Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Volume 77 , Issue 11
Showing 1-38 articles out of 38 articles from the selected issue
Reviews
  • – Differences and Similarities to Adult Disease –
    Tsutomu Saji
    2013 Volume 77 Issue 11 Pages 2639-2650
    Published: 2013
    Released: October 25, 2013
    [Advance publication] Released: October 22, 2013
    JOURNALS FREE ACCESS
    Children and adults with pulmonary arterial hypertension (PAH) have similarities and differences in their background characteristics, hemodynamics, and clinical manifestations. Regarding genetic background, mutations in BMPR2-related pathways seem to be pivotal; however, it is likely that other modifier genes and bioactive mediators have roles in the various forms of PAH in children and adults. In pediatric PAH, there are no clear sex differences in incidence, age at onset, disease severity, or prognosis but, as compared with adults, syncope incidence, pulmonary vascular resistance, and mean pulmonary artery pressure are higher, and vasoreactivity to acute drug testing is more frequent, among children. Nevertheless, the pharmacokinetic effects of 3 major pulmonary vasodilators appear to be similar in children and adults with PAH. This review focuses on the specific pathophysiologic features of PAH in children.  (Circ J 2013; 77: 2639–2650)
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  • – Novel HDL-Directed Pharmacological Intervention and Exercise –
    Bo Zhang, Emi Kawachi, Shin-ichiro Miura, Yoshinari Uehara, Akira Mats ...
    2013 Volume 77 Issue 11 Pages 2651-2663
    Published: 2013
    Released: October 25, 2013
    [Advance publication] Released: October 10, 2013
    JOURNALS FREE ACCESS
    High-density lipoprotein (HDL) and low-density lipoprotein (LDL) particles transport cholesterol in plasma and play an important role in cellular cholesterol homeostasis, which influences cell function. The risk of coronary artery disease (CAD) associated with high levels of LDL-cholesterol (LDL-C) can be reduced by treatment with statins, which reduce LDL-C levels by inhibiting cellular cholesterol synthesis. However, patients who are treated with high doses of statins, especially secondary CAD prevention, regardless of their resulting LDL-C levels, are still at high risk of CAD. Therefore, there has been growing interest in HDL-directed therapies. Inhibitors of cholesteryl ester transfer protein (CETP) substantially increase HDL-C levels (by 31–138%). However, it is still unclear whether or not CETP inhibitors can reduce the risk of CAD associated with low HDL-C levels, while reconstituted HDL or apolipoprotein A-I mimetic peptides increase the functionality of HDL. Low levels of HDL-C are often complicated with metabolic disorders, including hypertriglyceridemia, metabolic syndrome, and type 2 diabetes mellitus, and lifestyle changes are effective for correcting these conditions. Physical activity and exercise training increase HDL-C levels, especially HDL2-C levels, by multiple mechanisms. Therefore, although using HDL-directed therapies that increase HDL-C levels and/or improve the function of HDL is a reasonable approach for reducing the residual risk of CAD as a complement to LDL-C-lowering therapy, lifestyle modifications including exercise to improve metabolic disorders should be considered as the first option.  (Circ J 2013; 77: 2651–2663)
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  • Wai San Cheang, Xi Fang, Xiao Yu Tian
    2013 Volume 77 Issue 11 Pages 2664-2671
    Published: 2013
    Released: October 25, 2013
    [Advance publication] Released: October 10, 2013
    JOURNALS FREE ACCESS
    Peroxisome proliferator-activated receptors gamma (PPARγ) and delta (PPARδ) are nuclear receptors that have significant physiological effects on glucose and lipid metabolism. Experimental studies in animal models of metabolic disease have demonstrated their effects on improving lipid profile, insulin sensitivity, and reducing inflammatory responses. PPARγ and -δ are also expressed in the vasculature and their beneficial effects have been examined in various cardiovascular disease models such as atherosclerosis, hypertension, diabetic vascular complications, etc. using pharmacological ligands or genetic tools including viral vectors and transgenic mice. These studies suggest that PPARγ and δ are antiinflammatory, antiatherogenic, antioxidant, and antifibrotic against vascular diseases. Several signaling pathways, effector molecules, as well as coactivators/repressors have been identified as responsible for the protective effects of PPARγ and -δ in the vasculature. We discuss the pleiotropic effect of PPARγ and δ in vascular dysfunction, including atherosclerosis, hypertension, vascular remodeling, vascular injury, and diabetic vasculopathy, in various animal models, and the major underlying mechanisms. We also compare the phenotypes of several endothelial cell/vascular smooth muscle-specific PPARγ and -δ knockout and overexpressing transgenic mice in various disease models, and the implications underlying the functional importance of vascular PPARγ and δ in regulating whole-body homeostasis.  (Circ J 2013; 77: 2664–2671)
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  • – Review of Long-Term Complications –
    Lauren Lastinger, Ali N. Zaidi
    2013 Volume 77 Issue 11 Pages 2672-2681
    Published: 2013
    Released: October 25, 2013
    [Advance publication] Released: October 22, 2013
    JOURNALS FREE ACCESS
    The univentricular heart includes a spectrum of complex cardiac defects that are managed by staged palliative surgical procedures, ultimately resulting in a Fontan procedure. Since 1971, when it was first developed, the procedure has undergone several variations. These patients require lifelong management, including a thorough knowledge of their anatomic substrate, hemodynamic status, management of rhythm and ventricular function, together with multi-organ evaluation. As these patients enter middle age, there is increasing awareness of long-term complications and mortality. This review highlights the concept behind the staged surgical palliations, the unique single ventricle physiology and the long-term complications in this complex cohort of patients.  (Circ J 2013; 77: 2672–2681)
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  • Koichiro Kuwahara
