625, 95% CI: 0.460–0.832; HR: 0.681, 95% CI: 0.438–1.009, respectively) and the ‘inactive/active’ group showed less recurrent revascularization (HR: 0.761, 95% CI: 0.599–0.952).

    Conclusions:Smoking cessation and maintaining sufficient physical activity after AMI remain challenging for many Korean patients, and are associated with higher rates of mortality and recurrent revascularization. Systematic nationwide efforts such as cardiac rehabilitation (CR) to change health-related behaviors after AMI are required in Korea.

  • Takeshi Wada, Mihoko Hagiwara-Nagasawa, Katsunori Yoshihara, Yuji Naka ...
    Type: AUTHOR’S REPLY
    Article ID: CJ-18-0765
    Published: 2018
    [Advance publication] Released: August 01, 2018
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  • Ken Nakamura, Kazuhiro Hashimoto, Yoshimasa Sakamoto, Ko Bando, Michio ...
    Type: ORIGINAL ARTICLE
    Subject Area: Cardiovascular Surgery
    Article ID: CJ-17-1433
    Published: 2018
    [Advance publication] Released: July 31, 2018
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    Background:The aim of this study was to review our experience of mitral valve (MV) repair for acute and active infective endocarditis (AAIE) and to identify the feasibility of a new approach together with the mid-term results.

    Methods and Results:A retrospective analysis was performed on 35 consecutive AAIE patients surgically treated in the isolated mitral position. Mean follow-up after the surgery was 4.3±3.7 years. 30 of the 35 patients were successfully treated by MV plasty (MVP); however, MV replacement (MVR) was necessary in the remaining 5 patients. Our novel approach included resection of the infective lesion, approximation with direct suture and/or patch repair with bovine or autopericardium after 2-min treatment of it and the defective leaflet edge(s) with 0.625% glutaraldehyde solution, reconstruction with artificial chordae and ring annuloplasty. The success rate of MVP was 85.7%. The longest postoperative follow-up echocardiography showed no mitral regurgitation (MR) in 4, trivial MR in 4, mild MR in 16 and moderate MR in 5 patients in the MVP group. The 5-year survival rate in the MVP group was 89±6%. MVR was required in 1 patient 2 months after MVP because of increasing MR. Recurrence of endocarditis has not been observed in any case.

    Conclusions:Glutaraldehyde was safely used in a surgical intervention for AAIE in the mitral position with acceptable early and mid-term results.

  • Pyo Won Park, Byungjoon Park, Dong Seop Jeong, Kiick Sung, Wook Sung K ...
    Type: ORIGINAL ARTICLE
    Subject Area: Cardiovascular Surgery
    Article ID: CJ-18-0352
    Published: 2018
    [Advance publication] Released: July 31, 2018
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    Background:This study aimed to evaluate the early and late clinical outcomes after repeat aortic valve replacement (AVR) for subaortic pannus in patients with mechanical valves.

    Methods and Results:Between 2001 and 2017, 51 patients (median age, 59 years; 42 women) with prosthetic aortic stenosis (AS) caused by pannus ingrowth underwent repeat AVR because of acute malfunction of monoleaflet valve (3 patients), severe prosthetic AS (30 patients), and moderate prosthetic AS at the time of tricuspid or mitral valve surgery (18 patients). The median follow-up duration was 100 (interquartile range, 64–138) months. Double valve replacement was performed in 45 (88%) patients. Median time interval from previous operation was 161 (interquartile range, 121–194) months. The explanted mechanical AV was monoleaflet and bileaflet in 16 (31%) and 34 (67%) patients, respectively. Concomitant procedures included 16 mitral valve replacements (14 repeat) and 36 tricuspid valve surgeries (15 replacements, 21 repairs). No hospital deaths or cases of heart block occurred. Overall survival and event-free survival rates at 10 years were 88% and 51%, respectively. Late complications included recurrent prosthetic AS (4 patients), new paravalvular leakage of the mitral valve (5 patients), and severe tricuspid regurgitation (2 patients).

    Conclusions:Although repeat AVR for subaortic pannus had acceptable early and late survival, recurrent prosthetic AS was frequently observed during late follow-up.

