Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Volume 74 , Issue 11
Showing 1-46 articles out of 46 articles from the selected issue
Reviews
  • – Promising New Target in Cardiovascular Therapy –
    Kimio Satoh, Hiroaki Shimokawa, Bradford C. Berk
    2010 Volume 74 Issue 11 Pages 2249-2256
    Published: 2010
    Released: October 25, 2010
    [Advance publication] Released: October 15, 2010
    JOURNALS FREE ACCESS
    Cyclophilin A (CyPA) has been studied as a multifunctional protein that is upregulated in a variety of inflammatory conditions, such as rheumatoid arthritis, autoimmune disease, and cancer. CyPA has been classified as an immunophilin and has a variety of intracellular functions, including intracellular signaling, protein trafficking, and the regulation of other proteins activity. Besides its intracellular functions, CyPA is a secreted molecule that has a physiological and pathological role in cardiovascular diseases, making it a potential biomarker and mediator in cardiovascular diseases, such as vascular stenosis, atherosclerosis, and abdominal aortic aneurysms. (Circ J 2010; 74: 2249-2256)
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  • Hae-Young Lee, Byung-Hee Oh
    2010 Volume 74 Issue 11 Pages 2257-2262
    Published: 2010
    Released: October 25, 2010
    [Advance publication] Released: October 15, 2010
    JOURNALS FREE ACCESS
    Arterial walls stiffen with age. The most consistent and well-reported changes are luminal enlargement with wall thickening and a reduction of elastic properties at the level of large elastic arteries. Longstanding arterial pulsation in the central artery causes elastin fiber fatigue and fracture. Increased vascular calcification and endothelial dysfunction are also characteristic of arterial aging. These changes lead to increased pulse wave velocity, especially along central elastic arteries, and increases in systolic blood pressure and pulse pressure. Vascualar aging is accelerated by coexsiting cardiovascular risk factors, such as hypertension, metabolic syndrome and diabetes. Vascular aging is an independent risk factor for cardiovascular disease, from atherosclerosis to target organ damage, including coronary artery disease, stroke and heart failure. Various strategies, especially controlling hypertension, show benefit in preventing, delaying or attenuating vascular aging. (Circ J 2010; 74: 2257-2262)
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  • Tomoyuki Yasuda, Tatsuro Ishida, Daniel J. Rader
    2010 Volume 74 Issue 11 Pages 2263-2270
    Published: 2010
    Released: October 25, 2010
    [Advance publication] Released: October 15, 2010
    JOURNALS FREE ACCESS
    Endothelial lipase (EL) is a phospholipase that belongs to the lipoprotein lipase (LPL) family, which includes LPL and hepatic lipase (HL). Similar to LPL and HL, EL regulates lipoprotein metabolism, mainly high-density lipoprotein (HDL) metabolism and HDL cholesterol (HDL-C) levels in humans and mice. Existing data strongly suggest that inhibition of EL in humans would be expected to increase the HDL-C level. However, it has not been definitively established whether the effect of EL activity on HDL-C levels translates into effects on reverse cholesterol transport or atherosclerosis. The available data regarding the impact of EL expression and activity on HDL metabolism, reverse cholesterol transport, and atherosclerosis are reviewed. (Circ J 2010; 74: 2263-2270)
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  • Barry J. Maron
    2010 Volume 74 Issue 11 Pages 2271-2282
    Published: 2010
    Released: October 25, 2010
    [Advance publication] Released: October 16, 2010
    JOURNALS FREE ACCESS
    Hypertrophic cardiomyopathy (HCM) is the most common cause of sudden cardiac death (SCD) in young people, including trained athletes. It is now 30 years since the introduction of implantable cardioverter-defibrillators (ICDs) to clinical cardiovascular practice and coronary artery disease, and now device therapy represents the most significant therapeutic innovation and the only definitive strategy for prolonging the life of HCM patients. ICDs have proved effective in preventing SCD in young HCM patients with appropriate intervention rates of 11% for secondary and 4% for primary prevention, despite massive left ventricular (LV) hypertrophy, LV outflow obstruction, diastolic dysfunction or microvascular ischemia. Targeting candidates for prophylactic ICD therapy can be complex, compounded by the unpredictability of the arrhythmogenic substrate, the absence of a dominant risk factor, and difficulty in assembling randomized trials. However, a single major risk factor is often sufficient to justify an ICD, although additional markers and other disease features can resolve ambiguous decision-making. Nevertheless, the absence of all risk factors does not convey absolute immunity to SCD. The current risk factor algorithm, when combined with a measure of individual physician judgment (and patient autonomy considerations), is an effective guide to identifying high-risk HCM patients. ICDs have altered the natural history of HCM for many patients and provided an opportunity to achieve many decades of productive life, and the potential for normal or near-normal longevity. Indeed, prevention of SCD has now become a new paradigm in the management of HCM. (Circ J 2010; 74: 2271-2282)
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Editorials
Original Articles
Arrhythmia/Electrophysiology
  • – When Should You Resume Driving After an Implantable Cardioverter Defibrillator Replacement? –
    Hiro Kawata, Takashi Noda, Takashi Kurita, Kenichiro Yamagata, Yuko Ya ...
    2010 Volume 74 Issue 11 Pages 2301-2307
    Published: 2010
    Released: October 25, 2010
    [Advance publication] Released: September 18, 2010
    JOURNALS FREE ACCESS
    Background: The intervals of the driving restrictions after an implantable cardioverter defibrillator (ICD) replacement vary across the different countries around the world. However, little is known regarding the appropriate duration for driving restrictions after an ICD replacement. The aim of this study was to investigate the clinical effect of ICD replacements and to elucidate when to resume driving an automobile after an ICD replacement. Methods and Results: The study reviewed 139 consecutive patients with an ICD replacement in order to evaluate the incidence of ICD therapies before and after ICD replacements, and to assess the time-dependence of the ICD therapies after the ICD replacement. There was no significant difference in the incidence of ICD therapies delivered during durations of 3 months and 6 months before and after the ICD replacement (P=0.28, and 1.0, respectively). ICD therapies after the replacements were observed in 8.6% of the patients who were legally eligible to drive according to the Japanese guidelines at 1 year, and that was associated with a relatively low annual risk of death or injury to others. Conclusions: Implantable cardioverter defibrillator replacements did not affect the future ICD therapies under similar algorithms. The appropriate interval for driving restrictions after an ICD replacement is recommended to be a week or so, with a system integrity check performed before resumption of driving. (Circ J 2010; 74: 2301-2307)
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  • Satoshi Yasuda, Hirotaka Sawano, Hiroshi Hazui, Isao Ukai, Hiroyuki Yo ...