    2013 Volume 77 Issue 11 Pages 2682-2686
    Published: 2013
    Released: October 25, 2013
    [Advance publication] Released: October 12, 2013
    JOURNALS FREE ACCESS
    Alterations in the cardiac gene program affect both cardiac structure and function, and play a key role in the progression of pathological cardiac remodeling and heart failure. For instance, reactivation of fetal cardiac genes in adults is a consistent feature of cardiac hypertrophy and heart failure. Investigation of the transcriptional regulation of cardiac genes revealed a transcriptional repressor, neuron-restrictive silencer factor (NRSF), also called repressor element-1 silencing factor (REST), to be an important regulator of multiple fetal cardiac genes. Inhibition of NRSF in the heart leads to cardiac dysfunction and sudden arrhythmic death accompanied by re-expression of various fetal genes, including those encoding fetal ion channels, such as the HCN channels and T-type Ca2+ channels. These findings shed light on the crucial regulatory function of NRSF in the heart and its importance for maintaining normal cardiac integrity.  (Circ J 2013; 77: 2682–2686)
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2013 ESC Report
  • Yasuharu Matsumoto
    2013 Volume 77 Issue 11 Pages 2687-2690
    Published: 2013
    Released: October 25, 2013
    [Advance publication] Released: October 08, 2013
    JOURNALS FREE ACCESS
    The Annual Congress of the European Society of Cardiology (ESC) was held in Amsterdam from the 31st of August to the 4th of September 2013. The total attendance up to the 3rd was 29,990. Several important topics were presented and discussed, including a randomized trial of preventive angioplasty in myocardial infarction (PRAMI), transcatheter aortic valve implantation, renal denervation, management of vasospastic angina, plaque vulnerability and outcome assessed by OCT and diuretic resistance in heart failure (an ESC-JCS [Japanese Circulation Society] joint session), and OCT-guided percutaneous coronary intervention. The ESC congress has become one of the most important and attractive international scientific meetings. Importantly, Japan topped the number of abstracts submitted (1,459 abstracts) and accepted (565 abstracts) to ESC 2013. Thus, the ESC is eager to continue the strong collaboration with the JCS as the relationship between them gets closer year by year.  (Circ J 2013; 77: 2687–2690)
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Editorials
Original Articles
Arrhythmia/Electrophysiology
  • – Japanese HOME-ICD Study –
    Eiichi Watanabe, Atsunobu Kasai, Eitarou Fujii, Kohei Yamashiro, Pedro ...
    2013 Volume 77 Issue 11 Pages 2704-2711
    Published: 2013
    Released: October 25, 2013
    [Advance publication] Released: July 30, 2013
    JOURNALS FREE ACCESS
    Supplementary material
    Background: Remote monitoring (RM) technology has emerged as a potentially efficient method to manage patients with implantable cardioverter defibrillators (ICDs) or cardiac resynchronization therapy defibrillators (CRT-Ds). This study evaluated the reliability of daily RM in forecasting the need for regular in-hospital follow-ups (RFUs). Methods and Results: Two hundred and fifteen patients implanted with Biotronik Lumax devices (142 ICDs, 73 CRT-Ds) were enrolled. RFU was performed at 3, 6, 9, and 12 months after implantation. Immediately before an RFU, the physician forecasted the need for RFU based on RM data (pre-RFU assessment). A completed RFU session was classified as necessary if an action was undertaken potentially influencing patient safety, device therapy, or medication therapy (post-RFU assessment). Overall, 663 pairs of pre- and post-RFU assessments were compared. The number of pre-RFU assessments failing to predict the need for RFU was 38 (5.7%), fulfilling the study hypothesis of 5.0±4.0% (P<0.002; 95% confidence interval: 4.1–7.8%). Judged by an independent committee, the rate of false pre-RFU forecasts with high clinical relevance was 2 (0.3%). RM correctly forecasted non-necessity of 498 scheduled RFUs (75.1%). Patient acceptance of RM was evaluated using a targeted questionnaire. Of 182 interviewed patients, 172 (94.5%) felt security and comfort. Conclusions: RM-based forecasts appear sufficiently accurate to safely individualize RFU. Most patients have a positive attitude towards RM.  (Circ J 2013; 77: 2704–2711)
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  • Shih-Hung Hsiao, Kuan-Rau Chiou
    2013 Volume 77 Issue 11 Pages 2712-2721
    Published: 2013
    Released: October 25, 2013
    [Advance publication] Released: July 26, 2013
    JOURNALS FREE ACCESS
    Supplementary material
    Background: The left atrial (LA) expansion index for predicting atrial fibrillation (AF) in a relatively low-risk cohort is not fully understood. Methods and Results: In this prospective study of 2,200 dypnea patients, the LA expansion index was calculated as (Volmax–Volmin)×100%/Volmin, where Volmax was defined as maximum LA volume and Volmin was defined as minimum volume. The endpoints were 2-year frequency of AF, including both paroxysmal and persistent. Of the 180 participants (8.2%) who had AF attacks over a median follow-up of 2.7 years, 90 (4.1%) had at least 1 episode of persistent AF. Compared to patients with paroxysmal AF, those with persistent AF had a much lower LA expansion index (100±59% vs. 44±24%). LA expansion index was associated exponentially with the incidence of persistent AF. Independent predictors of AF included age, renal function impairment, pulmonary artery systolic pressure, and LA expansion index. Persistent AF, however, had significant independent associations only with prior heart failure, renal function impairment, diastolic dysfunction, and LA expansion index (odds ratio, 0.970; 95% confidence interval: 0.959–0.981 per 1% increase, P<0.0001). Compared to other parameters, LA expansion index <61.4% was the best cut-off point to predict persistent AF. Conclusions: The LA expansion index is associated with the presence of AF, and a reduced LA expansion index has a strong association with persistent AF.  (Circ J 2013; 77: 2712–2721)
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  • Takashi Uchiyama, Shinsuke Miyazaki, Hiroshi Taniguchi, Yuki Komatsu, ...
