Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Volume 77, Issue 2
Displaying 1-44 of 44 articles from this issue
Message From the Editor-in-Chief
Reviews
  • Damon L. Swift, Carl J. Lavie, Neil M. Johannsen, Ross Arena, Conrad P ...
    2013 Volume 77 Issue 2 Pages 281-292
    Published: 2013
    Released on J-STAGE: January 25, 2013
    Advance online publication: January 18, 2013
    JOURNAL FREE ACCESS
    Substantial data have established that higher levels of physical activity (PA), participating in exercise training (ET), and higher overall cardiorespiratory fitness (CRF) provide considerable protection in the primary and secondary prevention of coronary heart disease (CHD). This review surveys data from epidemiological and prospective ET studies supporting the favorable impact of PA, ET, and CRF in primary CHD prevention. Clearly, cardiac rehabilitation and ET (CRET) programs have been underutilized for patients with CHD, particularly considering the effect of CRET on CHD risk factors, including CRF, obesity indices, fat distribution, plasma lipids, inflammation, and psychological distress, as well as overall morbidity and mortality. These data strongly support the routine referral of patients with CHD to CRET programs and that patients should be vigorously encouraged to attend CRET following major CHD events.  (Circ J 2013; 77: 281–292)
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  • – Skeletal Muscle Dysfunction and Potential Therapies –
    Koichi Okita, Shintaro Kinugawa, Hiroyuki Tsutsui
    2013 Volume 77 Issue 2 Pages 293-300
    Published: 2013
    Released on J-STAGE: January 25, 2013
    Advance online publication: January 19, 2013
    JOURNAL FREE ACCESS
    Chronic heart failure (CHF) is characterized as a clinical disorder displaying exercise intolerance; patients typically complain of early muscular fatigue. Previously, it was thought to be simply a failure of perfusion to the exercising musculature and consequent early onset of intramuscular acidosis in CHF. However, improved hemodynamics by cardiotonic agents did not lead to an increase in exercise tolerance. Later studies have shown that intrinsic skeletal muscle abnormalities exist in patients with CHF and could induce the early anaerobic metabolism that limits exercise tolerance. We review the clinical importance of skeletal muscle abnormalities in patients with CHF. Considering the significance of peripheral muscle abnormalities and their development might help physicians and researchers better understand the mechanisms of well-established exercise training and pharmacological therapies that have been shown to improve the prognosis for CHF, and thus develop potential novel therapies.  (Circ J 2013; 77: 293–300)
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  • Keiji Kuba, Yumiko Imai, Josef M. Penninger
    2013 Volume 77 Issue 2 Pages 301-308
    Published: 2013
    Released on J-STAGE: January 25, 2013
    Advance online publication: January 18, 2013
    JOURNAL FREE ACCESS
    Angiotensin-converting enzyme 2 (ACE2) is a negative regulator of the renin-angiotensin system, and functions as the key SARS coronavirus receptor and stabilizer of neutral amino acid transporters. ACE2 catalyzes the conversion of angiotensin II to angiotensin 1–7, thereby counterbalancing ACE activity. Accumulating evidence indicates that the enzymatic activity of ACE2 has a protective role in cardiovascular diseases. Loss of ACE2 can be detrimental, as it leads to functional deterioration of the heart and progression of cardiac, renal, and vascular pathologies. Recombinant soluble human ACE2 protein has been demonstrated to exhibit beneficial effects in various animal models, including cardiovascular diseases. ACE2 is a multifunctional enzyme and thus potentially acts on other vasoactive peptides, such as Apelin, a vital regulator of blood pressure and myocardium contractility. In addition, ACE2 is structurally a chimeric protein that has emerged from the duplication of 2 genes: homology with ACE at the carboxypeptidase domain and homology with Collectrin in the transmembrane C-terminal domain. ACE2 has been implicated in the pathology of Hartnup’s disease, a disorder of amino acid homeostasis, and, via its function in amino acid transport, it has been recently revealed that ACE2 controls intestinal inflammation and diarrhea, thus regulating the gut microbiome. This review summarizes and discusses the structure and multiple functions of ACE2 and the relevance of this key enzyme in disease pathogenesis.  (Circ J 2013; 77: 301–308)
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Editorials
Original Articles
Arrythmia/Electrophysiology
  • – Atherosclerosis Risk in Communities (ARIC) Study –
    Jeffrey R. Misialek, Faye L. Lopez, Pamela L. Lutsey, Rachel R. Huxley ...
    2013 Volume 77 Issue 2 Pages 323-329
    Published: 2013
    Released on J-STAGE: January 25, 2013
    Advance online publication: October 06, 2012
    JOURNAL FREE ACCESS
    Supplementary material
    Background: Low serum magnesium (Mg) has been associated with an increased risk of cardiovascular disease (CVD), including ventricular arrhythmias, but the association between serum or dietary Mg and atrial fibrillation (AF) has not been investigated. Methods and Results: A total of 14,290 men and women (75% white; 53% female; mean age, 54 years) free of AF at baseline participating in the Atherosclerosis Risk in Communities study in the United States, were studied. Incident AF cases through 2009 were ascertained from electrocardiograms, hospital discharge codes, and death certificates. Multivariate Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for AF associated with serum and dietary Mg quintiles. Over a median follow-up time of 20.6 years, 1,755 incident AF cases were identified. In multivariate models, lower serum Mg was associated with higher AF risk: compared to individuals in the middle quintile (≥0.80–0.83mmol/L), the HR (95% CI) of AF in quintiles 1, 2, 4, and 5 were 1.34 (1.16–1.54), 0.99 (0.85–1.16), 1.04 (0.90–1.22), and 1.06 (0.91–1.23), respectively. There was no evidence of significant interactions between serum Mg and sex or race. No association between dietary Mg and AF risk was observed. Conclusions: Lower serum Mg was associated with a higher AF risk, and this association was not different between whites and African Americans. Dietary Mg was not associated with AF risk.  (Circ J 2013; 77: 323–329)
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  • Hiroko Miyazaki, Mikiko Nakagawa, Yukie Shin, Osamu Wakisaka, Tetsuji ...
