Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
Advance online publication
Showing 1-50 articles out of 81 articles from Advance online publication
  • Kyu Kim, Darae Kim, Sang-Eun Lee, In Jeong Cho, Chi Young Shim, Geu-Ru ...
    Type: ORIGINAL ARTICLE
    Subject Area: Valvular Heart Disease
    Article ID: CJ-18-0609
    Published: December 15, 2018
    [Advance publication] Released: December 15, 2018
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    Background: Infective endocarditis (IE) in cancer patients is increasing, but because little is known about it in these patients, we analyzed patient characteristics and outcomes and compared these factors in IE patients with and without cancer.

    Methods and Results: This retrospective cohort study included 170 patients with IE newly diagnosed between January 2011 and December 2015. Among 170 patients, 30 (17.6%) had active cancer. The median age of IE patients with cancer was higher than that of non-cancer patients. Nosocomial IE was more common in cancer patients. Non-dental procedures, such as intravenous catheter insertion and invasive endoscopic or genitourinary procedures, were more frequently performed before IE developed in cancer patients. Staphylococcus was the most common pathogen in cancer patients, whereas Streptococcus was the most common in non-cancer patients. In-hospital mortality was significantly higher in cancer patients with IE (34.4% vs. 12.4%, P<0.001). IE was an important reason for discontinuing antitumor therapy and withholding additional aggressive treatment in nearly all deceased cancer patients.

    Conclusions: IE is common in cancer patients and is associated with poorer outcomes. Patients with IE and cancer have different clinical characteristics. Additional studies regarding antibiotic prophylaxis before non-dental invasive procedures in cancer patients are needed, as cancer patients are not considered to be at higher risk of IE.

  • Younes Jahangiri, Masayuki Endo, Ramsey Al-Hakim, John A. Kaufman, Kha ...
    Type: ORIGINAL ARTICLE
    Subject Area: Cardiovascular Intervention
    Article ID: CJ-18-0592
    Published: December 14, 2018
    [Advance publication] Released: December 14, 2018
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    Background: Inflammation and platelet activation have been shown to be involved in acute thromobogenicity following venous occlusive conditions. The aim of this study was to identify the association of baseline platelet count and neutrophil/lymphocyte ratio (NLR) with venous stent failure.

    Methods and Results: Patients who underwent technically successful iliocaval venous stent placement with available baseline complete blood count and follow-up stent patency data were selected (n=50). Stent failure was defined as >50% stenosis or occlusion at follow-up angiography, contrast-enhanced CT, MRI or duplex US. Median patient age was 49.5 years (range, 13–76 years), and 62% were female. Median follow-up time was 10.2 months (range, 0.1–76.4 months). Stent failure occurred in 13 patients (26%) after a median of 1.2 months (range, 1 day–76.4 months). On multivariable-adjusted Cox modeling, baseline platelets (HR, 2.28; P=0.004) and WBC count (HR, 2.03; P=0.013) were significantly associated with stent failure on follow-up; neutrophils (HR, 16.10; P=0.050); and NLR (HR, 12.19; P=0.050) had borderline significance. Compared with patients without stent failure, those with early, but not late, stent failure had higher baseline platelets (P=0.031) and neutrophils (P=0.025), and NLR (P=0.026).

    Conclusions: Baseline platelet count and NLR are associated with early but not late failure of iliocaval venous stents. This suggests different pathophysiologic mechanisms and a role for both platelet activation and inflammatory mechanisms in early rather than late stent thrombosis. Future research is needed to better explain this novel finding.

  • Masataka Sugahara, Toshiaki Mano, Akiko Goda, Kumiko Masai, Yuko Soyam ...
    Type: ORIGINAL ARTICLE
    Subject Area: Imaging
    Article ID: CJ-18-0999
    Published: December 14, 2018
    [Advance publication] Released: December 14, 2018
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    Background: We used dual Doppler echocardiography to measure the time interval between the mitral and tricuspid valve opening (MO-TO time), which we expected would reflect the balance between left and right ventricular hemodynamics.

    Methods and Results: We prospectively enrolled 60 patients with heart failure (HF) and sinus rhythm. The MO-TO time was measured in addition to routine echocardiography parameters, invasive hemodynamic parameters and plasma B-type natriuretic peptide (BNP) level in all patients. Patients were divided into 2 groups based on the MO-TO time: MOP (mitral opening preceding tricuspid opening), and TOP (tricuspid opening preceding mitral opening) groups. We followed up the predefined adverse outcomes (cardiovascular [CV] death and hospitalization due to worsening HF) for 1 year. Pulmonary artery wedge pressure (PAWP) and mean pulmonary artery pressure (mPAP) were higher in the MOP than in the TOP group (P<0.001; P<0.001, respectively). The probability of an adverse CV outcome was higher in the MOP than in the TOP group (log-rank test; P=0.002). Addition of MOP improved the predictive power of univariate predictors (mitral E/A ratio and BNP) in the bivariate Cox analysis (P=0.017, P=0.024, respectively).

    Conclusions: MOP reflects pulmonary hypertension caused by left heart disease and has prognostic value in predicting adverse CV events in patients with HF.

  • Hirohisa Endo, Tomotaka Dohi, Takehiro Funamizu, Jun Shitara, Hideki W ...
    Type: ORIGINAL ARTICLE
    Subject Area: Ischemic Heart Disease
    Article ID: CJ-18-0962
    Published: December 12, 2018
    [Advance publication] Released: December 12, 2018
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    Background: High-sensitivity C-reactive protein (hs-CRP) is a well known risk factor for the development of cardiovascular disease and cancer. We investigated the long-term impact of hs-CRP on cancer mortality in patients with stable coronary artery disease (CAD).

    Methods and Results: This study was a retrospective analysis of 2,867 consecutive patients who underwent percutaneous coronary intervention for stable CAD from 2000 to 2016. The patients were divided into 2 groups according to median hs-CRP. We then evaluated the association between baseline hs-CRP and both all-cause and cancer deaths. Median hs-CRP was 0.10 mg/dL (IQR, 0.04–0.27 mg/dL). The median follow-up period was 5.8 years (IQR, 2.3–10.0 years). There were 416 deaths (14.5%), including 149 cardiovascular deaths (5.2%) and 115 (4.0%) cancer deaths. On Kaplan-Meier analysis the higher hs-CRP group had a significantly higher incidence of both all-cause and cancer death (log-rank, P<0.001 and P=0.001, respectively). On multivariable analysis higher hs-CRP was significantly associated with higher risk of cancer death (HR, 1.74; 95% CI: 1.18–2.61, P=0.005).

    Conclusions: Elevated baseline hs-CRP was significantly associated with cancer mortality in patients with stable CAD. Hs-CRP measurement may be useful for the identification of subjects with an increased risk of cancer death.

  • Toyoaki Murohara
    Type: MESSAGE FROM THE EDITOR-IN-CHIEF
    Article ID: CJ-66-0159
    Published: December 12, 2018
    [Advance publication] Released: December 12, 2018
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  • Tatsuo Aoki
    Type: EDITORIAL
    Article ID: CJ-18-1268
    Published: December 11, 2018
    [Advance publication] Released: December 11, 2018
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  • Shunsuke Saito, Koichi Toda, Teruya Nakamura, Shigeru Miyagawa, Yasush ...
    Type: ORIGINAL ARTICLE
    Subject Area: Heart Failure
    Article ID: CJ-18-0958
    Published: December 08, 2018
    [Advance publication] Released: December 08, 2018
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    Background: We evaluated clinical outcomes of left ventricular assist device (LVAD) support in patients with or without severe right heart failure, in order to determine what kind of organ allocation system could help severe biventricular failure patients to be safely bridged to heart transplantation (HTx), even in Japan where the waiting time for HTx is extremely long.

