Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Volume 79 , Issue 7
Showing 1-44 articles out of 44 articles from the selected issue
Message From the Editor-in-Chief
JCS Statement
Focus Reviews on Molecular Cardiology
  • Jian-Yan Wen, Chuan-Yu Wei, Khooshbu Shah, Johnson Wong, Cheng Wang, H ...
    Type: FOCUS REVIEWS ON MOLECULAR CARDIOLOGY
    2015 Volume 79 Issue 7 Pages 1402-1408
    Published: June 25, 2015
    Released: June 25, 2015
    [Advance publication] Released: May 12, 2015
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    Cellular reprogramming of somatic cells to patient-specific induced pluripotent stem cells (iPSCs) enables in-vitro modeling of human cardiac disorders for pathogenic and therapeutic investigations. However, using iPSC-derived cardiomyocytes (iPSC-CMs) to model an adult-onset heart disease remains challenging because of the uncertainty regarding the ability of relatively immature iPSC-CMs to fully recapitulate adult disease phenotypes. Arrhythmogenic right ventricular dysplasia (ARVD) is an inherited cardiomyopathy characterized by pathological fibrofatty infiltration and cardiomyocyte (CM) loss predominantly in the right ventricle (RV), leading to heart failure and lethal arrhythmias. Over 50% of affected individuals have desmosome gene mutations, most commonly inPKP2encoding plakophilin-2. Using Yamanaka’s pluripotent factors, we generated iPSC lines from ARVD patients withPKP2mutations. We first developed a method to induce metabolic maturation of iPSC-CMs and showed that induction of adult-like metabolic energetics from an embryonic/glycolytic state is essential to model an adult-onset cardiac disease using patient-specific iPSCs. Furthermore, we showed that coactivation of normal peroxisome proliferator-activated receptor (PPAR)-α and abnormal PPARγ pathways in ARVD iPSC-CMs resulted in exaggerated CM lipogenesis, CM apoptosis, Na+channel downregulation and defective intracellular calcium handling, recapitulating the pathological signatures of ARVD. Using this model, we revealed novel pathogenic insights that metabolic derangement in an adult-like metabolic milieu underlies ARVD pathologies, enabling us to propose novel disease-modifying therapeutic strategies. (Circ J 2015; 79: 1402–1408)
  • Elizabeth M. McNally, Megan J. Puckelwartz
    Type: FOCUS REVIEWS ON MOLECULAR CARDIOLOGY
    2015 Volume 79 Issue 7 Pages 1409-1415
    Published: June 25, 2015
    Released: June 25, 2015
    [Advance publication] Released: June 04, 2015
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    With the wider deployment of massively-parallel, next-generation sequencing, it is now possible to survey human genome data for research and clinical purposes. The reduced cost of producing short-read sequencing has now shifted the burden to data analysis. Analysis of genome sequencing remains challenged by the complexity of the human genome, including redundancy and the repetitive nature of genome elements and the large amount of variation in individual genomes. Public databases of human genome sequences greatly facilitate interpretation of common and rare genetic variation, although linking database sequence information to detailed clinical information is limited by privacy and practical issues. Genetic variation is a rich source of knowledge for cardiovascular disease because many, if not all, cardiovascular disorders are highly heritable. The role of rare genetic variation in predicting risk and complications of cardiovascular diseases has been well established for hypertrophic and dilated cardiomyopathy, where the number of genes that are linked to these disorders is growing. Bolstered by family data, where genetic variants segregate with disease, rare variation can be linked to specific genetic variation that offers profound diagnostic information. Understanding genetic variation in cardiomyopathy is likely to help stratify forms of heart failure and guide therapy. Ultimately, genetic variation may be amenable to gene correction and gene editing strategies. (Circ J 2015; 79: 1409–1415)
Reviews
  • Carole A. Warnes
    Type: REVIEW
    2015 Volume 79 Issue 7 Pages 1416-1421
    Published: June 25, 2015
    Released: June 25, 2015
    [Advance publication] Released: June 04, 2015
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    Because of the growing population of patients with congenital heart disease (CHD), most maternal cardiac disease is now congenital in origin. For women with complex CHD, pregnancy poses an increased risk for both the mother, with complications of arrhythmias and heart failure being the most common, and the baby, with a higher chance of miscarriage, intrauterine growth retardation, and the need for early delivery. Pre-pregnancy counseling must be performed by cardiologists who have expertise in both CHD and pregnancy, with a detailed clinical assessment of the patient and the current hemodynamic situation, including echocardiography and an exercise test. In each case the approach must be individualized with consideration of the risks in each case. In some cases, such as Eisenmenger syndrome, pregnancy is contraindicated. Optimum outcomes in these complex patients are achieved when a multidisciplinary approach is used, involving maternal-fetal medicine specialists, cardiologists with expertise in CHD and obstetric anesthesia. (Circ J 2015; 79: 1416–1421)