    2010 Volume 74 Issue 11 Pages 2308-2313
    Published: 2010
    Released: October 25, 2010
    [Advance publication] Released: September 18, 2010
    JOURNALS FREE ACCESS
    Background: Nifekalant hydrochloride (NIF) is an intravenous class-III antiarrhythmic agent that purely blocks the K+-channel without inhibiting β-adrenergic receptors. The present study was designed to investigate the feasibility of NIF as a life-saving therapy for out-of-hospital ventricular fibrillation (VF). Methods and Results: The Japanese Population-based Utstein-style study with basic and advanced Life Support Education study was a multi-center registry study with 4 participating institutes located at the northern urban area of Osaka, Japan. Eligible patients were those treated with NIF because of out-of-hospital VF refractory to 3 or more precordial shocks and intravenous epinephrine. Between February 2006 and February 2007, 17 patients were enrolled for the study. The time from a call for emergency medical service to the first shock was 12(6-26)min. The time from the first shock to the NIF administration was 25.5(9-264)min and the usage dose of NIF was 25(15-210)mg. When excluding 3 patients in whom percutaneous extracorporeal membrane oxygenation was applied before NIF administration, the rate of return of spontaneous circulation was 86% and the rate of admission alive to the hospital was 79%. One patient developed torsade de pointes. Conclusions: Intravenous administration of NIF seems to be feasible as a potential therapy for advanced cardiac life-support in patients with out-of-hospital VF, and therefore further study is warranted. (Circ J 2010; 74: 2308-2313)
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Cardiovascular Intervention
  • – The DATE (Duration of Dual Antiplatelet Therapy After Implantation of Endeavor Stent) Registry –
    Joo-Yong Hahn, Young Bin Song, Jin-Ho Choi, Sung-Hyuk Choi, Sung Yun L ...
    2010 Volume 74 Issue 11 Pages 2314-2321
    Published: 2010
    Released: October 25, 2010
    [Advance publication] Released: October 02, 2010
    JOURNALS FREE ACCESS
    Background: The optimal duration of dual antiplatelet therapy remains controversial. Methods and Results: Between December 2006 and March 2008, 823 patients were enrolled in a prospective multicenter registry for 3-month dual antiplatelet therapy (aspirin 100-200mg+clopidogrel 75mg daily) followed by aspirin mono-therapy after zotarolimus-eluting stents (ZES). Major exclusion criteria were: cardiogenic shock, stent thrombosis (ST)-segment elevation myocardial infarction (MI) within 48h, previous drug-eluting stent implantation, severe left ventricular dysfunction, bifurcation lesions requiring 2-stenting, left main and graft lesions. The primary outcome was a composite of cardiac death, MI, or ST at 1 year. The median duration of dual antiplatelet therapy was 95 days (interquartile range 90-101). At 1 year, 3 patients (0.4%) had cardiac deaths, 3 patients (0.4%) had MI, and 4 patients (0.5%) had definite or probable ST, leading to the primary outcome in 5 patients (0.6%). Death, MI, or any revascularization occurred in 68 patients (8.3%). Among patients who were event-free at 3 months (n=812), clopidogrel was discontinued at 3 months in 661 patients and was continued for longer than 3 months in 151 patients. Discontinuation of clopidogrel at 3 months did not increase the primary outcome (HR 0.90; 95%CI, 0.09-9.02), death, MI, or any revascularization (HR 0.89; 95%CI, 0.48-1.67) after adjustment for the propensity score. Conclusions: Three-month dual antiplatelet therapy seems to be feasible after ZES implantation in relatively low-risk patients. (Circ J 2010; 74: 2314-2321)
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  • - The COBIS (Coronary Bifurcation Stenting) Registry -
    Hyeon-Cheol Gwon, Seung-Hyuk Choi, Young Bin Song, Joo-Yong Hahn, Myun ...
    2010 Volume 74 Issue 11 Pages 2322-2328
    Published: 2010
    Released: October 25, 2010
    [Advance publication] Released: September 28, 2010
    JOURNALS FREE ACCESS
    Background: Limited data exists regarding long-term clinical results and predictors of adverse outcomes after drug-eluting stents (DES) implantation for coronary bifurcation lesions in a real-world practice. Methods and Results: A total of 1,691 non-left main bifurcation lesions with side branches ≥2.0mm in 1,668 patients undergoing DES implantation between January 2004 and June 2006 from 16 centers in Korea were evaluated. True bifurcation was found in 69.2% of lesions and 82.7% of lesions were treated with 1-stent technique. During follow-up (median 22 months), cardiac death occurred in 0.9%, myocardial infarction (MI) in 1.2%, target lesion revascularization (TLR) in 4.7% and stent thrombosis in 0.7% of patients. There was no significant difference in major adverse cardiac events (MACE: composite of cardiac death, MI and TLR) between the 1-stent and the 2-stent groups (6.1% vs 7.5%, P=0.36). Stent length in the main vessel (hazard ratio (HR) 1.02, 95% confidence interval (CI) 1.001-1.03, P=0.03), paclitaxel-eluting stent (HR 1.98, 95%CI 1.34-2.92, P=0.001) and kissing ballooning (HR 2.01, 95%CI 1.29-3.13, P=0.002) were independent predictors of MACE. Kissing ballooning increased the risk of MACE especially in the 1-stent group, but not in the 2-stent group. Conclusions: In this large real-world registry, overall outcomes after DES implantation in bifurcation lesions were favorable and similar between the 1-stent and 2-stent groups. (Circ J 2010; 74: 2322-2328)
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  • Kensaku Nishihira, Yoshisato Shibata, Tetsunori Ishikawa, Katsumasa No ...