    Methods and Results: One hundred and seventy consecutive patients who were implanted with continuous-flow LVAD at the present institution were included in this study. The patients were divided into 2 groups: 158 patients with isolated LVAD (group-LVF) and 12 patients who required long-term mechanical or inotropic right heart support (group-BVF). Post-LVAD survival in group-BVF was significantly worse than in group-LVF (P<0.0001). Given that many patients in group-BVF died between 1 and 2 years after LVAD implantation, Kaplan-Meier survival curve simulation was carried out under the condition that all the patients in group-BVF who died on LVAD support >1 year after LVAD implantation had received HTx at 365 days after LVAD implantation and survived thereafter. In this simulation, no significant difference in survival was seen between the groups (P=0.2424).

    Conclusions: A new allocation system that allows severe right heart failure patients to receive HTx at around 1 year would enable rescue of the patients with severe right heart failure.

  • Shinya Takase
    Type: EDITORIAL
    Article ID: CJ-18-1241
    Published: December 08, 2018
    [Advance publication] Released: December 08, 2018
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  • Christian O’Donnell, Hanjay Wang, Phat Tran, Shari Miller, Paul Shuttl ...
    Type: ORIGINAL ARTICLE
    Subject Area: Cardiovascular Surgery
    Article ID: CJ-18-0780
    Published: December 07, 2018
    [Advance publication] Released: December 07, 2018
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    Background: Studies assessing the safety and effectiveness of Del Nido cardioplegia for adult cardiac surgery remain limited. We investigated early outcomes after coronary artery bypass grafting (CABG) using single-dose Del Nido cardioplegia vs. conventional multi-dose blood cardioplegia.

    Methods and Results: The 81 consecutive patients underwent isolated CABG performed by a single surgeon. The initial 27 patients received anterograde blood cardioplegia, while the subsequent 54 patients received anterograde Del Nido cardioplegia. There were no differences in the baseline characteristics of each group nor any differences in the 30-day incidences of myocardial infarction, all-cause death, and readmission following surgery. The use of Del Nido cardioplegia was associated with shorter cardiopulmonary bypass time (98 vs. 115 min, P=0.011), shorter cross-clamp time (74 vs. 87 min, P=0.006), and decreased need for intraoperative defibrillation (13.0% vs. 33.3%, P=0.030) compared with blood cardioplegia. To control for the difference in cross-clamp time, we performed propensity score matching with a logistical treatment model and confirmed that Del Nido cardioplegia provided similar outcomes as blood cardioplegia and also reduced the need for defibrillation independent of cross-clamp time.

    Conclusions: Compared with conventional blood cardioplegia, Del Nido cardioplegia provided excellent myocardial protection with reduced need for intraoperative defibrillation, shorter bypass and cross-clamp times, and comparable early clinical outcomes for adult patients undergoing CABG.

  • Rajesh Prajapati, Takayuki Fujita, Kenji Suita, Takashi Nakamura, Wenq ...
    Type: ORIGINAL ARTICLE
    Subject Area: Arrhythmia/Electrophysiology
    Article ID: CJ-18-0743
    Published: December 06, 2018
    [Advance publication] Released: December 06, 2018
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    Background: It has been suggested that protein directly activated by cAMP (Epac), one of the downstream signaling molecules of β-adrenergic receptor (β-AR), may be an effective target for the treatment of arrhythmia. However, there have been no reports on the anti-arrhythmic effects or cardiac side-effects of Epac1 inhibitors in vivo.

    Methods and Results: In this study, the roles of Epac1 in the development of atrial and ventricular arrhythmias are examined. In addition, we examined the usefulness of CE3F4, an Epac1-selective inhibitor, in the treatment of the arrhythmias in mice. In Epac1 knockout (Epac1-KO) mice, the duration of atrial fibrillation (AF) was shorter than in wild-type mice. In calsequestrin2 knockout mice, Epac1 deficiency resulted in a reduction of ventricular arrhythmia. In both atrial and ventricular myocytes, sarcoplasmic reticulum (SR) Ca2+ leak, a major trigger of arrhythmias, and spontaneous SR Ca2+ release (SCR) were attenuated in Epac1-KO mice. Consistently, CE3F4 treatment significantly prevented AF and ventricular arrhythmia in mice. In addition, the SR Ca2+ leak and SCR were significantly inhibited by CE3F4 treatment in both atrial and ventricular myocytes. Importantly, cardiac function was not significantly affected by a dosage of CE3F4 sufficient to exert anti-arrhythmic effects.

    Conclusions: These findings indicated that Epac1 is involved in the development of atrial and ventricular arrhythmias. CE3F4, an Epac1-selective inhibitor, prevented atrial and ventricular arrhythmias in mice.

  • Yasutsugu Shiono, Takashi Akasaka
    Type: 2018 ESC REPORT
    Article ID: CJ-18-1056
    Published: December 06, 2018
    [Advance publication] Released: December 06, 2018
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  • Fu-Shan Xue, Qing Liu, Ya-Yang Liu, Gui-Zhen Yang
    Type: LETTER TO THE EDITOR
    Article ID: CJ-18-0080
    Published: December 05, 2018
    [Advance publication] Released: December 05, 2018
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  • Seon Hwa Lee, Soo-Jin Kim
    Type: AUTHOR’S REPLY
    Article ID: CJ-18-1140
    Published: December 05, 2018
    [Advance publication] Released: December 05, 2018
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  • Yukihiro Koretsune, Takuma Etoh, Yousuke Katsuda, Tetsuro Suetsugu, Ke ...
    Type: ORIGINAL ARTICLE
    Subject Area: Arrhythmia/Electrophysiology
    Article ID: CJ-18-0655
    Published: December 04, 2018
    [Advance publication] Released: December 04, 2018
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    Background: Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective non-interventional study of stroke prevention in patients with newly diagnosed non-valvular AF (NAVF) that is being conducted in 35 countries.

    Methods and Results: A total of 52,081 patients with a new diagnosis of NVAF were enrolled prospectively in GARFIELD-AF. Of these, 4859 (9.3%) were recruited in Japan (2010–2016). In cohort 1 (2010–2011), few patients were on non-vitamin K antagonist oral anticoagulants (NOAC) globally. From cohort 2 onwards (2011–2016), however, there was a rapid increase in NOAC use around the globe, especially in Japan. By the last year of enrolment (2015–2016), 67.9% of patients in Japan and 43.1% of patients globally were on NOAC±antiplatelet therapy (AP). In Japan and globally, 17.0% and 12.2% of patients, respectively, did not receive stroke prevention treatment. Few patients in Japan (5.7%) received AP only. Compared with the other countries, the unadjusted rates of all-cause mortality and major bleeding were low, while rates of stroke/systemic embolism were similar after 1 year of follow-up.

    Conclusions: GARFIELD-AF continues to provide important information on the homogeneity and heterogeneity of baseline characteristics and treatment patterns in patients with newly diagnosed NVAF. This diversity reflects the differences in outcomes in Japan compared with the rest of the world.

  • Akiomi Yoshihisa
    Type: EDITORIAL
    Article ID: CJ-18-1214
    Published: December 04, 2018
    [Advance publication] Released: December 04, 2018
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  • Eleni Geladari, Panagiota Tsamadia, Natalia G. Vallianou
    Type: REVIEW
    Article ID: CJ-18-0442
    Published: 2018
    [Advance publication] Released: November 30, 2018
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    Elevated plasma lipid levels are linked to atherosclerosis, a hallmark for coronary artery disease (CAD), documented by animal studies as well as angiographic and clinical studies. The ability to treat hyperlipidemia through lifestyle changes and lipid-lowering agents has been related to the slow progression of atherosclerosis and decreased incidence of major coronary events. Angiopoietin-like proteins (ANGPTLs) are a family of secreted glycoproteins expressed in the liver that share common domain characteristics with angiopoietins, the main regulators of angiogenesis. Although ANGPTLs cannot bind the angiopoietin receptors expressed on endothelial cells, 2 ANGPTL family members (ANGPTL3 and ANGPTL4) have clinical importance because of their unambiguous effects on lipoprotein metabolism in mice and humans. The regulation of plasma lipid levels by ANGPTL3 is controlled via affecting lipoprotein lipase and endothelial lipase-mediated hydrolysis of triglycerides (TGs) and phospholipids. ANGPTL 3, along with the other 2 members, 4 and 8, is a key to balancing the distribution of circulating TGs between white adipose tissue (WAT) and oxidative tissues. Thus, ongoing trials with newly discovered medications in the form of monoclonal antibodies or antisense oligonucleotides with novel targets are under analysis and may represent a fresh frontier in the treatment of hyperlipidemia and CAD.

