Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
最新号
選択された号の論文の40件中1~40を表示しています
Editorials
Original Articles
Arrhythmia/Electrophysiology
  • Shiro Nakahara, Yuichi Hori, Reiko Fukuda, Naoki Nishiyama, Sayuki Kob ...
    原稿種別: ORIGINAL ARTICLE
    専門分野: Arrhythmia/Electrophysiology
    2019 年 83 巻 6 号 p. 1206-1213
    発行日: 2019/05/24
    公開日: 2019/05/24
    [早期公開] 公開日: 2019/04/17
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    Background:The electrophysiological characteristics of residual conduction gaps between the left atrium (LA) and pulmonary veins (PVs) after HotBalloon-based wide antral ablation (HBWA) of atrial fibrillation (AF) remain incompletely understood. This study aimed to characterize the residual gaps by means of ultra-high-resolution mapping.

    Methods and Results:A total of 55 AF patients underwent HBWA by a predetermined protocol (6-shot total-based antral approach). LA-PV maps were created using 64-electrode minibasket catheters. In total, 55 residual gaps were identified among 26 (47%) patients. Residual gaps included 33 left superior (LS: 60%), 10 left inferior (18%), 6 right superior (11%), and 6 right inferior (11%) PVs. Those gaps demonstrated both extremely lower bipolar amplitudes (0.11 [interquartile range: 0.06–0.27] mV) and conduction velocities (0.75±0.27 m/s); however, the length was confined (10.3±4.1 mm) except for the LSPV anterior carina (12.2±2.4 mm) region. Among the carina regions, all gaps had far-field potentials consistently added to the PV potentials. Left atrial appendage pacing to split the far-field activity identified confined gap regions (6.7±1.9 mm). Touch-up ablation eliminated the residual PV potentials in all cases.

    Conclusions:HBWA resulted in a certain degree of residual gap conduction in particular antral regions. These gaps exhibited narrow lengths with lower amplitudes, and often had far-field recordings from the left atrial appendage. Combined with pacing maneuvers, ultra-high-resolution activation maps could both visualize all confined gaps and ensure a bare minimum of touch-up ablations in all patients with gap conduction.

Cardiovascular Intervention
  • Krzysztof L Bryniarski, Zhao Wang, Francesco Fracassi, Tomoyo Sugiyama ...
    原稿種別: ORIGINAL ARTICLE
    専門分野: Cardiovascular Intervention
    2019 年 83 巻 6 号 p. 1214-1219
    発行日: 2019/05/24
    公開日: 2019/05/24
    [早期公開] 公開日: 2019/04/13
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    Background: Fibrous cap thickness (FCT) is one of the key features of coronary vulnerable plaque. FCT is measured at an arbitrary point, determined on visual assessment of 2-D cross-sectional imaging. This method has poor reproducibility. The aim of this study was to compare the 3-D structure of FC in non-culprit lipid plaques between patients with ST-elevation myocardial infarction (STEMI) and with stable angina (SA) on optical coherence tomography.

    Methods and Results: A total of 54 non-culprit plaques from 23 STEMI and 23 SA patients were evaluated. Thin cap fibroatheroma (TCFA), defined as lipid plaque with FCT <80 µm, was identified using a novel algorithm. The number of TCFA, surface area of each TCFA, and the sum total area of TCFA in the target vessel were measured. Patients with STEMI had a greater median number of TCFA (9, IQR 1–17 vs. 2, IQR 0–5; P=0.002), the largest median single TCFA area (0.40, IQR 0.14–0.69 vs. 0.08, IQR 0.04–0.16 mm2; P<0.001) and median sum total area of TCFA (1.04, IQR 0.41–1.95 vs. 0.24, IQR 0.08–0.48 mm2, P<0.004).

    Conclusions: Patients with STEMI, as compared with those with SA, have greater vulnerability to non-culprit plaque.

  • Yoshihisa Kanaji, Taishi Yonetsu, Rikuta Hamaya, Tadashi Murai, Eisuke ...
    原稿種別: ORIGINAL ARTICLE
    専門分野: Cardiovascular Intervention
    2019 年 83 巻 6 号 p. 1220-1228
    発行日: 2019/05/24
    公開日: 2019/05/24
    [早期公開] 公開日: 2019/04/17
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    Background:Phase-contrast cine-magnetic resonance imaging (PC-CMR) of the coronary sinus (CS) is a promising approach for quantifying coronary sinus flow (CSF) and global coronary flow reserve (G-CFR). We evaluated the prognostic value of G-CFR using PC-CMR in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS).

    Methods and Results:The study prospectively enrolled 116 NSTE-ACS patients who underwent uncomplicated urgent PCI within 48 h of symptom onset. Post-PCI (median, 20 days) PC-CMR images of the CS were acquired to assess absolute CSF at rest and during maximum hyperemia. The association of G-CFR with major adverse cardiac events (cardiac death, nonfatal myocardial infarction, late revascularization, or hospitalization for congestive heart failure) was investigated. Rest and maximal hyperemic CSF and corrected G-CFR were 1.27 [interquartile range, 0.79–1.73] mL/min/g, 2.95 [2.02–3.84] mL/min/g, and 2.42 [1.69–3.34], respectively. At a median follow-up of 17 months, cardiac event-free survival was significantly worse in patients with a corrected G-CFR <2.33 (log-rank χ2=19.5, P<0.001). Cox proportional-hazards analysis showed that corrected G-CFR (hazard ratio, 0.434, 95% CI, 0.270–0.699, P<0.001) and NT-pro BNP at admission (hazard ratio, 1.0001, 95% CI, 1.0000–1.0001, P=0.007) were independent predictors of adverse cardiac events during follow-up.

