Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Volume 75 , Issue 11
Showing 1-36 articles out of 36 articles from the selected issue
Reviews
  • Makhosazane Zungu, Jonathan Schisler, Monte S. Willis
    2011 Volume 75 Issue 11 Pages 2513-2521
    Published: 2011
    Released: October 25, 2011
    [Advance publication] Released: October 15, 2011
    JOURNALS FREE ACCESS
    Mitochondria are dynamic organelles that undergo a constant cycle of division and fusion to maintain their function. The process of mitochondrial fusion has the effect of mixing their content, allowing complementation of protein components, mtDNA repair, and distribution of metabolic intermediates. Fission, on the other hand, enables mitochondria to increase in number and capacity, and to segregate mitochondria for autophagy by the lysosome ("mitophagy"). Disruption of these protein quality control mechanisms has recently been identified in multiple cardiac diseases, including cardiac hypertrophy, heart failure, dilated cardiomyopathy, and ischemic heart disease, and is intimately tied to mitochondrial control of apoptosis. Proteins that regulate mitochondrial fusion and fission have been discovered, including Mfn1, Mfn2, and Opa1 (fusion) and Drp1 and Fis1 (fission). In this review, we discuss how these proteins are regulated by post-translational modification with ubiquitin and SUMO (small ubiquitin-like modifier). We then present what is known about the ubiquitin and SUMO ligases that regulate these post-translational modifications and regulation of mitochondrial fusion and fission, exploring their potential as therapeutic targets of cardiac disease. (Circ J 2011; 75: 2513-2521)
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  • Toru Miyazaki, Jun Kurokawa, Satoko Arai
    2011 Volume 75 Issue 11 Pages 2522-2531
    Published: 2011
    Released: October 25, 2011
    [Advance publication] Released: October 05, 2011
    JOURNALS FREE ACCESS
    Metabolic syndrome (MetS) is a cascade of metabolic diseases, starting with obesity and progressing to atherosclerosis, and is often fatal because of serious cardiovascular problems such as heart/brain infarction and hemorrhage. Accumulating evidence has revealed a critical involvement of inflammatory responses triggered by lesional macrophages in the pathogenesis of MetS. Importantly, we found that macrophages are associated with disease progression, not only in the induction of inflammation but also in the production of apoptosis inhibitor of macrophages (AIM), which we initially identified as a soluble factor expressed by macrophages. In atherosclerotic plaques, AIM is highly expressed by foam macrophages and inhibits apoptosis of these cells, which results in the accumulation of macrophages, causing inflammatory responses within the lesion, and ultimately disease progression. In adipose tissue, macrophage-derived AIM is incorporated into adipocytes through CD36-mediated endocytosis, thereby reducing the activity of cytosolic fatty acid synthase. This unique response stimulates lipolysis, resulting in a decrease in adipocyte size, which is physiologically relevant to the prevention of obesity. The lipolytic response also stimulates inflammation of adipocytes in association with the induction of metabolic disorders subsequent to obesity. Thus, AIM is involved in the progression of MetS in both an advancing and inhibitory fashion. Regulation of AIM could therefore be therapeutically applicable for MetS. (Circ J 2011; 75: 2522-2531)
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Editorials
Original Articles
Aortic Disease
  • Shinji Katsuragi, Keiko Ueda, Kaoru Yamanaka, Reiko Neki, Chizuko Kami ...
    2011 Volume 75 Issue 11 Pages 2545-2551
    Published: 2011
    Released: October 25, 2011
    [Advance publication] Released: August 04, 2011
    JOURNALS FREE ACCESS
    Background: Aortic dilatation and dissection are severe complications of pregnancy that may cause maternal death. The purpose of the present study was to investigate risk factors for aortic dilatation or dissection in pregnant Japanese women with Marfan syndrome. Methods and Results: A total of 28 patients with Marfan syndrome were investigated retrospectively during pregnancy and after delivery at 1 institution. These patients were divided into 2 groups: those who experienced aortic dilatation or dissection (group D, n=11) and those who did not (group ND, n=17). In group D, aortic dilatation or dissection occurred in 7 cases during pregnancy (2 in the 2nd trimester, 5 in the 3rd trimester) and 4 cases after birth. The 2 cases in the 2nd trimester involved aortic dilatation >60mm and those patients underwent hemiarch replacement and a David operation, respectively. Delivery by cesarean section (64% vs. 18%, P<0.05), sinus of Valsalva ≥40mm (86% vs. 21%, P<0.05), aortic size index (size of sinus of Valsalva/body surface area) ≥25mm/m2 (7/7, 100% vs. 0/14, 0%, P<0.0001), and faster growth of the sinus of the Valsalva (median, [interquartile range]: 0.41mm/month [0.23-0.66mm/month] vs. 0.05mm/month [-0.13 to 0.22mm/month]; P<0.05) were significantly higher in group D than in group ND. Conclusions: A large sinus of Valsalva, increased aortic size index, and rapid growth of the sinus of Valsalva are risk factors for aortic dilatation or dissection in pregnant Japanese women with Marfan syndrome. (Circ J 2011; 75: 2545-2551)
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Arrhythmia/Electrophysiology
  • Gentaro Iribe, Honghua Jin, Keiji Naruse
    2011 Volume 75 Issue 11 Pages 2552-2558
    Published: 2011
    Released: October 25, 2011
    [Advance publication] Released: September 14, 2011
    JOURNALS FREE ACCESS
    Background: It remains unclear whether sarcolemmal BKCa channels in post-hatch chick ventricular myocytes contribute to stretch-induced extrasystoles (SIE), and whether they are stretch-activated BKCa (SAKCa) channels or a non-stretch-sensitive BKCa variant. Methods and Results: To determine the role of sarcolemmal BKCa channels in SIE and their stretch sensitivity, an isolated 2-week-old Langendorff-perfused chick heart and mathematical simulation were used. The ventricular wall was rapidly stretched by application of a volume change pulse. As the speed of the stretch increased, the probability of SIE also significantly increased, significantly shortening the delay between SIE and the initiation of the stretch. Application of 100nmol/L of Grammostola spatulata mechanotoxin 4, a cation-selective stretch-activated channel (SAC) blocker, significantly decreased the probability of SIE. The application of Iberiotoxin, however, a BKCa channel blocker, significantly increased the probability of SIE, suggesting that a K+ efflux via a sarcolemmal BKCa channel reduces SIE by balancing out stretch-induced cation influx via SACs. The simulation using a cardiomyocyte model combined with a new stretch sensitivity model that considers viscoelastic intracellular force transmission showed that stretch sensitivity in BKCa channels is required to reproduce the present wet experimental results. Conclusions: Sarcolemmal BKCa channels in post-hatch chick ventricular myocytes are SAKCa channels, and they have a suppressive effect on SIE. (Circ J 2011; 75: 2552-2558)
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  • Koichi Nagashima, Yasuo Okumura, Ichiro Watanabe, Toshiko Nakai, Kimie ...