    2013 Volume 77 Issue 11 Pages 2722-2727
    Published: 2013
    Released: October 25, 2013
    [Advance publication] Released: August 08, 2013
    JOURNALS FREE ACCESS
    Background: Although pulmonary vein (PV) antrum isolation is an established therapy for drug-resistant paroxysmal atrial fibrillation (PAF), long-term (>5 years) follow-up data are limited. This study investigated long-term clinical outcome of catheter ablation. Methods and Results: From September 2003 to August 2006, 161 patients (mean age, 60±9 years; 119 male) with symptomatic drug-refractory PAF who underwent extensive encircling PV isolation (EEPVI) with a double Lasso technique were included. Right-sided and left-sided circular lesions encircling the ipsilateral PVs were created. The procedure endpoint was electrical isolation of the PV antrum. Patients with recurrent atrial tachyarrhythmia (ATa) had their previous lesions assessed and consolidated. Trigger ablation was added if necessary. EEPVI was successfully performed at the initial procedure. During a median follow-up of 6.4 years (25th–75th percentile, 5.8–7.1 years), 86 patients (53.4%) had recurrent ATa. Among 78, 15 and 4 patients undergoing 2nd, 3rd and 4th procedures, PV reconnections were observed in 68, 10 and 2, respectively. During a median follow-up of 6.0 years (25th–75th percentile, 5.2–6.9 years) after a mean of 1.6±0.7 procedures per patient, 144 patients (89.4%) were free from ATa. No progression toward persistent AF was observed in any patients. Conclusions: The vast majority of drug-resistant PAF could be controlled by EEPVI without an additional atrial substrate modification. No progression toward persistent AF was observed during a median follow-up of 6 years.  (Circ J 2013; 77: 2722–2727)
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  • Shin Hibino, Norihiro Ueda, Mitsuru Horiba, Kenji Yasui, Yuusuke Kagam ...
    2013 Volume 77 Issue 11 Pages 2728-2735
    Published: 2013
    Released: October 25, 2013
    [Advance publication] Released: August 28, 2013
    JOURNALS FREE ACCESS
    Background: To establish a simple and accurate method for the automated identification of the end of a T wave, we approximated electrocardiograph (ECG) traces using a Gaussian mixture model in conjunction with a split-and-merge expectation-maximization algorithm. Methods and Results: A total of 286 ECG traces of heart beats of 50 healthy men were used as control data and ECGs from 15 subjects recorded before and after 400mg oral moxifloxacin as positive controls. An experienced cardiologist determined the reference points by visual inspection of the original ECGs. The primary estimated point for the end of the T wave was selected as the point 2ms before the point at which the gradient of the approximated wave was not steeper than the common threshold value. This point was then adjusted by applying modification rules proposed by an experienced cardiologist. The absolute value of the average interval between the resulting final estimated point and the manually selected reference point was 1.8±7.7ms for the control data. After treatment with moxifloxacin, the average QT interval, corrected by Bazett’s formula, showed a 17.2±27.1ms prolongation with a lower bound of the 95% confidence interval of 4.9ms. Conclusions: When the modification rules were applied, the accuracy of QT measurement was improved, and the present system was capable of detecting QT prolongation correctly.  (Circ J 2013; 77: 2728–2735)
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Cardiac Rehabilitation
  • Hiroaki Tanaka, Takuro Matsuda, Takuro Tobina, Yousuke Yamada, Tamihar ...
