Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Volume 77 , Issue 5
Showing 1-42 articles out of 42 articles from the selected issue
Message Frpm the Editor-in-Chief
Reviews
  • Rakesh Latchamsetty, Fred Morady
    2013 Volume 77 Issue 5 Pages 1091-1096
    Published: 2013
    Released: April 25, 2013
    [Advance publication] Released: April 02, 2013
    JOURNALS FREE ACCESS
    Catheter ablation has acquired a prominent role in the management of symptomatic atrial fibrillation (AF). Attempting to accurately assess the benefit of ablation can be quite challenging and is influenced by many variables, including the type of AF, procedural technique, operator experience, and duration and method of follow-up. Equally elusive is the proper definition of a successful ablation outcome. Should a “successful” ablation necessitate complete resolution of AF and AF symptoms documented by long-term monitoring, or does a more clinical approach evaluating for symptomatic improvement constitute a favorable outcome? Furthermore, at what point following an ablation should a recurrence be an acceptable, if not an expected, occurrence and should a significant decrease in AF burden warrant consideration as success? Our goal here will be to explore the current data evaluating outcomes for ablation of AF. We will examine electrophysiologic and other clinical endpoints, and hope to provide long-term expectations following ablation of paroxysmal and persistent AF.  (Circ J 2013; 77: 1091–1096)
    Download PDF (786K)
  • Yoshiya Toyoda, T. Sloane Guy, Abul Kashem
    2013 Volume 77 Issue 5 Pages 1097-1110
    Published: 2013
    Released: April 25, 2013
    [Advance publication] Released: April 03, 2013
    JOURNALS FREE ACCESS
    Heart transplantation has evolved as the “gold standard” therapy, with median survival exceeding 10 years, for patients with endstage heart failure (HF). Advancements in the fields of immunosuppression, infection prophylaxis, and surgical techniques have transformed heart transplantation from what was once considered an experimental intervention into a routine treatment. The number of heart transplants reported to the International Society of Heart and Lung Transplantation registry worldwide has been 3,500–4,000 annually, but has not been increased over the past 2 decades because of donor shortage despite the growing number of patients with HF. This imbalance between the supply of donor hearts and the demand of patients with endstage HF has led to increased use of mechanical circulatory support as destination therapy, because the supply of mechanical devices is virtually unlimited. Although mechanical circulatory support technology is improving, heart transplantation remains the preferred treatment for many patients because of major complications, such as stroke, bleeding and infection, and because of limited quality of life related to the driveline and the need for battery change. Therefore, significant efforts have been made to maximize the number of heart transplants and to ensure good outcomes.  (Circ J 2013; 77: 1097–1110)
    Download PDF (403K)
  • John W. Elrod, Jeffery D. Molkentin
    2013 Volume 77 Issue 5 Pages 1111-1122
    Published: 2013
    Released: April 25, 2013
    [Advance publication] Released: March 29, 2013
    JOURNALS FREE ACCESS
    This review focuses on the role of cyclophilin D (CypD) as a prominent mediator of the mitochondrial permeability transition pore (MPTP) and subsequent effects on cardiovascular physiology and pathology. Although a great number of reviews have been written on the MPTP and its effects on cell death, we focus on the biology surrounding CypD itself and the non-cell death physiologic functions of the MPTP. A greater understanding of the physiologic functions of the MPTP and its regulation by CypD will likely suggest novel therapeutic approaches for cardiovascular disease, both dependent and independent of programmed necrotic cell death mechanisms.  (Circ J 2013; 77: 1111–1122)
    Download PDF (605K)
  • Nathan Mewton, Thomas Bochaton, Michel Ovize
    2013 Volume 77 Issue 5 Pages 1123-1130
    Published: 2013
    Released: April 25, 2013
    [Advance publication] Released: April 09, 2013
    JOURNALS FREE ACCESS
    Over the past decade, the therapeutic strategies for acute myocardial infarction have changed considerably. Progress in experimental models, as well as noninvasive myocardial imaging techniques, has identified myocardial reperfusion injury as a significant contributor to the final infarct size in human patients. Following 3 decades devoted to the improvement of reperfusion therapy, recent major advances in myocardial protection after reperfusion slowly move the attention from the vessel to the muscle. In the past 20 years, several pharmacologic treatments or techniques applied at early reperfusion have been tested in experimental models and in the clinical setting. Numerous promising therapies in experimental models have failed to show significant benefit in the clinical realm. But to date, ischemic postconditioning applied at the onset of reperfusion is among the most promising therapies to treat reperfusion injury in myocardial infarction patients, with a 35% significant reduction of final infarct size in small groups of patients and different settings. However, clinical evidence in large population studies is still lacking for their widespread usage in the catheter laboratory at the time of reperfusion. After a brief review of the underlying molecular mechanisms of ischemic postconditioning, this review will focus on the clinical studies assessing the postconditioning effect in STEMI patients and review the findings and explore the future of this technique.  (Circ J 2013; 77: 1123–1130)
    Download PDF (867K)
  • Davide Capodanno
    2013 Volume 77 Issue 5 Pages 1131-1138
    Published: 2013
    Released: April 25, 2013
    [Advance publication] Released: March 30, 2013
    JOURNALS FREE ACCESS
    Risk stratification is an emerging topic in the modern management of patients with left main disease referred for percutaneous coronary intervention (PCI). Recent years have witnessed an explosive multiplication of risk models for prognostic stratification in complex PCI. Many of this models deal with modification of the angiographic SYNTAX score, or seek to overcome its known pitfalls and limitations, including lack of clinical and functional information, inter- and intra-observer variabilities, and poor calibration. Risk scoring systems beyond the SYNTAX score may be classified into angiographic (residual SYNTAX score, coronary artery bypass grafting SYNTAX score), clinical (EuroSCORE I and II, ACEF score and modified ACEF scores), combined clinical and angiographic (Global Risk Classification, Clinical SYNTAX score, logistic Clinical SYNTAX score, SYNTAX score II) and functional (Functional SYNTAX score). This article reviews current concepts in risk modeling and explores the advantages and limitations of the alternatives to the SYNTAX score in patients undergoing left main PCI.  (Circ J 2013; 77: 1131–1138)
    Download PDF (1132K)
2013 ACC Report
  • Hirotsugu Yamada
    2013 Volume 77 Issue 5 Pages 1139-1145
    Published: 2013
    Released: April 25, 2013
    [Advance publication] Released: April 05, 2013
    JOURNALS FREE ACCESS
    The American College of Cardiology’s (ACC) 62nd Annual Scientific Session was held at the Moscone Center, San Francisco, from March 9–11, 2013. The meeting focused on the “transformation of cardiovascular care, from discovery to delivery”, featured over 20 late-breaking clinical trials and 2,000 abstracts. These sessions gave notable exposure and recognition of studies likely to significantly affect clinical practice. There were 21 trials scheduled for presentation in 5 featured Late-Breaking Clinical Trial sessions, but one, the PREVAIL trial, was not presented because of a failure to observe an embargo. I summarize and overview both the late-breaking trials presented at ACC 2013 and the PREVAIL trial.  (Circ J 2013; 77: 1139–1145)
    Download PDF (940K)
Editorials
Original Articles
Arrhythmania/Electrophysiology
  • Anita Rahmawati, Akiko Chishaki, Hiroyuki Sawatari, Miyuki Tsuchihashi ...