    Conclusions:In NSTE-ACS patients successfully revascularized within 48 h of onset, post-PCI PC-CMR-derived G-CFR provided significant prognostic information independent of infarct size and conventional risk scores.

  • Shiro Uemura, Hiroshi Okamoto, Michikazu Nakai, Kunihiro Nishimura, Yo ...
    原稿種別: ORIGINAL ARTICLE
    専門分野: Cardiovascular Intervention
    2019 年 83 巻 6 号 p. 1229-1238
    発行日: 2019/05/24
    公開日: 2019/05/24
    [早期公開] 公開日: 2019/04/24
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    Background:Primary percutaneous coronary intervention (pPCI) is strongly recommended by guidelines for patients presenting with acute myocardial infarction (AMI), but its applications in elderly patients are less clear.

    Methods and Results:The JROAD-DPC is a Japanese nationwide registry for patients with cardiovascular diseases combined with an administrative claim-based database. Among 2,369,165 records from 2012 to 2015, data for 115,407 AMI patients were extracted for this study. Elderly patients (≥75 years) comprised 45,645 subjects (39.6%), and received pPCI less frequently (62.2%) than younger patients (79.2%, P<0.001). Clinical variables such as higher age, female sex, higher Killip class, and renal dysfunction, but not functional status on admission, were predictors of non-application of pPCI. Endpoint 30-day mortality increased with aging, and was significantly higher in elderly patients (10.7%) than in younger patients (3.8%, P<0.001). Indeed, pPCI was independently associated with lower 30-day mortality only in subgroups of patients aged ≥60 years. Propensity score-matching analysis confirmed a similar reduction in endpoint 30-day mortality with pPCI in elderly patients. Duration of hospitalization was significantly shorter and functional ability on discharge was significantly better in elderly patients who underwent pPCI.

    Conclusions:Elderly patients with AMI underwent pPCI less frequently, but it was consistently associated with better clinical outcome in these patients. Our findings support the proactive application of pPCI for elderly AMI patients when they are eligible for an invasive strategy.

  • Mei-Ling Chen, Jung-Lun Wu, Michael Yu-Chih Chen, Tsung-Cheng Hsieh
    原稿種別: ORIGINAL ARTICLE
    専門分野: Cardiovascular Intervention
    2019 年 83 巻 6 号 p. 1239-1246
    発行日: 2019/05/24
    公開日: 2019/05/24
    [早期公開] 公開日: 2019/04/23
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    Background:Data on clinical outcome after drug-eluting stent (DES) vs. bare-metal stent (BMS) implantation in patients with end-stage renal disease (ESRD) under hemodialysis are limited and controversial.

    Methods and Results:We identified 4,970 patients under chronic hemodialysis from Taiwan National Health Insurance Research Database (NHIRD) who had their first coronary stenting between 1 January 2007 and 31 December 2012. After 1:1 propensity score matching, we evaluated clinical outcomes for 1,151 patients in the DES group and 1,151 patients in the matched BMS group. We used ICD-9 CM codes or operation code to identify all outcomes in the study cohort after the index procedure. Primary outcomes including composite endpoints of mortality, non-fatal myocardial infarction (MI), non-fatal stroke, and revascularization after the index procedure were similar in both groups (HR, 0.94; 95% CI: 0.81–1.09; P=0.399). The results were consistent in various generations of DES vs. BMS groups. Secondary outcomes including mortality, non-fatal MI, non-fatal stroke, revascularization, cardiovascular death, hospitalization for heart failure, peptic ulcer bleeding or blood transfusion were similar in both groups, except for a lower risk of peptic ulcer disease in the DES group (HR, 0.59; 95% CI: 0.41–0.83; P=0.003) than the BMS group.

    Conclusions:In patients on chronic hemodialysis, implantation of DES did not have a better clinical outcome than BMS.

Critical Care
  • Yasushi Ueki, Masahiro Mohri, Tetsuya Matoba, Toshiaki Kadokami, Sator ...
    原稿種別: ORIGINAL ARTICLE
    専門分野: Critical Care
    2019 年 83 巻 6 号 p. 1247-1253
    発行日: 2019/05/24
    公開日: 2019/05/24
    [早期公開] 公開日: 2019/04/03
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    Background: Consciousness disturbance is one of the major clinical signs associated with shock state, but its prognostic value has not been previously evaluated in cardiovascular shock patients. We aimed to evaluate the prognostic value of neurological status for 30-day mortality in cardiovascular shock patients without out-of-hospital cardiac arrest (OHCA).

    Methods and Results: Patients with out-of-hospital onset cardiovascular shock were recruited from the Japanese Circulation Society Shock Registry. Neurological status upon hospital arrival was evaluated using the Japan Coma Scale (JCS). Patients were divided into 4 groups according to the JCS: alert, JCS 0; awake, JCS 1–3 (not fully alert but awake without any stimuli); arousable, JCS 10–30 (arousable with stimulation); and coma JCS 100–300 (unarousable). The primary endpoint was 30-day all-cause death. In total, 700 cardiovascular shock patients without OHCA were assessed. The coma group was associated with a higher incidence of 30-day all-cause death compared with other groups (alert, 15.3%; awake, 24.4%; arousable, 36.8%; coma, 48.5%, P<0.001). Similar trends were observed in etiologically divergent subgroups (acute coronary syndrome, non-ischemic arrhythmia, and aortic disease). On multivariate Cox regression analysis, arousable (hazard ratio [HR], 1.82; 95% CI: 1.16–2.85, P=0.009) and coma (HR, 2.72; 95% CI: 1.76–4.22, P<0.001) (reference: alert) independently predicted 30-day mortality.

