Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Volume 78 , Issue 8
Showing 1-44 articles out of 44 articles from the selected issue
Reviews
  • Federica De Paoli, Bart Staels, Giulia Chinetti-Gbaguidi
    Type: REVIEW
    2014 Volume 78 Issue 8 Pages 1775-1781
    Published: July 25, 2014
    Released: July 25, 2014
    [Advance publication] Released: July 07, 2014
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    Atherosclerosis is the result of a chronic inflammatory response in the arterial wall related to uptake of low-density lipoprotein by macrophages and their subsequent transformation in foam cells. Monocyte-derived macrophages are the principal mediators of tissue homeostasis and repair, response to pathogens and inflammation. However, macrophages are a homogeneous cell population presenting a continuum phenotypic spectrum with, at the extremes, the classically Th-1 polarized M1 and alternatively Th-2 polarized M2 macrophage phenotypes, which have been well described. Moreover, M2 macrophages also present several subtypes often termed M2a, b, c and d, each of them expressing specific markers and exhibiting specialized properties. Macrophage plasticity is mirrored also in the atherosclerotic lesions, where different stimuli can influence the phenotype giving rise to a complex system of subpopulations, such as Mox, Mhem, M(Hb) and M4 macrophages. An abundant literature has described the potential modulators of the reciprocal skewing between pro-inflammatory M1 and anti-inflammatory M2 macrophages including lesion stage and localization, miRNA, transcription factors such as PPARγ, KLF4 and NR4A family members, high-density lipoproteins and plaque lipid content, pathways such as the rapamycin-mTOR1 pathway, molecules such as thioredoxin-1, infection by helminths and irradiation. We hope to provide an overview of the macrophage phenotype complexity in cardiovascular diseases, particularly atherosclerosis. (Circ J 2014; 78: 1775–1781)
  • Takashi Matsumoto, Saibal Kar
    Type: REVIEW
    2014 Volume 78 Issue 8 Pages 1782-1790
    Published: July 25, 2014
    Released: July 25, 2014
    [Advance publication] Released: July 14, 2014
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    Recent advances in structural heart intervention have produced increasing demand for transseptal access, which was first introduced as a diagnostic tool to directly measure left atrial pressure. Transseptal access allows safe and adequate approach to the left atrium and surrounding structures. Percutaneous transcatheter mitral valve repair using the MitraClip device is a safe and less invasive treatment for selected patients with significant mitral regurgitation, who are at high risk for surgery. This is an echocardiographic- and fluoroscopic-guided procedure requiring accurate transseptal access of the left atrium and clipping of the mitral leaflets at the precise location of their malcoaptation. Percutaneous transcatheter closure of the left atrial appendage is another novel procedure that requires transseptal access of the left atrium, followed by closure or ligation of the left atrial appendage. This catheter-based therapy has been shown to be a safe and effective alternative to long-term anticoagulant therapy for the prevention of stroke in patients with atrial fibrillation. In this article, we systematically review these novel structural heart interventions. (Circ J 2014; 78: 1782–1790)
  • Nobuyoshi Azuma, Atsuhiro Koya, Daiki Uchida, Yukihiro Saito, Hisashi ...
    Type: REVIEW
    2014 Volume 78 Issue 8 Pages 1791-1800
    Published: July 25, 2014
    Released: July 25, 2014
    [Advance publication] Released: July 04, 2014
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    Complete ulcer healing is one of the most important goals of treatment for critical limb ischemia; however, it is still difficult to inform patients of the time to ulcer healing before performing revascularization. The time to ulcer healing has a great impact on the cost of treatment and patient’s quality of life. To predict it, the factors that influence delayed ulcer healing should be explored. According to a review of the literature investigating ulcer healing after revascularization, the influential factors can be classified into 5 categories: (1) systemic factors; (2) clinical state of tissue defect; (3) infection; (4) wound management strategy; and (5) revascularization strategy (endovascular or open repair, the angiosome concept). It is also important to ensure sufficient blood supply to predict ulcer healing probability in the individual patient. Several new methodologies, such as measuring tissue circulation around the tissue defect and intraoperative imaging techniques, have been reported. Because the status of ischemic tissue loss and wound healing ability can affect the decision-making process in selecting the revascularization strategy, understanding the many factors that influence ulcer healing after revascularization is indispensable for physicians performing revascularization. Accumulating ulcer healing data via well-designed clinical research can help to establish a new paradigm for the revascularization strategy from the viewpoint of ulcer healing. (Circ J 2014; 78: 1791–1800)
  • Joy Lincoln, Vidu Garg
    Type: REVIEW
    2014 Volume 78 Issue 8 Pages 1801-1807
    Published: July 25, 2014
    Released: July 25, 2014
    [Advance publication] Released: July 07, 2014