    2010 Volume 74 Issue 11 Pages 2329-2333
    Published: 2010
    Released: October 25, 2010
    [Advance publication] Released: September 28, 2010
    JOURNALS FREE ACCESS
    Background: In-stent restenosis (ISR) remains a persistent, unresolved issue even in the era of percutaneous coronary intervention (PCI) using drug-eluting stents. The present study compares the clinical and angiographic outcomes of using sirolimus-eluting stents (SES) for re-intervention against ISR that was originally treated with sirolimus-eluting or bare-metal (BMS) stents. Methods and Results: This prospective single-center registry investigated 179 ISR lesions in 158 consecutive patients (53 lesions in 49, and 126 in 109 patients originally treated with SES and BMS, respectively), who had undergone re-intervention with SES. The patients were clinically and angiographically followed up at 8 months after re-PCI. The incidence of re-restenosis (29 vs 12%, P<0.01), ischemia-driven target lesion revascularization (TLR; 21 vs 8%, P<0.05) and major adverse cardiac events (MACE; 21 vs 9%, P<0.05) were significantly greater in ISR lesions originally treated with SES than in those originally treated with BMS at 8 months after re-PCI. Moreover, late luminal loss was significantly greater in the group with post-SES restenosis (P<0.05). Even after adjustment, post-SES restenosis was the only independent predictor of re-restenosis and MACE (P<0.05, each). Conclusions: Although the re-restenosis rate is acceptable, the incidence rates of late restenosis, ischemia-driven TLR and MACE are higher after repeated SES implantation to treat SES, than BMS restenosis. These results might affect the mid-term clinical outcomes of re-intervention with SES. (Circ J 2010; 74: 2329-2333)
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  • - Pooled IVUS Results From the ZoMaxx I and II Trials -
    Katsuhisa Waseda, Takao Hasegawa, Junya Ako, Yasuhiro Honda, Eberhard ...
    2010 Volume 74 Issue 11 Pages 2334-2339
    Published: 2010
    Released: October 25, 2010
    [Advance publication] Released: September 28, 2010
    JOURNALS FREE ACCESS
    Background: The ZoMaxx I and II trials were randomized controlled studies of the zotarolimus-eluting, phosphorylcholine-coated, TriMaxx stent for the treatment of de novo coronary lesions. The aim of this study was to compare the vessel response between zotarolimus- (ZES) and paclitaxel-eluting stents (PES) using intravascular ultrasound (IVUS). Methods and Results: Data were obtained from the ZoMaxx I and II trials, in which a standard IVUS parameter was available in 263 cases (baseline and 9-months follow up). Neointima-free frame ratio was calculated as the number of frames without IVUS-detectable neointima divided by the total number of frames within the stent. While an increase in vessel and plaque was observed in PES from baseline to follow up, there was no significant change in ZES. At follow up, % neointimal obstruction was significantly higher (15.4±8.8% vs 11.3±9.7%), and minimum lumen area at follow up was significantly smaller in ZES compared to PES. However, the incidence of IVUS-defined restenosis (maximum cross-sectional narrowing >60%) was similar in the 2 groups (3.2% vs 6.7%). Neointima-free frame ratio was significantly lower in ZES. There were 5 cases of late incomplete stent apposition in PES and none in ZES. Conclusions: These IVUS results demonstrate a similar incidence of severe narrowing between these 2 DES. There was a moderate increase in neointimal hyperplasia that was associated with a greater extent of neointimal coverage in ZES compared with PES. (Circ J 2010; 74: 2334-2339)
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Cardiovascular Surgery
  • Sang-Ho Cho, Chun-Sung Byun, Kwan-Wook Kim, Byung-Chul Chang, Kyung-Jo ...
    2010 Volume 74 Issue 11 Pages 2340-2345
    Published: 2010
    Released: October 25, 2010
    [Advance publication] Released: September 29, 2010
    JOURNALS FREE ACCESS
    Background: Aortic valve replacement (AVR) improves left ventricular (LV) systolic function in patients with chronic aortic regurgitation (AR). The objective of this study is to determine predictors for normalization of impaired LV systolic function after valve replacement for chronic AR. Methods and Results: Between 1997 and 2007, 171 patients underwent AVR for severe chronic AR. Of these patients, 79 patients with LV systolic dysfunction or severe LV dilatation preoperatively, who were evaluated by echocardiography at predischarge and early follow up (mean, 6 months) were examined. The mean preoperative ejection fraction was 49%. The mean LV end-systolic and end-diastolic dimensions were 52.32±8.35mm and 69.59±7.80mm, respectively. In the early follow up, 62 of 79 patients exhibited restored normal LV function. LV end-systolic dimension and LV end-diastolic dimension were significantly decreased early after AVR (52.32±8.35mm vs 37.82±6.88mm, and 69.59±7.80mm vs 51.55±6.40mm, respectively). Operative mortality was 3.7%. Multivariate stepwise regression analysis revealed that preoperative indexed LV end-systolic and end-diastolic dimensions were independent predictors of restored LV systolic function. The sensitivity and specicity in predicting normalization of LV function were 88% and 92% for indexed LVESD <35.32mm/m2 and 71% and 86% for indexed LVEDD <44.42mm/m2. Conclusions: In patients who received a valve replacement for chronic AR, smaller indexed LV systolic and diastolic dimensions were associated with early restoration of LV systolic function. (Circ J 2010; 74: 2340-2345)
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Heart Failure
  • Kazuhide Ogino, Masahiko Kato, Yoshiyuki Furuse, Yoshiharu Kinugasa, Y ...