  • Masanari Kuwabara, Ichiro Hisatome
    Type: EDITORIAL
    Article ID: CJ-18-1233
    Published: 2018
    [Advance publication] Released: November 30, 2018
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  • Tomohiro Hayashi, Tomoya Yamashita, Hikaru Watanabe, Kenjiro Kami, Nao ...
    Type: ORIGINAL ARTICLE
    Subject Area: Heart Failure
    Article ID: CJ-18-0468
    Published: 2018
    [Advance publication] Released: November 29, 2018
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    Background: Gut microbiome composition or circulating microbiome-related metabolites in patients with heart failure (HF) have not been investigated at different time points (i.e., in the decompensated (Decomp) and compensated (Comp) phases).

    Methods and Results: We prospectively enrolled 22 patients admitted for HF and 11 age-, sex-, and comorbidity-matched hospitalized control subjects without a history of HF. Gut flora and plasma microbiome-related metabolites were evaluated by amplicon sequencing of the bacterial 16S ribosomal RNA gene and capillary electrophoresis time-of-flight mass spectrometry, respectively. HF patients were evaluated in both the Decomp and Comp phases during hospitalization. The phylum Actinobacteria was enriched in HF patients compared with control subjects. At the genus level, Bifiodobacterium was abundant while Megamonas was depleted in HF patients. Meanwhile, plasma concentration of trimethylamine N-oxide (TMAO), a gut microbiome-derived metabolite, was increased in HF patients (Decomp HF vs. control, P=0.003; Comp HF vs. control, P=0.004). A correlation analysis revealed positive correlations between the abundance of the genus Escherichia/Shigella and levels of TMAO and indoxyl sulfate (IS, a microbe-dependent uremic toxin) in Comp HF (TMAO: r=0.62, P=0.002; IS: r=0.63, P=0.002). Escherichia/Shigella was more abundant in Decomp than in Comp HF (P=0.030).

    Conclusions: Our results suggest that gut microbiome composition and microbiome-related metabolites are altered in HF patients.

  • Daisuke Nakamura, Keisuke Yasumura, Hitoshi Nakamura, Yutaka Matsuhiro ...
    Type: ORIGINAL ARTICLE
    Subject Area: Cardiovascular Intervention
    Article ID: CJ-18-0701
    Published: 2018
    [Advance publication] Released: November 29, 2018
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    Background: There are few reports about the differences between drug-eluting stents (DES) and bare metal stents (BMS) in neoatherosclerosis associated with in-stent restenosis (ISR), so we compared the frequency and characteristics of neoatherosclerosis with ISR evaluated by optical coherence tomography (OCT) in the present study.

    Methods and Results: Between March 2009 and November 2016, 98 consecutive patients with ISR who underwent diagnostic OCT were enrolled: 34 patients had a BMS, 34 had a 1st-generation DES, and 30 had a 2nd-generation DES. Neoatherosclerosis was defined as a lipid neointima (including a thin-cap fibroatheroma [TCFA] neointima, defined as a fibroatheroma with a fibrous cap <65 µm) or calcified neointima. As a result, lipid neointima, TCFA neointima and calcified neointima were detected in 39.8%, 14.3%, and 5.1%, respectively, of all patients. The frequency of neoatherosclerosis was significantly greater with DES than BMS (48.4% vs. 23.5%, P=0.018). The minimum fibrous cap thickness was significantly thicker with DES than BMS (110.3±41.1 µm vs. 62.5±17.1 µm, P<0.001). In addition, longitudinal extension of neoatherosclerosis in the stented segment was less with DES than BMS (20.2±15.1% vs. 71.8±27.1%, respectively, P=0.001).

    Conclusions: OCT imaging demonstrated that neoatherosclerosis with ISR was more frequent with DES than BMS and its pattern exhibited a more focal and thick fibrous cap as compared with BMS.

  • Nobuyuki Takakura
    Type: REVIEW
    Article ID: CJ-18-1180
    Published: 2018
    [Advance publication] Released: November 28, 2018
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    The roles that blood vessels play in the maintenance of organs and tissues in addition to the delivery of oxygen and nutrients are being gradually clarified. The maintenance of tissue-specific organ stem cells, such as hematopoietic and neuronal stem cells, is supported by endothelial cells (ECs), which represent an important component of the stem cell niche. The maintenance of organogenesis, for example, osteogenesis and liver generation/regeneration, is supported by molecules referred to as “angiocrine signals” secreted by EC. The mechanisms responsible for the well-known functions of blood vessels, such as thermoregulation and metabolism, especially removal of local metabolites, have now been determined at the molecular level. Following the development of single-cell genetic analysis, blood cell heterogeneity, especially of mural cell populations, has been established and tissue-specific blood vessel formation and function are now also understood at the molecular level. Among the heterogeneous populations of ECs, it seems that a stem cell population with the ability to maintain the production of ECs long-term is present in pre-existing blood vessels. Neovascularization by therapeutic angiogenesis yields benefits in many diseases, not only ischemic disease but also metabolic disease and other vascular diseases. Therefore, vascular endothelial stem cells should be considered to use in vascular regeneration therapy.

  • Michio Sato, Keishi Miyata, Zhe Tian, Tsuyoshi Kadomatsu, Yoshihiro Uj ...
    Type: ORIGINAL ARTICLE
    Subject Area: Heart Failure
    Article ID: CJ-18-0925
    Published: 2018
    [Advance publication] Released: November 27, 2018
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    Background: The rapid increase in the number of heart failure (HF) patients in parallel with the increase in the number of older people is receiving attention worldwide. HF not only increases mortality but decreases quality of life, creating medical and social problems. Thus, it is necessary to define molecular mechanisms underlying HF development and progression. HMGB2 is a member of the high-mobility group superfamily characterized as nuclear proteins that bind DNA to stabilize nucleosomes and promote transcription. A recent in vitro study revealed that HMGB2 loss in cardiomyocytes causes hypertrophy and increases HF-associated gene expression. However, it’s in vivo function in the heart has not been assessed.

    Methods and Results: Western blotting analysis revealed increased HMGB2 expression in heart tissues undergoing pressure overload by transverse aorta constriction (TAC) in mice. Hmgb2 homozygous knockout (Hmgb2−/−) mice showed cardiac dysfunction due to AKT inactivation and decreased sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)2a activity. Compared to wild-type mice, Hmgb2−/− mice had worsened cardiac dysfunction after TAC surgery, predisposing mice to HF development and progression.

    Conclusions: This study demonstrates that upregulation of cardiac HMGB2 is an adaptive response to cardiac stress, and that loss of this response could accelerate cardiac dysfunction, suggesting that HMGB2 plays a cardioprotective role.

  • Shohei Yoshida, Shigeru Miyagawa, Satsuki Fukushima, Yasushi Yoshikawa ...
    Type: ORIGINAL ARTICLE
    Subject Area: Cardiovascular Surgery
    Article ID: CJ-18-0625
    Published: 2018
    [Advance publication] Released: November 23, 2018
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    Background: To determine the impact of cardiac function and type of mitral valve (MV) surgery on blood flow and energy loss in the left ventricle (LV).

    Methods and Results: This study enrolled patients with ejection fraction (EF) <35% or >50%; both groups had native (n=27 and n=16), repaired (n=19 and n=33), or prosthetic MVs (n=18 and n=19). They were examined by echocardiography-based vector flow mapping to assess the LV blood flow pattern and energy loss per heartbeat. Among patients with preserved EF, those with native MVs displayed a clockwise vortex and relatively low energy loss. In contrast, MV replacement induced a counterclockwise vortex producing higher energy loss than MV repair, which induced a normal clockwise vortex. This indicated the need for MV repair to minimize LV energy loss after surgery. Among the patients with reduced EF, those with native MVs showed a blood flow pattern similar to those with preserved EF and native MVs; furthermore, those with repaired MVs and half of the patients with prosthetic MVs displayed a clockwise vortex, resulting in no difference in energy loss between the 2 types of MV surgery.