    2011 Volume 75 Issue 11 Pages 2559-2565
    Published: 2011
    Released: October 25, 2011
    [Advance publication] Released: August 26, 2011
    JOURNALS FREE ACCESS
    Background: Whether epicardial adipose tissue (EAT) is independently associated with atrial fibrillation (AF) and outcome after catheter ablation (CA) for AF remains unclear. Methods and Results: Three-dimensional volume-rendering reconstructed images of EAT (total EAT) and EAT surrounding the left atrium (LA-EAT) were measured on 320-row multidetector computed tomography in 40 patients with AF (paroxysmal AF [PAF], n=24; persistent AF [PerAF], n=16) who underwent CA, and in 37 age-matched control patients. EAT volumes were as follows for the control, PAF and PerAF patients: total EAT, 138.3±45.2cm3 vs. 158.3±47.2cm3 vs. 226.4±93.3cm3 (P<0.01 for control or PAF vs. PerAF); LA-EAT, 32.9±14.5cm3 vs. 41.3±15.3cm3 vs. 66.8±35.1cm3 (P<0.001 for control or PAF vs. PerAF). EAT volume was independently associated with the presence of AF after adjustment for possible confounding factors. EAT volume was significantly greater in patients with lone AF than in control patients (total EAT, 132.8±33.3cm3 vs. 106.2±27.3cm3, P=0.021; LA-EAT: 34.0±10.6cm3 vs. 21.8±6.9cm3, P=0.0006). EAT volumes were greater in the 15 AF patients (37.5%) with post-ablation recurrence than in patients without recurrence (total EAT: 239.0±90.2cm3 vs. 153.5±42.7cm3, P=0.0002; LA-EAT: 69.6±35.5cm3 vs. 40.7±13.9cm3, P=0.0008). Conclusions: EAT volume increases in AF patients independent of conventional risk factors and is greater in patients with lone AF than in non-AF patients. EAT volume might be useful for predicting AF recurrence after CA. (Circ J 2011; 75: 2559-2565)
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Cardiovascular Intervention
  • Manabu Ogita, Katsumi Miyauchi, Takeshi Kurata, Ken Yokoyama, Tomotaka ...
    2011 Volume 75 Issue 11 Pages 2566-2572
    Published: 2011
    Released: October 25, 2011
    [Advance publication] Released: August 09, 2011
    JOURNALS FREE ACCESS
    Background: In-stent restenosis (ISR) after bare-metal stent (BMS) implantation is thought to be clinically benign, although this notion remains controversial. The long-term clinical outcomes of ISR with BMS have not been established. Methods and Results: Among 983 consecutive patients (1,227 lesions) implanted with a BMS between 1999 and 2004 at the authors' institution, 746 underwent routine follow-up angiography. Angiographic ISR (ISR group) was evident in 215 patients (28.8%) and 136 of them underwent repeat revascularization. The incidence of major adverse cardiac events (MACE), acute coronary syndrome (ACS), target lesion revascularization and all-cause death were evaluated between patients with and without ISR (non-ISR group). Patients in the ISR group were older and more likely to have diabetes. The median follow-up period was 2,031 days. The rates of MACE and ACS were significantly higher in the ISR group compared with the non-ISR group (33.5% vs. 13.7%, P<0.0001 and 11.2% vs. 7.0%, P<0.05, respectively). Multivariate Cox regression analysis demonstrated that ISR was significantly associated with clinical outcomes (adjusted hazard ratio [HR] for MACE, 2.81; 95% confidence interval [CI]: 2.01-3.94, P<0.01; adjusted HR for ACS, 1.84; 95%CI: 1.08-3.13, P<0.05). Conclusions: ISR with BMS was significantly associated with long-term adverse clinical outcomes. Risk of future cardiovascular events due to ISR must be carefully considered. (Circ J 2011; 75: 2566-2572)
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  • Masato Nakamura, Jun-ichi Kotani, Ken Kozuma, Takahiro Uchida, Masashi ...
