Circulation Journal
Advance online publication
Advance online publication

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Showing 1-50 articles out of 135 articles from Advance online publication
  • Ran Liu, Wen Zheng, Guanqi Zhao, Xiao Wang, Xuedong Zhao, Shenghui Zho ...
    Type: ORIGINAL ARTICLE
    Subject Area: Ischemic Heart Disease
    Article ID: CJ-17-0760
    [Advance publication] Released: December 12, 2017
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    Background:The CRUSADE, ACTION and ACUITY-HORIZONS bleeding scores have been derived using Caucasian patients, and little is known about which has the better predictive ability in Chinese patients, especially for patients with STEMI.

    Methods and Results:We retrospectively analyzed 2,208 consecutive STEMI patients undergoing primary PCI (PPCI). Major bleeding events were defined according to Bleeding Academic Research Consortium criteria (type 3 or 5). Predictive ability of the 3 scores was assessed using logistic regression and AUC. Unadjusted HR for 1-year death were determined on Cox proportional hazard modeling. The major bleeding rate was 2.4%. The AUC of the CRUSADE, ACTION and ACUTIY-HORIZONS models was 0.88 (95% CI: 0.84–0.92), 0.90 (95% CI: 0.87–0.94), and 0.78 (95% CI: 0.87–0.94). The calibration of the ACUTIY-HORIZONS model was not acceptable overall, or in the subgroup of access site (P<0.05). In the high-risk category, 1-year mortality was approximately 4–7-fold greater than in the low-risk category (CRUSADE: HR, 7.27; 95% CI: 3.30–16.02, P<0.001; ACTION: HR, 7.13; 95% CI: 2.19–15.41, P<0.001; ACUITY-HORIZONS: HR, 4.06; 95% CI: 1.62–10.16; P=0.003).

    Conclusions:The CRUSADE and ACTION scores have greater predictive ability for in-hospital major bleeding than the ACUITY-HORIZONS risk score in Chinese STEMI patients undergoing PPCI. Mortality would increase with the transition from low- to high-risk category in 1 year.

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  • Rashad Zayat, Mohammad Amen Khattab, Oliver Grottke, Markus Honickel, ...
    Type: ORIGINAL ARTICLE
    Subject Area: Heart Failure
    Article ID: CJ-17-0897
    [Advance publication] Released: December 12, 2017
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    Background:In long-term left ventricular assist device (LVAD) therapy, recurrent bleeding events may justify cessation of anticoagulation therapy (AT). However, data about THE safety and risks of AT cessation in LVAD patients are scarce.

    Methods and Results:Between 2010 and 2015, 128 patients received a HeartMate II (HMII). Following recurrent bleeding events, we ceased vitamin K antagonist (VKA) therapy in 13 patients (10%) (no-VKA group). To characterize the hemostatic profile, we performed von Willebrand factor (vWF), platelet function (PF), and other hemostatic tests in all HMII patients. The incidence of pump thrombosis (PT), ischemic stroke (IS) and bleeding events in this HMII population was 4.7 %, 6.2% and 36.7%, respectively. Median survival without VKA was 435 days. No cases of PT and only 1 of IS occurred after AT discontinuation. All patients had impaired PF and acquired von Willebrand syndrome (AvWS). However, the vWF collagen-binding activity to antigen ratio before and after VKA cessation was significantly lower in the no-VKA group compared with the HMII population (0.60±0.12 vs. 0.73±0.14, P=0.006). The thrombin-antithrombin III complex (TAT) value was significantly higher in the no-VKA group (P=0.0005).

    Conclusions:We experienced good results with AT cessation in specific HMII patients. The simultaneous onset of AvWS and high TAT values could explain at least in part the low thromboembolic rate in HMII patients without VKA.

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  • Toyoaki Murohara
    Type: MESSAGE FROM THE EDITOR-IN-CHIEF
    Article ID: CJ-66-0147
    [Advance publication] Released: December 12, 2017
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  • Keiichi Kohashi, Akihiro Nakagomi, Taichirou Morisawa, Ikuko Endoh, Na ...
    Type: ORIGINAL ARTICLE
    Subject Area: Preventive Medicine
    Article ID: CJ-17-0644
    [Advance publication] Released: December 09, 2017
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    Background:Smoking increases the risk of atherothrombotic events. Tissue factor (TF) mainly expressed on monocytes plays an important role in thrombosis and atherosclerosis. Metabolic syndrome (MetS) is being increasingly recognized as a major atherothrombotic risk factor, but the effects of smoking on monocyte TF activity (MTFA), carotid atherosclerosis estimated on carotid intima-media thickness (CIMT), and long-term prognosis in MetS remain unclear.

    Methods and Results:A total of 301 MetS patients lacking any known cardiovascular disease were prospectively investigated and classified into 4 groups according to smoking status at entry and at 12 months as follows: never smokers, past smokers, quitters, and persistent smokers. Peripheral blood mononuclear cells (PBMC) were isolated, and MTFA was measured using a coagulation assay. Linear trends for higher baseline MTFA and CIMT were observed among persistent smokers, quitters, and past smokers compared with never smokers. At 12 months, MTFA and CIMT decreased in never and past smokers and quitters but increased in persistent smokers. Six acute myocardial infarctions and 8 strokes occurred during a median follow-up of 66.0 months. Persistent smoking was associated with an increased risk of events (P<0.001).

    Conclusions:Smoking is associated with upregulated MTFA and progression of CIMT, which may be related to the risk of atherothrombotic events in MetS patients.

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  • Yoshimori An, Masaharu Akao
    Type: EDITORIAL
    Article ID: CJ-17-1257
    [Advance publication] Released: December 09, 2017
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  • Naohiko Kawaguchi, Kaoru Okishige, Yasuteru Yamauchi, Manabu Kurabayas ...
    Type: ORIGINAL ARTICLE
    Subject Area: Arrhythmia/Electrophysiology
    Article ID: CJ-17-0734
    [Advance publication] Released: December 08, 2017
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    Background:Pulmonary vein isolation (PVI) using a cryoballoon (CB) is utilized for treating atrial fibrillation. This study aimed to assess the effect of the procedural characteristics of CB-based PVI (CB-PVI) on late PV reconnections.

    Methods and Results:A total of 389 consecutive patients underwent the CB-PVI as their index procedure; 45 consecutive patients underwent re-do procedures (184±87 days after the index CB-PVI). A total of 146 of 178 PVs (82%) remained isolated. The occlusion grade was evaluated in 171 PVs. Complete PV occlusion by the CB (grade 4) was obtained in 122 of 171 PVs (71%) during the index CB-PVI and the PVI status was maintained in 111 PVs (91%). Among the remaining 49 CB-PVIs without complete PV occlusion (grades 1–3), 20 PVs (41%) had late PV reconnections despite successful PVI during the index CB-PVI. A “pull-down maneuver” was performed in 20 PVs because of leakage of blood at the inferior aspect of the PVs, and all those PVs with a successful pull-down maneuver maintained their PVI status. A multivariate analysis demonstrated that the presence of complete PV occlusion was the only independent predictor for persistence of PVI.

    Conclusions:The occlusion grade was a reliable predictor of the long-term durability of PVI.

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  • Ryutaro Ikegami, Ippei Shimizu, Yohko Yoshida, Tohru Minamino
    Type: REVIEW
    Article ID: CJ-17-1184
    [Advance publication] Released: December 08, 2017
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    It is thought that at least 6,500 low-molecular-weight metabolites exist in humans, and these metabolites have various important roles in biological systems in addition to proteins and genes. Comprehensive assessment of endogenous metabolites is called metabolomics, and recent advances in this field have enabled us to understand the critical role of previously unknown metabolites or metabolic pathways in the cardiovascular system. In this review, we will focus on heart failure and how metabolomic analysis has contributed to improving our understanding of the pathogenesis of this critical condition.

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  • Kiyoshi Hibi, Shinjo Sonoda, Masanori Kawasaki, Yutaka Otsuji, Toyoaki ...
    Type: ORIGINAL ARTICLE
    Subject Area: Ischemic Heart Disease
    Article ID: CJ-17-0598
    [Advance publication] Released: December 07, 2017
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    Background:The results of previous clinical trials on the effects of ezetimibe-statin combination therapy on atherosclerosis are inconsistent, and the anti-atherosclerotic effect of ezetimibe remains controversial.