    Conclusions: Cardiac function and the type of MV surgery are factors affecting the postoperative LV blood flow pattern. MV replacement resulted in abnormal blood flow with normal cardiac function, whereas advanced cardiomyopathy modified the blood flow pattern post-MV replacement.

  • Doyeon Hwang, Joo Myung Lee, Hyun Kuk Kim, Ki Hong Choi, Tae-Min Rhee, ...
    Type: ORIGINAL ARTICLE
    Subject Area: Ischemic Heart Disease
    Article ID: CJ-18-0662
    Published: 2018
    [Advance publication] Released: November 22, 2018
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    Background: The differential prognostic impact of β-blocker dose after acute myocardial infarction (AMI) has been under debate. The current study sought to compare clinical outcome after AMI according to β-blocker dose using the Korea Acute Myocardial Infarction Registry-National Institutes of Health (KAMIR-NIH).

    Methods and Results: Of the total population of 13,104 consecutive AMI patients enrolled in the KAMIR-NIH, the current study analyzed 11,909 patients. These patients were classified into 3 groups (no β-blocker; low-dose [<25% of target dose]; and high-dose [≥25% of target dose]). The primary outcome was cardiac death at 1 year. Compared with the no β-blocker group, both the low-dose and high-dose groups had significantly lower risk of cardiac death (HR, 0.435; 95% CI: 0.363–0.521, P<0.001; HR, 0.519; 95% CI: 0.350–0.772, P=0.001, respectively). The risk of cardiac death, however, was similar between the high- and low-dose groups (HR, 1.194; 95% CI: 0.789–1.808, P=0.402). On multivariable adjustment and inverse probability weighted analysis, the result was the same.

    Conclusions: The use of β-blockers in post-AMI patients had significant survival benefit compared with no use of β-blockers. There was no significant additional benefit of high-dose β-blockers compared with low-dose β-blockers, however, in terms of 1-year risk of cardiac death.

  • Soichiro Tamura, Shinichi Iwata, Asahiro Ito, Sera Ishikawa, Kazuki Mi ...
    Type: ORIGINAL ARTICLE
    Subject Area: Valvular Heart Disease
    Article ID: CJ-18-0818
    Published: 2018
    [Advance publication] Released: November 22, 2018
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    Background: Although careful monitoring of asymptomatic severe aortic stenosis (AS) is recommended to prevent missing the optimal timing of surgical or transcatheter aortic valve replacement, prophylactic treatment that could extend the asymptomatic period remains unknown. In a hypertensive population, high blood pressure (BP) measured at the doctor’s office is known to be associated with B-type natriuretic peptide (BNP) level, a surrogate marker for symptomatic deterioration in AS. Little is known regarding the association between nocturnal BP variables and BNP in severe AS with preserved ejection fraction (EF).

    Methods and Results: The subjects consisted of 78 severe AS patients (mean age, 79±6 years) with preserved EF. Nocturnal BP was measured hourly using a home BP monitoring device. On multiple regression analysis, nocturnal mean systolic BP (SBP) remained independently associated with BNP after adjustment for age, sex, body mass index, estimated glomerular filtration rate, antihypertensive medication class, early diastolic mitral annular velocity, and left ventricular mass index (P=0.03), whereas diastolic BP (DBP) and variables of BP variability were not.

    Conclusions: Higher nocturnal SBP rather than DBP or indices of BP variability was independently associated with BNP in AS patients with preserved EF. Intervention for nocturnal SBP may therefore extend the asymptomatic period and improve prognosis.

  • Satoru Mitomo, Ozan M. Demir, Francesco Giannini, Azeem Latib, Antonio ...
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-18-0795
    Published: 2018
    [Advance publication] Released: November 20, 2018
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  • Toru Kondo, Takahiro Okumura, Yuya Matsue, Atsushi Shiraishi, Nobuyuki ...
    Type: ORIGINAL ARTICLE
    Subject Area: Heart Failure
    Article ID: CJ-18-0724
    Published: 2018
    [Advance publication] Released: November 15, 2018
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    Background: The aim of this study was to assess specialty-related differences in the treatment for patients with acute heart failure (AHF) in the acute phase and subsequent prognostic differences.

    Methods and Results: We analyzed hospitalizations for AHF in REALITY-AHF, a multicenter prospective registry focused on very early presentation and treatment in patients with AHF. All patients were classified according to the medical specialty of the physicians responsible for contributed most to decisions regarding the initial diagnosis and treatment after the emergency department (ED) arrival. Patients initially managed by emergency physicians (n=614) or cardiologists (n=911) were analyzed. After propensity-score matching, vasodilators were used less often by emergency physicians than by cardiologists at 90 min after ED arrival (29.8% vs. 46.1%, P<0.001); this difference was also observed at 6, 24, and 48 h. Cardiologists administered furosemide earlier than emergency physicians (67 vs. 102 min, P<0.001). However, the use of inotropes, noninvasive ventilation, and endotracheal intubation were similar between groups. In-hospital mortality did not differ between patients managed by emergency physicians and those managed by cardiologists (4.1% vs. 3.8%, odds ratio 1.12; 95% confidence interval 0.58–2.14).

    Conclusions: Despite differences in initial management, no prognostic difference was observed between emergency physicians and cardiologists who performed the initial management of patients with AHF.

  • Yoshinori Kobayashi, Kaoru Tanno, Akira Ueno, Seiji Fukamizu, Hiroshig ...
    Type: ORIGINAL ARTICLE
    Subject Area: Arrhythmia/Electrophysiology
    Article ID: CJ-18-0785
    Published: 2018
    [Advance publication] Released: November 15, 2018
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    Background: Recurrent ventricular tachycardia (VT) and fibrillation (VF), the so-called “electrical storm” (ES) occurs at various stages of acute myocardial infarction (AMI), but its incidence, background, and short-term prognosis remain unclear.

    Methods and Results: A retrospective observational study was performed using the registry database of the Tokyo CCU Network. The individual data of 6,003 patients with AMI during 2011–2012 was corrected. ES was defined as more than 3 episodes of sustained VT/VF during a 24-h period as first documented after hospitalization. ES occurred in 55 patients after admission (0.9%). The ES(+) group had more severe heart failure (Killip class >III), more extensive MI (peak-CK), greater inflammatory reaction (CRP), history of diabetes, and more frequent application of hemodialysis as compared with the ES(−) group (n=5,865). When the ES patients were divided into Early-ES (n=37: ES occurred ≤48 h after the onset of MI) and Late-ES (n=15 >48 h after onset of MI) groups, logistic regression analysis revealed that Early-ES was associated with severity of MI, whereas Late-ES was related to systemic disorders, including inflammation, renal dysfunction, or diabetes. Late-ES was an independent predictor of in-hospital death.

    Conclusions: In-hospital ES was a rare clinical manifestation of AMI. The features and background of the ES varied as time elapsed after admission for MI.

  • Manuel Monti, Giuseppe Murdolo, Paolo Diego L’Angiocola, Giovanni Mari ...
    Type: LETTER TO THE EDITOR
    Article ID: CJ-18-1151
    Published: 2018
    [Advance publication] Released: November 15, 2018
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  • Ken Takarada, Erwin Ströker, Carlo de Asmundis, Juan Sieira, Juan-Pabl ...
    Type: ORIGINAL ARTICLE
    Subject Area: Arrhythmia/Electrophysiology
    Article ID: CJ-18-0650
    Published: 2018
    [Advance publication] Released: November 14, 2018
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    Background: Pulmonary vein isolation (PVI) by means of cryoballoon is increasingly being used for the treatment of atrial fibrillation (AF). This study assessed whether the left atrial volume index (LAVI) predicts AF recurrence following PVI by means of 2nd-generation cryoballoon (Cryoballoon Advance; CB-A) when comparing persistent AF (PeAF) and paroxysmal AF (PAF).