    2013 Volume 77 Issue 5 Pages 1158-1165
    Published: 2013
    Released: April 25, 2013
    [Advance publication] Released: January 22, 2013
    JOURNALS FREE ACCESS
    Background: Implantable cardioverter-defibrillator (ICD) has improved prognosis in fatal arrhythmia and the number of ICD implantations has increased. ICD-related psychological problems and impaired quality of life (QOL), however, have been observed. This study examined whether gender differences exist in QOL and psychological disturbances in ICD patients. Methods and Results: Consecutive outpatients (n=179; mean age, 60.5±15.9 years; 81% male) with ICD implantations completed questionnaires consisting of the Short Form-8 (SF-8), Beck Depression Inventory, Impact of Event Scale-Revised (IES-R), State-Trait Anxiety Inventory, and Worries about ICD. One-way multivariate analysis of variance (MANOVA) showed women to have impaired QOL on the role physical functioning (F15,157=4.57, P<0.05) and bodily pain (F15,157=5.26, P<0.05) subscales of the SF-8. More women reported depression (F15,157=5.37, P<0.05) and worry about ICD than men (F15,157=6.62, P<0.05). Moreover, women also had higher IES-R scores indicating post-traumatic stress disorder (PTSD) than men (F15,157=5.87, P<0.05). Conclusions: Women reported poorer QOL on 2 subscales: role physical functioning and bodily pain. There was a significant relationship between gender and depression, worry about ICD, and PTSD, but not for anxiety. Female patients need more psychological interventions following ICD implantation.  (Circ J 2013; 77: 1158–1165)
    Download PDF (352K)
  • Takekazu Miyoshi, Chizuko A. Kamiya, Shinji Katsuragi, Hiroto Ueda, Yo ...
    2013 Volume 77 Issue 5 Pages 1166-1170
    Published: 2013
    Released: April 25, 2013
    [Advance publication] Released: December 29, 2012
    JOURNALS FREE ACCESS
    Background: There are few studies of pregnancy and delivery in patients with an implantable cardioverter-defibrillator (ICD). The purpose of this study was to investigate maternal and fetal outcome in these patients. Methods and Results: Six pregnant women with an ICD were retrospectively reviewed. All women underwent implantation of an ICD before pregnancy and delivered at the National Cerebral and Cardiovascular Center. The mean age at pregnancy and the mean follow-up period after ICD implantation were 28±3 years old and 5±3 years, respectively. There was no device-related complication during pregnancy. In 4 women, the number of tachyarrhythmias such as non-sustained ventricular tachycardia increased after the end of the second trimester of pregnancy and anti-arrhythmic medications were gradually increased. No patient received discharges or shocks from the ICD during pregnancy, however, and only one required anti-tachycardia pacing at 27 weeks’ gestation. Mean gestational age at delivery was 37±2 weeks and all deliveries were by cesarean section, including 5 as emergency deliveries due to a fetal indication. After delivery, 2 mothers had reduced cardiac function and 1 received an ICD shock for the first time. Conclusions: Pregnancy did not increase the risk of an ICD-related complication under appropriate management. Additional caution might be required in the postpartum period as well as during pregnancy and labor.  (Circ J 2013; 77: 1166–1170)
    Download PDF (267K)
  • Reginald Liew, Katwadi Khairunnisa, Yacui Gu, Nicole Tee, New Oo Yin, ...
    2013 Volume 77 Issue 5 Pages 1171-1179
    Published: 2013
    Released: April 25, 2013
    [Advance publication] Released: February 01, 2013
    JOURNALS FREE ACCESS
    Background: Although tumor necrosis factor-α (TNF-α) levels are increased in patients with atrial fibrillation (AF), its role in the pathogenesis of AF is unclear. We investigated whether direct delivery of TNF-α could induce atrial fibrosis. Methods and Results: TNF-α (4μg/kg) was injected into the tail vein of 20 male Swiss albino mice (TNF group) and saline into 20 control mice (CON group). The dose was carefully chosen to avoid any significant decrease in left ventricular (LV) function. Animals were killed after 16 weeks and their atria examined for fibrosis. We found increased atrial fibrosis in the TNF group compared with the CON group [372.8±21.5 arbitrary units (a.u.) vs. 56.9±6.5 a.u., respectively, mean±SEM; P<0.0001] and decreased connexin-40 immunofluorescence [7.5±0.4 a.u vs. 40.4±1.9 a.u, respectively; P<0.0001]. Transforming growth factor-β [TGF-β: 95.6±1.8 a.u vs. 29.4±5.8 a.u; P<0.001], α-smooth muscle actin (α-SMA: 97.9±13.0 a.u vs. 50.1±18.5 a.u; P<0.05] and matrix metalloproteinase 2 (MMP-2)/GAPDH levels [157.3±26.4 a.u vs. 105.8±13.3 a.u; P<0.05] were also increased in the TNF group. Conclusions: TNF-α is involved in the pathogenesis of atrial fibrosis and altered connexin-40 expression in mice through the TGF-β signaling pathway, activation of myofibroblasts and increased secretion of MMPs. Collectively, these changes may contribute to the arrhythmogenic substrate and development of AF.  (Circ J 2013; 77: 1171–1179)
    Download PDF (1376K)
Cardiovascular Intervention
  • Jun Yamashita, Nobuhiro Tanaka, Hiroshi Fujita, Takashi Akasaka, Tadat ...