    Conclusions: Neurological status upon hospital arrival was useful to predict 30-day mortality in cardiovascular shock patients without OHCA.

Epidemiology
  • Keiko Kondo, Katsuyuki Miura, Sachiko Tanaka-Mizuno, Aya Kadota, Hisat ...
    原稿種別: ORIGINAL ARTICLE
    専門分野: Epidemiology
    2019 年 83 巻 6 号 p. 1254-1260
    発行日: 2019/05/24
    公開日: 2019/05/24
    [早期公開] 公開日: 2019/04/19
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    Background:Many studies show that dietary factors such as vegetables, fruit, and salt are associated with cardiovascular disease (CVD) risk. However, a risk assessment chart for CVD mortality according to combinations of dietary factors has not been established.

    Methods and Results:Participants were 9,115 men and women aged 30–79 years enrolled in the National Nutritional Survey of Japan in 1980 with a 29-year follow-up. Dietary intake was assessed using a 3-day weighed dietary record at baseline. Cox regression models were used to estimate the hazard ratio (HR) of CVD mortality stratified by vegetables, fruit, fish, and salt consumption. HRs of CVD mortality according to combinations of dietary factors were color coded on an assessment chart. Higher intakes of vegetables, fruit, and fish, and lower salt intake were associated with lower CVD mortality risk. HRs calculated from combinations of dietary factors were displayed using 5 colors corresponding to the magnitude of the HR. People with the lowest intake of vegetables, fruit, and fish, and higher salt intake had a HR of 2.87 compared with those with the highest intake of vegetables, fruit, and fish, and lower salt intake.

    Conclusions:Vegetables, fruit, fish, and salt intake were independently associated with CVD mortality risk. The assessment chart generated could be used in Japan as an educational tool for CVD prevention.

Heart Failure
  • Keitaro Akita, Takashi Kohno, Shun Kohsaka, Yasuyuki Shiraishi, Yuji N ...
    原稿種別: ORIGINAL ARTICLE
    専門分野: Heart Failure
    2019 年 83 巻 6 号 p. 1261-1268
    発行日: 2019/05/24
    公開日: 2019/05/24
    [早期公開] 公開日: 2019/04/03
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    Background: The natural course of heart failure (HF) is typically associated with repeated hospitalizations, and subsequently, patient prognosis deteriorates. However, the precise relationship between repeated admissions for HF and long-term prognosis remains unknown.

    Methods and Results: We analyzed data from 1,730 consecutive acute HF patients registered in the West Tokyo Heart Failure (WET-HF) registry between June 2005 and April 2014 (median age, 76 years). Patients were divided into 3 groups according to the number of previous HF admissions at the time of the index admission (0, n=876 [55.4%]; 1, n=425 [26.9%]; ≥2, n=279 [17.7%] previous admissions). A history of multiple previous admissions was an independent predictor for all-cause death and HF readmission in reference to a history of a single previous admission (hazard ratio (HR), 1.53; 95% confidence interval (CI) 1.10–2.13; HR, 1.90 95% CI, 1.47–2.44, respectively) or no previous admissions (HR, 1.37, 95% CI, 1.01–1.85; HR, 2.83, 95% CI, 2.19–3.65, respectively). On the other hand, a history of a single previous admission was an independent predictor for HF readmission in reference to a history of no previous admissions (HR, 1.51, 95% CI, 1.18–1.92), but not for all-cause death (HR, 0.89, 95% CI, 0.66–1.20).

    Conclusions: Based on a contemporary multicenter HF registry, a history of multiple previous HF admissions was revealed as an independent, strong risk factor of adverse events following the index admission. The number of hospitalizations could be a simple and important surrogate indicating subsequent adverse events in patients with HF.

  • Hiroyuki Tsutsui, Shin-ichi Momomura, Tohru Masuyama, Yoshihiko Saito, ...
    原稿種別: ORIGINAL ARTICLE
    専門分野: Heart Failure
    2019 年 83 巻 6 号 p. 1269-1277
    発行日: 2019/05/24
    公開日: 2019/05/24
    [早期公開] 公開日: 2019/04/06
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    Background: The comparative tolerability, efficacy, and safety of bisoprolol and carvedilol have not been established in Japanese patients with heart failure and reduced ejection fraction (HFrEF).

    Methods and Results: The CIBIS-J trial is a multicenter, open-label, non-inferiority randomized controlled trial of bisoprolol vs. carvedilol in 217 patients with HFrEF (EF ≤40%). The primary endpoint was tolerability, defined as reaching and maintaining the maximum maintenance dose (bisoprolol 5 mg/day or carvedilol 20 mg/day) during 48 weeks of treatment. The primary endpoint was achieved in 41.4% of patients in bisoprolol (n=111) and 42.5% in carvedilol (n=106) groups. The non-inferiority of tolerability of bisoprolol compared with carvedilol was not supported, however, neither β-blocker was superior with regard to tolerability. Heart rate (HR) decreased in both groups and its decrease from baseline was significantly greater in the bisoprolol group (20.3 vs. 15.4 beats/min at 24 week, P<0.05). Plasma B-type natriuretic peptide (BNP) levels decreased in both groups and the decrease was significantly greater in the carvedilol group (12.4 vs. 39.0 % at 24 weeks, P<0.05).

    Conclusions: There were no significant differences between bisoprolol and carvedilol in the tolerability of target doses in Japanese HFrEF patients. The clinical efficacy and safety were also similar despite the greater reduction in HR by bisoprolol and plasma BNP by carvedilol.

