Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Volume 78 , Issue 7
Showing 1-43 articles out of 43 articles from the selected issue
Message From the Editor-in-Chief
Reviews
  • Hind Lal, Firdos Ahmad, Shan Parikh, Thomas Force
    Type: REVIEW
    2014 Volume 78 Issue 7 Pages 1514-1519
    Published: June 25, 2014
    Released: June 25, 2014
    [Advance publication] Released: June 05, 2014
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    Coronary artery disease is the leading cause of death and disability worldwide. In patients with acute coronary syndromes, timely and effective myocardial reperfusion by percutaneous coronary intervention is the primary treatment of choice to minimize the ischemic injury and limit the size of the myocardial infarction (MI). However, reperfusion can itself promote cardiomyocyte death, which leads to cardiac dysfunction via reperfusion injury. The molecular mechanisms of ischemia-reperfusion (IR) injury are not completely understood and new drug targets are needed. Recently, we reported that cardiac troponin I-interacting protein kinase (TNNI3K), a cardiomyocyte-specific kinase, promotes IR injury via profound oxidative stress, thereby promoting cardiomyocyte death. By using novel genetic animal models and newly developed small-molecule TNNI3K inhibitors, we demonstrated that TNNI3K-mediated IR injury occurs through impaired mitochondrial function and is in part dependent on p38 MAPK. Here we discuss the emerging role of TNNI3K as a promising new drug target to limit IR-induced myocardial injury. We will also examine the underlying mechanisms that drive the profoundly reduced infarct size in mice in whichTNNI3Kis specifically deleted in cardiomyocytes. Because TNNI3K is a cardiac-specific kinase, it could be an ideal molecular target, as inhibiting it would have little or no effect on other organ systems, a serious problem associated with the use of kinase inhibitors targeting kinases that are more widely expressed. (Circ J 2014; 78: 1514–1519)
  • Lei Xiao, Zihui Zhang, Xiaoqin Luo
    Type: REVIEW
    2014 Volume 78 Issue 7 Pages 1520-1530
    Published: June 25, 2014
    Released: June 25, 2014
    [Advance publication] Released: May 26, 2014
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    The pregnane X receptor (PXR) and constitutive androstane receptor (CAR), 2 closely related and liver-enriched members of the nuclear receptor superfamily, and aryl hydrocarbon receptor (AhR), a nonnuclear receptor transcription factor (TF), are major receptors/TFs regulating the expression of genes for the clearance and detoxification of xenobiotics. They are hence defined as “xenobiotic receptors”. Recent studies have demonstrated that PXR, CAR and AhR also regulate the expression of key proteins involved in endobiotic responses such as the metabolic homeostasis of lipids, glucose, and bile acid, and inflammatory processes. It is suggested that the functions of PXR, CAR and AhR may be closely implicated in the pathogeneses of metabolic vascular diseases, such as hyperlipidemia, atherogenesis, and hypertension. Therefore, manipulation of the activities of these receptors may provide novel strategies for the treatment of vascular diseases. Here, we review the pathophysiological roles of PXR, CAR and AhR in the vascular system. (Circ J 2014; 78: 1520–1530)
  • Salvatore Brugaletta, Manel Sabaté
    Type: REVIEW
    2014 Volume 78 Issue 7 Pages 1531-1539
    Published: June 25, 2014
    Released: June 25, 2014
    [Advance publication] Released: June 16, 2014
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    Atherosclerosis is the main cause of coronary artery disease (CAD), which is today the leading cause of death worldwide and will continue to be the first in the world in 2030. Vulnerable coronary plaques are usually characterized by a high content of necrotic core, a thin inflamed fibrous cap (intense accumulation of macrophages) and scarce presence of smooth muscle cells. None of these characteristics can be estimated by coronary angiography, which on the contrary underestimates the magnitude of atherosclerotic burden, particularly in earlier stage disease when positive vascular remodeling may allow “normal” lumen caliber despite substantial vascular wall plaque. The recognition of the ubiquity of substantial but non-flow limiting lesions that may be at high risk for subsequent plaque rupture has resulted in a paradigm shift in thinking about the pathophysiology of CAD, with the focus no longer solely on the degree of arterial luminal narrowing. This growing need for more information about coronary atherosclerosis in order to identify patients and lesions at risk for complications during PCI and for future adverse cardiac events has been the primary impetus for the development of novel intracoronary imaging methods able to detect plaque composition, in particular presence of a necrotic core/lipid pool, such as intravascular ultrasound virtual histology and near-infrared spectroscopy. These imaging technologies and their clinical and clinical/research applications are discussed in detail. (Circ J 2014; 78: 1531–1539)
  • Osami Kawarada, Satoshi Yasuda, Janice Huang, Yasuhiro Honda, Peter J. ...
    Type: REVIEW
    2014 Volume 78 Issue 7 Pages 1540-1549
    Published: June 25, 2014
    Released: June 25, 2014
    [Advance publication] Released: June 12, 2014
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    Infrapopliteal arterial disease is a significant cause of critical limb ischemia (CLI), whether single-segment or multisegment disease. The collaboration between the tremendous advancements in endovascular technology and the refinement of endovascular techniques has renewed the classic infrapopliteal interventions during the past decade. With this paradigm shift in the treatment of CLI, the role of a comprehensive approach of different disciplines for tissue loss is becoming greater. Given the increasing global burden of CLI, we review the cutting-edge diagnostic and endovascular approaches to infrapopliteal artery disease, and the importance of wound management in optimizing clinical outcomes. (Circ J 2014; 78: 1540–1549)
Focus Issue on Takotsubo Cardiomyopathy
  • Peter T. Wright, Matthew H. Tranter, Andrew C. Morley-Smith, Alexander ...