    2013 Volume 77 Issue 11 Pages 2736-2741
    Published: 2013
    Released: October 25, 2013
    [Advance publication] Released: September 03, 2013
    JOURNALS FREE ACCESS
    Supplementary material
    Background: The double product (DP) breakpoint of heart rate (HR) and systolic blood pressure has been identified as coincident with anaerobic threshold (AT), but there are no simple methods for measuring cardiac metabolic stress (CMS) during an exercise test. It was hypothesized that the DP of HR and the amplitude of the first heart sound (AHS1) (DP-AHS1) would reflect CMS, and thus, the breakpoint in the DP-AHS1 (DPBP-AHS1) could be an alternative method for determining AT. Methods and Results: Subjects (age range, 18–73 years) were recruited to perform a graded exercise test on a cycle ergometer with continuous monitoring of DP-AHS1, with left ventricular pressure (LVP; experiment 1, Ex1), plasma catecholamine and blood lactate (experiment 2, Ex2) and gas exchange (experiment 3, Ex3). Ex1: in all subjects there was a strong correlation between AHS1 and LVdP/dtmax (r=0.94–0.98), and between the DP-AHS1 and the triple product of HR, LVdP/dtmax, and max LVP (r=0.98–0.99). Ex2: DP-AHS1 was strongly correlated with adrenaline (r=0.97–1.00) and lactate (r=0.96–1.00) levels in all subjects. Ex3: there was a strong correlation between DPBP-AHS1, AT and maximum oxygen consumption. Conclusions: The present simple measure of DP-AHS1 can reflect plasma adrenaline and lactate levels during graded exercise testing. Further, DPBP-AHS1 is a surrogate marker of AT and a good index of functional aerobic capacity.  (Circ J 2013; 77: 2736–2741)
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Critical Care
  • – Nationwide Observational Study –
    Japanese Circulation Society Resuscitation Science Study Group
    2013 Volume 77 Issue 11 Pages 2742-2750
    Published: 2013
    Released: October 25, 2013
    [Advance publication] Released: August 08, 2013
    JOURNALS FREE ACCESS
    Background: The compression-to-ventilation ratio for basic cardiopulmonary resuscitation (CPR) was changed from 15:2 to 30:2, but there are few human studies comparing chest-compression-only CPR with standard CPR. Methods and Results: From the All-Japan Utstein Registry in the 30:2 CPR era, 173,565 adult cardiac arrests witnessed by bystanders were included. On arrival at the scene, emergency medical services responders assessed the status of dispatcher-assisted CPR instruction and bystander CPR technique (chest compression with or without rescue breathing). The primary endpoint was favorable neurological outcome 30 days after cardiac arrest. The prevalence of dispatcher-assisted CPR instruction increased year by year, contributing to an overall increase of chest-compression-only bystander CPR from 20.6% to 35.0%. Among 78,150 patients receiving bystander CPR, favorable neurological outcome did not differ between dispatcher-assisted and -unassisted CPR (adjusted odds ratio [OR], 1.00; 95% confidence interval [CI]: 0.94–1.08). Chest-compression-only CPR resulted in better favorable neurological outcome than standard CPR in the whole cohort (adjusted OR, 1.09; 95% CI: 1.00–1.18) and in the subgroup with cardiac etiology (adjusted OR, 1.12; 95% CI: 1.02–1.22). The addition of rescue breathing provided no neurological benefit in the non-cardiac etiology subgroup. Conclusions: In the 30:2 CPR era, dispatcher-assisted CPR instruction contributed to an increase of chest-compression-only bystander CPR, supporting the use of chest-compression-only CPR for bystander-witnessed out-of-hospital cardiac arrest in all adults.  (Circ J 2013; 77: 2742–2750)
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Heart Failure
  • Toshihiko Yamamoto, Masayuki Shimano, Yasuya Inden, Shinjiro Miyata, Y ...
    2013 Volume 77 Issue 11 Pages 2751-2756
    Published: 2013
    Released: October 25, 2013
    [Advance publication] Released: August 02, 2013
    JOURNALS FREE ACCESS
    Supplementary material
    Background: Cardiac resynchronization therapy (CRT) has been reported to improve symptoms and cardiac performance in patients with severe heart failure (HF), but CRT recipients with advanced HF do not always experience improved mortality rates. Cystatin C has recently been involved in HF, but the association of serum cystatin C level with adverse events and long-term prognosis after CRT is unknown. This study investigated whether cystatin C level can predict mortality and cardiovascular events after CRT. Methods and Results: A total of 117 consecutive patients receiving a CRT device for the treatment of advanced HF were assessed according to cystatin C level and long-term outcome after implantation of the device. Over a median follow-up of 3.2 years, 34 patients (29.1%) died and 59 patients (50.4%) developed cardiovascular events. Kaplan-Meier survival analysis indicated that elevated cystatin C level was significantly associated with higher all-cause mortality and prevalence of cardiovascular events, including hospitalization for progressive HF. After multivariate Cox regression analysis, serum cystatin C level and QRS duration, but not conventional echocardiographic parameters, were found to independently predict all-cause death or cardiovascular events. Of importance, only cystatin C level was an independent predictor of all-cause mortality after CRT. Conclusions: Cystatin C level independently predicts cardiac mortality or morbidity in patients receiving CRT. The assessment of cystatin C level could provide valuable information about long-term prognosis after CRT.  (Circ J 2013; 77: 2751–2756)
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  • Hiroyuki Iwano, Satoshi Yamada, Masaya Watanabe, Hirofumi Mitsuyama, K ...