  • Nami Uchiyama, Toshinori Yuasa, Masaaki Miyata, Yoshihisa Horizoe, Hid ...
    原稿種別: ORIGINAL ARTICLE
    専門分野: Heart Failure
    2019 年 83 巻 6 号 p. 1278-1285
    発行日: 2019/05/24
    公開日: 2019/05/24
    [早期公開] 公開日: 2019/04/09
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    Background: This study was designed to investigate the relationship between right ventricular wall stress (RVWS) and plasma B-type natriuretic peptide (BNP) levels in patients with pulmonary hypertension (PH).

    Methods and Results: The 57 consecutive PH patients and 8 control subjects were enrolled. Right heart catheterization (RHC), echocardiography, and BNP measurements were performed, and RVWS and left ventricular wall stress (LVWS) were calculated with the formula based on Laplace’s law. Systolic RVWS and end-diastolic RVWS were higher in PH patients compared with controls (systolic RVWS: 77±41 vs. 17±5 kdynes/cm2(P<0.0001), end-diastolic RVWS: 15±12 vs. 8±2 kdynes/cm2(P<0.0005)). Univariate analyses showed that logBNP at baseline correlated with systolic RVWS (r=0.58, P<0.0001) and end-diastolic RVWS (r=0.61, P<0.0001). We performed multivariate regression analysis and determined that end-diastolic RVWS was an independent determinant of logBNP in patients with PH. In addition, change in plasma BNP levels after treatment correlated with change in systolic RVWS (r=0.70, P<0.0001) and change in end-diastolic RVWS (r=0.68, P<0.0001).

    Conclusions: Both systolic and end-diastolic RVWS were elevated in patients with PH, and correlated with the symptoms of PH. End-diastolic RVWS was an independent determinant of plasma BNP levels in PH patients.

  • Teruhiko Imamura, Koichiro Kinugawa, Minoru Ono, Osamu Kinoshita, Nori ...
    原稿種別: ORIGINAL ARTICLE
    専門分野: Heart Failure
    2019 年 83 巻 6 号 p. 1286-1292
    発行日: 2019/05/24
    公開日: 2019/05/24
    [早期公開] 公開日: 2019/04/24
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    Background:Hemocompatibility-related adverse events (HRAEs) are substantial issues in patients with left ventricular assist devices (LVADs). Atrial fibrillation (AF) is associated with worse prognosis in patients with heart failure (HF), but its effect on HRAEs following LVAD implantation remain uncertain.

    Methods and Results:Data from the Japanese Mechanically Assisted Circulatory Support registry of consecutive patients who received HeartMate II LVADs and were followed for 1 year were retrospectively reviewed. Among 190 patients, 23 had AF and 167 had sinus rhythm. The AF group had comparable baseline characteristics with the non-AF group except for their higher age (53 vs. 42 years, P<0.001). Following LVAD implantation, most cases of AF (73%) persisted. Antiplatelet therapy, anticoagulation therapy, and LVAD speed following LVAD implantation were comparable between groups (P>0.05 for all). The 1-year survival free from HRAEs was comparable between groups (83% vs. 76%, P=0.52). Event rates of the breakdown of HRAEs were comparable between groups except for a relatively higher rate of surgically managed pump thrombosis in the AF group (0.16 vs. 0.04, incidence rate ratio 3.75, 95% confidence interval 0.87–16.1, P=0.075). These trends still remained with propensity score-matched comparison.

    Conclusions:Existence of AF had no effect on the development of HRAEs following LVAD implantation. The need to aggressively treat AF before or after LVAD implantation needs further investigation.

Imaging
  • Yasutsugu Shiono, Hitoshi Matsuo, Tomohiro Kawasaki, Tetsuya Amano, Hi ...
    原稿種別: ORIGINAL ARTICLE
    専門分野: Imaging
    2019 年 83 巻 6 号 p. 1293-1301
    発行日: 2019/05/24
    公開日: 2019/05/24
    [早期公開] 公開日: 2019/04/18
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    Background:Coronary computed tomography angiography (cCTA)-derived fractional flow reserve (FFRCT) is a promising diagnostic method for the evaluation of coronary artery disease (CAD). However, clinical data regarding FFRCTin Japan are scarce, so we assessed the clinical impact of using FFRCTin a Japanese population.

    Methods and Results:The ADVANCE registry is an international prospective FFRCTregistry of patients suspected of CAD. Of 5,083 patients, 1,829 subjects enrolled from Japan were analyzed. Demographics, symptoms, cCTA, FFRCT, treatment strategy, and 90-day major cardiovascular events (MACE) were assessed. Reclassification of treatment strategy between cCTA alone and cCTA+FFRCToccurred in 55.8% of site investigations and in 56.9% in the core laboratory analysis. Patients with positive FFR (FFRCT≤0.80) were less likely to have non-obstructive disease on invasive coronary angiography than patients with negative FFR (FFRCT>0.80) (20.5% vs. 46.1%, P=0.0001). After FFRCT, 67.0% of patients with positive results underwent revascularization, whereas 96.1% of patients with negative FFRCTwere medically treated. MACE occurred in 5 patients with positive FFRCT, but none occurred in patients with negative FFRCTwithin 90 days.

    Conclusions:In this Japanese population, FFRCTmodified the treatment strategy in more than half of the patients. FFRCTshowed potential for stratifying patients suspected of CAD properly into invasive or non-invasive management pathways.

Ischemic Heart Disease
  • Yuki Fujihara, Takamitsu Nakamura, Takeo Horikoshi, Jun-ei Obata, Dais ...
    原稿種別: ORIGINAL ARTICLE
    専門分野: Ischemic Heart Disease
    2019 年 83 巻 6 号 p. 1302-1308
    発行日: 2019/05/24
    公開日: 2019/05/24
    [早期公開] 公開日: 2019/04/18
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    Background:This study examined the predictive value of remnant lipoprotein levels for cardiovascular events (CVEs) in patients with stable coronary artery disease (CAD) and low-density lipoprotein cholesterol (LDL-C) levels <70 mg/dL on statin treatment.