    Type: Focus Issue on Takotsubo Cardiomyopathy
    2014 Volume 78 Issue 7 Pages 1550-1558
    Published: June 25, 2014
    Released: June 25, 2014
    [Advance publication] Released: June 23, 2014
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    Takotsubo syndrome (TTS), also known as takotsubo cardiomyopathy, is an acute heart failure syndrome that typically occurs after a period of great emotional stress. The archetypal patient is a postmenopausal woman who presents with chest pain, ST-segment elevation and acute hypokinesia of the apical and middle segment of the left ventricle that extends beyond the territory of a single coronary artery, coupled with hyperkinesia of the basal myocardium. Recent preclinical and clinical studies have shown the importance of high catecholamine levels in precipitating TTS. We propose that this is caused by activation of β-adrenoceptors and the subsequent activation of a negatively-inotropic pathway, perhaps to protect the heart from catecholamine overload. We explore the pathophysiology of TTS according to its “phases”, both preclinically and clinically. This will show that the condition is not one of static apical hypokinesia that simply improves, but rather a dynamic condition that changes as the disease progresses. We hope that further exploration of TTS using its “phases” will aid in its characterization, diagnosis and treatment. (Circ J 2014; 78: 1550–1558)
  • Satoshi Kurisu, Yasuki Kihara
    Type: Focus Issue on Takotsubo Cardiomyopathy
    2014 Volume 78 Issue 7 Pages 1559-1566
    Published: June 25, 2014
    Released: June 25, 2014
    [Advance publication] Released: June 12, 2014
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    Takotsubo cardiomyopathy was first reported by Sato et al at Hiroshima City Hospital in 1990 and has become increasingly recognized worldwide. In the clinical setting, takotsubo cardiomyopathy is an important disease that must be differentiated from AMI promptly for the appropriate management. Prognosis of takotsubo cardiomyopathy is generally favorable, but serious complications can occur, especially in the early stage. In this review, we summarize the current knowledge on the clinical management of takotsubo cardiomyopathy. (Circ J 2014; 78: 1559–1566)
Editorials
Original Articles
Arrhythmia/Electrophysiology
  • Seung-Jung Park, Young Keun On, June Soo Kim, Dong Seop Jeong, Wook Su ...
    2014 Volume 78 Issue 7 Pages 1584-1592
    Published: 2014
    Released: June 25, 2014
    [Advance publication] Released: April 30, 2014
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    Background: Although the maze procedure reduces the risk of adverse cardiac events, the clinical importance of post-maze left atrial (LA) activity on long-term surgical outcomes is not well defined. Methods and Results: Between January 2000 and December 2009, 416 consecutive patients with sinus conversion after a modified Cox III procedure with cryoablation were enrolled and subdivided into patients with restored LA activity (group ReA; n=231) and those without LA activity (group NoA; n=185) assessed using Doppler echocardiographic examination at 3–6 months after the maze procedure. During the long-term follow-up (4.6±2.6 years), the NoA group showed more frequent major adverse events (P=0.001) including cardiac death (P=0.145), heart failure events (P=0.032), and thromboembolic stroke (P=0.048) than the ReA group. In multivariate analysis, lack of LA activity was associated with a 2.2-fold increased risk for major adverse events (95% confidence interval [CI], 1.1–6.8; P=0.029) and with a 2.4-fold increased risk for late progression of tricuspid regurgitation (95% CI, 1.0–3.5; P=0.041). Conclusions: Absence of LA activity after the maze procedure was independently associated with a significantly increased risk of major adverse events and late progression of tricuspid regurgitation.  (Circ J 2014; 78: 1584–1592)
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  • Ken Okumura, Hiroshi Inoue, Hirotsugu Atarashi, Takeshi Yamashita, Hir ...
    2014 Volume 78 Issue 7 Pages 1593-1599
    Published: 2014
    Released: June 25, 2014
    [Advance publication] Released: April 22, 2014
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    Background: Recent European guidelines recommended the CHA2DS2-VASc score for thromboembolic and the HAS-BLED score for bleeding risk stratifications. We validated these scores in 7,384 Japanese patients with nonvalvular atrial fibrillation (NVAF) enrolled in the J-RHYTHM Registry. Methods and Results: Of the study cohort, 6,387 patients taking warfarin and the other 997 not taking warfarin were prospectively examined for 2 years. Thromboembolic and major bleeding risks were stratified by modified CHA2DS2-VASc (mCHA2DS2-VASc) and HAS-BLED (mHAS-BLED) scores, respectively. Of the patients with mCHA2DS2-VASc score 0, 1, and ≥2, thromboembolism occurred in 2/141 (0.7%/year), 4/233 (0.9%/year), and 24/623 (1.9%/year), respectively, in the non-warfarin group, and in 1/346 (0.1%/year, P=0.19 vs. non-warfarin), 4/912 (0.2%/year, P=0.05), and 92/5,129 (0.9%/year, P=0.0005), respectively, in the warfarin group. When female sex was excluded from the score, thromboembolism occurred in 2/180 patients (0.6%/year), 5/245 (1.0%/year), and 23/572 (1.6%/year), respectively, in the non-warfarin group, and in 1/422 (0.1%/year, P=0.20 vs. non-warfarin), 5/1,096 (0.2%/year, P=0.02), and 91/4,869 (0.9%/year, P=0.0005), respectively, in the warfarin group. Patients with mHAS-BLED scores ≥3 were at high risk for major bleeding irrespective of warfarin treatment (1.3 and 2.6%/year in the non-warfarin and warfarin groups, respectively). Conclusions: In Japanese NVAF patients, the mCHA2DS2-VASc score is useful for identifying patients at truly low risk of thromboembolism. Female sex may be excluded as a risk from the score. mHAS-BLED score ≥3 is useful for identifying patients at high risk of major bleeding.  (Circ J 2014; 78: 1593–1599)
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  • Satoshi Numa, Tadakazu Hirai, Keiko Nakagawa, Kazumasa Ohara, Nobuyuki ...
    2014 Volume 78 Issue 7 Pages 1600-1605
    Published: 2014
    Released: June 25, 2014
    [Advance publication] Released: May 08, 2014
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    Background: There is no clear consensus on thromboprophylaxis in patients with nonvalvular atrial fibrillation (AF) at low-intermediate thromboembolic risk. Although hyperuricemia is a risk factor for cardiovascular diseases, the relationship between serum uric acid (UA) levels and thromboembolic risk has not been fully elucidated in patients with AF. Methods and Results: Serum UA levels and the score for congestive heart failure, hypertension, age, diabetes mellitus, prior stroke/transient ischemic attack, vascular disease and sex (ie, CHA2DS2-VASc score) were determined in 470 patients with nonvalvular AF who underwent transesophageal echocardiography (TEE) to evaluate their risk of thromboembolism. Serum UA levels were similar between the low-intermediate risk (CHA2DS2-VASc score=0 or 1) and high-risk (≥2) groups, although serum D-dimer levels were lower in the low-intermediate risk than in the high-risk group. Among patients at low-intermediate risk, serum UA levels were higher in those with TEE thromboembolic risk (TEE risk: low left atrial appendage flow, spontaneous echo contrast, thrombi, or aortic atherosclerosis) than in those without TEE risk. On multivariate analysis, the serum UA level was an independent predictor of TEE risk in AF patients at low-intermediate risk (odds ratio, 1.45; 95% confidence interval 1.09–2.00; P=0.016). Conclusions: The serum UA level was associated with thromboembolic risk on TEE in patients with nonvalvular AF at low-intermediate risk stratified by clinical risk factors.  (Circ J 2014; 78: 1600–1605)
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  • Soichiro Yamashita, Akihiro Yoshida, Koji Fukuzawa, Ryudo Fujiwara, At ...