    Methods and Results: Patients with drug-resistant AF and undergoing preprocedural computed tomography (CT) and PVI with CB-A were included. LAV was estimated from 3D CT images. A total of 417 patients with AF were included (95 PeAF, 322 PAF patients). After a mean of 22.1±9.4 months follow-up, 45/95 (47%) PeAF patients and 254/322 (79%) PAF patients had no recurrence. LAVI was an independent predictor for AF recurrence in PeAF patients (hazard ratio 1.042 per 1 mL/m2; 95% confidence interval 1.006–1.080, P=0.02), but not in PAF patients. In PeAF patients with LAVI ≤61 mL/m2, the freedom from recurrence was 78.5% vs. 22.2% in those with LAVI >61 mL/m2 (hazard ratio 5.771, 95% confidence interval 2.434–13.682, P<0.001), and the mid-term success rate was comparable with PAF patients.

    Conclusions: LAVI predicted AF recurrence after PVI using CB-A in PeAF patients but not in PAF patients. If LAVI was ≤61 mL/m2, the mid-term efficacy among PeAF patients was equivalent to that for PAF patients.

  • Junya Takagawa, Hidetsugu Asanoi, Tomoyuki Tobushi, Naoto Kumagai, Tos ...
    Type: ORIGINAL ARTICLE
    Subject Area: Heart Failure
    Article ID: CJ-18-0519
    Published: 2018
    [Advance publication] Released: November 13, 2018
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    Background: The respiratory instability frequently observed in advanced heart failure (HF) is likely to mirror the clinical status of worsening HF. The present multicenter study was conducted to examine whether the noble respiratory stability index (RSI), a quantitative measure of respiratory instability, reflects the recovery process from HF decompensation.

    Methods and Results: Thirty-six of 44 patients hospitalized for worsening HF completed all-night measurements of RSI both at deterioration and recovery phases. Based on the signs, symptoms, and laboratory data during hospitalization, the Central Adjudication Committee identified 22 convalescent patients and 14 patients with less extent of recovery in a blinded manner without any information on RSI or other respiratory variables. The all-night RSI in the convalescent patients was increased from 27.8±18.4 to 34.6±15.8 (P<0.05). There was no significant improvement of RSI, however, in the remaining patients with little clinical improvement. Of the clinical and laboratory variables, on stepwise linear regression modeling, body weight, peripheral edema, and lung congestion were closely related to the RSI of recovered patients and accounted for 56% of the changes in RSI (coefficient of determination, R2=0.56).

    Conclusions: All-night RSI, a quantitative measure of respiratory instability, could faithfully reflect congestive signs and clinical status of HF during the recovery process from acute decompensation.

  • Jun-Seop Song, Jaehyeok Kim, Byounghyun Lim, Young-Seon Lee, Minki Hwa ...
    Type: ORIGINAL ARTICLE
    Subject Area: Arrhythmia/Electrophysiology
    Article ID: CJ-18-0615
    Published: 2018
    [Advance publication] Released: November 13, 2018
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    Background: The arrhythmogenic role of complex atrial morphology has not yet been clearly elucidated. We hypothesized that bumpy tissue geometry can induce action potential duration (APD) dispersion and wavebreak in atrial fibrillation (AF).

    Methods and Results: We simulated a 2D-bumpy atrial model by varying the degree of bumpiness, and 3D-left atrial (LA) models integrated by LA computed tomographic (CT) images taken from 14 patients with persistent AF. We also analyzed wave-dynamic parameters with bipolar electrograms during AF and compared them with LA-CT geometry in 30 patients with persistent AF. In the 2D-bumpy model, APD dispersion increased (P<0.001) and wavebreak occurred spontaneously when the surface bumpiness was greater, showing phase transition-like behavior (P<0.001). The bumpiness gradient 2D-model showed that spiral wave drifted in the direction of higher bumpiness, and phase singularity (PS) points were mostly located in areas with higher bumpiness. In the 3D-LA model, PS density was higher in the LA appendage (LAA) compared with other parts of the LA (P<0.05). In 30 persistent-AF patients, the surface bumpiness of LAA was 5.8-fold that of other LA parts (P<0.001), and exceeded critical bumpiness to induce wavebreak. Wave dynamics complexity parameters were consistently dominant in the LAA (P<0.001).

    Conclusions: Bumpy tissue geometry promoted APD dispersion, wavebreak, and spiral wave drift in in-silico human atrial tissue, and corresponded to clinical electroanatomical maps.

  • Toshiki Sakuma, Toru Akaike, Susumu Minamisawa
    Type: ORIGINAL ARTICLE
    Subject Area: Pediatric Cardiology and Adult Congenital Heart Disease
    Article ID: CJ-18-0761
    Published: 2018
    [Advance publication] Released: November 10, 2018
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    Background:Patent ductus arteriosus (PDA) is common in premature infants. Cyclooxygenase inhibitors such as indomethacin, which inhibit prostaglandin E2(PGE2) synthesis, are currently the sole treatments for patients with PDA. Their efficacy are, however, frequently limited, and adverse effects are problematic. Because the PGE2-specific receptor EP4 selectively expresses in rat ductus arteriosus (DA), it is hypothesized that EP4 inhibition would promote DA closure with fewer side-effects.

    Methods and Results:A new chemical compound EP4 antagonist, RQ-15986 (renamed from CJ-042794), was used. Whether RQ-15986 selectively contracted the DA was examined by measuring the isometric tension of rat DA ex vivo at embryonic day 19 (e19) and e21. RQ-15986 at a dose of 10−6mol/L increased the isometric tension of the DA up to 44.8±6.2% and 69.1±12.9% to the maximal KCl-induced tension at e19 and e21 respectively. The effect of RQ-15986 on rat DA in vivo was also tested by using a rapid whole-body freezing method. RQ-15986 inhibited PGE1-induced DA dilatation in neonatal rats. Furthermore, RQ-15986 contracted the DA in a dose-dependent manner, and the constriction was greater at e21 than at e19. Moreover, RQ-15986 did not contract the aorta or the marginal artery of the colon.

    Conclusions:EP4 inhibition contracts rat DA with fewer side-effects. EP4 inhibition is a promising alternative strategy to treat patients with PDA.

  • Kyohei Marume, Seiji Takashio, Toshiyuki Nagai, Kenichi Tsujita, Yoshi ...
    Type: ORIGINAL ARTICLE
    Subject Area: Heart Failure
    Article ID: CJ-18-0639
    Published: 2018
    [Advance publication] Released: November 09, 2018
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    Background:Statins might be associated with improved survival in patients with heart failure with preserved ejection fraction (HFpEF). The effect of statins in HFpEF without coronary artery disease (CAD), however, remains unclear.

    Methods and Results:From the JASPER registry, a multicenter, observational, prospective cohort with Japanese patients aged ≥20 years requiring hospitalization with acute HF and LVEF ≥50%, 414 patients without CAD were selected for outcome analysis. Based on prescription of statins at admission, we divided patients into the statin group (n=81) or no statin group (n=333). We followed them for 25 months. The association between statin use and primary (all-cause mortality) and secondary (non-cardiac death, cardiac death, or rehospitalization for HF) endpoints was assessed in the entire cohort and in a propensity score-matched cohort. In the propensity score-matched cohort, 3-year mortality was lower in the statin group (HR, 0.21; 95% CI: 0.06–0.72; P=0.014). The statin group had a significantly lower incidence of non-cardiac death (P=0.028) and rehospitalization for HF (P<0.001), but not cardiac death (P=0.593). The beneficial effect of statins on mortality did not have any significant interaction with cholesterol level or HF severity.

    Conclusions:Statin use has a beneficial effect on mortality in HFpEF without CAD. The present findings should be tested in an adequately powered randomized clinical trial.