    Methods and Results:Serum levels of remnant lipoproteins (remnant-like lipoprotein particles cholesterol: RLP-C) were measured by an immunoseparation method in 247 consecutive patients with CAD who had on-statin LDL-C levels <70 mg/dL. All the patients were followed prospectively for a period of ≤60 months or until the occurrence of the primary composite endpoint of cardiac death, nonfatal myocardial infarction, unstable angina requiring coronary revascularization, worsening heart failure, peripheral artery disease, aortic event, and ischemic stroke. During a mean follow-up period of 38 months, 33 CVEs occurred. Kaplan-Meier analysis demonstrated that higher RLP-C levels (≥3.9 mg/dL, determined by ROC curve) resulted in a significantly higher probability for the primary endpoint than did lower RLP-C levels (<3.9 mg/dL) (P<0.01 by log-rank test). Stepwise multivariate Cox proportional hazard analysis showed that RLP-C was a significant predictor of the primary endpoint after adjustment for known risk factors and lipid variables including triglycerides, and total apolipoprotein B (hazard ratio 1.62, 95% confidence interval 1.26–2.07, P<0.01).

    Conclusions:RLP-C levels are a residual risk factor for future CVEs in patients with CAD and on-statin LDL-C <70 mg/dL.

  • Shinya Ichikawa, Kengo Tsukahara, Shinnosuke Kikuchi, Yugo Minamimoto, ...
    原稿種別: ORIGINAL ARTICLE
    専門分野: Ischemic Heart Disease
    2019 年 83 巻 6 号 p. 1309-1316
    発行日: 2019/05/24
    公開日: 2019/05/24
    [早期公開] 公開日: 2019/04/11
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    Background: Few reports have evaluated the total antithrombotic effect of multiple antithrombotic agents.

    Methods and Results: Thrombus formation was evaluated with the Total Thrombus-formation Analysis System (T-TAS®) using 2 types of microchips in 145 patients with stable coronary artery disease receiving oral anticoagulants plus single- or dual-antiplatelet therapy. The PL-chip coated with collagen is designed for analysis of the platelet thrombus formation process under shear stress condition (18 µL/min). The AR-chip coated with collagen and tissue thromboplastin is designed for analysis of the fibrin-rich platelet thrombus formation process under shear stress condition (4 µL/min). The results were expressed as an area under the flow pressure curve (PL18-AUC10and AR4-AUC30, respectively). Bleeding events occurred in 43 patients during a 22-month follow-up. AR4-AUC30was significantly lower in patients with bleeding events than in those without (584 [96–993] vs. 1,028 [756–1,252], P=0.0003). Multivariate logistic regression analysis identified AR4-AUC30(odds ratio 3.18) as a significant predictor of bleeding events, in addition to baseline anemia and usage of the standard dose of direct oral anticoagulants. However, PL18-AUC10was not significantly related to bleeding events.

    Conclusions:A lower AR4-AUC30level was associated with increasing risk of subsequent bleeding complications in patients with stable coronary artery disease who received multiple antithrombotic agents.

  • Yi-Heng Li, Yu-Wei Chiu, Jun-Jack Cheng, I-Chang Hsieh, Ping-Han Lo, M ...
    原稿種別: ORIGINAL ARTICLE
    専門分野: Ischemic Heart Disease
    2019 年 83 巻 6 号 p. 1317-1323
    発行日: 2019/05/24
    公開日: 2019/05/24
    [早期公開] 公開日: 2019/04/27
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    Background:Little information is available in Asia about the real-world practice of dual antiplatelet therapy (DAPT) duration for acute coronary syndrome (ACS) and its influence on clinical outcomes.

    Methods and Results:The Taiwan ACS STENT Registry was a prospective, multicenter study to observe ACS patients using clopidogrel-based DAPT after percutaneous coronary intervention (PCI). The primary outcome was a composite of cardiovascular death, myocardial infarction, and stroke. Overall, 2,221 ACS patients (62 years, 83% men) were included. DAPT duration was ≤9 months in 935 (42.1%). The incidence of primary outcome was higher in patients receiving DAPT ≤9 months compared with those receiving DAPT >9 months at 1 year (3.5% vs. 1.6%, P=0.0026). The incidence of stent thrombosis (overall 0.5%) was similar between groups. Multivariable analysis showed that DAPT >9 months was associated with a significantly lower risk of primary outcome (odds ratio 0.725, 95% confidence interval 0.545–0.965).

    Conclusions:Our data showed that short duration of DAPT (≤9 months) was common (42.1%) in Taiwan for ACS patients undergoing PCI. DAPT ≤9 months increased the risk of the primary outcome.

  • Daisuke Kamon, Hiroyuki Okura, Akihiko Okamura, Yasuki Nakada, Yukihir ...
    原稿種別: ORIGINAL ARTICLE
    専門分野: Ischemic Heart Disease
    2019 年 83 巻 6 号 p. 1324-1329
    発行日: 2019/05/24
    公開日: 2019/05/24
    [早期公開] 公開日: 2019/04/20
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    Background:Plasma renin activity (PRA) is associated with cardiovascular events in patients with heart failure (HF), but its prognostic role in acute myocardial infarction (AMI) is unclear.