    2010 Volume 74 Issue 11 Pages 2346-2352
    Published: 2010
    Released: October 25, 2010
    [Advance publication] Released: September 04, 2010
    JOURNALS FREE ACCESS
    Background: Angiotensin II and insulin resistance (IR) have clinical implications in the pathophysiology of chronic heart failure (CHF). However, it is still unclear whether the combination of an angiotensin-receptor blocker and angiotensin-converting enzyme inhibitor (ACEI) improves IR in CHF patients who do not receive β-blockers. Thus, the aim of the present study was to evaluate the effects of losartan on glucose metabolism and inflammatory cytokines in CHF patients treated with ACEI but not β-blockers. Methods and Results: The effect of losartan treatment for 16 weeks on IR was analyzed in 16 CHF patients in a randomized crossover trial. Insulin level and homeostasis model IR index (HOMA-IR) decreased significantly (P<0.05), but fasting plasma glucose did not change significantly. Serum tumor necrosis factor (TNF)-α, interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1 levels were significantly decreased with losartan (P<0.05). Furthermore, the changes in IL-6 and MCP-1 levels were significantly correlated with the reduction in HOMA-IR (P<0.05), but the change in TNF-α levels was not significantly correlated. Conclusions: The addition of losartan to ACEI therapy improved IR and decreased inflammatory cytokines in CHF patients who did not receive β-blockers. (Circ J 2010; 74: 2346-2352)
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Hypertension and Circulatory Control
  • Yumiko Hiura, Yasuharu Tabara, Yoshihiro Kokubo, Tomonori Okamura, Tet ...
    2010 Volume 74 Issue 11 Pages 2353-2359
    Published: 2010
    Released: October 25, 2010
    [Advance publication] Released: September 18, 2010
    JOURNALS FREE ACCESS
    Supplementary material
    Background: Large-scale genome-wide association studies (GWAS) have been successful in identifying genes that contribute to common diseases and phenotypes. A GWAS of hypertension-related phenotypes in a Japanese population was conducted in the current study. Methods and Results: A total of 936 participants were recruited from the Suita Study and a GWAS with 538,732 single nucleotide polymorphisms (SNP) was performed. The phenotypes included were systolic and diastolic blood pressure (SBP and DBP), body mass index (BMI), waist-to-hip ratio (WHR), plasma renin activity (PRA), plasma aldosterone concentration (PAC), plasma brain natriuretic peptide (BNP) concentration and alcohol consumption (AC). The SNP exceeding the genome-wide significance level were subjected to subsequent association studies using samples available from the Suita Study and Nomura Study. There is no master gene in the Japanese population that profoundly affects SBP, DBP, BMI, WHR, PRA and PAC. AC was influenced by the functional polymorphism in ALDH2, which affected BP levels in men. The BNP concentration was influenced by a polymorphism in the 3' region of the gene encoding for BNP. However, this polymorphism did not influence blood pressure (BP). Six SNP were identified to be associated with hypertension in both the Suita and Nomura studies. Conclusions: Although several candidate SNP relevant to hypertension and those influencing AC and BNP were identified, our middle-sized GWAS indicated that there is no master gene in Japanese people that profoundly affects BP-related phenotypes. (Circ J 2010; 74: 2353-2359)
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Imaging
  • – A Study Comparing Acutely Symptomatic and Asymptomatic Patients –
    Chengcheng Zhu, Zhongzhao Teng, Umar Sadat, Victoria E. Young, Martin ...
    2010 Volume 74 Issue 11 Pages 2360-2364
    Published: 2010
    Released: October 25, 2010
    [Advance publication] Released: September 08, 2010
    JOURNALS FREE ACCESS
    Background: Biomechanical stresses play an important role in determining plaque stability. Quantification of these simulated stresses can be potentially used to assess plaque vulnerability and differentiate different patient groups. Methods and Results: 54 asymptomatic and 45 acutely symptomatic patients underwent in vivo multicontrast magnetic resonance imaging (MRI) of the carotid arteries. Plaque geometry used for nite element analysis was derived from in vivo MRI at the sites of maximum and minimum plaque burden. In total, 198 slices were used for the computational simulations. A pre-shrink technique was used to refine the simulation. Maximum principle stress at the vulnerable plaque sites (ie, critical stress) was extracted for the selected slices and a comparison was performed between the 2 groups. Critical stress in the slice with maximum plaque burden is significantly higher in acutely symptomatic patients as compared to asymptomatic patients (median, inter quartile range: 198.0 kPa (119.8-359.0 kPa) vs 138.4 kPa (83.8-242.6 kPa), P=0.04). No significant difference was found in the slice with minimum plaque burden between the 2 groups (196.7 kPa (133.3-282.7 kPa) vs 182.4 kPa (117.2-310.6 kPa), P=0.82). Conclusions: Acutely symptomatic carotid plaques have significantly high biomechanical stresses than asymptomatic plaques. This might be potentially useful for establishing a biomechanical risk stratification criteria based on plaque burden in future studies. (Circ J 2010; 74: 2360-2364)
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Ischemic Heart Disease
  • – A Pilot, Randomized, Placebo-Controlled Study –
    Norimasa Taniguchi, Takeshi Nakamura, Takahisa Sawada, Kinya Matsubara ...