  • Lee Stoner, Erik D. Hanson, Martin Gram, Jason D. Allen, Steven K. Mal ...
    Type: REVIEW
    Article ID: CJ-18-0283
    Published: 2018
    [Advance publication] Released: July 28, 2018
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    In 2010, more than 200 million people were afflicted with peripheral arterial disease (PAD). Because it is atherosclerotic in etiology, it is not surprising that PAD is a leading cause of cardiovascular morbidity. Cardiovascular disease (CVD) risk can be decreased if ambulatory physical function is improved. However, physical function is limited by a mismatch between oxygen supply and demand in the legs, which results in exertional pain, leg weakness, and balance problems. Therefore, a key factor for improving physical function, and decreasing CVD outcomes, is ensuring oxygen supply meets the oxygen demand. The purpose of this review is to highlight and evaluate practical and minimally invasive tools for assessing PAD etiology, with a specific focus on tools suited to studies focusing on improving physical function and CVD outcomes. Specifically, the macrovascular, microvascular, and skeletal muscle pathology of PAD is briefly outlined. Subsequently, the tools for assessing each of these components is discussed, including, where available, the evidence to contextualize these tools to PAD pathology as well as physical function and CVD outcomes. The goal of this review is to guide researchers to the appropriate tools with respect to their methodological design.

  • Tetsuma Kawaji, Satoshi Shizuta, Shintaro Yamagami, Takanori Aizawa, T ...
    Type: ORIGINAL ARTICLE
    Subject Area: Arrhythmia/Electrophysiology
    Article ID: CJ-18-0214
    Published: 2018
    [Advance publication] Released: July 27, 2018
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    Background:The incidence of subsequent need for permanent pacemaker implantation (PMI) after radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) in real world patients with and without pre-existing bradycardia has not yet been fully evaluated.

    Methods and Results:A total of 1,131 consecutive patients undergoing first-time RFCA for AF who had no previous or planned device implantation, were enrolled in the present study. Of 799 paroxysmal AF (PAF) patients, 121 (15.1%) had sinus node dysfunction (SND). Of 332 non-PAF patients, 73 (22.0%) had slow ventricular response (VR), defined as heart rate <80 beats/min at rest without any rate-control drugs. The 5-year cumulative incidence of PMI after RFCA in PAF patients with and without SND was 14.8% and 1.7%, respectively (P<0.001). The 5-year cumulative incidence of PMI after RFCA in non-PAF patients with and without slow VR was 14.8% and 4.7%, respectively (P<0.001). SND and female gender in PAF patients, as well as slow VR and age ≥75 years in non-PAF patients, were independent and additive predictors of PMI. The 5-year cumulative incidence of PMI was 26.3% in female PAF patients with SND and 33.3% in elderly non-PAF patients with slow VR.

    Conclusions:PMI was avoided in >85% of patients undergoing RFCA for PAF with pre-existing SND, although care should be taken for female patients. Decision-making regarding RFCA for non-PAF patients with slow VR, especially in the elderly, should be cautious.

  • Naoyuki Takashima, Hisatomi Arima, Yoshikuni Kita, Takako Fujii, Naomi ...
    Type: ORIGINAL ARTICLE
    Subject Area: Epidemiology
    Article ID: CJ-18-0346
    Published: 2018
    [Advance publication] Released: July 27, 2018
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    Background:Stroke is one of the leading causes of disability and mortality in Japan. The aim of the present analysis was to determine the non-acute survival rate after first-ever stroke using data from a large-scale population-based stroke registry in Japan.

    Methods and Results:Shiga Stroke Registry is an ongoing population-based registry of stroke, which covers approximately 1.4 million residents of Shiga Prefecture in central Japan. A total of 2,176 first-ever stroke patients, who were registered in 2011, were followed up until December 2013. The 2-year cumulative survival rates were estimated using Kaplan-Meier method according to index stroke subtype. Cox proportional hazards models were used to assess predictors of all-cause death. During a 2-year follow-up period, 663 patients (30.5%) died. The 2-year cumulative survival rate after first-ever stroke was 69.5%. There was heterogeneity in 2-year cumulative survival according to stroke subtype: lacunar infarction, 87.2%; large artery infarction, 76.1%; cardioembolic infarction, 55.4%; intracerebral hemorrhage, 65.9%; and subarachnoid hemorrhage, 56.7%. Older age, male sex, medical history, higher Japan coma scale score on admission, and stroke subtype were associated with risk of all-cause death in ≤2 years.