    2013 Volume 77 Issue 2 Pages 330-337
    Published: 2013
    Released on J-STAGE: January 25, 2013
    Advance online publication: October 23, 2012
    JOURNAL FREE ACCESS
    Background: Although J-waves are seen in both patients with idiopathic ventricular fibrillation (IVF) and the general population, their genesis remains unclear. To assess the relationship between J-waves and autonomic tone we investigated the circadian variation of J-waves in individuals with and without IVF. Methods and Results: In study 1, we obtained resting 12-lead ECG and Holter ECG recordings in 258 individuals undergoing screening for heart disease. In 60 of these subjects (23.3%), we detected J-waves on Holter ECGs; 40 of them (66.7%) had shown no J-waves on 12-lead ECGs. In study 2, we measured the J-wave amplitude, heart rate (HR), and HR variability [high frequency (HF) and the ratio of low- to high-frequency (LF/HF)] on Holter ECGs recorded in 5 patients with IVF and 20 control subjects who had manifested J-waves. The J-wave amplitude increased at night and decreased during the day in both groups; it was significantly higher in the IVF patients (P<0.0001). In both groups, the J-wave amplitude showed a significant negative correlation with HR and LF/HF and a significant positive correlation with HF. The slope of the J/HR and J/(LF/HF) relationship was significantly steeper in the IVF patients. Conclusions: The J-wave amplitude was more significantly influenced by the autonomic balance in IVF patients than in the controls. Autonomic J-wave modulation may yield important information on the genesis of J-waves.  (Circ J 2013; 77: 330–337)
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  • Tatsuya Hayashi, Koji Kumagai, Shigeto Naito, Koji Goto, Kenichi Kasen ...
    2013 Volume 77 Issue 2 Pages 338-344
    Published: 2013
    Released on J-STAGE: January 25, 2013
    Advance online publication: October 20, 2012
    JOURNAL FREE ACCESS
    Background: Safety of atrial fibrillation (AF) ablation in conditions of periprocedural therapeutic international normalized ratio (INR) in combination with heparin is still uncertain, and little is known about the pre-procedural therapeutic INR influence on bleeding complications (BC) in this method. Methods and Results: The subjects were 150 consecutive patients who underwent catheter ablation for AF with therapeutic INR. The patients were classified into 2 groups, BC (Group BC) and no BC (Group No BC), by whether they did or did not have BC, respectively. Differences in various parameters, including pre- and post-procedural prothrombin time-INR and activated partial thromboplastin time (APTT), were compared between the 2 groups. None of the patients experienced stroke or transient ischemic attack. In the 22 patients (15%) who had BC (Group BC), 3 patients had major and 19 patients had minor BC. There were no significant differences between the 2 groups in pre-procedural INR, APTT, and amount of heparin administered during the procedure. However, post-procedural INR and APTT were significantly prolonged in Group BC (2.5±0.5 vs. 2.2±0.5, P=0.016, 65±45 vs. 44±11, P<0.0001 respectively). Multivariable analysis showed that post-procedural APTT was the only independent bleeding risk factor (P=0.022). Conclusions: AF ablation with peri-procedural therapeutic INR in combination with heparin seems to be safe. Presence or absence of BC are not related to the pre-procedural INR level, but to post-procedural APTT.  (Circ J 2013; 77: 338–344)
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  • Yukoh Hirai, Yukiko Nakano, Hideya Yamamoto, Hiroshi Ogi, Yoshiyuki Ya ...
    2013 Volume 77 Issue 2 Pages 345-351
    Published: 2013
    Released on J-STAGE: January 25, 2013
    Advance online publication: October 26, 2012
    JOURNAL FREE ACCESS
    Background: Distinguishing left-and right-sided atrial tachycardia (AT) is often challenging. The coronary sinus (CS) provides information only concerning the anterior left atrium (LA). Potentials recorded in the pulmonary artery (PA) have been substituted for those of the upper posterior LA because of their anatomical relationship. Methods and Results: Three patterns were designed, using potentials in the PA, right atrium (RA) and CS, to predict the side of AT. Two patterns were for left-sided AT and 1 pattern was for right-sided AT. Ten left-sided and 11 right-sided ATs were investigated regardless of mechanism. Electrode catheters were inserted in the RA, His bundle region, and CS, and an ablation catheter was inserted into the left and/or right PA. The sequences from these catheters were analyzed before detailed electroanatomical mapping. Patterns were obtained for 20 of 21 ATs. The mechanism was focal in 16 ATs and macroreentry in 5. The method predicted left-sided AT with a sensitivity of 78%, a specificity of 100%, a positive predictive value of 100%, a negative predictive value of 84%, and an accuracy of 90%. Conclusions: The use of potentials in PA combined with conventional RA and CS electrograms is useful for distinguishing left-sided AT from right-sided AT, regardless of mechanism.  (Circ J 2013; 77: 345–351)
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  • – Prevalence and Electrophysiological Properties –
    Shinsuke Miyazaki, Hiroshi Taniguchi, Shigeki Kusa, Takashi Uchiyama, ...