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    Valvular heart disease occurs as either a congenital or acquired condition and advances in medical care have resulted in valve disease becoming increasingly prevalent. Unfortunately, treatments remain inadequate because of our limited understanding of the genetic and molecular etiology of diseases affecting the heart valves. Therefore, surgical repair or replacement remains the most effective option, which comes with additional complications and no guarantee of life-long success. Over the past decade, there have been significant advances in our understanding of cardiac valve development and, not surprisingly, mutations in these developmental genes have been identified in humans with congenital valve malformations. Concurrently, there has been a greater realization that acquired valve disease is not simply a degenerative process. Molecular investigation of acquired valve disease has identified that numerous signaling pathways critical for normal valve development are re-expressed in diseased valves. This review will discuss recent advances in our understanding of the development of the heart valves, as well as the implications of these findings on the genetics of congenital and acquired valvular heart disease. (Circ J 2014; 78: 1801–1807)
  • Jae-Kwan Song
    Type: REVIEW
    2014 Volume 78 Issue 8 Pages 1808-1815
    Published: July 25, 2014
    Released: July 25, 2014
    [Advance publication] Released: July 08, 2014
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    Left ventricular outflow tract obstruction (LVOTO) has important prognostic implications in patients with hypertrophic cardiomyopathy (HCM). Echocardiography provides critical information to establish LVOTO as a unique feature of HCM by demonstrating heterogeneity of hypertrophy patterns and the systolic anterior motion of mitral leaflets, resulting in mitral-septal contact. Currently, 2 treatment strategies are available for reduction of muscle mass to relieve LVOTO: surgical myectomy and percutaneous alcohol septal ablation. Both focus on mechanical removal of the hypertrophied septum. However, this alone is not the best approach to abolishing LVOTO, because recurrence is common and requires additional septal reduction. Recent 3-dimensional in vivo measurements and other noninvasive cardiac imaging modalities have confirmed primary alterations of the mitral valvular apparatus, including leaflet elongation with increased surface area and abnormal displacement of papillary muscles. More importantly, these extra-myocardial changes appear to be independent factors associated with the development of LVOTO. Other important anatomical changes include anomalous papillary muscle insertion into the anterior mitral leaflet and midventricular obstruction because of apposition of the hypertrophied mid-septum and the papillary muscle. Thus, the myocardium is not the only tissue affected in patients with HCM. A tailored approach to correcting primary changes of the mitral valvular apparatus and hypertrophy pattern based on a comprehensive evaluation using noninvasive imaging modalities is necessary to improve long-term outcomes. (Circ J 2014; 78: 1808–1815)
  • Kaoru Dohi, Masaaki Ito
    Type: REVIEW
    2014 Volume 78 Issue 8 Pages 1816-1823
    Published: July 25, 2014
    Released: July 25, 2014
    [Advance publication] Released: July 09, 2014
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    Fluid management is of paramount importance in the treatment strategy of heart failure (HF), but the therapeutic efficacy of loop diuretic-based treatment for HF patients is limited by insufficient response and adverse effects. Clinical data establishing the efficacy and safety of tolvaptan, a selective oral vasopressin V2 receptor antagonist that induces aquaresis, have recently been accumulated over 3 years of daily clinical experience in Japan. Intravenous infusion of carperitide, a synthetic α-human atrial natriuretic peptide, has also been widely used as acute-phase therapy for acute decompensated HF in Japan. Combination therapy using loop diuretics, tolvaptan, and carperitide with differing and complementary mechanisms of action may maximize therapeutic activity, to minimize the dosage of loop diuretics and thereby reduce the adverse effects not only for volume removal but also for the stability of cardiorenal hemodynamics. (Circ J 2014; 78: 1816–1823)
Editorials
Original Articles
Arrhythmia/Electrophysiology
  • Junya Hosoda, Toshiyuki Ishikawa, Kohei Matsushita, Katsumi Matsumoto, ...
    Type: ORIGINAL ARTICLE
    Subject area: Arrhythmia/Electrophysiology
    2014 Volume 78 Issue 8 Pages 1846-1850
    Published: July 25, 2014
    Released: July 25, 2014
    [Advance publication] Released: May 22, 2014
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    Background:Obstruction of the access vein is a well-known complication after cardiovascular implantable electronic device (CIED) implantation. In that case, well-developed collateral superficial veins are frequently observed on the skin surface around the CIED. The aim of this study was to clarify the relationship between venous obstruction and development of a superficial vein across the clavicle.Methods and Results:A total of 107 patients scheduled for generator replacement, device upgrade, or lead extraction were enrolled. The skin surface around the device was photographed. A 20-ml bolus of contrast medium was injected into a peripheral arm vein on the side of CIED implantation, and contrast venography was performed. Venous obstruction was defined as luminal diameter narrowing >75%. Venography showed venous obstruction in 27 patients (25.2%). There were no statistically significant differences in patient characteristics between the venous obstruction and no venous obstruction group. Of 107 patients, 44 (41.1%) had a superficial vein across the clavicle on the side of CIED implantation. The sensitivity of the presence of a superficial vein across the clavicle in the diagnosis of venous obstruction was 96.3% and specificity was 77.5% (P<0.001).Conclusions:The presence of a superficial vein across the clavicle is useful for the prediction of venous obstruction in patients with CIED. (Circ J 2014; 78: 1846–1850)
  • Yuichi Hori, Shiro Nakahara, Tohru Kamijima, Naofumi Tsukada, Akiko Ha ...