    Conclusions:In the present population-based stroke registry with a real-world setting in Japan, 2-year cumulative mortality after first-ever stroke is still high (>30%), particularly for cardioembolic infarction, subarachnoid hemorrhage and intracerebral hemorrhage.

  • Hiroyuki Tsutsui, Shin-ichi Momomura, Yoshihiko Saito, Hiroshi Ito, Ka ...
    Type: ORIGINAL ARTICLE
    Subject Area: Heart Failure
    Article ID: CJ-17-1424
    Published: 2018
    [Advance publication] Released: July 26, 2018
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    Background:The objective of the present analyses was to describe the baseline characteristics and treatment of the Japanese patients with HFrEF in THE PARALLEL-HF study.

    Methods and Results:Key demographic, clinical and laboratory findings, along with treatment, were reported and compared with patients enrolled in the PARADIGM-HF trial and other contemporary randomized clinical trials and registries of Japanese patients with HFrEF. In addition, the MAGGIC and EMPHASIS-HF risk scores were calculated. A total of 225 Japanese patients were randomized in PARALLEL-HF with a mean age of 67.9 years and the majority of the patients being male (85.8%) and in NYHA Class II (93.8%). Key baseline characteristics in PARALLEL-HF were generally comparable with PARADIGM-HF, and other contemporary clinical trials and registries of Japanese HFrEF patients. Patients enrolled in PARALLEL-HF were well treated with conventional evidence-based therapy at baseline (angiotensin-converting enzyme inhibitor inhibitor/angiotensin receptor blocker, 62.7%/37.3%; β-blockers, 94.7%; mineralocorticoid receptor antagonist, 59.1%). Despite the evidence-based treatment and most patients being in NYHA Class II, these patients had a low LVEF (mean 28.1%) and were at high risk of cardiovascular mortality and morbidity as assessed by the MAGGIC and EMPHASIS-HF risk scores.

    Conclusions:Overall, the patients in PARALLEL-HF were largely representative of contemporary ambulatory patients with HFrEF who are well treated with evidence-based therapies. PARALLEL-HF will determine whether sacubitril/valsartan provides similar improvements in clinical outcomes in Japanese HFrEF patients as observed in the PARADIGM-HF study.

  • Itsuko Miyazawa, Takayoshi Ohkubo, Sayaka Kadowaki, Akira Fujiyoshi, T ...
    Type: ORIGINAL ARTICLE
    Subject Area: Epidemiology
    Article ID: CJ-18-0153
    Published: 2018
    [Advance publication] Released: July 26, 2018
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    Background:Pericardial fat volume (PFV), defined as the volume of ectopic fat in and around the heart, is associated with the atherosclerotic process in coronary arteries. The magnitude of change in PFV over time and the factors affecting this change in a general population, however, have not been investigated.

    Methods and Results:Cardiac computed tomography (CT) was carried out at baseline and at follow-up in 623 Japanese men aged 40–79 years without a history of cardiovascular disease who were selected randomly in Kusatsu (Shiga, Japan). PFV was measured on cardiac CT in a qualified laboratory. Age, heart rate, triglycerides, and obesity measurements (weight, body mass index, and waist circumference) were significantly and positively associated with PFV at baseline. Over an average interval of 4.7 years, median PFV increased significantly from 64.1 cm3(IQR, 47.2–90.0 cm3) to 73.6 cm3(IQR, 53.3–98.1 cm3; P<0.001). Current smoking and heart rate were significantly and independently associated with changes in PFV (B=3.336, P<0.001 and B=6.409, P=0.003, respectively).