    2013 Volume 77 Issue 2 Pages 352-358
    Published: 2013
    Released on J-STAGE: January 25, 2013
    Advance online publication: October 23, 2012
    JOURNAL FREE ACCESS
    Background: Superior vena cava (SVC) is an infrequent yet an important source of atrial fibrillation (AF). The data on SVC reconnection are limited. Methods and Results: Following pulmonary vein (PV) antrum isolation for AF, SVC isolation was systemically performed under angiographic and mapping guidance using 4-mm non-irrigated tip catheter. SVC reconnection could be evaluated in 76 consecutive patients (65±9 years, 59 male) who underwent repeat AF ablation after 16±16 months. SVC was isolated at the 1st, 2nd, 3rd and 4th AF ablation procedure in 63, 7, 5 and 1 patient by 7.3±3.1 radiofrequency applications. SVC reconnection was observed in 56 patients (74%). In the majority, the conduction gap was located at the anterolateral SVC-right atrium (RA) junction. After re-isolation of SVC, 2/7 patients (29%) had reconnection at the following procedure. Among 63 patients who underwent PV and SVC isolation at the initial procedure, the prevalence of reconnection for PV and that for SVC were similar (53/63, 84% vs. 46/63, 73%; P=0.129). Dissociated activity, however, was more frequently observed in the PVs than in the SVC (47/63, 73% vs. 10/63, 16%; P<0.0001). During the procedure, AF initiation from a thoracic vein was identified in 19/63 patients (30%). Conclusions: SVC reconnection is common after 1 or more previous isolation procedures undertaken for AF ablation. Its prevalence is similar to that of PV reconnection. The location of the conduction gap varies widely but is most frequently found at the anterolateral SVC-RA junction.  (Circ J 2013; 77: 352–358)
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Cardiovascular Intervention
  • Koichi Maeda, Toru Kuratani, Isamu Mizote, Kazuo Shimamura, Yasuharu T ...
    2013 Volume 77 Issue 2 Pages 359-362
    Published: 2013
    Released on J-STAGE: January 25, 2013
    Advance online publication: October 13, 2012
    JOURNAL FREE ACCESS
    Background: Transcatheter aortic valve replacement (TAVR) is a new alternative treatment with acceptable early results for patients with aortic valve stenosis considered to be inoperable. The first TAVR was performed in Japan in October 2009, and a total of 51 have been performed up to February 2012. Methods and Results: Because it is not possible to disclose details for 36 patients at the time of writing due to ongoing clinical trials, the early and mid-term results of 15 patients are presented for the Edwards SAPIEN valves. Age was 83.4±6.1 years. Mean pressure gradient and aortic valve area were 60.3±21.1mmHg and 0.64±0.19cm2, respectively. Left ventricular ejection fraction was 55.5±15.4%. The Logistic EuroSCORE, EuroSCORE II, and Society of Thoracic Surgeons score were 28.5±21.5%, 11.1±15.8%, and 10.0±7.4%, respectively. All of the procedures were successful and did not require conversion to surgery. Perioperative stroke did not occur, although pacemakers were implanted in 2 patients (13.3%). At discharge, mean pressure gradient and aortic valve area were improved to 10.8±4.4mmHg and 1.77±0.36cm2, respectively. Except for 1 patient who died of cancer 7 months after operation, all patients were alive at the time of writing (11–848 days after procedure; mean follow-up period, 184 days). Conclusions: Satisfactory early and mid-term results have been achieved with TAVR, indicating that this is a good alternative to treat aortic valve stenosis.  (Circ J 2013; 77: 359–362)
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  • – Comparison Between Zotarolimus-Eluting Stents and Paclitaxel-Eluting Stents –
    Yoshitaka Muraoka, Shinjo Sonoda, Kuninobu Kashiyama, Fumihiko Kamezak ...
    2013 Volume 77 Issue 2 Pages 363-371
    Published: 2013
    Released on J-STAGE: January 25, 2013
    Advance online publication: October 27, 2012
    JOURNAL FREE ACCESS
    Background: Out-stent plaque characteristics and eosinophilic inflammatory response, which correlates with positive remodeling after first-generation drug-eluting stent implantation, may be associated with late restenosis and very late stent thrombosis. The differences of out-stent plaque characteristics were compared between paclitaxel-eluting stents (PES) and zotarolimus-eluting stents (ZES), using integrated backscatter-intravascular ultrasound (IB-IVUS). Methods and Results: Of 78 patients enrolled, 25 receiving PES and 25 receiving ZES had adequate IVUS assessment. Volumetric IVUS analysis was performed after stenting and at 8-month follow-up. Out-stent plaque change in the stented segment was compared on IB-IVUS. The relationship between systemic inflammatory response and out-stent plaque change was evaluated. In PES, vessel volume significantly increased (365–389mm3, P<0.0001), whereas it did not change in ZES (315–314mm3, P=0.81). In culprit lesions at baseline in PES, fibrous plaque tended to increase (3.1–3.6mm2, P=0.051) and lipid plaque significantly increased (4.3–5.1mm2, P=0.02), whereas in ZES the fibrous plaque significantly increased (2.9–4.0mm2, P<0.0001) but lipid plaque significantly decreased (5.1–3.6mm2, P<0.0001). Systemic eosinophil increase was significantly correlated with positive remodeling and out-stent lipid plaque increase. Conclusions: Chronic out-stent plaque change in ZES consisted of less positive remodeling and more favorable effects on out-stent plaque characteristics than PES. Systemic eosinophil change might be a marker of out-stent lipid plaque change.  (Circ J 2013; 77: 363–371)
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  • – An Aggregate Data Meta-Analysis of 11,148 Patients –
    Mahboob Alam, Henry D. Huang, Saima A. Shahzad, Biswajit Kar, Salim S. ...
