Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Volume 79 , Issue 8
Showing 1-39 articles out of 39 articles from the selected issue
Message From the Editor-in-Chief
Reviews
  • Deepak K. Gupta, Thomas J. Wang
    Type: REVIEW
    2015 Volume 79 Issue 8 Pages 1647-1655
    Published: July 24, 2015
    Released: July 24, 2015
    [Advance publication] Released: June 23, 2015
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    Natriuretic peptides are cardiac-derived hormones with a range of protective functions, including natriuresis, diuresis, vasodilation, lusitropy, lipolysis, weight loss, and improved insulin sensitivity. Their actions are mediated through membrane-bound guanylyl cyclases that lead to production of the intracellular second-messenger cyclic guanosine monophosphate. A growing body of evidence demonstrates that genetic and acquired deficiencies of the natriuretic peptide system can promote hypertension, cardiac hypertrophy, obesity, diabetes mellitus, the metabolic syndrome, and heart failure. Clinically, natriuretic peptides are robust diagnostic and prognostic markers, and augmenting natriuretic peptides is a target for therapeutic strategies in cardiometabolic disease. This review will summarize current understanding and highlight novel aspects of natriuretic peptide biology. (Circ J 2015; 79: 1647–1655)
  • Amit K Mehrotra, David Callans
    Type: REVIEW
    2015 Volume 79 Issue 8 Pages 1656-1661
    Published: July 24, 2015
    Released: July 24, 2015
    [Advance publication] Released: July 02, 2015
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    Treatment for ventricular tachycardia (VT) generally includes 1 or more of the following options: antiarrhythmic therapy, an implantable cardioverter-defibrillator and/or catheter ablation. Catheter ablation is performed with an electroanatomic mapping system to define the heart’s 3D anatomy, as well as regions of scar. Radiofrequency energy is then applied to areas of abnormal substrate within which are located channels critical to the VT circuit. Cardiac magnetic resonance (CMR) imaging is a non-invasive modality that provides high-resolution images of cardiac structure and function. CMR has become a very useful tool for sudden cardiac death risk stratification and to facilitate successful radiofrequency ablation of VT in patients with abnormal cardiac substrate. The role of CMR in the management and treatment of VT in patients with structural heart disease is reviewed. (Circ J 2015; 79: 1656–1661)
  • Rachel R. Huxley, Yoichiro Hirakawa, Mohammad Akhtar Hussain, Wichai A ...
    Type: REVIEW
    2015 Volume 79 Issue 8 Pages 1662-1674
    Published: July 24, 2015
    Released: July 24, 2015
    [Advance publication] Released: July 07, 2015
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    Cardiovascular disease (CVD) is the leading cause of mortality worldwide, causing an estimated 18 million deaths annually. Much of the burden of CVD resides in lower- and middle-income countries, particularly those Asian countries comprising the Western Pacific Region. Epidemiological studies have convincingly shown that up to 90% of all CVD can be explained by a small number of modifiable risk factors, including blood pressure, smoking, diabetes, total cholesterol and excess body weight. However, the relationship between these risk factors and coronary artery disease and stroke often differ by age and sex, and yet these differences are often overlooked in burden of disease estimations. As such, that can result in either an over- or under-estimation of the disease burden in specific population subgroups, which may affect resource allocation of healthcare. In this review, we derive the most reliable and previously unpublished estimates of the age- and sex-specific burden of vascular disease attributable to the aforementioned risk factors for 10 of the most populous Asian countries in the Western Pacific Region. Understanding how the burden of vascular disease is distributed within and between populations is crucial for developing appropriate health policies and effective treatment strategies, particularly in resource-poor settings. (Circ J 2015; 79: 1662–1674)
2015 JCS Report
  • Seiji Hokimoto, Satoshi Yasuda, Daisuke Sueta, Kenichi Tsujita, Kenji ...
    Type: 2015 JCS REPORT
    2015 Volume 79 Issue 8 Pages 1675-1679
    Published: July 24, 2015
    Released: July 24, 2015
    [Advance publication] Released: July 03, 2015
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    The 79thAnnual Scientific Meeting of the Japanese Circulation Society was held in Osaka on April 24–26, 2015. The main theme was “Late-breaking Cardiovascular Medicine from Japan”. Recently, optimal medical treatment has been guided by evidence-based medicine. We aim to emphasize the research findings and advances in cardiology from Japan, in the hope that Japan will become one of the leaders in the field worldwide. Unlike previous meetings, this annual scientific meeting was held in late April. Approximately 18,000 people, including medical doctors, healthcare professionals, and management staff, attended. The meeting was successfully completed, and included discussions on state-of-the art medicine. (Circ J 2015; 79: 1675–1679)
Editorials
Original Articles
Aortic Disease
  • Kiyohito Yamamoto, Kimihiro Komori, Hiroshi Banno, Hiroshi Narita, Aki ...