    Conclusions:PFV increased significantly over time in a population-based observational study of Japanese men. PFV change was significantly and independently associated with smoking status and heart rate, suggesting that quitting smoking might help reduce PFV, which could be expected to decrease the risk of coronary artery disease.

  • Daisuke Hazeki, Yumiko Ninomiya, Kentaro Ueno, Masao Yoshinaga
    Type: ORIGINAL ARTICLE
    Subject Area: Pediatric Cardiology and Adult Congenital Heart Disease
    Article ID: CJ-18-0213
    Published: 2018
    [Advance publication] Released: July 26, 2018
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    Background:While the prevalence of short QT syndrome (SQTS) in children and adolescents is low, early detection is important because SQTS can cause life-threatening arrhythmia. The aim of this study was to determine the tentative screening criteria for short QT interval in children and adolescents.

    Methods and Results:A total of 75,040 digitally stored electrocardiograms (ECG) of participants in a school-based ECG screening program were obtained between 2009 and 2013 in Kagoshima, Japan. ECG with a corrected QT interval (QTc) below the 10th percentile for each grade and sex were selected: 2,581 first graders (M/F, 1,296/1,285); 2,792 7th graders (M/F, 1,400/1,392); and 2018 10th graders (M/F, 979/1,039). Three consecutive QT/RR intervals were manually measured and corrected using Bazett’s formula. The prevalence of SQTS was estimated at 1/30,000–1/10,000, which was set compared with the prevalence of long QT syndrome, then the screening points of the prevalence of short QT interval were assumed to be between 1/5,000 and 1/2,000 to exclude the possibility of false negative. We obtained the following tentative criteria based on frequency distribution charts: 325, 315 and 305 ms for male 1st, 7th and 10th graders, respectively; and 320 ms for female 1st, 7th, and 10th graders.

    Conclusions:For primary SQTS screening of children and adolescents, the QTc values for short QT interval should be adapted according to grade and sex.

  • Kenta Yashiro, Shigeru Miyagawa, Yoshiki Sawa
    Type: EDITORIAL
    Article ID: CJ-18-0775
    Published: 2018
    [Advance publication] Released: July 26, 2018
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  • Hidehiro Kaneko, Mitsunobu Kitamura, Michael Neuss, Maki Okamoto, Tobi ...
    Type: RAPID COMMUNICATION
    Article ID: CJ-18-0536
    Published: 2018
    [Advance publication] Released: July 25, 2018
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    Background:The effect of the unique Japanese indication for MitraClip based on left ventricular ejection fraction (LVEF) is unclear.

    Methods and Results:We analyzed 874 patients who underwent MitraClip because of mitral regurgitation (MR) and compared the characteristics and outcomes between patients with LVEF <30% and ≥30%. Patients with LVEF ≤30% accounted for 33% of the study population and had a higher prevalence of functional MR. Severity of MR after MitraClip was comparable, and LVEF <30% did not independently affect survival.

    Conclusions:Japanese unique indication based on LVEF may exclude one third of patients who were treated with MitraClip in Europe.

  • Hiroya Mizuno
    Type: EDITORIAL
    Article ID: CJ-18-0791
    Published: 2018
    [Advance publication] Released: July 25, 2018
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  • Jin Ueda, Akihiro Tsuji, Takeshi Ogo, Ryotaro Asano, Nao Konagai, Shig ...
    Type: ORIGINAL ARTICLE
    Subject Area: Peripheral Vascular Disease
    Article ID: CJ-17-1210
    Published: 2018
    [Advance publication] Released: July 21, 2018
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    Background:Post-thrombotic syndrome (PTS), the most common complication of deep venous thrombosis (DVT), develops in ≥50% of patients with iliofemoral DVT. However, the benefit of endovascular treatment in Japanese patients with chronic DVT and PTS remains unclear.