    2013 Volume 77 Issue 2 Pages 372-382
    Published: 2013
    Released on J-STAGE: January 25, 2013
    Advance online publication: October 31, 2012
    JOURNAL FREE ACCESS
    Supplementary material
    Background: Patients with unprotected left main coronary artery (LMCA) disease are increasingly treated with percutaneous coronary intervention (PCI) using drug-eluting stents (DES), but its benefits compared with coronary artery bypass grafting (CABG) remain controversial. We hypothesized that PCI with DES for unprotected LMCA disease is safe and effective compared with CABG. Methods and Results: We performed aggregate data meta-analyses of clinical outcomes [death; non-fatal myocardial infarction (MI); stroke; repeat revascularization; and major adverse cardiac and cerebrovascular events (MACCE)] in studies comparing PCI with DES vs. CABG in patients with LMCA disease. A comprehensive literature search (01/01/2003 to 12/01/2011) identified 27 studies comparing PCI and CABG (11,148 patients). Summary odds ratios (OR) were calculated using a random-effects model. At 30 days, PCI for unprotected LMCA disease was associated with lower MACCE [odds ratio (OR) 0.57, 95% confidence interval (CI) 0.36–0.89) and stroke rates (OR 0.22, 95% CI 0.11–0.44) compared with CABG. At 12 months, the PCI group experienced higher rates of repeat revascularization (OR 3.72, 95% CI 2.75–5.03), but lower rates of stroke (OR 0.25, 95% CI 0.14–0.44) and all-cause death (OR 0.69, 95% CI 0.49–0.97). At the longest follow-up of 60 months, PCI was associated with equivalent mortality, lower rates of stroke (OR 0.42, 95% CI 0.28–0.62) and higher rates of MACCE (OR 1.30, 95% CI 1.10–1.55) and repeat revascularization (OR 3.54, 95% CI 2.75–4.54). Conclusions: In the DES era, PCI for unprotected LMCA disease is associated with equivalent mortality and MI, lower stroke rates and higher rates of repeat revascularization compared with CABG.  (Circ J 2013; 77: 372–382)
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Critical Care
  • – Experience of 15 Primary Percutaneous Coronary Intervention Centers in Taiwan –
    Su-Kiat Chua, Jun-Jack Cheng, Kou-Gi Shyu, Jen-Yuan Kuo, Yu-Lin Ko, Ch ...
    2013 Volume 77 Issue 2 Pages 383-389
    Published: 2013
    Released on J-STAGE: January 25, 2013
    Advance online publication: November 03, 2012
    JOURNAL FREE ACCESS
    Background: Currently, the door-to-balloon (D2B) times observed in clinical practice in Taiwan are different from those recommended by evidence-based guidelines. D2B Alliance, a countrywide initiative for quality supported by the Taiwan Joint Commission on Hospital Accreditation, sought to achieve the goal of administering treatment to 75% of patients with ST-elevation myocardial infarction (STEMI) within 90min of hospital presentation. Methods and Results: The current study was designed to be prospective, national, and multicenter. We conducted a longitudinal study of the D2B times recorded in 15 primary percutaneous coronary intervention centers and examined the changes caused by implementing the D2B Alliance strategies. A total of 1,726 patients were enrolled in the D2B Alliance and implementation of the D2B Alliance strategies resulted in a significant decrease in the average D2B times (128.8±42.9min vs. 83.2±16.2min; P<0.001) from those at baseline. By the end of the year-long study, the percentage of patients treated under 90min had increased from 46.2% to 80.1% in the hospitals enrolled in the D2B Alliance. Conclusions: Over the 1 year, hospitals enrolled in the D2B Alliance achieved the goal of reducing the D2B times of 75% of STEMI patients to less than 90min.  (Circ J 2013; 77: 383–389)
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Heart Failure
  • Shuzo Shimazu, Akihiro Hirashiki, Takahiro Okumura, Takashi Yamada, Ri ...
    2013 Volume 77 Issue 2 Pages 390-396
    Published: 2013
    Released on J-STAGE: January 25, 2013
    Advance online publication: October 26, 2012
    JOURNAL FREE ACCESS
    Background: Serum indoxyl sulfate (IS) is a uremic toxin that accelerates the progression of chronic kidney disease (CKD). The aim of this study was to determine whether serum IS is associated with hemodynamic parameters or cardiac events in patients with nonischemic dilated cardiomyopathy (DCM). Methods and Results: The 76 patients with DCM had their serum IS and plasma brain natriuretic peptide (BNP) levels measured, and underwent echocardiographic examination. Mean (±standard deviation) left ventricular ejection fraction (LVEF) and BNP levels in the patients were 32.5±10.7% and 204±219pg/ml, respectively. Patients were divided into 2 groups, low IS (<0.9μg/ml) and high IS (≥0.9μg/ml), based on the median value of serum IS. Although there were no significant differences in LVEF and BNP between the groups, E/e’ was significantly greater in the high IS group than in the low IS group. Furthermore, E/e’ was an independent determinant of serum IS level. The risk of a cardiac event was significantly higher in the high IS group than in the low IS group (P=0.014). Moreover, serum IS was a significant predictor of cardiac events even after adjustment for BNP. Conclusions: Cardiac dysfunction is associated with the serum IS level, which might serve as a new prognostic marker in DCM patients with normal renal function or mild to moderate CKD.  (Circ J 2013; 77: 390–396)
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  • – Association Between Non-Responders and Chronic Kidney Disease –
    Teruhiko Imamura, Koichiro Kinugawa, Taro Shiga, Naoko Kato, Hironori ...