    2013 Volume 77 Issue 5 Pages 1180-1185
    Published: 2013
    Released: April 25, 2013
    [Advance publication] Released: February 02, 2013
    JOURNALS FREE ACCESS
    Background: In recent years there has been a debate about the functional severity of restenosis of drug-eluting stents. The aim of the present study was to assess the functional severity of stenosis in patients with moderate angiographic restenosis after paclitaxel-eluting stents (PES) deployment. Methods and Results: Forty-two patients with moderate angiographic restenosis at the in-stent segment and/or approximately 5mm from the stent edge were enrolled. For comparison, furthermore, 42 patients with de novo stenosis lesions matched for angiographic severity were assigned to the control group. Quantitative coronary angiography and functional assessment using fractional flow reserve (FFR) were performed. Although percent diameter stenosis was not significantly different between the 2 groups (PES group, 40.6±11.2%; de novo group, 40.6±9.0%, P=0.981), the functional severity of stenosis was significantly less in the PES group than in the de novo group (FFR: PES group, 0.86±0.07; de novo group, 0.79±0.10, P=0.002). Conclusions: FFR was preserved in patients with moderate angiographic restenosis after PES deployment, and the functional severity of restenosis is often limited. Therefore, revascularization should be performed with caution for patients with moderate angiographic restenosis after PES deployment.  (Circ J 2013; 77: 1180–1185)
    Download PDF (699K)
  • Takayuki Ishihara, Masaki Awata, Fusako Sera, Masashi Fujita, Tetsuya ...
    2013 Volume 77 Issue 5 Pages 1186-1192
    Published: 2013
    Released: April 25, 2013
    [Advance publication] Released: February 15, 2013
    JOURNALS FREE ACCESS
    Background: Arterial repair in the early phase following implantation of a zotarolimus-eluting stent (ZES) remains unknown. Methods and Results: Following implantation of 49 Endeavor ZES in 33 patients, follow-up angioscopy was performed in 13 patients (26 ZES) in the early phase (EP; 123±24 days) and in 20 patients (23 ZES) in the middle phase (MP; 247±17 days). Neointimal coverage (NIC) was graded as follows: grade 0, stent struts exposed; grade 1, struts bulging into the lumen, although covered; grade 2, struts were embedded by the neointima but were seen translucently; grade 3, struts fully embedded and invisible. NIC was defined as heterogeneous for NIC grade variation ≥1. The presence of thrombus and yellow plaque was also investigated. Although NIC heterogeneity tended to be more frequent in EP than in MP (50% vs. 22%, P=0.070), and yellow plaque significantly more frequent (58% vs. 13%, P=0.0025), the majority of stents were dominant NIC grade 3 at both follow-up periods (73% in EP vs. 78% in MP, P=0.75). There was no significant difference in thrombus (23% in EP vs. 4% in MP, P=0.10) between the follow-ups. Conclusions: Sufficient arterial repair may have occurred by 4 months after ZES implantation.  (Circ J 2013; 77: 1186–1192)
    Download PDF (847K)
  • Hirotoshi Hariki, Toshiro Shinke, Hiromasa Otake, Junya Shite, Masayuk ...
    2013 Volume 77 Issue 5 Pages 1193-1201
    Published: 2013
    Released: April 25, 2013
    [Advance publication] Released: February 27, 2013
    JOURNALS FREE ACCESS
    Background: Treatment of coronary bifurcation lesions using a single stenting strategy is preferable over that using a 2-stent technique. The benefit of final kissing inflation (FKI), however, has not been established. Methods and Results: Seventy-two patients (76 lesions) with true bifurcation lesions treated with a single drug-eluting stent with FKI (n=33 lesions) or without FKI (non-FKI, n=43 lesions) were enrolled in this study. Optical coherence tomography (OCT) was performed at 6–12 months after implantation. Based on the OCT findings, the percentage of jailing struts (number of jailing struts/total number of struts at the bifurcation lesion) was calculated. Percentage of uncovered struts and frequency of thrombus attachment were each evaluated at the proximal, bifurcation, and distal segments. Major adverse cardiac events (MACE) were also evaluated. The percentage of jailing struts was significantly lower in the FKI than in the non-FKI group (5.8±6.2% vs. 17.3±6.1%, P<0.01). Thrombus attachment was less frequent in the FKI group (24.2% vs. 46.5%, P=0.046), especially at side-branch orifices (3.0% vs. 27.9%, P<0.001). The percentage of uncovered struts was lower in the FKI than non-FKI group at the proximal, bifurcation, and distal segments. The incidence of MACE was not different in this small cohort. Conclusions: FKI might reduce the frequency of subclinical thrombus possibly by reducing the number of jailing struts.  (Circ J 2013; 77: 1193–1201)
    Download PDF (1584K)
Cardiovascular Surgery
  • Takaya Hoashi, Koji Kagisaki, Naoki Okuda, Isao Shiraishi, Toshikatsu ...
    2013 Volume 77 Issue 5 Pages 1202-1207
    Published: 2013
    Released: April 25, 2013
    [Advance publication] Released: February 08, 2013
    JOURNALS FREE ACCESS
    Background: Intrapulmonary tunnel repair, called the Takeuchi technique, is a unique procedure for repairing anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA). Since 1986, we have clearly defined the indication for the Takeuchi technique based on the location of the left coronary artery (LCA) orifice. Methods and Results: From 1986 to 2011, 19 consecutive patients with ALCAPA underwent surgical repair; the dual-coronary system was reconstructed in 16 of these patients with either Takeuchi (n=9: 1 male; median age 14.7 years; median weight 42.7kg) or a translocation procedure (n=7, 3 males; 0.4 years old, 5.6kg). Takeuchi was performed in patients whose LCA arose far from the aorta (middle of posterior facing sinus in 3 patients, left side of posterior facing sinus in 2, non-facing sinus in 4). The mean postoperative follow-up period was 7.4±6.1 years in the Takeuchi group and 9.3±8.5 years in the Translocation group. Actuarial survival rate at 10 years was 87.5% and 71.4%, respectively, and the freedom from either reoperation or re-intervention rate at 10 years was 67.7% and 85.7%, respectively. All the patients who died had a preoperative left ventricular ejection fraction ≤30%. Conclusions: The long-term outcome of the Takeuchi technique was acceptable. Although late reoperation and/or re-intervention cannot be disregarded, Takeuchi can be recommended when the LCA arises far from the aorta.  (Circ J 2013; 77: 1202–1207)
    Download PDF (708K)
Heart Failure
  • Teruhiko Imamura, Koichiro Kinugawa, Shun Minatsuki, Hironori Muraoka, ...