    Methods and Results:Between June 2014 and May 2016, endovascular treatment was performed in 11 consecutive Japanese patients with chronic iliofemoral DVT and PTS refractory to anticoagulant therapy and elastic compression stockings. We evaluated the technical success rate, complications, patency, Villalta score, calf circumference, and popliteal vein reflux in both the acute stage (the day following endovascular treatment) and chronic stage (after 6 months). Imaging follow-up included venous duplex scanning and/or magnetic resonance venography. The technical success rate was 81.8%, without complications. In patients with successful intervention, the Villalta score improved significantly, from 9.0±3.7 preoperatively to 3.6±2.5 in the acute phase (P<0.01) and 2.9±2.1 in the chronic phase (P<0.001). The bilateral difference in lower thigh circumference also improved significantly, from 2.6±1.0 cm preoperatively to 1.4±1.0 cm in the chronic phase (P<0.001). However, popliteal vein reflux did not improve. In patients with successful intervention, venous patency rate was 100% at 6 months post-intervention.

    Conclusions:Endovascular treatment is safe and effective in Japanese patients with chronic iliofemoral DVT and PTS.

  • Satoshi Kodera, Hiroyuki Morita, Arihiro Kiyosue, Jiro Ando, Tomoyuki ...
    Type: ORIGINAL ARTICLE
    Subject Area: Ischemic Heart Disease
    Article ID: CJ-17-1455
    Published: 2018
    [Advance publication] Released: July 21, 2018
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    Background:The addition of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor to statin therapy reduces the rate of cardiovascular events. This study examined the cost-effectiveness of PCSK9 inhibitor+statin compared with standard therapy (statin monotherapy) in the treatment of triple-vessel coronary artery disease (CAD) in Japan.

    Methods and Results:A Markov model was applied to assess the costs and benefits associated with PCSK9 inhibitor+statin over a projected 30-year period from the perspective of a public healthcare payer in Japan. The incremental cost-effectiveness ratio (ICER), expressed as the quality-adjusted life-years (QALYs), was estimated. The effects on survival and numbers of events were based on the FOURIER trial and the CREDO Kyoto registry. The ICER of PCSK9 inhibitor+statin over standard therapy was 13.5 million (95% confidence interval 7.6–23.5 million) Japanese Yen (JPY) per QALY gained for triple-vessel CAD. The probability of the cost-effectiveness of PCSK9 inhibitor+statin vs. standard therapy was 0.0008% at a cost-effectiveness threshold of 5 million JPY. In patients with poorly controlled familial hypercholesterolemia (FH) with triple-vessel CAD, the ICER was 3.4 million JPY per QALY gained.

    Conclusions:PCSK9 inhibitor plus statin did not show good cost-effectiveness for triple-vessel CAD; however, it showed good cost-effectiveness for patients with triple-vessel CAD and poorly controlled FH in Japan.

  • Ken-ichiro Sasaki, Yoshihiro Fukumoto
    Type: EDITORIAL
    Article ID: CJ-18-0768
    Published: 2018
    [Advance publication] Released: July 21, 2018
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  • Stefan Baumann, Dirk Lossnitzer, Matthias Renker, Martin Borggrefe, Ib ...
    Type: LETTER TO THE EDITOR
    Article ID: CJ-17-0702
    Published: 2018
    [Advance publication] Released: July 20, 2018
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  • Hiromasa Otake, Charles A. Taylor, Hitoshi Matsuo, Nobuhiro Tanaka, Ta ...
    Type: AUTHOR’S REPLY
    Article ID: CJ-18-0677
    Published: 2018
    [Advance publication] Released: July 20, 2018
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  • Eitaro Kodani
    Type: EDITORIAL
    Article ID: CJ-18-0759
    Published: 2018
    [Advance publication] Released: July 20, 2018
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  • Kumiko Masai, Toshiaki Mano, Akiko Goda, Masataka Sugahara, Aika Daimo ...
    Type: ORIGINAL ARTICLE
    Subject Area: Heart Failure
    Article ID: CJ-18-0417
    Published: 2018
    [Advance publication] Released: July 19, 2018
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    Background:Mid-diastolic mitral forward flow (L wave) is occasionally detected in heart failure (HF), but its correlates and prognostic value are still unknown, particularly in light of the type of HF, that is, HF with preserved or with reduced ejection fraction (HFpEF, HFrEF).