    2013 Volume 77 Issue 2 Pages 397-404
    Published: 2013
    Released on J-STAGE: January 25, 2013
    Advance online publication: November 03, 2012
    JOURNAL FREE ACCESS
    Background: A newly-developed vasopressin type 2 receptor antagonist, tolvaptan (TLV), has a unique feature of diuresis, but the response to this drug can be unpredictable. Methods and Results: Data were collected from hospitalized patients with decompensated congestive heart failure who were administered TLV at 3.75–15mg/day (n=61). A responder/non-responder to TLV was determined as having any increase/decrease in urine volume (UV) during the next 24h after TLV treatment on the first day. Logistic regression analyses for increases in UV were performed, and independent predictors of the responder were the following: C1, baseline urine osmolality (U-OSM) >352mOsm/L; and C2, %decrease in U-OSM >26% at 4–6h after TLV administration. Criteria consisting of C1 and C2 had a good predictability for responders by receiver-operating characteristic analysis (area under the curve=0.960). Kidneys of the non-responders no longer had diluting ability (%decrease of U-OSM at 4–6h=2.7±14.6%*), but also barely kept concentrating ability (baseline U-OSM=296.4±68.7*mOsm/L) with markedly reduced estimated glomerular filtration ratio (35.5±29.4ml·min–1·1.73m−2*) (*P<0.05 vs. patients who had at least 1 positive condition [n=42]). Conclusions: More than 26% decrease in U-OSM from a baseline >352mOsm/L for the first 4–6h predicts responders to TLV. Unresponsiveness to TLV is attributable to nephrogenic diabetes insipidus complicated by chronic renal disease.  (Circ J 2013; 77: 397–404)
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Hypertension and Circulatory Control
  • – A Nationwide Cohort Study –
    Chien-Yi Hsu, Chin-Chou Huang, Wan-Leong Chan, Po-Hsun Huang, Chia-Hun ...
    2013 Volume 77 Issue 2 Pages 405-410
    Published: 2013
    Released on J-STAGE: January 25, 2013
    Advance online publication: November 10, 2012
    JOURNAL FREE ACCESS
    Supplementary material
    Background: Although emerging evidence shows angiotensin-receptor blockers (ARBs) may have a beneficial effect against Alzheimer’s disease (AD), the association is not consistent. We investigated the association between ARB use and the risk of development of AD using a nationwide, population-based cohort database in Taiwan. Methods and Results: In total, 16,426 newly diagnosed hypertensive patients who were administered ARB without a previous diagnosis of AD were identified from the Taiwan National Health Insurance database. The comparison group consisted of hypertensive patients who did not receive ARB, and were matched to exposed individuals using propensity score by enrolled time, age, sex, and comorbidities. During an average of 5.24±2.01 years of follow-up, a total of 1,031 cases (3.13%) of new AD occurred. The log-rank test showed no significant difference in the AD occurrence rate between subjects exposed to ARBs and non-exposed controls [488 (2.97%) vs. 543 (3.29%), P=0.221]. After adjusting for age, sex, comorbidities, and medications, only advanced age [hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.12–1.13, P<0.001), female sex (HR 1.18, 95% CI 1.04–1.33, P=0.011), diabetes (HR 1.53, 95% CI 1.31–1.79, P<0.001), but not ARB (HR 1.08, 95% CI 0.96–1.22, P=0.222) were independently associated with AD development. Conclusions: The use of ARB was not significantly associated with a reduction of risk of AD in Asian patients with essential hypertension.  (Circ J 2013; 77: 405–410)
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Imaging
  • – Potential Application of Computed Tomography Angiography and Myocardial Perfusion Imaging –
    Sadako Motoyama, Masayoshi Sarai, Kaori Inoue, Hideki Kawai, Hajime It ...
    2013 Volume 77 Issue 2 Pages 411-417
    Published: 2013
    Released on J-STAGE: January 25, 2013
    Advance online publication: October 13, 2012
    JOURNAL FREE ACCESS
    Background: The role of combined evaluation of myocardial perfusion imaging (MPI; by single-photon emission computed tomography) and computed tomography angiography (CTA) for risk stratification of coronary artery disease was evaluated. For CTA, the extent of luminal stenosis, and also the features of high-risk plaques (HRP, including positive remodeling and low attenuation) were evaluated. Methods and Results: A total of 304 patients (65±11 years, male 72%, median follow-up: 24 months) who underwent CTA and MPI were enrolled in the study. Summed stress scores and summed difference scores (SDS) for MPI, stenosis, and HRP were evaluated, and event rates were compared. Cardiac events were defined as acute coronary event including cardiac death or non-fatal acute myocardial infarction, and unstable angina requiring revascularization. Of 304 patients, 51 (16.8%) underwent early revascularization. In the remaining 253 patients, an event occurred in 11 (4.3%). HRP (hazard ratio [HR], 4.75, P=0.00171) and stenosis (+) with SDS >0 (HR, 4.58, P=0.0461) were significant independent predictors of cardiac event. The event rate for stenosis (+) with SDS >0 was significantly higher than others (log-rank P=0.0490). The event rates were significantly different between HRP(+) and HRP(–) (16.1% vs. 2.7%, log-rank P=0.0013). Conclusions: HRP on CTA was an independent predictor of acute coronary events, as was stenosis (+) with SDS >0, and HRP had increased prognostic value over stenosis and abnormal MPI findings.  (Circ J 2013; 77: 411–417)
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  • – Identification of Subprosthetic Pannus in the Aortic Position –
    Tomohiro Ueda, Hideki Teshima, Shuji Fukunaga, Shigeaki Aoyagi, Hiroyu ...
    2013 Volume 77 Issue 2 Pages 418-423
    Published: 2013
    Released on J-STAGE: January 25, 2013
    Advance online publication: October 19, 2012
    JOURNAL FREE ACCESS
    Background: This study was performed to evaluate the diagnostic role of electrocardiographically gated multidetector-row computed tomography (MDCT) for prosthetic valve obstruction (PVO) in the aortic position. Methods and Results: Between 2002 and 2006, 9 patients were diagnosed with PVO of an aortic bileaflet mechanical valve based on echocardiographic and cineradiographic criteria. These 9 patients were examined using MDCT before replacement of the mechanical valve, and intraoperative findings were compared to morphologic periprosthetic abnormalities observed on MDCT. CT attenuation (Hounsfield units; HU) of the periprosthetic abnormalities was measured to investigate the underlying cause of the PVO. MDCT showed subprosthetic masses extending beyond the prosthetic ring into the orifice of the valve. At reoperation, presence of subprosthetic pannus was confirmed in all of the 9 patients, but no periprosthetic thrombus was found. The mean CT attenuation of the subprosthetic pannus was 170 HU, and it was significantly greater than that obtained from the interventricular septum (108 HU; P<0.0001). Conclusions: MDCT can be used to clearly visualize subprosthetic pannus causing PVO and the mean CT attenuation of subprosthetic pannus is significantly higher than that of the interventricular septum on MDCT.  (Circ J 2013; 77: 418–423)
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  • Naoki Nakayama, Kiyoshi Hibi, Mitsuaki Endo, Akiyoshi Miyazawa, Hiroyu ...