    Type: ORIGINAL ARTICLE
    Subject area: Arrhythmia/Electrophysiology
    2014 Volume 78 Issue 8 Pages 1851-1857
    Published: July 25, 2014
    Released: July 25, 2014
    [Advance publication] Released: July 09, 2014
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    Background:Atrial low-voltage areas are suggested to be related to maintenance of atrial fibrillation (AF). The influence of the left atrium (LA) contact area (CoA) has not been investigated.Methods and Results:Twenty-two persistent AF patients underwent high-density mapping during AF and sinus rhythm (SR). Three representative CoA regions in the LA (ascending aorta: anterior wall; descending aorta: left inferior pulmonary vein [LIPV]; and vertebrae: posterior wall) were identified. Electrogram analysis of both high dominant frequency (high-DF; >8 Hz) and complex fractionated atrial electrogram (con-CFAE; <50 ms) regions during SR was done. The anatomical relationship between CoA and both the very low-voltage areas (vLVA; <0.2 mV) and high-frequency sources was determined. Forty-seven vLVA (194.4 cm2) and 60 CoA (337.0 cm2) were documented, and 32 vLVA directly overlapped CoA. The vLVA were preferentially found in the anterior (45%) and posterior (13%) walls of the LA, and in the LIPV (13%), and corresponded to CoA sites. The mean voltage during SR at high-DF sites was significantly lower than that at con-CFAE sites (0.62 vs.1.54 mV; P<0.0001). Seventy-two percent of high-DF sites overlapped CoA, while 54% of con-CFAE did. Furthermore, 44% of high-DF surface area directly overlapped CoA, while only 19% of con-CFAE did.Conclusions:Very low-voltage regions had a strong association with CoA. Sites with CoA had a higher incidence of fractionated electrograms both during SR and AF. (Circ J 2014; 78: 1951–1857)
Cardiovascular Intervention
  • Gian Battista Danzi, Raffaele Piccolo, Gennaro Galasso, Federico Pisci ...
    Type: ORIGINAL ARTICLE
    Subject area: Cardiovascular Intervention
    2014 Volume 78 Issue 8 Pages 1858-1866
    Published: July 25, 2014
    Released: July 25, 2014
    [Advance publication] Released: June 03, 2014
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    Background:Permanent polymer coatings on drug-eluting stents (DES) surface have been identified as triggers of adverse events following percutaneous coronary intervention (PCI). However, efficacy and safety data for the Nobori biolimus-eluting stent (BES), a biodegradable polymer DES, are limited, so the aim of this study was to evaluate clinical outcomes associated with the Nobori BES compared with permanent polymer DES in patients undergoing PCI.Methods and Results:Randomized trials comparing Nobori BES vs. other DES were included in the meta-analysis. The 12-month clinical endpoints were: target lesion revascularization (TLR), all-cause mortality, myocardial infarction (MI) and stent thrombosis (ST). Seven trials totaling 12,090 PCI patients met the inclusion criteria. Nobori BES vs. other DES had a comparable risk of TLR (odds ratio [OR] 0.94; 95% confidence interval [CI], 0.66–1.34; P=0.74), mortality (OR 1.00; 95% CI, 0.78–1.28; P=0.98), MI (OR 1.10; 95% CI, 0.87–1.40; P=0.42) and definite/probable ST (OR 1.01; 95% CI, 0.45–2.25; P=0.99). Despite Nobori BES showing similar clinical results to sirolimus-, everolimus- and zotarolimus-eluting stents, it was superior to paclitaxel-eluting stents in reducing the risk of TLR (OR 0.31; 95% CI, 0.10–0.90; P=0.03)Conclusions:Nobori BES use is associated with a similar safety and efficacy as permanent polymer DES at 1-year follow-up, albeit it is superior to paclitaxel-eluting stents in terms of TLR. Long-term follow-up data are needed in order to establish whether polymer degradation related to Nobori BES implantation improves clinical outcomes. (Circ J 2014; 78: 1858–1866)
  • Hiroto Yabushita, Kensuke Takagi, Satoko Tahara, Yusuke Fujino, Takayu ...
    Type: ORIGINAL ARTICLE
    Subject area: Cardiovascular Intervention
    2014 Volume 78 Issue 8 Pages 1867-1872
    Published: July 25, 2014
    Released: July 25, 2014
    [Advance publication] Released: June 12, 2014
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    Background:There is little data on percutaneous coronary intervention (PCI) using rotational atherectomy (Rota) for severely calcified unprotected left main (ULM) lesions.Methods and Results:Between January 2005 and August 2011, 64 consecutive patients who underwent drug-eluting stent implantation using Rota were retrospectively evaluated. Of these, 54.7% and 20.3% patients had diabetes and were undergoing hemodialysis (HD), respectively. The mean EuroSCORE and SYNTAX score was 5.6 and 35.4, respectively. Procedural success, defined as residual stenosis <30%, was achieved in 95.3% of patients without fatal complications. Periprocedural myocardial infarction occurred in 7.8% patients. At the 1-year follow up, cardiac death was observed in 6.3% of patients, and target lesion revascularization (TLR) and TLR in the main branch (TLR-MB) were required in 18.8% and 10.9% patients, respectively. Optimal stent expansion was achieved in the majority of 33 patients with available intravascular ultrasound (IVUS) data. However, 5 of 9 HD patients who underwent IVUS required TLR-MB despite optimal stent expansion. The rate of TLR-MB was significantly lower in the non-HD patients than in the HD patients (2.1% vs. 46.2%; P=0.003).Conclusions:PCI using Rota for calcified ULM lesions might guarantee high procedural success and a low complication rate. Although acceptable results were obtained at the 1-year follow up for non-HD patients, the rate of TLR-MB was considerably high for HD patients despite optimal stent expansion. (Circ J 2014; 78: 1867–1872)
  • Shimpei Nakatani, Yoshinobu Onuma, Yuki Ishibashi, Jeroen Eggermont, Y ...