    Methods and Results:Of 151 patients with HF, L wave was observed in 23 of 82 HFrEF patients and in 25 of 69 HFpEF patients. Mitral early diastolic velocity (E), the ratio of E to mitral annulus velocity, and left atrial volume index were greater in the patients with L wave than in those without L wave in both subsets. Left ventricular (LV) mass index and relative wall thickness were greater in the patients with L wave than in those without L wave in the HFpEF group, but there was no difference in either parameter in the HFrEF group. Prognosis was poorer in those with L wave than in those without L wave both in the HFrEF and HFpEF groups.

    Conclusions:Appearance of L wave is associated with the degree of LV diastolic dysfunction, but there was a difference in LV geometrical correlates of the appearance of L wave between the HFpEF and HFrEF groups. Detection of L wave is suggestive of poor prognosis independent of LVEF in HF.

  • Yusuf Ziya Şener, Metin Okşul, Cem Çöteli
    Type: LETTER TO THE EDITOR
    Article ID: CJ-18-0616
    Published: 2018
    [Advance publication] Released: July 18, 2018
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  • Wei-Syun Hu, Fung-Chang Sung, Cheng-Li Lin
    Type: AUTHOR’S REPLY
    Article ID: CJ-18-0673
    Published: 2018
    [Advance publication] Released: July 18, 2018
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  • Mitsuyoshi Takahara, Osamu Iida, Yoshimitsu Soga, Nobuyoshi Azuma, Shi ...
    Type: ORIGINAL ARTICLE
    Subject Area: Peripheral Vascular Disease
    Article ID: CJ-18-0289
    Published: 2018
    [Advance publication] Released: July 14, 2018
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    Background:The aim of the current study was to identify the distribution of length and cost of hospital stay and their associated risk factors in poor-risk Japanese critical limb ischemia (CLI) patients undergoing revascularization.

    Methods and Results:We analyzed prospectively collected data from 507 CLI patients who required assistance in their daily lives due to disability in activities of daily living and/or cognitive function impairment and who underwent revascularization. The median length and cost of hospital stay were 23 days (IQR, 9–52 days) and ¥2.25m (IQR, ¥1.33m–3.58m), respectively. Reduced albumin, tissue loss, infection, surgical reconstruction, and bilateral revascularization were associated with prolonged hospital stay (P=0.012, 0.019, <0.001, <0.001, and <0.001, respectively). Doubling the length of the hospital stay was associated with a 44% increase in hospital cost. Regular dialysis, surgical reconstruction, and bilateral revascularization were independently associated with an approximately 20% increase in the cost of hospital stay (all P<0.001).

    Conclusions:Length and cost of hospital stay varied considerably between patients. Low serum albumin, tissue loss, infection, surgical reconstruction, and bilateral revascularization were associated with longer hospital stay. Regular dialysis, surgical reconstruction, and bilateral revascularization were independently associated with an approximately 20% increase in the cost of hospital stay.

  • Hidetoshi Hattori, Atsushi Suzuki, Tsuyoshi Shiga, Tomohiro Nishinaka, ...
    Type: ORIGINAL ARTICLE
    Subject Area: Cardiovascular Surgery
    Article ID: CJ-18-0294
    Published: 2018
    [Advance publication] Released: July 13, 2018
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    Background:Recurrent ventricular tachyarrhythmias (VTA) are “A factor” modifiers in the Interagency Registry for Mechanically Assisted Circulatory Support profile. The effect of recurrent VTA on clinical outcome, however, is controversial. We evaluated the impact of recurrent VTA on outcome in Japanese heart transplant candidates with a left ventricular assist device (LVAD).

    Methods and Results:Sixty-six adult patients with advanced heart failure who were listed for heart transplantation between January 2005 and October 2017 were enrolled in the study. Recurrent VTA (modifier A status) was defined as a sustained ventricular tachycardia or fibrillation that required implantable cardioverter defibrillator shocks or an external defibrillator more than twice weekly. The primary outcome was death from any cause. The secondary outcomes were the first occurrence of VTA and recurrent VTA after LVAD implantation. Sixteen patients (24%) met the criteria for modifier A status, and 15 patients had an LVAD implanted. During a median follow-up of 1,124 days, 21 of 60 patients with an LVAD died. There was a significantly higher mortality rate in LVAD patients with modifier A status than in those who did not meet the modifier A criteria. On multivariate analysis, patients with modifier A status had an increased risk of mortality (HR, 3.43; 95% CI: 1.30–8.61, P=0.001).