    2014 Volume 78 Issue 7 Pages 1606-1611
    Published: 2014
    Released: June 25, 2014
    [Advance publication] Released: May 09, 2014
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    Background: The utility of the upper limit of vulnerability (ULV) test in patients undergoing defibrillator implantation has been reported, so the purpose of this study was to evaluate the difference in the clinical outcomes between patients with ULV ≤15J or >15J. Methods and Results: A total of 165 patients receiving an implantable cardioverter-defibrillator underwent a vulnerability test. At the time of the implantation, we delivered a 15-J shock on the T-peak and ±20ms later to cover the most vulnerable part of the cardiac cycle. The clinical outcomes were prospectively analyzed. A 15-J shock induced ventricular fibrillation (VF) in 30 patients (ULV >15J) and did not in 135 (ULV ≤15J). The characteristics of the 2 groups were comparable. After a mean follow-up of 757 days, Kaplan-Meier curve analysis showed that the ULV ≤15J group experienced less VF than the ULV >15J group (log-rank P=0.003). The occurrence of ventricular tachycardia was similar between the 2 groups (P=0.140). Furthermore, the effectiveness of ATP was comparable. After adjusting for other known predictors of shock therapy, a ULV >15J was independently associated with the occurrence of VF (hazard ratio: 6.25; 95% confidence interval: 1.913–20.40; P<0.01). Conclusions: A high ULV value was associated with a high incidence of VF, which suggests that cardiac vulnerability to electrical shock may be linked to electrical instability.  (Circ J 2014; 78: 1606–1611)
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  • Maciej Wójcik, Alexander Berkowitsch, Harald Greis, Sergey Zaltsberg, ...
    Type: ORIGINAL ARTICLE
    Subject area: Arrhythmia/Electrophysiology
    2014 Volume 78 Issue 7 Pages 1612-1618
    Published: June 25, 2014
    Released: June 25, 2014
    [Advance publication] Released: May 19, 2014
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    Background:We analyzed the procedural experience cryoballoon ablation (CBA) of atrial fibrillation (AF) gained over 8 years in a high-volume centre to understand the influence of the learning curve on feasibility, safety and clinical outcome.Methods and Results:In 424 patients (62% male) with drug-refractory AF, CBA was performed between 2005 and 2012. The analyzed period was divided into 8 calendar years. The endpoint of the study was arrhythmia recurrence after the 3-month blanking period in the 1-year follow-up since the index procedure, in the absence of anti-arrhythmic drugs class I and III. A combined AF type, Left Atrium size, Renal insufficiency, MEtabolic syndrome, cardiomyopathy (ALARMEc) risk score was calculated for each patient. The overall 1-year success rate of a single CBA was 73%. Continuous increase in 1-year success rate was observed with successive years of the study. The gradual improvement in outcome was related to gradual fall in ALARMEc risk score in successive patients. A continuous decrease in fluoroscopy and procedure time was observed in each subsequent year.Conclusions:CBA, followed by the proper selection of patients, facilitates a satisfactory outcome, especially in patients at an early stage of PV-trigger-dependent AF. Still, as with each new technology, it requires completion of a learning curve. (Circ J 2014; 78: 1612–1618)
  • Kazumasa Sonoda, Yasuo Okumura, Ichiro Watanabe, Koichi Nagashima, Mas ...
    Type: ORIGINAL ARTICLE
    Subject area: Arrhythmia/Electrophysiology
    2014 Volume 78 Issue 7 Pages 1619-1627
    Published: June 25, 2014
    Released: June 25, 2014
    [Advance publication] Released: May 21, 2014
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    Background:Atrial fibrillation (AF) causes atrial electrical and structural remodeling, which are linked to recurrence of AF after ablation. Atrial fibrillatory cycle length (AFCL) and AF wall motion velocity (AFW-V) obtained by tissue velocity imaging (TVI) might characterize such atrial electrical and structural remodeling. The purpose of this study was to assess the clinical and electrophysiologic correlates of these parameters and their relation to ablation outcomes.Methods and Results:The study group comprised 80 patients who underwent transthoracic echocardiography followed by AF ablation. Atrial TVI traces were used to determine AFCL-tvi and AFW-V-tvi at the left atrial septal wall. AFCL that was measured from intracardiac electrograms correlated well with AFCL-tvi (R=0.6094; P=0.0002). AFW-V-tvi was significantly lower and AFCL-tvi was significantly shorter in patients with non-paroxysmal AF than in those with paroxysmal AF (1.63±0.76 cm/s vs. 2.85±1.00 cm/s, respectively, P<0.0001; and 118.2±23.0 ms vs. 145.0±35.0 ms, respectively, P=0.0001). These findings held true for patients with and without post-ablation recurrence. Upon multivariate analysis, a reduced AFW-V-tvi remained the strongest predictor of post-ablation recurrence (hazard ratio for +1-cm/s change, 0.573; 95% confidence interval, 0.337–0.930; P=0.0234).Conclusions:TVI of atrial fibrillatory wall motion might enhance the non-invasive characterization of atrial remodeling in patients with AF and thus be used for predicting AF recurrence after ablation. (Circ J 2014; 78: 1619–1627)
Cardiovascular Intervention
  • Tetsuma Kawaji, Hiroki Shiomi, Takeshi Morimoto, Toshihiro Tamura, Ryu ...