    2010 Volume 74 Issue 11 Pages 2365-2371
    Published: 2010
    Released: October 25, 2010
    [Advance publication] Released: September 08, 2010
    JOURNALS FREE ACCESS
    Background: Erythropoietin (EPO) enhances re-endothelialization and anti-apoptotic action. Larger clinical studies to examine the effects of high-dose EPO are in progress in patients with acute myocardial infarction (AMI). Methods and Results: The aim of this multi-center pilot study was to investigate the effect of `low-dose EPO' (6,000 IU during percutaneous coronary intervention (PCI), 24 h and 48 h) in 35 patients with a first ST-elevated AMI undergoing PCI who was randomly assigned to EPO or placebo (saline) treatment. Neointimal volume, cardiac function and infarct size were examined in the acute phase and 6 months later (ClinicalTrials.gov identifier: NCT00423020). No significant regression in in-stent neointimal volume was observed, whereas left ventricular (LV) ejection fraction was significantly improved (49.2% to 55.7%, P=0.003) and LV end-systolic volume was decreased in the EPO group (47.7 ml to 39.0 ml, P=0.036). LV end-diastolic volume tended to be reduced from 90.2% to 84.5% (P=0.159), whereas in the control group it was inversely increased (91.7% to 93.7%, P=0.385). Infarction sizes were significantly reduced by 38.5% (P=0.003) but not in the control group (23.7%, P=0.051). Hemoglobin, peak creatine kinase values, and CD34+/CD133+/CD45dim endothelial progenitors showed no significant changes. No adverse events were observed during study periods. Conclusions: This is a first study demonstrating that short-term `low-dose' EPO to PCI-treated AMI patients did not prevent neointimal hyperplasia but rather improved cardiac function and infarct size without any clinical adverse effects. (Circ J 2010; 74: 2365-2371)
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  • – Pathophysiological and Clinical Implications –
    Roberto Nerla, Antonio Di Monaco, Gregory A. Sgueglia, Irma Battipagli ...
    2010 Volume 74 Issue 11 Pages 2372-2378
    Published: 2010
    Released: October 25, 2010
    [Advance publication] Released: September 04, 2010
    JOURNALS FREE ACCESS
    Background: Drug-eluting stents (DES) have reduced restenosis following percutaneous coronary intervention (PCI), but they seem to be associated with increased coronary endothelial dysfunction compared to bare metal stents (BMS). No data are available about the prognostic value of exercise stress test (EST) in PCI patients in the DES era. Methods and Results: The 160 patients with coronary artery disease (CAD) who underwent PCI with either BMS (n=86) or DES (n=74) were studied. EST was performed 1 month after PCI. DES patients had a higher rate of positive EST compared to BMS patients (49% vs 32%; P=0.03). At a median follow-up of 18 months DES showed a lower rate of target vessel revascularization (TVR) (hazard ratio (HR) 0.37, P=0.07), but a higher rate of acute myocardial infarction (AMI) (HR 3.33, P=0.08). At multivariate Cox-regression time to 1 mm ST and low-workload ischemia were independent predictors of AMI (HR 0.96, P=0.03; and HR 6.24, P=0.009, respectively), as well as of TVR (HR 0.96, P=0.007; and HR 6.43, P=0.001, respectively). Conclusions: DES implantation is associated with a higher rate of positive EST, compared to BMS, 1 month after PCI, likely due to a higher prevalence of endothelial dysfunction. EST seems to be helpful in predicting clinical outcome in patients with coronary stent implantation. (Circ J 2010; 74: 2372-2378)
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  • – An Angioscopic Study –
    Yasumi Uchida, Yasuto Uchida, Takeshi Sakurai, Masahito Kanai, Seiichi ...
    2010 Volume 74 Issue 11 Pages 2379-2385
    Published: 2010
    Released: October 25, 2010
    [Advance publication] Released: September 04, 2010
    JOURNALS FREE ACCESS
    Background: Approximately 15% of acute coronary syndrome (ACS) cases have no significant coronary stenosis. Mechanisms underlying the attacks are, however, unknown. Methods and Results: The clinical study had 254 patients with ACS; 38 patients (31 females and 7 males; aged 51.0±8.0 years) had no significant coronary stenosis on angiography. They underwent a dye-staining angioscopy of the suspected culprit coronary artery using Evans blue, which selectively stains fibrin and damaged endothelial cells. A fluffy coronary luminal surface was observed in the suspected culprit artery in all 38 patients. The fluffy luminal surface was stained blue with Evans blue. In animal experiments involving 5 beagles, 10% hydrogen peroxide solution was injected into the iliac arteries to damage endothelial cells, which was then followed by blood reperfusion, and then the artery was examined by intravascular microscopy and histology. In the beagles, the arterial segment, where the thrombus had been formed, exhibited a fluffy luminal surface after a washout of the thrombus, and the surface was stained blue. Histologically, the fluffy surfaces were composed of damaged endothelial cells attached by multiple fibrin threads and platelets. Conclusions: It was considered that the coronary segment exhibiting a fluffy luminal surface was the culprit lesion and that the fluffy surface was caused by residual thrombi after dispersion of an occlusive thrombus, which had formed on the damaged endothelial cells. (Circ J 2010; 74: 2379-2385)
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  • Sarah Chua, Judy Hung, Sheng-Ying Chung, Yu-Chun Lin, Morgan Fu, Chiun ...
    2010 Volume 74 Issue 11 Pages 2386-2392
    Published: 2010
    Released: October 25, 2010
    [Advance publication] Released: September 28, 2010
    JOURNALS FREE ACCESS
    Background: The impact of primary percutaneous coronary intervention (PCI) for acute ST-elevated myocardial infarction (STEMI) on the incidence of ischemic mitral regurgitation (IMR) is unclear. Methods and Results: Between January 2000 and December 2004, 318 patients presenting with first acute STEMI were enrolled in this study. Two hundred and twelve (66.67%) patients received PCI (PCI group), and 106 age- and Killip class-matched patients received medical management (non-PCI group). The median duration of follow up was 40.46 months. Compared to the non-PCI group, the PCI group had 14.6% (9.9% vs 24.5%) fewer patients with moderate or severe IMR (P<0.001). Univariate analysis demonstrated IMR was significantly associated with advanced age, higher Killip score, and posterior myocardial infarction (MI). Moreover, IMR was strongly associated with a lower left ventricular (LV) ejection fraction, larger left atrial dimension (LAd), and a larger LV end-systolic and LV end-diastolic volumes (LVEDV) (all P<0.01). Multivariate analysis revealed the odds of IMR in the PCI group was 0.208 times those of the non-PCI group (P<0.001). Additionally, moderate or severe IMR was independently correlated with advanced age, inferior MI, Killip class ≥3, larger LAd, and larger LVEDV (all P<0.05). Furthermore, long-term survival time was longer in the PCI group without IMR than in the non-PCI group with IMR (all P<0.01). Conclusions: PCI for first acute STEMI was associated with lower incidence of IMR. Advanced age, inferior MI, Killip class ≥3, larger LAd and LVEDV were risk factors associated with IMR development. (Circ J 2010; 74: 2386-2392)
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Myocardial Disease
  • Akira Moriguchi, Hajime Otani, Kei Yoshioka, Takayuki Shimazu, Masanor ...