    2013 Volume 77 Issue 11 Pages 2757-2765
    Published: 2013
    Released: October 25, 2013
    [Advance publication] Released: August 08, 2013
    JOURNALS FREE ACCESS
    Supplementary material
    Background: We previously reported that the strain rate dispersion index (SRDI), an index of left ventricular (LV) contractility loss because of mechanical dyssynchrony, better predicted the acute response to cardiac resynchronization therapy (CRT) than time-delay indices. However, it remains unclear whether the SRDI can predict the chronic response. Additionally, the SRDI needs to be simplified for use in clinical practice. Methods and Results: Echocardiography was performed in 40 heart failure patients who underwent CRT. The SRDI, the average of segmental peak systolic strain rates minus global peak systolic strain rate, was calculated, together with strain-derived time-delay indices (St-SD) in the longitudinal, circumferential and radial directions using a speckle-tracking method. As simplified indices, the longitudinal parameters were calculated from the apical 4-chamber view in addition to 3 apical views. LV end-systolic volume (ESV) significantly decreased 6 months after CRT. Although circumferential St-SD and all SRDIs correlated with the changes in ESV (ΔESV), multivariate analysis revealed that the circumferential SRDI was the single independent determinant of ΔESV. During the 20±14 months after CRT, cardiac events occurred in 14 patients. Kaplan-Meier analyses revealed that all SRDIs were significant predictors of cardiac events whereas none of St-SDs was. Conclusions: The SRDI predicted the reduction in both LV volume and cardiac events after CRT better than time-delay indices. Additionally, a simplified SRDI could be as good a predictor of CRT response as the original.  (Circ J 2013; 77: 2757–2765)
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  • Tomoya Ueda, Rika Kawakami, Manabu Horii, Yu Sugawara, Takaki Matsumot ...
    2013 Volume 77 Issue 11 Pages 2766-2771
    Published: 2013
    Released: October 25, 2013
    [Advance publication] Released: August 24, 2013
    JOURNALS FREE ACCESS
    Background: Accumulating evidence suggests that hematopoiesis, especially erythropoiesis, is disturbed in heart failure (HF) for many reasons. Low hemoglobin and red blood cell distribution width have emerged as prognostic indicators of HF independent of classic predictors. The prognostic implication of mean corpuscular volume (MCV) in HF, however, is unknown. In this context, we investigated the relationship between MCV and prognosis of acute decompensated HF (ADHF). Methods and Results: This retrospective cohort study consisted of 458 consecutive patients with ADHF who had emergency admission to hospital. Patients were divided into 2 groups: MCV ≤100fl (non-macrocytic group, n=400); and MCV >100fl (macrocytic group, n=58). The relationship between MCV and all-cause death was tested using Cox proportional hazard models, adjusting for other predictors. Mean patient age was 72.4 years and mean MCV was 93.0±7.1fl. Hemoglobin was significantly lower in the macrocytic group than the non-macrocytic group. During the mean follow-up of 20.8 months, a total of 173 deaths (37.9%) occurred. Kaplan-Meier analysis showed that all-cause death was significantly higher in the macrocytic group (log-rank P<0.0001). Cox proportional hazards analysis indicated that macrocytosis was an independent predictor of all-cause death (hazard ratio, 2.288; 95% confidence interval: 1.390–3.643; P=0.0015) after adjustment in the multivariate model. Conclusions: It is proposed for the first time that MCV is an independent predictor of all-cause death in patients with ADHF.  (Circ J 2013; 77: 2766–2771)
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Imaging
  • Hirokazu Tanaka, Taishiro Chikamori, Satoshi Hida, Yuko Igarashi, Chie ...
    2013 Volume 77 Issue 11 Pages 2772-2777
    Published: 2013
    Released: October 25, 2013
    [Advance publication] Released: August 01, 2013
    JOURNALS FREE ACCESS
    Background: Although the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score is used to characterize coronary anatomy based on 9 anatomic criteria such as lesion location and complexity, the relationship between SYNTAX score and myocardial ischemia has yet to be elucidated. Methods and Results: A total of 158 consecutive patients with suspected or known coronary artery disease (CAD), who underwent both 99mTc-sestamibi single-photon emission computed tomography (SPECT) and coronary angiography, were evaluated. Stress SPECT was assessed using a 17-segment model, and the percentage of the myocardial defect scores (DS) was calculated. In 37 patients with intermediate-high SYNTAX scores (>22), the number of men and the prevalence of multi-vessel CAD were significantly higher, and the % stress and ischemic DS were significantly greater than in 121 patients with low SYNTAX scores (≤22). Coronary risk factors, however, were similar between the 2 groups. The % stress and ischemic DS significantly correlated with SYNTAX score. In patients with a low SYNTAX score, % stress and ischemic DS also significantly correlated with the SYNTAX score, whereas no such correlation was observed in the intermediate-high SYNTAX score group. Conclusions: SYNTAX score correlated well with myocardial ischemia as assessed on stress SPECT in general. The higher the SYNTAX score, however, the less clear was the correlation with the extent of myocardial ischemia.  (Circ J 2013; 77: 2772–2777)
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Ischemic Heart Disease
  • – Results From the Nagoya Acute Myocardial Infarction Study (NAMIS) –
    Yasuhiro Morita, Kengo Maeda, Takahisa Kondo, Hideki Ishii, Kyoko Mats ...