    2013 Volume 77 Issue 2 Pages 424-431
    Published: 2013
    Released on J-STAGE: January 25, 2013
    Advance online publication: November 10, 2012
    JOURNAL FREE ACCESS
    Background: Intravascular ultrasound (IVUS) analysis software enables precise planimetry measurement and tissue characterization of coronary plaque. Recently, a new IVUS analysis software compatible with integrated backscatter-IVUS, VISIATLASTM, was developed. The validity and reliability of VISIATLASTM were evaluated. Methods and Results: Forty patients who underwent IVUS-guided percutaneous coronary intervention were enrolled, and planimetry measurements were performed by 2 observers using VISIATLASTM and echoPlaqueTM. IVUS analysis was performed in non-stent segments in 10 patients (non-target vessel, n=5; target vessel before stent implantation, n=5) at every 2.5mm for 20 slices in each patient. Stent segments were analyzed in the remaining 30 patients. With VISIATLASTM, the intraobserver and interobserver intraclass correlation coefficients (ICC) for the area of external elastic membrane (EEM), lumen, and plaque plus media (P+M) were 0.999 and 0.999, 0.996 and 0.993, and 0.993 and 0.991, respectively. The intersoftware ICC for EEM, lumen, and P+M area were 0.997, 0.993, and 0.985, respectively. The ICC of stent volume for intraobserver, interobserver and intersoftware comparisons were 0.997, 0.993, and 0.998, respectively. Bland-Altman plots showed small differences and narrow limits of agreement for all of the above parameters. Conclusions: VISIATLASTM has high repeatability and reproducibility of measurement. This new IVUS analysis software is suitable for accurate measurement of coronary artery and stent structure in future IVUS studies.  (Circ J 2013; 77: 424–431)
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Ischemic Heart Disease
  • Kyoko Hoshida, Yosuke Miwa, Mutsumi Miyakoshi, Takehiro Tsukada, Sator ...
    2013 Volume 77 Issue 2 Pages 432-438
    Published: 2013
    Released on J-STAGE: January 25, 2013
    Advance online publication: October 12, 2012
    JOURNAL FREE ACCESS
    Background: T-wave alternans based on the modified moving average method (MMA-TWA) and heart rate turbulence (HRT) have been introduced as predictors for cardiac mortality. In this study, we simultaneously recorded MMA-TWA and HRT in patients after myocardial infarction (MI) and designed a prospective observational study. Methods and Results: We prospectively enrolled 313 consecutive post-MI patients (age 70±12 years, 232 men). The MMA-TWA and HRT were simultaneously measured using algorithms based on 24-h Holter ECG monitoring during daily activity. MMA-TWA was determined positive when the maximal voltage was >64μV, and HRT was determined positive when both turbulence onset and turbulence slope were abnormal. The endpoint was defined as overall cardiac mortality and fatal arrhythmic events. MMA-TWA was positive in 14 patients (4.4%) and HRT was positive in 61 patients (19.5%). During follow-up of 1,190±441 days, 28 patients (9%) reached the endpoint, including 12 patients with fatal arrhythmic events. Both MMA-TWA and HRT were significant predictors for the endpoint. On multivariate analysis, HRT had the most significant value, with a hazard ratio (HR) of 5.7 (P=0.0008). When focused on fatal arrhythmic events including sudden cardiac death, MMA-TWA had the most significant value (HR 5.8, P=0.0072). Conclusions: The present study revealed that both MMA-TWA and HRT were significant predictors. MMA-TWA is more associated with arrhythmic events than cardiac mortality in post-MI patients.  (Circ J 2013; 77: 432–438)
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  • Daisaku Nakatani, Yasuhiko Sakata, Shinichiro Suna, Masaya Usami, Sen ...
    2013 Volume 77 Issue 2 Pages 439-446
    Published: 2013
    Released on J-STAGE: January 25, 2013
    Advance online publication: October 17, 2012
    JOURNAL FREE ACCESS
    Background: In the percutaneous coronary intervention (PCI) era, little evidence exists regarding the incidence, predictors and long-term mortality of recurrent myocardial infarction (Re-MI) following discharge for acute myocardial infarction (AMI). Methods and Results: A total of 7,870 patients who survived AMI were studied with a median follow-up period of 3.9 years: 353 patients (4.5%) experienced Re-MI, with 7 of those dying within 30 days, which was classified as fatal Re-MI. The incidence of Re-MI per year was 2.65% for the first year, and 0.91–1.42% thereafter up to 5 years. Multivariate Cox regression analyses revealed that predictors of Re-MI were diabetes mellitus (hazard ratio (HR): 2.079, P<0.001), history of MI (HR: 1.767, P=0.001), and advanced age (HR: 1.021, P=0.001). These 3 predictors remained significant when angiographic and procedural parameters were incorporated into the analyses. The incidence and adjusted risk of Re-MI increased when these variables were clustered (P<0.001). The all-cause mortality rate was significantly higher in patients with Re-MI than in those without (HR: 2.206, P<0.001). Conclusions: In post-AMI patients treated in the PCI era, the incidence of Re-MI is low compared with that reported during the past 30 years. Patients’ clinical factors of diabetes mellitus, history of MI, and advanced age appear to affect the occurrence of Re-MI after hospital discharge, and Re-MI still carries a risk for subsequent mortality.  (Circ J 2013; 77: 439–446)
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  • Kimio Satoh, Yoshihiro Fukumoto, Koichiro Sugimura, Yutaka Miura, Tats ...