    2010 Volume 74 Issue 11 Pages 2393-2402
    Published: 2010
    Released: October 25, 2010
    [Advance publication] Released: September 18, 2010
    JOURNALS FREE ACCESS
    Background: Although ischemic postconditioning (IPost) confers cardioprotection by protecting the mitochondria though the activation of phosphatidylinositol 3-kinase (PI3K), a potential drawback of IPost is impairment of aerobic ATP generation during reperfusion by repeated ischemia. This decrease in ATP might inhibit the restoration of sarcolemmal dystrophin, which is translocated during ischemia, and render cardiomyocytes susceptible to contraction-induced oncosis. Methods and Results: Isolated rat hearts were subjected to 30min ischemia and 120min reperfusion. IPost induced by 20 cycles of 10-s reperfusion and 10-s ischemia enhanced the activation of PI3K as evidenced by the increased phosphorylation of Akt, but had no effect on myocardial ATP, restoration of sarcolemmal dystrophin, or cardiomyocyte oncosis during IPost. Administration of the contractile blocker, 2,3-butanedione monoxim (BDM), during IPost increased myocardial ATP and facilitated the redistribution of dystrophin to the sarcolemma. This led to reduced cardiomyocyte oncosis and infarct size, and improved the left ventricular function. The anti-oncotic effect of BDM occurred without changing the anti-apoptotic effect of IPost. The PI3K inhibitor, LY294002, prevented the phosphorylation of Akt, decreased the recovery of ATP and restoration of sarcolemmal dystrophin, and blocked the anti-oncotic and anti-apoptotic effects of IPost. Conclusions: These results suggest that the inhibition of contractile activity during IPost prevents cardiomyocyte oncosis and enhances cardioprotection through PI3K-dependent restoration of sarcolemmal dystrophin. (Circ J 2010; 74: 2393-2402)
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  • Farouk Mookadam, Travis Smith, Panupong Jiamsripong, Sherif E Moustafa ...
    2010 Volume 74 Issue 11 Pages 2403-2409
    Published: 2010
    Released: October 25, 2010
    [Advance publication] Released: September 29, 2010
    JOURNALS FREE ACCESS
    Background: In patients with primary hyperoxaluria (PH), oxalate overproduction can result in recurrent urolithiasis and nephrocalcinosis, which in some cases results in a progressive decline in renal function, oxalate retention, and systemic oxalosis involving bone, retina, arterial media, peripheral nerves, skin, and heart. Oxalosis involving the myocardium or conduction system can potentially lead to heart failure and fatal arrhythmias. Methods and Results: A retrospective review of our institution's database was conducted for all patients with a confirmed diagnosis of PH between 1/1948 and 1/2006 (n=103). Electrocardiogram (ECG) and echocardiography were used to identify cardiac abnormalities. Ninety-three patients fulfilled the inclusion criteria, 58% were male. Mean follow-up was 11.9 (median 8.8) years. In 38 patients who received an ECG or echocardiography, 31 were found to have any cardiac abnormalities. Cardiac findings correlated with decline in renal function. Conclusions: Our data suggests that physicians caring for patients with PH should pay close attention to cardiac status, especially if renal function is impaired. (Circ J 2010; 74: 2403-2409)
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Pediatric Cardiology and Adult Congenital Heart Disease
  • Hong-Kun Jiang, Guang-Rong Qiu, Jesse Li-Ling, Na Xin, Kai-Lai Sun
    2010 Volume 74 Issue 11 Pages 2410-2418
    Published: 2010
    Released: October 25, 2010
    [Advance publication] Released: October 15, 2010
    JOURNALS FREE ACCESS
    Background: The Cardiac α actin 1 gene (ACTC1) has been related to familial atrial septal defects. This study was set to explore a potential role of this gene in the formation of sporadic congenital heart disease (CHD). Methods and Results: Assessment of cardiac tissue samples from 33 patients with sporadic CHD (gestational age (GA) 18 weeks-49 months) with real-time RT-PCR, Western blotting and immunohistochemistry has revealed a markedly decreased ACTC1 expression in the majority of samples (78.8%) compared with autopsied normal heart tissue from aged-matched subjects (GA 17 weeks-36 months). Also, as shown by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay, the proportion of apoptotic cardiomyocytes in samples featuring down-regulated ACTC1 expression (Group 1) was significantly greater than those with normal expression (Group 2) and the controls (P<0.01). The proportion of apoptotic cells strongly correlated with the expression of ACTC1 (r=-0.918, P<0.01). A study of 2 essential genes involved in apoptosis, Caspase-3 and Bcl-2, confirmed that the former has significantly increased expression, whilst the latter has decreased expression in Group 1 than in the other groups (P<0.01). Transfection of a small interfering RNA targeting, Actc1 (Actc1-siRNA), to a cardiomyocyte cell line, H9C2, also detected more apoptotic cells. Conclusions: Reduced ACTC1 expression might play a role in the onset of CHD through induction of cardiomyocyte apoptosis. (Circ J 2010; 74: 2410-2418)
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  • Maria Salonen, Sirpa Tenhola, Tomi Laitinen, Tiina Lyyra-Laitinen, Jar ...
