Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
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Showing 1-50 articles out of 108 articles from Advance online publication
  • Wei-Syun Hu, Fung-Chang Sung, Cheng-Li Lin
    Type: ORIGINAL ARTICLE
    Subject Area: Arrhythmia/Electrophysiology
    Article ID: CJ-17-0519
    [Advance publication] Released: February 16, 2018
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    Background:This retrospective cohort study sought to follow up patients with aplastic anemia (AA) to evaluate their risk of developing atrial fibrillation (AF).

    Methods and Results:From the National Health Insurance Research Database of Taiwan, this study identified an AA cohort (n=3,921), a general population cohort (n=17,617,843) and a propensity score-matched none AA cohort (PSM non-AA cohort in brief, n=15,684) in 2000–2010. By the end of 2011, the incident AF was higher in the AA cohort than in the general population and PSM non-AA cohorts (8.94 vs. 1.14 and 6.47 per 1,000 person-years, respectively). The adjusted hazards ratio of AF for the AA cohort was 2.12 (95% confidence interval 1.46–3.08) compared with the PSM non-AA cohort, after controlling for covariates. However, after further controlling for the competing risk of death, adjusted subhazard ratio was 1.21 (95% CI 0.97–1.50). Among those who developed AF, the AA cohort had a higher mortality rate (83.7 vs. 51.1 per 100), but a lower rate of incident stroke (26.0 vs. 41.5 per 100), compared with the PSM non-AA cohort.

    Conclusions:Patients with AA could have an elevated risk for AF. The mortality risk increased further for those who develop AF.

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  • Yutaka Matsuhiro, Koji Yasumoto, Keisuke Yasumura, Akihiro Tanaka, Nao ...
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-17-1028
    [Advance publication] Released: February 16, 2018
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  • Alessia Faccini, Luca Giugno, Mario Carminati, Gianfranco Butera
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-17-1207
    [Advance publication] Released: February 16, 2018
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  • Yoshiyuki Ikeda, Takeshi Sasaki, So Kuwahata, Masakazu Imamura, Kanyo ...
    Type: ORIGINAL ARTICLE
    Subject Area: Hypertension and Circulatory Control
    Article ID: CJ-17-1015
    [Advance publication] Released: February 15, 2018
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    Background:Patient-physician concordance is an important concern in the treatment of elderly patients with hypertension (HT). Treatment that considers concordance is necessary for mutual understanding and therapeutic satisfaction between patients and physicians. However, there have been no studies addressing concordance that objectively analyzed both patient and physician satisfaction before and after treatment.

    Methods and Results:An exploratory open-label, multicenter, intervention study was conducted. Patients with HT undergoing treatment with angiotensin-receptor blocker (ARB) or a calcium-channel blocker (CCB) monotherapy were enrolled. Medication was switched to an ARB/CCB combination tablet and taken for 12 weeks. Physicians and patients participated in satisfaction surveys concerning treatment. Discrepancies in satisfaction levels between patients and physicians were found at baseline for the following survey items: treatment, involvement in treatment, understanding of HT, reliance, medication, and blood pressure. After treatment, the satisfaction levels of both patients and physicians increased; discrepancies in satisfaction between the groups also improved.

    Conclusions:The rates of satisfaction were relatively higher for patients compared with physicians at baseline. After HT treatment addressing concordance, both patient and physician satisfaction rates and the gap in satisfaction rates between patients and physicians improved. This indicates that addressing concordance has clinical significance in the treatment of elderly HT patients. (UMIN000017270)

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  • Kosuke Kiyohara, Junya Sado, Tetsuhisa Kitamura, Mamoru Ayusawa, Masah ...
    Type: ORIGINAL ARTICLE
    Subject Area: Epidemiology
    Article ID: CJ-17-1237
    [Advance publication] Released: February 15, 2018
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    Background:A better understanding of the epidemiology of pediatric out-of-hospital cardiac arrest (OHCA) occurring in school settings is important to establish an evidence-based strategy for prevention and better prognosis.

    Methods and Results:The Stop and Prevent cardIac aRrest, Injury, and Trauma in Schools (SPIRITS) is a nationwide prospective observational study linking databases from 2 nationally representative registries, the Injury and the Accident Mutual Aid Benefit System of The Japan Sport Council and the All-Japan Utstein Registry of the Fire and Disaster Management Agency. Using these databases, we described the detailed characteristics and outcomes of pediatric OHCAs that occurred in school settings in Japan between 2009 and 2014. During the 6-year study period, 295 OHCA cases were confirmed. Overall incidence rate was 0.4 per 100,000 students per year. The majority of OHCA cases had a cardiac origin (71%), occurred during exercise (65%), were witnessed by bystanders (70%), and received bystander-initiated cardiopulmonary resuscitation (73%). In approximately one-third of cases the student was defibrillated by public-access automated external defibrillator (38%). The proportion of patients with 1-month survival and a favorable neurological outcome was 34% among all OHCAs and 43% among OHCAs of cardiac origin.

    Conclusions:In Japan, approximately 50 pediatric cases of OHCA consistently occur yearly in school settings. The majority of students received basic life support from bystanders, and patients with OHCA of cardiac origin had a relatively good prognosis.

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  • Masato Furuhashi, Satoshi Yuda, Atsuko Muranaka, Mina Kawamukai, Megum ...
    Type: ORIGINAL ARTICLE
    Subject Area: Metabolic Disorder
    Article ID: CJ-17-1295
    [Advance publication] Released: February 15, 2018
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    Background:Fatty acid-binding protein 4 (FABP4), which is expressed in both adipocytes and macrophages, is secreted from the cells and acts as an adipokine. An elevated circulating FABP4 level is associated with insulin resistance and atherosclerosis.

    Methods and Results:We investigated the causative association between FABP4 level and progression of atherosclerosis in subjects of the Tanno-Sobetsu Study, a population-based cohort. In 281 subjects without medication (male/female: 109/172) in the year 2010 or 2013, the carotid intima-media thickness (CIMT) assessed using carotid ultrasonography was significantly correlated with age, adiposity, blood pressure, renal dysfunction and levels of cholesterol, triglycerides, fasting glucose, HbA1c and FABP4 (r=0.331, P<0.001). Multiple regression analysis demonstrated that age, sex and FABP4 concentration were independent predictors of CIMT. A total of 78 (male/female: 29/49) of the 156 subjects in 2010 underwent carotid ultrasonography again in 2013. The change in CIMT each year during that 3-year period (mean±SD: 3.8±22.3 µm/year) was positively correlated with basal levels of high-sensitivity C-reactive protein (hsCRP) (r=0.231, P=0.046) and FABP4 (r=0.267, P=0.018) in 2010. After adjustment for age, sex and hsCRP level, the basal FABP4 level was independently associated with the change in CIMT per year.

    Conclusions:FABP4 concentration is an independent predictor of the progression of carotid atherosclerosis.

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  • Hironori Imano, Hiroyasu Iso, Akihiko Kitamura, Kazumasa Yamagishi, Mi ...
    Type: ORIGINAL ARTICLE
    Subject Area: Epidemiology
    Article ID: CJ-17-0950
    [Advance publication] Released: February 14, 2018
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    Background:The effect of postprandial glucose on the risk of cardiovascular disease has been emphasized, but it is controversial whether nonfasting glucose is related to incident stroke and its types.

    Methods and Results:We investigated the associations of nonfasting glucose with incident stroke and its types among 7,198 participants aged 40–74 years from the Circulatory Risk in Communities Study, enrolled in 1995–2000. We estimated multivariable hazard ratios (HR) using Cox proportional hazard models. Over a median follow-up of 14.1 years, 291 cases of total stroke (ischemic strokes: 191 including 109 lacunar infarctions) were identified. Nonfasting glucose concentration was associated with greater risk of incident total stroke, ischemic stroke and lacunar infarction when modeled categorically (for prediabetic type: 7.8–11.0 mmol/L vs. normal type: <7.8 mmol/L among all subjects, HR for lacunar infarction was 2.02, 95% confidence interval (CI): 1.19, 3.43) or continuously (per one standard deviation increment among all subjects, HR for lacunar infarction was 1.29, 95% CI: 1.15, 1.45). Diabetic type showed similar results. Population attributable fractions of nonfasting hyperglycemia were 13.2% for ischemic stroke and 17.4% for lacunar infarction.