    2013 Volume 77 Issue 5 Pages 1208-1213
    Published: 2013
    Released: April 25, 2013
    [Advance publication] Released: January 12, 2013
    JOURNALS FREE ACCESS
    Background: Urine osmolality (U-OSM) is valuable to predict response to tolvaptan (TLV) in decompensated heart failure patients, but measurement of U-OSM is not always available on site. Methods and Results: Data were collected from 66 hospitalized patients with decompensated heart failure who had received TLV at 3.75–15mg/day. U-OSM, which was estimated using the following formula: 1.07×{2×[(urine sodium (mEq/L)]+[urine urea nitrogen (mg/dl)]/2.8+[urine creatinine (mg/dl)]×2/3}+16, was well correlated with the actual measurement (r=0.938, P<0.001). Criteria consisting of C1 (estimated baseline U-OSM >358mOsm/L) and C2 (%decrease in estimated U-OSM >24% at 4–6h after the first TLV dose) significantly discriminated responders from non-responders (P<0.05). Conclusions: Response to TLV can be predicted using U-OSM, which can be estimated using urine urea nitrogen, sodium, and creatinine concentration data.  (Circ J 2013; 77: 1208–1213)
    Download PDF (783K)
  • Shiro Yamada, Mamoru Sakakibara, Takashi Yokota, Kiwamu Kamiya, Naoya ...
    2013 Volume 77 Issue 5 Pages 1214-1220
    Published: 2013
    Released: April 25, 2013
    [Advance publication] Released: January 30, 2013
    JOURNALS FREE ACCESS
    Background: Adaptive servo-ventilation (ASV) improves cardiac function in patients with heart failure (HF). We compared the hemodynamics of control and HF patients, and identified the predictors for acute effects of ASV in HF. Methods and Results: We performed baseline echocardiographic measurements and hemodynamic measurements at baseline and after 15min of ASV during cardiac catheterization in 11 control and 34 HF patients. Heart rate and blood pressure did not change after ASV in either the control or HF group. Stroke volume index (SVI) decreased from 49.3±7.6 to 41.3±7.6ml/m2 in controls (P<0.0001) but did not change in the HF patients (from 34.8±11.5 to 32.8±8.9ml/m2, P=0.148). In the univariate analysis, pulmonary capillary wedge pressure (PCWP), mitral regurgitation (MR)/left atrial (LA) area, E/A, E/e’, and the sphericity index defined by the ratio between the short-axis and long-axis dimensions of the left ventricle significantly correlated with % change of SVI from baseline during ASV. PCWP and MR/LA area were independent predictors by multivariate analysis. Moreover, responders (15 of 34 HF patients; 44%) categorized by an increase in SVI showed significantly higher PCWP, MR, and sphericity index. Conclusions: Left ventricular structure and MR, as well as PCWP, could predict acute favorable effects on hemodynamics by ASV therapy in HF patients.  (Circ J 2013; 77: 1214–1220)
    Download PDF (915K)
  • Masanobu Miura, Yasuhiko Sakata, Kotaro Nochioka, Jun Takahashi, Tsuyo ...
    2013 Volume 77 Issue 5 Pages 1221-1228
    Published: 2013
    Released: April 25, 2013
    [Advance publication] Released: February 07, 2013
    JOURNALS FREE ACCESS
    Background: Elevated blood urea nitrogen (BUN) observed in patients hospitalized for acute heart failure syndrome (AHFS) may represent increased neurohumoral activation. The purpose of this study was to examine the prognostic impact of BUN changes during hospitalization on the long-term prognosis of AHFS patients. Methods and Results: The Tohoku Acute Heart Failure Registry (n=497) is a multicenter retrospective cohort study enrolling AHFS patients who were admitted in 2007. The 337 survivors (mean age, 76 years; 52% male) were divided into 3 groups according to tertiles of BUN change during hospitalization: Decreased (D-BUN, ΔBUN (BUN level at discharge–BUN level at hospitalization) ≤–1.63mg/dl, n=112); Unchanged (U-BUN, ΔBUN –1.64 to 5.73mg/dl, n=113); Increased (I-BUN, ΔBUN >5.73mg/dl, n=112). The D-BUN group had higher prevalence of lowest glomerular filtration rate during hospitalization, whereas the I-BUN group had higher systolic blood pressure. During a median follow-up period of 2.3 years after discharge, the Kaplan-Meier curve showed that D-BUN and I-BUN had worse prognosis compared with U-BUN. Multivariable logistic model showed that all-cause death was more frequent in I-BUN (hazard ratio, 2.94; 95% confidence interval, 1.51–5.73; P<0.001). Subgroup analysis revealed that BUN increase during hospitalization was associated with all-cause death, regardless of renal function. Conclusions: AHFS patients with a BUN increase during hospitalization have worse long-term prognosis, independent of renal function.  (Circ J 2013; 77: 1221–1228)
    Download PDF (1056K)
Imaging
  • Yosuke Inoue, Daiji Yoshikawa, Hideki Ishii, Satoshi Isobe, Soichiro K ...
    2013 Volume 77 Issue 5 Pages 1229-1234
    Published: 2013
    Released: April 25, 2013
    [Advance publication] Released: February 02, 2013
    JOURNALS FREE ACCESS
    Background: After abdominal aortic aneurysm (AAA) repair, relatively low survival during long-term follow-up remains an unresolved issue. Stress myocardial perfusion single-photon emission computed tomography (SPECT) well predicts future mortality overall, as well as providing diagnoses of coronary artery disease. The prognostic value of myocardial SPECT findings after AAA repair, however, remains unclear. Methods and Results: This study followed 285 patients, all undergoing preoperative pharmacologic stress myocardial perfusion SPECT to determine summed stress score (SSS), then elective AAA repair by open AAA repair or endovascular aneurysm repair. The endpoint of the study was cardiac death. The median follow-up duration was 925 days (range, 541–1,095 days). Twenty-four (8%) died during follow-up. Kaplan-Meier analysis showed that patients with SSS ≥9 had a significantly poorer prognosis than those with SSS <9 (76% vs. 93%, P=0.003). Multivariate Cox proportional hazards analysis indicated that SSS ≥9, diabetes, and chronic kidney disease ≥stage 3 could significantly and independently predict long-term cardiovascular mortality in patients after AAA repair (hazard ratio [HR], 4.2; 95% confidence interval [CI]: 1.8–9.7, P=0.001; HR, 3.0; 95% CI: 1.2–7.4, P=0.020; and HR, 4.1; 95% CI: 1.7–10.1, P=0.029, respectively). Conclusions: Preoperative pharmacologic stress myocardial perfusion SPECT is a useful method to predict long-term cardiovascular mortality for patients undergoing elective AAA repair.  (Circ J 2013; 77: 1229–1234)
    Download PDF (625K)
  • Tomoyuki Kido, Michinobu Nagao, Teruhito Kido, Akira Kurata, Masao Miy ...