    Type: ORIGINAL ARTICLE
    Subject area: Aortic Disease
    2015 Volume 79 Issue 8 Pages 1699-1705
    Published: July 24, 2015
    Released: July 24, 2015
    [Advance publication] Released: May 26, 2015
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    Background:To validate the criteria for endovascular aneurysm repair (EVAR) or open repair of abdominal aortic aneurysm (AAA) at Nagoya University Hospital, the results of both treatments were retrospectively compared.Methods and Results:Patient selection for EVAR was primarily based on suitable anatomy, minimum age 75 years, and significant comorbidity. From June 2007 to April 2014, 426 patients were treated via EVAR (EVAR group) and 346 patients were treated with open surgery (OS group). The mortality rates of the EVAR and OS groups were not significantly different (0.2% vs. 1.1%; P=0.33). Patient age, operation time, amount of bleeding, and duration of hospital stay were significantly lower in the EVAR group compared with the OS group. The incidence of comorbidity was higher in the EVAR group compared with the OS group. The incidence of early postoperative complications was significantly higher in the OS group, whereas the incidence of late complications for both groups was similar. The cumulative aneurysm-related survival rates were similar (98.9% vs. 98.5%; P=0.767). The cumulative survival rates and reintervention-free rates at 5 years were lower for the EVAR group (76% vs. 89%, P=0.019; 81% vs. 89%, P=0.046).Conclusions:Patient selection practices and criteria for EVAR and open repair at Nagoya University Hospital are generally acceptable. (Circ J 2015; 79: 1699–1705)
Arrhythmia/Electrophysiology
  • Hideyuki Kishima, Takanao Mine, Kenki Ashida, Masataka Sugahara, Takes ...
    Type: ORIGINAL ARTICLE
    Subject area: Arrhythmia/Electrophysiology
    2015 Volume 79 Issue 8 Pages 1706-1711
    Published: July 24, 2015
    Released: July 24, 2015
    [Advance publication] Released: May 09, 2015
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    Background:The shape of the left atrial appendage (LAA) might affect thrombus formation. The chicken wing-type LAA (CW) has been reported as unlikely to influence stroke events in atrial fibrillation (AF) patients, so we investigated whether LAA shapes could influence LAA function.Methods and Results:We studied 102 patients (64 men, age 65±9 years) who underwent transthoracic echocardiography, transesophageal echocardiography (TEE), and cardiac computed tomography prior to catheter ablation (CA) for AF. LAA morphology were classified into 2 types: (1) CW: LAA with a bend in its shape and (2) non-CW type (NCW): LAA without any bends. All patients were classified into these groups using a cutoff value of LAA flow velocity (LAAFV). Patients with LAAFV <35 cm/s were classified as the low LAAFV group (Low FV, n=37). The patients with LAAFV >35 cm/s were classified as normal LAAFV group (Normal FV, n=65). The NCW type was detected in 25/102 patients (25%). In multivariate analysis, the patients with Low FV were associated with NCW type (P=0.0429, odds ratio [OR] 9.664, 95% confidence interval [CI] 1.075–86.900) and higher B-type natriuretic peptide (BNP) (P=0.0350, OR 1.012 for each 1 pg/ml increase in BNP, 95% CI 1.001–1.022).Conclusions:The NCW-type LAA and higher BNP were associated with lower LAAFV. One reason for the frequent cardiogenic stroke in patients with the NCW-type LAA may be the lower LAAFV. (Circ J 2015; 79: 1706–1711)
  • Masato Okada, Kazunori Kashiwase, Akio Hirata, Takayoshi Nemoto, Koshi ...
    Type: ORIGINAL ARTICLE
    Subject area: Arrhythmia/Electrophysiology
    2015 Volume 79 Issue 8 Pages 1712-1718
    Published: July 24, 2015
    Released: July 24, 2015
    [Advance publication] Released: May 13, 2015
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    Background:Bacterial cultures of cardiovascular implantable electronic devices removed from patients without clinical infection are often positive, and the cultured bacteria are different from those at the time of clinical infection. This discrepancy has not been adequately explained. We hypothesized that the cause is bacterial contamination at operation and compared the results of bacterial cultures between patients with de novo pacemaker implantation and those with pacemaker replacement.Methods and Results:We prospectively enrolled consecutive 100 patients who underwent cardiac pacemaker implantation (49 de novo implantations, 51 replacements). We took swab cultures from inside the generator pocket (1) immediately after the creation of new pocket or removal of old generator, (2) after connection of leads to new generator, and (3) after pocket lavage. Swab cultures were positive in 272 (45%) of 600 samples. The majority of the cultured bacteria werePropionibacteriumspecies. No statistical difference was detected between de novo implantations and replacements in the positive ratio of swab cultures. The positive ratio was not correlated with the number of previous device replacements.Conclusions:The positive ratio of swab cultures was not different between new implantations and replacements, suggesting that a positive culture merely indicates contamination of bacteria during operation rather than colonization. (Circ J 2015; 79: 1712–1718)
  • Hirofumi Tomita, Ken Okumura, Hiroshi Inoue, Hirotsugu Atarashi, Takes ...