    Conclusions:Nonfasting glucose concentration, either as a diagnosis of prediabetic and diabetic types or as a continuous variable, proved to be an independent predictor significantly attributed to incident total stroke, especially ischemic stroke and lacunar infarction, in the general population.

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  • Masanari Kuwabara, Koichiro Niwa, Tomohiko Toyoda, Takeaki Shirai, Shi ...
    Type: ORIGINAL ARTICLE
    Subject Area: Pediatric Cardiology and Adult Congenital Heart Disease
    Article ID: CJ-17-1053
    [Advance publication] Released: February 14, 2018
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    Background:Fontan-associated liver disease (FALD) is an important late complication involving liver dysfunction, such as liver cirrhosis (LC) and hepatocellular carcinoma (HCC), in patients undergoing the Fontan procedure. However, the prevalence, clinical manifestation, and methods of diagnosis of FALD are still not well established.

    Methods and Results:This study comprised 2 nationwide surveys in Japan. First, the prevalence of LC and/or HCC in patients undergoing the Fontan procedure was determined. Second, clinical manifestations in patients with LC and/or HCC were analyzed, along with data from blood tests, echocardiography, and right heart catheterization. In the 1st survey, of the 2,700 patients who underwent the Fontan procedure, 31 were diagnosed with LC and/or HCC (1.15%), and 5 died due to liver diseases (mortality: 0.19%). In the 2nd survey, data were collected from 17 patients (12 with LC, 2 with HCC, and 3 with LC+HCC. Of these 17 patients, 5 died (mortality: 29.4%). The mean age at diagnosis of LC and HCC was 23 and 31 years, respectively. Computed tomography followed by ultrasound was most frequently used for diagnosis. Blood tests revealed low platelet counts, increased hemoglobin, aspartate aminotransferase, γ-guanosine triphosphate, and total bilirubin levels, and an elevated international normalized ratio of prothrombin time.

    Conclusions:LC and/or HCC in patients undergoing the Fontan procedure were not rare late complications and were associated with high mortality rates.

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  • Shinichi Niwano, Yukio Sekiguchi, Yosuke Ishii, Yuki Iwasaki, Ritsushi ...
    Type: REVIEW
    Article ID: CJ-17-1336
    [Advance publication] Released: February 14, 2018
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    Prevention of sudden cardiac death (SCD) has become an important issue in today’s cardiovascular field, together with various developments in secondary prevention of basic cardiac diseases. The importance of the implantable cardioverter defibrillator (ICD) is now widely accepted because it has exhibited significant improvement in patients’ prognoses in ischemic and non-ischemic cardiovascular diseases. However, there is an unignorable gap between the ICD indication in the guidelines and real-world high-risk patients for SCD, especially in the acute recovery phase of cardiac injury. Although various studies have demonstrated a clinical benefit of defibrillation devices, the studies of immediate ICD use in the acute recovery phase have failed to exhibit a benefit in patients from the point of the view of a decrease in total deaths. To bridge this gap, the wearable cardioverter defibrillator (WCD) provides a safer observation period in the acute phase and eliminates inappropriate overuse of ICD in the subacute phase. Here, we discuss the usefulness of the WCD and current understanding of its indications based on various clinical data. In conclusion, WCD is a feasible bridge to therapy and/or safe observation for patients at high risk of SCD, especially in the acute recovery phase of cardiac diseases.

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  • Sung-Jin Hong, Byeong-Keuk Kim, Sanghoon Shin, Yongsung Suh, Seunghwan ...
    Type: ORIGINAL ARTICLE
    Subject Area: Ischemic Heart Disease
    Article ID: CJ-17-1173
    [Advance publication] Released: February 09, 2018
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    Background:The long-term outcome of percutaneous coronary intervention (PCI) vs. coronary artery bypass graft (CABG), particularly for patients with non-ST-elevation acute coronary syndrome (NSTE-ACS), remains controversial.

    Methods and Results:We retrospectively analyzed 2,827 patients (stable coronary artery disease [SCAD], n=1,601; NSTE-ACS, n=1,226) who underwent either PCI (n=1,732) or CABG (n=1,095). The 8-year composite of cardiac death and myocardial infarction (MI) was compared between PCI and CABG before and after propensity matching. For patients with NSTE-ACS, PCI was performed more frequently for those with higher Thrombolysis in Myocardial Infarction risk score and 3-vessel disease, and PCI led to significantly higher 8-year composite of cardiac death and MI than CABG (14.1% vs. 5.9%, hazard ratio [HR]=2.22, 95% confidence interval [CI]=1.37–3.58, P=0.001). There was a significant interaction between clinical presentation and revascularization strategy (P-interaction=0.001). However, after matching, the benefit of CABG vs. PCI was attenuated in patients with NSTE-ACS, whereas it was pronounced in those with SCAD. Interactions between clinical presentation and revascularization strategy were not observed (P-interaction=0.574).

    Conclusions:Although the determinants of PCI vs. CABG in real-world clinical practice differ according to the clinical presentation, a significant interaction between clinical presentation and revascularization strategy was not noted for long-term outcomes. The revascularization strategy for patients with NSTE-ACS can be based on the criteria applied to patients with SCAD.

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  • Seiji Hokimoto
    Type: EDITORIAL
    Article ID: CJ-18-0137
    [Advance publication] Released: February 09, 2018
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  • Giulio Zucchelli, Giusy Sirico, Luca Rebellato, Massimiliano Marini, G ...
    Type: ORIGINAL ARTICLE
    Subject Area: Arrhythmia/Electrophysiology
    Article ID: CJ-17-0421
    [Advance publication] Released: February 08, 2018
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    Background:Our aim was to evaluate the clinical outcome of paroxysmal atrial fibrillation (AF) ablation with contact force technology, using an automated lesion tagging system (VISITAGTM module) with strict criteria of catheter stability.

    Methods and Results:We enrolled 200 consecutive patients who underwent pulmonary vein isolation (PVI) in 11 centers and were followed up for 12 months. The stability setting was within 3 mm for ≥10 s and for ≥15 s in 47% and 53% of patients, respectively. A mean of 67.2±21.9 VISITAGs was acquired. Freedom from atrial tachyarrhythmias at follow-up was 77.5% (155/200), and the contiguity between lesions was associated with a higher chronic success rate (96% vs. 77.1%; log-rank P=0.036). Radiofrequency (RF), fluoroscopy times, and recurrence rates at the 12-month follow-up were significantly lower than in a comparison group of 80 patients without VISITAGTM module (42.7±14.5 vs. 50.9±23.6 min; P=0.032; 11.6±7.8 vs. 18.4±12.8 min; P=0.003 and 22.5% vs. 41.2%; P=0.02). Two major complications (1 cardiac tamponade and 1 minor stroke) were observed only in the control group.

    Conclusions:Paroxysmal AF ablation with contact force technology and strict criteria of stability using the VISITAG module was a safe procedure, associated with an improvement in efficiency and a reduction of atrial tachyarrhythmia recurrence at the 12-month follow-up compared with manual annotation. Contiguity between lesions seemed to enhance effectiveness outcomes.

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  • Toyoaki Murohara
    Type: MESSAGE FROM THE EDITOR-IN-CHIEF
    Article ID: CJ-66-0149
    [Advance publication] Released: February 08, 2018
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  • Toshihisa Anzai
    Type: REVIEW
    Article ID: CJ-18-0063
    [Advance publication] Released: February 07, 2018
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    Inflammation and fibrosis play an important role in the development and progression of cardiovascular diseases. Acute coronary syndrome (ACS) is caused by rupture of inflamed atherosclerotic plaque and subsequent atherothrombosis. Recent studies have shown that inflammatory markers such as C-reactive protein (CRP) can predict ACS development and have demonstrated the effectiveness of new therapeutic approaches targeting inflammation. Studies have also shown that an enhanced inflammatory response after myocardial infarction (MI) is associated with cardiac rupture, ventricular aneurysm formation, and exacerbation of left ventricular (LV) remodeling. Inflammation is a physiological reaction in which fibrosis is induced to facilitate the healing of tissue damage. However, when an excessive inflammatory response consisting mainly of monocytes/macrophages is induced by various factors, impaired reparative fibrosis and resulting pathological remodeling processes may occur. A similar phenomenon is observed in abdominal aortic aneurysm (AAA) expansion. In contrast, myocardial diseases such as inflammatory dilated cardiomyopathy (DCMI) and valvular diseases such as aortic valve stenosis (AS) are characterized by chronic inflammation mediated mainly by T lymphocytes and the associated enhancement of reactive fibrosis. Thus, inflammation can take 2 paths (the inhibition or promotion of fibrosis), depending on the phase of inflammation, inducing pathological cardiovascular remodeling. Elucidation of the regulatory mechanisms of inflammation and fibrosis will contribute to the development of new therapeutic approaches for cardiovascular diseases.