    Type: ORIGINAL ARTICLE
    Subject area: Cardiovascular Intervention
    2014 Volume 78 Issue 7 Pages 1628-1635
    Published: June 25, 2014
    Released: June 25, 2014
    [Advance publication] Released: May 14, 2014
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    Background: Recent randomized clinical trials have reported favorable clinical outcomes after the use of drug-eluting stents (DES) in patients with acute coronary syndrome (ACS). However, the long-term efficacy and safety outcomes, bleeding outcome in particular, after DES implantation in ACS patients have not been thoroughly evaluated in a real-world population. Methods and Results: We evaluated long-term clinical outcomes in 565 consecutive ACS patients who underwent DES implantation in an emergency setting between 2004 and 2011 (ST-segment elevation acute myocardial infarction [STEMI]: n=269, non-STEMI/unstable angina pectoris: n=296). Mean clinical follow-up period in this study was 4.6±2.0 years. The cumulative incidence of all-cause death, cardiac death, myocardial infarction, stent thrombosis and target-lesion revascularization was 6.9%, 4.0%, 2.2%, 1.3% and 8.4% at 1 year, and 19.6%, 6.7%, 5.6%, 3.0% and 13.9% at 5 years, respectively. The cumulative 5-year incidence of major bleeding events was 8.4% (n=42). Fatal bleeding events, however, occurred in only 4 patients, even including 2 patients who required resuscitation upon arrival at the hospital. Of the 42 patients with major bleeding events, 39 were taking dual antiplatelet therapy (DAPT) at the time of bleeding. Conclusions: DES implantation provided favorable long-term clinical outcomes with an acceptably low incidence of fatal bleeding in a real-world population of ACS patients. However, prolonged DAPT seems to be associated with major bleeding after DES implantation. (Circ J 2014; 78: 1628–1635)
Cardiac Rehabilitation
  • Zhe Hao, Shan-Shan Pan, Yu-Jun Shen, Jun Ge
    2014 Volume 78 Issue 7 Pages 1636-1645
    Published: 2014
    Released: June 25, 2014
    [Advance publication] Released: April 28, 2014
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    Background: Exercise preconditioning (EP) can provide powerful protection to the heart. Evidence supports the contention that EP directly enhances myocardial tolerance to ischaemia through a protein kinase C (PKC)-mediated mechanism. However, studies investigating the role of isoform-specific PKC after EP are lacking. Methods and Results: In this study, a male Sprague-Dawley rat model of EP was established (4 periods of 30m/min for 10min exercise then a 10min rest at 0% grade treadmill exercise). Rats were subjected to exhaustive exercise to induce myocardial injury. Chelerythrine (5mg/kg) was injected before EP to investigate the role of PKC in EP. EP was found to attenuate exhaustive exercise-induced myocardial injury in both of EP’s 2 protective phases, especially the latter phase. After EP, PKCε was markedly upregulated, and PKCε was translocated to myocardial intercalated disks, and p-PKCεSer729 was translocated to the myocardial cytomembrane. Even though PKCε was markedly upregulated and translocated to intercalated disks during exhaustive exercise, p-PKCεSer729 was mainly distributed in the cytoplasm. A chelerythrine injection before EP did not suppress the activation of PKC and the protection of EP. Conclusions: These results indicate that PKCε plays an important role in EP-mediated protection of the myocardium during exhaustive exercise-induced myocardial injury, and that a chelerythrine injection during exercise is not suitable for demonstrating the role of PKCε.  (Circ J 2014; 78: 1636–1645)
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  • Masahiko Saito, Kenji Ueshima, Muneyasu Saito, Toshiji Iwasaka, Hiroyu ...
    Type: ORIGINAL ARTICLE
    Subject area: Cardiac Rehabilitation
    2014 Volume 78 Issue 7 Pages 1646-1653
    Published: June 25, 2014
    Released: June 25, 2014
    [Advance publication] Released: May 19, 2014
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    Background:The safety of exercise-based cardiac rehabilitation (CR) has not been investigated in Japan, so a nationwide survey was conducted to investigate the incidence of adverse events (AEs) associated with CR and exercise testing.Methods and Results:In total, 136 hospitals reported operating recovery-phase CR programs, amounting to 383,096 patient-hours of exercise training. The incidence rates of all AEs and life-threatening AEs (LAE: death, cardiac arrest, acute myocardial infarction, cardiac rupture) during exercise sessions were 12 and 1 event/383,096 patient-hours (3.13 and 0.26 events/100,000patient-hours), respectively. When CR programs were categorized as “Formal” in which an exercise prescription based on exercise testing was issued to individual patients or “Non-formal” without exercise prescription, the incidence of AEs during and within the 24 h after an exercise session was significantly lower in the Formal than the Non-formal CR programs (P<0.001), despite similar hospital size and coronary intervention volumes between the 2 category hospitals. Moreover, LAEs did not occur in 277,721 patient-hours in Formal CR, whereas 2 LAEs occurred in 105,375 patient-hours in Non-formal CR (P<0.05). During 469,215 exercise testing sessions, 3 LAEs (0.64 event/100,000tests) and 31 non-LAEs (6.61 events/100,000tests) occurred.Conclusions:This first nationwide survey in Japan revealed that both exercise-based CR and exercise testing are generally safe, and that Formal CR, in which an individual exercise prescription is determined by exercise testing, is particularly safe. (Circ J 2014; 78: 1646–1653)
Cardiovascular Surgery
  • Gwan Sic Kim, Jae-Joong Kim, Joon Bum Kim, Dae-Hee Kim, Jong-Min Song, ...
    2014 Volume 78 Issue 7 Pages 1654-1660
    Published: 2014
    Released: June 25, 2014
    [Advance publication] Released: April 25, 2014
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    Background: Long-term echocardiographic data on quantitative assessment of tricuspid and mitral regurgitation after heart transplantation are scarce. Methods and Results: From November 1992 to December 2008, the medical records for 201 patients (mean age, 42.8±12.4 years, 47 females) who underwent heart transplantation were reviewed. Quantitative assessment of mitral and tricuspid valve function was performed using transthoracic echocardiography through long-term follow-up. A total of 196 (97.5%) patients were evaluated with echocardiography for more than 6 months postoperatively. During a mean echocardiography follow-up duration of 89.9±54.3 months, 23 (11.4%) patients showed either tricuspid regurgitation (TR >mild; n=21, 10.4%) or mitral regurgitation (MR >mild; n=6, 3.0%); 4 (2.0%) patients experienced both significant TR and MR. Freedom from moderate-to-severe TR at 10 years was 85.5±5.1% and 93.4±2.2% for the standard and bicaval techniques, respectively (P=0.531). Freedom from moderate-to-severe MR at 10 years was 96.0±2.7% and 98.6±1.0%, respectively, for the 2 techniques (P=0.252). In multivariate analysis, older-age donor emerged as the only independent predictor of significant TR (hazard ratio 1.06, 95% confidence interval 1.01–1.12, P=0.012). Conclusions: The long-term results of atrioventricular function after heart transplantation in adults were excellent regardless of anastomotic technique. Older-age donor was significantly associated with the development of postoperative TR.  (Circ J 2014; 78: 1654–1660)
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  • Na Young Kim, Jae-Kwang Shim, Jong Wook Song, Eui-Kyung Kim, Young-Lan ...