    2011 Volume 75 Issue 11 Pages 2573-2580
    Published: 2011
    Released: October 25, 2011
    [Advance publication] Released: August 06, 2011
    JOURNALS FREE ACCESS
    Background: The TAXUS Japan Postmarket Surveillance Study (TAXUS-PMS) enrolled patients receiving percutaneous coronary intervention in real-world clinical practice. This analysis focuses on outcomes in the overall patient population and in a subgroup of diabetic patients. Methods and Results: Between July 2007 and December 2008, 2,132 patients (with 2,504 lesions) were consecutively enrolled at 56 sites in Japan. One-year outcomes were analyzed. The prevalence of patients with diabetes was 44% (21% of diabetics were insulin-treated) and 5.5% of patients were receiving ongoing hemodialysis. The majority of patients received paclitaxel-eluting stents (PES) for `off-label' indications (68.2%). The rate of major adverse cardiovascular events (cardiac death, myocardial infarction, and target vessel revascularization (TVR)) at 1 year was 8.2%, driven mainly by TVR (6.9%). No differences in TVR, late loss or restenosis rates were found between diabetic and non-diabetic patients; outcomes in insulin- compared with oral hypoglycemic-treated diabetic patients, were similar. Multiple stent implantation and ostial lesion location were independent predictors for both major adverse cardiac events (MACE) and target lesion revascularization (TLR). Hemodialysis was an independent predictor for MACE but not TLR whereas in-stent restenosis was an independent predictor for TLR. Conclusions: TAXUS-PMS demonstrated a consistent, positive effect of PES in complex clinical cases. PES diminished the increased risk of clinical restenosis in diabetic patients, leading to a similar low risk of cardiac events in diabetic and non-diabetic patients. (Circ J 2011; 75: 2573-2580)
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  • Seung-Pyo Lee, Jang-Whan Bae, Kyung Woo Park, Seung-Woon Rha, Jang-Ho ...
    2011 Volume 75 Issue 11 Pages 2581-2589
    Published: 2011
    Released: October 25, 2011
    [Advance publication] Released: August 20, 2011
    JOURNALS FREE ACCESS
    Background: The clinical effect of, and additive measures to overcome the possible inhibitory calcium channel blocker (CCB)-clopidogrel interaction in Asian patients undergoing percutaneous coronary intervention is unknown. Methods and Results: A total of 900 Korean patients enrolled for the multicenter, prospective, randomized Influence of CILostazol-based triple antiplatelet therapy ON ischemic complication after drug-eluting stenT implantation (CILON-T) trial were divided into 4 groups depending on CCB prescription and type of anti-platelet therapy (dual [DAT] vs. triple [TAT; addition of cilostazol to DAT]) in a 2×2 factorial manner. The primary endpoint was a composite of cardiac death, non-fatal myocardial infarction and ischemic stroke at 6 months after PCI. On-treatment platelet reactivity (OPR) was assessed on VerifyNow P2Y12 assay. Concomitant CCB use increased OPR in the DAT group (mean±SEM: 251.2±7.6 vs. 225.6±5.1; P=0.008), but not in the TAT group (214.5±9.1 vs. 203.4±5.6; P=0.294). Primary endpoint increased by use of CCB in patients with DAT (4.9% vs. 0.9%, P=0.016), but not in those with TAT (0% vs. 1.8%, P=0.346). Addition of cilostazol to DAT reduced OPR and clinical events in patients taking CCB (P=0.007 for P2Y12 reaction units; P=0.027 for thrombotic events). CCB without concomitant cilostazol use was a significant predictor of total thrombotic events. Conclusions: Concomitant use of CCB may weaken the anti-platelet effect of clopidogrel and increase subsequent thrombotic events in Asian subjects. This hazardous CCB-clopidogrel interaction may be overcome by addition of cilostazol. (Circ J 2011; 75: 2581-2589)
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  • Peter Damman, Andres Iñiguez, Margo Klomp, Marcel Beijk, Pier W ...
    2011 Volume 75 Issue 11 Pages 2590-2597
    Published: 2011
    Released: October 25, 2011
    [Advance publication] Released: September 14, 2011
    JOURNALS FREE ACCESS
    Background: We evaluated the GenousTM Bio-engineered R stentTM in elderly patients undergoing non-urgent percutaneous coronary intervention. The elderly have an increased risk of (temporary) discontinuation of clopidogrel, which is associated with a higher risk of developing stent thrombosis (ST). Methods and Results: In the e-HEALING registry, 2,651 patients were <65, 1,403 were 65-74 and 869 were ≥75 years old. The 12-month primary outcome was target vessel failure (TVF), defined as target vessel-related car-diac death or myocardial infarction and target vessel revascularization. Secondary outcomes included target lesion revascularization (TLR) and ST. Cumulative event rates were estimated with the Kaplan-Meier method and compared with a log-rank test. TVF occurred significantly more often in elderly patients compared with younger patients (7.0% in patients aged <65, 8.8% in patients aged 65-74 and 11.7% in patients aged ≥75 years, P<0.001). There was a trend to higher TLR with increasing age (log-rank P=0.06) and no difference in ST. Conclusions: The 1-year results of the Genous stent in a population of elderly patients show a significantly higher TVF rate compared with younger patients, mainly driven by a higher mortality. Although there was a trend to higher TLR rates with increasing age, there was no difference in ST. This attests to the safety of this therapy for the elderly, in whom there could be concerns with administering long-term dual antiplatelet therapy. (Circ J 2011; 75: 2590-2597)
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Epidemiology
  • Shinya Goto, Yasuo Ikeda, Kazuyuki Shimada, Shinichiro Uchiyama, Hidek ...