    2013 Volume 77 Issue 11 Pages 2778-2785
    Published: 2013
    Released: October 25, 2013
    [Advance publication] Released: August 06, 2013
    JOURNALS FREE ACCESS
    Supplementary material
    Background: Low adiponectin levels and high leptin levels are associated with a high incidence of developing cardiovascular disease. However, the relationship between the levels of these adipokines and the development of adverse events after acute myocardial infarction (AMI) remains unclear. Methods and Results: This study enrolled 724 Japanese subjects with AMI who underwent successful emergency percutaneous coronary intervention (PCI). Their serum adiponectin and leptin levels were measured 7 days after AMI onset. There were 63 adverse events during the 3-year follow-up. The levels of adiponectin and leptin and the leptin to adiponectin ratio, were significantly associated with adverse events [hazard ratio 2.08 (95% confidence interval (CI) 1.33–3.24), P=0.001; hazard ratio 0.62 (95% CI 0.43–0.90), P=0.012; hazard ratio 0.59 (95% CI 0.45–0.76), P<0.001, respectively]. The leptin to adiponectin ratio remained a significant independent predictor of adverse events during long-term follow-up in a multivariable analysis [adjusted hazard ratio 0.60 (95% CI 0.43–0.83), P=0.002]. Conclusions: Higher adiponectin and lower leptin levels are associated with a high incidence of adverse events in Japanese patients after AMI, and the leptin to adiponectin ratio independently predicts prognosis after AMI.  (Circ J 2013; 77: 2778–2785)
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  • Andrew P. DeFilippis, Oluwasegun S. Oloyede, Efstathia Andrikopoulou, ...
    2013 Volume 77 Issue 11 Pages 2786-2792
    Published: 2013
    Released: October 25, 2013
    [Advance publication] Released: August 27, 2013
    JOURNALS FREE ACCESS
    Supplementary material
    Background: Aspirin’s therapeutic action is via inhibition of platelet cyclooxygenase 1 (COX-1) thromboxane A2 (TxA2) production. The aim of this study was to evaluate TxA2 production, in the absence of platelet COX-1 activity, in coronary atherosclerotic heart disease patients with and without atherothrombotic myocardial infarction (MI). Methods and Results: TxA2 production, in the absence of platelet COX-1 activity, was evaluated in 44 patients taking aspirin on 3 commercially available assays that detect metabolites of TxA2 in the urine. Two assays measure urine 11-dehydro-thromboxane B2 (TxB2) alone and 1 measures urine 11-dehydro-TxB2 plus 11-dehydro-2,3-dinor-TxB2. Platelet COX-1 inhibition was confirmed on <10% platelet aggregation in response to ≥1mmol/L arachidonic acid. Median urine 11-dehydro-TxB2 was no different in those with and without a diagnosis of atherothrombotic MI (325 vs. 311pg/mg creatinine, P=0.59 via polyclonal ELISA) and (312 vs. 244pg/mg creatinine, P=0.11 via LC-MS/MS). Median urine 11-dehydro-TxB2 plus 11-dehydro-2,3-dinor-TxB2, however, was higher in those with vs. those without a diagnosis of atherothrombotic MI (1,035 vs. 606pg/mg creatinine, P=0.03 via monoclonal ELISA). Conclusions: Differences in TxA2 production, in the absence of platelet COX-1 activity, between those with vs. without atherothrombotic MI were not observed when TxA2 generation was assessed on 11-dehydro-TxB2 production alone (polyclonal ELISA or LC-MS/MS), but differences were observed when TxA2 generation was assessed using 11-dehydro-TxB2 plus 11-dehydro-2,3-dinor-TxB2 (monoclonal ELISA). These findings highlight important differences between different commercially available assays for TxA2 generation and suggest that 11-dehydro-2,3-dinor-TxB2 may be critical to the biology of atherothrombosis.  (Circ J 2013; 77: 2786–2792)
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Molecular Cardiology
  • Romy Franken, Alexander W. den Hartog, Liz van de Riet, Janneke Timmer ...
    2013 Volume 77 Issue 11 Pages 2793-2798
    Published: 2013
    Released: October 25, 2013
    [Advance publication] Released: August 29, 2013
    JOURNALS FREE ACCESS
    Background: Prevention of aortic dissection and sudden death in patients with Marfan syndrome (MFS) requires accurate diagnosis. MFS is diagnosed by the Ghent criteria, which are primarily based on clinical features of Caucasian MFS populations. We determined whether the Ghent criteria apply to Asian MFS populations. Methods and Results: In this multicenter study, we included 255 adult MFS patients according to the Ghent criteria of 2010. Patients were excluded if they were neither Caucasian nor Asian. The Asian MFS population (n=49) had a smaller body surface area (BSA: 1.8m² vs. 2.0m², P<0.001), a more severely affected aortic root (absolute aortic diameter: 42.9mm vs. 43.3mm, P=0.802; corrected for BSA: 24.9mm vs. 21.7mm, P<0.001; Z-score: 4.5 vs. 3.6, P=0.013), and more often a positive systemic score (75.5% vs. 60.0%, P=0.045), but less frequently ectopia lentis (24.5% vs. 48.1%, P=0.004) compared with the Caucasian population (n=206). Conclusions: The Ghent criteria do not necessarily apply to Asian MFS populations, resulting in a more severely affected cardiovascular system. This may be related to under diagnosis of MFS by multiple factors, including the use of Z-score, and genetic and racial differences. The Ghent criteria should be adapted for Asian populations in order to accurately diagnose MFS.  (Circ J 2013; 77: 2793–2798)
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Myocardial Disease
  • – Clinical and Molecular Features –
    Pedro Villar, Begoña Bretón, Pablo García-Pav&iac ...