    2013 Volume 77 Issue 5 Pages 1235-1241
    Published: 2013
    Released: April 25, 2013
    [Advance publication] Released: February 06, 2013
    JOURNALS FREE ACCESS
    Background: Adenosine triphosphate (ATP) induces relative hypoperfusion in significantly stenotic coronary arteries, but its effect on myocardial strain has not been used clinically for the detection of ischemia. The purpose of this study was to quantify ATP-stress-induced contractile impairment as altered myocardial strain in coronary artery disease (CAD) using tagged magnetic resonance (MR) and to evaluate its diagnostic capability in comparison with ATP-stress myocardial perfusion-MR. Methods and Results: Tagged MR and perfusion-MR under ATP-stress and rest conditions and late gadolinium enhancement (LGE) MR imaging were performed in 22 patients with suspected CAD. The peak absolute value of the circumferential strain (C-strain) was measured in 12 segments. Myocardial segments were categorized as non-ischemic (n=201), ischemic (n=42), or infarcted (n=21) according to the perfusion-MR and LGE MR imaging results. The absolute C-strain was significantly greater under ATP-stress (19±13%) (mean±SD) than under at-rest (15±11%, P<0.001) conditions in non-ischemic segments. Conversely, the absolute C-strain was significantly lower under ATP-stress (10±13%) than under at-rest (16±6%, P<0.01) conditions in ischemic segments. Optimal cutoff values for stress C-strain (–17.5%) could successfully differentiate segments with ischemia or infarction from non-ischemic ones with a sensitivity of 86%, a specificity of 65%, and an area under the curve of 0.79. Conclusions: C-strain analysis using tagged MR could detect ATP-stress-induced contractile impairment in ischemic myocardium.  (Circ J 2013; 77: 1235–1241)
    Download PDF (1037K)
Ischemic Heart Disease
  • Tomohiro Nishino, Yutaka Furukawa, Shuichiro Kaji, Natsuhiko Ehara, Hi ...
    2013 Volume 77 Issue 5 Pages 1242-1252
    Published: 2013
    Released: April 25, 2013
    [Advance publication] Released: December 29, 2012
    JOURNALS FREE ACCESS
    Background: It is controversial whether angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) provide significant survival benefits in patients with coronary artery disease (CAD) but without myocardial infarction (MI). This study investigated whether the association of ACEI/ARB therapy with clinical outcome in patients undergoing percutaneous coronary intervention (PCI) was affected by history of MI. Methods and Results: A total of 11,590 patients undergoing first PCI were divided into 2 groups: those with MI and those without MI. All-cause and cardiovascular mortality were compared between the patients with and without ACEI/ARB at discharge in each group. In patients with MI, significantly lower 3-year all-cause/cardiovascular mortality for patients with ACEI/ARB relative to those without ACEI/ARB was noted in the total patients (all-cause: 6.6% vs. 11.7%, P<0.0001; cardiovascular: 3.8% vs. 6.9%, P<0.0001) and in the 1,007 propensity score-matched pairs (all-cause: 8.2% vs. 11.3%, P=0.018; cardiovascular: 3.7% vs. 5.7%, P=0.014). In patients without MI, however, all-cause (5.2% vs. 5.6%, P=0.56) and cardiovascular (3.2% vs. 3.0%, P=0.23) mortality were similar regardless of whether ACEI/ARB were used or not; and similarly in the 2,061 propensity score-matched pairs (all-cause: 4.1% vs. 5.4%, P=0.33; cardiovascular: 1.4% vs. 2.1%, P=0.30). Conclusions: Use of ACEI/ARB at hospital discharge was associated with lower all-cause/cardiovascular mortality in revascularized CAD patients with MI, but not in those without MI.  (Circ J 2013; 77: 1242–1252)
    Download PDF (982K)
  • Moo Hyun Kim, Hong-Zhe Zhang, Dong Keun Jung
    2013 Volume 77 Issue 5 Pages 1253-1259
    Published: 2013
    Released: April 25, 2013
    [Advance publication] Released: January 30, 2013
    JOURNALS FREE ACCESS
    Background: Previous studies involving a loading dose (LD) of 60mg prasugrel have suggested that active metabolite exposure and pharmacodynamic responses may be higher in persons of Asian ethnicity than in Caucasian subjects. The aim of this study was to determine the pharmacodynamic effect of an LD of 30mg prasugrel and 600mg clopidogrel in healthy Korean volunteers. Methods and Results: Twelve volunteers were randomly assigned to a prasugrel or a clopidogrel group. Following a 2-week washout period, group designations and treatments were switched (6 per group). Platelet function was serially measured via light transmission aggregometry (LTA), VerifyNow and multiple electrode platelet aggregometry (MEA) assays at baseline and 0.5, 2, 6, and 24h after LD. Inhibition of platelet aggregation (IPA) at 0.5–24h after prasugrel was significantly higher (P<0.001) than that achieved by clopidogrel. The prasugrel peak IPA at 2h after LD was 93.7% (±6.2%) compared to the clopidogrel peak IPA at 6h after LD at 65.8% (±17.2%). The VerifyNow and MEA assay yielded results similar to those obtained by LTA. Conclusions: In healthy Korean subjects, a 30-mg LD of prasugrel yields a more rapid, potent and consistent inhibition of platelet function than a 600-mg LD of clopidogrel.  (Circ J 2013; 77: 1253–1259)
    Download PDF (1059K)
  • Takashi Hisamatsu, Takayoshi Ohkubo, Katsuyuki Miura, Takashi Yamamoto ...