    2011 Volume 75 Issue 11 Pages 2598-2604
    Published: 2011
    Released: October 25, 2011
    [Advance publication] Released: August 20, 2011
    JOURNALS FREE ACCESS
    Background: There remains uncertainty about the risk of cardiovascular events in stable outpatients with a history of myocardial infarction (MI), stroke, and atrial fibrillation in Japan. Methods and Results: In the Japan Thrombosis Registry for Atrial Fibrillation, Coronary, or Cerebrovascular Events (J-TRACE), a nationwide prospective cohort of stable outpatients with a history of MI (n=2,291), stroke (n=3,554), and/or atrial fibrillation (n=2,242), 1-year follow-up data were available for 7,513 of 8,087 patients (follow-up rate: 92.9%). The primary endpoint (death/MI/stroke) was reported in 3.53 events per 100 person-years (95% confidence interval [CI]: 3.11-3.99) within 1 year. The rates of all-cause death, death from stroke, and death from MI within 1 year were 1.35 (95%CI: 1.10-1.65), 0.15 (95%CI: 0.08-0.27), and 0.06 (95%CI: 0.02-0.14) per 100 person-years, respectively. The rate of non-fatal stroke was 1.85 (95%CI: 1.55-2.19), while that of non-fatal MI was 0.33 (95%CI: 0.21-0.49). The rate of non-fatal stroke was highest among stroke patients (2.95; 95%CI: 2.39-3.60 per 100 person-years), while that of non-fatal MI was similar across all disease categories. Investigator-decided serious non-fatal bleeding events occurred in 0.21 events (95%CI: 0.12-0.34) per 100 person-years. Conclusions: In this large, nationwide Japanese registry, the highest stroke event rate was seen in patients with a history of stroke. (Circ J 2011; 75: 2598-2604)
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Heart Failure
  • Tatsuo Aoki, Yoshihiro Fukumoto, Koichiro Sugimura, Minako Oikawa, Kim ...
    2011 Volume 75 Issue 11 Pages 2605-2613
    Published: 2011
    Released: October 25, 2011
    [Advance publication] Released: August 06, 2011
    JOURNALS FREE ACCESS
    Background: Although myocardial fibrosis plays an important role in the progression of heart failure (HF), its prognostic impact still remains to be clarified. Methods and Results: A total of 172 consecutive patients with chronic HF, who underwent cardiac catheterization and endomyocardial biopsy between January 2001 and September 2008, were examined. They were divided into 2 groups: HF with preserved ejection fraction (HFPEF; left ventricular ejection fraction [LVEF] ≥50%, n=81); and HF with reduced LVEF (HFREF; LVEF <50%, n=91). The collagen volume fraction (CVF) in biopsy samples was calculated and its prognostic impact examined. Mean follow-up in the HFPEF and the HFREF groups was 41±33 months and 41±26 months, respectively. Although CVF was similar between the 2 groups (1.83±1.54% vs. 2.07±2.35%), CVF was significantly correlated with LV end-diastolic pressure in the HFREF group but not in the HFPEF group. When HF stage was adjusted, the long-term prognosis was comparable between the 2 groups. When the patients were divided into 2 groups according to median CVF, however, severe fibrosis was a significant predictor for all-cause death (P=0.014) and cardiac events (P=0.02) in the HFREF, but not in the HFPEF group. Conclusions: Myocardial fibrosis evaluated on biopsy samples is a useful indicator for long-term survival, suggesting that it may be an important therapeutic target as well. (Circ J 2011; 75: 2605-2613)
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  • Yukio Sekiguchi, Hiroshi Tada, Kentaro Yoshida, Yoshihiro Seo, Shelby ...
    2011 Volume 75 Issue 11 Pages 2614-2620
    Published: 2011
    Released: October 25, 2011
    [Advance publication] Released: September 02, 2011
    JOURNALS FREE ACCESS
    Background: Cardiac resynchronization therapy defibrillator (CRT-D) devices are now capable of monitoring changes in intrathoracic impedance. Intrathoracic impedance monitoring resulting in a fluid index threshold crossing has been proven to predict heart failure (HF) exacerbations. We retrospectively investigated the relationship between changes in intrathoracic impedance and the occurrence of arrhythmic events. Methods and Results: From 282 patients with New York Heart Association class III or IV HF who were implanted with a CRT-D device with a fluid index feature based on intrathoracic impedance monitoring capabilities, arrhythmic events were retrospectively analyzed in terms of the threshold crossings. The patients were divided into 2 groups: those with fluid index threshold crossings and those without threshold crossings. A total of 4,725 tachyarrhythmic events were reported in 129 patients (46%), and there were 221 fluid index crossing events in 145 patients (51%) during 10.0±3.2 months. Tachyarrhythmic events were more frequently recorded in patients with threshold crossing events than in those who did not experience a threshold crossing (3,241 vs. 1,484 events, P<0.0001). Ventricular tachyarrhythmic events mainly occurred within the first 30 days after the threshold crossing event; however, a similar trend was not observed for the atrial tachyarrhythmic events. Conclusions: Intrathoracic impedance monitoring may predict arrhythmic events, especially ventricular arrhythmias, in patients with HF and provides an additional management tool. (Circ J 2011; 75: 2614-2620)
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Imaging
  • Tsunenari Soeda, Shiro Uemura, Satoshi Okayama, Rika Kawakami, Yu Suga ...