    Type: ORIGINAL ARTICLE
    Subject area: Arrhythmia/Electrophysiology
    2015 Volume 79 Issue 8 Pages 1719-1726
    Published: July 24, 2015
    Released: July 24, 2015
    [Advance publication] Released: May 13, 2015
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    Background:Because the current Japanese guideline recommends CHADS2score-based risk stratification in nonvalvular atrial fibrillation (NVAF) patients and does not list female sex as a risk for thromboembolic events, we designed the present study to compare the CHA2DS2-VASc and CHA2DS2-VA scores in the J-RHYTHM Registry.Methods and Results:We prospectively assessed the incidence of thromboembolic events for 2 years in 997 NVAF patients without warfarin treatment (age 68±12 years, 294 females). The predictive value of the CHA2DS2-VASc and CHA2DS2-VA scores for thromboembolic events was evaluated by c-statistic difference and net reclassification improvement (NRI). Thromboembolic events occurred in 7/294 females (1.2%/year) and 23/703 males (1.6%/year) (odds ratio 0.72 for female to male, 95% confidence interval (CI) 0.28–1.62, P=0.44). No sex difference was found in patient groups stratified by CHA2DS2-VASc and CHA2DS2-VA scores. There were significant c-statistic difference (0.029, Z=2.3, P=0.02) and NRI (0.11, 95% CI 0.01–0.20, P=0.02), with the CHA2DS2-VA score being superior to the CHA2DS2-VASc score. In patients with CHA2DS2-VASc scores 0 and 1 (n=374), there were markedly significant c-statistic difference (0.053, Z=6.6, P<0.0001) and NRI (0.11, 95% CI 0.07–0.14, P<0.0001), again supporting superiority of CHA2DS2-VA to CHA2DS2-VASc score.Conclusions:In Japanese NVAF patients, the CHA2DS2-VA score, a risk scoring system excluding female sex from CHA2DS2-VASc, may be more useful in risk stratification for thromboembolic events than CHA2DS2-VASc score, especially in identifying truly low-risk patients. (Circ J 2015; 79: 1719–1726)
  • Kunihiko Kiuchi, Katsunori Okajima, Naoko Tanaka, Yoko Yamamoto, Nahok ...
    Type: ORIGINAL ARTICLE
    Subject area: Arrhythmia/Electrophysiology
    2015 Volume 79 Issue 8 Pages 1727-1732
    Published: July 24, 2015
    Released: July 24, 2015
    [Advance publication] Released: May 20, 2015
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    Background:The incidence of hematoma formation following implantation of a cardiovascular implantable electronic device (CIED) is estimated to be 5% even if a pressure dressing is applied. It is unclear whether a pressure dressing can really compress the pocket in different positions. Furthermore, the adhesive tape for fixing pressure dressings can tear the skin. We developed a new compression tool for preventing hematomas and skin erosions.Methods and Results:We divided 46 consecutive patients receiving anticoagulation therapy who underwent CIED implantation into 2 groups (Group I: conventional pressure dressing, Group II: new compression tool). The pressure on the pocket was measured in both the supine and standing positions. The incidence of hematomas was compared between the 2 groups. The pressure differed between the supine and standing positions in Group I, but not in Group II (Group I: 14.8±7.1 mmHg vs. 11.3±9.9 mmHg, P=0.013; Group II: 13.5±2.8 mmHg vs. 13.5±3.5 mmHg, P=0.99). The incidence of hematomas and skin erosions was documented in 2 (8.7%) and 3 (13%) Group I patients, respectively. No complications were documented in Group II.Conclusions:The new compression tool can provide adequate continuous pressure on the pocket, regardless of body position. This device may reduce the incidence of hematomas and skin erosions after CIED implantation. (Circ J 2015; 79: 1727–1732)
  • Yuko Wada, Takeshi Aiba, Taka-aki Matsuyama, Ikutaro Nakajima, Kohei I ...
    Type: ORIGINAL ARTICLE
    Subject area: Arrhythmia/Electrophysiology
    2015 Volume 79 Issue 8 Pages 1733-1741
    Published: July 24, 2015
    Released: July 24, 2015
    [Advance publication] Released: May 27, 2015
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    Background:The natural history of hypertrophic cardiomyopathy (HCM) varies from an asymptomatic benign course to a poor prognosis. Myocardial fibrosis may play a critical role in ventricular tachyarrhythmias (VT/VF); however, the clinical significance of tissue fibrosis by right ventricular (RV) biopsy in the long-term prognosis of HCM patients remains unclear.Methods and Results:We enrolled 185 HCM patients (mean age, 57±14 years). The amount of fibrosis (%area) was quantified using a digital microscope. Hemodynamic, echocardiographic, and electrophysiologic parameters were also evaluated. Patients with severe fibrosis had longer QRS duration and positive late potential (LP) on signal-averaged ECG, resulting in a higher incidence of VT/VF. At the 5±4 year follow-up, VT/VF occurred in 31 (17%) patients. Multivariate Cox regression analysis revealed that tissue fibrosis (hazard ratio (HR): 1.65; P=0.003 per 10% increase), lower left ventricular ejection fraction (HR: 0.64; P=0.001 per 10% increase), and positive SAECG (HR: 3.14; P=0.04) led to a greater risk of VT/VF. The combination of tissue fibrosis severity and lower left ventricular ejection fraction could be used to stratify the risk of lethal arrhythmic events in HCM patients.Conclusions:Myocardial fibrosis in RV biopsy samples may contribute to abnormal conduction delay and spontaneous VT/VF, leading to a poor prognosis in HCM patients. (Circ J 2015; 79: 1733–1741)
  • Masatoshi Miyamura, Shu-ichi Fujita, Hideaki Morita, Kazushi Sakane, Y ...