    2013 Volume 77 Issue 5 Pages 1260-1266
    Published: 2013
    Released: April 25, 2013
    [Advance publication] Released: January 26, 2013
    JOURNALS FREE ACCESS
    Background: An early repolarization pattern, characterized by an elevation of the QRS-ST junction (J-point) on 12-lead electrocardiography (ECG) is associated with cardiac and sudden death. However, little is known about the prognostic significance of J-point elevation for various disease-specific cardiovascular outcomes, including coronary artery disease (CAD). Methods and Results: To investigate the association between the presence of J-point elevation ≥0.1mV and various disease-specific cardiovascular outcomes, we conducted a 15-year prospective study in a representative general Japanese population of 7,630 individuals (41% men, mean age 52.4 years) who participated in the National Survey of Circulatory Disorders. Cox models were used to estimate the hazard ratios (HRs) adjusted for possible confounding factors. J-point elevation was present in 264 individuals (3.5%) and was associated with an increased risk of cardiac death (adjusted HR, 2.54; 95% confidence interval [CI] 1.40–4.58; P=0.002) and death from CAD (adjusted HR, 4.66; 95% CI 2.30–9.46; P<0.001). In a subgroup analysis by age, the association between J-point elevation and cardiovascular outcomes was more remarkable in middle-aged (<60 years) than in older individuals (≥60 years) (all P for interaction <0.05). Conclusions: J-point elevation on standard 12-lead ECG was an independent predictor of cardiac death and death from CAD in a representative sample of the general Japanese population, particularly among the middle-aged.  (Circ J 2013; 77: 1260–1266)
    Download PDF (793K)
  • Akiko Kawana, Jun Takahashi, Yusuke Takagi, Satoshi Yasuda, Yasuhiko S ...
    2013 Volume 77 Issue 5 Pages 1267-1274
    Published: 2013
    Released: April 25, 2013
    [Advance publication] Released: January 31, 2013
    JOURNALS FREE ACCESS
    Background: Accumulating evidence has demonstrated the gender differences in the clinical characteristics and outcomes of patients with ischemic heart disease. However, it remains to be elucidated whether it is also the case for vasospastic angina (VSA). Methods and Results: We enrolled a total of 1,429 VSA patients (male/female, 1090/339; median age 66 years) in our nationwide multicenter registry by the Japanese Coronary Spasm Association. As compared with male patients, female patients were characterized by older age (median 69 vs. 66 years), lower incidence of smoking (20% vs. 72%) and less significant organic stenosis (9% vs. 16%) (all P=0.001). Multivariate analysis demonstrated that the predictors of major adverse cardiac events (MACE) were considerably different by genders; women were more associated with age and electrical abnormalities, whereas men with structural abnormalities. Overall 5-year MACE-free survival was comparable between both genders. However, when the patients were divided into 3 groups by age [young (<50 years), middle-aged (50–64 years) and elderly (≥65 years)], the survival was significantly lower in the young female group (young 82%, middle-aged 92%, elderly 96%, P<0.01), where a significant interaction was noted between age and smoking. In contrast, the survival was comparable among the 3 age groups of male patients. Conclusions: These results indicate that there are gender differences in the characteristics and outcomes of VSA patients, suggesting the importance of gender-specific management of the disorder.  (Circ J 2013; 77: 1267–1274)
    Download PDF (552K)
  • Kensaku Nishihira, Kinta Hatakeyama, Yoshisato Shibata, Kazuo Kitamura ...
    2013 Volume 77 Issue 5 Pages 1275-1280
    Published: 2013
    Released: April 25, 2013
    [Advance publication] Released: February 02, 2013
    JOURNALS FREE ACCESS
    Background: Thrombus propagation on disrupted atherosclerotic plaque leads to acute myocardial infarction (AMI). Recent studies have shown that the histopathology of the coronary thrombus is associated with myocardial reperfusion, ST-segment recovery, distal embolization and long-term mortality in patients with AMI. Therefore, we investigated the histopathologic characteristics of material aspirated during percutaneous coronary intervention (PCI) in patients with AMI, and assessed whether the histologic findings are related to in-hospital mortality. Methods and Results: In this prospective single-center registry, coronary materials were obtained during PCI from 264 AMI patients within 24h of the onset of anginal symptoms. Organized thrombus, calcification and plaque components in the aspirated material were morphologically assessed. In-hospital deaths occurred in 17 (6%) patients. Organized thrombi were found in 91 (34%) of 264 patients, calcification was identified in 44 (17%) and plaque components in 117 (44%) patients. Rates of in-hospital all-cause mortality were significantly higher among patients with than without organized thrombus (P<0.05). Multivariate analysis also identified organized thrombus as an independent predictor of in-hospital death, as well as age, a history of myocardial infarction and the presence of shock (P<0.05). In contrast, calcification and plaque components were not significantly associated with in-hospital mortality. Conclusions: Our results suggest that organized thrombus in aspirated coronary material is an independent predictor of in-hospital mortality of patients with AMI.  (Circ J 2013; 77: 1275–1280)
    Download PDF (783K)
Metabolic Disorder
  • Aapo Veijalainen, Tuomo Tompuri, Tomi Laitinen, Niina Lintu, Anna Viit ...
    2013 Volume 77 Issue 5 Pages 1281-1288
    Published: 2013
    Released: April 25, 2013
    [Advance publication] Released: January 25, 2013
    JOURNALS FREE ACCESS
    Background: Childhood metabolic syndrome (MetS) has been found to predict adulthood MetS, type 2 diabetes and cardiovascular disease, emphasizing the early identification of children at increased risk of these diseases. Children with clustering of metabolic risk factors have been reported to have a mild arterial stiffness and endothelial dysfunction, but limited evidence is available from population-based samples of children. Methods and Results: The associations of metabolic risk factors with arterial stiffness, tone and endothelial function were studied in 173 prepubertal children (90 girls) 6–8 years of age. MetS was assessed both by continuous MetScore and dichotomously. Stiffness index (SI), reflection index (RI) and finger skin temperature (FST) were measured before and after maximum exercise test, and percent change was calculated for RI (RI%Δ) and FST (FST%Δ). MetScore (r=0.26, P=0.001), fasting insulin (r=0.24, P=0.002), fasting triglycerides (r=0.20, P=0.009), systolic (SBP; r=0.24, P=0.002) and diastolic blood pressure (DBP; r=0.19, P=0.013) correlated with SI. MetScore (r=–0.17, P=0.024, r=0.21, P=0.006), waist circumference (r=–0.19, P=0.012, r=0.23, P=0.003) and SBP (r=–0.16, P=0.035, r=0.21, P=0.005) correlated with RI and FST. High-density lipoprotein cholesterol correlated with FST (r=–0.22, P=0.004) and FST%Δ (r=–0.24, P=0.002). RI decreased and FST increased with exercise (P<0.001). Waist circumference correlated inversely with RI%Δ in boys (r=–0.22, P=0.046) and directly with RI%Δ in girls (r=0.27, P=0.011). Conclusions: Metabolic risk factors are associated with arterial stiffness, tone and endothelial function in prepubertal children.  (Circ J 2013; 77: 1281–1288)
    Download PDF (823K)
Molecular Cardiology
  • Jin Joo Park, Kyung Woo Park, Jeehoon Kang, Ki-Hyun Jeon, Si-Hyuck Kan ...