    2011 Volume 75 Issue 11 Pages 2621-2627
    Published: 2011
    Released: October 25, 2011
    [Advance publication] Released: August 06, 2011
    JOURNALS FREE ACCESS
    Background: Clinical studies using invasive modalities have reported that statin therapy stabilizes coronary plaque vulnerability. The serial changes of lipid-rich coronary plaques (LRCPs) during rosuvastatin treatment were evaluated non-invasively in patients with acute coronary syndrome (ACS) using dual-source computed tomography (DSCT). Methods and Results: A total of 11 consecutive ACS patients, and 13 LRCPs were serially evaluated on DSCT before and 24 weeks after rosuvastatin treatment. Compared with the baseline, there was no change in post-treatment minimal lumen diameter, lumen volume, or longitudinal length of LRCPs. By contrast, the ratio of lipid core volume to plaque volume significantly decreased from 48.0±9.9% to 43.7±10.6% (P=0.04), and plaque volume decreased from 144.5±85.5mm3 to 119.8±78.0mm3 (P=0.07). The remodeling index of target LRCPs significantly decreased from 1.16±0.10 to 1.06±0.12 (P=0.02). Percent reduction of plaque volume was significantly greater in patients with a lower ratio of low-density lipoprotein to high-density lipoprotein (L/H ratio ≤1.5) at follow-up than patients with higher L/H ratio (>1.5; median -31.7% vs. -6.8%, P=0.03). Conclusions: Rosuvastatin therapy reduced the volume of lipid cores and LRCPs and increased the CT attenuation value of LRCPs. DSCT is an effective modality for the non-invasive evaluation of LRCPs in patients with ACS. (Circ J 2011; 75: 2621-2627)
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  • Keiichiro Yoshinaga, Chietsugu Katoh, Osamu Manabe, Ran Klein, Masanao ...
    2011 Volume 75 Issue 11 Pages 2628-2634
    Published: 2011
    Released: October 25, 2011
    [Advance publication] Released: August 27, 2011
    JOURNALS FREE ACCESS
    Background: Myocardial blood flow (MBF) can be measured with positron emission tomography (PET) and its quantification should provide diagnostic information beyond that obtained through standard visual analysis. However, this possibility has not been fully studied with PET and generator-produced rubidium-82 (82Rb). We evaluated regional MBF in segments with and without ischemia using 82Rb PET in patients with coronary artery disease (CAD). Methods and Results: Rest and stress 82Rb PET and coronary angiography were performed for 12 patients with CAD. Based on angiography and relative 82Rb perfusion images, segments were classified into 4 groups (Group A: myocardial ischemia with >70% diameter stenosis; Group B: no ischemia with stenosis; Group C: no ischemia without stenosis; Group D: ischemia without stenosis). Rest MBF was similar among the 4 groups. Groups A and B showed reduced hyperemic MBF compared with Group C (P<0.05 vs. Group C) [Group A (n=16) 1.28±0.58ml·min-1·g-1; Group B (n=11) 1.72±0.64ml·min-1·g-1; Group C (n=9) 2.60±1.09ml·min-1·g-1; Group D (n=2) 2.33ml·min-1·g-1]. Coronary flow reserves were inversely correlated with percent diameter stenosis (r=0.76, P<0.0001). Conclusions: Segments with ischemia and coronary stenosis had reduced hyperemic MBF. Segments with coronary stenosis without ischemia also had reduced hyperemic MBF compared with non-stenotic segments. MBF quantification using 82Rb PET may provide additional diagnostic information. (Circ J 2011; 75: 2628-2634)
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Ischemic Heart Disease
  • R. Goekmen Turan, C. Hakan Turan, Ilkay Bozdag-Turan, Jasmin Ortak, Ib ...
    2011 Volume 75 Issue 11 Pages 2635-2641
    Published: 2011
    Released: October 25, 2011
    [Advance publication] Released: August 09, 2011
    JOURNALS FREE ACCESS
    Background: The influence of the number of diseased coronary arteries on the mobilization of CD133/45+ bone marrow-derived circulating progenitor cells (BM-CPCs) in peripheral blood (PB) in patients with ischemic heart disease (IHD) was analyzed. Methods and Results: Mobilization of CD133/45+ BM-CPCs by flow cytometry was measured in 120 patients with coronary 1 vessel (IHD1, n=40), coronary 2 vessel (IHD2, n=40), and coronary 3 vessel disease (IHD3, n=40), and in a control group (n=40). The mobilization of CD133/45+ BM-CPCs was significantly reduced in patients with IHD compared to the control group (P<0.001). The mobilization of CD133/45+ BM-CPCs was impaired in patients with IHD3 compared to IHD1 (P<0.001) and to IHD2 (P<0.001). But there was no significant difference in mobilization of CD133/45+ BM-CPCs between the patients with IHD2 and IHD1 (P=0.35). Moreover, we found significantly reduced CD133/45+ cell mobilization in patients with a high SYNTAX-Score (SS) compared to a low SS (P<0.001) and an intermediate SS (P<0.001). In subgroup analyzes, we observed a significantly negative correlation between levels of hemoglobin A1c and the mobilization of CD133/45+ BM-CPCs (P=0.001, r=-0.6). Conclusions: The mobilization of CD133/45+ BM-CPCs in PB is impaired in patients with IHD. This impairment might augment with increased number of diseased coronary arteries. Moreover, mobilization of CD133/45+ BM-CPCs in ischemic tissue is further impaired by diabetes in patients with IHD. (Circ J 2011; 75: 2635-2641)
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  • Tsuyoshi Nakata, Kenichi Fujii, Masashi Fukunaga, Daizo Kawasaki, Masa ...