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  • Louis W. Wang, Scott H. Kesteven, Inken G. Huttner, Michael P. Feneley ...
    Type: REVIEW
    Article ID: CJ-18-0027
    [Advance publication] Released: February 06, 2018
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    Echocardiography is an invaluable tool for characterizing cardiac structure and function in vivo. Technological advances in high-frequency ultrasound over the past 3 decades have increased spatial and temporal resolution, and facilitated many important clinical and basic science discoveries. Successful reverse translation of established echocardiographic techniques, including M-mode, B-mode, color Doppler, pulsed-wave Doppler, tissue Doppler and, most recently, myocardial deformation imaging, from clinical cardiology into the basic science laboratory has enabled researchers to achieve a deeper understanding of myocardial phenotypes in health and disease. With high-frequency echocardiography, detailed evaluation of ventricular systolic function in a range of small animal models is now possible. Furthermore, improvements in frame rate and the advent of diastolic strain rate imaging, when coupled with the use of select pulsed-wave Doppler parameters, such as isovolumic relaxation time and E wave deceleration, have enabled nuanced interpretation of ventricular diastolic function. Comparing pulsed-wave Doppler indices of atrioventricular inflow during early and late diastole with parameters that describe the simultaneous myocardial deformation (e.g., tissue Doppler é and á, global longitudinal strain rate and global longitudinal velocity) may yield additional insights related to myocardial compliance. This review will provide a historical perspective of the development of high-frequency echocardiography and consider how ongoing innovation will help future-proof this important imaging modality for 21st century translational research.

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  • Eitaro Kodani, Takehiko Nagao
    Type: EDITORIAL
    Article ID: CJ-18-0045
    [Advance publication] Released: February 06, 2018
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  • Ikuo Hashimoto, Fukiko Ichida
    Type: EDITORIAL
    Article ID: CJ-18-0102
    [Advance publication] Released: February 06, 2018
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  • Yu Natsume, Kasumi Oaku, Kentaro Takahashi, Wakana Nakamura, Ai Oono, ...
    Type: ORIGINAL ARTICLE
    Subject Area: Arrhythmia/Electrophysiology
    Article ID: CJ-17-1194
    [Advance publication] Released: February 05, 2018
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    Background:Recent experimental studies have demonstrated that several microRNAs (miRNAs) expressed in atrial tissue promote a substrate of atrial fibrillation (AF). However, because it has not been fully elucidated whether these experimental data contribute to identifying circulating miRNAs as biomarkers for AF, we used a combined analysis of human serum and murine atrial samples with the aim of identifying these biomarkers for predicting AF.

    Methods and Results:Comprehensive analyses were performed to screen 733 miRNAs in serum from 10 AF patients and 5 controls, and 672 miRNAs in atrial tissue from 6 inducible atrial tachycardia model mice and 3 controls. We selected miRNAs for which expression was detected in both analyses, and their expression levels were changed in the human analyses, the murine analyses, or both. This screening identified 11 candidate miRNAs. Next, we quantified the selected miRNAs using a quantitative RT-PCR in 50 AF and 50 non-AF subjects. The individual assessment revealed that 4 miRNAs (miR-99a-5p, miR-192-5p, miR-214-3p, and miR-342-5p) were significantly upregulated in AF patients. A receiver-operating characteristics curve indicated that miR-214-3p and miR-342-5p had the highest accuracy. The combination of the 4 miRNAs modestly improved the predictive accuracy for AF (76% sensitivity, 80% specificity).

    Conclusions:Novel circulating miRNAs were upregulated in the serum of AF patients and might be potential biomarkers of AF.

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  • Allan Böhm, Vasil Hricak, Branislav Tomasovic, Martin Bena, Peter Mich ...
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-17-0740
    [Advance publication] Released: February 03, 2018
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  • Ryota Teramoto, Noboru Fujino, Tetsuo Konno, Akihiro Nomura, Yoji Naga ...
    Type: ORIGINAL ARTICLE
    Subject Area: Myocardial Disease
    Article ID: CJ-17-1012
    [Advance publication] Released: February 03, 2018
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    Background:Cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) revealed a substantial variation in the extent of myocardial scarring, a pathological hallmark of hypertrophic cardiomyopathy (HCM). However, few data exist regarding the relationship between the presence of gene mutations and the extent of LGE. Therefore, we aimed to investigate whether variations in the extent of LGE in HCM patients can be explained by the presence or absence of disease-causing mutations.

    Methods and Results:We analyzed data from 82 unrelated HCM patients who underwent both LGE-CMR and next-generation sequencing. We identified disease-causing sarcomere gene mutations in 44 cases (54%). The extent of LGE on CMR was an independent factor for predicting mutation-positive HCM (odds ratio 2.12 [95% confidence interval 1.51–3.83], P<0.01). The area under the curve of %LGE was greater than that of the conventional Toronto score for predicting the presence of a mutation (0.96 vs. 0.69, P<0.01). Sensitivity, specificity, positive predictive value, and negative predictive value of %LGE (cutoff >8.1%) were 93.2%, 89.5%, 91.1%, and 91.9%, respectively.

    Conclusions:The results demonstrated that %LGE clearly discriminated mutation-positive from mutation-negative HCM in a clinically affected HCM population. HCM with few or no myocardial scars may be genetically different from HCM with a higher incidence of myocardial scars.

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  • Tetsuo Minamino, Shuichiro Higo, Ryo Araki, Shungo Hikoso, Daisaku Nak ...
    Type: ORIGINAL ARTICLE
    Subject Area: Ischemic Heart Disease
    Article ID: CJ-17-0889
    [Advance publication] Released: February 02, 2018
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    Background:Erythropoietin (EPO) has antiapoptotic and tissue-protective effects, but previous clinical studies using high-dose EPO have not shown cardioprotective effects, probably because of platelet activation and a lack of knowledge regarding the optimal dose. In contrast, a small pilot study using low-dose EPO has shown improvement in left ventricular function without adverse cardiovascular events.

    Methods and Results:We performed a multicenter (25 hospitals), prospective, randomized, double-blind, placebo-controlled, dose-finding study to clarify the efficacy and safety of low-dose EPO in patients with ST-segment elevation myocardial infarction (STEMI) under the Evaluation System of Investigational Medical Care of the Ministry of Health, Labor and Welfare of Japan. In total, 198 STEMI patients with low left ventricular ejection fraction (LVEF <50%) were randomly assigned to receive intravenous administration of EPO (6,000 or 12,000 IU) or placebo within 6 h of successful percutaneous coronary intervention. At 6 months, there was no significant dose-response relationship in LVEF improvement among the 3 groups tested (EPO 12,000 IU: 5.4±9.3%, EPO 6,000 IU: 7.3±7.7%, Placebo: 8.1±8.3%, P=0.862). Low-dose EPO also did not improve cardiac function, as evaluated by 99 mTc-MIBI SPECT or NT-proBNP at 6 months and did not increase adverse events.

    Conclusions:Administration of low-dose EPO did not improve LVEF at 6 months in STEMI patients (UMIN000005721).

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  • Kazuhisa Kondo, Kenji Yanishi, Ryo Hayashida, Satoshi Shintani, Rei Sh ...
    Type: ORIGINAL ARTICLE
    Subject Area: Peripheral Vascular Disease
    Article ID: CJ-17-0510
    [Advance publication] Released: January 30, 2018
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    Background:The Therapeutic Angiogenesis by Cell Transplantation (TACT) trial demonstrated the efficacy and safety of autologous bone marrow-derived mononuclear cells (BM-MNCs) in patients with critical limb ischemia (CLI). The present study aimed to assess the long-term clinical outcomes of therapeutic angiogenesis using autologous BM-MNC implantation under advanced medical treatment in Japan.