    Methods and Results:We conducted a prospective, randomized open-label study at 10 centers. One hundred and twenty-eight statin-naïve patients with acute coronary syndrome (ACS) undergoing intravascular ultrasound (IVUS)-guided percutaneous coronary intervention were randomized to receive either 2 mg/day pitavastatin plus 10 mg/day ezetimibe, or 2 mg/day pitavastatin. One hundred and 3 patients had evaluable IVUS of non-culprit coronary lesions at baseline and at follow-up. The primary endpoint was the percentage change in non-culprit coronary plaque volume (PV) and lipid PV on integrated backscatter IVUS. Mean low-density lipoprotein cholesterol was reduced from 123 mg/dL to 64 mg/dL in the combination therapy group (n=50) and 126 mg/dL to 87 mg/dL in the statin alone group (n=53; between-group difference, 16.9%, P<0.0001). The percent change in PV was −5.1% in the combination therapy group and −6.2% in the statin alone group (P=0.66), although both groups had reduction of PV compared with baseline (both P<0.01). The percent change in lipid PV did not differ between the groups (4.3 vs. −3.0%, P=0.37).

    Conclusions:In statin-naïve patients with ACS, combined therapy with ezetimibe and statin did not result in a significant change in coronary plaque regression or tissue component compared with statin alone. [Clinical Trial Registration: www.clinicaltrials.gov (NCT00549926)]

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  • Masatoshi Minamisawa, Takashi Miura, Hirohiko Motoki, Yasushi Ueki, Hi ...
    Type: ORIGINAL ARTICLE
    Subject Area: Heart Failure
    Article ID: CJ-17-0255
    [Advance publication] Released: December 06, 2017
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    Background:The geriatric nutritional risk index (GNRI) is a simple and objective nutritional assessment tool for elderly patients. Lower GNRI values are associated with a worse prognosis in patients with heart failure (HF). However, few data are available regarding the prognostic effect of the GNRI value for risk stratification in patients at risk for HF.

    Methods and Results:We retrospectively investigated 1,823 consecutive patients at risk for HF (Stage A/B) enrolled in the IMPACT-ABI Study. GNRI on admission was calculated as follows: 14.89×serum albumin (g/dL)+41.7×body mass index/22. Patients were divided into 2 groups according to the median GNRI value (107.1). The study endpoint was a composite of cardiovascular (CV) events, including CV death and hospitalization for worsening HF. Over a 4.7-year median follow-up, CV events occurred in 130 patients. In the Kaplan-Meier analysis, patients with low GNRI (<107.1, n=904) showed worse prognoses than those with high GNRI (≥107.1, n=919) (20.2% vs. 12.4%, P<0.001). In the multivariable Cox proportional hazards analysis, low GNRI was significantly associated with the incidence of CV events (hazard ratio: 1.48, 95% confidence interval: 1.02–2.14; P=0.040).

    Conclusions:The simple and practical assessment of GNRI may be useful for predicting CV events in patients with Stage A/B HF.

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  • Toru Adachi, Akira Sato, Akihiko Nogami, Kazutaka Aonuma
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-17-1043
    [Advance publication] Released: December 06, 2017
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  • Min Hur, Karam Nam, Woo Young Jo, Gahyun Kim, Won Ho Kim, Jae-Hyon Bah ...
    Type: ORIGINAL ARTICLE
    Subject Area: Renal Disease
    Article ID: CJ-17-0660
    [Advance publication] Released: December 05, 2017
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    Background:The ratio of the early transmitral flow velocity to early diastolic velocity of the mitral annulus (E/e′) is an echocardiographic index of mean left ventricular (LV) filling pressure. We investigated the association between the preoperative E/e′ ratio and postoperative acute kidney injury (AKI) during off-pump coronary artery bypass surgery (OPCAB).

    Methods and Results:We reviewed 585 patients who underwent OPCAB and with preserved LV ejection fraction determined by preoperative echocardiography. AKI was determined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Multivariable logistic regression analysis was performed. E/e′ was also analyzed as 3 categories (E/e′ <8, 8≤E/e′≤15, and E/e′ >15) and as a continuous variable. A propensity score analysis was used to match the patients with E/e′ >15 and E/e′ ≤15. A preoperative E/e′ >15 was an independent predictor for AKI (odds ratio 3.01, 95% confidence interval 1.40–6.17). E/e′ >15 was also an independent predictor for AKI when E/e′ was analyzed with 3 categories or as a continuous variable. In the matched sample, the incidence of AKI and 1-year mortality was significantly higher in patients with E/e′ >15.

    Conclusions:Among patients undergoing OPCAB with preserved LV systolic function, a preoperative E/e′ ratio >15 was an independent predictor of postoperative AKI. Measurement of the preoperative E/e′ ratio may help to assess the risk of postoperative AKI.

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  • Makoto Tanaka, Takashi Kohno, Hideaki Obara, Seishi Nakatsuka, Takahik ...
    Type: LETTER TO THE EDITOR
    Article ID: CJ-17-0937
    [Advance publication] Released: December 02, 2017
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  • Noriko Tsuda, Shinya Shiraishi, Seitaro Oda, Koji Ogasawara, Fumi Saka ...
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-17-1111
    [Advance publication] Released: December 02, 2017
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  • Masao Yoshinaga, Mari Iwamoto, Hitoshi Horigome, Naokata Sumitomo, Hir ...
    Type: ORIGINAL ARTICLE
    Subject Area: Pediatric Cardiology and Adult Congenital Heart Disease
    Article ID: CJ-17-0735
    [Advance publication] Released: December 01, 2017
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    Background:Reference values and the characteristics of the electrocardiographic (ECG) findings using a large number of subjects are lacking for children and adolescents.

    Methods and Results:A total of 56,753 digitally stored ECGs of participants in a school-based ECG screening system were obtained between 2006 and 2009 in Kagoshima, Japan. Each ECG was manually reviewed by 2 pediatric cardiologists and only ECGs with sinus rhythm were included. A final total of 48,401 ECGs from 16,773 1st (6 years old, 50% girls), 18,126 7th (12 years old, 51% girls), and 13,502 10th graders (15 years old, 52% girls) were selected. ECG variables showed differences in age and sex. However, the effects of age and sex on ECG variables such as the PQ interval, QRS voltage, and STJ segment were also different. The 98th percentile values of well-known surrogate parameters for ventricular hypertrophy in the present study were much higher than the conventional criteria.

    Conclusions:The present study of a large number of pediatric subjects showed that the effects of age and sex on ECG parameters are different, and that criteria for ventricular hypertrophy should be newly determined by age and sex. We have developed reference data for STJ segment elevation for children and adolescents. These findings are useful for creating guidelines and recommendations for interpretation of pediatric ECG.

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  • Géraud Souteyrand, Mathieu Valladier, Nicolas Amabile, François Derima ...
    Type: ORIGINAL ARTICLE
    Subject Area: Ischemic Heart Disease
    Article ID: CJ-17-0810
    [Advance publication] Released: December 01, 2017
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    Background:Spontaneous reanalyzed coronary thrombus (SRCT) has been reported in autopsy series, but little is known about SRCT, and it is potentially under-diagnosed in clinical practice.

    Methods and Results:SRCT identified on OCT were included in a French multicenter series, the Lotus Root French Registry. A total of 34 SRCT were identified on OCT in 33 patients (23 male; median age, 56 years; IQR, 52–65 years); 23/33 patients (70%) presented with angina pectoris and/or dyspnea. Three angiographic aspects were distinguished retrospectively: braided, pseudo-dissected, and hazy. Stenosis severity on quantitative coronary analysis varied between 11% and 100% (median, 45%), whereas the reduction in lumen area on OCT varied between 20% and 92% (median, 68%). A typical “lotus root” aspect was confirmed on OCT, consisting of multiple circular concave-edged channels of varying size, numbering between 3 and 12 depending on the slice, separated by smooth-edged septa of high luminosity without posterior attenuation. OCT also served to guide treatment, with stenting in 91% of cases. During the 17-month follow-up 91% of patients had excellent evolution. One death and 3 ACS events occurred.

    Conclusions:In this large SRCT cohort, angiography had limited diagnostic value whereas OCT could be used to define disease characteristics and guide treatment of lesions inducing angina pectoris and/or silent myocardial ischemia. OCT-guided management was associated with good prognosis.