    2011 Volume 75 Issue 11 Pages 2642-2647
    Published: 2011
    Released: October 25, 2011
    [Advance publication] Released: August 11, 2011
    JOURNALS FREE ACCESS
    Background: Previous studies described that inadequate tissue perfusion after primary angioplasty in ST-elevation myocardial infarction (STEMI) patients is associated with adverse cardiac events. This study evaluated whether plaque morphological intravascular ultrasound (IVUS) characteristics affects tissue perfusion after stent implantation in STEMI patients. Methods and Results: A total of consecutive 306 STEMI patients who underwent primary angioplasty with IVUS were analyzed. Maximum ST-segment elevation before angioplasty was compared with ST-segment levels 60min after angioplasty. Percent ST-segment resolution (STR) was calculated and categorized as complete (>70%), partial (30-70%), and absent (<30%). Qualitative and quantitative IVUS analyses were performed using standard methods. Plaque with ultrasound attenuation was defined as IVUS finding with backward signal attenuation behind plaque >180° without dense calcium. One-hundred-fifty patients had complete, 101 had partial, and 55 had absent STR. The incidence of in-hospital death tended to be higher in absent STR than in partial and complete STR groups. Multivariate analysis indicated that remodeling index (P=0.004), the presence of ultrasound attenuation (P=0.02), percentage stent expansion (P=0.03), and the presence of deep calcium (P=0.049) were the independent predictors related to the occurrence of absent STR after angioplasty. Conclusions: Positive vessel remodeling, plaque with ultrasound attenuation >180°, deep calcium, and stent overexpansion as assessed by IVUS are associated with the absence of STR after primary angioplasty in patients with STEMI. (Circ J 2011; 75: 2642-2647)
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  • Laurenz Jaberg, Stefan Toggweiler, Marietta Puck, Michelle Frank, Kasp ...
    2011 Volume 75 Issue 11 Pages 2648-2653
    Published: 2011
    Released: October 25, 2011
    [Advance publication] Released: September 03, 2011
    JOURNALS FREE ACCESS
    Background: Patients undergoing acute left main (LM) coronary artery revascularization have a high mortality and natriuretic peptides such as N-terminal pro-B-type (NT-proBNP) have been shown to have prognostic value in patients with acute coronary syndromes. The present study looked at the prognostic value of NT-proBNP in these patients. Methods and Results: We studied all consecutive patients undergoing acute LM coronary artery percutaneous coronary intervention between January 2005 and December 2008 in whom NT-proBNP was measured (n=71). We analyzed the clinical characteristics and the short- and long-term outcomes in relation to NT-proBNP level at admission. Median NT-proBNP was 1,364ng/L, ranging from 46 to 70,000ng/L. NT-proBNP was elevated in 63 (89%) patients and was ≥1,000ng/L in 42 (59%). Log NT-proBNP (hazard ratio [HR] 3.51, 95% confidence interval [CI] 1.55-7.97, P=0.003) and left ventricular ejection fraction (HR 0.95, 95%CI 0.91-0.99, P=0.007) were predictors for all-cause mortality. Log NT-proBNP was the only independent significant predictor of cardiovascular mortality. In-hospital mortality was 0% for patients with NT-proBNP <1,000, but 17% for those with NT-proBNP ≥1,000 (P=0.036). Conclusions: NT-proBNP is a strong predictor of outcome in patients undergoing acute LM coronary artery stenting. Mortality in such patients is high, but those with NT-proBNP <1,000ng/L may have a favorable short- and long-term prognosis. Further research, including a larger patient population, is needed to determine the optimal cut-off value for NT-proBNP in patients undergoing acute LM coronary artery intervention. (Circ J 2011; 75: 2648-2653)
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Molecular Cardiology
  • Toru Kubo, Hiroaki Kitaoka, Makoto Okawa, Yuichi Baba, Takayoshi Hirot ...
    2011 Volume 75 Issue 11 Pages 2654-2659
    Published: 2011
    Released: October 25, 2011
    [Advance publication] Released: July 29, 2011
    JOURNALS FREE ACCESS
    Background: Hypertrophic cardiomyopathy (HCM) is a primary myocardial disorder with an autosomal-dominant pattern of inheritance mainly caused by single heterozygous mutations in sarcomere genes. Although multiple gene mutations have recently been reported in Western countries, clinical implications of multiple mutations in Japanese subjects are not clear. Methods and Results: A comprehensive genetic analysis of 5 sarcomere genes (cardiac β-myosin heavy chain gene [MYH7], cardiac myosin-binding protein C gene [MYBPC3], cardiac troponin T gene [TNNT2], α-tropomyosin gene [TPM1] and cardiac troponin I gene [TNNI3]) was performed in 93 unrelated patients and 14 mutations were identified in 28 patients. Twenty-six patients had single heterozygosity (20 in MYBPC3, 4 in MYH7, 1 in TNNT2, 1 in TNNI3), whereas 2 proband patients with familial HCM had double heterozygosity: 1 with P106fs in MYBPC3 and R869C in MYH7 and 1 with R945fs in MYBPC3 and E1049D in MYH7. From the results of the family survey and the previous literature on HCM mutations, P106fs, R945fs and R869C seemed to be pathological mutations and E1049D might be a rare polymorphism. The proband patient with P106fs and R869C double mutation was diagnosed as having HCM at an earlier age (28 years of age) than her relatives with single mutation, and had greater wall thickness with left ventricular outflow obstruction. Conclusions: One double mutation was identified in a Japanese cohort of HCM patients. Further studies are needed to clarify the clinical significance of multiple mutations including phenotypic severity. (Circ J 2011; 75: 2654-2659)
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Preventive Medicine
  • Minoru Hongo, Setsuo Kumazaki, Atsushi Izawa, Hiroya Hidaka, Takeshi T ...