    Methods and Results:The study was retrospective, observational, and non-controlled. We assessed no-option CLI patients who had BM-MNC implantation performed in 10 institutes. Overall survival (OS), major amputation-free (MAF), and amputation-free survival (AFS) rates were primary endpoints of this study. The median follow-up duration was 31.7 months. The 10-year OS rate was 46.6% in patients with arteriosclerosis obliterans (ASO) (n=168), 90.5% in patients with thromboangiitis obliterans (TAO) (n=108), and 67.6% in patients with collagen disease-associated vasculitis (CDV) (n=69). The 10-year MAF rate was 70.1%, 87.9%, and 90.9%, respectively. The 10-year AFS rate was 37.8%, 80.9%, and 61.2%, respectively. Major adverse cardiovascular events occurred in 6.0% of patients with ASO, 1.9% of patients with TAO, and no patients with CDV.

    Conclusions:Therapeutic angiogenesis using autologous BM-MNC implantation may be feasible and safe in patients with no-option CLI, particularly those with CLI caused by TAO or CDV.

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  • Motoyuki Nakamura, Yasuhiro Ishibashi, Fumitaka Tanaka, Shinichi Omama ...
    Type: ORIGINAL ARTICLE
    Subject Area: Epidemiology
    Article ID: CJ-17-1124
    [Advance publication] Released: January 30, 2018
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    Background:The ability of cardiovascular biomarkers to predict the incidence of stroke subtypes remains ill-defined in the general population.

    Methods and Results:The blood levels of B-type natriuretic peptide (BNP) and high-sensitivity C-reactive protein (hs-CRP) and urinary albumin corrected by urinary creatinine (UACR) were determined in a general population (n=13,575). The ability to predict the incidence of ischemic stroke subtypes (lacunar, atherothrombotic, cardioembolic) for each biomarker was assessed based on the area under the receiver-operating characteristic curve (AUC-ROC) and using Cox proportional hazard modeling. The predictive abilities of UACR and hs-CRP for any subtype of ischemic event were found to be suboptimal. However, the ability of BNP to predict the incidence of cardioembolic stroke was excellent (AUC-ROC=0.81). When BNP was added to established stroke risk factors, the ability to predict cardioembolic stroke in terms of the AUC-ROC significantly improved (4-year follow-up, P=0.018; 8-year follow-up, P=0.009). Furthermore, when BNP was added to the JPHC score, the ability to predict cardioembolic stroke was significantly improved (net reclassification improvement=0.968, P<0.0001: integrated discrimination improvement=0.039, P<0.05).

    Conclusions:In the general population, plasma BNP was an excellent biomarker for predicting the incidence of cardioembolic stroke when used alone or in combination with established stroke risk factors.

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  • Michał Ciurzyński, Katarzyna Kurnicka, Barbara Lichodziejewska, Marta ...
    Type: ORIGINAL ARTICLE
    Subject Area: Pulmonary Circulation
    Article ID: CJ-17-0940
    [Advance publication] Released: January 26, 2018
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    Background:Patients with intermediate-risk acute pulmonary embolism (APE) are a heterogeneous group with an early mortality rate of 2–15%. The tricuspid annulus plane systolic excursion (TAPSE) and tricuspid regurgitation peak gradient (TRPG) can be used for risk stratification, so we analyzed the prognostic value of a new echo parameter (TRPG/TAPSE) for prediction of APE-related 30-day death or need for rescue thrombolysis in initially normotensive APE patients.

    Methods and Results:The study group consists of 400 non-high-risk APE patients (191 men, age: 63.1±18.9 years) who had undergone echocardiography within the first 24 h of admission. The TRPG/TAPSE parameter was calculated. The clinical endpoint (CE) was a combination of 30-day APE-related death and/or rescue thrombolysis. The CE occurred in 8 (2%) patients. All patients with TAPSE ≥20 mm (n=193, 48.2%) had a good prognosis. Among 206 patients with TAPSE <20 mm, 8 cases of the CE occurred (3.9%). NPV and PPV for TRPG/TAPSE >4.5 were 0.2 and 0.98, respectively. The CE was significantly more frequent in 19 (9.2%) patients with TRPG/TAPSE >4.5 than in 188 (90.8%) with TRPG/TAPSE ≤4.5 (4 (21.1%) vs. 4 (2.1%), P=0.0005). Among normotensive APE patients with TAPSE <20 mm, TRPG/TAPSE >4.5 was associated with 21.1% risk of APE-related death or rescue thrombolysis.

    Conclusions:TRPG/TAPSE, a novel echocardiographic parameter, may be useful for stepwise echocardiographic risk stratification in normotensive patients with APE, and it identifies patients with a poor prognosis.

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  • Junya Sado, Kosuke Kiyohara, Taku Iwami, Yuri Kitamura, Emiko Ando, Te ...
    Type: RAPID COMMUNICATION
    Article ID: CJ-17-1003
    [Advance publication] Released: January 26, 2018
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    Background:We assessed whether the occurrence of out-of-hospital cardiac arrest (OHCA) with cardiac origin increased in the disaster areas during the 3-year period after the Great East Japan Earthquake (GEJE).

    Methods and Results:From the OHCA registry in Japan, yearly changes in occurrence after the GEJE were assessed by applying Poisson regression models. The risk ratio of the first year after the earthquake was significantly greater in both men and women, but the difference disappeared in the second and third years.

    Conclusions:The GEJE significantly increased the occurrence of OHCA with cardiac origin in the first year after the earthquake.

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  • Masato Okada, Koichi Inoue, Koji Tanaka, Yuichi Ninomiya, Yuko Hirao, ...
    Type: ORIGINAL ARTICLE
    Subject Area: Arrhythmia/Electrophysiology
    Article ID: CJ-17-1213
    [Advance publication] Released: January 26, 2018
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    Background:This study evaluated the safety and efficacy of venous figure-of-eight (FoE) suture to achieve femoral venous hemostasis after radiofrequency (RF) catheter ablation (CA) for atrial fibrillation (AF).

    Methods and Results:We retrospectively examined 517 consecutive patients undergoing RFCA for AF. The control group (n=247) underwent manual compression for femoral venous hemostasis after sheath removal with 6 h of bed rest. The FoE group (n=270) underwent FoE suture technique with 4 h of bed rest. All patients achieved successful hemostasis within 24 h after CA. Although the incidence of hematoma was similar between the groups, the incidence of rebleeding was lower in the FoE group than in the control group (FoE vs. control, 3.7% vs. 18.6%, P<0.001). The post-procedural use of analgesic and/or anti-emetic agents was less frequent in the FoE group (19.3% vs. 32.0%, P<0.001). On multiple logistic regression analysis after adjustment for age and sex, the use of a vitamin K antagonist (OR, 2.42; 95% CI: 1.18–4.99, P=0.02) and the FoE suture technique (OR, 0.17; 95% CI: 0.08–0.35, P<0.001) were independent predictors of rebleeding after CA.

    Conclusions:FoE suture technique effectively achieved femoral venous hemostasis after RFCA for AF. It reduced the risk of rebleeding, shortened bed rest duration, and relieved patient discomfort.

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  • Fumiyasu Seike, Teruyoshi Uetani, Kazuhisa Nishimura, Hiroshi Kawakami ...
    Type: ORIGINAL ARTICLE
    Subject Area: Ischemic Heart Disease
    Article ID: CJ-17-1042
    [Advance publication] Released: January 25, 2018
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    Background:Fractional flow reserve (FFR) is widely used for the assessment of myocardial ischemia. Intravascular ultrasound (IVUS) is an intracoronary imaging method that provides information about lumen and vessel morphology. Previous studies on the expanded use of IVUS to identify functional ischemia have noted an association between anatomy and physiology, but IVUS-derived minimum lumen area (MLA) has a weak-moderate correlation with myocardial ischemia compared with FFR. We developed a method to calculate FFR using IVUS-derived anatomical information for the assessment of myocardial ischemia. The aims of this study were to investigate the relationship between wire-based FFR and IVUS-derived FFR (IVUS-FFR) and to compare the usefulness of IVUS-FFR and IVUS-derived MLA for functional assessment.