    2014 Volume 78 Issue 7 Pages 1661-1666
    Published: 2014
    Released: June 25, 2014
    [Advance publication] Released: April 16, 2014
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    Background: Preoperative fibrinogen concentration is associated with increased blood loss at the lower end, and with hypercoagulability-related ischemic event at the higher end in cardiac patients. We evaluated the influence of preoperative fibrinogen concentration on blood loss and outcome in patients who received clopidogrel in proximity to off-pump coronary artery bypass surgery (OPCAB). Methods and Results: Medical records of 538 patients who received clopidogrel within 5 days of OPCAB (April 2007 to March 2012) were retrospectively reviewed. Perioperative bleeding and composite of morbidity endpoints including myocardial infarction were compared in relation to the tertile distribution of the fibrinogen concentration. The amount of blood loss was significantly larger in the first tertile, whereas the incidence of composite of morbidity endpoints was significantly higher in the third tertile. In multivariate analysis for risk factors of perioperative blood loss, body mass index and duration of surgery were identified as independent risk factors but not the fibrinogen level. And hypertension and preoperative fibrinogen level were identified as independent risk factors about composite of morbidity. The third tertile was associated with a 2-fold increased risk of developing composite of morbidity endpoints. Conclusions: In patients who received dual antiplatelet therapy in proximity to OPCAB, increased preoperative fibrinogen concentration could serve as a valuable predictor for composite of morbidity endpoints, whereas low fibrinogen concentration was not found to be a risk factor of bleeding.  (Circ J 2014; 78: 1661–1666)
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Imaging
  • Yasuto Uchida, Nobuyuki Hiruta, Daisuke Yamanoi, Ei Shimoyama, Yuko Ma ...
    2014 Volume 78 Issue 7 Pages 1667-1675
    Published: 2014
    Released: June 25, 2014
    [Advance publication] Released: April 25, 2014
    JOURNALS FREE ACCESS
    Background: High-density lipoprotein (HDL) plays a key role in reverse cholesterol transport, and halts the progression of atherosclerosis. The aim of the present study was to visualize native HDL in the human coronary arterial wall. Methods and Results: The fluorescence characteristics of HDL were investigated by color fluorescent microscopy (CFM) using excitation at 470nm and emission at 515nm with Fast green dye (FG) as the biomarker. HDL in 30 normal coronary segments, and in 25 white and 25 yellow plaques in excised human coronary arteries, was visualized by color fluorescent angioscopy (CFA) and CFM. Localization of HDL visualized by CFM was compared with that stained by immunostaining using an anti-HDL antibody. FG elicited a characteristic brown fluorescence of HDL. By CFA, the percent incidence of HDL in normal segments, white (early stage of plaque growth) and yellow (advanced stage of plaque growth) plaques was, respectively, 33%, 76% (P<0.05 vs. normal segments and yellow plaques) and 21%. Localization of HDL visualized by CFM did not differ from that stained by immunostaining. Conclusions: In the human coronary arterial wall, HDL deposits infrequently in normal segments, but increasingly deposits with plaque formation, and decreases in the advanced stage of plaque growth.  (Circ J 2014; 78: 1667–1675)
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  • Tatsuhiko Furuhashi, Masao Moroi, Toru Awaya, Megumi Minakawa, Hirofum ...
    Type: ORIGINAL ARTICLE
    Subject area: Imaging
    2014 Volume 78 Issue 7 Pages 1676-1683
    Published: June 25, 2014
    Released: June 25, 2014
    [Advance publication] Released: May 21, 2014
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    Background:Stress myocardial perfusion imaging (MPI) is a well-established diagnostic and prognostic tool for coronary artery disease (CAD). However, fixed and/or reversible stress MPI defects vary considerably among patients with CAD. The usefulness of stress MPI and baseline clinical factors as independent predictors of cardiovascular events in patients with prior CAD were assessed.Methods and Results:Stress MPI was performed in 354 patients with prior CAD. Their mean age was 71 years; the mean duration from first revascularization and/or myocardial infarction (MI) onset until stress MPI was 7.1 years; and the mean follow-up period was 34 months. Cardiovascular events were observed in 100 patients (28%), and were categorized as cardiac-related death, non-fatal MI, unstable angina, heart failure and late (>2 months from stress MPI) coronary revascularization. Multivariate Cox regression analysis revealed that peripheral arterial disease (hazard ratio [HR]=2.95; P<0.001), current smoking (HR=2.36; P=0.006), chronic kidney disease (HR=2.15; P<0.001), left ventricular ejection fraction (HR=0.98; P=0.017), and grade of myocardial ischemia assessed by stress MPI (HR=1.14; P=0.007) were independent and significant predictors of cardiovascular events.Conclusions:In patients with prior CAD, baseline clinical factors and grade of myocardial ischemia assessed by stress MPI results are significant predictors of cardiovascular events. (Circ J 2014; 78: 1676–1683)
Ischemic Heart Disease
  • Shigeru Saito, Takaaki Isshiki, Takeshi Kimura, Hisao Ogawa, Hiroyoshi ...