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  • Miyuki Yokoyama, Tetsu Watanabe, Yoichiro Otaki, Ken Watanabe, Taku To ...
    Type: ORIGINAL ARTICLE
    Subject Area: Peripheral Vascular Disease
    Article ID: CJ-17-0731
    [Advance publication] Released: November 30, 2017
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    Background:Peripheral artery disease (PAD) is an athero-occlusive disease and a known risk factor for cardiovascular events. The controlling nutritional status (CONUT) score and geriatric nutritional risk index (GNRI) are objective tools for evaluating malnutrition and are reportedly associated with poor clinical outcomes in patients with fatal diseases. However, the effect of malnutrition on the clinical outcomes in patients with PAD remains unclear.

    Methods and Results:We enrolled 357 patients with PAD who underwent endovascular therapy. Malnutrition was diagnosed by CONUT score and GNRI as in previous reports. During a median follow-up period of 1,071 days, there were 67 major adverse cardiovascular and leg events (MACLEs). The CONUT score- and GNRI-based malnutrition statuses were identified in 56% and 46% of the patients, respectively. Proportion of malnutrition increased with advancing Fontaine class. The multivariate Cox proportional hazard regression analysis demonstrated that both the CONUT score- and GNRI-based malnutrition status was an independent predictor of MACLEs. The Kaplan-Meier analysis demonstrated that the MACLE ratio increased with deteriorating malnutrition. Finally, the addition of the CONUT score or GNRI to the known risk factors significantly improved the net reclassification index and integrated discrimination index.

    Conclusions:Malnutrition was common and closely associated with the clinical outcomes in patients with PAD, indicating that it is a novel therapeutic target in the management of these patients.

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  • Hideharu Okamatsu, Ken Okumura
    Type: REVIEW
    Article ID: CJ-17-1205
    [Advance publication] Released: November 30, 2017
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    Pulmonary vein (PV) antrum isolation (PVAI) is effective in treating paroxysmal atrial fibrillation (AF) but is less so for persistent AF. A recent randomized study on the ablation strategies for persistent AF demonstrated that 2 common atrial substrate modifications, creation of linear lesions in the left atrium and ablation of complex fractionated electrogram sites, in addition to PVAI did not improve the outcome compared with stand-alone PVAI, suggesting the necessity of a more individualized, selective approach to persistent AF. There are emerging technologies, including high-resolution mapping with the use of multi-electrode catheter and auto mapping system and contact force (CF) guide ablation; the former allows rapid and accurate confirmation of the completeness of PVAI, and the latter enhances the achievement of durable ablation lesions more securely. Ablation for fibrotic area(s) has been proposed as a new approach for substrate modification, and high-resolution mapping is useful to define the area with low-voltage electrograms, a surrogate marker for atrial fibrosis. Ablation for non-PV triggers in addition to PVAI improves the outcome of persistent AF. Further, durable isolation of the left atrial posterior wall may reduce AF recurrence. These ablation strategies with concomitant use of the emerging technologies are strongly expected to enhance the effectiveness of catheter ablation for persistent AF.

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  • Kana Yazaki, Ken Takahashi, Sachie Shigemitsu, Mariko Yamada, Takeshi ...
    Type: ORIGINAL ARTICLE
    Subject Area: Heart Failure
    Article ID: CJ-17-0874
    [Advance publication] Released: November 29, 2017
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    Background:Anthracycline cardiotoxicity affects clinical outcomes, and its early detection using methods that rely on conventional echocardiography, such as left ventricular ejection fraction (LVEF) is difficult. This study aimed to evaluate the characteristics and the differences in cardiac dysfunction among childhood cancer survivors in 3 age groups using layer-specific strain analysis in a wide age range.

    Methods and Results:The 56 patients (median age: 15 [range: 6.8–40.2] years) who had been treated with anthracycline for childhood cancer were divided into 3 age groups (C1: 6–12 years, C2: 13–19 years, C3: 20–40 years) after anthracycline treatment, and 72 controls of similar ages were divided into 3 corresponding groups (N1, N2, and N3). Layer-specific longitudinal strain (LS) and circumferential strain (CS) of 3 myocardial layers (endocardium, midmyocardium, and epicardium) were determined using echocardiography. Myocardial damage had not occurred yet in C1. Endocardial CS at the basal level was less in C2 than in N2. Endocardial CS at all levels and midmyocardial CS at the basal and papillary levels were lower in C3 than in N3. LVEF and LS were not significantly different between patients and controls.

    Conclusions:Among survivors of childhood cancer, impaired myocardial deformation starts in adolescence and extends from the endocardium towards the epicardium and from the base towards the apex with age. These findings are a novel insight into the time course of anthracycline cardiotoxicity.

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  • Dagmar Krajíčková, Antonín Krajina, Ivo Šteiner, Oldřich Vyšata, Roman ...
    Type: ORIGINAL ARTICLE
    Subject Area: Stroke
    Article ID: CJ-17-0375
    [Advance publication] Released: November 23, 2017
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    Background:The composition of intra-arterial clots might influence the efficacy of mechanical thrombectomy (MT) in ischemic stroke (IS) due to the acute occlusions within large cerebral arteries. The aims were to assess the factors associated with blood clot structure and the impact of thromboembolus structure on MT using stent-retrievers in patients with acute large artery IS in the anterior circulation.

    Methods and Results:In an observational cohort study, we studied the components of intra-arterial clots retrieved from large cerebral arteries in 80 patients with acute IS treated with MT with or without i.v. thrombolysis (IVT). Histology of the clots was carried out without knowledge of the clinical findings, including the treatment methods. The components of the clots, their age, origin and semi-quantitative graded changes in the architecture of the fibrin components (e.g., “thinning”) were compared via neuro-interventional, clinical and laboratory data. The most prominent changes in the architecture of the fibrin components in the thromboemboli were associated with IVT (applied in 44 patients; OR, 3.50; 95% CI: 1.21–10.10, P=0.02) and platelet count (OR, 2.94; 95% CI: 1.06–8.12, P=0.04).

    Conclusions:In patients with large artery IS treated with the MT using stent-retrievers, bridging therapy with IVT preceding MT and higher platelet count were associated with significant changes of the histological structure of blood clots.

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  • Hironobu Toda, Kazufumi Nakamura, Koji Nakagawa, Atsuyuki Watanabe, To ...
    Type: ORIGINAL ARTICLE
    Subject Area: Ischemic Heart Disease
    Article ID: CJ-17-0747
    [Advance publication] Released: November 18, 2017
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    Background:High-sensitivity cardiac troponin T (hs-cTnT) is useful for detecting myocardial injury and is expected to become a prognostic marker in patients undergoing non-cardiac surgery. The aim of this pilot study evaluating the efficacy of β-blocker therapy in a perioperative setting (MAMACARI study) was to assess perioperative myocardial injury (PMI) in elderly patients with preserved ejection fraction (EF) undergoing non-cardiac surgery.

    Methods and Results:In this prospective observational cohort study of 151 consecutive patients with preserved EF and aged >60 years who underwent non-cardiac surgery, serum levels of hs-cTnT were measured before and on postoperative days 1 and 3 after surgery. PMI was defined as postoperative hs-cTnT >0.014 ng/mL and relative hs-cTnT change ≥20%. A total of 36 (23.8%) of the patients were diagnosed as having PMI. The incidence of a composite of cardiovascular events within 30 days after surgery, including myocardial infarction, stroke, worsening heart failure, atrial fibrillation and pulmonary embolism, was significantly higher in patients with PMI than in patients without PMI (odds ratio (OR) 9.25, P<0.001, 95% confidence interval (CI) 2.65–32.3). Multivariate analysis revealed that left ventricular diastolic dysfunction defined by echocardiography was independently associated with PMI (OR: 3.029, 95% CI: 1.341–6.84, P=0.008).

    Conclusions:PMI is frequently observed in elderly patients undergoing non-cardiac surgery. Diastolic dysfunction is an independent predictor of PMI.

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  • Hideaki Takahashi, Michishige Ozeki, Tomohiro Fujisaka, Hideaki Morita ...
    Type: ORIGINAL ARTICLE
    Subject Area: Ischemic Heart Disease
    Article ID: CJ-17-0826
    [Advance publication] Released: November 18, 2017
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    Background:Fibroblast growth factor 23 (FGF23) induces cardiac remodeling. We investigated the changes in serum FGF23 levels in patients diagnosed with acute myocardial infarction (AMI).