    Methods and Results:We retrospectively analyzed 50 lesions in 48 patients with coronary stenosis who underwent IVUS and FFR simultaneously. IVUS-FFR was calculated using our original algorithm and fluid dynamics. Mean percent diameter stenosis determined on quantitative coronary angiography and on FFR was 56.4±10.7 and 0.69±0.08, respectively. IVUS-FFR had a stronger linear correlation with FFR (R=0.78, P<0.001; root mean square error, 0.057 FFR units) than with IVUS-derived MLA (R=0.43, P=0.002).

    Conclusions:IVUS-FFR may be a more valuable method to identify myocardial ischemia, compared with IVUS-derived MLA.

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  • Hsi-Yu Yu, Ming-Hsien Lin, Lian-Yu Lin, Chih-Hsien Wang, Nai-Hsin Chi, ...
    Type: ORIGINAL ARTICLE
    Subject Area: Valvular Heart Disease
    Article ID: CJ-17-1172
    [Advance publication] Released: January 25, 2018
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    Background:Asian patients on warfarin therapy usually have lower international normalized ratio (INR) intensities than those recommended by Western clinical practice guidelines. This study evaluated whether a high INR reduces the incidence of thromboembolism (TE) or bleeding events in Asian patients with high CHA2DS2-VASc scores after valve surgery.

    Methods and Results:Data of adult patients after valve surgery were retrieved from an integrated healthcare information system of a single hospital between 2014 and 2016. The INR was derived from the closest laboratory data before the index outpatient-clinic visit date. The endpoint of every record was determined as emergency room visit or hospitalization because of TE or bleeding event. A total of 37 TE or bleeding events were retrieved from 8,207 records; the annual incidence rate were 1.2% and 2.8% for low (0–2) and high (3–8) CHA2DS2-VASc score groups, respectively (P=0.007). The incidence rates were lowest for both groups at an INR of 1.5–2.0. High INR intensities did not reduce TE or bleeding incidence. INR >3.0 was associated with increased TE or bleeding incidence in the high-score group (6.8%/year vs. 2.0%/year, P=0.079).

    Conclusions:The optimal INR is 1.5–2.5 for low- or high-score Asian patients after valve surgery. INR >3.0 was associated with increased TE or bleeding incidence in the high-score group.

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  • Manuel Barreiro-Perez, Ignacio Cruz-Gonzalez, Jose Carlos Moreno-Samos ...
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-17-1229
    [Advance publication] Released: January 24, 2018
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  • Aritomo Katsura, Yoshiyasu Minami, Taiki Tojo, Junya Ako
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-17-1239
    [Advance publication] Released: January 24, 2018
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  • Satoshi Kodera, Hiroyuki Morita, Arihiro Kiyosue, Jiro Ando, Issei Kom ...
    Type: ORIGINAL ARTICLE
    Subject Area: Ischemic Heart Disease
    Article ID: CJ-17-0995
    [Advance publication] Released: January 23, 2018
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    Background:The addition of eicosapentaenoic acid (EPA) to statin therapy has been shown to reduce cardiovascular events. This study examined the cost-effectiveness of EPA plus statin (EPA+statin) combination therapy compared with statin monotherapy for primary and secondary prevention of cardiovascular disease (CVD) in Japan.

    Methods and Results:A Markov model was applied to assess the costs and benefits associated with EPA+statin combination therapy over a projected 30-year period from the perspective of a public healthcare funder in Japan. The incremental cost-effectiveness ratio (ICER), expressed as quality-adjusted life-years (QALY), was estimated for primary prevention and secondary prevention of CVD in patients with hypercholesterolemia. Impact on survival and number of events were based on the Japan EPA Lipid Intervention Study. Sensitivity analyses examined the influence of various input parameters on costs and outcomes of treatment. ICER was ¥29.6 million per QALY gained in primary prevention and ¥5.5 million per QALY gained in secondary prevention. The probabilities that EPA+statin combination therapy would be cost-effective compared with statin monotherapy were 39% in primary prevention and 49% in secondary prevention at a cost-effectiveness threshold of ¥5 million per QALY gained. Sensitivity analyses showed that EPA was cost-effective in secondary prevention.

    Conclusions:EPA+statin combination therapy showed acceptable cost-effectiveness for secondary prevention, but not primary prevention, of CVD in patients with hypercholesterolemia in Japan.

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  • Yukio Hiroi, Kensuke Noma, Hyung-Hwan Kim, Nikola Sladojevic, Corey E. ...
    Type: ORIGINAL ARTICLE
    Subject Area: Vascular Biology and Vascular Medicine
    Article ID: CJ-17-0732
    [Advance publication] Released: January 19, 2018
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    Background:Rho-associated kinases (ROCK1 and ROCK2) are important regulators of the actin cytoskeleton and endothelial nitric oxide synthase (eNOS). Because the phosphorylation of eukaryotic elongation factor-1A1 (eEF1A1) by ROCK2 is critical for eNOS expression, we hypothesized that this molecular pathway may play a critical role in neuroprotection following focal cerebral ischemia.

    Methods and Results:Adult male wild-type (WT) and mutant ROCK2 and eNOS−/−mice were subjected to middle cerebral artery occlusion (MCAO), and cerebral infarct size, neurological deficit and absolute cerebral blood flow were measured. In addition, aortic endothelium-dependent response to acetylcholine, NG-nitro-L-arginine methyl ester (L-NAME) and sodium nitroprusside were assessed ex vivo. Endothelial cells from mouse brain or heart were used to measure eNOS and eEF1A activity, as well as NO production and eNOS mRNA half-life. In global hemizygous ROCK2+/−and endothelial-specific EC-ROCK2−/−mice, eNOS mRNA stability and eNOS expression were increased, which correlated with enhanced endothelium-dependent relaxation and neuroprotection following focal cerebral ischemia. Indeed, when ROCK2+/−mice were place on an eNOS−/−background, the neuroprotective effects observed in ROCK2+/−mice were abolished.

    Conclusions:These findings indicate that the phosphorylation of eEF1A1 by ROCK2 is physiologically important for eNOS expression and NO-mediated neuroprotection, and suggest that targeting endothelial ROCK2 and eEF1A may have therapeutic benefits in ischemic stroke and cardiovascular disease.

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  • Takashi Kido, Takayoshi Ueno, Masaki Taira, Hideto Ozawa, Koichi Toda, ...
    Type: ORIGINAL ARTICLE
    Subject Area: Pediatric Cardiology and Adult Congenital Heart Disease
    Article ID: CJ-17-1088
    [Advance publication] Released: January 19, 2018
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    Background:This study aimed to identify the clinical predictors of the degree of right ventricular (RV) myocardial fibrosis in patients with repaired tetralogy of Fallot (TOF) with special focus on the RV pressure load.

    Methods and Results:From April 2004 to March 2017, 30 patients with repaired TOF underwent pulmonary valve replacement and concomitant RV myocardial biopsy. The stroke volume ratio (RV stroke volume/left ventricular stroke volume), RV end-diastolic volume index, and right-to-left ventricular systolic pressure ratio were evaluated with respect to their prognostic value for the degree of RV myocardial fibrosis. Significant positive linear correlations were detected between the stroke volume ratio and the degree of RV myocardial fibrosis (P=0.003, r=0.52). Patients with a right-to-left ventricular systolic pressure ratio >0.45 showed a significantly greater degree of RV myocardial fibrosis under an equivalent stroke volume ratio.

    Conclusions:Under conditions of RV volume overload, a right-to-left ventricular systolic pressure ratio >0.45 was a predisposing factor for progression of RV myocardial fibrosis in patients with repaired TOF.

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  • Brent A. Williams, Shikhar Agarwal
    Type: ORIGINAL ARTICLE
    Subject Area: Heart Failure
    Article ID: CJ-17-0670
    [Advance publication] Released: January 18, 2018
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    Background:Prediction models such as the Seattle Heart Failure Model (SHFM) can help guide management of heart failure (HF) patients, but the SHFM has not been validated in the office environment. This retrospective cohort study assessed the predictive performance of the SHFM among patients with new or pre-existing HF in the context of an office visit.