    2010 Volume 74 Issue 11 Pages 2419-2425
    Published: 2010
    Released: October 25, 2010
    [Advance publication] Released: September 29, 2010
    JOURNALS FREE ACCESS
    Background: Small birth size is associated with increased cardiovascular disease risk, but the mediating factors are poorly understood. Methods and Results: Serum lipids, blood pressure (BP), carotid artery intima-media thickness (CA-IMT), and brachial artery flow-mediated dilatation (BA-FMD) were studied in 70 20-year-old subjects [35 sex- and age-matched pairs born small (SGA) and appropriate for gestational age (AGA)]. The SGA subjects had higher serum levels of low-density lipoprotein (LDL) cholesterol, total/high-density lipoprotein (HDL) and LDL/HDL cholesterol ratios, and lower HDL cholesterol levels than the AGA subjects (2.71 vs 2.37mmol/L, P<0.05; 3.12 vs 2.80, P<0.01; 1.98 vs 1.61, P=0.002; 1.43 vs 1.56mmol/L, P<0.05, respectively). In the SGA group, total and LDL cholesterol levels correlated inversely with adult height SD score (r=0.463, P=0.006 and r=0.413, P=0.015, respectively). CA-IMT or BA-FMD did not differ between the groups, but cigarette smoking, higher diastolic BP, and shorter birth length associated with higher CA-IMT in the whole study population. A clear tracking of cholesterol levels was found from 12 to 20 years. Conclusions: SGA subjects had more unfavorable lipid profiles than the controls, the shortest having the highest LDL cholesterol. Cigarette smoking, higher diastolic BP, and shorter birth length associated with higher CA-IMT in the whole study population. A clear tracking of cholesterol levels through adolescence enables early targeting of lifestyle counseling for reducing cardiovascular disease risk. (Circ J 2010; 74: 2419-2425)
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Peripheral Vascular Disease
  • Junichi Hoshino, Yo Fujimoto, Yoshihiro Naruse, Eiko Hasegawa, Tatsuya ...
    2010 Volume 74 Issue 11 Pages 2426-2433
    Published: 2010
    Released: October 25, 2010
    [Advance publication] Released: October 02, 2010
    JOURNALS FREE ACCESS
    Background: Limb ischemia is a major complication in patients who are receiving hemodialysis (HD). In this study, distinctive features and factors affecting the outcome of HD patients with limb ischemia are identified. Methods and Results: One hundred and eighty consecutive symptomatic limb ischemic patients who were or were not receiving HD and who successfully underwent surgical bypass grafting (bypass, n=75) or endovascular angioplasty (percutaneous transluminal angioplasty (PTA), n=105) were retrospectively compared at our hospital. The endpoint of this study was amputation of the ischemic leg or death. Median follow up was 2.25 years. The amputation-free survival of HD patients was significantly lower than that of non-HD patients (P<0.0001). In the bypass group, the amputation-free survival of HD patients was significantly lower than that of non-HD patients (P=0.0002), even if the graft was patented or not (P=0.77). In contrast, in the PTA group, the amputation-free survival of HD patients was lower than that of non-HD patients (P=0.03), and with a significantly lower patency rate (P=0.0004). Predictors of amputation-free survival differed between HD and non-HD patients; predictors were diabetes mellitus and gender in HD patients, while they were Fontaine classification and hyperlipidemia in non-HD patients. The infectious death rate was higher in HD patients than in non-HD patients (53% vs 22%, P<0.05). Conclusions: This study clearly showed a poorer prognosis in HD patients than in non-HD patients especially after bypass surgery, even if the the graft was patented or not. (Circ J 2010; 74: 2426-2433)
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Preventive Medicine
  • Mitsumasa Kamaura, Kiyoko Nishijima, Mitsuo Takahashi, Toshihiko Ando, ...
    2010 Volume 74 Issue 11 Pages 2434-2440
    Published: 2010
    Released: October 25, 2010
    [Advance publication] Released: September 08, 2010
    JOURNALS FREE ACCESS
    Background: Although lifestyle modification is the key treatment of metabolic syndrome (MetS), clinical data on the dynamical relationship between metabolic state and MetS has been limited. This study investigated the mutual correlations between demographic and biochemical variables, and the metabolic state based on the plasma amino acid (AA) concentrations, during a lifestyle modification for MetS. Methods and Results: Japanese subjects, consisting of 54 patients with MetS [MetS(+)] and 35 persons without MetS [MetS(-)] were included in the study. Before a lifestyle modification program, the levels of glutamate metabolism-related AA (Glu-mAA), aromatic AA metabolism-related AA (Aromatic-mAA) and alanine metabolism-related AA (Ala-mAA) were significantly higher, while those of glycine-serine-threonine metabolism-related AA (Gly-Ser-Thr-mAA) were significantly lower compared to those in MetS(-). After a lifestyle modification, significant reductions (P<0.05) in the BMI (-1.4 kg/m2), mean blood pressure (-7.9 mmHg), hemoglobin A1c (-0.4%), and triglycerides (-30.6 mg/dl) were observed, and significant differences in the plasma AA levels between MetS(+) and MetS(-) were resolved. In addition, the diagnostic items of MetS were positively correlated with the levels of Glu-mAA, Ala-mAA, branched chain AA (BCAA)-mAA, Aromatic-mAA, and negatively correlated with the levels of Gly-Ser-Thr-mAA. Conclusions: As MetS subsided, the abnormality of mean plasma AA levels of the MetS(+) group returned to similar values as those in the MetS(-) group, suggesting a novel viewpoint regarding the metabolic mechanism of lifestyle modification. (Circ J 2010; 74: 2434-2440)
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Renal Disease
  • Arihiro Kiyosue, Yasunobu Hirata, Jiro Ando, Hideo Fujita, Toshihiro M ...