    2011 Volume 75 Issue 11 Pages 2660-2667
    Published: 2011
    Released: October 25, 2011
    [Advance publication] Released: August 20, 2011
    JOURNALS FREE ACCESS
    Background: The treatment effects of rosuvastatin on arterial stiffness were assessed and compared to those of fluvastatin in high-risk Japanese patients with dyslipidemia in a primary prevention group. Methods and Results: Patients were randomly assigned to either 2.5-5mg/day of rosuvastatin (Group A) or 20-40mg/day of fluvastatin (Group B) and followed up for 12 months. In Group A (n=38), there was a progressive reduction in brachial-ankle pulse wave velocity (baPWV) along with a decrease in the low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (L/H) ratio and high-sensitivity C-reactive protein (hsCRP), and the change in baPWV correlated significantly with that of the L/H ratio and that of hsCRP after rosuvastatin treatment. In Group B (n=37), although fluvastatin achieved a significant improvement in baPWV, L/H ratio, and hsCRP, baPWV was significantly greater than that in Group A and showed a significant correlation with that of hsCRP alone after fluvastatin treatment. In a subgroup of patients (n=26), switching from fluvastatin to rosuvastatin further improved baPWV and the L/H ratio without altering hsCRP after 12 months. Conclusions: Low-dose rosuvastatin would be more effective than fluvastatin in improving arterial stiffness in high-risk Japanese patients with dyslipidemia. The results suggest that improvement in arterial stiffness by rosuvastatin mainly depends on its strong lipid-lowering effects, whereas that by fluvastatin is strongly dependent on the pleiotropic effects, especially an anti-inflammatory action. (Circ J 2011; 75: 2660-2667)
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Pulmonary Circulation
  • Saori Miyamichi-Yamamoto, Yoshihiro Fukumoto, Koichiro Sugimura, Tomon ...
    2011 Volume 75 Issue 11 Pages 2668-2674
    Published: 2011
    Released: October 25, 2011
    [Advance publication] Released: August 27, 2011
    JOURNALS FREE ACCESS
    Background: Pulmonary arterial hypertension (PAH) remains a serious disease characterized by elevated pulmonary artery pressure (PAP) and increased pulmonary vascular resistance (PVR). Among its subtypes, PAH associated with connective tissue disease (CPAH) has the worse prognosis, because of resistance to conventional vasodilator therapy. We hypothesized that intensive immunosuppressive therapy (IIT) could improve the pulmonary hemodynamics in CPAH. Methods and Results: In our pulmonary hypertension (PH) cohort of 182 patients, we evaluated 13 consecutive patients with CPAH who received IIT combined with cyclophosphamide and glucocorticosteroids (IIT group, mean age 45±8 years, 12 females and 1 male). We compared them with 8 historical controls (control group: mean age 52±18 years, 8 females) for pulmonary hemodynamics and prognosis. Both groups were treated with conventional vasodilator therapy. Although the mean PAP (mPAP) remained unchanged in the control group, IIT significantly decreased mPAP (40±9 to 29±11mmHg, P<0.01) and tended to decrease PVR (700±434 to 481±418 dyne·s·cm-5, P=0.07). Importantly, in 6 of the 13 patients in the IIT group, mPAP was almost normalized (<25mmHg) and remained stabilized for more than 1 year. Furthermore, the IIT group showed significantly better prognosis compared with the control group (P<0.01). Conclusions: These results suggest that IIT as well as conventional vasodilator therapy improves the pulmonary hemodynamics and long-term prognosis of patients with CPAH. (Circ J 2011; 75: 2668-2674)
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  • Toshiaki Yano, Kazuyuki Sogawa, Hiroshi Umemura, Seiichiro Sakao, Yasu ...
    2011 Volume 75 Issue 11 Pages 2675-2682
    Published: 2011
    Released: October 25, 2011
    [Advance publication] Released: September 02, 2011
    JOURNALS FREE ACCESS
    Background: The cause of chronic thromboembolic pulmonary hypertension is unknown and there is no specific circulating biomarker for its detection. The aim of the present study was to use proteomic analysis to detect serum biomarkers by evaluating the serum profiles of low-molecular-weight peptides using matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry in patients with chronic thromboembolic pulmonary hypertension.Methods and Results: Serum low-molecular-weight peptide profiling using the spectrophotometric technique was studied retrospectively in patients with chronic thromboembolic pulmonary hypertension and in controls matched for sex and age. The serum level of a 2989-Da peptide in the sera of patients was significantly higher compared to that of controls. Tandem mass spectrometry indicated that the peptide was a fragment of fibrinogen Aα chain (KMADEAGSEADHEGTHSTKRGHAKSRPV). The serum level of fibrinogen Aα chain fragment, measured using a heavy isotope internal standard, tended toward negative correlation with plasmin-α2-plasmin inhibitor complex (P=0.073) and had a positive correlation with thrombin-anti-thrombin complex (P=0.031).Conclusions: This fragment may be a potential diagnostic biomarker for chronic thromboembolic pulmonary hyper-tension. (Circ J 2011; 75: 2675-2682)
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Regenerative Medicine
  • Xi-ren Gao, Yu-zhen Tan, Hai-jie Wang
    2011 Volume 75 Issue 11 Pages 2683-2691
    Published: 2011
    Released: October 25, 2011
    [Advance publication] Released: August 09, 2011
    JOURNALS FREE ACCESS
    Background: The high death rate of the transplanted stem cells in the infarcted heart and low efficiency of differentiation toward cardiomyocytes show that mesenchymal stem cell (MSC) transplantation after myocardial infarction (MI) is not effective. Csx/Nkx2.5 and GATA-4 are considered to be key regulators of cardiogenesis. The aim of the present study was to investigate the effect of transplanting MSC overexpressing Csx/Nkx2.5 and GATA-4 (MSCs-CG) after MI. Methods and Results: According to acridine orange/ethidium bromide staining, MSCs-CG were more resistant to anoxia as compared with MSCs in vitro. In a mouse MI model, ejection fraction and fractional shortening were higher in the MSC-CG group than in the MSC or phosphate-buffered saline group. Wall thickness of the infarct area was increased and collagen deposition was clearly reduced in the MSC-CG group as compared with the other groups. There were more surviving MSCs in the MSC-CG group than in the MSC group. Most of the Y chromosome-positive cells expressed cardiac troponin T and connexin43 (Cx-43). Cx-43 was localized between Y chromosome-positive cells and recipient cardiomyocytes. Microvessel density in the peri-infarct regions and infarct regions increased significantly in the MSC-CG group. Conclusions: Transplantation of MSCs overexpressing Csx/Nkx2.5 and GATA-4 represents a new treatment strategy with the potential to improve cardiac function after MI. (Circ J 2011; 75: 2683-2691)
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Valvular Heart Disease
  • Kentaro Yamane, Hitoshi Hirose, Benjamin A. Youdelman, Linda J. Bogar, ...