    Methods and Results:SHFM elements were ascertained through electronic medical records at an office visit. The primary outcome was all-cause mortality. A “warranty period” for the baseline SHFM risk estimate was sought by examining predictive performance over time through a series of landmark analyses. Discrimination and calibration were estimated according to the proposed warranty period. Low- and high-risk thresholds were proposed based on the distribution of SHFM estimates. Among 26,851 HF patients, 14,380 (54%) died over a mean 4.7-year follow-up period. The SHFM lost predictive performance over time, with C=0.69 and C<0.65 within 3 and beyond 12 months from baseline respectively. The diminishing predictive value was attributed to modifiable SHFM elements. Discrimination (C=0.66) and calibration for 12-month mortality were acceptable. A low-risk threshold of ∼5% mortality risk within 12 months reflects the 10% of HF patients in the office setting with the lowest risk.

    Conclusions:The SHFM has utility in the office environment.

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  • Pierre Abraham, Christophe Colas-Ribas, Isabelle Signolet, Myriam Ammi ...
    Type: ORIGINAL ARTICLE
    Subject Area: Peripheral Vascular Disease
    Article ID: CJ-17-0948
    [Advance publication] Released: January 18, 2018
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    Background:Exercise transcutaneous oximetry (Ex-tcPO2) is used to argue for the vascular origin of lower limb pain, especially at the proximal level, where the diagnosis of peripheral artery disease can be difficult. This study analyzed the principal indications, mean results, and limitations of Ex-tcPO2, as well as the relationship between the annual number of Ex-tcPO2 tests and internal iliac artery (IIA) revascularizations.

    Methods and Results:Data from our first 15 years’ experience (3,631 patients, 5,080 tests) with Ex-tcPO2 were analyzed retrospectively using the minimal value of the decrease from rest of oxygen pressure (DROPmin). We had 99.7% of expected DROPminresults. The proportion of tests showing isolated proximal unilateral or bilateral ischemia ranged from ~5% to ~20%. A gradual increase with time was observed in both the annual number of Ex-tcPO2 tests (from 0 to ~500 per year) and the annual number of IIA revascularizations performed (from 0 up to 18 per year). At least 85% of patients (77/91) showed function improvement after IIA revascularization.

    Conclusions:Ex-tcPO2 (using DROPmin) provides an objective argument for exercise-induced ischemia, bilaterally at the distal and/or proximal level. Using Ex-tcPO2 has improved our diagnostic performance and markedly changed our therapeutic decisions, specifically for proximal claudication. The increased number of Ex-tcPO2 tests is associated with an increased number of IIA revascularizations, although a causal relationship was not proven.

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  • Akiomi Yoshihisa
    Type: EDITORIAL
    Article ID: CJ-17-1362
    [Advance publication] Released: January 17, 2018
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  • Hiroki Emori, Takashi Kubo, Takeyoshi Kameyama, Yasushi Ino, Yoshiki M ...
    Type: ORIGINAL ARTICLE
    Subject Area: Ischemic Heart Disease
    Article ID: CJ-17-0949
    [Advance publication] Released: January 16, 2018
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    Background:A novel index of the functional severity of coronary stenosis, quantitative flow ratio (QFR), may not consider the amount of viable myocardium in prior myocardial infarction (MI) because QFR is calculated from 3D quantitative coronary angiography.

    Methods and Results:We analyzed QFR (fixed-flow QFR [fQFR] and contrast-flow QFR [cQFR]) and fractional flow reserve (FFR) in prior-MI-related coronary arteries (n=75) and non-prior-MI-related coronary arteries (n=75). Both fQFR and cQFR directly correlated with FFR in the prior-MI-related coronary arteries (fQFR: r=0.84, P<0.001; and cQFR: r=0.88, P<0.001) and the non-prior-MI-related coronary arteries (fQFR: r=0.91, P<0.001; and cQFR: r=0.94, P<0.001). fQFR was significantly smaller than FFR in the prior-MI-related coronary arteries (0.73±0.14 vs. 0.79±0.11, P=0.002), but there was no significant difference between fQFR and FFR in the non-prior-MI-related coronary arteries. The value of cQFR minus FFR was significantly lower in the prior-MI-related coronary arteries compared with the non-prior-MI-related coronary arteries (−0.02±0.06 vs. 0.00±0.04, P=0.010). The diagnostic accuracy of fQFR ≤0.8 and cQFR ≤0.8 for predicting FFR ≤0.80 was numerically lower in the prior-MI-related coronary arteries compared with the non-prior-MI-related coronary arteries (fQFR: 77% vs. 87%; and cQFR: 87% vs. 92%).

    Conclusions:When FFR is used as the gold standard, the accuracy of QFR for assessing the functional severity of coronary stenosis might be reduced in the prior-MI-related coronary arteries compared with non-prior-MI-related coronary arteries.

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  • Toru Kubo, Takayoshi Hirota, Yuichi Baba, Yuri Ochi, Asa Takahashi, Na ...
    Type: ORIGINAL ARTICLE
    Subject Area: Myocardial Disease
    Article ID: CJ-17-0845
    [Advance publication] Released: January 13, 2018
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    Background:There have been few studies on the clinical course of hypertrophic cardiomyopathy (HCM) in a community-based patient cohort in Japan.

    Methods and Results:In 2004, we established a cardiomyopathy registration network in Kochi Prefecture (the Kochi RYOMA study) that consisted of 9 hospitals, and finally, 293 patients with HCM were followed. The ages at registration and at diagnosis were 63±14 and 56±16 years, respectively, and 197 patients (67%) were male. HCM-related deaths occurred in 23 patients during a mean follow-up period of 6.1±3.2 years. The HCM-related 5-year survival rate was 94%. In addition, a total of 77 cardiovascular events that were clinically severe occurred in 70 patients, and the HCM-related 5-year event-free rate was 80%. Multivariate Cox proportional hazards model analysis showed that the presence of NYHA class III at registration was a significant predictor of HCM-related deaths and that the presence of atrial fibrillation, lower fractional shortening and presence of left ventricular outflow tract obstruction in addition to NYHA class III were significant predictors of cardiovascular events.

    Conclusions:In our unselected registry in an aged Japanese community, HCM mortality was favorable, but one-fifth of the patients commonly suffered from HCM-related adverse cardiovascular events during the 5-year follow-up period. Careful management of HCM patients is needed, particularly for those with the above-mentioned clinical determinants.

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  • Jun Negishi, Hideo Ohuchi, Aya Miyazaki, Etsuko Tsuda, Isao Shiraishi, ...
    Type: ORIGINAL ARTICLE
    Subject Area: Pediatric Cardiology and Adult Congenital Heart Disease
    Article ID: CJ-17-0801
    [Advance publication] Released: December 29, 2017
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    Background:Heart failure (HF) is an important complication in adults with congenital heart disease (CHD), but because only a few studies have focused on acute HF hospitalization in adults with CHD, we study aimed to define the clinical characteristics of such patients and examine the differences in acute HF between adults with CHD and acquired heart disease.

    Methods and Results:We retrospectively evaluated 50 adults with CHD admitted for treatment of acute HF and compared their data with those from Japanese HF registries. Patient mean age was 37±15 years and 58% were male. In total, 86% of the patients had complex forms of CHD and 62% had undergone corrective surgery, including the Fontan procedure; 66% of patients showed right heart hemodynamic abnormality. In-hospital mortality was 4%, which was comparable to the Japanese HF registries. Survival rate was 93% at 1 year and 75% at 3 years, which was similarly poor to the rates of HF secondary to acquired heart disease.

    Conclusions:We clarified the clinical characteristics of adults with CHD requiring HF hospitalization. Young adults with complex CHD were hospitalized for management of acute right HF. Short-term and mid-term outcomes were similarly poor compared with acute HF secondary to acquired heart disease.