    Type: ORIGINAL ARTICLE
    Subject area: Cardiovascular Intervention
    2014 Volume 78 Issue 8 Pages 1873-1881
    Published: July 25, 2014
    Released: July 25, 2014
    [Advance publication] Released: June 18, 2014
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    Background:Quantitative light intensity analysis of the strut core by optical coherence tomography (OCT) may enable assessment of changes in the light reflectivity of the bioresorbable polymeric scaffold from polymer to provisional matrix and connective tissues, with full disappearance and integration of the scaffold into the vessel wall. The aim of this report was to describe the methodology and to apply it to serial human OCT images post procedure and at 6, 12, 24 and 36 months in the ABSORB cohort B trial.Methods and Results:In serial frequency-domain OCT pullbacks, corresponding struts at different time points were identified by 3-dimensional foldout view. The peak and median values of light intensity were measured in the strut core by dedicated software. A total of 303 corresponding struts were serially analyzed at 3 time points. In the sequential analysis, peak light intensity increased gradually in the first 24 months after implantation and reached a plateau (relative difference with respect to baseline [%Dif]: 61.4% at 12 months, 115.0% at 24 months, 110.7% at 36 months), while the median intensity kept increasing at 36 months (%Dif: 14.3% at 12 months, 75.0% at 24 months, 93.1% at 36 months).Conclusions:Quantitative light intensity analysis by OCT was capable of detecting subtle changes in the bioresorbable strut appearance over time, and could be used to monitor the bioresorption and integration process of polylactide struts. (Circ J 2014; 78: 1873–1881)
  • Akihide Konishi, Toshiro Shinke, Hiromasa Otake, Tomofumi Takaya, Masa ...
    Type: ORIGINAL ARTICLE
    Subject area: Cardiovascular Intervention
    2014 Volume 78 Issue 8 Pages 1882-1890
    Published: July 25, 2014
    Released: July 25, 2014
    [Advance publication] Released: June 09, 2014
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    Background:Nobori is a novel biolimus A9-eluting stent (BES) coated with a biodegradable polymer only on the abluminal side, which degrades over 6–9 months post-stent deployment. The course of vessel reaction after deployment at these time points remains unclear.Methods and Results:We serially evaluated 28 BES implanted in de novo coronary lesions of 23 patients using optical coherence tomography (OCT) at 6 and 12 months post-stenting. Standard OCT variables, the percentage of stent with peri-strut low-intensity area (PLIA, a region around stent struts homogenously showing lesser intensity than the surrounding tissue, suggesting fibrin deposition or impaired neointima maturation) and that with in-stent thrombi were evaluated. There was a significant, but small increase in neointimal thickness (72±23 to 82±25 µm, P=0.006) from the 6- to the 12-month follow-up, without a significant decrease in minimum lumen area (P=0.30). The incidences of uncovered and malapposed struts were low at 6 months and reduced further at 12 months (3.96±3.97% to 1.51±1.63%, P=0.001, and 0.50±1.84% to 0.06±0.24%, P=0.20, respectively). The frequency of stent with PLIA decreased during the follow-up (57% to 32%, P=0.05) and that with in-stent thrombi also numerically decreased (7% to 0%, P=0.24).Conclusions:Neointimal hyperplasia was persistently suppressed following BES implantation up to 12 months. Simultaneously, favorable vessel healing was achieved at 6 months without a delaying adverse reaction for up to 12 months. (Circ J 2014; 78: 1882–1890)
Cardiovascular Surgery
  • Maki Sumida, Kent Doi, Osamu Kinoshita, Mitsutoshi Kimura, Minoru Ono, ...
    Type: ORIGINAL ARTICLE
    Subject area: Cardiovascular Surgery
    2014 Volume 78 Issue 8 Pages 1891-1899
    Published: July 25, 2014
    Released: July 25, 2014
    [Advance publication] Released: June 13, 2014
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    Background:Perioperative complication of end-organ injury including acute kidney injury (AKI) is a frequent and severe problem for patients undergoing left ventricular assist device (LVAD) implantation. This study evaluated an emerging AKI biomarker, plasma neutrophil gelatinase-associated lipocalin (NGAL), in a LVAD implantation cohort.Methods and Results:Of 31 LVAD implantation patients enrolled to this study, 17 (55%) patients were diagnosed as having AKI. Six AKI patients showed severe AKI requiring renal replacement therapy (RRT). Plasma NGAL values in the AKI-with-RRT group (n=6) were significantly higher than that in other patients, although the AKI-without-RRT (n=11) group showed a similar level of plasma NGAL to that of the non-AKI group (n=14). Multiple logistic regression analysis revealed that plasma NGAL measured at pre-operation and central venous pressure at pre-operation and 12 h after surgery independently discriminated against postoperative RRT requirement. In the AKI-with-RRT group, plasma NGAL decreased before termination of RRT in 4 patients who eventually showed renal recovery, although no decline of plasma NGAL was observed in 2 patients who showed no recovery of renal function. Removal of blood NGAL by continuous hemodiafiltration was shown to be 70–75% lower than that of creatinine.Conclusions:Measurement of perioperative plasma NGAL is useful for predicting severe AKI requiring RRT and renal recovery in patients who have had LVAD implantation surgery. Further investigation is necessary to confirm these findings because this study examined a low number of patients. (Circ J 2014; 78: 1891–1899)
  • Nai-Hsin Chi, Nai-Kuan Chou, Ya-Hui Yu, Hsi-Yu Yu, I-Hui Wu, Yih-Sharn ...