    Methods and Results:A total of 44 patients diagnosed with AMI were included in the current study. All patients underwent emergency percutaneous coronary intervention (PCI). The median of peak creatine kinase (CK) and CKMB values was 1,816 U/L and 159 U/L, respectively. Serum levels of FGF23, calcium, and inorganic phosphate (iP) were measured before PCI, and on days 1, 3, 5, 7 after PCI. Serum FGF23 levels showed a slight, but significant decrease on days 1 and 3 after PCI, and a 1.5- and 2.0-fold increase on days 5 and 7, respectively, after PCI. As compared with propensity score-matched patients without AMI, serum FGF23 was significantly lower among the current cohort of AMI patients. In 22 subjects who underwent a follow-up echocardiographic examination at 6 months after the onset of AMI, the log-transformed relative increase in FGF23 on day 7 significantly and negatively correlated with changes between LVEF on admission and that at 6 months afterward.

    Conclusions:After a slight decrease on days 1 and 3 after admission, serum FGF23 increased significantly on days 5 and 7. The underlying mechanism and potential clinical importance of these observations require further investigation.

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  • Hee Tae Yu, Pil-Sung Yang, Hancheol Lee, Seng Chan You, Tae-Hoon Kim, ...
    Type: ORIGINAL ARTICLE
    Subject Area: Arrhythmia/Electrophysiology
    Article ID: CJ-17-0669
    [Advance publication] Released: November 14, 2017
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    Background:Rate control is now a front-line therapy in the management of atrial fibrillation (AF). However, the survival benefits of different rate-control medications remain controversial, so we assessed the efficacy of rate-control medications in AF patients with concomitant heart failure (HF).

    Methods and Results:From January 2002 to December 2008, a total of 7,034 AF patients with a single type of rate-control drug or without rate-control treatment were enrolled from the Korea National Health Insurance Service database. The death rates over a mean follow-up of 4.5±1.2 years were 12.6% (580 of 4,593) and 29.0% (709 of 2,441) in non-HF and HF patients, respectively. Among the total subjects, the risk of death was lower in patients receiving β-blockers (adjusted hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.64–0.88) and calcium-channel blockers (adjusted HR 0.74, 95% CI 0.55–0.98) compared with those who did not receive rate-control medications. In patients without HF, use of rate-control medications did not affect the risk of death. In patients with HF, β-blockers significantly decreased the mortality risk (adjusted HR 0.63, 95% CI 0.50–0.79), whereas use of calcium-channel blockers or digoxin was not associated with death. The results were observed consistently among the cohorts after propensity matching.

    Conclusions:Use of β-blockers was associated with a reduced mortality rate for AF patient with HF but not for those without HF. These findings should be examined in a large randomized trial.

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  • Yuichi Saito, Yoshio Kobayashi
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-17-0989
    [Advance publication] Released: November 14, 2017
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  • Kizuku Yamashita, Tomoyuki Fujita, Satsuki Fukushima, Yusuke Shimahara ...
    Type: RAPID COMMUNICATION
    Article ID: CJ-17-0851
    [Advance publication] Released: November 11, 2017
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    Background:The valve-in-valve procedure, in which a transcatheter heart valve (THV) is implanted over a prosthetic valve, has been shown to be safe and therapeutically effective, depending on the size of the replacement valve.

    Methods and Results:We report 3 cases of successful valve-in-valve procedure to replace a degenerated 19-mm stented prosthetic aortic valve. Balloon-expanding THVs were implanted: 20-mm in the 1st case and 23-mm in the next 2. Aortic stenosis was almost completely resolved in all patients, who recovered promptly and without cardiac adverse events.

    Conclusions:Using the valve-in-valve procedure for a 19-mm degenerated bioprosthesis was feasible and safe.

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  • Seungho Ryu, Yoosoo Chang, Jeong Gyu Kang, Jidong Sung, Jang-Young Kim ...
    Type: ORIGINAL ARTICLE
    Subject Area: Heart Failure
    Article ID: CJ-17-0231
    [Advance publication] Released: November 09, 2017
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    Background:There is sparse research on whether if early menarche is related to left ventricular (LV) diastolic dysfunction. The present study examined this relationship in Korean women.

    Methods and Results:In a cross-sectional study we analyzed the records of 18,910 Korean women (≥30 years) who underwent echocardiography as part of a comprehensive health examination. Age at menarche was assessed using standardized, self-administered questionnaires. Presence of LV diastolic dysfunction was determined from the echocardiographic findings. Of the 18,910 women, 3,449 had LV diastolic dysfunction. Age at menarche was inversely associated with prevalence of LV diastolic dysfunction. In a multivariable-adjusted model, odds ratios (95% confidence interval) for LV diastolic dysfunction comparing menarche age to menarche at 15–18 years were 1.77 (1.38–2.27) for <12 years, 1.31 (1.11–1.54) for 12 years, 1.26 (1.11–1.43) for 13 years, and 1.03 (0.91–1.15) for 14 years (P for trend <0.001). Adjusting for body mass index or percent fat mass partially reduced these associations.

    Conclusions:This large study found an inverse relationship between menarche age and LV diastolic dysfunction. Future prospective studies are needed to investigate potential causal relationships.

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  • Ke Wan, Jiayu Sun, Yuchi Han, Hong Liu, Dan Yang, Weihao Li, Jie Wang, ...
    Type: ORIGINAL ARTICLE
    Subject Area: Imaging
    Article ID: CJ-17-0464
    [Advance publication] Released: November 02, 2017
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    Background:Late gadolinium enhancement (LGE) pattern is a powerful imaging biomarker for prognosis of cardiac amyloidosis. It is unknown if the query amyloid late enhancement (QALE) score in light-chain (AL) amyloidosis could provide increased prognostic value compared with LGE pattern.

    Methods and Results:Seventy-eight consecutive patients with AL amyloidosis underwent contrast-enhanced cardiovascular magnetic resonance imaging. Patients with cardiac involvement were grouped by LGE pattern and analyzed using QALE score. Receiver operating characteristic curve was used to identify the optimal cut-off for QALE score in predicting all-cause mortality. Survival of these patients was analyzed with the Kaplan-Meier method and multivariate Cox regression. During a median follow-up of 34 months, 53 of 78 patients died. The optimal cut-off for QALE score to predict mortality at 12-month follow-up was 9.0. On multivariate Cox analysis, QALE score ≥9 (HR, 5.997; 95% CI: 2.665–13.497; P<0.001) and log N-terminal pro-brain natriuretic peptide (HR, 1.525; 95% CI: 1.112–2.092; P=0.009) were the only 2 independent predictors of all-cause mortality. On Kaplan-Meier analysis, patients with subendocardial LGE can be further risk stratified using QALE score ≥9.

    Conclusions:The QALE scoring system provides powerful independent prognostic value in AL cardiac amyloidosis. QALE score ≥9 has added value to differentiate prognosis in AL amyloidosis patients with a subendocardial LGE pattern.

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  • Hiroshi Matsuo, Kaoru Dohi, Hirofumi Machida, Hideyuki Takeuchi, Toshi ...
    Type: ORIGINAL ARTICLE
    Subject Area: Valvular Heart Disease
    Article ID: CJ-17-0393
    [Advance publication] Released: October 31, 2017
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    Background:The aim of this study was to assess the echocardiographic characteristics of chronic hemodialysis (HD) patients with end-stage renal disease (ESRD) in a multicenter prospective cohort study.

    Methods and Results:Three hundred and fifteen patients with ESRD (67.9±10.6 years, 47.6% male) on chronic HD for ≥1 year were examined on transthoracic echocardiography, including Doppler-derived aortic valve area (AVA) measurement. Only 11.5% and 3.4% of all patients had normal left ventricular (LV) geometry and normal LV filling pattern, respectively. The majority of patients had aortic and mitral valvular calcification, and approximately 50% of all 315 patients had aortic valve narrowing with AVA <2.0 cm2. Patients were divided into 3 groups according to AVA index tertile: group 1, highest tertile; group 2, middle tertile; and group 3, lowest tertile. Group 3 was older, had a greater cardiothoracic ratio on chest X-ray, higher plasma brain natriuretic peptide and total LV afterload, and lower stroke volume index than the other 2 groups. Age and intact parathyroid hormone (PTH) level were independently associated with low AVA index.