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  • Mike Saji, Ryosuke Higuchi, Tetsuya Tobaru, Nobuo Iguchi, Shuichiro Ta ...
    Type: ORIGINAL ARTICLE
    Subject Area: Valvular Heart Disease
    Article ID: CJ-17-0816
    [Advance publication] Released: December 29, 2017
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    Background:Various frailty markers have been developed to guide better patient selection for transcatheter aortic valve implantation (TAVI). This study aimed to investigate the frequency and specific causes of unplanned hospital readmission after TAVI, and to investigate which frailty markers better predicted outcomes.

    Methods and Results:We retrospectively reviewed 155 patients for whom we calculated their Short Physical-Performance Battery (SPPB), Placement of AoRTic TraNscathetER Valve (PARTNER) frailty scale, frailty index, clinical frailty scale, modified Fried scale, and gait speed. The primary endpoint was unplanned readmission following TAVI. The clinical model was established using variables that were identified as independent predictors in multivariate analysis. Incremental values were assessed after adding each frailty marker to the clinical model, and were compared between frailty markers. Although unplanned readmission <30 days was 1.9%, 23% of patients had an unplanned readmission following TAVI mainly because of heart failure and pneumonia within 1 year. Frailty markers other than the modified Fried scale were independently associated with unplanned readmission. The SPPB and the PARTNER frailty scale significantly increased discriminatory performance for predicting unplanned readmission.

    Conclusions:Unplanned readmissions following TAVI in the present study were fewer than previously reported. There seems to be a difference between frailty markers in their predictive performance. Precise frailty assessment may result in reducing unplanned admissions after TAVI and therefore better quality of life.

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  • Masahiro Nakabachi, Satoshi Yamada, Hiroyuki Iwano, Taichi Hayashi, Ka ...
    Type: ORIGINAL ARTICLE
    Subject Area: Heart Failure
    Article ID: CJ-17-1019
    [Advance publication] Released: December 29, 2017
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    Background:Early-diastolic mitral annular velocity (e′) and the ratio of early-diastolic left ventricular (LV) inflow velocity (E) to e′ (E/e′) have been widely used as indexes of LV relaxation and filling pressure, respectively. However, many recent studies have demonstrated that they are not reliable in various clinical settings. We thus investigated the factors influencing these echocardiographic parameters in a multicenter study.

    Methods and Results:The study group comprised 69 patients, referred for cardiac catheterization, and enrolled in 5 university hospitals. Time constant (τ) and LV mean diastolic pressure (LVMDP) were measured using a micromanometer-tipped catheter. Although e′ only weakly correlated with τ (r=−0.35, P<0.01), E/e′ modestly correlated with LVMDP (r=0.48, P<0.001). Multivariable analysis revealed that hypertension (β=−0.33, P<0.01) and LV ejection fraction (LVEF) (β=0.44, P<0.001) were the independent determinants of e′, and LV mass index (LVMI) (β=0.37, P<0.001) and LVMDP (β=0.47, P<0.001) were those of E/e′. Additionally, E/e′ significantly correlated with LVMDP in patients with normal LVMI (r=0.74, P<0.001) but not in those with increased LVMI.

    Conclusions:The coincidence of hypertension and LVEF affected the relationship between LV relaxation and e′, whereas LVMI altered the relationship between LV filling pressure and E/e′. Thus, clinical conditions associated with an increase in LVMI, such as LV hypertrophy and LV dilatation, should be considered when estimating the filling pressure from E/e′.

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  • Altayyeb Yousef, Zachary MacDonald, Trevor Simard, Juan J. Russo, Josh ...
    Type: ORIGINAL ARTICLE
    Subject Area: Valvular Heart Disease
    Article ID: CJ-17-0672
    [Advance publication] Released: December 28, 2017
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    Background:Transcatheter aortic valve implantation (TAVI) has become the standard of care for management of high-risk patients with aortic stenosis. Limited data is available regarding the performance of TAVI in patients with native aortic valve regurgitation (NAVR).

    Methods and Results:We performed a systematic review from 2002 to 2016. The primary outcome was device success as per VARC-2 criteria. Secondary endpoints included procedural complications, and 30-day and 1-year mortality rates. A total of 175 patients were included from 31 studies. Device success was reported in 86.3% of patients – with device failure driven by moderate aortic regurgitation (AR ≥3+) and/or need for a second device. Procedural complications were rare, with no procedural deaths, myocardial infarctions or annular ruptures reported. Procedural safety was acceptable with a low 30-day incidence of stroke (1.5%). The 30-day and 1-year overall mortality rates were 9.6% and 20.0% (cardiovascular death, 3.8% and 10.1%, respectively). Patients receiving 2nd-generation valves demonstrated similar safety profiles with greater device success compared with 1st-generation valves (96.2% vs. 78.4%). This was driven by the higher incidence of second-valve implantation (23.4% vs. 1.7%) and significant paravalvular leak (8.3% vs. 0.0%).

    Conclusions:TAVI demonstrates acceptable safety and efficacy in high-risk patients with severe NAVR. Second-generation valves may afford a similar safety profile with improved device success. Dedicated studies are needed to definitively establish the efficacy of TAVI in this population.

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  • Bruno Reissmann, Michael Schlüter, Francesco Santoro, Tilman Maurer, C ...
    Type: ORIGINAL ARTICLE
    Subject Area: Arrhythmia/Electrophysiology
    Article ID: CJ-17-0956
    [Advance publication] Released: December 27, 2017
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    Background:Real-time recording of pulmonary vein isolation (PVI) using a circular mapping catheter has become a key aspect of cryoballoon (CB) ablation. The aim of this study was to investigate the procedural safety, efficacy and rate of real-time pulmonary vein (PV) recording using a novel circular mapping catheter with a 25-mm loop size for CB-based PVI.

    Methods and Results:A total of 40 patients with symptomatic atrial fibrillation (AF) underwent PVI using a second-generation CB and a novel 25-mm circular mapping catheter. A total of 159 PV were identified and successfully isolated. Real-time PV recording was achieved in 80% of the PV. In 3 right inferior PV the circular mapping catheter had to be exchanged for a stiff guidewire due to insufficient mechanical support. Therefore, acute PVI using exclusively the circular mapping catheter was achieved in 156/159 PV (98%). Mean procedure and fluoroscopy times were 66±21 min and 15±6 min, respectively. Transient phrenic nerve palsy occurred in 1 patient as the only procedural complication.

    Conclusions:The exclusive use of a novel 25-mm circular mapping catheter for CB ablation of AF results in a real-time PV recording rate of 80% and isolation of 98% of targeted PV.

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  • Keitaro Senoo, Yusuke Kondo, Yoshio Kobayashi, Gregory YH Lip
    Type: ORIGINAL ARTICLE
    Subject Area: Arrhythmia/Electrophysiology
    Article ID: CJ-17-1164
    [Advance publication] Released: December 27, 2017
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    Background:Atrial fibrillation (AF) is the most common arrhythmia in the ageing population in East Asia. Silent cerebral infarction (SCI) is defined as cerebral infarction in the absence of corresponding clinical symptoms, and is a highly prevalent and morbid condition in AF. SCI is increasingly being recognized as a risk factor for future stroke, which can lead to cognitive decline or dementia. The latter is an increasingly common health problem in East Asia.

    Methods and Results:We conducted a meta-analysis to compare the association of AF and SCI between East Asian and non-Asian patients. AF was associated with SCI in patients with no symptomatic stroke history (relative risk [RR], 2.24; 95% CI: 1.26–3.99, I2=83%; P=0.006) although the prevalence varied widely between studies (P for heterogeneity<0.001). In non-Asian patients, the prevalence of SCI in AF is higher than that in controls (RR, 1.85; 95% CI: 1.65–2.08, I2=17%; P<0.001). There was no significant racial difference between Asian and non-Asian studies (P=0.53).

    Conclusions:In East Asia, AF was significantly associated with SCI and no racial difference was seen between East Asian and non-Asian patients. The present findings offer clinicians new insights into the association between AF and SCI.

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  • Saurabh P. Nagar, Pratik P. Rane, Kathleen M. Fox, Juliana Meyers, Kei ...
    Type: ORIGINAL ARTICLE
    Subject Area: Epidemiology
    Article ID: CJ-17-0811
    [Advance publication] Released: December 23, 2017
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    Background:This study examined treatment patterns, possible statin intolerance, and incidence of cardiovascular events (CVEs) in 2 cohorts of patients with high cardiovascular risk (i.e., patients with atherosclerotic cardiovascular disease [ASCVD] and patients with diabetes mellitus).