    Type: ORIGINAL ARTICLE
    Subject area: Arrhythmia/Electrophysiology
    2015 Volume 79 Issue 8 Pages 1742-1748
    Published: July 24, 2015
    Released: July 24, 2015
    [Advance publication] Released: May 27, 2015
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    Background:Atrial fibrillation (AF) occurs more frequently among patients with renal dysfunction. We investigated the possible association between prevalence of AF and serum fibroblast growth factor 23 (FGF23), which has been shown to be increased in subjects with renal dysfunction.Methods and Results:Among the total enrollment of 851 cardiac patients, 188 patients had AF (paroxysmal AF, 95; non-paroxysmal AF, 93). Prevalence of AF for FGF23 octile had a U-shaped relationship with the lowest prevalence at the fifth octile. On logistic regression analysis, when the third FGF23 quartile was used as the reference, the first and fourth FGF23 quartiles were associated with prevalence of AF with an odds ratio (OR) of 3.34 (95% confidence interval [CI]: 1.89–5.88) and 2.58 (95% CI: 1.45–4.58), respectively, after adjusting for confounding factors including estimated glomerular filtration rate (eGFR). Among the subgroup of 416 patients for whom serum parathyroid hormone and 25-hydroxy vitamin D data were available, OR of the first and the fourth FGF23 quartile were calculated to be 3.52 and 2.97, respectively, when further adjusted for these two variables in the statistical model.Conclusions:Serum FGF23 had a U-shaped relationship with prevalence of AF among Japanese cardiac patients, which was independent of other calcium/phosphate metabolism-related parameters and eGFR. Pathophysiology underlying the observed link, if at all, awaits further investigation. (Circ J 2015; 79: 1742–1748)
Heart Failure
  • Mami Enomoto, Tomoko Ishizu, Yoshihiro Seo, Masayoshi Yamamoto, Hiroak ...
    Type: ORIGINAL ARTICLE
    Subject area: Heart Failure
    2015 Volume 79 Issue 8 Pages 1749-1755
    Published: July 24, 2015
    Released: July 24, 2015
    [Advance publication] Released: May 27, 2015
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    Background:It remains uncertain whether diabetes itself causes specific echocardiographic features of myocardial morphology and function in the absence of hypertension or ischemic heart disease. The purpose of the present study was to determine the characteristics of pure diabetic cardiomyopathy-related echocardiographic morphology and function using layer-by-layer evaluation with myocardial strain echocardiography.Methods and Results:We enrolled 104 patients with poorly controlled type 2 diabetes mellitus (mean HbA1c level, 10%) with (n=74) or without (n=40) hypertension and 24 age- and sex-matched healthy volunteers. Patients with coronary artery stenosis or structural heart disease were excluded. Myocardial layer-specific strain was analyzed by speckle tracking echocardiography. Compared with the healthy control group, the normotensive diabetes group showed no significant difference in ejection fraction, left ventricular mass index, diastolic properties, left atrial volume index, or B-type natriuretic protein (BNP) level, but global longitudinal strain and subendocardial radial strain were significantly deteriorated. The deterioration of longitudinal strain correlated with body mass index (R=0.49, P<0.01) and blood pressure (R=0.36, P<0.01) in the normotensive diabetes group.Conclusions:Deterioration of left ventricular longitudinal shortening accompanied by decreased subendocardial wall thickening are the characteristic functional abnormalities of diabetic cardiomyopathy in patients without hypertrophy, diastolic dysfunction, or elevated BNP. Obesity and blood pressure may also play important roles in this strain abnormality in asymptomatic patients with type 2 diabetes. (Circ J 2015; 79: 1749–1755)
  • Maria Teresa La Rovere, Roberto Maestri, Angelo Caporotondi, Daniela C ...
    Type: ORIGINAL ARTICLE
    Subject area: Heart Failure
    2015 Volume 79 Issue 8 Pages 1756-1763
    Published: July 24, 2015
    Released: July 24, 2015
    [Advance publication] Released: June 04, 2015
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    Background:We aimed to investigate whether the assessment of functional capacity by the 6-minute walking test (6MWT) might improve the predictive ability of 2 validated clinical scores for risk stratification in heart failure (HF).Methods and Results:The Cardiac and Comorbid Conditions HF (3C-HF) and the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) scores were evaluated in 466 consecutive HF patients who completed a pre-discharge 6MWT. The 12-month event rate was 7.7%. Both the 2 scores and the 6MWT predicted all-cause mortality (all P<0.0001), with a hazard ratio of 2.650 [95%CI 1.879–3.737], 2.754 [95%CI 1.870–4.056] for each one SD increase in the 3C-HF and MAGGIC, respectively, and of 2.080 [95% CI 1.619–2.671] for each one SD decrease in the meters walked. The addition of a 6MWT to both the 3C-HF and MAGGIC scores significantly improved predictive discrimination (c-index 0.793 [95% CI 0.722–0.864] and 0.802 [95% CI 0.733–0.871], respectively) and risk classification (integrated discrimination improvement, IDI 0.052 [95% CI 0.024–0.101] and 0.046 [95% CI 0.020–0.102], respectively). In the intermediate and high risk strata identified on the basis of both the 3C-HF and MAGGIC scores, mortality rates significantly differed according to a distance walked < or ≥376 m.Conclusions:In HF patients, a pre-discharge evaluation combining the 6MWT to clinical scores improves prediction of 12-month mortality. (Circ J 2015; 79: 1756–1763)
  • Masanobu Miura, Yasuhiko Sakata, Satoshi Miyata, Kotaro Nochioka, Tsuy ...