    2014 Volume 78 Issue 7 Pages 1684-1692
    Published: 2014
    Released: June 25, 2014
    [Advance publication] Released: April 22, 2014
    JOURNALS FREE ACCESS
    Background: Prasugrel is an antiplatelet agent that shows more prompt, potent, and consistent platelet inhibition than clopidogrel. The objective of this study was to confirm the efficacy and safety of prasugrel at loading/maintenance doses of 20/3.75mg. Methods and Results: Japanese patients (n=1,363) with acute coronary syndrome undergoing percutaneous coronary intervention were randomized to either prasugrel (20/3.75mg) or clopidogrel (300/75mg), both in combination with aspirin (81–330mg for the first dose and 81–100mg/day thereafter), for 24–48 weeks. The primary efficacy endpoint was the incidence of major adverse cardiovascular events (MACE) at 24 weeks, defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal ischemic stroke. We compared the incidence of MACE between the 2 groups using point estimates. Safety outcomes included the incidence of bleeding events until 2 weeks after the last dose. The incidence of MACE at 24 weeks was 9.4% in the prasugrel group and 11.8% in the clopidogrel group (risk reduction 23%, hazard ratio 0.77, 95% confidence interval 0.56–1.07). The incidence of non-coronary artery bypass graft-related major bleeding was similar in both groups (1.9% vs. 2.2%). Conclusions: Prasugrel 20/3.75mg was associated with a low incidence of ischemic events, similar to the results of TRITON-TIMI 38, and with a low risk of clinically serious bleeding in Japanese ACS patients.  (Circ J 2014; 78: 1684–1692)
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Myocardial Disease
  • Michael Glaubitz, Stephan Block, Jeannine Witte, Klaus Empen, Stefan G ...
    Type: ORIGINAL ARTICLE
    Subject area: Myocardial Disease
    2014 Volume 78 Issue 7 Pages 1693-1700
    Published: June 25, 2014
    Released: June 25, 2014
    [Advance publication] Released: June 03, 2014
    JOURNALS FREE ACCESS FULL-TEXT HTML
    Background:Ventricular dilation is known as a pivotal predictor in recent-onset cardiomyopathy (ROCM), but its pathophysiology is not fully understood. In the present study we investigated whether single-cell stiffness of right and left ventricular-derived fibroblasts has an effect on cardiac phenotype in patients with ROCM.Methods and Results:Patients with endomyocardial biopsy-proven ROCM were included (n=10). Primary cardiac fibroblasts (CFBs) were cultured from left and right ventricular endomyocardial biopsies and their single-cell stiffness was analyzed by quantification of Young’s modulus using colloidal probe atomic force microscopy. Cardiac fibrosis was analyzed by Masson’s trichrome staining. CFBs from the left ventricle showed significantly decreased stiffness when compared with CFBs from the right ventricle, indexed by decreased stiffness (Young’s modulus 3,374±389 vs. 4,837±690 Pa; P<0.05). Young’s modulus of CFBs derived from the left ventricle correlated negatively with the left ventricular end-diastolic dimension derived from 2-dimensional echocardiography (R2=0.77; P<0.01). Neither left nor right ventricular fibrosis correlated with the respective ventricular dimensions.Conclusions:Our data suggest that a decrease in single-cell stiffness of left ventricular fibroblasts could trigger left ventricular dilation in patients with ROCM. This implies a new potential mechanism for the ventricular dilation with this disease. (Circ J 2014; 78: 1693–1700)
Pediatric Cardiology and Adult Congenital Heart Disease
  • Katsuaki Toyoshima, Satoshi Masutani, Hideaki Senzaki, Motoyoshi Kawat ...
    2014 Volume 78 Issue 7 Pages 1701-1709
    Published: 2014
    Released: June 25, 2014
    [Advance publication] Released: May 09, 2014
    JOURNALS FREE ACCESS
    Background: This study was undertaken to establish the appropriate correction of left atrial volume (LAV) to body surface area (BSA) to provide reference values and to assess the hypotheses that LAV is useful for assessing patent ductus arteriosus (PDA) severity in extremely low birth weight infants (ELBWI) and could overcome the limitations of the LA-to-aortic dimension ratio (LA/Ao). Methods and Results: Echocardiograms with 318 data points from 53 consecutive ELBWIs were assessed. PDA surgery was performed within the first 2 weeks in 6 patients. LAV was measured using the biplane (LAV) and single-plane (LAV4CV) area-length methods. The allometric model was used to correlate LAV to BSA. LAV4CV had a good correlation with LAV (R=0.93). Although LAV/BSA1 had a residual relationship with BSA, LAV/BSA1.54 (23.5±9.3ml/m3.08) and LAV4CV/BSA1.52 (21.4±9.4ml/m3.04) did not. Receiver-operating characteristic analysis to detect hemodynamic status just before PDA surgery showed the superiority of LAV/BSA1.54 (area under the curve (AUC) 0.97) and LAV4CV/BSA1.52 (AUC 0.98) over LA/Ao (AUC 0.92). Moreover, LAV/BSA1.54 and LAV4CV/BSA1.52 were better correlated with left pulmonary arterial end-diastolic velocity than was LA/Ao. Conclusions: This study provided appropriate BSA correction of LAV and its reference values in ELBWIs. LAV indices may be superior to LA/Ao for PDA severity assessment. Measurement of single-plane LAV is easy, with similar usefulness to biplane LAV.  (Circ J 2014; 78: 1701–1709)
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  • Tsugutoshi Suzuki, Naokata Sumitomo, Jun Yoshimoto, Aya Miyazaki, Kazu ...
    2014 Volume 78 Issue 7 Pages 1710-1716
    Published: 2014
    Released: June 25, 2014
    [Advance publication] Released: April 24, 2014
    JOURNALS FREE ACCESS
    Background: In Japan, the use of implantable cardioverter defibrillators (ICDs), cardiac resynchronization therapy with a biventricular pacemaker (CRTP) and CRT with a defibrillator (CRTD) in children has not been studied statistically, and dual-chamber (DDD) pacemakers are still used for pediatric CRT because of current government regulations. Methods and Results: Data were obtained from 15 children’s and 74 general hospitals through a questionnaire survey regarding the aforementioned therapies performed before 2012 in Japanese children (<16 years old). ICD, CRT with DDD, CRTP and CRTD were used in 64 (42%), 47 (31%), 34 (22%) and 7 (5%), respectively, of all cases reported (n=152). Among all CRTP and CRT-DDD cases (n=81), the use of DDD accounted for 41% in general hospitals vs. 89% in children’s hospitals, and CRT-DDD and CRTP were effective in 67 cases (83%). Of 64 ICD cases, appropriate shocks were experienced in 28 cases (44%), and inappropriate shocks in 19 cases (29%). Additionally, data from the Japan Arrhythmia Device Industry Association obtained for overall device usage analysis revealed that CRTP was more commonly used in children than in adults. Conclusions: There is an increasing need for pediatric device therapy, especially CRTP. However, many children’s hospitals were still using DDD pacemakers in 2012. Although the demand for device therapy in children may be small, it is indispensable in pediatric cardiology.  (Circ J 2014; 78: 1710–1716)
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  • Andreas Kuehn, Manfred Vogt, Markus Schwaiger, Peter Ewert, Michael Ha ...