    Type: ORIGINAL ARTICLE
    Subject area: Cardiovascular Surgery
    2014 Volume 78 Issue 8 Pages 1900-1907
    Published: July 25, 2014
    Released: July 25, 2014
    [Advance publication] Released: June 26, 2014
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    Background:Rheumatic heart disease (RHD) remains a significant cause of cardiovascular disease in developing countries. The nonsuppurative cardiovascular sequel of group A streptococcal infection is sustained inflammatory and immune reactions toward the myocardium and valves. This study attempted to determine the long-term outcome of heart transplantation in endstage RHD patients.Methods and Results:The 23 patients with endstage RHD at National Taiwan University Hospital between June 1987 and March 2012 were enrolled. In the same period, 226 dilated cardiomyopathy (DCM) patients were enrolled as the control group. The RHD group experienced more right ventricular failure and higher central venous pressure than the control group, which resulted in impaired liver and kidney function. The RHD patients had a lower 15-year survival rate than the DCM patients after transplantation (22.7% vs. 45.7%, P=0.038) and higher incidence of tricuspid regurgitation than the control group (32.2% vs. 11.4%). No differences existed between the groups for the mitral regurgitation rate (RHD 37.7% vs. DCM 29.4%, P=0.562).Conclusions:Preoperatively, the RHD patients suffered more tricuspid regurgitation than the control group. The aortic and mitral valves in both groups functioned well over the long term. Heart transplantation for endstage RHD had a long-term survival rate that was inferior to that for DCM patients. (Circ J 2014; 78: 1900–1907)
  • Shunsuke Sato, Tomoyuki Fujita, Yusuke Shimahara, Hiroki Hata, Junjiro ...
    Type: ORIGINAL ARTICLE
    Subject area: Cardiovascular Surgery
    2014 Volume 78 Issue 8 Pages 1908-1914
    Published: July 25, 2014
    Released: July 25, 2014
    [Advance publication] Released: July 04, 2014
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    Background:This study investigated the impact of prosthesis-patient mismatch (PPM) after mitral valve replacement (MVR) with cryoablation using a maze procedure.Methods and Results:We evaluated 142 patients who underwent MVR with a cryomaze procedure. Echocardiography was performed at 1 week and at 1, 3, 5, 7, and 10 years. An effective orifice area index of 1.2 cm2/m2was used to define PPM. Mean transmitral pressure gradient (mean MPG) >5 mmHg was defined as high. PPM was a risk for overall mortality and a predictor of admission for heart failure. Mean MPG at 1 week was significantly higher in PPM patients (4.8±1.5 mmHg vs. 3.7±1.2 mmHg, P<0.001). Left atrium (LA) dimension decreased after the operation and did not change in patients without high mean MPG, while it increased after 7 years in patients with high mean MPG. The significant predictor of AF recurrence after 1 year was LA dimension ≥52.9 mm. Yearly AF recurrence was 10.6% in patients with LA dimension ≥52.9 mm, and 1.8% in the others. In patients with high mean MPG, tricuspid regurgitation pressure gradient (TRPG), related to pulmonary artery pressure, was increased after 7 years.Conclusions:PPM is a risk for late mortality, admission for heart failure, and high mean MPG, while the last was related to risk of enlargement of LA and increase of TRPG after 7 years. LA dimension after surgery is a predictor of late recurrence of AF, especially when ≥52.9 mm. (Circ J 2014; 78: 1908–1914)
Hypertension and Circulatory Control
  • Dong-hong Zhang, Xue-mei Wen, Lin Zhang, Wei Cui
    Type: ORIGINAL ARTICLE
    Subject area: Hypertension and Circulatory Control
    2014 Volume 78 Issue 8 Pages 1915-1923
    Published: July 25, 2014
    Released: July 25, 2014
    [Advance publication] Released: May 30, 2014
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    Background:Elevated homocysteine (Hcy) levels might play a role in the development of essential hypertension (EH). Telomere dynamics provide valuable insight into the pathogenesis of age-related diseases. The contribution of Hcy to leukocyte telomere length (LTL) shortening in EH and the underlying mechanism was examined.Methods and Results:LTL (ratio of the copy number of telomere [T] repeats to that of a single [S] gene, T/S ratio) was inversely associated with age in patients with EH (n=258) and healthy controls (n=137), but significantly decreased with the Hcy level only in patients with hypertension after adjustment for age and sex. Age, hypertension and levels of Hcy and low-density lipoprotein combined contributed to LTL shortening; an increased serum folate level could reverse the Hcy effect seen on multivariate regression analysis. In addition, qPCR and methylation-specific PCR assay revealed that LTL shortening and mRNA expression and the methylation ratio of human telomerase reverse transcriptase (hTERT) were lower in patients with EH than in controls, and gradually decreased with increasing Hcy level, but not with blood pressure, in EH patients (Ptrend<0.0001, 0.004 and 0.012, respectively). Furthermore, Hyperhomocysteinemia, but not hypertension, promoted telomerase reverse transcriptase DNA hypomethylation and reduced mRNA levels, which contributed to shortened LTL in the hypertension rat model.Conclusions:Elevated Hcy but not hypertension was related to hTERT DNA hypomethylation and reduced mRNA level, thus contributing to the shortening of LTL hypertension. (Circ J 2014; 78: 1915–1923)
  • Mosaburo Kainuma, Norihiro Furusyo, Shin-ichi Ando, Haru Mukae, Eiichi ...