    Type: ORIGINAL ARTICLE
    Subject area: Heart Failure
    2015 Volume 79 Issue 8 Pages 1764-1772
    Published: July 24, 2015
    Released: July 24, 2015
    [Advance publication] Released: May 22, 2015
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    Background:It is unclear whether the prognostic impact of diabetes mellitus (DM) in chronic heart failure (CHF) is influenced by ischemic heart disease (IHD) and/or nephropathy.Methods and Results:We enrolled 4,065 consecutive patients with stage C/D CHF (mean age, 69.0 years; 68.7% male) in the CHART-2 Study (n=10,219). We defined DM as current history of DM treatment or HbA1c ≥6.5% (National Glycohemoglobin Standardization Program [NGSP]), and nephropathy as urine albumin:creatinine ratio ≥30 mg/g or urine dipstick test ≥(±) at enrollment. Impacts of DM and nephropathy on the composite of death, myocardial infarction, stroke, and HF admission were examined. Among the 4,065 patients, 1,448 (35.6%) had DM, while IHD and nephropathy were also noted in 1,644 (40.4%) and in 1,549 (38.1%), respectively. During the median follow-up of 2.88 years, 1,025 (25.2%) reached the composite endpoint. On multivariate Cox regression, DM was significantly associated with the composite endpoint in all patients (HR, 1.17; P=0.02), and in those with IHD (HR, 1.38; P=0.004), but not in those without IHD (HR, 1.12; P=0.22; P for interaction=0.12). Furthermore, when the patients were stratified by nephropathy, DM was associated with worse prognosis only in the IHD patients with nephropathy.Conclusions:The prognostic impact of DM was more evident in patients with IHD than in those without IHD, particularly when complicated with nephropathy. (Circ J 2015; 79: 1764–1772)
Imaging
  • Hiromu Yamazaki, Koji Yamaguchi, Takeshi Soeki, Tetsuzo Wakatsuki, Tos ...
    Type: ORIGINAL ARTICLE
    Subject area: Imaging
    2015 Volume 79 Issue 8 Pages 1773-1779
    Published: July 24, 2015
    Released: July 24, 2015
    [Advance publication] Released: May 12, 2015
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    Background:Uremic toxin has emerged as an important determinant of cardiovascular risk. The aim of this study was to examine the relationship between serum uremic toxin and coronary plaque composition on integrated backscatter intravascular ultrasound (IB-IVUS).Methods and Results:IB-IVUS was performed in 47 patients with planned treatment for angina pectoris. Non-culprit intermediate plaque analyzed in this study had to be >5 mm apart from the intervention site. 3-D IB-IVUS analysis was performed to determine percent lipid volume (LV) and fibrous volume (FV). We also measured serum uremic toxins (indoxyl sulfate [IS], asymmetric dimethylarginine [ADMA], and p-cresol [PC]). Glomerular filtration rate correlated with IS (r=–0.329, P=0.04), but did not correlate with ADMA or PC. Percent LV correlated with IS (r=0.365, P=0.02), but did not correlate with ADMA or PC. Percent FV also correlated with IS (r=–0.356, P=0.03), but did not correlate with ADMA or PC. On multivariate regression, only IS was associated with percent LV (r=0.359, P=0.04) and percent FV (r=–0.305, P=0.04) independently of potentially confounding coronary risk factors.Conclusions:Among the uremic toxins, serum IS might be a novel useful biomarker to detect and monitor lipid-rich coronary plaque on IB imaging. (Circ J 2015; 79: 1773–1779)
Ischemic Heart Disease
  • Seung Hwa Lee, Jeong Hoon Yang, Seung-Hyuk Choi, Young Bin Song, Joo-Y ...
    Type: ORIGINAL ARTICLE
    Subject area: Ischemic Heart Disease
    2015 Volume 79 Issue 8 Pages 1780-1786
    Published: July 24, 2015
    Released: July 24, 2015
    [Advance publication] Released: May 28, 2015
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    Background:Limited data are available on the clinical outcomes of medical therapy (MT) compared with revascularization in elderly patients with coronary chronic total occlusion (CTO).Methods and Results:Between March 2003 and February 2012, we retrospectively analyzed 311 patients aged ≥75 years in the Samsung Medical Center CTO registry. Among these, 153 patients were treated with MT and 158 patients with revascularization by intervention or surgery. Inverse probability of treatment weighting (IPTW) and propensity score-matching were performed. The primary outcome was cardiac death during follow-up. Median follow-up duration was 34 (interquartile range: 15–58) months. Overall, patients in the MT group were high-risk subjects. Cardiac death of 30 patients (19.6%) occurred in the MT group vs. 17 patients (10.8%) in revascularization group (P=0.027). In the multivariate analysis, there was no significant difference between groups in the rate of cardiac death (hazard ratio [HR], 1.67; 95% confidence interval [CI], 0.86–3.24, P=0.13). After adjustment with IPTW, MT showed comparable risk of cardiac death with revascularization therapy (HR, 1.26; 95% CI, 0.71–2.21, P=0.43). In the propensity score-matched population, there was no significant difference in the rate of cardiac death between the MT and revascularization groups (HR, 1.52; 95% CI, 0.76–3.07, P=0.24).Conclusions:In the treatment of CTO in elderly patients, MT alone did not increase the risk of long-term cardiac death when compared with aggressive revascularization treatment. (Circ J 2015; 79: 1780–1786)
  • Kensuke Nishimiya, Yasuharu Matsumoto, Tomohiko Shindo, Kenichiro Hana ...