  • Kazunori Ono, Kenji Yanishi, Makoto Ariyoshi, Satoshi Kaimoto, Motoki ...
    Type: ORIGINAL ARTICLE
    Subject Area: Peripheral Vascular Disease
    Article ID: CJ-18-0815
    Published: 2018
    [Advance publication] Released: November 09, 2018
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    Background: Therapeutic angiogenesis with basic fibroblast growth factor (bFGF) with atelocollagen was confirmed in a study using a limb ischemia mouse model. Because the number of elderly patients with critical limb ischemia (CLI) is increasing, particularly that caused by arteriosclerosis obliterans (ASO), the development of less invasive angiogenesis therapies desired.

    Methods and Results: This first-in-man clinical study was designed to assess the safety and efficacy of i.m. injection of bFGF with atelocollagen. Human recombinant bFGF (200 μg), combined with 4.8 mL 3% atelocollagen solution, was prepared and injected into the gastrocnemius muscle of the ischemic leg. The primary endpoint was safety, evaluated on all adverse events over 48 weeks after this treatment. The secondary endpoint was efficacy, evaluated by improvement of ischemic symptoms. No serious procedure-related adverse events were observed during the follow-up period. Visual analogue scale (VAS) score was significantly improved at 4, 24 and 48 weeks compared with baseline (P<0.05), and 7 patients became pain free during the follow-up period. Fontaine classification was improved in 4 of 10 patients at 48 weeks. Cyanotic lesions disappeared in 2 patients at 4 weeks.

    Conclusions: I.m. injection of bFGF with atelocollagen is safe and feasible in patients with CLI. Randomized controlled trials are therefore needed to confirm these results.

  • Hirooki Higami, Mamoru Toyofuku, Takeshi Morimoto, Masanobu Ohya, Yasu ...
    Type: ORIGINAL ARTICLE
    Subject Area: Ischemic Heart Disease
    Article ID: CJ-18-0896
    Published: 2018
    [Advance publication] Released: November 09, 2018
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    Background:Data on the clinical outcomes of percutaneous coronary intervention (PCI) for unprotected left main coronary artery (LMCA) in patients with acute coronary syndrome (ACS) are limited. Therefore, this study aimed to assess the clinical outcome of patients with ACS who underwent PCI for LMCA culprit lesion.

    Methods and Results:Of 1,809 patients enrolled in the Assessing Optimal Percutaneous Coronary Intervention for the LMCA (AOI-LMCA) registry (a retrospective 6-center registry of consecutive patients undergoing LMCA stenting in Japan), the current study population consisited of 1,500 patients with unprotected LMCA stenting for LMCA ACS (ACS with shock: 115 patients, ACS without shock: 281 patients) and stable CAD (1,104 patients). The cumulative 180-day incidence of death was markedly higher in the ACS with shock group than in the other groups (49.5%, 8.6%, and 3.3%, respectively; P<0.0001), but mortality beyond 180-day was not significantly different among the 3 groups (30.2%, 20.4%, and 19.5%, respectively; P=0.65). In the ACS with shock group, the initial TIMI flow grade did not affect 5-year mortality (57.1% and 62.2%, P=0.99), but in the ACS without shock group, 5-year mortality was significantly higher in patients with initial TIMI flow grade ≤1 than in patients with TIMI flow grade ≥2 (44.4% and 23.7%, respectively; P=0.008).

    Conclusions:In patients with LMCA ACS, survival correlates with baseline hemodynamic and coronary flow status.

  • Miho Nishitani-Yokoyama, Katsumi Miyauchi, Kazunori Shimada, Takayuki ...
    Type: ORIGINAL ARTICLE
    Subject Area: Cardiac Rehabilitation
    Article ID: CJ-18-0738
    Published: 2018
    [Advance publication] Released: November 08, 2018
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    Background:Cardiac rehabilitation (CR) is an established multidisciplinary secondary preventive program. We investigated the effects of CR involving intensive physical activity (PA) on coronary plaque volume and components in patients with acute coronary syndrome (ACS).

    Methods and Results:We enrolled 32 consecutive patients with ACS in early phase II CR and randomly assigned them to an intensive CR group (n=18; CR participation ≥twice/week, daily PA ≥9,000 steps) or a standard CR group (n=14; CR participation ≥once/2weeks, daily PA ≥6,000 steps). Serial integrated backscatter intravascular ultrasound was performed for non-culprit lesions at baseline and after 8 months. Baseline clinical data were identical between the 2 groups. Unexpectedly, CR participation and PA did not differ significantly between the 2 groups, and there was no significant difference in plaque volume (PV) or components between the 2 groups. Subsequently, we classified the patients into 2 groups according to median PA (7,000 steps). There were significant differences in percent change of PV and of lipid volume between these 2 groups. In addition, these changes were negatively and independently correlated with PA.

    Conclusions:No significant difference was observed in PV or components between the intensive CR and the standard CR groups. Intensive PA, however, may retard coronary PV and ameliorate lipid component in patients with ACS participating in late phase II CR.

  • Jun Hwan Cho, Won-Seok Choe, Hyun-Jai Cho, Hae-Young Lee, Jieun Jang, ...
    Type: ORIGINAL ARTICLE
    Subject Area: Heart Failure
    Article ID: CJ-18-0543
    Published: 2018
    [Advance publication] Released: November 06, 2018
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    Background:The clinical characteristics and outcomes of acute heart failure (AHF) according to left ventricular ejection fraction (LVEF) have not been fully elucidated, especially for patients with mid-range LVEF. We performed a comprehensive comparison of the epidemiology, patterns of in-hospital management, and clinical outcomes in AHF patients with different LVEF categories.

    Methods and Results:The Korean Acute Heart Failure (KorAHF) registry is a prospective multicenter cohort of hospitalized AHF patients in Korea. A total of 5,374 patients enrolled in the KorAHF registry were classified according to LVEF based on the 2016 ESC guidelines. More than half of the HF patients (58%) had reduced EF (HFrEF), 16% had mid-range EF (HFmrEF), and 25% had preserved EF (HFpEF). The HFmrEF patients showed intermediate epidemiological profiles between HFrEF and HFpEF and had a propensity to present as de-novo HF with ischemic etiology. Patients with lower LVEF had worse short-term outcomes, and the all-cause in-hospital mortality, including urgent heart transplantation, of HFrEF, HFmrEF, and HFpEF was 7.1%, 3.6%, and 3.0%, respectively. Overall, discharged AHF patients showed poor 3-year all-cause death up to 38%, which was comparable between LVEF subgroups (P=0.623).

    Conclusions:Each LVEF subgroup of AHF patients was a heterogeneous population with diverse characteristics, which have a significant effect on the clinical outcomes. This finding suggested that focused phenotyping of AHF patients could help identify the optimal management strategy and develop novel effective therapies.

  • Takumi Yamada
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-18-0968
    Published: 2018
    [Advance publication] Released: November 06, 2018
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  • Toshiyuki Yamada, Takeshi Adachi, Yasuo Ido, Nobuyuki Masaki, Takumi T ...
    Type: ORIGINAL ARTICLE
    Subject Area: Vascular Biology and Vascular Medicine
    Article ID: CJ-18-0714
    Published: 2018
    [Advance publication] Released: November 03, 2018
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    Background: To obtain a saphenous vein graft (SVG) for coronary artery bypass grafting (CABG), the benefit of using a no-touch (NT) technique in vascular function has not been fully investigated.

    Methods and Results: The pathological and physiological functions of human SVGs with a NT technique to preserve the perivascular adipose tissue (PVAT) and ones obtained by using a conventional (CON) technique removing PVAT, were examined. Immunohistochemistry of the section of SVGs showed that the phosphorylation of endothelial nitric oxide synthase in the endothelium of the NT group was more responsive to vascular endothelial growth factor. A myograph of SVGs showed greater contraction with phenylephrine in the NT group. However, the strong contraction was eliminated in SVGs taken by electrocautery. In the 10 patients whose SVGs were taken without electrocautery, endothelial-dependent relaxation with bradykinin was apparently increased in the CON group more than in the NT group. Smooth muscle relaxation with nitroprusside was higher in the CON group at the lower concentrations; however, the relaxation became greater in the NT group at the high concentrations. Therefore, the effect of neutralizing PVAT-released factors in the both groups was further examined. After medium of NT and CON were exchanged in half, relaxation of SVGs was immediately restored in the NT group.