    Conclusions:Recurrent VTA might be a marker for worse outcome in Japanese heart transplant candidates with an LVAD.

  • Byung Mun Park, Hoang Thi Ai Phuong, Lamei Yu, Suhn Hee Kim
    Type: ORIGINAL ARTICLE
    Subject Area: Ischemic Heart Disease
    Article ID: CJ-17-1381
    Published: 2018
    [Advance publication] Released: July 12, 2018
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    Background:Alamandine differs from angiotensin-(1–7) in a single N-terminal alanine residue. The aim of this study was to investigate whether alamandine protects the heart against reperfusion injury.

    Methods and Results:After euthanizing Sprague-Dawley rats, hearts were perfused with Krebs-Henseleit buffer for a 20-min pre-ischemic period with or without alamandine, followed by 20 min global ischemia and 50 min reperfusion. Alamandine (0.1 mg/kg) improved the postischemic left ventricular developed pressure and ±dP/dt, decreased the infarct size, and decreased the lactate dehydrogenase levels in the effluent. Alamandine increased the coronary flow and the amount of atrial natriuretic peptide (ANP) in the coronary effluent, and it decreased the expression of apoptotic proteins and increased the expression of antioxidative proteins. Pretreatment with the MrgD receptor antagonist or PD123319, but not the angiotensin type 1 receptor antagonist, attenuated the cardioprotective effects of alamandine. A similar cardioprotective effect with alamandine was also observed with high plasma ANP levels in an in vivo study. Alamandine directly stimulated ANP secretion from isolated atria, which was completely blocked by pretreatment with the MrgD receptor antagonist and was partially blocked by PD123319.

    Conclusions:These results suggest that the cardioprotective effects of alamandine against I/R injury are, in part, related to the activation of antioxidant and antiapoptotic enzymes via the MrgD receptor.

  • Philip Sarajlic, Alicja Wolk, Magnus Bäck, Susanna C. Larsson
    Type: RAPID COMMUNICATION
    Article ID: CJ-18-0598
    Published: 2018
    [Advance publication] Released: July 12, 2018
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    Background:Physical activity is associated with lower risk of coronary and cerebrovascular disease but its potential role in prevention of aortic valve stenosis (AVS) is unclear.

    Methods and Results:We investigated whether physical activity influences AVS risk in a cohort of 69,288 adults. During a mean follow-up of 15.3 years, 1,238 AVS cases were diagnosed. No associations were observed between AVS and walking/bicycling (≥1 h/day vs. almost never: hazard ratio 0.92, 95% CI 0.74–1.15) or exercise (≥4 hs/week vs. <1 h/week: hazard ratio 1.18, 95% CI 0.97–1.43).

    Conclusions:Physical activity did not reduce the incidence of AVS.

  • Masahiro Shimoda, Hirohiko Ando, Kazuhiro Naito, Akihiro Suzuki, Shini ...
    Type: ORIGINAL ARTICLE
    Subject Area: Ischemic Heart Disease
    Article ID: CJ-18-0230
    Published: 2018
    [Advance publication] Released: July 11, 2018
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    Background:Despite the revolution of coronary stents, there remain concerns about the risk of stent thrombosis, especially in patients with ST-elevation myocardial infarction (STEMI). The present study compared early vascular healing as a contributing factor to reducing stent thrombosis between Xience everolimus-eluting stents (X-EES) and Synergy everolimus-eluting stents (S-EES) in patients with STEMI.

