Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Volume 75 , Issue 4
Showing 1-45 articles out of 45 articles from the selected issue
Massage From the Editor-in-Chief
Reviews
  • Seung-Jung Park, Duk-Woo Park
    2011 Volume 75 Issue 4 Pages 749-755
    Published: 2011
    Released: March 25, 2011
    [Advance publication] Released: March 10, 2011
    JOURNALS FREE ACCESS
    For several decades, based on clinical trials comparing coronary-artery bypass grafting (CABG) with medical therapy, bypass surgery has been regarded as the treatment of choice for patients with unprotected left main coronary artery (LMCA) disease. However, because of marked advancements in the techniques of percutaneous coronary intervention (PCI) with stenting and CABG and adjunctive pharmacologic therapy, reevaluation and review of current indications for optimal revascularization therapy for LMCA disease are required to determine the standard of care for these patients. The available current evidence suggests that the composite outcome of death, myocardial infarction and stroke is similar in patients with LMCA disease who are treated with either PCI with stenting or CABG, the only difference being the rate of repeat revascularization. Cumulative and emerging data from several extensive registries and a large clinical trial may have prompted many interventional cardiologists to select PCI with stenting as an alternative revascularization strategy for such patients. In addition, these data not only may change future guidelines, but support the need for prospective, large randomized trials comparing the 2 revascularization treatments. Finally, this evidence will change the current clinical practice of revascularization strategy for unprotected LMCA disease. (Circ J 2011; 75: 749-755)
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  • Bryan P Yan, Darragh Moran, Brian G Hynes, Thomas J Kiernan, Cheuk-Man ...
    2011 Volume 75 Issue 4 Pages 756-765
    Published: 2011
    Released: March 25, 2011
    [Advance publication] Released: March 12, 2011
    JOURNALS FREE ACCESS
    Critical limb ischemia (CLI) represents the most severe clinical manifestation of peripheral arterial disease. In the absence of timely revascularization, CLI carries high risk of mortality and amputation. Over the past decade, endovascular revascularization has rapidly become the preferred primary treatment strategy for CLI, especially for the treatment of below-the-knee disease. Advances in percutaneous devices and techniques have expanded the spectrum of patients with CLI who are deemed candidates for revascularization. This review will focus on advances in endovascular options for the treatment of CLI, in particular for below-the-knee disease. (Circ J 2011; 75: 756-765)
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  • Soichiro Kitamura
    2011 Volume 75 Issue 4 Pages 766-772
    Published: 2011
    Released: March 25, 2011
    [Advance publication] Released: March 10, 2011
    JOURNALS FREE ACCESS
    The internal thoracic artery (ITA) has become the gold standard graft material for modern coronary artery bypass grafting (CABG) because of its excellent long-term patency. The use of ITA grafts has also prolonged the postoperative survival of patients when applied to the left anterior descending artery or used bilaterally as 2 grafts for the left coronary system. Moreover, recent large-scale randomized clinical trials comparing the survival rates between CABG and percutaneous coronary intervention (PCI) with stents have shown that CABG is more effective for improving the survival of patients with severe coronary artery disease and/or in those with diabetes mellitus. The fundamental principle underlying these clinical benefits of CABG is the excellent endothelial function of the ITA, which provides physiological and metabolic effects that are beneficial not only for the graft itself, but also for the recipient coronary system. The production of nitric oxide and prostanoids by the ITA endothelium and their beneficial effects on the downstream coronary artery should therefore be taken into consideration when debating the merits of CABG vs. PCI. (Circ J 2011; 75: 766-772)
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Editorials
Late Breaking Clinical Trials (JCS 2011)
  • Amane Ike, Hiroaki Nishikawa, Kazuyuki Shirai, Ken Mori, Takashi Kuwan ...
    2011 Volume 75 Issue 4 Pages 791-799
    Published: 2011
    Released: March 25, 2011
    [Advance publication] Released: March 18, 2011
    JOURNALS FREE ACCESS
    Background: It is not yet clear whether glycemic control affects the clinical outcome of percutaneous coronary intervention (PCI) in diabetic patients. Methods and Results: This study compared the effects of glycemic control on the clinical outcome in 2 groups of patients with diabetes mellitus (DM) who underwent PCI: a poor-glycemic-control group, who showed greater than 6.9% HbA1c at the time of PCI (Pre-HbA1c) (`≥6.9 group', n=334 patients) and a good-glycemic-control group, who showed less than <6.9% at Pre-HbA1c (`<6.9 group', n=212 patients). The patients in the ≥6.9 group were further divided into 2 groups for further comparisons: a `DM control group' and a `Poor control group'. At follow-up (300 days), the incidence of major adverse cardiac event (MACE) was significantly (P<0.05) lower in the <6.9 group (18.4% vs. 26.2%). However, there was no difference in MACE between the DM control group and the Poor control group. In a multivariate analysis, there was no relationship between the incidence of MACE and Pre-HbA1c, Pre-HbA1c≥6.9% or the HbA1c difference (Pre-HbA1c-HbA1c at follow-up). Conclusions: Clinical outcomes in the <6.9 group were superior to those in the ≥6.9 group as pre-PCI glycemic control affected the baseline characteristics. The results suggested that glycemic control started at PCI was not associated with an improvement in the clinical outcome at follow-up. (Circ J 2011; 75: 791-799)
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  • Masatsugu Hori, Stuart J. Connolly, Michael D. Ezekowitz, Paul A. Reil ...