    Conclusions: The results suggest that the NT technique preserves the functions of vasoconstriction and relaxation. Also, the presence of PVAT-released vasoconstrictive factors was suspected.

  • Shusuke Yagi, Hiromu Yamazaki, Susumu Nishio, Kenya Kusunose, Hirotsug ...
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-18-0898
    Published: 2018
    [Advance publication] Released: November 03, 2018
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  • Shin Kawasoe, Takuro Kubozono, Shiro Yoshifuku, Satoko Ojima, Masaaki ...
    Type: ORIGINAL ARTICLE
    Subject Area: Epidemiology
    Article ID: CJ-18-0508
    Published: 2018
    [Advance publication] Released: November 02, 2018
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    Background: The independent role of uric acid (UA) as a risk factor for atrial fibrillation (AF) has not been fully elucidated.

    Methods and Results: We studied 111,566 subjects (53,416 men; 58,150 women) who underwent annual health check-ups. We divided them by sex into tertile of baseline UA. To investigate the predictive power of UA for new-onset AF, we performed Cox proportional hazard analysis including UA tertiles, body mass index, creatinine, smoking and drinking status, and presence of hypertension, diabetes, and dyslipidemia. During 4.1 years, 467 men (0.87%) and 180 women (0.31%) had AF (P<0.001). Cut-off points for tertiles of UA were as follows: women, ≤3.9, 4.0–4.8, and ≥4.9 mg/dL; men, ≤5.4, 5.5–6.4, and ≥6.5 mg/dL. Hazard ratio (HR) for third to first tertile was 1.74 (95% CI: 1.15–2.70; P=0.008), whereas there were no differences between tertiles in men. Rate of new-onset AF was significantly higher in the group with initially increased UA (ΔUA ≥0.3 mg/dL) than that with unchanged UA (ΔUA, −0.2 or +0.2 mg/dL) in the third tertile of baseline UA in both sexes.

    Conclusions: Higher baseline UA was significantly associated with higher AF incidence in women. Initial increase in UA was significantly associated with AF incidence when baseline UA was ≥6.5 mg/dL in men, and ≥4.9 mg/dL in women.

  • Masahiko Shibuya, Kenichi Fujii, Hiroyuki Hao, Takahiro Imanaka, Ten S ...
    Type: ORIGINAL ARTICLE
    Subject Area: Imaging
    Article ID: CJ-18-0671
    Published: 2018
    [Advance publication] Released: November 02, 2018
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    Background: Coronary angioscopy (CAS) is used to comprehensively evaluate vascular responses after drug-eluting stent (DES) implantation. This study sought to evaluate the capability of CAS for evaluating DES strut coverage grade and color grade of the intima compared with histological images in coronary autopsy specimens.

    Methods and Results: A total of 23 DES extracted from 11 autopsy hearts were imaged by CAS. All stent segments were graded as white or yellow according to the luminal surface color, and thrombus was evaluated according to a previous report. Neointimal coverage over the DES was graded as 0 (stent struts fully visible) to grade 3 (stent struts fully embedded and invisible). Of 76 segments, neointimal coverage was graded as 0 in 35 (46%), 1 in 22 (29%), 2 in 8 (11%), and 3 in 11 (14%). The neointimal thickness increased significantly with increasing neointimal coverage grade on angioscopy. Neointimal color was graded as white in 40 (53%) and yellow in 36 segments (47%). Histological analysis revealed that yellow neointima contained fibroatheroma, foam cells accumulation or superficial calcium deposition. A thrombus was identified in 13 segments. Thrombi adherent around the stent strut were partly intimal erythrocyte accumulation around the strut.

    Conclusions: In-stent yellow segment had atherosclerotic components. CAS could evaluate vascular status comprehensively after DES implantation.

  • Masato Okada, Kazunori Kashiwase, Akio Hirata, Mayu Nishio, Yasuharu T ...
    Type: ORIGINAL ARTICLE
    Subject Area: Arrhythmia/Electrophysiology
    Article ID: CJ-17-1436
    Published: 2018
    [Advance publication] Released: October 31, 2018
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    Background: Identifying who among current Japanese patients with prior myocardial infarction (MI) would benefit from an implantable cardioverter-defibrillator (ICD) is imperative. Accordingly, this study seeks to determine whether single-photon emission computed tomography (SPECT) can help identify such patients.

    Methods and Results: This retrospective study enrolled 60 consecutive patients with prior MI who underwent stress thallium-201 SPECT and ICD implantation from February 2000 to October 2014. Occurrence of arrhythmic death and/or or appropriate ICD therapy, defined as shock or antitachycardia pacing for ventricular fibrillation or tachycardia, was identified until November 2016. During the median follow-up interval of 6.6 years, 18 (30%) patients experienced arrhythmic death and/or appropriate ICD therapy. Multivariate Cox proportional hazard regression analysis revealed that the summed stress score (SSS) [hazard ratio (HR)=1.14; P=0.005] and left ventricular ejection fraction (LVEF) at rest (HR=0.92; P=0.038) were significantly associated with the occurrence of arrhythmic events. Patients with SSS ≥21 and LVEF ≤30%, which were determined to be the best cutoff points, had significantly higher incidence of the arrhythmic events than the other patients (64% vs. 11%; HR=7.18; log-rank P=0.001).

    Conclusions: SSS using stress thallium-201 SPECT in combination with LVEF can help determine the need for ICD therapy among current Japanese patients with prior MI.

  • Yosuke Nakatani, Tamotsu Sakamoto, Yoshiaki Yamaguchi, Yasushi Tsujino ...
    Type: ORIGINAL ARTICLE
    Subject Area: Arrhythmia/Electrophysiology
    Article ID: CJ-18-0911
    Published: 2018
    [Advance publication] Released: October 30, 2018
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    Background: The effects of catheter ablation for atrial fibrillation (AF) on hemodynamic parameters in patients with preserved left ventricular (LV) systolic function are unclear.

    Methods and Results: We enrolled 178 patients with AF (paroxysmal, 108; persistent, 70) with preserved LV systolic function who underwent AF ablation. The stroke volume index (SVI) was repeatedly measured using impedance cardiography. Reduced SVI (SVI, <33 mL/m2) was observed in 55% of patients before ablation. In patients with paroxysmal AF, the SVI did not change immediately after ablation (from 35±6 mL/m2to 35±5 mL/m2; P=0.652); however, it increased 1 month after ablation and further increased 6 months after ablation (1 month, 37±6 mL/m2, P<0.001; 6 months, 38±6 mL/m2, P<0.001). In patients with persistent AF, the SVI increased immediately after ablation (from 30±5 mL/m2to 36±6 mL/m2; P<0.001) and further increased until 6 months after ablation (1 month, 37±6 mL, P<0.001; 6 months, 38±5 mL/m2, P<0.001). The baseline SVI was the strongest predictor of the cardiac function improvement with an area under the curve of 0.828.

    Conclusions: The restoration and maintenance of sinus rhythm using catheter ablation increased the SVI in patients with preserved LV systolic function.

  • Hong Rae Kim, Sung-Ho Jung, Jae-Joong Kim, Dong Hyun Yang, Tae-Jin Yun ...
    Type: ORIGINAL ARTICLE
    Subject Area: Cardiovascular Surgery
    Article ID: CJ-18-0567
    Published: 2018
    [Advance publication] Released: October 27, 2018
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    Background: Orthotopic heart transplantation (HT) is the treatment of choice for patients with end-stage heart failure (HF). The bicaval technique was introduced as a safe alternative minimizing modification of atrial geometry. The modification of bicaval anastomosis is suggested to compensate for caliber mismatch and small donor. The present study was performed to compare these 2 techniques in terms of postoperative CT scan and clinical outcomes.