    2011 Volume 75 Issue 11 Pages 2692-2698
    Published: 2011
    Released: October 25, 2011
    [Advance publication] Released: August 20, 2011
    JOURNALS FREE ACCESS
    Background: Because of the rising expectation of prolonged life in the general population and the recent recognition of undertreated aortic valve disease in the elderly, updating the available results of aortic valve surgery is imperative, especially considering the rapid evolution of the transcatheter valve implantation procedure. Methods and Results: Between 1997 and 2010, 308 patients aged 70 years or older underwent aortic valve replacement (AVR) for aortic stenosis (AS). Short- and long-term results were analyzed and risk factors for long-term mortality were determined. Mean age was 78.5 years and 124 patients were aged 80 or older. Concomitant coronary artery bypass grafting (CABG) was performed in 46% of the cases. Mean left ventricular ejection fraction (LVEF) was 52%. Overall observed and expected operative mortality using the Society of Thoracic Surgeons-Predicted Risk of Mortality score was 3.9% and 4.8%, respectively. Overall survival rates at 1, 5, and 10 years were 88.6%, 71.6%, and 31.8%, respectively. Predictors of long-term mortality included diabetes; preoperative shock; LVEF ≤40%; New York Heart Association functional class III or IV; and age. Conclusions: Short- and long-term results of conventional AVR in the elderly prove it to be durable and, especially in relatively low-risk patients and patients who require concomitant CABG, operative mortality is reasonably low. Conventional AVR±CABG remains the gold standard for elderly patients with AS. (Circ J 2011; 75: 2692-2698)
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  • Hiroyuki Okura, Yuko Takada, Azusa Yamabe, Takeshi Ozaki, Hiroyuki Yam ...
    2011 Volume 75 Issue 11 Pages 2699-2704
    Published: 2011
    Released: October 25, 2011
    [Advance publication] Released: September 01, 2011
    JOURNALS FREE ACCESS
    Background: Although echo Doppler machines have consistently advanced within a quarter of a century, age related prevalence of valvular regurgitation detected by currently available echo machines remains uncertain. The aim of this study was to investigate the prevalence and correlates of valvular regurgitation in healthy individuals. Methods and Results: A total of 1,333 apparently healthy individuals were enrolled in this study. Echocardiographic examinations were performed using a currently available echo machine. Aortic regurgitation (AR) was detected less frequently (<10%) in younger subjects. Prevalence of aortic regurgitation increased with advancing age and reached 46% in their 9th decade. Mitral regurgitation (MR) was detected in two-thirds of the subjects >30 years old. Tricuspid regurgitation (TR) was frequently (>80%) detected in all age groups. In general, prevalence of valvular regurgitation was higher than those reported previously, except for a relatively lower prevalence of AR in the elderly population. Age was an independent correlate of AR and MR, but not of TR. The presence of AR and MR were independent correlates of TR. Conclusions: In healthy subjects, AR, MR or TR are commonly detected by using a current echo machine. These "physiological" valvular regurgitations should not be considered as a "pathological" valvular heart disease. (Circ J 2011; 75: 2699-2704)
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Vascular Medicine
  • Ricardo Villa-Bellosta, Víctor Sorribas
    2011 Volume 75 Issue 11 Pages 2705-2710
    Published: 2011
    Released: October 25, 2011
    [Advance publication] Released: July 28, 2011
    JOURNALS FREE ACCESS
    Background: Calcium phosphate deposition (CPD) is the hallmark of vascular smooth muscle cell (VSMC) calcification. CPD is a thermodynamically-favored process under physiological conditions. Hydroxyapatite, the most common calcium phosphate in calcified arteries, is passively formed during VSMC calcification, independently on any direct cellular activity. Furthermore, in recent years it has been demonstrated there is an anti-calcifying effect by extracellular pyrophosphate, an endogenous inhibitor of CPD, both in vitro and in vivo, which directly blocks hydroxyapatite formation.Methods and Results: We have used the in vitro calcification model without cellular activity, by treating confluent rat aortic VSMC with paraformaldehyde. Fixed cells were incubated with the indicated media to obtain or inhibit calcification. The calcium content was determined colorimetrically. Calcification was observed after 3 weeks (21 days) using a physiological concentration of calcium (1.8mmol/L) and phosphate (1mmol/L). Calcium deposition was directly proportional to the amount of phosphate in the media, with a calcification rate of 3.5, 7.5, and 14.3μg·cm-2·day-1, using 1, 2, and 4mmol/L of phosphate, respectively. Under physiological conditions, pyrophosphate inhibits CPD with an IC50 of ≈200nmol/L.Conclusions: CPD occurs under a physiological concentration of calcium and phosphate, but this deposition is completely inhibited in the presence of a physiological concentration of pyrophosphate (3-5μmol/L). (Circ J 2011; 75: 2705-2710)
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