    Conclusions:Patients with ESRD on chronic HD have a high prevalence of cardiac structural and functional abnormalities including calcified aortic sclerosis. High age and PTH were associated with aortic valve narrowing in these patients.

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  • Cai-Xia Lin, Xiao-Fei Lv, Feng Yuan, Xiang-Yu Li, Ming-Ming Ma, Can-Zh ...
    Type: ORIGINAL ARTICLE
    Subject Area: Vascular Biology and Vascular Medicine
    Article ID: CJ-17-0585
    [Advance publication] Released: October 28, 2017
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    Background:TMEM16A is a critical component of Ca2+-activated chloride channels (CaCCs) and mediates basilar arterial smooth muscle cell (BASMC) proliferation in hypertensive cerebrovascular remodeling. CaMKII is a negative regulator of CaCC, and four CaMKII isoforms (α, β, γ and δ) are expressed in vasculature; however, it is unknown which and how CaMKII isoforms affect TMEM16A-associated CaCC and BASMC proliferation.

    Methods and Results:Patch clamp and small interfering RNA (siRNA) knockdown of different CaMKII isoforms revealed that only CaMKIIγ inhibited native Ca2+-activated chloride currents (ICl.Ca) in BASMCs. The TMEM16A overexpression evoked TMEM16A Clcurrent and inhibited angiotensin II (Ang II)-induced proliferation in BASMCs. The co-immunoprecipitation and pull-down assay indicated an interaction between CaMKIIγ and TMEM16A protein. TMEM16A Clcurrent was modulated by CaMKIIγ phosphorylation at serine residues in TMEM16A. Serine525 and Serine727 in TMEM16A were mutated to alanine, and only mutation at Ser727 (S727A) reversed the CaMKIIγ inhibition of the TMEM16A Clcurrent. Phosphomimetic mutation S727D markedly decreased TMEM16A Clcurrent and reversed TMEM16A-mediated suppression of BASMC proliferation, mimicking the inhibitory effects of CaMKIIγ on TMEM16A. A significant increase in CaMKIIγ isoform content was observed in parallel to the decrease of TMEM16A and ICl.Cain basilar artery proliferative remodeling in Ang II-infused mice.

    Conclusions:Serine 727 phosphorylation in TMEM16A by CaMKIIγ provides a new mechanism for regulating TMEM16A CaCC activity and Ang II-induced BASMC proliferation.

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  • Akinori Sawamura, Takahiro Okumura, Akihiro Hirakawa, Masaaki Ito, Yuk ...
    Type: ORIGINAL ARTICLE
    Subject Area: Heart Failure
    Article ID: CJ-17-0549
    [Advance publication] Released: October 27, 2017
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    Background:Cardiac recovery and prevention of end-organ damage are the cornerstones of establishing successful bridge to recovery (BTR) in patients with fulminant myocarditis (FM) supported with percutaneous venoarterial extracorporeal membrane oxygenation (VA-ECMO). However, the timing and method of successful BTR prediction still remain unclear. We aimed to develop a prediction model for successful BTR in patients with FM supported with percutaneous VA-ECMO.

    Methods and Results:This was a retrospective multicenter chart review enrolling 99 patients (52±16 years; female, 42%) with FM treated with percutaneous VA-ECMO. The S-group comprised patients who experienced percutaneous VA-ECMO decannulation and subsequent discharge (n=46), and the F-group comprised patients who either died in hospital or required conversion to other forms of mechanical circulatory support (n=53). At VA-ECMO initiation (0-h), the S-group had significantly higher left ventricular ejection fraction (LVEF) and lower aspartate aminotransferase (AST) concentration than the F-group. At 48 h, the LVEF, increase in the LVEF, and reduction of AST from 0-h were identified as independent predictors in the S-group. Finally, we developed an S-group prediction model comprising these 3 variables (area under the curve, 0.844; 95% confidence interval, 0.745–0.944).

    Conclusions:We developed a model for use 48 h after VA-ECMO initiation to predict successful BTR in patients with FM.

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  • Kazuya Nagao, Tomohiko Taniguchi, Takeshi Morimoto, Hiroki Shiomi, Ken ...
    Type: ORIGINAL ARTICLE
    Subject Area: Valvular Heart Disease
    Article ID: CJ-17-0610
    [Advance publication] Released: October 27, 2017
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    Background:Clinical profiles of acute heart failure (AHF) complicating severe aortic stenosis (AS) remain unclear.

    Methods and Results:From a Japanese multicenter registry enrolling consecutive patients with severe AS, 3,813 patients were categorized into the 3 groups according to the symptom of heart failure (HF); No HF (n=2,210), chronic HF (CHF) (n=813) and AHF defined as hospitalized HF at enrolment (n=790). Median follow-up was 1,123 days with 93% follow-up rate at 2 years. Risk factors for developing AHF included age, female sex, lower body mass index, untreated coronary artery stenosis, anemia, history of HF, left ventricular ejection fraction <50%, presence of any combined valvular disease, peak aortic jet velocity ≥5 m/s and tricuspid regurgitation pressure gradient ≥40 mmHg, and negative risk factors included dyslipidemia, history of percutaneous coronary intervention and hemodialysis. Respective cumulative 5-year incidences of all-cause death and HF hospitalization in No HF, CHF and AHF groups were 37.1%, 41.8% and 61.8% (P<0.001) and 20.7%, 33.8% and 52.3% (P<0.001). Even in the initial aortic valve replacement (AVR) stratum, AHF was associated with excess 5-year mortality risk relative to No HF and CHF (adjusted hazard ratio [HR] 1.64; 95% confidence interval [CI]: 1.14–2.36, P=0.008; adjusted HR 1.47; 95% CI: 1.03–2.11, P=0.03, respectively).

    Conclusions:AHF complicating severe AS was associated with an extremely dismal prognosis, which could not be fully resolved by AVR. Careful management to avoid the development of AHF is crucial.

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  • Cheng-Han Lee, Ching-Lan Cheng, Yea-Huei Kao Yang, Ting-Hsing Chao, Ju ...
    Type: ORIGINAL ARTICLE
    Subject Area: Ischemic Heart Disease
    Article ID: CJ-17-0632
    [Advance publication] Released: October 27, 2017
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    Background:There are few data on ticagrelor in Asian patients. This study evaluated clinical outcomes with ticagrelor and clopidogrel in Taiwanese patients with acute myocardial infarction (AMI).

    Methods and Results:We used the Taiwan National Health Insurance Research Database to identify 27,339 AMI patients aged ≥18 years between January 2012 and December 2014, and only patients who survived greater than or equal to 30 days after AMI and took dual antiplatelet therapy were included. Cohorts of ticagrelor and clopidogrel were matched 1:8, based on propensity score matching, to balance baseline covariates. The primary efficacy endpoints were death from any cause, AMI, or stroke. The safety endpoints consisted of major gastrointestinal bleeding or intracerebral hemorrhage. Following propensity matching, the primary efficacy endpoint rate was 22% lower in the ticagrelor group than in the clopidogrel group (10.6% and 16.2%, respectively; adjusted HR, 0.779; 95% CI: 0.684–0.887). The safety endpoint rate was similar between the ticagrelor and clopidogrel groups (3.2% and 4.1% respectively; adjusted HR, 0.731; 95% CI: 0.522–1.026).

    Conclusions:In real-world AMI Taiwanese patients, ticagrelor seemed to offer better anti-ischemic protection than clopidogrel, without an increase in the rate of major bleeding. A large-scale randomized trial is needed to assess the efficacy and safety of ticagrelor in East Asian AMI patients.

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  • Satoshi Ota, Akimasa Matsuda, Yoshito Ogihara, Norikazu Yamada, Mashio ...
    Type: ORIGINAL ARTICLE
    Subject Area: Pulmonary Circulation
    Article ID: CJ-17-0579
    [Advance publication] Released: October 25, 2017
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    Background:This study aimed to determine the incidence, characteristics and management of venous thromboembolism (VTE) in Japan during 2011.