    Methods and Results:A total of 878 patients with information on baseline PRA on admission were selected from 1,055 AMI patients who underwent emergency coronary angiography between 2007 and 2016. The patients were divided into 2 groups according to their median PRA (2.0 ng/mL/h). The primary endpoint was major adverse cardiac events (MACE), defined as a composite of cardiovascular death and hospitalization because of HF. During follow-up (median 4.5±3.1 years), MACE occurred in 108 patients. Kaplan-Meier analysis showed that the high PRA group had significantly lower MACE-free survival than the low PRA group (log-rank P=0.0009). By multivariate analysis, high PRA was an independent predictor of MACE (hazard ratio (HR) 1.573; 95% confidence interval (CI) 1.049–2.396, P=0.0282). Similarly, among 580 patients who had not been previously treated with renin-angiotensin system inhibitors or β-blockers on admission, high PRA was an independent predictor of MACE (HR 1.732; 95% CI 1.010–3.047, P=0.0460).

    Conclusions:In the studied AMI patients, elevated levels of PRA were independently associated with poor prognosis.

Myocardial Disease
  • Takeshi Iso, Ken Takahashi, Kana Yazaki, Mayumi Ifuku, Masaki Nii, Tos ...
    原稿種別: ORIGINAL ARTICLE
    専門分野: Myocardial Disease
    2019 年 83 巻 6 号 p. 1330-1337
    発行日: 2019/05/24
    公開日: 2019/05/24
    [早期公開] 公開日: 2019/04/24
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    Background:Although the subclinical left ventricular (LV) dysfunction caused by diabetes mellitus (DM) results in a high risk of death and heart failure, the details of cardiac dysfunction across a wide age range remain unclear. The aim of this study was to assess LV dysfunction in patients with type 1 DM (T1DM) using layer-specific strain analysis by echocardiography.

    Methods and Results:The 52 patients (median age: 23 [range: 5–40] years) with T1DM were divided into 3 age groups (D1: 5–14 years, D2: 15–24 years, D3: 25–40 years); 78 age- and sex-similar controls were divided into 3 corresponding groups (C1, C2, and C3). Layer-specific longitudinal strain (LS) and circumferential strain (CS) of the 3 myocardial layers (endocardium, midmyocardium, and epicardium) were determined using echocardiography. Strains did not decrease in D1. Epicardial and midmyocardial CS at the basal level and LS in all layers were decreased in D2 compared with C2. CS at the basal level and LS in all layers were lower in D3 than in C3. The strains correlated with the duration of T1DM and LV wall thickness.

    Conclusions:In patients with T1DM, longitudinal deformation in all layers and epicardial and midmyocardial circumferential deformation at the basal level decreased from the late teens, which correlated with the duration of the disease and LV hypertrophy.

Pediatric Cardiology and Adult Congenital Heart Disease
  • Eiko Terashi, Yoshihiko Kodama, Ayako Kuraoka, Yuichi Ishikawa, Makoto ...
    原稿種別: ORIGINAL ARTICLE
    専門分野: Pediatric Cardiology and Adult Congenital Heart Disease
    2019 年 83 巻 6 号 p. 1338-1341
    発行日: 2019/05/24
    公開日: 2019/05/24
    [早期公開] 公開日: 2019/04/23
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    Background:Liver stiffness on ultrasound shear-wave elastography (SWE) reflects central venous pressure (CVP) in adult patients with heart failure, but the association of liver stiffness on SWE with CVP in pediatric patients is not clear. The present study evaluated whether liver stiffness on SWE is useful as a non-invasive indicator of CVP in pediatric patients.

    Methods and Results:Liver stiffness was measured using ultrasound SWE in 79 patients aged <20 years with congenital heart diseases. None of the patients was found to have liver disease. Correlations between liver stiffness and other clinical variables, including CVP, were analyzed. CVP was the only factor independently and significantly correlated with liver stiffness in multivariate analysis. However, variables related to hepatic fibrosis did not correlate with liver stiffness.

    Conclusions:Liver stiffness on ultrasound SWE is useful as a non-invasive indicator of CVP in children with heart diseases.

Peripheral Vascular Disease
  • Koji Sato, Kenji Sakamoto, Yoichiro Hashimoto, Kazuhiko Hanzawa, Daisu ...
    原稿種別: ORIGINAL ARTICLE
    専門分野: Peripheral Vascular Disease
    2019 年 83 巻 6 号 p. 1342-1348
    発行日: 2019/05/24
    公開日: 2019/05/24
    [早期公開] 公開日: 2019/04/06
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    Background: After previous earthquakes, a high prevalence of deep vein thrombosis (DVT) has been reported. We examined DVT prevalence and risk factors in evacuees of the Kumamoto earthquakes by performing mobile DVT screening at various evacuation centers around the epicenter.

    Methods and Results: For 1 month after the Kumamoto earthquake on 14 April 2016, mobile DVT screening using portable ultrasonography (US) was performed at 80 evacuation centers. Questionnaires, physical examination, and US of the lower limb were carried out, and simple D-dimer measurements were undertaken for DVT-positive examinees. The total number of examinees was 1,673, of whom 178 (10.6%) had DVT. The prevalence of DVT seemed to be gradually decreasing in the screening period, but age, use of sleep medication, prevalence of hypertension, dyslipidemia, leg edema, and lower leg varix were significantly higher in the DVT positive group than in the negative group. On multivariable logistic regression analysis, high age (≥70 years old), use of sleep medication, lower leg edema, and lower leg varix were significant predictors of DVT. In examinees with these 4 predictors, the DVT positive rate was 71.4%.

    Conclusions: In the first month after the Kumamoto earthquakes, DVT prevalence and severity, evaluated on D-dimer level, decreased with the passage of time. Mobile DVT screening indicated significant factors stratifying DVT risk in the evacuees.