    Type: ORIGINAL ARTICLE
    Subject area: Pediatric Cardiology and Adult Congenital Heart Disease
    2014 Volume 78 Issue 7 Pages 1717-1722
    Published: June 25, 2014
    Released: June 25, 2014
    [Advance publication] Released: May 30, 2014
    JOURNALS FREE ACCESS FULL-TEXT HTML
    Background:Coronary flow reserve (CFR) is reduced in patients with transposition of the great arteries (TGA) after the arterial switch operation (ASO). Dissection of the great arteries and coronary reimplantation may result in sympathetic denervation, with a negative effect on myocardial perfusion.Methods and Results:18 patients with TGA participated in the study; 9 had ASO (20.8±5.8 years). Controls were 9 patients after Rastelli procedure (22.1±6.8 years). Sympathetic innervation was measured by positron emission tomography using11C epinephrine (EPI). Left ventricular EPI-retention ranged from 6.1% to 15.9%/min. Patients undergoing more than 1 operation had significantly reduced EPI-retention (P<0.001). EPI-retention and time interval after surgery correlated significantly (r=0.81, P<0.001) and was higher in patients undergoing surgery at an earlier age (P<0.001). No significant difference could be found between patients after ASO or Rastelli repair. Aortic cross-clamp time inversely correlated with EPI-retention (r=−0.72; P<0.001).Conclusions:The ASO procedure had a negative effect on sympathetic innervation of the myocardium, but because of reinnervation myocardial perfusion is not essentially altered by this mechanism. Heart surgery and prolonged aortic cross-clamp time have a negative effect on the norepinephrine content of cardiac sympathetic nerve terminals. Parameters such as ventricular performance and cardiopulmonary exercise capacity were unaffected by the degree of EPI-retention. (Circ J 2014; 78: 1717–1722)
Peripheral Vascular Disease
  • Hiroyuki Suzuki, Yasushi Matsuzawa, Masaaki Konishi, Eiichi Akiyama, K ...
    2014 Volume 78 Issue 7 Pages 1723-1732
    Published: 2014
    Released: June 25, 2014
    [Advance publication] Released: April 28, 2014
    JOURNALS FREE ACCESS
    Background: Venous thromboembolism (VTE) is a common and sometimes lethal postoperative complication of arthroplasty. Endothelial dysfunction is important in the pathogenesis of thrombus formation. Reactive hyperemia-peripheral arterial tonometry (RH-PAT) can noninvasively evaluate endothelial function. This study investigated the predictive value of RH-PAT for deep vein thrombosis (DVT) after lower limb arthroplasty. Methods and Results: A prospective observational study of 126 osteoarthritic patients who underwent total knee arthroplasty (TKA) or hip arthroplasty (THA) was conducted. The RH-PAT index (RHI) was measured on the day before surgery, and presence of DVT was checked by ultrasonography or phlebography before and after surgery. Following arthroplasty, DVT was diagnosed in 51 patients (40.5%). RHI in the DVT group (0.58±0.25) was significantly lower than in the non-DVT group (0.71±0.25, P=0.004). RHI was a significant and independent predictor of postoperative DVT in multivariate logistic regression analyses and improved a net reclassification index (23.8%, P=0.022). Subgroup analyses according to operation site with adjustment for Qthrombosis score demonstrated that RHI significantly predicted postoperative DVT in the THA group (odds ratio per 0.1, 0.77; 95% confidence interval 0.60–0.98; P=0.03), but did not reach statistical significance in the TKA group. Conclusions: Low RHI was significantly associated with DVT after lower limb arthroplasty. Endothelial dysfunction, as assessed by RH-PAT, is potentially useful for identifying patients at high risk for VTE especially after THA.  (Circ J 2014; 78: 1723–1732)
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  • Kotaro Suehiro, Noriyasu Morikage, Masanori Murakami, Osamu Yamashita, ...
    2014 Volume 78 Issue 7 Pages 1733-1739
    Published: 2014
    Released: June 25, 2014
    [Advance publication] Released: April 30, 2014
    JOURNALS FREE ACCESS
    Background: Our objectives were to elucidate the pathophysiology of leg edema in immobile patients and to discuss reasonable management of this condition. Methods and Results: The 30 patients with leg edema had visited our clinic between April 2009 and March 2013; they suffered from severe gait disturbance, had no significant venous abnormalities detected using duplex ultrasound, and did not have any systemic diseases that could cause leg edema. Here, we review their symptoms, examinations, and treatments. Among 59 edematous legs of the 30 patients, 30 legs (51%) had symptoms that indicated advanced chronic venous insufficiency. The ankle range of motion and calf : ankle circumference ratio were abnormal in only 3 (5%) and 10 (17%) of the legs, respectively. The severity of edema and subcutaneous inflammation, which was confirmed using ultrasonography, was significantly influenced by gravity. Air plethysmography and lymphangioscintigraphy were completed in 15 and 10 patients, respectively, neither of which revealed any significant abnormalities. Reasonable success for all patients was achieved by compression therapy and physical therapy without medications. Conclusions: It was assumed that leg edema in these immobile patients was mainly caused by venous stasis because of the immobility itself, not because of anatomical problems. The patients were successfully managed by compression and physical therapy alone.  (Circ J 2014; 78: 1733–1739)
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  • Masato Kajikawa, Tatsuya Maruhashi, Yumiko Iwamoto, Akimichi Iwamoto, ...