    Methods and Results:A retrospective study assessed responses to a questionnaire regarding treating newly diagnosed VTE at all admitting hospitals throughout Japan during 2011. More individuals were diagnosed with VTE than ever before, with 16,096 cases of diagnosed pulmonary embolism (PE) and 24,538 cases of diagnosed deep vein thrombosis (DVT). Almost half (47.2%) of the PE patients had a relatively mild condition with no right ventricular overload. Similarly, almost half (43.8%) of the DVT patients had a relatively mild condition with isolated calf thrombus. Most of PE patients were treated by anticoagulation, and fewer were treated using thrombolytic agent or inferior vena cava (IVC) filter.

    Conclusions:The present study showed a remarkable increase in the incidence of VTE in Japan during 2011. Relatively mild conditions such as non-massive PE and isolated calf DVT were frequently diagnosed. Among PE patients, thrombolytic therapy or IVC filter implantation decreased compared with previous surveys. The appropriate management of isolated calf DVT requires further investigation.

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  • Chieko Sakai, Tatsuya Kawasaki, Michiyo Yamano, Hirokazu Shiraishi, Ta ...
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-17-0714
    [Advance publication] Released: October 24, 2017
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  • Daisuke Yoshioka, Koichi Toda, Minoru Ono, Takeshi Nakatani, Akira Shi ...
    Type: ORIGINAL ARTICLE
    Subject Area: Cardiovascular Surgery
    Article ID: CJ-17-0881
    [Advance publication] Released: October 21, 2017
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    Background:Advanced age has an adverse impact on clinical results in left ventricular assist device (LVAD) patients. We compared the clinical results of patients aged >60 years with younger patients using a national Japanese database.

    Methods and Results:Between April 2013 and December 2016, 300 patients underwent HeartMateII implantation. Of these, 37 patients were ≥60 years at LVAD implantation, and the clinical results of these patients were compared with the other younger 263 patients. At 1 and 3 years the on-device survival was 95%, 91% in younger patients, and 85%, 75% in older patients, respectively (P=0.016), although age was not a risk factor on the multivariate analysis. There was no significant difference between the groups in incidence of various adverse events except stroke. In the propensity-matching cohort, the incidence of stroke was significantly higher in patients aged >60 years (P=0.047). In patients aged >60 years, improvement of renal function was transient and there was no improvement later than 3 months, and recovery of serum albumin level to preoperative value was delayed.

    Conclusions:There were significant differences in the stroke incidence and recovery of end-organ functions after LVAD implantation. This may have important implications for patient selection in future destination therapy in Japan, where quality of life is an important issue in LVAD support.

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  • Tatsuyuki Sato, Jiro Aoki, Ken Kozuma, Yasuyuki Maruyama, Kenya Nasu, ...
    Type: ORIGINAL ARTICLE
    Subject Area: Cardiovascular Intervention
    Article ID: CJ-17-0649
    [Advance publication] Released: October 20, 2017
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    Background:Elevated serum phosphorus level is an important risk factor for cardiovascular death in general patients on hemodialysis (HD). However, the effect of serum phosphorus levels on outcomes after drug-eluting stent (DES) implantation in HD patients is unknown.

    Methods and Results:This was a post-hoc study of the OUCH study series, a series of prospective multicenter registries of HD patients who underwent DES implantation comprising 359 patients from 31 centers in Japan. Patients were categorized into 3 groups according to their preprocedural serum phosphorus levels. The 1-year clinical outcomes of the 336 patients treated for de novo lesions were evaluated. Compared with patients with high (>5.5 mg/dL; n=65) or normal (3.5–5.5 mg/dL; n=219) serum phosphorus levels, those with low serum phosphorus levels (<3.5 mg/dL; n=52) had significantly fewer target lesion revascularization events (13.9% vs. 16.9% vs. 1.9%; P=0.0090) and major adverse cardiac and cerebrovascular events (29.2% vs. 31.1% vs. 13.5%; P=0.032). Multivariate logistic regression analysis revealed that low serum phosphorus level was an independent negative predictor for major adverse cardiac and cerebrovascular events (adjusted odds ratio, 0.31; 95% confidence interval, 0.12–0.70; P=0.0036).

    Conclusions:Lowering of serum phosphorus levels beyond the current recommended range may be considered in HD patients who undergo DES implantation.

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  • Piotr Futyma, Agnieszka Wysokińska, Jarosław Sander, Marian Futyma, Pi ...
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-17-0782
    [Advance publication] Released: October 18, 2017
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  • Satoru Mitomo, Damiano Regazzoli, Luciano Candilio, Akihito Tanaka, Az ...
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-17-0850
    [Advance publication] Released: October 13, 2017
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  • Koji Nishida, Kenji Nakatsuma, Hiroki Shiomi, Masahiro Natsuaki, Kazuy ...
    Type: ORIGINAL ARTICLE
    Subject Area: Cardiovascular Intervention
    Article ID: CJ-17-0746
    [Advance publication] Released: October 05, 2017
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    Background:The comparative efficacy of second-generation (G2) vs. first-generation (G1) drug-eluting stents (DES) for calcified coronary lesions is unknown.

    Methods and Results:We compared the 3-year clinical outcomes of patients with G1- or G2-DES according to the presence or absence of calcified coronary lesions as assessed in an angiographic core laboratory using data from 2 large-scale prospective multicenter randomized trials, RESET and NEXT. G1-DES and G2-DES were implanted in 299 and 1,033 patients, respectively, in the Calc stratum (≥1 lesion with moderate/severe calcification), and 1,208 and 3,550 patients, respectively, in the Non-calc stratum (no/mild calcification). The patients in the Calc stratum had a significantly higher adjusted risk for the primary outcome measure (any target-lesion revascularization (TLR)) than those in the Non-calc stratum (HR: 1.38, 95% CI: 1.11–1.71, P=0.004). The cumulative 3-year incidence of any TLR was not significantly different between the G1-DES and G2-DES groups in both the Calc and Non-calc strata (12.1% vs. 9.7%, P=0.22, and 6.8% vs. 6.1%, P=0.44, respectively). After adjusting for confounders, the effect of G2DES relative to G1-DES for any TLR remained insignificant in both the Calc and Non-calc strata (HR: 0.78, 95% CI: 0.48–1.25, P=0.3, and HR: 0.84, 95% CI: 0.61–1.17, P=0.31, respectively, P interaction=0.55).

    Conclusions:The effect of G2-DES relative to G1-DES for TLR was not significantly different regardless of the presence or absence of lesion calcification.

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  • Kyung Woo Park, Tae-Min Rhee, Hyun-Jae Kang, Bon-Kwon Koo, Hyeon-Cheol ...
    Type: ORIGINAL ARTICLE
    Subject Area: Cardiovascular Intervention
    Article ID: CJ-17-0677
    [Advance publication] Released: September 30, 2017
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    Background:Everolimus-eluting stents (EES) have equivalent short-term angiographic and clinical outcomes to sirolimus-eluting stents (SES), but EES may be superior to SES with regard to long-term clinical safety. We report the 3-year clinical outcomes of EES and SES from the prospective EXCELLENT Randomized Trial (NCT00698607).

    Methods and Results:We randomly assigned 1,443 patients undergoing percutaneous coronary intervention 3:1 to receive EES and SES, respectively. We investigated endpoints including target lesion failure (TLF) and individual clinical outcomes including stent thrombosis (ST) at 3 years. For EES and SES, the TLF rate was 4.82% and 4.12% (risk ratio [RR], 1.16, 95% CI: 0.65–2.06, P=0.62), respectively. Results were similar in other efficacy endpoints including target lesion revascularization. For safety endpoints, rate of all-cause death was significantly lower for EES (1.67%) than SES (3.57%; RR, 0.46; 95% CI: 0.23–0.94, P=0.03), while the incidence of cardiac death or myocardial infarction was numerically lower in EES. On 1-year landmark analysis, rates of all-cause death and major adverse cardiovascular events were significantly lower for EES than SES. Definite or probable ST was numerically 3-fold higher for SES (1.37%) compared with EES (0.46%).

    Conclusions:EES and SES had similar efficacy with regard to 3-year outcomes in the EXCELLENT trial, while delayed safety events all trended to favor EES.