  • Michela Noseda, Marta Abreu-Paiva, Michael D. Schneider
    Type: REVIEW
    2015 Volume 79 Issue 7 Pages 1422-1430
    Published: June 25, 2015
    Released: June 25, 2015
    [Advance publication] Released: June 12, 2015
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    Over the past 2 decades, cardiac regeneration has evolved from an exotic fringe of cardiovascular biology to the forefront of molecular, genetic, epigenetic, translational, and clinical investigations. The unmet patient need is the paucity of self-repair following infarction. Robust regeneration seen in models such as zebrafish and newborn mice has inspired the field, along with encouragement from modern methods that make even low levels of restorative growth discernible, changing the scientific and technical landscape for effective counter-measures. Approaches under study to augment cardiac repair complement each other, and encompass grafting cells of diverse kinds, restarting the cell cycle in post-mitotic ventricular myocytes, reprogramming non-myocytes, and exploiting the dormant progenitor/stem cells that lurk within the adult heart. The latter are the emphasis of the present review. Cardiac-resident stem cells (CSC) can be harvested from heart tissue, expanded, and delivered to the myocardium as a therapeutic product, whose benefits may be hoped to surpass those achieved in human trials of bone marrow. However, important questions are prompted by such cells’ discovery. How do they benefit recipient hearts? Do they contribute, measurably, as an endogenous population, to self-repair? Even if “no,” might CSCs be targets for activation in situ by growth factors and other developmental catalysts? And, what combination of distinguishing markers best demarcates the cells with robust clonal growth and cardiogenic potential? (Circ J 2015; 79: 1422–1430)
  • Peter Ong, Ahmed Aziz, Henrik Steen Hansen, Eva Prescott, Anastasios A ...
    Type: REVIEW
    2015 Volume 79 Issue 7 Pages 1431-1438
    Published: June 25, 2015
    Released: June 25, 2015
    [Advance publication] Released: June 18, 2015
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    Coronary spasm is involved in many clinical scenarios, such as stable angina, acute coronary syndrome, sudden cardiac death, non-ischemic cardiomyopathy, arrhythmia and syncope. In recent years, imaging tools such as computerized tomographic angiography, intravascular ultrasound or optical coherence tomography have been applied to study the coronary pathology in patients with vasospastic angina. Patients with vasospastic angina represent a heterogeneous cohort of patients with regard to the extent of concomitant coronary atherosclerosis. They share the common pathophysiological phenomenon of vascular smooth muscle hyperreactivity leading to spasm caused by various factors that may also overlap. Focal coronary spasm is related to epicardial atherosclerosis and in the presence of obstructive coronary artery disease it may be useful to treat the lesion to prevent further spasm. The aim of this article is to review structural and functional coronary artery abnormalities in patients with vasospastic angina. (Circ J 2015; 79: 1431–1438)
Editorials
Original Articles
Aortic Disease
  • Carmen Ciavarella, Francesco Alviano, Enrico Gallitto, Francesca Ricci ...
    Type: ORIGINAL ARTICLE
    Subject area: Aortic Disease
    2015 Volume 79 Issue 7 Pages 1460-1469
    Published: June 25, 2015
    Released: June 25, 2015
    [Advance publication] Released: April 07, 2015
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    Background:The main histopathological features of abdominal aortic aneurysm (AAA) are tissue proteolysis mediated by matrix metalloproteinases (MMPs) and inflammation. This study aimed at verifying the presence and contribution of mesenchymal stromal cells (MSCs) to aneurysmal tissue remodeling.Methods and Results:MSCs were successfully isolated from the AAA wall of 12 male patients and were found to express mesenchymal and stemness markers. MMP-2/-9 are involved in AAA progression and their mRNA levels in AAA-MSCs resulted higher than healthy MSCs (cMSCs), especially MMP-9 (400-fold increased). Moreover, MMP-9 protein and activity were pronounced in AAA-MSCs. Immunomodulation was tested in AAA-MSCs after co-culture with activated peripheral blood mononuclear cells (PBMCs) and revealed a weak immunosuppressive action on PBMC proliferation (bromodeoxyuridine incorporation, flow cytometry assay), together with a reduced expression of anti-inflammatory molecules (HLA-G, IL-10) by AAA-MSCs compared to cMSCs. MMP-9 expression in AAA-MSCs was shown to be negatively modulated under the influence of cMSCs and exogenous IL-10.Conclusions:MSCs with stemness properties are niched in human AAA tissues and display a dysregulation of functional activities; that is, upregulation of MMP-9 and ineffective immunomodulatory capacity, which are crucial in the AAA progression; the possibility to modulate the increased MMP-9 expression by healthy MSCs and IL-10 suggests that novel therapeutic strategies are possible for slowing down AAA progression. (Circ J 2015; 79: 1460–1469)
  • Takuma Yoshihara, Kazunori Shimada, Kosuke Fukao, Eiryu Sai, Yayoi Sat ...