    Type: ORIGINAL ARTICLE
    Subject area: Ischemic Heart Disease
    2015 Volume 79 Issue 8 Pages 1787-1798
    Published: July 24, 2015
    Released: July 24, 2015
    [Advance publication] Released: June 01, 2015
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    Background:The importance of adventitial inflammation has been implicated for the pathogenesis of coronary artery disease. However, the roles of adventitial changes in drug-eluting stent (DES)-induced coronary hyperconstriction remain largely unknown. In the present study, this issue in pigs in vivo with a special reference to adventitial vasa vasorum (VV) formation and Rho-kinase activation, a central mechanism of coronary vasospasm, was examined.Methods and Results:Each animal received a sirolimus-eluting stent (SES) and a biolimus A9-eluting stent (BES), one in the left anterior descending and another in the left circumflex coronary arteries in a randomized manner (n=18). After 1, 3 and 6 months, coronary vasomotion was examined. At 1 month, coronary vasoconstriction to serotonin was significantly enhanced at the SES edges as compared with the BES edges (SES, 52±7% vs. BES, 22±3%, P<0.01), which was equally prevented by a selective Rho-kinase inhibitor, hydroxyfasudil. A significant difference in vasoconstriction between SES and BES was sustained for 6 months. A micro-CT showed VV augmentation at the SES site, extending to the proximal and distal edges. Immunostainings demonstrated that VV formation, macrophage infiltration in the adventitia and Rho-kinase expressions/activation were significantly enhanced at the SES edges as compared with the BES edges.Conclusions:The DES with durable polymers enhances VV formation and inflammation in the adventitia, associating with the pathogenesis of DES-induced coronary hyperconstriction through Rho-kinase activation in pigs in vivo. (Circ J 2015; 79: 1787–1798)
Metabolic Disorder
  • Gyung-Min Park, Hyonggin An, Seung-Whan Lee, Young-Rak Cho, Eun Ha Gil ...
    Type: ORIGINAL ARTICLE
    Subject area: Metabolic Disorder
    2015 Volume 79 Issue 8 Pages 1799-1806
    Published: July 24, 2015
    Released: July 24, 2015
    [Advance publication] Released: May 08, 2015
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    Background:Little is known about subclinical atherosclerosis on coronary computed tomographic angiography (CCTA) in asymptomatic individuals with metabolic syndrome (MetS).Methods and Results:We analyzed 5,213 asymptomatic individuals who underwent CCTA. A cardiac event was defined as a composite of all-cause death, myocardial infarction, unstable angina, or coronary revascularization. Of the study participants, 2,042 (39.2%) had MetS. MetS was an independent predictor of significant coronary artery disease (CAD) in at least 1 coronary artery (odds ratio [OR]=1.992, 95% confidence interval [CI]=1.623–2.445, P<0.001) and significant CAD in the left main (LM) or proximal left anterior descending (LAD) artery (OR=2.151, 95% CI=1.523–3.037, P<0.001). During the follow-up period (median 28.1 [interquartile range, 19.2–36.5] months), 111 individuals had 114 cardiac events. Individuals with MetS were significantly associated with more cardiac events than those without (RR [rate ratio]=1.67, 95% CI=1.15–2.43, P=0.007). In the MetS group, individuals with significant CAD had the majority of cardiac events (RR=64.33, 95% CI=29.17–141.88, P<0.001). Furthermore, in the MetS with significant CAD group, those with significant CAD in the LM or proximal LAD had more cardiac events (RR=2.63, 95% CI=1.51–4.59, P=0.001).Conclusions:MetS was associated with subclinical atherosclerosis on CCTA with subsequent high risk for cardiac events. These findings suggest the importance of reducing unfavorable metabolic conditions in asymptomatic individuals. (Circ J 2015; 79: 1799–1806)
Molecular Cardiology
  • Hyewon Park, Chang-Myung Oh, Junbeom Park, Hyelim Park, Shanyu Cui, Hy ...
    Type: ORIGINAL ARTICLE
    Subject area: Molecular Cardiology
    2015 Volume 79 Issue 8 Pages 1807-1815
    Published: July 24, 2015
    Released: July 24, 2015
    [Advance publication] Released: May 15, 2015
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    Background:The serotonin receptor type 3 (Htr3) blocker is associated with QT prolongation and torsades de pointes. However, little is known about effects of Htr3 on the heart arrhythmia.Methods and Results:An electrophysiological study Involving knock-out (KO) female mice lacking functional Htr3a (Htr3a–/–) and their wild-type littermates during non-pregancy (NP) and late pregnancy (LP) was performed. Htr3a mRNA was present in the wild-type, but not in theHtr3a–/–mouse hearts. Serotonin and tryptophan hydroxylase 1 (Tph1), a rate-limiting enzyme of serotonin synthesis in hearts, is increased during pregnancy. The heart weight and size were increased in the pregnant mice regardless of a mutation. The QTc intervals were prolonged after pregnancy in both the wild (NP: 171.2±16.8 vs. LP: 247.7±14.3 ms; P<0.001) andHtr3a–/–mice (NP: 187.9±18.7 vs. LP: 275.6±11.0 ms, P<0.001). Compared with wild-type LP mice,Htr3a–/–LP mice had increased spontaneous ventricle tarchycardia (VT; 56% vs. 0%, P=0.002), VT inducibility (66% vs. 25%, P=0.002) and mortality (56% vs. 0%, P=0.002). Pharmacologic administration of serotonin and Htr3 agonists (m-CPBG) decreased the QT interval in wild mice, but not inHtr3a–/–mice.Conclusions:Htr3a is present in mouse hearts. Serotonin and Tph1 were increased during pregnancy. The deletion of Htr3a was related to fatal arrhythmias and sudden cardiac death during pregnancy, and its activation reversed the QT prolongation. (Circ J 2015; 79: 1807–1815)
Myocardial Disease
  • Kyoung-Min Park, Jihye Kim, Hayoung Na, Kwang Jin Chun, Sung Il Im, Se ...