    Type: ORIGINAL ARTICLE
    Subject area: Hypertension and Circulatory Control
    2014 Volume 78 Issue 8 Pages 1924-1927
    Published: July 25, 2014
    Released: July 25, 2014
    [Advance publication] Released: July 01, 2014
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    Background:The Yo/Yin concept is fundamental to making a Kampo (sho) diagnosis and may be deeply related to the autonomic nervous system. There is, however, little objective data to confirm the validity of these concepts.Methods and Results:After diagnosis using standardized Kampo techniques, 20 men and 67 women (mean age, 52.4 years) for whom the prescribed Kampo medication was effective were judged to be correctly classified as Yo- (n=49) or Yin-sho (n=38) and enrolled. Autonomic nervous function was assessed at first visit using HRV obtained from 24-h Holter ECG. Nocturnal ultra low frequency-1 (ULF-1, 0.0001–0.0003 Hz) and ULF-2 (0.0003–0.003 Hz) were significantly higher in the Yin-sho than in the Yo-sho group (P=0.030, P=0.016), suggesting a higher variation of autonomic nervous activity according to sleep stage. On multivariate analysis BMI (≥23.0 kg/m2) and ULF-1 (≥1,150 ms2) were identified as independent factors associated with a differential diagnosis of Yo- or Yin-sho (odds ratio [OR], 11.63, P=0.002; OR, 0.30, P=0.038, respectively). When the sleep period was divided into 3 phases, the ULF-1 of the Yin-sho group was significantly higher than that of the Yo-sho group in the late phase of sleep (P=0.023).Conclusions:On heart rate variability analysis there was a sleep stage-related difference in the autonomic nervous activity of patients treated with standard Yo- and Yin-sho Kampo medicines. (Circ J 2014; 78: 1924–1927)
Imaging
  • Manabu Kurabayashi, Kaoru Okishige, Daisuke Ueshima, Kojiro Yoshimura, ...
    Type: ORIGINAL ARTICLE
    Subject area: Imaging
    2014 Volume 78 Issue 8 Pages 1928-1934
    Published: July 25, 2014
    Released: July 25, 2014
    [Advance publication] Released: June 09, 2014
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    Background:The diagnostic value of unenhanced computed tomography (CT) for diagnosing acute aortic dissection (AAD) and ruptured thoracic aortic aneurysm (TAA) remains unclear.Methods and Results:We examined 219 consecutive patients who visited the emergency room with suspected acute aortic syndrome (AAS) because of chest or back pain and who underwent both unenhanced and contrast-enhanced 64-row multi-detector CT. The unenhanced CT findings were evaluated by the cardiologist on duty who was blind to the findings of contrast-enhanced CT. Diagnosis of AAS was confirmed in 103 patients (47%, 95 AAD and 8 ruptured TAA patients) based on evaluation of both unenhanced and contrast-enhanced CT images, which was used as the reference standard for validating the diagnostic value of the unenhanced CT findings. Sensitivity and specificity of the findings of a high-attenuation crescent, which represents hematoma in the aortic wall, were 61.2% and 99.1%, respectively. Sensitivity and specificity of linear high density in the aorta, which represents an intimal flap, were 59.2% and 96.6%, respectively. If unenhanced CT showed none of high-attenuation crescent, linear high density, internal displacement of intimal calcification, or TAA, the negative predictive value was 93.3%.Conclusions:Unenhanced CT is a good tool for ruling AAS in, but the false-negative rate of 6.7% is high for ruling AAS out because it has to be the minimum possible. (Circ J 2014; 78: 1928–1934)
Ischemic Heart Disease
  • Giampaolo Niccoli, Giancarla Scalone, Nicola Cosentino, Alessandro Fab ...
    Type: ORIGINAL ARTICLE
    Subject area: Ischemic Heart Disease
    2014 Volume 78 Issue 8 Pages 1935-1941
    Published: July 25, 2014
    Released: July 25, 2014
    [Advance publication] Released: May 26, 2014
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    Background:Pre-infarction angina (PIA) has been shown to reduce the microvascular obstruction (MVO) rate in patients with ST-segment elevation myocardial infarction (STEMI). We sought to evaluate the potential modulator role of cardiovascular risk factors (CRFs) on this protective effect.Methods and Results:Two hundred patients with STEMI were enrolled. PIA was defined as typical chest pain within the 48 h preceding STEMI onset. Angiographic MVO was defined as TIMI flow grade <2 or TIMI flow 3 with myocardial blush grade <2; electrocardiographic (ECG) MVO was defined as ST-segment elevation resolution <70%. Common CRFs were collected. In the absence of hypertension, both angiographic and ECG MVO rates were lower in patients with PIA as compared with those without, whereas, in the presence of hypertension, they were similar in both study groups (P for interaction=0.01 and P=0.014, respectively). Among nonsmokers, angiographic and ECG MVO rates were lower in patients with PIA as compared with those without, whereas within smokers, they were similar in both study groups (P for interaction=0.037 and P=0.037, respectively). In the absence of dyslipidemia, the angiographic and ECG MVO rates were lower in patients with PIA as compared with those without, whereas within dyslipidemic patients, they were similar in both study groups (P for interaction=0.012 and P=0.04, respectively).Conclusions:The protective effect of PIA on MVO is blunted by CRFs. (Circ J 2014; 78: 1935–1941)
  • Carlos M. Campos, David van Klaveren, Javaid Iqbal, Yoshinobu Onuma, Y ...