    2013 Volume 77 Issue 11 Pages 2799-2806
    Published: 2013
    Released: October 25, 2013
    [Advance publication] Released: August 20, 2013
    JOURNALS FREE ACCESS
    Supplementary material
    Background: Mitochondrial disorders (MD) are multisystem diseases that arise as a result of dysfunction of the oxidative phosphorylation system. The predominance of neuromuscular manifestations in MD could mask the presence of other clinical phenotypes such as cardiac dysfunction. Reported here is a retrospective study, the main objective of which was to characterize the clinical and molecular features of a cohort of patients with cardiomyopathy and MD. Methods and Results: Hospital charts of 2,520 patients, evaluated for presumed MD were reviewed. The clinical criterion for inclusion in this study was the presence of a cardiac disturbance accompanied by a mitochondrial dysfunction. Only 71 patients met this criterion. The mitochondrial genome (mtDNA) could be sequenced only in 45 and the pathogenicity of 2 of the found changes was investigated using transmitochondrial cybrids. Three nucleotide changes in mtDNA that may be relevant and 3 with confirmed pathogenicity were identified but no mutations were found in the 13 nuclear genes analyzed. Conclusions: The mtDNA should be sequenced in patients with cardiac dysfunction accompanied by symptoms suggestive of MD; databases should be carefully and periodically screened to discard mitochondrial variants that could be associated with MD; functional assays are necessary to classify mitochondrial variants as pathogenic or polymorphic; and additional efforts must be made in order to identify nuclear genes that can explain some as yet uncharacterized molecular features of mitochondrial cardiomyopathy.  (Circ J 2013; 77: 2799–2806)
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Preventive Medicine
  • Yasushi Matsuzawa, Seigo Sugiyama, Koichi Sugamura, Hitoshi Sumida, Hi ...
    2013 Volume 77 Issue 11 Pages 2807-2815
    Published: 2013
    Released: October 25, 2013
    [Advance publication] Released: August 28, 2013
    JOURNALS FREE ACCESS
    Supplementary material
    Background: Simple office-based counseling for diet and exercise does not appear to positively affect success rates in metabolic syndrome (MetS) patients. The utility of the lifestyle modification self-assessment score (Self-AS) in the improvement of endothelial function by office-based counseling for patients with MetS was investigated. Methods and Results: Patients with MetS (n=207) and age- and sex-matched individuals without MetS (n=124) were enrolled in this cross-sectional study. Endothelial function was assessed using reactive hyperemia-peripheral arterial tonometry index (RHI). Patients with MetS had significant endothelial dysfunction compared with those without MetS (RHI, 0.502±0.178 vs. 0.614±0.229; P<0.001). Seventy MetS patients participating in the prospective interventional study received simple office-based lifestyle modification counseling that was accompanied by Self-AS questionnaire after 10 months. RHI was significantly improved following lifestyle modifications (from 0.452±0.136 to 0.547±0.202, P<0.001). Reductions in waist circumference (R2=0.094, P=0.01) and increased high-density lipoprotein cholesterol (R2=0.227, P<0.001) independently correlated with improved RHI. Self-AS significantly correlated with changes in waist circumference (r=−0.57, P<0.001) and RHI (r=0.30, P=0.02). Patients with a good achievement of lifestyle modifications (higher Self-AS) had significant improvement in endothelial function compared with those with lower scores (% change in RHI, +48.7±61.6 vs. +7.8±35.1, P=0.001). Conclusions: Good achievement of lifestyle modifications as evaluated on Self-AS significantly improved endothelial function with concomitant reductions in waist circumferences in MetS patients.  (Circ J 2013; 77: 2807–2815)
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Renal Disease
  • Susumu Ogawa, Kazuhiro Nako, Masashi Okamura, Miho Senda, Takuya Sakam ...