    Methods and Results:A retrospective cohort study examined adults initiating either a statin or ezetimibe from 1 January 2006 to 31 May 2014 in the Japan Medical Data Center database. The first observed statin or ezetimibe prescription defined the index date. Patients had ≥12 months of pre- and post-index date plan enrollment. Two high-risk cohorts, the ASCVD cohort and diabetes cohort, were created based on diagnoses observed during the 12 months’ pre-index date. Treatment patterns, possible statin intolerance, and incidence of CVEs were reported. In the ASCVD cohort (n=5,302), 32.9% discontinued therapy, 7.7% switched to a non-index statin or non-statin lipid-lowering therapy, and 11.2% augmented index therapy in the 12 months’ post-index date; only 0.3% were using high-intensity statins and 10% had possible statin intolerance. Also, 8.1% had any new CVE during the follow-up period. Treatment patterns and incidence of CVEs among the diabetes cohort were similar to those of the ASCVD cohort.

    Conclusions:High cardiovascular risk Japanese patients had frequent treatment modifications, although use of high-intensity statin doses was rare. These patterns may indicate that alternative therapies for lipid lowering are needed.

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  • Thibault Ronchard, Nicolas Combaret, Guilhem Malcles, Pascal Motreff, ...
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-17-0985
    [Advance publication] Released: December 23, 2017
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  • Naoya Kurata, Osamu Iida, Tatsuya Shiraki, Masashi Fujita, Masaharu Ma ...
    Type: ORIGINAL ARTICLE
    Subject Area: Peripheral Vascular Disease
    Article ID: CJ-17-0726
    [Advance publication] Released: December 21, 2017
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    Background:Although stent-to-vessel (S/V) diameter ratio has been described as a restenotic factor after superficial femoral artery (SFA) stenting, the reference vessel diameter is commonly measured distally at a healthy site. It remains unclear whether S/V ratio assessed at the lesion site would be more predictive than that assessed distally at a healthy site.

    Methods and Results:A total of 117 patients (mean age, 73±7 years; 74% male) who underwent successful nitinol stent implantation in SFA lesions (mean lesion length, 172±104 mm) on intravascular ultrasound (IVUS) were retrospectively analyzed. S/V ratio at the proximal and distal healthy site, and at the smallest lesion site, was evaluated on IVUS. One-year restenosis predictors were evaluated on multivariate analysis. Mean S/V diameter ratio on IVUS at proximal and distal healthy sites, and at the lesion site, was 0.98±0.11, 1.02±0.11 and 1.15±0.16, respectively. One-year primary patency was 77%. On multivariate analysis, lesion length (OR, 1.06 per 10-mm increment; P=0.046) and S/V ratio measured at the lesion site (OR, 1.34 per 0.1 increment; P=0.032), but not that at the distal healthy site (OR, 1.05 per 0.1 increment; P=0.705), were significantly associated with 1-year restenosis.

    Conclusions:S/V ratio assessed on IVUS at the lesion site, but not at the distal healthy site, was independently associated with 1-year restenosis after SFA stenting.

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  • Yuki Sakamoto, Seiji Okubo, Chikako Nito, Satoshi Suda, Noriko Matsumo ...
    Type: ORIGINAL ARTICLE
    Subject Area: Stroke
    Article ID: CJ-17-1110
    [Advance publication] Released: December 21, 2017
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    Background:Insufficient anticoagulant intensity on admission is common in stroke patients with atrial fibrillation (AF) on vitamin K antagonist (VKA) therapy. Nevertheless, the effects of VKA under-treatment on stroke severity or arterial occlusion are not well known. The aim of the present study was to investigate the relationship between insufficient VKA therapy and stroke severity, or the site of arterial occlusion in patients with acute ischemic stroke (AIS) and AF.

    Methods and Results:From March 2011 through July 2016, 446 consecutive patients with AF and AIS were recruited. Of the 446 patients, 364 (167 women; median age, 79 years; IQR, 71–86 years) with anterior-circulation stroke were assessed to investigate the effects of insufficient VKA. Of these, 281 were on no anticoagulant, 53 were undertreated with a VKA, and 30 were sufficiently treated with VKA on admission (PT-INR ≥2.0 for patients <70 years and PT-INR ≥1.6 for ≥70 years old). On multivariate analysis, insufficient VKA was independently associated with severe stroke (i.e., initial NIHSS score ≥10; OR, 2.70, P=0.022) and higher prevalence of proximal artery occlusion (OR, 1.91; P=0.039) compared with no anticoagulant therapy.

    Conclusions:Insufficient VKA therapy on admission was associated with higher severity of stroke and higher prevalence of proximal artery occlusion in patients with AF and acute anterior-circulation stroke compared with no anticoagulant medication.

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  • Masanobu Ohya, Takeshi Morimoto, Shunsuke Kubo, Seiji Habara, Akimune ...
    Type: ORIGINAL ARTICLE
    Subject Area: Ischemic Heart Disease
    Article ID: CJ-17-1092
    [Advance publication] Released: December 19, 2017
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    Background:Data on outcomes of non-left main coronary bifurcation lesions treated with the 2-stent strategy using 2nd-generation drug-eluting stents (DES) are insufficient.

    Methods and Results:The 2-year outcomes and predictors of target lesion revascularization (TLR) in 356 patients with 364 non-left main coronary bifurcation lesions treated with the 2-stent strategy using 2nd-generation DES were retrospectively evaluated. The primary outcome measure was defined as TLR. The median follow-up duration was 3.6 years (interquartile range, 2.7–4.9 years). A 2-year clinical follow-up was achieved in 99.2%. The 2-year cumulative incidence of TLR was 9.2%. Multiple stents implanted in either the main branch (adjusted odds ratio [OR] 3.01; 95% confidence interval [CI]: 1.37–6.62; P=0.006) or the side branch (adjusted OR 4.55; 95% CI: 1.99–10.4; P<0.001) and the culprit in the left anterior descending artery and its diagonal branch (adjusted OR 0.33; 95% CI: 0.15–0.75: P=0.008) were independent predictors of TLR within 2 years.

    Conclusions:The 2-year outcomes for the 2-stent strategy using 2nd-generation DES in non-left main coronary bifurcation lesions were acceptable. Coronary bifurcation location in the left anterior descending artery and its diagonal branch is protective against TLR, whereas multiple stents implanted in either the main branch or the side branch was associated with TLR.

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  • Naoki Masaki, Yuriko Saiki, Masato Endo, Kay Maeda, Osamu Adachi, Masa ...
    Type: ORIGINAL ARTICLE
    Subject Area: Cardiovascular Surgery
    Article ID: CJ-17-0379
    [Advance publication] Released: December 16, 2017
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    Background:Histomorphometric evidence of the effect of pulmonary artery banding (PAB) in infancy on pulmonary vascular reverse remodeling has not been fully described.

    Methods and Results:We retrospectively reviewed 34 patients who underwent serial lung biopsies before and after PAB.Index of pulmonary vascular disease (IPVD) as a measure of the degree of progression of pulmonary arteriopathy significantly decreased after PAB (1.22±0.25 at 1st and 1.13±0.21 at 2nd biopsy, P=0.04). Additionally,DR=100 µmas an indicator of medial thickness of pulmonary arteries significantly decreased after PAB (15.6±3.7 at 1st and 11.4±2.6 at 2nd biopsy, P<0.0001). Patients were divided into 3 groups by age at PAB: <3 months (Group 1), between 3 and 6 months (Group 2), and >6 months (Group 3). The average secondDR=100 µmof groups 1 and 2 was significantly lower than that of group 3 (11.1±2.2 and 9.8±2.0 vs. 14.9±2.8, respectively; P<0.0001). Additionally, the second IPVD was also significantly lower in groups 1 and 2 than in group 3 (1.1±0.2 and 1.1±0.2 vs. 1.3±0.4, respectively; P=0.02).

    Conclusions:Histomorphometric evidence of post-PAB pulmonary vascular reverse remodeling is robust. The magnitude of vascular reversibility is pronounced when PAB is performed before 6 months of age.

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