    Type: ORIGINAL ARTICLE
    Subject area: Ischemic Heart Disease
    2014 Volume 78 Issue 8 Pages 1942-1949
    Published: July 25, 2014
    Released: July 25, 2014
    [Advance publication] Released: July 07, 2014
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    Background:SYNTAX score II (SSII) provides individualized estimates of 4-year mortality after coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in order to facilitate decision-making between these revascularization methods. The purpose of the present study was to assess SSII in a real-world multicenter registry with distinct regional and epidemiological characteristics.Methods and Results:Long-term mortality was analyzed in 3,896 patients undergoing PCI (n=2,190) or CABG (n=1,796) from the Coronary REvascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto) PCI/CABG registry cohort-2. SSII discriminated well in both CABG and PCI patient groups (concordance index [c-index], 0.70; 95% CI: 0.68–0.72; and 0.75, 95% CI: 0.72–0.78) surpassing anatomical SYNTAX score (SS; c-index, 0.50; 95% CI: 0.47–0.53; and 0.59, 95% CI: 0.57–0.61). SSII had the best discriminative ability to separate low-, medium- and high-risk tertiles, and calibration plots showed good predictive performance for CABG and PCI groups. Use of anatomical SS as a reference improved the overall reclassification provided by SSII, with a net reclassification index of 0.5 (P<0.01).Conclusions:SSII has robust prognostic accuracy, both in CABG and in PCI patient groups and, compared with the anatomical SS alone, was more accurate in stratifying patients for late mortality in a real-world complex coronary artery disease Eastern population. (Circ J 2014; 78: 1942–1949)
Molecular Cardiology
  • Sayaka Kurokawa, Shinichi Niwano, Hiroe Niwano, Masami Murakami, Shoko ...
    Type: ORIGINAL ARTICLE
    Subject area: Molecular Cardiology
    2014 Volume 78 Issue 8 Pages 1950-1959
    Published: July 25, 2014
    Released: July 25, 2014
    [Advance publication] Released: May 23, 2014
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    Background:This study was designed to investigate the role of a primary hyperoxidative stress in myocardial electrical remodeling using heterozygous heart/muscle-specific manganese superoxide dismutase-deficient (H/M-Sod2+/–) mice treated with L-buthionine-sulfoximine (BSO).Methods and Results:Both H/M-Sod2+/–and wild-type (WT) mice were treated with intra-peritoneal BSO or saline for 7 days, and divided into 4 groups: H/M-Sod2+/–+BSO, WT+BSO, H/M-Sod2+/–control, and WT control. The ventricular effective refractory period (ERP) and the monophasic action potential duration (MAPD) were determined. Levels of oxidative stress, potassium channel-related molecules, and K+channel-interacting protein-2 (KChIP2) were also evaluated. The H/M-Sod2+/–+BSO group exhibited markedly prolonged MAPD20, MAPD90and ERP in comparison with the other groups (MAPD20: 14±1 vs. 11±1 ms, MAPD90: 77±7 vs. 58±4 ms, ERP: 61±6 vs. 41±3 ms, H/M-Sod2+/–+BSO vs. WT control; P<0.05). Mitochondrial superoxide and hydrogen peroxide formation in the myocardium increased in the H/M-Sod2+/–+BSO group in comparison with the WT+BSO group (P<0.05). Real-time RT-PCR and Western blotting revealed that Kv4.2 expression was downregulated in both BSO-treated groups, whereas KChIP2 expression was downregulated only in the H/M-Sod2+/–+BSO group (P<0.05).Conclusions:BSO treatment caused hyperoxidative stress in the myocardium of H/M-Sod2+/–mice. Changes in the expression and function of potassium channels were considered to be involved in the mechanism of electrical remodeling in this model. (Circ J 2014; 78: 1950–1959)
Pediatric Cardiology and Adult Congenital Heart Disease
  • Akihiro Nakamura, Hitoshi Horigome, Yoshihiro Seo, Tomoko Ishizu, Ryo ...
    Type: ORIGINAL ARTICLE
    Subject area: Pediatric Cardiology and Adult Congenital Heart Disease
    2014 Volume 78 Issue 8 Pages 1960-1966
    Published: July 25, 2014
    Released: July 25, 2014
    [Advance publication] Released: May 23, 2014
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    Background:The aim of the present study was to assess the impact of pulmonary regurgitation (PR) and right ventricle (RV) volume on left ventricle (LV) longitudinal strain (LS) in patients with surgically repaired tetralogy of Fallot (r-TOF).Methods and Results:The study subjects were 32 adolescent asymptomatic r-TOF subjects and 30 adolescent healthy controls. Two-dimensional (2-D) and 3-dimensional (3-D) echocardiography were performed in all subjects using Vivid E9 (GE Healthcare). On 3-D analysis, LV and RV volumes were measured using 4D auto LVEF and TomTec RV analysis. PR fraction (PRF) was calculated by the volumetric method (PRF=[RV stroke volume–LV stroke volume]/RV stroke volume). LV-LS was assessed on 2-D speckle tracking echocardiography, and “free wall LS” represented the average of 3 lateral segments. Although RVEF and LVEF were not different between the 2 groups, free wall LS (–17.1±3.2%) was reduced significantly in the r-TOF group compared to the control (–20.5±4.9%, P=0.008), and correlated with the RV variables RVEDVI, RV/LV EDVI ratio and PRF. On multivariate stepwise linear regression analysis, RVEDVI was the only risk factor for the reduction of free wall LS (P=0.004).Conclusions:Free wall LS was significantly reduced despite preserved LVEF. The severity of LS reduction was correlated with RV dilation even in asymptomatic r-TOF patients. (Circ J 2014; 78: 1960–1966)
  • Ikuo Hashimoto, Kazuhiro Watanabe
    Type: ORIGINAL ARTICLE
    Subject area: Pediatric Cardiology and Adult Congenital Heart Disease
    2014 Volume 78 Issue 8 Pages 1967-1973
    Published: July 25, 2014
    Released: July 25, 2014
    [Advance publication] Released: May 22, 2014
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    Background:Many studies have investigated tricuspid annular plane systolic excursion (TAPSE) as a longitudinal right ventricular (RV) contraction. The aim of this study was to clarify the mechanism of RV systolic function compared with longitudinal and radial RV contractions in healthy children.Methods and Results:A total of 815 consecutive healthy children and adolescents were enrolled. We measured TAPSE on M-mode echocardiography as a longitudinal RV contraction. RV wall displacement (RVWD) toward the center of the left ventricle (LV) was measured in the short-axis view on M-mode echocardiography. RV stroke volume (RVSV) was obtained using pulse Doppler echocardiography as an indicator of RV global systolic function. RVSV and TAPSE had a positive but non-linear correlation with a definite inflection point around 15 mm of TAPSE. Subjects were stratified into 2 groups according to TAPSE (≤15 mm or >15 mm). In subjects with TAPSE ≤15 mm, RVWD and TAPSE were identified as independent predictors of RVSV. In contrast, in subjects with TAPSE >15 mm, TAPSE were identified as an independent predictor of RVSV.Conclusions:Normal RV contraction pattern shifts from radial to longitudinal directions at approximately 15 mm of TAPSE. RVSV is primarily generated by longitudinal contraction, but in neonates, RVSV is supported not only by longitudinal contraction but also by radial contraction. (Circ J 2014; 78: 1967–1973)
  • Kazuhiro Takahashi, Wataru Shimizu, Akira Miyake, Taisuke Nabeshima, M ...