    2011 Volume 75 Issue 4 Pages 800-805
    Published: 2011
    Released: March 25, 2011
    [Advance publication] Released: March 19, 2011
    JOURNALS FREE ACCESS
    Background: RE-LY (Randomized Evaluation of Long-term Anticoagulation Therapy) is an international multicenter study (18,113 patients from 967 centers in 44 countries) that demonstrated the ability of dabigatran to reduce the occurrence of both stroke and hemorrhage in patients who had atrial fibrillation (AF) with high risks of stroke compared with patients who received warfarin. From Japan, 326 patients were randomized in RE-LY. Methods and Results: RE-LY was designed to compare 2 fixed doses (110mg or 150mg, twice daily) of dabigatran, each administered in a blinded manner, with open-label use of warfarin. There were no major differences in patient demographic information among the overall study population and Japanese patients. However, in Japanese patients, the proportion of prior stroke was higher but prior myocardial infarction was lower than in the overall. The yearly rate for the primary endpoints (stroke and systemic embolism) was 1.38, 0.67 and 2.65%/year for 110mg and 150mg dabigatran twice daily and warfarin, respectively. These results were similar to the overall results (1.54, 1.11 and 1.71%/year for each group, respectively). For any bleeding, the relative risk of dabigatran at 110mg and 150mg twice daily over warfarin was 0.79 and 1.06, respectively, which was similar to the findings overall (dabigatran 110mg twice daily: 0.78; 150mg twice daily: 0.91). Conclusions: In RE-LY, the efficacy and safety profiles of dabigatran for Japanese AF patients at high risk of stroke were essentially the same as for the study population overall. (Circ J 2011; 75: 800 - 805)
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  • Jun Shiraishi, Takahisa Sawada, Shinzo Kimura, Hiroyuki Yamada, Hiroak ...
    2011 Volume 75 Issue 4 Pages 806-814
    Published: 2011
    Released: March 25, 2011
    [Advance publication] Released: March 19, 2011
    JOURNALS FREE ACCESS
    This article was retracted. See the Notification.
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  • Hiroyuki Yokoyama, Naohiro Yonemoto, Kazuya Yonezawa, Jun Fuse, Naoki ...
    2011 Volume 75 Issue 4 Pages 815-822
    Published: 2011
    Released: March 25, 2011
    [Advance publication] Released: March 20, 2011
    JOURNALS FREE ACCESS
    Background: In-hospital cardiopulmonary arrest (CPA) is an important issue, but data in Japan are limited. Methods and Results: To investigate in-hospital CPA, we conducted a prospective multicenter observational registry of in-hospital CPA and resuscitation in Japan (J-RCPR). During January 2008 to December 2009, patients were registered from 12 participating hospitals. All patients, visitors and employees within the facility campus who experience a cardiopulmonary resuscitation event defined as either a pulseless or a pulse with inadequate perfusion requiring chest compressions and/or defibrillation of ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT) were registered. Data were collected in 6 major categories of variables: facility data, patient demographic data, pre-event data, event data, outcome data, and quality improvement data. Data for 491 adults were analyzed. The prevalence of pulseless VT/VF as first documented rhythm was 28.1%, asystole was 29.5% and pulseless electrical activity was 41.1%. Immediate causes of event were arrhythmia 30.6%, acute respiratory insufficiency 26.7%, and hypotension 15.7%. Return of spontaneous circulation was 64.7%; the proportion of survival 24h after CPA was 49.8%, the proportion of survival to hospital discharge was 27.8% and proportion of favorable neurological outcome at 30 days was 21.4%. Conclusions: This is the first report of the registry for in-hospital CPA in Japan and shows that the registry provides important observational data. (Circ J 2011; 75: 815-822)
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  • Nobuyuki Shiba, Kotaro Nochioka, Masanobu Miura, Haruka Kohno, Hiroaki ...
    2011 Volume 75 Issue 4 Pages 823-833
    Published: 2011
    Released: March 25, 2011
    [Advance publication] Released: March 20, 2011
    JOURNALS FREE ACCESS
    Background: Hospitalization due to acute heart failure syndrome (AHFS) is an indicator of worsened prognosis for patients with cardiovascular disease (CVD). The Chronic Heart Failure Analysis and Registry in the Tohoku District 2 (CHART-2) Study was designed to elucidate characteristics and prognosis of patients at high risk for CVD progression due to AHFS. Methods and Results: The CHART-2 Study is a prospective observational multicenter cohort study. Patients with overt HF, structural cardiac disorder but without HF, or with coronary artery disease (CAD) have been consecutively enrolled from October 2006. As of March 2010, a total of 10,219 patients have been recruited, making the Study the largest multicenter prospective cohort of HF patients in Japan. The mean patient age was 68.2±12.3 years and male patients accounted for 69.8%. Overt HF was observed in 46.3% of patients; and 53.7% did not have HF but were at high risk for AHFS. As HF stage progressed, the prognostic risks (eg, chronic kidney disease, reduced ejection fraction, and increased B-type natriuretic peptide level) became more prominent. Compared with the previous CHART-1 study, the prevalence of ischemic etiology and risk factors (hypertension, diabetes) have increased, as in Western studies. Conclusions: This first report demonstrates the trend of westernization of ischemic etiology and clinical characteristics of HF patients in Japan, indicating the importance of appropriate management and prevention of CAD to prevent AHFS. (Circ J 2011; 75: 823-833)
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Original Articles
Arrhythmia/Electrophysiology
  • Boyoung Joung, Hyung-Wook Park, Mitsunori Maruyama, Liang Tang, Juan S ...