    2013 Volume 77 Issue 11 Pages 2816-2822
    Published: 2013
    Released: October 25, 2013
    [Advance publication] Released: August 06, 2013
    JOURNALS FREE ACCESS
    Supplementary material
    Background: In diabetic patients with renal artery arteriosclerosis (RAAS), the factors associated with a greater risk for cardiovascular-renal events (CVREs) remain unclear: the decline in estimated glomerular filtration rate (eGFR) caused by RAAS or the advance of arteriosclerosis that causes RAAS. Hence, the features to determine which best predicts the onset of CVREs in such patients were compared. Methods and Results: The renal arteries of 162 type 2 diabetes patients were assessed by using magnetic resonance angiography (RAAS diagnosed as arteriosclerotic stenosis ≥50%) and they were studied longitudinally over 7 years. The influence of the presence/absence of RAAS, a decline in eGFR, clinical factors, surrogate arteriosclerotic markers and ischemic markers on patient’s CVREs were assessed. A Cox regression analysis showed the detection of RAAS to be an independent risk factor for CVREs (bilateral RAAS was an extremely strong risk factor for the development of CVREs within 1,000 days), as was the decline in eGFR in a logistic regression analysis; the latter being a more powerful risk factor for CVREs. A multiple regression analysis revealed angiopoietin-2, a marker of ischemia, to be a risk factor for the decline in eGFR. Conclusions: A decline in renal function but not the renal arterial stenotic lesion itself appears to be associated with an increased incidence of CVREs in type 2 diabetic patients with RAAS.  (Circ J 2013; 77: 2816–2822)
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Vascular Biology and Vascular Medicine
  • Jiazhang Wei, Kazuhiko Takeuchi, Hiroshi Watanabe
    2013 Volume 77 Issue 11 Pages 2823-2830
    Published: 2013
    Released: October 25, 2013
    [Advance publication] Released: July 25, 2013
    JOURNALS FREE ACCESS
    Supplementary material
    Background: Linoleic acid (LA) promotes monocyte chemotaxis and cell adhesion molecules such as MCP-1 and VCAM-1, which contribute to atherosclerogenesis. These molecules are restrained by endothelium-derived relaxing factors (EDRFs), such as nitric oxide (NO) and prostaglandin I2 (PGI2). Hence, the expressions of MCP-1 and VCAM-1 upregulated by LA may be partly attributable to decreased EDRF production. However, effect of LA on EDRF production remains controversial. Methods and Results: The present study aimed to examine the effects of LA and other free fatty acids on EDRF production and the endothelial Ca2+ responses that mediate EDRF production, using primary cultured porcine aortic endothelial cells (PAECs). LA at 0.1–5μmol/L attenuated bradykinin (BK)-induced NO and PGI2 production while suppressing the BK-induced Ca2+ response dose-dependently. The inhibitory effect of LA on the Ca2+ response was eliminated by adenylate cyclase inhibitor SQ22536, boosted by cAMP-hydrolyzing phosphodiesterase (PDE) inhibitor, rolipram, and mimicked by plasma membrane permeable 8-bromo-cAMP. Moreover, LA was confirmed to dose-dependently increase intracellular cAMP levels and selectively inhibit cAMP-hydrolyzing PDE activity in vitro. In contrast, none of palmitic, stearic, or oleic acid affected BK-induced EDRF production or Ca2+ responses, or induced intracellular cAMP accumulation. Conclusions: LA induced intracellular cAMP accumulation by inhibiting cAMP-hydrolyzing PDE activity, thus resulting in attenuation of Ca2+ responses and EDRF production in PAECs.  (Circ J 2013; 77: 2823–2830)
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  • Hideaki Tagashira, Takayuki Matsumoto, Kumiko Taguchi, Chen Zhang, Fen ...
    2013 Volume 77 Issue 11 Pages 2831-2840
    Published: 2013
    Released: October 25, 2013
    [Advance publication] Released: August 20, 2013
    JOURNALS FREE ACCESS
    Background: We previously reported that σ1-receptor (σ1R) expression in the thoracic aorta decreased after pressure overload (PO) induced by abdominal aortic banding in ovariectomized (OVX) rats. Here, we asked whether stimulation of σ1R with the selective agonist SA4503 elicits functional recovery of aortic vasodilation and constriction following vascular injury in OVX rats with PO. Methods and Results: SA4503 (0.3–1.0mg/kg) and NE-100 (a σ1R antagonist, 1.0mg/kg) were administered orally for 4 weeks (once daily) to OVX-PO rats. Vascular functions of isolated descending aorta were measured following phenylephrine (PE)- or endothelin-1 (ET-1)-induced vasoconstriction and acetylcholine (ACh)- or clonidine-induced vasodilation. SA4503 administration rescued PO-induced σ1R decreases in aortic smooth muscle and endothelial cells. SA4503 treatment also rescued PO-induced impairments in ACh- and clonidine-induced vasodilation without affecting PE- and ET-1-induced vasoconstriction. Ameliorated ACh- and clonidine-induced vasodilation was closely associated with increased Akt activity and in turn endothelial nitric oxide synthase (eNOS) phosphorylation. The SA4503-mediated improvement of vasodilation was blocked by NE-100 treatment. Conclusions: σ1R is downregulated following PO-induced endothelial injury in OVX rats. The selective σ1R agonist SA4503 rescues impaired endothelium-dependent vasodilation in the aorta from OVX-PO rats through σ1R stimulation, enhancing eNOS-cGMP signaling in vascular endothelial cells. These observations encourage development of novel therapeutics targeting σ1R to prevent vascular endothelial injury in vascular diseases.  (Circ J 2013; 77: 2831–2840)
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Rapid Communication
  • Sunao Kojima, Kunihiko Matsui, Hisao Ogawa, on behalf of the Kumamoto ...
    2013 Volume 77 Issue 11 Pages 2841-2843
    Published: 2013
    Released: October 25, 2013
    [Advance publication] Released: September 25, 2013
    JOURNALS FREE ACCESS
    Supplementary material
    Background: The Kumamoto Acute Coronary Events Study explored trends for acute myocardial infarction (AMI). Methods and Results: The number of people of advanced age in Kumamoto Prefecture has gradually increased. In 2004–2011, 8,131 AMI patients were registered. Although the age-adjusted AMI incidence in men decreased from 93.1 in 2004 to 70.7 in 2011 (P=0.0294), the age-adjusted in-hospital cardiac death rate was maintained at ∼7%; however, the all-cause mortality and noncardiac death rate increased and appeared to be related. Conclusions: A steady trend of decreasing AMI incidence was observed. Urgent measures should be established against non-cardiac mortality in this era of an aging population.  (Circ J 2013; 77: 2841–2843)
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