    Type: ORIGINAL ARTICLE
    Subject area: Aortic Disease
    2015 Volume 79 Issue 7 Pages 1470-1478
    Published: June 25, 2015
    Released: June 25, 2015
    [Advance publication] Released: April 30, 2015
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    Background:Dietary intake of ω3 polyunsaturated fatty acids (ω3-PUFAs) reduces progression of atherosclerosis and prevents future cardiovascular events. Macrophages are key players in the pathogenesis of aortic aneurysm. The effects of ω3-PUFAs on abdominal aortic aneurysm (AAA) formation and macrophage-mediated inflammation remain unclear.Methods and Results:The AAA model was developed by angiotensin II infusion in apolipoprotein E-deficient mice. Mice were supplemented with eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA). The development of AAA lesions and macrophage infiltration in the aorta were analyzed. Gene expression of inflammatory markers in aortic tissues and peritoneal macrophages were measured by using quantitative polymerase chain reaction. AAA formation and macrophage infiltration were significantly suppressed after EPA and DHA administration. EPA administration and DHA administration significantly decreased the expression of tumor necrosis factor-α, monocyte chemoattractant protein-1, transforming growth factor-β, matrix metalloproteinases (MMP)-2, MMP-9, and vascular cell adhesion molecule-1 in the aortas. The expression of arginase 2, which is a marker of pro-inflammatory macrophages, was significantly lower and that of Ym1, which is a marker of anti-inflammatory macrophages, and was significantly higher after EPA and DHA administration. The same trends were observed in peritoneal macrophages after EPA and DHA administration.Conclusions:Dietary intake of EPA and DHA prevented AAA development through the inhibition of aortic and macrophage-mediated inflammation. (Circ J 2015; 79: 1470–1478)
Arrhythmia/Electrophysiology
  • Kensuke Ihara, Takeshi Sasaki, Yasuhiro Shirai, Susumu Tao, Shingo Mae ...
    Type: ORIGINAL ARTICLE
    2015 Volume 79 Issue 7 Pages 1479-1485
    Published: June 25, 2015
    Released: June 25, 2015
    [Advance publication] Released: March 27, 2015
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    Background:The purpose of this study was to clarify the relation between atrial defibrillation threshold (ADFT) for internal cardioversion (IC) and arrhythmogenicity of the superior vena cava (SVC).Methods and Results:A total of 159 consecutive patients (139 male, age 59.9±10.3 years) who underwent radiofrequency catheter ablation of atrial fibrillation (AF) were assessed. IC was performed in 50 patients with non-long-standing persistent AF (non-LSAF) with a purpose-built cardioversion catheter in which direct current is delivered between the right atrium and the coronary sinus. SVC arrhythmogenicity was defined as SVC firing initiating AF, SVC associated with maintenance of AF, or frequent ectopy in the SVC. In all 50 non-LSAF patients, AF termination was obtained on IC during the procedure except in 1 patient with SVC AF. In the patients with ADFT >10 J (n=10), SVC arrhythmogenicity was observed more often than in those with ADFT ≤10 J (n=40; 60% vs. 13%; P=0.004). There were no significant differences between the 2 groups in left atrial diameter (40.8±7.6 vs. 40.6±6.3 mm; P=0.92), persistent AF (33% vs. 50%; P=0.46), or other clinical parameters. The patients who underwent SVC isolation, however, had higher ADFT before SVC isolation than those who did not (15.5±8.8 vs. 9.2±4.4 J; P=0.01).Conclusions:High IC ADFT is associated with SVC arrhythmogenicity in non-LSAF patients. (Circ J 2015; 79: 1479–1485)
  • Yukihiro Koretsune, Takeshi Yamashita, Tetsuya Kimura, Masayuki Fukuza ...