    2011 Volume 75 Issue 4 Pages 834-843
    Published: 2011
    Released: March 25, 2011
    [Advance publication] Released: February 02, 2011
    JOURNALS FREE ACCESS
    Background: Anodal stimulation hyperpolarizes the cell membrane and increases the intracellular Ca2+ (Cai) transient. This study tested the hypothesis that the maximum slope of the Cai decline (-(dCai/dt)max) corresponds to the timing of anodal dip on the strength-interval curve and the initiation of repetitive responses and ventricular fibrillation (VF) after a premature stimulus (S2). Methods and Results: We simultaneously mapped the membrane potential (Vm) and Cai in 23 rabbit ventricles. A dip in the anodal strength-interval curve was observed. During the anodal dip, ventricles were captured by anodal break excitation directly under the S2 electrode. The Cai following anodal stimuli is larger than that following cathodal stimuli. The S1-S2 intervals of the anodal dip (203±10ms) coincided with the -(dCai/dt)max (199±10ms, P=NS). BAPTA-AM (n=3), inhibition of the electrogenic Na+-Ca2+ exchanger current (INCX) by low extracellular Na+ (n=3), and combined ryanodine and thapsigargin infusion (n=2) eliminated the anodal supernormality. Strong S2 during the relative refractory period (n=5) induced 29 repetitive responses and 10 VF episodes. The interval between S2 and the first non-driven beat was coincidental with the time of -(dCai/dt)max. Conclusions: Larger Cai transient and INCX activation induced by anodal stimulation produces anodal supernormality. The time of maximum INCX activation is coincidental to the induction of non-driven beats from the Cai sinkhole after a strong premature stimulation. (Circ J 2011; 75: 834-843)
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  • Akashi Miyamoto, Hideki Hayashi, Takeru Makiyama, Tomohide Yoshino, Yu ...
    2011 Volume 75 Issue 4 Pages 844-851
    Published: 2011
    Released: March 25, 2011
    [Advance publication] Released: February 18, 2011
    JOURNALS FREE ACCESS
    Background: Spontaneous coved ST-segment elevation ≥2mm followed by a negative T-wave in the right precordial leads (type 1 Brugada ECG) is diagnostic of Brugada syndrome (BS), but there is a false-positive rate. Methods and Results: Computer-processed analysis of a 12-lead ECG database containing 49,286 females and 52,779 males was performed to select patients with a spontaneous type 1 Brugada ECG for an examination of the association of this ECG characteristic with long-term prognosis. There were 185 patients with a spontaneous type 1 Brugada ECG and of these, 16 (15 males; mean age, 46.7±14.0 years) were diagnosed with BS and 15 patients (all males; mean age, 50.1±13.4 years) were undiagnosed. The PQ interval was significantly longer in the diagnosed patients than in the undiagnosed patients (187.4±28.3ms vs. 161.2±21.5ms; P=0.0073). The T-wave in lead V1 was more negative in the diagnosed patients than in the undiagnosed patients (-170.2±174.6μV vs. -43.2±122.3μV, P=0.027). Multivariate analysis revealed that a PQ interval ≥170ms and T-wave amplitude <105μV in lead V1 were independent risk stratifiers of life-threatening events. Survival analysis (mean follow-up, 78.6±81.8 months) showed that the PQ interval and a negative T-wave in lead V1 were significantly associated with poor prognosis. Conclusions: Analysis of a standard 12-lead ECG can stratify the prognosis of patients with a spontaneous type 1 Brugada ECG. (Circ J 2011; 75: 844-851)
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Biomedical Engineering
  • Alexander Weymann, Sivakkanan Loganathan, Hiroaki Takahashi, Carsten S ...
    2011 Volume 75 Issue 4 Pages 852-860
    Published: 2011
    Released: March 25, 2011
    [Advance publication] Released: February 02, 2011
    JOURNALS FREE ACCESS
    Background: Reports about the generation of 3-dimensional neoscaffolds for myocardial tissue engineering are limited. The architecture provided by perfusion decellularization of whole hearts would support the production of human-sized 3-dimensional living tissues from an acellular matrix. The aim of this study was to evaluate the potential of a perfusion decellularization model for whole heart tissue engineering. Methods and Results: Hearts were obtained from 12 German Landrace pigs from a selected abattoir. After preparation, the hearts were mounted and perfused on a modified Langendorff decellularization model specifically constructed for this reason. Decellularization was achieved by an ionic detergent-based perfusion protocol. The quality of the decellularization process was quantified by histology and fluorescence microscopy. Data regarding the presence of residual DNA within the decellularized hearts was measured with spectrophotometric quantification and compared to controls. After histological examination, all hearts lacked intracellular components but retained various types of collagen, proteoglycan and elastin. Quantitative DNA analysis demonstrated a significant reduction of DNA in decellularized hearts compared to controls (84.32±3.99ng DNA/mg tissue vs. 470.13±18.77ng DNA/mg tissue (P<0.05)). Conclusions: The modified Langendorff perfusion decellularization model described here is applicable for whole porcine hearts by removing cellular content and DNA. The resulting 3-dimensional matrix provides an interesting tool for further studies in the field of whole heart tissue engineering. (Circ J 2011; 75: 852-860)
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Cardiovascular Intervention
  • Ung Kim, Sang-Hoon Seol, Doo-Il Kim, Dong-Kie Kim, Jae-Sik Jang, Tae-H ...