    Type: ORIGINAL ARTICLE
    Subject area: Myocardial Disease
    2015 Volume 79 Issue 8 Pages 1816-1822
    Published: July 24, 2015
    Released: July 24, 2015
    [Advance publication] Released: May 09, 2015
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    Background:High ventricular premature depolarization (VPD) burden is associated with left ventricular (LV) dysfunction that typically resolves after successful ablation. Some patients, however, have persistent LV dysfunction, even after successful radiofrequency (RF) ablation. Identifying factors associated with irreversibility of LV cardiomyopathy (CMP) may help predict clinical outcome.Methods and Results:Patients with frequent VPD (>10%/day) who underwent successful VPD suppression were divided into 2 groups according to transthoracic echocardiography (TTE) before and after suppression: group A (n=38) had depressed LV function that normalized after VPD suppression; group B (n=19) had depressed LV function before and after suppression. Of 57 patients (43 men; mean age, 54±15 years), RF ablation was performed in 39. Clinical, electrocardiographic, and TTE parameters were compared between groups. LV end-diastolic dimension (LVEDD; group A vs. B: 54±5 mm vs. 60±10 mm, P=0.01), end-systolic dimension (group A vs. B: 42±6 mm vs. 48±11 mm, P=0.01) before VPD suppression differed significantly between groups. Pre-suppression LVEDD was ≤66 mm in all reversible-CMP patients. LVEDD >66 mm predicted irreversible CMP with 50% sensitivity, 100% specificity, 100% positive predictive value, and 81% negative predictive value.Conclusions:LVEDD was a good predictor of irreversible LV CMP with frequent VPD, with 50% sensitivity and 100% specificity. (Circ J 2015; 79: 1816–1822)
Pediatric Cardiology and Adult Congenital Heart Disease
  • Clara Kurishima, Ryo Inuzuka, Seiko Kuwata, Yoichi Iwamoto, Masaya Sug ...
    Type: ORIGINAL ARTICLE
    Subject area: Pediatric Cardiology and Adult Congenital Heart Disease
    2015 Volume 79 Issue 8 Pages 1823-1827
    Published: July 24, 2015
    Released: July 24, 2015
    [Advance publication] Released: May 20, 2015
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    Background:Although left ventricular (LV) stiffening with age is believed to increase left-to-right shunting in patients with atrial septal defects (ASD), clinical data have not confirmed this. We sought determinants of the pulmonary-to-systemic flow ratio (Qp/Qs) in patients with untreated ASD.Methods and Results:We retrospectively studied 180 patients with ASD who underwent percutaneous ASD closure between 2007 and 2011. Qp/Qs and LV stiffness were measured before ASD closure.The median age of the subjects was 18 years, and 117 (65.0%) were female. The mean ASD size adjusted for square root of body surface area (BSA) was 14.4±4.2 mm/m, and the Qp/Qs was 2.28±0.74. Adjusted ASD size most strongly related to Qp/Qs (r=0.74, P<0.0001). Multivariate analysis revealed that LV stiffness was a significant predictor of Qp/Qs, independently of adjusted ASD size and vascular resistance (P=0.0015). Based on the multivariate model that accounts for the effects of LV stiffness and vascular resistance, the minimal adjusted diameter that can cause a Qp/Qs of 2.0 was predicted to be 7.3 mm/m.Conclusions:Qp/Qs in ASD can change significantly depending on LV stiffness, suggesting that it would increase with age. An ASD >7.3 mm/m in diameter has the potential to cause significant left-to-right shunting, and may require closure regardless of hemodynamic status at the time of assessment. (Circ J 2015; 79: 1823–1827)
  • Daiji Takeuchi, Kei Honda, Tokuko Shinohara, Kei Inai, Keiko Toyohara, ...
    Type: ORIGINAL ARTICLE
    Subject area: Pediatric Cardiology and Adult Congenital Heart Disease
    2015 Volume 79 Issue 8 Pages 1828-1834
    Published: July 24, 2015
    Released: July 24, 2015
    [Advance publication] Released: May 27, 2015
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    Background:Although amiodarone (AMD)-induced thyroid dysfunction (AITD) is an important complication of AMD therapy, little is known about AITD in adult Japanese patients with congenital heart disease (CHD).Methods and Results:We retrospectively studied 131 adult patients with CHD who were on low-dose AMD (median, 150 mg/day). The median patient age was 28 years, and the median follow-up was 44 months. The incidence, clinical course, and risk factors of AITD, including AMD-induced thyrotoxicosis (AIT) and AMD-induced hypothyroidism (AIH), were evaluated. The total incidence of AITD was 30% (AIT: 18%, n=24; AIH: 12%, n=16). Approximately 67% of patients with AIT displayed deterioration of tachyarrhythmia, and 38% patients underwent steroid therapy. Although thyroid function and symptoms associated with AIT improved within 6 months after diagnosis in most patients with AIT (92%), 1 patient died suddenly during an acute phase of AIT. No patient with AIH exhibited deterioration of tachyarrhythmia, and 9 patients underwent thyroid hormone replacement therapy. Cox multivariate analysis identified no independent risk factor for AIT, whereas liver dysfunction (hazard ratio 2.573; 95% confidence interval 1.102–5.795) was an independent risk factor for AIH.Conclusions:AITD commonly occurred in adult Japanese patients with CHD even though they were on a low-dose AMD regimen. Risk factors for AITD may vary according to ethnicity and diet. (Circ J 2015; 79: 1828–1834)
Stroke
  • Junichi Hasegawa, Tomoaki Ikeda, Akihiko Sekizawa, Hiroaki Tanaka, Mas ...