    2013 Volume 77 Issue 2 Pages 447-455
    Published: 2013
    Released on J-STAGE: January 25, 2013
    Advance online publication: November 08, 2012
    JOURNAL FREE ACCESS
    Supplementary material
    Background: Oxidative stress induces secretion of cyclophilin A (CyPA) from vascular smooth muscle cells and it plays a crucial role in the pathogenesis of atherosclerosis in mice. Therefore, we tested our hypothesis that plasma CyPA levels are increased in patients with coronary artery diseases (CAD). Methods and Results: In 320 consecutive patients undergoing coronary angiography, we examined the relationship between plasma CyPA levels and the severity of CAD. We measured plasma CyPA by an immunoassay based on the sandwich technique. Plasma CyPA levels were significantly higher in patients with significant coronary stenosis compared to those without it (P<0.001). A positive correlation was noted between plasma CyPA levels and significant coronary stenosis. The average number of stenotic coronary arteries and the need for coronary intervention were significantly increased in the quartiles of higher CyPA levels (both P<0.001). Indeed, the plasma CyPA level significantly correlated with the presence of CAD (adjusted odds ratio for CAD, 6.20; 95% confidence interval, 3.14–12.27; P<0.001). Interestingly, plasma levels of CyPA increased according to the number of atherosclerotic risk factors, all of which induce oxidative stress. Furthermore, plasma levels of CyPA significantly reduced after medical treatment of risk factors. Finally, CyPA was strongly expressed in coronary atherosclerotic plaque in patients with myocardial infarction. Conclusions: Plasma CyPA level is a novel biomarker for oxidative stress and CAD in humans.  (Circ J 2013; 77: 447–455)
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  • Shuta Tsuboi, Katsumi Miyauchi, Takatoshi Kasai, Manabu Ogita, Tomotak ...
    2013 Volume 77 Issue 2 Pages 456-461
    Published: 2013
    Released on J-STAGE: January 25, 2013
    Advance online publication: October 17, 2012
    JOURNAL FREE ACCESS
    Background: Red blood cell distribution width (RDW) is a novel prognostic marker that reflects oxidative stress and chronic inflammation in patients with cardiovascular disease. Diabetes mellitus increases oxidative stress and vascular inflammation, which accelerate atherosclerosis. However, the relationship between RDW and long-term outcome in diabetic patients with coronary artery disease (CAD) is unclear. Methods and Results: Subjects comprised 560 consecutive diabetic patients (mean age, 66.6 years; male, 80%) with stable CAD who had undergone elective percutaneous coronary intervention (PCI). Patients were divided into 2 groups according to median RDW at baseline (13.1%): a high RDW group (mean RDW, 14.0%; interquartile range, 13.3–14.2%); and a low RDW group (mean RDW, 12.6%; interquartile range, 12.4–12.9%). All-cause mortality rates were compared between groups. Mean duration of follow up was 3.9 years. Patients with high RDW were more likely to be older, show dyslipidemia and have a lower ejection fraction and decreased hemoglobin level. Twenty-nine patients (5.2%) died during follow up. The cumulative incidence of all-cause death was significantly higher in the high RDW group than in the low RDW group (log-rank P=0.0015). Multivariate analysis identified high RDW as being associated with all-cause mortality (hazard ratio, 2.56; 95% confidence interval, 1.12–6.62; P=0.025). Conclusions: Increased RDW was significantly associated with increased long-term all-cause mortality in diabetic patients after PCI.  (Circ J 2013; 77: 456–461)
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Myocardial Disease
  • Jin-Oh Choi, Eun Young Kim, Ga Yeon Lee, Sang-Chol Lee, Seung Woo Park ...
    2013 Volume 77 Issue 2 Pages 462-469
    Published: 2013
    Released on J-STAGE: January 25, 2013
    Advance online publication: October 24, 2012
    JOURNAL FREE ACCESS
    Supplementary material
    Background: Optimal medical therapy can lead to left ventricular (LV) reverse remodeling (LVRR) in nonischemic dilated cardiomyopathy (NIDCM). However, because the clinical variables associated with LVRR are poorly defined, we sought to identify them and their prognostic role, and to evaluate the role of initial and midterm levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in the long-term follow-up of patients with NIDCM. Methods and Results: We evaluated 329 consecutive hospitalized patients with NIDCM by reviewing the records in the institutional heart failure database. Clinical and echocardiographic data were available for 253 (77%) patients at the midterm follow-up (16±7 months). The patients were followed thereafter until the combined endpoint of cardiovascular death, heart transplantation, or hospitalization for heart failure. LVRR was noted in 97 (38%) of 253 patients at midterm. The baseline predictors of LVRR were higher systolic blood pressure, QRS duration <120ms, use of a β-blocker, and a small indexed LV end-systolic dimension. In landmark survival analysis from the midterm evaluation, LVRR, low midterm NT-proBNP level, and continuous use of a β-blocker were independently related to good long-term results. Conclusions: Monitoring of patients with NIDCM using both cardiac imaging of the LV structure and by assessing neurohormonal status (NT-proBNP level) at the midterm follow-up might be clinically useful for predicting the long-term clinical prognosis of NIDCM.  (Circ J 2013; 77: 462–469)
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Pediatric Cardiology and Adult Congenital Heart Disease
  • Hideo Ohuchi, Yuka Tanabe, Chizuko Kamiya, Kanae Noritake, Kenji Yasud ...