    2010 Volume 74 Issue 11 Pages 2441-2447
    Published: 2010
    Released: October 25, 2010
    [Advance publication] Released: September 29, 2010
    JOURNALS FREE ACCESS
    Background: This study examines whether the serum concentration of cystatin C (Cys C) correlates with the severity of coronary artery disease (CAD) and whether it provides additional information on the risk for CAD in patients without chronic kidney disease (CKD) estimated by the creatinine-based glomerular filtration rate (GFR). Methods and Results: The relationship between serum Cys C and the severity of CAD in 526 patients was investigated. Based on GFR, patients were divided into those with and without CKD. The relationship of serum Cys C with the severity of CAD was examined. Serum Cys C was closely correlated with GFR in all cases and in CKD patients, but not in non-CKD patients. The average number of stenotic coronary arteries was significantly higher in the quartiles of higher concentration of Cys C as well as in those of GFR. In 348 patients (66%) the GFR was ≥60ml·min-1·1.73m-2. Those patients with increased Cys C (>0.90mg/L, 143 patients) had a significantly larger number of stenotic coronary arteries than those patients with normal Cys C. Conclusions: Among patients considered to be at low risk based on the estimated GFR using serum creatinine, those with high concentrations of Cys C could have severe CAD. Besides CKD, Cys C might serve as a marker of CAD severity. (Circ J 2010; 74: 2441-2447)
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Vascular Medicine
  • – Effect of Androgen-Deprivation Therapy and Possible Role of Testosterone –
    Kaori Ezaki, Mikiko Nakagawa, Yayoi Taniguchi, Yasuko Nagano, Yasushi ...
    2010 Volume 74 Issue 11 Pages 2448-2454
    Published: 2010
    Released: October 25, 2010
    [Advance publication] Released: September 08, 2010
    JOURNALS FREE ACCESS
    Background: ST-segment elevation in a structurally normal heart is observed in Brugada- and early repolarization syndrome. The incidence of both syndromes is much higher in males than females. Clinical and basic studies suggest that testosterone plays an important role in ventricular repolarization. Methods and Results: Standard surface 12-lead electrocardiograms recorded in 640 healthy subjects were studied (310 males, 330 females ranging in age from 5 to 89 years) (Study 1). The 3 ST levels (ST-J, -M, and -E) were measured in leads V2 and V5, which are representative of the right and left ventricles, respectively. The effect of androgen-deprivation therapy on the ST segment was also evaluated in 21 prostate cancer patients (Study 2). In both leads, the 3 ST levels were significantly higher in adult males than females (P<0.0001) due to a marked increase after puberty in males. As their age increased, males manifested a gradual reduction in the ST level in both leads; in females, there was a reduction in lead V5 only. In both sexes, all 3 ST levels were significantly higher in lead V2 than V5 (P<0.0001). Androgen-deprivation therapy significantly decreased all 3 ST segments in both leads. Conclusions: Significant age- and gender differences in the ST segment in healthy adults were found, suggesting that testosterone modulates the early phase of ventricular repolarization. (Circ J 2010; 74: 2448-2454)
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Controversies in Cardiovascular Medicine
  • – Do Patients With Drug-Induced Brugada Type ECG Have Poor Prognosis? (Pro) –
    Akihiko Shimizu
    2010 Volume 74 Issue 11 Pages 2455-2463
    Published: 2010
    Released: October 25, 2010
    [Advance publication] Released: October 15, 2010
    JOURNALS FREE ACCESS
    Brugada syndrome (BS) has an intermittent or concealed type, which can be unmasked by the sodium (Na+)-channel-blocker challenge test. The appropriate risk stratification of patients with a drug-induced Brugada-type electrocardiographic (ECG), especially those without a history of syncope or aborted sudden cardiac death, remains unclear. The prognosis of patients with BS depends on the clinical type, cardiac arrest, syncope or if asymptomatic. The ratio of the asymptomatic group varies from 56.9% to 63.6% and, furthermore, their annual cardiac event rate is relatively lower at 0.24-3.6% compared with the cardiac arrest group. Patients with a drug-induced Brugada-type ECG have a poor prognosis if they had a history of ventricular fibrillation (VF) or aborted sudden cardiac death, because their risk becomes similar to that of patients with spontaneous Brugada-type ECG. They have the disturbance of the Na+-channel and the electrophysiologic substrate of VF, proven by the high inducibility of VF by stimulation test even in patients without spontaneous VF. Spontaneous VF will never occur if there is no VF substrate. Implantable cardioverter-defibrillators will certainly protect them, so patients with a drug-induced Brugada-type ECG, even without a history of VF or aborted sudden cardiac death, should be considered to have a poor prognosis. (Circ J 2010; 74: 2455-2463)
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  • – Do Patients With Drug-Induced Brugada Type ECG Have Poor Prognosis? (Con) –
    Mitsuhiro Nishizaki, Harumizu Sakurada, Noriyoshi Yamawake, Akiko Ueda ...
    2010 Volume 74 Issue 11 Pages 2464-2473
    Published: 2010
    Released: October 25, 2010
    [Advance publication] Released: October 15, 2010
    JOURNALS FREE ACCESS
    The type 1 ST-segment elevation is diagnostic for Brugada syndrome (BS) and its presence may sometimes be associated with a high risk of arrhythmic events. The type 1 ECG is also known to be unmasked by administration of sodium-channel blockers in equivocal or suspected cases of BS, and the drug-challenge test is frequently used in the diagnostic approach. In large cohort studies the spontaneous appearance of the type 1 ECG with symptoms of aborted sudden death or unexplained syncope are indicative of a poor prognosis for patients with BS compared with not having clinical symptoms. Therefore, the spontaneous type 1 ECG appears to represent an important predictive sign for cardiac events. It is unknown, however, whether or not the drug-induced type 1 ECG is as useful as the spontaneous type 1 for predicting cardiac events in asymptomatic subjects showing non-type 1 ECG. Review of the literature for large cohort studies indicates that there is a low incidence of arrhythmic events in asymptomatic patients with either the spontaneous or drug-induced type 1 ECG compared with symptomatic subjects, and the drug-induced type1 ECG in asymptomatic patients does not add to an increase in arrhythmic risk. Therefore, drug testing to unmask the type 1 ECG in asymptomatic patients with a non-type 1 BS ECG does not have an additional value for risk stratification of cardiac events, although it might be useful in symptomatic patients showing only the non-type 1 ECG. (Circ J 2010; 74: 2464-2473)
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