    Type: ORIGINAL ARTICLE
    Subject area: Stroke
    2015 Volume 79 Issue 8 Pages 1835-1840
    Published: July 24, 2015
    Released: July 24, 2015
    [Advance publication] Released: May 26, 2015
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    Background:The aim of this study was to clarify the clinical features of maternal death due to stroke associated with pregnancy-induced hypertension (PIH) in Japan.Methods and Results:Reported maternal deaths occurring between 2010 and 2012 throughout Japan were analyzed by the Maternal Death Exploratory Committee. Among a total of 154 reports of maternal death, those due to stroke with (n=12) or without (n=13) PIH were compared. Cerebral stroke occurred more frequently in the third trimester and during the second stage of labor in deaths with PIH, whereas it occurred at any time point in deaths not involving PIH. Although 83% of patients with PIH who died had experienced initial symptoms in a hospital, more than half of them required maternal transport due to lack of medical resources. Among the patients without PIH, some vascular abnormalities were identified, but no evidence was found among the patients with PIH. In addition, 58% of PIH cases resulting in stroke were complicated by hemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome.Conclusions:Appropriate management of PIH during pregnancy and labor, including anti-hypertensive therapy and early maternal transport to tertiary hospital, may reduce the maternal death rate. (Circ J 2015; 79: 1835–1840)
  • Tsuyoshi Yoshimuta, Hiroyuki Yokoyama, Toshiya Okajima, Hiroshi Tanaka ...
    Type: ORIGINAL ARTICLE
    Subject area: Stroke
    2015 Volume 79 Issue 8 Pages 1841-1845
    Published: July 24, 2015
    Released: July 24, 2015
    [Advance publication] Released: May 21, 2015
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    Background:Plasma d-dimer is known to be a useful clinical marker of thrombogenic status, and d-dimer is used as a diagnostic marker for acute aortic dissection (AAD). Little is known, however, regarding the clinical value of d-dimer for diagnosis of asymptomatic AAD in patients with ischemic stroke. We investigated whether d-dimer could be used for early diagnosis of AAD with isolated neurological symptoms in ischemic stroke patients.Methods and Results:We evaluated a total of 1,236 consecutive patients with symptomatic ischemic stroke without chest or back pain who underwent either head computed tomography or magnetic resonance imaging. d-dimer was measured within 24 h after onset. There were 9 patients with Stanford type A AAD and they had significantly higher d-dimer than the patients without AAD (mean, 46.47±54.48 μg/ml; range, 6.9–167.1 μg/ml vs. 2.33±3.58 μg/ml, 0.3–57.9 μg/ml, P<0.001). When a cut-off of 6.9 μg/ml was adopted for d-dimer on the basis of receiver operating characteristics analysis, the sensitivity and specificity for AAD were 100% and 94.8%, respectively, while the positive and negative predictive values were 14.7% and 100%, respectively.Conclusions:d-dimer might be a useful marker for the early diagnosis of AAD with isolated neurological symptoms in ischemic stroke patients. Whole-body contrast-enhanced computed tomography should be performed in ischemic stroke patients who have high d-dimer. (Circ J 2015; 79: 1841–1845)
Vascular Biology and Vascular Medicine
  • Maja Colic, Suzana Pantovic, Marija Jeremic, Vuk Jokovic, Zdravko Obra ...
    Type: ORIGINAL ARTICLE
    Subject area: Vascular Biology and Vascular Medicine
    2015 Volume 79 Issue 8 Pages 1846-1852
    Published: July 24, 2015
    Released: July 24, 2015
    [Advance publication] Released: May 20, 2015
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    Background:Atherosclerosis is a chronic fibroproliferative disease that includes accumulation of cholesterol-rich lipids in the arterial wall. Though numerous studies have investigated atherosclerosis, not enough is known about the exact mechanisms of low-density lipoprotein (LDL) transport into the blood vessel wall. Therefore, we explored the 125I-LDL transport into the arterial wall under constant perfusion flow and pressure as well as the influence of duration of atherogenic diet on 125I-LDL transport and biomechanical properties of carotid artery.Methods and Results:The isolated segment of rabbit carotid artery was used under constant perfusion flow and pressure-induced (0 mmHg and 140 mmHg) blood vessel distension, with the possibility to change and precisely calculate shear stress during the experiment. Obtained results indicate the influence of atherogenic diet duration and consequent variation of shear stress on 125I-LDL transport into the blood vessel wall. 125I-LDL transport into the blood vessel wall at low pressure-induced blood vessel distension decreases by the increase of the shear stress and in relation to the atherogenic diet duration. At high pressure-induced blood vessel distension, 125I-LDL transport increases in relation to the atherogenic diet duration and the increase of shear stress.Conclusions:The influence of shear stress is a more dominant parameter on LDL uptake at low pressure-induced blood vessel distension; however, the atherogenic diet duration has more of a dominant influence on LDL uptake at high pressure-induced vessel distension. (Circ J 2015; 79: 1846–1852)
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