    2013 Volume 77 Issue 2 Pages 470-476
    Published: 2013
    Released on J-STAGE: January 25, 2013
    Advance online publication: October 12, 2012
    JOURNAL FREE ACCESS
    Background: Maternal New York Heart Association (NYHA) class is associated with pregnancy outcome in women with congenital heart disease (WCHD), but objective predictive criteria of exercise capacity have not been established. Methods and Results: A total of 33 WCHD (age, 28±5 years; NYHA class, 1.3±0.6) who had undergone cardiopulmonary exercise testing (CPX) 1.8±2.2 years before their delivery were retrospectively identified. Maternal, cardiac, and neonatal events occurred in 8 (24%), 12 (36%), and 14 (42%), respectively. All CPX parameters correlated with neonatal birth weight (P<0.05–0.001). Exercise time, peak heart rate (HR), peak systolic blood pressure, and peak oxygen uptake (VO2) were associated with cardiac events (P<0.05–0.01), and exercise time and peak VO2 were also associated with neonatal events (P<0.05). Exercise time, peak HR, and peak VO2 were associated with at least 1 of the 3 events (P<0.05–0.01). Receiver operating characteristic analysis showed that peak HR <150beats/min and/or peak VO2 <22.0ml·kg–1·min–1, peak VO2 <26.2ml·kg–1·min–1, and peak HR <150beats/min and/or peak VO2 <25.3ml·kg–1·min–1 predicted a high probability of maternal cardiac, neonatal, and maternal cardiac and/or neonatal event, respectively. Conclusions: CPX parameters predict pregnancy outcome and peak HR ≥150beats/min and/or peak VO2 ≥25ml·kg–1·min–1 may be reference value(s) for a safer pregnancy outcome in WCHD.  (Circ J 2013; 77: 470–476)
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Peripheral Vascular Disease
  • Takashi Ishihara, Go Haraguchi, Daisuke Tezuka, Tetsuo Kamiishi, Hiros ...
    2013 Volume 77 Issue 2 Pages 477-483
    Published: 2013
    Released on J-STAGE: January 25, 2013
    Advance online publication: October 26, 2012
    JOURNAL FREE ACCESS
    Supplementary material
    Background: Patients with Takayasu arteritis (TA) often show recurrence under steroid treatment without an elevation of C-reactive protein (CRP). There is a report that matrix metalloproteinase (MMP)-2, MMP-3, MMP-9 and pentraxin3 (PTX3) could be sensitive biomarkers, but the characteristics of these biomarkers have not been established. Methods and Results: We enrolled 45 consecutive patients; 28 were grouped in an active phase as evidenced by clinical recurrence within 2 years of blood sampling. Circulating levels of high-sensitivity (hs)CRP, MMPs, and PTX3 were determined. Patients in an active phase showed higher levels of hsCRP, MMP-9, and PTX3. Area under the receiving operating characteristics curves of hsCRP and PTX3 were significantly higher than that of MMP-9. Among the 28 patients with active TA, 71% was positive for hsCRP and 82% for PTX3. Patients without recurrence showed significantly higher plasma levels of MMP-9. There was a positive correlation between the plasma MMP-3 level and the prednisolone dose. However, PTX3 and MMP-9 levels did not have such a correlation. Conclusions: PTX3 and MMP-9, which are not affected by prednisolone, could be sensitive biomarkers for assessing TA activity. Evaluation of MMP-9 may suggest prior existence of TA.  (Circ J 2013; 77: 477–483)
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Renal Disease
  • Akira Funayama, Tetsuro Shishido, Takehiko Miyashita, Shunsuke Netsu, ...
    2013 Volume 77 Issue 2 Pages 484-489
    Published: 2013
    Released on J-STAGE: January 25, 2013
    Advance online publication: October 31, 2012
    JOURNAL FREE ACCESS
    Background: Urinary β2 microglobulin (U-β2MG) is a more sensitive and accurate marker of tubulointerstitial damage. The etiology of glomerular damage is related to the occurrence of major adverse cardiovascular events (MACE) in patients with myocardial infarction (MI); however, the prognostic importance of tubulointerstitial damage in patients with ST-segment elevation MI (STEMI) has not been established. The aim of this study was to elucidate whether renal tubulointerstitial damage is associated with the occurrence of MACE in patients after STEMI undergoing percutaneous coronary intervention. Methods and Results: The degree of renal tubulointerstitial damage was evaluated by measuring the U-β2MG level in 89 consecutive STEMI patients. There were 22 MACEs during the follow-up period. Patients with MACE had higher U-β2MG levels than those without MACE, and the U-β2MG level was an independent predictor for MACE. A Kaplan-Meier analysis revealed that the group with higher U-β2MG levels corrected for urinary creatinine was associated with a greater risk for MACE. Conclusions: An elevated U-β2MG level was associated with the occurrence of MACE in STEMI patients who underwent PCI. Renal tubulointerstitial damage is therefore considered to be associated with the occurrence of MACE.  (Circ J 2013; 77: 484–489)
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Rapid Communication
  • – Report From the 10 Hospitals in the Disaster Area –
    Tatsuo Aoki, Jun Takahashi, Yoshihiro Fukumoto, Satoshi Yasuda, Kenta ...
    2013 Volume 77 Issue 2 Pages 490-493
    Published: 2013
    Released on J-STAGE: January 25, 2013
    Advance online publication: January 18, 2013
    JOURNAL FREE ACCESS
    Background: We reported an increased occurrence of cardiovascular diseases (CVDs) after the Great East Japan Earthquake by examining ambulance records, but it had to be confirmed by cardiologists. Methods and Results: We enrolled patients admitted to the cardiology department of the 10 hospitals in the disaster area from 4 weeks prior to 15 weeks after March 11 in the years 2008–2011 (n=14,078). The weekly occurrence of several CVDs, including heart failure (HF), pulmonary thromboembolism (PTE) and infectious endocarditis (IE), was sharply and significantly increased after the Earthquake. Conclusions: The Disaster caused significantly increases in the occurrence of HF, PTE and IE.  (Circ J 2013; 77: 490–493)
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