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  • Shigeo Ichihashi, Tomoko Hashimoto, Shinichi Iwakoshi, Kenji Obayashi, ...
    Type: ORIGINAL ARTICLE
    Subject Area: Aortic Disease
    Article ID: CJ-17-0462
    [Advance publication] Released: September 29, 2017
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    Background:Detection of aortic aneurysm (AA) prior to rupture is crucial to decreasing its mortality. Towards this purpose, a novel detection algorithm was developed from pulse volume recording (PVR), analyzing the propagation loss of pulse waves caused by expansion of the aortic wall. The diagnostic ability of the algorithm was evaluated in this prospective study.

    Methods and Results:PVR were measured for 30 s using the oscillometric device designed for automatic measurement of the ankle-brachial index (ABI). The algorithm processed the data automatically and assessed whether the patient had an AA. CT angiography was used as the reference standard. Sensitivity and specificity of the algorithm were evaluated. A total of 152 AA patients, including 21 patients with thoracic AAs (TAA), and 64 non-aneurysm control subjects were enrolled. The mean diameter of all AAs was 47.2±10.3 mm. After measurements, 121 AA patients and 33 control subjects were judged by the algorithm as having or not having AAs, resulting in sensitivity of 80% and specificity of 52%. The sensitivity was higher for larger AAs. There was no sensitivity difference according to the location of the AA.

    Conclusions:The new diagnostic algorithm installed in the oscillometric device detected AAs with high sensitivity, especially larger aneurysms. For application as a screening tool, the specificity needs to be improved.

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  • Mitsuo Sobajima, Hiroshi Ueno, Hiroshi Onoda, Hiroyuki Kuwahara, Shuhe ...
    Type: ORIGINAL ARTICLE
    Subject Area: Valvular Heart Disease
    Article ID: CJ-17-0817
    [Advance publication] Released: September 29, 2017
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    Background:There is a consensus that overactivation of the cardiac sympathetic nervous system (CSN) proportionately increases the severity of heart failure and is accompanied by worse prognosis. Because it is unknown whether patients with aortic valve stenosis (AS) have similar CSN activation, we investigated the effect of transcatheter aortic valve implantation (TAVI).

    Methods and Results:We enrolled 31 consecutive patients with AS treated by TAVI. 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy was performed at baseline and at 2 weeks after TAVI. At baseline, the early heart-mediastinum ratio (H/M) was within normal limits (3.0±0.5), but the delayed H/M was low (2.6±0.6) and the washout rate (WR) was high (34±13%). WR negatively correlated with aortic valve area (r=−0.389, P<0.01) and cardiac output (r=−0.595, P<0.01) and positively correlated with norepinephrine (r=0.519, P<0.01) and log NT-proBNP level (r=0.613, P<0.01). After TAVI, there were significant decreases in the norepinephrine level (366±179 ng/mL vs. 276±125 ng/mL, P<0.01) and WR (34±13 vs. 26±11%, P<0.01).

    Conclusions:The WR of MIBG was a useful marker of CSN activity and severity of AS. Immediate improvement of CSN activity after TAVI implied that AS hemodynamics per se enhanced CSN.

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  • Shoko Nakagawa, Osami Kawarada, Takeshi Yagyu, Teruo Noguchi, Satoshi ...
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-17-0864
    [Advance publication] Released: September 29, 2017
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  • Kenzo Hirao, Kazutaka Aonuma, Koichiro Kumagai, Koichi Inoue, Masaomi ...
    Type: ORIGINAL ARTICLE
    Subject Area: Arrhythmia/Electrophysiology
    Article ID: CJ-17-0509
    [Advance publication] Released: September 28, 2017
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    Background:The JACRE-R Registry, in which 42 Japanese institutions participated, monitored the efficacy and safety of rivaroxaban in catheter ablation (CA) of atrial fibrillation (AF). In the present analysis, we sought to elucidate the effects and risks of heparin bridging and different patterns of interruption/resumption of rivaroxaban on complications of CA.

    Methods and Results:We administered rivaroxaban during the perioperative period and recorded the incidence of complications up to 30 days after CA. A total of 1,118 patients were registered; 546 received heparin bridging and 572 did not. The bridging group showed a significantly higher incidence of non-major bleeding than the no-bridging group (4.03% vs. 0.87%; P=0.001). In the group receiving their last dose of rivaroxaban at 8–28 h before CA, neither thromboembolism nor major bleeding was observed during or after CA and the incidence of non-major bleeding was low (4/435, 0.92%). The incidence of non-major bleeding was significantly higher in the group resuming rivaroxaban ≥12 h after CA than in the group resuming <12 h (1.79% vs. 0.27%, P=0.045).

    Conclusions:Heparin bridging increased the risk of non-major bleeding perioperatively. It was safe to stop rivaroxaban 8–28 h before the CA procedure, whereas resumption of the drug within 12 h of CA was associated with a lower incidence of non-major bleeding.

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  • Eisaku Ito, Naoki Toya, Soichiro Fukushima, Yuri Murakami, Tadashi Aki ...
    Type: ORIGINAL ARTICLE
    Subject Area: Aortic Disease
    Article ID: CJ-17-0786
    [Advance publication] Released: September 27, 2017
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    Background:Aneurysm expansion, and consequent endoleaks, after endovascular aneurysm repair (EVAR) is a major problem. Accurate prediction of aneurysm expansion is demanding for surgeons and remains difficult.

    Methods and Results:We retrospectively analyzed 157 cases of EVAR for abdominal aortic aneurysm (AAA) using a bifurcated main-body stent-graft. There were 62 cases of aneurysm shrinkage after EVAR, 63 cases of stable aneurysm, and 32 cases of aneurysm expansion. Type I endoleaks were significantly increased in the aneurysm expansion group (EXP) compared with the stable (STB) and shrinkage (SHR) groups (EXP: 15.6% vs. STB: 4.8% vs. SHR: 0%, P=0.005). Type II endoleaks were also significantly increased in EXP (EXP: 65.6% vs. STB: 36.5% vs. SHR: 6.5%, P<0.001). Aneurysm wall enhancement (AWE) on imaging, however, was significantly decreased in the EXP group (EXP: 18.8% vs. STB: 23.8% vs. SHR: 53.2%, P<0.001). In multivariate analysis, the occurrence of type II endoleaks significantly decreased (P<0.001) and that of AWE significantly increased the likelihood of aneurysm shrinkage (P=0.032).

    Conclusions:AWE following EVAR may be associated with aneurysm shrinkage.

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  • Fumi Sato, Norikazu Maeda, Takayuki Yamada, Hideyuki Namazui, Shiro Fu ...
    Type: ORIGINAL ARTICLE
    Subject Area: Metabolic Disorder
    Article ID: CJ-17-0820
    [Advance publication] Released: September 27, 2017
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    Background:Excess of visceral fat is a central factor in the pathogenesis of metabolic syndrome (MetS) and atherosclerosis. However, little is known about how much epicardial fat affects cardiometabolic disorders in comparison with visceral or subcutaneous fat.

    Methods and Results:Participants suspected as having angina pectoris underwent cardiac computed tomography (CT) imaging. Of them, 374 subjects were analyzed the association of clinical characteristics and CT-based fat distribution measured as epicardial fat volume (EFV), visceral fat area (VFA), and subcutaneous fat area (SFA). EFV was highly associated with VFA (R=0.58). Serum adiponectin was significantly decreased in high VFA subjects (VFA ≥100 cm2) and was also reduced in the high EFV group (EFV ≥80 cm3). Among the low VFA groups, the numbers of subjects with diabetes and coronary atherosclerosis were increased in high EFV group. Among the low EFV groups, the numbers of subjects with diabetes, hyperuricemia, and coronary atherosclerosis were increased among the high VFA subjects. In an age-, sex-, and body mass index (BMI)-adjusted model, EFV was associated with dyslipidemia and MetS, and VFA was significantly associated with hypertension, dyslipidemia, MetS, and coronary atherosclerosis, while SFA was not related with coronary risks and atherosclerosis.

    Conclusions:Epicardial fat accumulation may be a risk for coronary atherosclerosis in subjects without visceral fat accumulation. Visceral fat is the strongest risk for cardiometabolic diseases among the 3 types of fat depot.

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  • Naoto Kawaguchi, Hideki Okayama, Go Kawamura, Tatsuya Shigematsu, Tats ...
    Type: ORIGINAL ARTICLE
    Subject Area: Ischemic Heart Disease
    Article ID: CJ-17-0745
    [Advance publication] Released: September 26, 2017
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    Background:This study aimed to evaluate the diagnostic performance of coronary flow reserve (CFR), hyperemic myocardial blood flow (hMBF), and CFR ratio for detecting significant coronary artery disease (CAD) on 13N-ammonia positron emission tomography (PET).