    2011 Volume 75 Issue 4 Pages 861-867
    Published: 2011
    Released: March 25, 2011
    [Advance publication] Released: January 18, 2011
    JOURNALS FREE ACCESS
    Background: There is only limited data on coronary artery aneurysms (CAA) after drug-eluting stent (DES) implantation. Methods and Results: Two hundred-fifty one patients who had 2 angiographic follow-ups at 8 months and 28-36 months, respectively, after the index procedure with DES from 2003 to 2007 were enrolled. A CAA was defined as a localized dilatation exceeding 1.5 times the diameter of the adjacent artery. The independent risk factors and major adverse cardiac events (MACE) were determined, including cardiac death, myocardial infarction (MI) and target-vessel revascularization (TVR), between the patients with CAA (n=35) and without them (n=216). On multivariate analysis, a lesion in an infarct-related artery (IRA) (odds ratio (OR): 6.1, P=0.001), a lesion in the left anterior descending artery (OR: 4.9, P=0.005), a lesion length >33mm (OR: 3.9, P=0.022), and a lesion with chronic total occlusion (CTO) (OR: 3.4, P=0.044) were the independent risk factors for CAA. Follow-up duration was 1,046±516 days. Although most patients (71.4%) were asymptomatic, MACE was found in 10 patients (28.6%). No deaths occurred. MI with stent thrombosis occurred in 5 patients (14.3%) and TVR occurred in 10 patients (28.6%). Conclusions: The risk factors for the development of CAA after DES are a long lesion over 33mm, a lesion in the left anterior descending artery, a lesion in an IRA, and CTO. Long-term follow-up and large clinical trials are warranted for patients with CAA. (Circ J 2011; 75: 861-867)
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  • Yu Kataoka, Nobuhito Yagi, Nobuaki Kokubu, Yoichiro Kasahara, Mitsuru ...
    2011 Volume 75 Issue 4 Pages 868-873
    Published: 2011
    Released: March 25, 2011
    [Advance publication] Released: March 01, 2011
    JOURNALS FREE ACCESS
    Background: Experimental and clinical studies have shown that paclitaxel-eluting stent (PES) attenuates the effect of diabetes on re-stenosis after percutaneous coronary intervention. Although impaired glucose tolerance (IGT) is a pre-diabetic phase characterized as post-prandial hyperglycemia and hyperinsulinemia, the efficacy of PES in these pre-diabetic patients remains unknown. The purpose of the present study was therefore to compare the efficacy of PES in IGT patients with that of sirolimus-eluting stent (SES). Methods and Results: A total of 370 IGT patients with coronary artery disease were examined (SES, n=229; PES, n=141). The incidence of major adverse cardiovascular events (MACE; all-cause death, non-fatal myocardial infarction or repeat revascularization) was compared between the 2 groups. The PES group had lower body mass index, total cholesterol and low-density lipoprotein cholesterol levels and higher prevalence of previous myocardial infarction than the SES group. The incidence of repeat revascularization in the PES group was similar to that in the SES group (22% vs. 19%, P=0.71). The incidence of hard cardiac events such as all-cause death and non-fatal myocardial infarction were also similar between the 2 groups. Finally, there were no significant differences in MACE between the SES and PES groups (23% vs. 21%, P=0.76). Conclusions: In patients with IGT, the efficacy of PES was similar to that of SES, and any advantage of PES over SES was not observed in these pre-diabetic patients. (Circ J 2011; 75: 868-873)
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Heart Failure
  • Cheng-Han Lee, Synthia H. Sun, Shing-Hong Lin, Chih-Cheng Chen
    2011 Volume 75 Issue 4 Pages 874-883
    Published: 2011
    Released: March 25, 2011
    [Advance publication] Released: February 04, 2011
    JOURNALS FREE ACCESS
    Background: The mechanically sensitive volume receptors, primarily located in the venoatrial junction area, are essential for blood volume homeostasis. However, the molecular basis of the volume receptors is still unknown. Methods and Results: We hypothesized that the acid-sensing ion channel 3 (ASIC3) might be a candidate for the mechanically sensitive molecules expressed in the volume receptors. We examined the effect of Asic3 null mutation (Asic3-/-) on blood volume expansion (BVE)-induced urine flow, neural activation, and atrial natriuretic peptide (ANP) release in mice. BVE-induced urine flow was lower in Asic3-/- mice than in wild-type littermates. In addition, the stretch-activated channel blocker GdCl3 further reduced the BVE-induced urine flow in Asic3-/- mice. BVE increased phosphorylated extracellular signal-related kinase (pERK) immunoreactivity in nodose ganglia and many segments of dorsal root ganglia (DRG) in all mice, but pERK-positive neurons were fewer in Asic3-/- mice or mice pretreated with GdCl3 than in wild-type mice. Asic3 knockout selectively decreased BVE-induced pERK-immunoreactive neurons in nodose ganglia, and in C8 and T2 DRG. Moreover, BVE increased the circulating ANP level, which was abolished in Asic3-/- mice and wild-type mice treated with GdCl3. Asic3 knockout reduced the BVE-induced plasma ANP elevation in a GdCl3-independent manner. Conclusions: ASIC3 is a molecular substrate involved in detecting the vessel stretch caused by BVE. (Circ J 2011; 75: 874-883)
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Imaging
  • Umar Sadat, Zhongzhao Teng, Victoria E. Young, Zhi Yong Li, Jonathan H ...
    2011 Volume 75 Issue 4 Pages 884-889
    Published: 2011
    Released: March 25, 2011
    [Advance publication] Released: February 02, 2011
    JOURNALS FREE ACCESS
    Background: Biomechanical stress analysis has been used for plaque vulnerability assessment. The presence of plaque hemorrhage (PH) is a feature of plaque vulnerability and is associated with thromboembolic ischemic events. The purpose of the present study was to use finite element analysis (FEA) to compare the stress profiles of hemorrhagic and non-hemorrhagic profiles. Methods and Results: Forty-five consecutive patients who had suffered a cerebrovascular ischemic event with an underlying carotid artery disease underwent high-resolution magnetic resonance imaging (MRI) of their symptomatic carotid artery in a 1.5-T MRI system. Axial images were manually segmented for various plaque components and used for FEA. Maximum critical stress (M-CstressSL) for each slice was determined. Within a plaque, the maximum M-CstressSL for each slice of a plaque was selected to represent the maximum critical stress of that plaque (M-CstressPL) and used to compare hemorrhagic and non-hemorrhagic plaques. A total of 62% of plaques had hemorrhage. It was observed that plaques with hemorrhage had significantly higher stress (M-CstressPL) than plaques without PH (median [interquartile range]: 315kPa [247-434] vs. 200kPa [171-282], P=0.003). Conclusions: Hemorrhagic plaques have higher biomechanical stresses than non-hemorrhagic plaques. MRI-based FEA seems to have the potential to assess plaque vulnerability. (Circ J 2011; 75: 884-889)
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Ischemic Heart Disease
  • Hiroshi Nakashima, Shigenori Muto, Kentarou Amenomori, Yosinori Shirai ...