    2013 Volume 77 Issue 5 Pages 1289-1296
    Published: 2013
    Released: April 25, 2013
    [Advance publication] Released: February 09, 2013
    JOURNALS FREE ACCESS
    Background: Calcium-channel blockers (CCBs) inhibit the CYP3A4 enzyme, which is involved in clopidogrel activation. Studies have shown conflicting results regarding the effect of concomitant CCB administration on clopidogrel response. We investigated the relationship between CYP3A4 genotype and the inhibitory effect of CCBs on clopidogrel response. Methods and Results: Clopidogrel on-treatment platelet reactivity (OPR) was measured and CYP3A4 (IVS10+12G>A) genotyped in 1,247 consecutive patients with drug-eluting stent implantation. The mean OPR was 231±83 (P2Y12 reaction units: PRU). In total, 332 (26.6%) CCB users had higher OPR compared with 915 (73.4%) non-CCB users (245±84 vs. 227±83 PRU, P=0.001). The distribution of CYP3A4 (IVS10+12G>A) genotype was 63.6%, 32.6% and 3.8% for GG, GA and AA genotypes, respectively. After adjustment for possible confounding factors, the number of A-alleles was associated with increased vulnerability to CCB use (effect of CCB use ΔPRU: +8 PRU, P=0.210, +24 PRU, P=0.012, +50 PRU, P=0.025, for patients with 0, 1, and 2 A-alleles, respectively, +24 PRU, P=0.005 for GA/AA genotypes). Furthermore, only in the GA/AA-genotype did CCB use result in a significantly increased risk for high-OPR (odds ratio 1.84, 95% confidence interval 1.15–2.92, P=0.010). Conclusions: CCB use is associated with increased OPR. The number of CYP3A4 (IVS10+12G>A) A-alleles may be associated with an increased vulnerability to the effects of CCBs on clopidogrel response variation.  (Circ J 2013; 77: 1289–1296)
    Download PDF (698K)
Regenerative Medicine
  • Tao Yu, Shigeru Miyagawa, Kenji Miki, Atsuhiro Saito, Satsuki Fukushim ...
    2013 Volume 77 Issue 5 Pages 1297-1306
    Published: 2013
    Released: April 25, 2013
    [Advance publication] Released: February 08, 2013
    JOURNALS FREE ACCESS
    Background: Induced pluripotent stem cells (iPSCs) hold promise for a new era in treating heart failure. However, the functional microstructure of iPSC-derived cardiomyocytes (iPSC-CMs) and their ability to attach to the extracellular matrix of the recipient myocardium require further elucidation. Thus, we analyzed the functional microstructure and adhesion molecules of iPSC-CM. Methods and Results: Immunostaining analysis showed that iPSC-CMs were similar to neonatal cardiomyocytes (CMs) in expressing the cytoskeletal proteins myosin heavy chain (MHC), myosin light chain (MLC) 2a, MLC2v, and especially β-MHC (a neonatal CM marker), as well as the adhesion molecules N-cadherin, α7-integrin, dystrophin, α-dystroglycan, α-sarcoglycan, and laminin-α2. Electron microscopy showed abundant myofibrillar bundles with transverse Z-bands and a developed mitochondrial structure in both iPSC-CMs and neonatal CMs, although the iPSC-CMs contained fewer mitochondria with lower-density cristae. When transplanted from in vitro conditions to nude rat hearts, iPSC-CMs acquired the ability to express α-MHC, a molecule specific to adult CMs. Mechanical stretch or stimulation by insulin-like growth factor-1 enhanced the α-MHC expression in iPSC-CMs in vitro. Conclusions: Our findings in vitro and in vivo indicate that CMs derived from iPSCs contain cardiac-specific organelles and adhesion systems. These results indicate that iPSC-derived CMs may be useful in new cell therapies for heart failure.  (Circ J 2013; 77: 1297–1306)
    Download PDF (2064K)
  • Tsukasa Kamakura, Takeru Makiyama, Kenichi Sasaki, Yoshinori Yoshida, ...
    2013 Volume 77 Issue 5 Pages 1307-1314
    Published: 2013
    Released: April 25, 2013
    [Advance publication] Released: February 09, 2013
    JOURNALS FREE ACCESS
    Background: In the short- to mid-term, cardiomyocytes generated from human-induced pluripotent stem cells (hiPSC-CMs) have been reported to be less mature than those of adult hearts. However, the maturation process in a long-term culture remains unknown. Methods and Results: A hiPSC clone generated from a healthy control was differentiated into CMs through embryoid body (EB) formation. The ultrastructural characteristics and gene expressions of spontaneously contracting EBs were analyzed through 1-year of culture after cardiac differentiation was initiated. The 14-day-old EBs contained a low number of myofibrils, which lacked alignment, and immature high-density Z-bands lacking A-, H-, I-, and M-bands. Through the long-term culture up to 180 days, the myofibrils became more tightly packed and formed parallel arrays accompanied by the appearance of mature Z-, A-, H-, and I-bands, but not M-bands. Notably, M-bands were finally detected in 360-day-old EBs. The expression levels of the M-band-specific genes in hiPSC-CMs remained lower in comparison with those in the adult heart. Immunocytochemistry indicated increasing number of MLC2v-positive/MLC2a-negative cells with decreasing number of MLC2v/MLC2a double-positive cells, indicating maturing of ventricular-type CMs. Conclusions: The structural maturation process of hiPSC-CMs through 1-year of culture revealed ultrastructural sarcomeric changes accompanied by delayed formation of M-bands. Our study provides new insight into the maturation process of hiPSC-CMs.  (Circ J 2013; 77: 1307–1314)
    Download PDF (1999K)
Renal Disease
  • Masaki Ohsawa, Kozo Tanno, Kazuyoshi Itai, Tanvir Chowdhury Turin, Tom ...