    2014 Volume 78 Issue 7 Pages 1740-1745
    Published: 2014
    Released: June 25, 2014
    [Advance publication] Released: May 10, 2014
    JOURNALS FREE ACCESS
    Background: An ankle-brachial index (ABI) value of 0.91–0.99 is considered borderline and associated with an increased risk of cardiovascular events. However, there is no information on the relationship between borderline ABI and endothelial function. Methods and Results: We measured ABI and assessed vascular function by flow-mediated vasodilation (FMD) and nitroglycerin-induced vasodilation in 389 subjects who underwent health examinations. Subjects were divided into 3 groups according to ABI (normal group: 1.00–1.40, borderline group: 0.91–0.99, abnormal group: ≤0.90 or >1.40). FMD was significantly smaller in both the borderline and the abnormal group than in the normal group. There was no significant difference in the vascular responses to nitroglycerin between the normal and borderline groups. Vascular response to nitroglycerin was significantly higher in the normal group than in the abnormal group. Borderline and abnormal ABI values were significantly associated with an increased odds ratio of low tertile of FMD levels, using the normal ABI group as the reference. Multiple logistic regression analysis for FMD revealed that age, sex, hypertension, diabetes mellitus, and borderline ABI independently remained associated with FMD. Conclusions: ABI of 0.91–0.99 is associated with endothelial dysfunction. ABI examination is a simple and cost-effective method for obtaining the additional information on the initial step of atherosclerosis beyond the assessment of peripheral artery disease.  (Circ J 2014; 78: 1740–1745)
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  • Norihiro Kobayashi, Keisuke Hirano, Masatsugu Nakano, Toshiya Muramats ...
    2014 Volume 78 Issue 7 Pages 1746-1753
    Published: 2014
    Released: June 25, 2014
    [Advance publication] Released: May 08, 2014
    JOURNALS FREE ACCESS
    Background: The differences in wound healing according to wound location remain unclear. Methods and Results: Between April 2007 and October 2011, 138 patients (166 limbs) with critical limb ischemia with tissue loss were treated with endovascular treatment. On these limbs, 177 individual wounds were identified on the foot and were evaluated for wound healing rates and time to healing according to their locations. Wound locations were divided into 3 groups: group T (Toe wounds, n=112), group H (Heel wounds, n=25), and group E (Extensive wounds extending onto the fore- or mid-foot along with dorsum or plantar surfaces, n=40). The mean follow-up period was 23±19 months. At 3, 6, 9, and 12 months, wound healing rates were 51%, 64%, 75%, and 75%, respectively, in group T; 12%, 36%, 36%, and 52%, respectively, in group H; and 0%, 5%, 8%, and 13%, respectively, in group E. The median time to healing was 64 days (interquartile range 25–156 days) in group T, 168 days (interquartile range 123–316 days) in group H, and 267 days (interquartile range 177–316 days) in group E (P=0.038). Conclusions: Extensive wounds extending onto the fore- or mid-foot along with dorsum or plantar surfaces were the most difficult type of wound to heal.  (Circ J 2014; 78: 1746–1753)
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Pulmonary Circulation
  • Fumiaki Kato, Nobuhiro Tanabe, Takashi Urushibara, Hajime Kasai, Takao ...
    Type: ORIGINAL ARTICLE
    Subject area: Pulmonary Circulation
    2014 Volume 78 Issue 7 Pages 1754-1761
    Published: June 25, 2014
    Released: June 25, 2014
    [Advance publication] Released: June 06, 2014
    JOURNALS FREE ACCESS FULL-TEXT HTML
    Background:It is unclear whether abnormalities of coagulation or fibrinolysis are associated with disease progression of chronic thromboembolic pulmonary hypertension (CTEPH). The aim of this study was to investigate the association of these factors with the severity and prognosis of CTEPH.Methods and Results:Between 1986 and 2011, plasma fibrinogen and plasminogen were measured in 89 of 106 consecutive patients with inoperable CTEPH (17 men; mean age, 55.9±14.1 years old; mean pulmonary arterial pressure, 44.0±12.4 mmHg) and the association of level with severity and prognosis were also examined. Seventeen patients had high fibrinogen and low plasminogen (medians, ≥291 mg/dl and <101%, respectively). These patients had significantly lower cardiac index (2.26±0.68 vs. 2.70±0.57 L·min–1·m–2, P=0.007), higher pulmonary vascular resistance (PVR; 13.29±7.54 vs. 9.15±4.14 Wood units, P=0.003), and poor survival (5-year survival, 35.3% vs. 88.0%, P<0.001) compared to the other 72 patients. Additional analysis showed significantly poor survival in these patients compared with the other patients who did not have modern therapy. On multivariate analysis plasma fibrinogen, plasminogen and PVR were independent predictors of survival in medically treated patients.Conclusions:High plasma fibrinogen and low plasminogen are associated with poor survival in CTEPH patients without modern therapy. (Circ J 2014; 78: 1754–1761)
Regenerative Medicine
  • Tomohiko Sato, Masao Takahashi, Daishi Fujita, Shigeyoshi Oba, Hiroaki ...
    2014 Volume 78 Issue 7 Pages 1762-1769
    Published: 2014
    Released: June 25, 2014
    [Advance publication] Released: April 24, 2014
    JOURNALS FREE ACCESS
    Background: Although drug-eluting stents (DES) have been widely used for the treatment of coronary artery disease, they potentially increase the risk of late thrombosis. It is, therefore, desirable to establish a strategy to stimulate reendothelialization. Endothelial injury models have been widely used to analyze the mechanisms of coronary restenosis. However, animal models deployed with coronary stents in the blood vessels are necessary to accurately analyze the mechanisms of coronary restenosis and late thrombosis because persistent inflammation occurs around the coronary stents. Methods and Results: Coronary stents were implanted into rat abdominal aorta and adipose tissue-derived stem cells (ASC) were administered from the adventitial side. Reendothelialization was then visualized by Evans blue staining, and neointimal formation was analyzed histologically. ASC significantly stimulated reendothelialization and inhibited neointimal formation in bare metal stents (BMS)-implanted aorta. In addition, ASC promoted reendothelialization in DES-implanted aorta; however, the effects were weaker than in BMS-implanted aorta. Among the cytokines that ASC produce, adrenomedullin (AM) significantly stimulated reendothelialization and inhibited neointimal formation in BMS-implanted aorta, when an adenovirus expressing AM was administered from the adventitial side. Conclusions: These results suggest that ASC produce several cytokines that stimulate reendothelialization and inhibit neointimal formation in stent-deployed vessels, and that AM could mediate these effects.  (Circ J 2014; 78: 1762–1769)
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