    2011 Volume 75 Issue 4 Pages 890-896
    Published: 2011
    Released: March 25, 2011
    [Advance publication] Released: February 02, 2011
    JOURNALS FREE ACCESS
    Background: Vascular endothelial dysfunction has been recognized as an essential feature of obstructive sleep apnea (OSA). This study was designed to examine the hypothesis that OSA may impair the coronary microcirculation in patients with ST-segment elevation myocardial infarction (STEMI). Methods and Results: The present study included 100 patients with a first STEMI who underwent primary percutaneous coronary intervention (PCI) within 12h from onset. Coronary flow velocity at baseline and at maximum hyperemia was measured using a Doppler guidewire following PCI. Total ST-segment elevation was calculated at baseline and 30min after PCI. All patients underwent polysomnography at 14 days to diagnose OSA. Coronary flow velocity reserve (CFVR) was used for quantitative analysis of myocardial tissue perfusion. Systolic retrograde flow (SRF) and ST-segment resolution (STR) <50% were used as an index of microvascular injury. Forty-eight patients presented with OSA. CFVR was comparable between the 2 groups. The incidence of SRF was higher in OSA patients than in the control patients (6% vs. 31%, P=0.005). Patients with OSA had a higher incidence of STR <50% (31% vs. 60%, P=0.003). Multiple logistic regression showed that OSA was an independent positive predictor of SRF and STR <50% (odds ratio=4.46, P=0.044; odds ratio=3.79, P=0.010). Conclusions: OSA may impair myocardial tissue perfusion following primary PCI. (Circ J 2011; 75: 890-896)
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  • Tetsuya Matsumoto, Yutaka Eguchi, Hiroshi Oda, Tetsunobu Yamane, Yasuh ...
    2011 Volume 75 Issue 4 Pages 897-904
    Published: 2011
    Released: March 25, 2011
    [Advance publication] Released: February 11, 2011
    JOURNALS FREE ACCESS
    Background: Lipocalin-type prostaglandin D synthase (L-PGDS) catalyzes the biosynthesis of PGD2, which acts as an anticoagulant, vasodilator, and inflammatory mediator. We examined the serum L-PGDS level, coronary macro- and microvasomotor functions, and their relationship in patients with chest pain and angiographically normal coronary arteries. Methods and Results: The study included 96 patients who underwent diagnostic coronary angiography and had angiographically normal coronary arteries. Blood flow of the left anterior descending coronary artery (LAD) was analyzed by Doppler guidewire examination. Serum L-PGDS level was determined by ELISA. Infusion of acetylcholine (ACh) induced vasospasm of the LAD in all patients with vasospastic angina (VSA) (n=45), but in none of the patients without VSA (n=51). There were no significant differences in the baseline clinical characteristics of the nonVSA and VSA groups, except for the frequency of smoking. Serum L-PGDS level in the VSA group was significantly higher than that in the nonVSA group (77.1±4.4 vs. 63.9±2.5μg/dl, P<0.01). Significant negative correlations were observed between the degree of LAD vasomotion in response to ACh and serum L-PGDS level (3μg/min: r=-0.33; 10μg/min: r=-0.35; 30μg/min: r=-0.33, P<0.01). Conclusions: The L-PGDS level was elevated in patients with VSA and was associated with epicardial coronary vasomotion in response to ACh. (Circ J 2011; 75: 897-904)
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  • Ichiro Matsumoto, Yuichi Miyake, Mizuki Mizukawa, Yuichiro Takagi
    2011 Volume 75 Issue 4 Pages 905-910
    Published: 2011
    Released: March 25, 2011
    [Advance publication] Released: February 11, 2011
    JOURNALS FREE ACCESS
    Background: Several studies have demonstrated that the low-density lipoprotein cholesterol/high-denisty lipoprotein-cholesterol (LDL-C/HDL-C) ratio is an excellent predictor of cardiovascular disease. The aim of the present study was to determine whether the LDL-C/HDL-C ratio would affect outcome in patients after percutaneous coronary intervention (PCI). Methods and Results: Six-hundred-eighty-seven participants who underwent successful PCI for acute coronary syndromes or stable angina were enrolled. They were divided into 3 groups on the basis of the LDL-C/HDL-C ratio recorded 6 months after PCI: those with LDL-C/HDL-C≤1.5 (n=125); 1.5<LDL-C/HDL-C≤2.0 (n=205); LDL-C/HDL-C>2 (n=357). In the 3 groups, the incidence of major adverse cardiac events (MACE) was measured during the 5 years after baseline evaluation. MACE was defined as cardiac death, non-fatal myocardial infarction, new lesions, and restenosis. The median follow-up duration was 33 months. Kaplan-Meier analysis demonstrated that patients with LDL-C/HDL-C≤1.5 had a significantly lower incidence of MACE after PCI than patients with 1.5<LDL-C/HDL-C≤2.0 (P=0.014) or with LDL-C/HDL-C>2.0 (P<0.001). In addition, Cox proportional hazards analysis indicated that the LDL-C/HDL-C ratio was correlated with the incidence of MACE (HR=1.39, 95% confidence interval: 1.20-1.61, P<0.001). Conclusions: The LDL-C/HDL-C ratio had an impact on long-term outcome in patients undergoing PCI. (Circ J 2011; 75: 905-910)
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Molecular Cardiology
  • Fumihiko Takeuchi, Masato Isono, Toru Nabika, Tomohiro Katsuya, Takao ...