  • Shinsuke Mii, Atsushi Guntani, Eisuke Kawakubo, Hirofumi Shimazoe, Mas ...
    原稿種別: ORIGINAL ARTICLE
    専門分野: Peripheral Vascular Disease
    2019 年 83 巻 6 号 p. 1349-1355
    発行日: 2019/05/24
    公開日: 2019/05/24
    [早期公開] 公開日: 2019/04/25
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    Background:Nutritional status has been reported to be a predictor of the outcomes of critical limb ischemia. However, there have been no reports of the association between nutritional status and the prognosis of patients with intermittent claudication (IC). The aim of this study was to examine whether or not the geriatric nutritional risk index (GNRI) is independently associated with the long-term outcomes of elderly patients following open bypass for IC.

    Methods and Results:The preoperative nutritional status of patients aged ≥65 years undergoing infrainguinal bypass for IC between 1991 and 2017 was retrospectively evaluated using the GNRI. Patients were divided into 3 groups based on the GNRI: Group I (normal nutritional risk), GNRI >98; Group II (low nutritional risk), GNRI 92 to ≤98; Group III (moderate to high nutritional risk), GNRI <92. The amputation-free survival (AFS), overall survival, and freedom from cardiovascular death up to 5 years were calculated by Kaplan-Meier method and a multivariate analysis was performed to detect independent predictors of each outcome. Group I showed superior outcomes to Group III for each of the 3 outcomes and the multivariate analysis showed that GNRI was an independent predictor of AFS.

    Conclusions:The GNRI was independently associated with the AFS of elderly patients who underwent open bypass for IC.

Preventive Medicine
  • Shifei Wang, Jiancheng Xiu, Wangjun Liao, Yulin Liao, Jianping Bin
    原稿種別: ORIGINAL ARTICLE
    専門分野: Preventive Medicine
    2019 年 83 巻 6 号 p. 1356-1367
    発行日: 2019/05/24
    公開日: 2019/05/24
    [早期公開] 公開日: 2019/04/19
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    Background:We aimed to investigate the comparative cardiovascular benefits of high-dose statin, ezetimibe-statin, and PCSK9 inhibitor-statin treatments in secondary prevention patients.

    Methods and Results:We selected 12 randomized controlled trials (n=131,978 patients) using PubMed and Embase (inception–June 1, 2018). Subgroup differences were explored by meta-regression and Cochran Q test. The relative effects of high-dose statin, ezetimibe-statin, and PCSK9 inhibitor-statin on major cardiovascular events (MACE), and revascularization were varied and decreased gradually, of which high-dose statin resulted in lower risk of MACE and revascularization than PCSK9 inhibitor-statin per 1 mmol/L reduction of low-density lipoprotein cholesterol (LDL-C): risk ratio (RR) for MACE, 0.86 (95% confidence interval (CI), 0.81–0.90) for high-dose statin, 0.90 (95% CI, 0.83–0.96) for ezetimibe-statin, and 0.94 (95% CI, 0.92–0.96) for PCSK9 inhibitor-statin; RR for revascularization, 0.84 (95% CI, 0.77–0.90) for high-dose statin, 0.91 (95% CI, 0.81–1.00) for ezetimibe-statin, and 0.94 (95% CI, 0.90–0.97) for PCSK9 inhibitor-statin. Similar relative effects of intensive lipid-lowering treatment were also observed in analyses of myocardial infarction and stroke, although no significant difference between groups was identified.

    Conclusions:In secondary prevention patients, the relative benefits of high-dose statin, ezetimibe-statin, and PCSK9 inhibitor-statin treatments were varied and decreased gradually, of which high-dose statin was significantly superior to PCSK9 inhibitor-statin for improving MACE and revascularization per 1 mmol/L reduction of LDL-C.

  • Akira Sezai, Satoshi Unosawa, Makoto Taoka, Shunji Osaka, Kazuaki Obat ...
    原稿種別: ORIGINAL ARTICLE
    専門分野: Preventive Medicine
    2019 年 83 巻 6 号 p. 1368-1376
    発行日: 2019/05/24
    公開日: 2019/05/24
    [早期公開] 公開日: 2019/04/19
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    Background:Numerous studies have demonstrated a reduction in cardiovascular events when the low-density lipoprotein cholesterol (LDL) level is decreased by statin therapy. However, despite good control of LDL, cardiovascular events may increase if the triglyceride (TG) level is high. We conducted a long-term comparison of treatment of hypertriglyceridemia with ethyl icosapentate (EPA) vs. omega-3-acid ethyl (EPA+docosahexaenoic acid [DHA]).

    Methods and Results:Cardiac surgery patients with hypertriglyceridemia were randomized to an EPA group (1.8 g t.i.d.) or an EPA+DHA group (2 g s.i.d.) and observed for 3 years. The primary endpoints were the serum TG level and its percent change. Secondary endpoints included lipid markers, fatty acid parameters, serum creatinine, cystatin-C, oxidized LDL, high-sensitivity C-reactive protein, and MACCE. An interview to assess study drug adherence was conducted 6 months after completing the study. TG levels were significantly lower in the EPA+DHA group than in the EPA group. Levels of remnant-like particles-cholesterol, oxidized LDL, and cystatin-C were also significantly lower in the EPA+DHA group than in the EPA group. Compliance with treatment was significantly worse in the EPA group.

    Conclusions:Better results were obtained in the EPA+DHA group, but more patients showed poor compliance with treatment in the EPA group, making detailed comparison of the 2 groups difficult. Even so, TG were reduced while EPA and DHA levels were increased in the EPA+DHA group, together with a reduction in oxidative stress and remnant-like particles-cholesterol. Decreased compliance with medication in the EPA group significantly affected the results of this study, clearly indicating the importance of good compliance.