    Methods and Results: Retrospectively, 158 consecutive patients with end-stage HF underwent orthotopic HT between January 2009 and June 2013 were analyzed. Of these, we excluded 3 patients with total HT. The study group was divided into modified technique (n=37) or conventional technique (n=118). A total of 113 patients (modified: n=29, conventional: n=84) were examined with cardiac CT. Discrepancy in the size of the vena cava compared with that of the anastomosis site was assessed. There was no significant difference in the complication and survival rates. There was 1 incident of moderate-to-severe tricuspid valve regurgitation in the modified group (n=1, 2.7%). Both the SVC ratio (1.07±0.13 vs. 1.28±0.32, P=0.001) and IVC ratio (1.06±0.07 vs. 1.13±0.19, P=0.009) were higher in the conventional group, which meant more stenotic imaging findings were observed in the conventional group.

    Conclusions: Orthotopic HT with modified bicaval anastomosis is an attractive alternative with easy orientation and equivocal outcomes.

  • Yangsin Lee, Takayuki Ohno, Yukari Uemura, Akira Osanai, Sumio Miura, ...
    Type: ORIGINAL ARTICLE
    Subject Area: Cardiovascular Surgery
    Article ID: CJ-18-0653
    Published: 2018
    [Advance publication] Released: October 27, 2018
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    Background: The long-term outcomes of complete revascularization (CR) in patients with left ventricular (LV) dysfunction undergoing coronary artery bypass grafting (CABG) remain unclear.

    Methods and Results: We evaluated a consecutive series of 111 patients with LV ejection fraction ≤35% who underwent isolated first-time CABG: 63 underwent CR and 48 underwent incomplete revascularization (IR). At a median follow-up of 10.1 years, the rates of death from any cause, cardiac death, and major adverse cardiac and cerebrovascular events (MACCE) were significantly greater in the IR group. After adjusting for propensity score, no significant difference was found between the CR and IR groups regarding death from any cause (hazard ratio [HR], 1.45; 95% CI: 0.75–2.81; P=0.271) and cardiac death (HR, 1.45; 95% CI: 0.68–3.10; P=0.337). In contrast, IR increased the risk of MACCE (HR, 1.92; 95% CI: 1.08–3.41; P=0.027), which was principally attributed to an increased risk of repeat revascularization (HR, 3.92; 95% CI: 1.34–11.44; P=0.013).

    Conclusions: Although IR was not significantly associated with an increased risk of long-term mortality in patients with LV dysfunction who underwent CABG, CR might reduce the risks of repeat revascularization and subsequent MACCE.

  • Taro Nakazato, Hiroki Hata, Koichi Toda, Shigeru Miyagawa, Yasushi Yos ...
    Type: ORIGINAL ARTICLE
    Subject Area: Cardiovascular Surgery
    Article ID: CJ-18-0483
    Published: 2018
    [Advance publication] Released: October 25, 2018
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    Background: The aim of this single-center study was to report the midterm clinical outcomes and hemodynamic performance of the St Jude Medical Epic porcine bioprosthesis, a tricomposite glutaraldehyde-preserved porcine bioprosthesis, in mitral position.

    Methods and Results: Between January 2011 and March 2017, 117 patients (62 men, 55 women; mean age, 66.7±12.8 years) who underwent mitral valve replacement (MVR) with the Epic valve were retrospectively analyzed for early and mid-term morbidity and mortality. The mean follow-up period was 2.6±1.7 years. Three operative deaths occurred, and the operative mortality rate was 2.6%. Sixteen patients died during the follow-up period. On Kaplan-Meier analysis, freedom from all-cause death and major adverse cardiovascular and cerebrovascular events at 5-year follow-up were 80.9% and 54.8%, respectively. There were 6 reoperations: 2 for structural valve deterioration (SVD), 2 for prosthetic valve endocarditis, and 2 for thrombosis. Freedom from valve-related reoperation and SVD at 5 years were 89.0% and 93.1%, respectively. On multivariate analysis, age ≥71 years (HR, 6.78; 95% CI: 2.12–25.2, P<0.01), and NYHA functional class ≥III (HR, 3.20; 95% CI: 1.03–10.4, P=0.04) were independent predictors for all-cause death. Mean mitral pressure gradient at 1 year and 2 years were 5.1±1.9 mmHg and 4.5±1.4 mmHg, respectively.

    Conclusions: Mid-term clinical results and durability of the Epic valve in the mitral position are satisfactory.

  • Naonori Kawamoto, Satsuki Fukushima, Yusuke Shimahara, Takuma Yamasaki ...
    Type: ORIGINAL ARTICLE
    Subject Area: Valvular Heart Disease
    Article ID: CJ-18-0751
    Published: 2018
    [Advance publication] Released: October 24, 2018
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    Background: Despite the cosmetic benefits of the minimally invasive approach for mitral disease, the clinical benefit and risk are not fully known. We investigated the benefit and risk of minimally invasive mitral valve (MV) repair for type II dysfunction using propensity score-matched analysis.

    Methods and Results: Since 2001, 602 patients have undergone MV repair for type II dysfunction (464 with conventional median sternotomy and 138 with the minimally invasive approach). One-to-one matched analysis using the estimated propensity score based on 23 factors resulted in 93 well-matched patient pairs. There was no in-hospital death in both groups. The operation time was significantly shorter (P=0.002), blood transfusion was less frequent (P=0.04), extubation at the day of surgery was more frequently performed (P=0.017), and the length of hospital stay was significantly shorter in the minimally invasive group than in the sternotomy group (P<0.0001). On postoperative (P=0.02) and 1-year echocardiography (P=0.04), ejection fraction was lower in the minimally invasive group than in the sternotomy group. There were no significant differences in postoperative cerebral infarction, aortic dissection, deep sternal infection, or mid-term outcome between the groups.

    Conclusions: Standard sternotomy and the minimally invasive approach provide similar good quality of MV repair for type II dysfunction. The minimally invasive approach is more likely to contribute to fast-track perioperative treatment than the standard sternotomy approach.

  • Luis A. Gonano, Marisa Sepúlveda, Malena Morell, Tamara Toteff, María ...
    Type: ORIGINAL ARTICLE
    Subject Area: Arrhythmia/Electrophysiology
    Article ID: CJ-18-0247
    Published: 2018
    [Advance publication] Released: October 23, 2018
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    Background: It has been shown that carvedilol and its non β-blocking analog, VK-II-86, inhibit spontaneous Ca2+ release from the sarcoplasmic reticulum (SR). The aim of this study is to determine whether carvedilol and VK-II-86 suppress ouabain-induced arrhythmogenic Ca2+ waves and apoptosis in cardiac myocytes.

    Methods and Results: Rat cardiac myocytes were exposed to toxic doses of ouabain (50 µmol/L). Cell length (contraction) was monitored in electrically stimulated and non-stimulated conditions. Ouabain treatment increased contractility, frequency of spontaneous contractions and apoptosis compared to control cells. Carvedilol (1 µmol/L) or VK-II-86 (1 µmol/L) did not affect ouabain-induced inotropy, but significantly reduced the frequency of Ca2+ waves, spontaneous contractions and cell death evoked by ouabain treatment. This antiarrhythmic effect was not associated with a reduction in Ca2+ calmodulin-dependent protein kinase II (CaMKII) activity, phospholamban and ryanodine receptor phosphorylation or SR Ca2+ load. Similar results could be replicated in human cardiomyocytes derived from stem cells and in a mathematical model of human myocytes.

    Conclusions: Carvedilol and VK-II-86 are effective to prevent ouabain-induced apoptosis and spontaneous contractions indicative of arrhythmogenic activity without affecting inotropy and demonstrated to be effective in human models, thus emerging as a therapeutic tool for the prevention of digitalis-induced arrhythmias and cardiac toxicity.

  • Takaya Ozawa, Shoji Kawakami, Manabu Matsumoto, Hatsue Ishibashi-Ueda, ...
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-18-0632
    Published: 2018
    [Advance publication] Released: October 23, 2018
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