    2011 Volume 75 Issue 4 Pages 911-918
    Published: 2011
    Released: March 25, 2011
    [Advance publication] Released: March 01, 2011
    JOURNALS FREE ACCESS
    Background: Normative alcohol use (or drinking behavior) influences the risk of cardiovascular disease in a multi-faceted manner. To identify susceptibility gene variants for drinking behavior, a 2-staged genome-wide association study was performed in a Japanese population. Methods and Results: In the stage-1 scan, 733 cases and 729 controls were genotyped with 456,827 SNP markers. The associated loci without redundancy of linkage disequilibrium were further examined in the stage-2 general population panel comprising 2,794 drinkers (≥once per week), 1,521 chance drinkers (<once per week), and 1,351 non-drinkers. Along with genome-wide exploration, we aimed to replicate the trait association of a candidate gene SNP previously reported (rs1229984 in ADH1B). A cluster of 12 SNPs on 12q24 were found to significantly (P<5×10-8) associate with drinking behavior in stage 1, among which rs671 (a Glu-to-Lys substitution at position 504) in the ALDH2 gene showed the strongest association (odds ratio (OR)=0.16, P=3.6×10-211 in the joint analysis). The association was also replicated for rs1229984 (OR=1.20, P<3.6×10-4). Furthermore, ALDH2 504Lys was associated with several metabolic traits, eg, lower levels of high-density lipoprotein cholesterol and liver enzymes-AST, ALT, and γGTP-by interacting with alcohol intake. Conclusions: Our results confirm ALDH2 as a major locus regulating drinking behavior in the Japanese, indicating that the ALDH2 504Lys variant exerts pleiotropic effects on risk factors of cardiovascular disease among drinkers. (Circ J 2011; 75: 911-918)
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Myocardial Disease
  • Toru Kubo, Hiroaki Kitaoka, Makoto Okawa, Shigeo Yamanaka, Takayoshi H ...
    2011 Volume 75 Issue 4 Pages 919-926
    Published: 2011
    Released: March 25, 2011
    [Advance publication] Released: February 04, 2011
    JOURNALS FREE ACCESS
    Background: Although serum cardiac troponin I (cTnI) and plasma brain natriuretic peptide (BNP) have become clinically important tools as diagnostic and prognostic markers for ischemic heart disease and heart failure, the usefulness of these biomarkers for risk stratification of hypertrophic cardiomyopathy (HCM) is not clear. Methods and Results: We studied 167 patients with HCM, and cTnI and BNP were measured. During follow-up (38.5 months), 20 patients suffered from cardiovascular events: HCM-related deaths in 6, hospitalization for heart failure in 8, embolic stroke in 5 and 1 patient with spontaneous sustained ventricular tachycardia. Patients with high cTnI values (≥0.04ng/ml) had more frequent cardiovascular events than did those with low cTnI values (P=0.008). Similarly, there were more frequent adverse events in the high BNP group (≥200pg/ml) than in the low BNP group (P=0.002). When groups were allocated according to both cTnI and BNP measurements, serum cTnI used in conjunction with BNP further improved the prognostic value; patients with both high cTnI and BNP values had an 11.7-fold increased risk of cardiovascular events compared with those with both low cTnI and BNP values. Conclusions: CTnI and BNP are useful parameters for identifying patients at risk for clinical deteriorations, and combined measurements of these biomarkers further improves the prognostic value of increased cardiovascular events in HCM. (Circ J 2011; 75: 919-926)
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Pediatric Cardiology and Adult Congenital Heart Disease
  • Li Chen, Li Wang, Jinghui Sun, Jiong Qin, Chaoshu Tang, Hongfang Jin, ...
    2011 Volume 75 Issue 4 Pages 927-931
    Published: 2011
    Released: March 25, 2011
    [Advance publication] Released: February 02, 2011
    JOURNALS FREE ACCESS
    Background: The study was carried out to examine the effect of selective α1 adrenoceptor agonist midodrine hydrochloride vs. β-adrenergic blockade metoprolol in the treatment of children with postural orthostatic tachycardia syndrome (POTS). Methods and Results: Fifty-three children with POTS were divided into group I (midodrine hydrochloride plus conventional therapy), group II (metoprolol plus conventional therapy) and group III (conventional therapy). Standing test was conducted for all participants. The cure rate, improvement rate, effective rate and score of symptoms were compared among the 3 groups. A Kaplan-Meier survivorship curve was used to describe the proportion of symptom-free cases during a long term follow-up. The cure rate and effective rate at the end of short term follow-up in group I were significantly higher than those of group II and group III (68.42% vs. 42.11% vs. 20.00%, P<0.05; 89.47% vs. 57.89% vs. 53.33%, P<0.05). After treatment, the symptom score in group I was significantly lower than group II and group III, respectively (1.1±2.2 vs. 2.8±2.4 vs. 3.7±2.0, P<0.05), and it also had significant difference between group II and group III (P<0.05). The symptom recurrent rate in group I was significantly lower than that of group II and group III, respectively (P<0.05), but it did not differ between group II and group III (P>0.05). Conclusions: Midodrine hydrochloride is effective in the treatment of children with POTS. (Circ J 2011; 75: 927-931)
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  • Rie Ichikawa, Naokata Sumitomo, Akiko Komori, Yuriko Abe, Takahiro Nak ...