Pulmonary Circulation
  • Yuji Nishimoto, Yugo Yamashita, Takeshi Morimoto, Syunsuke Saga, Hidew ...
    原稿種別: ORIGINAL ARTICLE
    専門分野: Pulmonary Circulation
    2019 年 83 巻 6 号 p. 1377-1384
    発行日: 2019/05/24
    公開日: 2019/05/24
    [早期公開] 公開日: 2019/03/30
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    Background: Differences in the clinical characteristics and outcomes of venous thromboembolisms (VTEs) based on different clinical situations surrounding the onset might be important for directing appropriate treatment strategies, but have not yet been appropriately evaluated.

    Methods and Results: The COMMAND VTE Registry is a multicenter registry enrolling 3,027 consecutive patients with acute symptomatic VTEs in Japan between January 2010 and August 2014. We divided the study population into 3 groups: Out-of-hospital onset (n=2,308), In-hospital onset with recent surgery (n=310), and In-hospital onset without recent surgery (n=374). Active cancer was most prevalent in the In-hospital onset without recent surgery group, and least in the Out-of-hospital onset group (Out-of-hospital onset group: 20%, In-hospital onset with recent surgery group: 26%, and In-hospital onset without recent surgery group: 38%, P<0.001). The cumulative 5-year incidence of recurrent VTEs did not significantly differ across the 3 groups (11.4%, 5.8%, and 8.7%, respectively; P=0.11). The cumulative 5-year incidences of major bleeding and all-cause death were highest in the In-hospital onset without recent surgery group (11.1%, 8.5%, and 23.3%, P<0.001; 26.8%, 24.9%, and 48.4%, P<0.001, respectively).

    Conclusions: In the real-world VTE registry, the clinical characteristics and long-term outcomes substantially differed according to the clinical situation of VTE onset, suggesting the need for different treatment strategies for VTEs in different clinical settings.

Stroke
  • Tomotaka Tanaka, Hiroshi Yamagami, Masafumi Ihara, Toshiyuki Miyata, S ...
    原稿種別: ORIGINAL ARTICLE
    専門分野: Stroke
    2019 年 83 巻 6 号 p. 1385-1393
    発行日: 2019/05/24
    公開日: 2019/05/24
    [早期公開] 公開日: 2019/04/19
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    Background:CYP2C19variants are associated with the antiplatelet effects of clopidogrel against recurrent cardiovascular events. However, it remains unknown whether the elapsed time from stroke onset affects the relationship between the genetic variants and such events. To address this, we conducted a prospective cohort study to determine the effect ofCYP2C19variants on clinical outcomes in the chronic phase.

    Methods and Results:In total, 518 Japanese non-acute stroke patients treated with clopidogrel were registered at 14 institutions. Patients were classified into 3 clopidogrel-metabolizing groups according toCYP2C19genotype: extensive metabolizer (EM:*1/*1), intermediate metabolizer (IM:*1/*2or*1/*3), and poor metabolizer (PM:*2/*2,*2/*3, or*3/*3). Antiplatelet effects of clopidogrel were assessed by adenosine diphosphate (ADP)-induced platelet aggregation and vasodilator-stimulated phosphoprotein (VASP) phosphorylation. The endpoint was composite cerebrocardiovascular events (CVEs). In 501 successfully followed-up patients, the median time from index stroke to enrollment was 181 days. There were 28 cardiovascular and 2 major bleeding events. There were no significant differences in the rates of cardiovascular events among the groups.

    Conclusions:Despite associations betweenCYP2C19variants and on-clopidogrel platelet reactivity, there was no significant difference in rates of CVEs in the chronic stroke phase among the 3 clopidogrel-metabolizing groups ofCYP2C19variants.

Vascular Biology and Vascular Medicine
  • Mashio Nakamura, Norikazu Yamada, Tomohiko Asamura, Kazuhito Shiosakai ...
    原稿種別: ORIGINAL ARTICLE
    専門分野: Vascular Biology and Vascular Medicine
    2019 年 83 巻 6 号 p. 1394-1404
    発行日: 2019/05/24
    公開日: 2019/05/24
    [早期公開] 公開日: 2019/05/10
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    Background:ETNA-VTE-Japan is an ongoing prospective observational study conducted as part of a postmarketing observational study to investigate the safety and effectiveness of edoxaban in Japanese patients for whom the drug has been newly prescribed to treat venous thromboembolism (VTE) and prevent VTE recurrence. The results of an interim analysis of data collected at 3 months are presented.

    Methods and Results:A total of 1,732 patients were enrolled. The safety and effectiveness analyses included data from 1,703 and 1,699 patients, respectively. In the safety analysis set, 39.4% of patients were aged ≥75 years, 58.2% had body weight ≤60 kg, and 22.2% had creatinine clearance <50 mL/min. Approximately 90% of patients received a dose in accordance with the package insert. Approximately 80% of patients continued treatment; the mean treatment period was 74.5 days. The incidence of bleeding adverse events and major bleeding was 6.3% and 1.4%, respectively. The incidence of VTE recurrence and symptomatic VTE recurrence in the on-treatment population was 0.8% and 0.4%, respectively. Safety and effectiveness profiles of edoxaban in patients receiving the low dose (30 mg/day), generally administered to patients with high bleeding risk, were similar to those of the standard dose (60 mg/day).

    Conclusions:The results confirm no major concerns about the safety and effectiveness of edoxaban in Japanese patients with VTE in the first 3 months of treatment. (Trial registration No.: UMIN000016387.)

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