    Methods and Results:The present study included 47 patients with STEMI requiring primary percutaneous coronary intervention with X-EES (n=25) or S-EES (n=22). Optical coherence tomography (OCT) assessments of the stented lesions were performed 2 weeks and 4 months after stent implantation. Neointimal strut coverage, malapposition and the frequency of thrombus formation were evaluated. In the 2-week OCT analysis, the proportion of covered struts in S-EES (42.4±15.4%) was significantly higher than in X-EES (26.3±10.1%, P<0.001). In the 4-month OCT analysis, the proportion of covered struts in S-EES (72.2±17.9%) was still significantly higher than in X-EES (62.0±14.9%, P=0.04).

    Conclusions:Compared with X-EES, S-EES showed a higher proportion of covered struts in the early phase after stent implantation for STEMI patients.

  • Hong Li, Qiang Liu, Ningfu Wang, Yizhou Xu, Lan Kang, Yaqi Ren, Gangji ...
    Type: ORIGINAL ARTICLE
    Subject Area: Ischemic Heart Disease
    Article ID: CJ-17-1251
    Published: 2018
    [Advance publication] Released: July 10, 2018
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    Background:In a previous study, a low level of miR-126-3p in endothelial progenitor cells (EPCs) was linked to the outcome of ischemic cardiomyopathy (ICM) patients. However, it remains unclear whether transplantation with miR-126-3p-overexpressing EPCs (MO-EPCs) can improve the cardiac function of ICM animal models.

    Methods and Results:miR-126-3p overexpression by lentiviral vector significantly increased migration and tube-like structures of EPCs from ICM patients. MO-EPCs or non-modified EPCs (NM-EPCs) were transplanted into nude rats with ICM induced by coronary artery ligation. MO-EPC transplantation increased capillary density and EPC survival rate in myocardial tissues of nude rats. Cytokines were also assessed by antibody array and real-time RT-PCR. G-CSF, VEGF-A, IL-3, IL-10, IGF-1, angiogenin, HGF, TIMP-1 and TIMP-2 were upregulated, and IL-8, MCP-1, MCP-2, TNF-α, TNF-β and MIP-1β were downregulated after miR-126-3p overexpression in EPCs. The same results were obtained in infarction tissues of nude rats after MO-EPC transplantation. Eight weeks after MO-EPC transplantation, left ventricular function improved significantly with clearly decreased infarction size, increased anterior wall thickness, and inhibition of inflammation compared with the results for NM-EPC transplantation. However, MO-EPC transplantation showed no increase in survival time of nude rats with ICM during 8 weeks of observation.

    Conclusions:miR-126-3p can restore the biology of EPCs from ICM patients. Moreover, MO-EPC transplantation improves cardiac function effectively, representing a promising future treatment for ICM.

  • Takekazu Miyoshi, Hiroshi Hosoda, Takashi Umekawa, Takashi Asada, Akih ...
    Type: ORIGINAL ARTICLE
    Subject Area: Pediatric Cardiology and Adult Congenital Heart Disease
    Article ID: CJ-18-0235
    Published: 2018
    [Advance publication] Released: July 10, 2018
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    Background:We have previously demonstrated that umbilical cord plasma natriuretic peptide (NP) levels reflect the severity of heart failure (HF) in fetuses with congenital heart defects (CHD). The aim of this study was to evaluate the significance of amniotic fluid (AF) NP levels in the assessment of HF in fetuses with CHD or arrhythmia.

    Methods and Results:This was a prospective observational study at a tertiary pediatric cardiac center. A total of 95 singletons with CHD or arrhythmia, and 96 controls from 2012 to 2015 were analyzed. AF concentrations of atrial NP (ANP), B-type NP (BNP) and N-terminal pro-B-type NP (NT-proBNP) at birth were compared with ultrasonographic assessment of fetal HF using the cardiovascular profile (CVP) score. Multivariate analysis showed that a CVP score ≤5 and preterm birth are independently associated with high AF NT-proBNP levels. AF NT-proBNP levels of fetuses with CHD or arrhythmia inversely correlated with CVP score (P for trend <0.01). In contrast, AF concentrations of ANP and BNP were extremely low, and it was difficult to assess the degree of fetal HF based on them.

    Conclusions:AF NT-proBNP concentrations increase in stepwise fashion with the severity of HF in fetuses with CHD or arrhythmia; it was the optimal NP for assessing the fetal HF.

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