    Type: ORIGINAL ARTICLE
    Subject area: Pediatric Cardiology and Adult Congenital Heart Disease
    2014 Volume 78 Issue 8 Pages 1974-1979
    Published: July 25, 2014
    Released: July 25, 2014
    [Advance publication] Released: May 28, 2014
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    Background:Genetic testing for long QT syndrome (LQTS) is now in clinical practice. We conducted molecular genetic analyses to definitively diagnose LQTS and to determine its subtypes for gene-specific treatment. We conducted a retrospective study to determine the characteristics of schoolchildren with LQTS living on the Okinawa Islands.Methods and Results:The study population included children identified in a school-based electrocardiographic (ECG) screening program for cardiovascular diseases who were referred to Okinawa Children’s Medical Center between 2007 and 2012; 23 children met the diagnostic criteria for LQTS. Of them, 17 were genotype-positive and 14 were found to harbor theSCN5AE1784K mutation exclusively among the LQTS genotype-positive children. The children were divided into genotype-positive and -negative groups. Clinical characteristics and ECG data were analyzed and compared. The median Schwartz score was 3. The median QT interval was 521 ms.Conclusions:The major finding is that the prevalent subtype of LQTS in Okinawa is discordant with other cohorts living in other regions of Japan or overseas. We cannot exclude the possibility of the presence of a specific founder mutation in this geographically clustered population, particularly considering that the hospital is the only tertiary heart center for children in Okinawa. However, this uniquely high prevalence of theSCN5AE1784K mutation serves as a compelling justification to conduct a larger study. (Circ J 2014; 78: 1974–1979)
Vascular Biology and Vascular Medicine
  • Kazuaki Mawatari, Emiko Yoshioka, Satomi Toda, Sonoko Yasui, Hiroko Fu ...
    Type: ORIGINAL ARTICLE
    Subject area: Vascular Biology and Vascular Medicine
    2014 Volume 78 Issue 8 Pages 1980-1988
    Published: July 25, 2014
    Released: July 25, 2014
    [Advance publication] Released: May 23, 2014
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    Background:Left atrial (LA) thrombosis is an important cause of systemic embolization. The SPORTS rat model of LA thrombi (Spontaneously-Running Tokushima-Shikoku), which have a unique characteristic of high voluntary wheel running, was previously established. The aim of the present study was to investigate how SPORTS rats develop LA thrombi.Methods and Results:Nitric oxide (NO) produced from cardiovascular endothelial cells plays an important protective role in the local regulation of blood flow, vascular tone, and platelet aggregation. No evidence of atrial fibrillation or hypercoagulability in SPORTS rats regardless of age was found; however, SPORTS rats demonstrated endothelial dysfunction and a decrease of NO production from a young age. In addition, endothelial NO synthase activity was significantly decreased in the LA and thoracic aorta endothelia of SPORTS rats. While voluntary wheel running was able to intermittently increase NO levels, running did not statistically decrease the incidence of LA thrombi at autopsy. However, L-arginine treatment significantly increased NO production and provided protection from the development of LA thrombi in SPORTS rats.Conclusions:They present study results indicate that NO has an important role in the development of LA thrombus, and endothelia pathways could provide new targets of therapy to prevent LA thrombosis. (Circ J 2014; 78: 1980–1988)
Rapid Communication
  • Takashi Noda, Takashi Kurita, Takashi Nitta, Haruhiko Abe, Shigeyuki W ...
    Type: RAPID COMMUNICATION
    2014 Volume 78 Issue 8 Pages 1989-1991
    Published: July 25, 2014
    Released: July 25, 2014
    [Advance publication] Released: July 15, 2014
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    Background:Little is known regarding the appropriate duration for driving restrictions after inappropriate implantable cardiac shock device (ICSD) therapy.Methods and Results:We evaluated the Nippon Storm Study data, and found that inappropriate ICSD therapy occurred in 114 (7.6%) patients during a median follow-up of 464 days. Among those patients, 25 experienced further inappropriate ICSD therapy during a subsequent median follow-up of 380 days. Time-dependent recurrence of inappropriate ICSD therapy occurred in 19 (76%) patients within 180 days.Conclusions:The interval for driving restrictions after inappropriate ICSD therapy can be reduced. (Circ J 2014; 78: 1989–1991)
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