    2011 Volume 75 Issue 4 Pages 932-938
    Published: 2011
    Released: March 25, 2011
    [Advance publication] Released: February 18, 2011
    JOURNALS FREE ACCESS
    Background: Fulminant myocarditis involves various serious arrhythmias that sometimes have lethal consequences. The purpose of the present study was to investigate the electrocardiogram findings, arrhythmogenicity and abnormalities of the cardiac conduction system in children with fulminant myocarditis. Methods and Results: Between 1999 and 2008, 7 consecutive patients (mean age: 7 years) who suffered from fulminant myocarditis were included in the study. A 12-lead electrocardiogram, Holter monitoring and signal-averaged electrocardiograms were performed and compared between the acute, convalescent, and recovery phases in the 4 surviving patients. Also, electrophysiologic assessment was carried out during the convalescent phase. Five out of 7 patients developed complete atrioventricular block, 3 developed ventricular tachycardia, 2 had cardiac arrest, 2 developed sinus tachycardia, 1 developed ventricular fibrillation, 1 had advanced atrioventricular block, and 1 developed sick sinus syndrome. Among the surviving patients, all arrhythmias resolved during the convalescent and remote phases. No atrial or ventricular arrhythmias were induced in any patients during the programmed stimulation study. In the convalescent phase, no arrhythmias could be induced and there were no signs of any conduction abnormalities on electrophysiological assessment. Conclusions: Close follow-up should be performed to observe for the occurrence of any new arrhythmias and/or a decrease in cardiac function in children with fulminant myocarditis. (Circ J 2011; 75: 932-938)
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Peripheral Vascular Disease
  • Kenji Suzuki, Osamu Iida, Yoshimitsu Soga, Keisuke Hirano, Naoto Inoue ...
    2011 Volume 75 Issue 4 Pages 939-944
    Published: 2011
    Released: March 25, 2011
    [Advance publication] Released: February 11, 2011
    JOURNALS FREE ACCESS
    Background: The use of a stent in the treatment of lesions of the superficial femoral artery (SFA) remains controversial. Although some reports have suggested that use of a nitinol stent in conjunction with aggressive medical management is effective for long SFA lesions, few long-term, large-scale studies have been done. Methods and Results: A retrospective analysis was conducted of data from a multicenter study in which the S.M.A.R.T. ControlTM stent was used for treatment of de novo SFA lesions. A total of 528 lesions in 432 patients were included. Mean patient age was 72.5±9.1 years; mean stent length was 15.7±8.1cm; 259 lesions (49%) were classified as C/D according to the TransAtlantic Inter-Society Consensus (TASC) II classification. Primary and secondary patency at 4 years was 66% and 87%, respectively. No cilostazol administration (41% re-stenosis group vs. 29% no-restenosis group, P<0.01), female gender (42% vs. 26%, P<0.01), younger age (70.7±9.3 years vs. 72.9±9.0 years, P<0.05), and chronic total occlusion (CTO; 72% vs. 52%, P<0.01) were independent predictors of re-stenosis. Conclusions: The S.M.A.R.T. ControlTM stent provided good long-term durability in the treatment of SFA lesions, and no cilostazol administration, female gender, younger age and CTO were associated with re-stenosis. (Circ J 2011; 75: 939-944)
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Pulmonary Circulation
  • Yuichiro Ohata, Sho Ogata, Kuniaki Nakanishi, Fumiko Kanazawa, Maki Ue ...
    2011 Volume 75 Issue 4 Pages 945-954
    Published: 2011
    Released: March 25, 2011
    [Advance publication] Released: March 03, 2011
    JOURNALS FREE ACCESS
    Background: The experimental pulmonary hypertension that develops in hypobaric hypoxia is characterized by structural remodeling of the heart. The P2X4 receptor (P2X4R) controls vascular tone and vessel remodeling in several blood vessels, and it has emerged as a key factor in the enhancement of cardiovascular performance. Methods and Results: To study the possible effects of hypobaric hypoxia on the P2X4R-synthesis system, 150 male Wistar rats were housed in a chamber at the equivalent of the 5,500m altitude level for 21 days. After 14 days' exposure to hypobaric hypoxia, pulmonary arterial pressure (PAP) was significantly increased. In the right ventricle (RV) of the heart, P2X4R expression was significantly increased on days 1 and 14 (mRNA) and on days 7 and 21 (protein) of hypobaric hypoxic exposure. Immunohistochemical staining for P2X4R protein became more intense in RV in the late phase of exposure. These changes in P2X4R synthesis in RV occurred alongside the increase in PAP. In addition, P2X1R and P2Y2R mRNA levels in the RV were significantly increased on days 1, 14, and 21, and day 5, respectively, of exposure. The level of P2X1R protein in the RV was significantly increased on day 21 of exposure. Conclusions: Conceivably, P2 receptors, including P2X4R and P2X1R, might play roles in modulating the RV hypertrophy that occurs due to pulmonary hypertension in hypobaric hypoxia. (Circ J 2011; 75: 945-954)
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Regenerative Medicine
  • Xiang Gu, Yong Xie, Jian Gu, Lei Sun, Shenghu He, Rixin Xu, Junfei Dua ...