    2013 Volume 77 Issue 5 Pages 1315-1325
    Published: 2013
    Released: April 25, 2013
    [Advance publication] Released: February 21, 2013
    JOURNALS FREE ACCESS
    Background: Whether estimated glomerular filtration rate (eGFR) calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Study equation (eGFRCKDEPI) improves risk prediction compared to that calculated using the Modification of Diet in Renal Disease (MDRD) study equation (eGFRMDRD) has not been examined in a prospective study in Japanese people. Methods and Results: Participants (n=24,560) were divided into 4 stages (1, ≥90; 2, 60–89 (reference); 3a, 45–59; 3b+ <45ml·min–1·1.73m–2) according to eGFRCKDEPI or eGFRMDRD. Endpoints were all-cause death, myocardial infarction (MI) and stroke. Area under the receiver operating characteristic curves (95% confidence intervals) for predicting all-cause death, MI and stroke by eGFRCKDEPI vs. eGFRMDRD were 0.680 (0.662–0.697) vs. 0.582 (0.562–0.602); 0.718 (0.665–0.771) vs. 0.642 (0.581–0.703); and 0.656 (0.636–0.676) vs. 0.576 (0.553–0.599), respectively. Multivariate-adjusted Cox regression and Poisson regression analysis results were similar for adjusted incidence rates and adjusted hazard ratios in each corresponding stage between the 2 models and no differences were found in model assessment parameters. Net reclassification improvement (NRI) for predicting all-cause death, MI and stroke were estimated to be 6.7% (P<0.001), –1.89% (P=0.029) and –0.20% (P=0.421), respectively. Conclusions: Better discrimination was achieved using eGFRCKDEPI than eGFRMDRD on univariate analysis. NRI analysis indicated that the use of eGFRCKDEPI instead of eGFRMDRD offered a significant improvement in reclassification of death risk.  (Circ J 2013; 77: 1315–1325)
    Download PDF (1108K)
Vascular Biology and Vascular Medicine
  • Yelixiati Adelibieke, Hidehisa Shimizu, Shinichi Saito, Roumyana Miron ...
    2013 Volume 77 Issue 5 Pages 1326-1336
    Published: 2013
    Released: April 25, 2013
    [Advance publication] Released: January 19, 2013
    JOURNALS FREE ACCESS
    Background: Erythropoietin (EPO) is used to treat anemia in patients with chronic kidney disease (CKD). A wide variation in individual response to EPO, however, is often observed, causing EPO resistance. EPO exhibits not only hematopoietic but also extra-hematopoietic functions such as endothelial effects. Indoxyl sulfate, a uremic toxin, is involved in endothelial dysfunction, and consequently, the pathogenesis of CKD-associated cardiovascular disease. The aim of the present study was to determine the effect of indoxyl sulfate on the extra-hematopoietic functions of EPO in human umbilical vein endothelial cells (HUVECs). Methods and Results: HUVECs were incubated with or without indoxyl sulfate or an Akt inhibitor, and then stimulated with or without EPO. Indoxyl sulfate suppressed EPO-induced survival/proliferation, anti-apoptosis function, phosphorylation of endothelial nitric oxide synthase, and the expression of thrombospondin-1, an erythroid-stimulating factor, in HUVECs. Although EPO induced phosphorylation of both Akt and extracellular signal-regulated kinases (ERK) in HUVECs, indoxyl sulfate suppressed phosphorylation of Akt but not ERK. An Akt kinase inhibitor or Akt small interfering RNA suppressed all the EPO-induced cellular effects in HUVECs. As a site of action of indoxyl sulfate on EPO signaling, indoxyl sulfate attenuated EPO-induced tyrosine phosphorylation of EPO receptor (EPOR) in HUVECs. Conclusions: Indoxyl sulfate negatively regulates the EPOR-Akt pathway in endothelial cells, and might contribute to EPO resistance and endothelial dysfunction in patients with CKD.  (Circ J 2013; 77: 1326–1336)
    Download PDF (4248K)
  • Junichi Matsubara, Seigo Sugiyama, Eiichi Akiyama, Satomi Iwashita, Hi ...
    2013 Volume 77 Issue 5 Pages 1337-1344
    Published: 2013
    Released: April 25, 2013
    [Advance publication] Released: February 02, 2013
    JOURNALS FREE ACCESS
    Background: Dipeptidyl peptidase 4 (DPP4) inhibitors are used for treatment of diabetes mellitus (DM). We hypothesized that sitagliptin, a DPP4-inhibitor, could improve endothelial dysfunction in DM patients with coronary artery disease (CAD). Methods and Results: The 40 patients with CAD and uncontrolled DM, aged 68.7±9.4 years (mean±standard deviation) (50% males, hemoglobin A1c [HbA1c] 7.4±1.0%) were assigned to either additional treatment with sitagliptin (50mg/day, n=20) or aggressive conventional treatment (control, n=20) for 6 months. Endothelial function was assessed by the reactive hyperemia peripheral arterial tonometry index (RHI). The clinical characteristics at baseline were not different between the groups. After treatment, fasting blood glucose and insulin levels, and lipid profiles were not different between the groups. HbA1c levels significantly improved similarly in both groups. The percent change in RHI was greater in the sitagliptin group than in the control group (62.4±59.2% vs. 15.9±22.0%, P<0.01). Furthermore, treatment with sitagliptin resulted in a significant decrease in the high-sensitivity C-reactive protein (hsCRP) level, but no such change was noted in the control group. Linear regression analysis demonstrated a significant negative relation between changes in RHI and hsCRP, but not between RHI and HbA1c. Conclusions: Sitagliptin significantly improved endothelial function and inflammatory state in patients with CAD and uncontrolled DM, beyond its hypoglycemic action. These findings suggest that sitagliptin has beneficial effects on the cardiovascular system in DM patients.  (Circ J 2013; 77: 1337–1344)
    Download PDF (994K)
Images in Cardiovascular Medicine
Letter to the Editor
feedback
Top