    Methods and Results:We analyzed 63 patients (mean age, 71±9 years; 43 males) with suspected CAD who underwent both pharmacological stress/rest 13N-ammonia PET and coronary angiography. CFR and hMBF for PET were calculated automatically using quantitative PET software, and the CFR ratio was defined as the ratio of per-vessel CFR to maximum CFR in a standard 17-segment model. We compared the diagnostic performance among the 3 quantitative values. In the per-vessel analysis, 55 vessels were diagnosed as significant CAD (≥70% stenosis and/or fraction flow reserve ≤0.8). CFR, hMBF, and CFR ratio of significant CAD were significantly lower than for non-significant CAD (1.85±0.69 vs. 2.38±0.69; P<0.01, 1.67±0.54 vs. 2.19±0.52 mL·min−1·g−1; P<0.01, and 0.66±0.15 vs. 0.82±0.09; P<0.01, respectively). In the receiver-operating characteristic curve analysis, CFR, hMBF, and CFR ratio had areas under the curve of 0.71, 0.75, and 0.85 respectively, and the CFR ratio was significantly higher than CFR and hMBF (P<0.05). The sensitivity, specificity, and accuracy of the CFR ratio with an optimal cutoff value of 0.75 were 75%, 85%, and 82%, respectively.

    Conclusions:Clinically, the CFR ratio in 13N-ammonia PET was more effective in detecting significant CAD.

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  • Takanori Yasu, Akiko Mutoh, Hiroshi Wada, Mayumi Kobayashi, Yuji Kikuc ...
    Type: ORIGINAL ARTICLE
    Subject Area: Metabolic Disorder
    Article ID: CJ-17-0809
    [Advance publication] Released: September 26, 2017
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    Background:Levels of triglycerides and free fatty acids (FFAs) are elevated in patients with diabetes and may contribute to endothelial dysfunction through renin-angiotensin system (RAS) activation and oxidative stress. The present study investigated how systemic FFA loading affected myocardial microcirculation during hyperemia via RAS.

    Methods and Results:Eight healthy men received candesartan, perindopril, or a placebo for 2 days in a double-blind crossover design, and then myocardial microcirculation during hyperemia induced by a 2-h infusion of lipid/heparin was assessed using dipyridamole stress-myocardial contrast echocardiography (MCE). Leukocyte activity and hemorheology were also assessed ex vivo using a microchannel flow analyzer, serum levels of oxidative stress markers, and IκB-α expression in mononuclear cells. Serum FFA elevation by the infusion of lipid/heparin significantly decreased myocardial capillary blood velocity and myocardial blood flow during hyperemia. Both candesartan and perindopril significantly prevented the FFA-induced decrease in capillary blood velocity and myocardial blood flow during hyperemia. Systemic FFA loading also caused an increase in the number of adherent leukocytes and prolonged the whole blood passage time. These effects were blocked completely by candesartan and partially by perindopril. Both agents prevented the FFA-induced enhancement of oxidative stress and IκB-α degradation in mononuclear cells.

    Conclusions:Both candesartan and perindopril can prevent FFA-induced myocardial microcirculatory dysfunction during hyperemia via modulation of leukocyte activation and microvascular endothelial function.

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  • Takashi Fujimoto, Yoichi Morofuji, Yuki Matsunaga, Nobutaka Horie, Tsu ...
    Type: ORIGINAL ARTICLE
    Subject Area: Imaging
    Article ID: CJ-17-0212
    [Advance publication] Released: September 23, 2017
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    Background:Because infective endocarditis (IE) carries a high risk of morbidity and mortality, rapid diagnosis and effective treatment are essential to achieving a good patient outcome. However, the diagnosis of IE is often difficult in patients presenting with nonspecific clinical manifestations. An association between IE and hypointense signal spots on brain T2*-weighted magnetic resonance imaging (MRI) has been reported, but the clinical significance remains unclear.

    Methods and Results:To assess the clinical importance of silent lesions in the brains of IE patients, hypointense signal spots detected on their brain T2*-weighted MRI scans were investigated in a retrospective review of 44 consecutive patients with definite or suspected IE evaluated by MRI between June 2006 and January 2014. Hypointense signal spots on T2*-weighted MRI were detected in 37 (84%) patients; of these, 21 (46%) had ischemic lesions, 10 (22%) had subarachnoid hemorrhage, 4 (9%) had intraparenchymal hemorrhage, and 4 (9%) had infectious aneurysm. The hypointense signal spots on T2*-weighted images were preferentially distributed in cortical areas.

    Conclusions:T2*-weighted hypointense signal spots are highly frequent in patients with IE and their presence may be informative in the monitoring of IE-associated brain lesions, even those that are neurologically asymptomatic. The strong association between IE and T2*-weighted hypointense signal spots supports the need to consider additional criteria in the diagnosis of IE.

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  • Daisuke Yoshioka, Ryoto Sakaniwa, Koichi Toda, Takaaki Samura, Shunsuk ...
    Type: ORIGINAL ARTICLE
    Subject Area: Heart Failure
    Article ID: CJ-17-0541
    [Advance publication] Released: September 23, 2017
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    Background:Blood stream infection is thought to increase the risk of hemorrhagic stroke, a major adverse event with devastating outcome, in patients with continuous-flow left ventricular assist devices (LVADs). We analyzed the risk factors of hemorrhagic stroke in LVAD patients, as well as the time relationship between systemic bacteremia and hemorrhagic stroke.

    Methods and Results:We evaluated the incidence of systemic bacteremia and stroke in 164 patients who underwent continuous-flow LVAD implantation between 2005 and 2016. At 1 and 2 years after implantation, the incidence of bacteremia was 29% and 36%, and the incidence of hemorrhagic stroke was 22% and 22% in patients without bacteremia, and 32% and 44% in those with bacteremia, respectively (P=0.035). This higher prevalence of hemorrhagic stroke in patients with bacteremia was notable particularly in the chronic phase (>90 days after implantation). Multivariate analysis revealed that bacteremia was an independent risk factor of hemorrhagic stroke in the chronic phase [hazard ratio, 2.36 (1.02–5.62); P=0.044]. The hazard rate was the highest immediately after the onset of bacteremia, and the risk steadily declined by 90 days after the last episode of bacteremia and flattened thereafter.

    Conclusions:Bacteremia was an independent risk factor of hemorrhagic stroke in patients in the chronic phase, with the highest risk seen in the early phase following an episode of bacteremia.

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  • Léo Cuenin, Sophie Lamoureux, Mathieu Schaaf, Thomas Bochaton, Jean-Pi ...
    Type: ORIGINAL ARTICLE
    Subject Area: Ischemic Heart Disease
    Article ID: CJ-17-0671
    [Advance publication] Released: September 23, 2017
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    Background:Up to 25% of patients with ST elevation myocardial infarction (STEMI) have ST segment re-elevation after initial regression post-reperfusion and there are few data regarding its prognostic significance.

    Methods and Results:A standard 12-lead electrocardiogram (ECG) was recorded in 662 patients with anterior STEMI referred for primary percutaneous coronary intervention (PPCI). ECGs were recorded 60–90 min after PPCI and at discharge. ST segment re-elevation was defined as a ≥0.1-mV increase in STMax between the post-PPCI and discharge ECGs. Infarct size (assessed as creatine kinase [CK] peak), echocardiography at baseline and follow-up, and all-cause death and heart failure events at 1 year were assessed. In all, 128 patients (19%) had ST segment re-elevation. There was no difference between patients with and without re-elevation in infarct size (CK peak [mean±SD] 4,231±2,656 vs. 3,993±2,819 IU/L; P=0.402), left ventricular (LV) ejection fraction (50.7±11.6% vs. 52.2±10.8%; P=0.186), LV adverse remodeling (20.1±38.9% vs. 18.3±30.9%; P=0.631), or all-cause mortality and heart failure events (22 [19.8%] vs. 106 [19.2%]; P=0.887) at 1 year.

    Conclusions:Among anterior STEMI patients treated by PPCI, ST segment re-elevation was present in 19% and was not associated with increased infarct size or major adverse events at 1 year.

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