    2011 Volume 75 Issue 4 Pages 955-963
    Published: 2011
    Released: March 25, 2011
    [Advance publication] Released: February 11, 2011
    JOURNALS FREE ACCESS
    Background: Recent investigations have suggested the clinical efficacy of granulocyte colony-stimulating factor (G-CSF) infusion alone or in combination with a single dose delivery of peripheral blood stem cells (PBSC) infusion in patients with myocardial infarction (MI) and congestive heart failure (HF). The current study tested the feasibility and effect of repeated intracoronary infusions PBSC and the mobilization of G-CSF in patients with refractory HF after MI. Methods and Results: Patients with recent large MI and a lower left ventricular ejection fraction (LVEF) were enrolled into one of the following 3 groups: Group R (n=15) received repeated intracoronary infusion of PBSC and one-dose of G-CSF; Group S (n=15) received a single infusion of PBSC and a G-CSF dose; and Group C (n=15) received neither PBSC nor a G-CSF dose. Cardiac performance was evaluated by echocardiography and single photon-emission computed tomography (SPECT). All the patients underwent 12-month follow-up. LVEF in Group R (47.00±4.90%) was significantly higher than that in Group S (44.40±3.87%, P<0.01) and Group C (40.80±3.41%, P<0.01). Similarly, the improvement of myocardial perfusion assessed by SPECT in Group R was more than that in Group S (P=0.012) and Group C (P<0.01). Neither death nor new MI occurred. Conclusions: Repeated intracoronary infusions of PBSC plus mobilization of G-CSF might be an optional effective strategy for treating patients with refractory HF after recent large MI. (Circ J 2011; 75: 955-963)
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Vascular Medicine
  • Ji Eun Yun, Sang Yeun Kim, Hee-Cheol Kang, Sun Ju Lee, Heejin Kimm, Su ...
    2011 Volume 75 Issue 4 Pages 964-969
    Published: 2011
    Released: March 25, 2011
    [Advance publication] Released: February 04, 2011
    JOURNALS FREE ACCESS
    Background: Few studies have examined the effect of insulin resistance on the association between alanine aminotransferase (ALT) and metabolic syndrome. The association between ALT levels and metabolic syndrome were determined, independently of insulin resistance in Korean populations. Methods and Results: The association between ALT and metabolic syndrome were examined in 28,456 subjects who visited 7 Health Promotion Centers at University Hospitals in Korea from 2006 to 2008. HOMA-IR index was used to represent insulin resistance index. ALT levels were found to be positively associated with metabolic syndrome after adjusting for age, alcohol intake, and smoking status. Furthermore, when additional adjustment was made for insulin resistance, this association between ALT and metabolic syndrome, although slightly attenuated, remained strongly significant. Subjects in the highest ALT quartile were found to have a higher risk of having metabolic syndrome than those in the lowest quartile (odds ratio (OR)=4.45, 95% confidence interval (CI)=3.96-4.99 for men and OR=3.51, 95%CI=2.73-4.52 for women). In addition, the association between ALT level and the risk of metabolic syndrome was significantly higher in the relatively low risk group. Conclusions: ALT levels were found to be significantly associated with metabolic syndrome independently of insulin resistance and with an interaction by age. Further cohort studies are needed to determine the usefulness of ALT levels for predicting the risk of metabolic syndrome. (Circ J 2011; 75: 964-969)
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Controversies in Cardiovascular Medicine
  • Masaomi Chinushi, Kenichi Iijima
    2011 Volume 75 Issue 4 Pages 970-978
    Published: 2011
    Released: March 25, 2011
    [Advance publication] Released: March 11, 2011
    JOURNALS FREE ACCESS
    Congestive heart failure (CHF) and atrial fibrillation (AF) often coexist, and each increase the morbidity and mortality associated with the other. Until now, many studies have reported that a strategy of rate control, in combination with anticoagulation in patients at risk of thromboembolic events, appears to be at least equivalent to a strategy of maintaining sinus rhythm with currently available pharmacological therapeutic options. As compared to rhythm control therapy, rate control treatment is simple and relatively easy. Therefore, pharmacological rate control should be considered initially in patients with AF associated with CHF. However, cardiac symptoms associated with AF may continue after achieving reasonable ventricular rate control. Either pharmacological or non-pharmacological rhythm control needs to be considered at that time. Amiodarone is the only recommended antiarrhythmic drug in the recent therapeutic guidelines for CHF, and can be used for both rhythm and rate control of AF. However, there is no question that some patients require early non-pharmacological rhythm control instead of long-lasting rate control. Catheter ablation (CA) can be applicable even in AF associated with CHF, but the results of CA are closely associated with the clinical and electrophysiological characteristics in each patient, as well as with the experience with this procedure in each institution. Indications for and the appropriate period of CA need to be carefully examined in each individual. (Circ J 2011; 75: 970 - 978)
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  • Takashi Kurita, Koichiro Motoki, Ryobun Yasuoka, Takayoshi Hirota, Yuz ...
    2011 Volume 75 Issue 4 Pages 979-985
    Published: 2011
    Released: March 25, 2011
    [Advance publication] Released: March 11, 2011
    JOURNALS FREE ACCESS
    The incidence of atrial fibrillation (AF) increases with advancing NHYA cardiac functional class, and it significantly affects the cardiac function of a failing heart. In such situations, clinicians should aim to maintain sinus rhythm in these patients with heart failure (HF) in order to improve their prognosis. However, according to various randomized clinical studies demonstrating the non-superiority of rhythm control over rate control, many clinicians seem to prefer to take the line of least resistance (ie, rate control). Curative catheter ablation mainly based on isolation procedure of the pulmonary veins in patients with AF and HF has demonstrated a significant improvement in left ventricular function, even in the presence of adequate ventricular rate control before the ablation. On the other hand, ablation and biventricular pacing therapy, which is an extreme rate control strategy, has not shown any beneficial effects for these patients. Therefore, a regular RR interval with an appropriate cycle length only is not sufficient to improve cardiac performance, and maintenance of sinus rhythm, which restores atrial contraction and the atrioventricular synchrony, is thought to be essential for an improvement in HF. Thoughtful clinicians should do their best to find a way to keep HF patients in sinus rhythm. (Circ J 2011; 75: 979-985)
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