    Type: ORIGINAL ARTICLE
    Subject area: Arrhythmia/Electrophysiology
    2015 Volume 79 Issue 7 Pages 1486-1495
    Published: June 25, 2015
    Released: June 25, 2015
    [Advance publication] Released: April 28, 2015
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    Background:The short-term safety and plasma concentrations of edoxaban 15 mg once daily in Japanese patients with non-valvular atrial fibrillation (NVAF) and severe renal impairment (SRI; creatinine clearance [CLCR] ≥15 to <30 ml/min) were compared with those in NVAF patients with normal renal function or mild renal impairment (normal/MiRI; CLCR≥50 ml/min) treated with edoxaban 30 or 60 mg.Methods and Results:In this Phase 3 multicenter open-label 3 parallel-group study, SRI patients received once-daily edoxaban 15 mg (n=50), whereas normal/MiRI patients were randomized to receive either once-daily edoxaban 30 or 60 mg (n=22 and 21, respectively) for 12 weeks. Plasma edoxaban concentrations and biomarkers of blood coagulation and fibrinolysis were measured. Adverse events and thromboembolic events were recorded throughout the study. Rates of any bleeding were comparable between SRI patients receiving edoxaban 15 mg (20.0%) and normal/MiRI patients receiving edoxaban 30 or 60 mg (22.7% and 23.8%, respectively). No major bleeding or thromboembolic events occurred in any treatment group. Similar plasma concentrations and biomarker profiles were observed in SRI patients receiving edoxaban 15 mg and normal/MiRI patients receiving edoxaban 30 or 60 mg.Conclusions:In this 12-week short-term study in Japanese NVAF patients with SRI, edoxaban 15 mg once daily exhibited similar safety, plasma concentration, and biomarker profiles as did the 30-mg and 60-mg doses in patients with normal/MiRI. (Circ J 2015; 79: 1486–1495)
Cardiovascular Intervention
  • Takahide Arai, Thierry Lefèvre, Kentaro Hayashida, Yusuke Watanabe, St ...
    Type: ORIGINAL ARTICLE
    Subject area: Cardiovascular Intervention
    2015 Volume 79 Issue 7 Pages 1496-1503
    Published: June 25, 2015
    Released: June 25, 2015
    [Advance publication] Released: May 01, 2015
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    Background:We assessed the predictive accuracy of a simple risk score, modified age, creatinine clearance, ejection fraction (ACEFmodif) score, for outcome of transcatheter aortic valve implantation (TAVI).Methods and Results:We prospectively included 703 consecutive patients undergoing TAVI. Patients were divided into low, middle and high ACEFmodif tertiles. Increased ACEFmodif score was associated with a significantly higher 1-year mortality rate (22%, 28% and 36%, P<0.01) and higher risk of acute kidney injury (AKI; 10%, 10% and 22%, P<0.01). On multivariate logistic regression analysis, ACEFmodif score was the only independent predictor of AKI. On multivariate Cox regression, ACEFmodif score was an independent predictor of 1-year cumulative mortality. Although the area under curve (AUC) showed that all risk scores poorly predicted the incidence of AKI and 1-year cumulative mortality, ACEFmodif score was more efficient in predicting the incidence of AKI compared with STS, LES and ES II (AUC, 0.61, 0.55, 0.54, 0.57, respectively). Furthermore, ACEFmodif score had similar accuracy in predicting 1-year mortality compared with other risk scores (AUC, 0.61, 0.61, 0.61, 0.61, respectively).Conclusions:ACEFmodif score may provide useful information for predicting AKI, 30-day and 1-year mortality in patients undergoing TAVI, but these results need further confirmation. (Circ J 2015; 79: 1496–1503)
Cardiovascular Surgery
  • Shigeyuki Ozaki, Isamu Kawase, Hiromasa Yamashita, Shin Uchida, Mikio ...
    Type: ORIGINAL ARTICLE
    2015 Volume 79 Issue 7 Pages 1504-1510
    Published: June 25, 2015
    Released: June 25, 2015
    [Advance publication] Released: March 30, 2015
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    Background:To determine the feasibility of original aortic valve reconstruction (AVRec) for patients with aortic stenosis (AS), 416 consecutive cases were reviewed.Methods and Results:AVRecs for AS were performed for 416 patients from April 2007 through April 2013. All 416 patients were retrospectively reviewed. One hundred and fourteen patients had bicuspid valves and 16 had unicuspid valves. There were 182 men and 234 women. Mean age was 71.2±12.0 years old. On preoperative echocardiography, peak pressure gradient averaged 79.0±33.6 mmHg. Surgical annular diameter was 20.1±2.8 mm. The procedure is based on independent tricuspid replacement by autologous pericardium using original sizing apparatus and template. There was no conversion to prosthetic valve replacement. There were 8 in-hospital mortalities due to non-cardiac cause. On postoperative echocardiography, peak pressure gradient averaged 21.2±10.7 mmHg 1 week after surgery and 14.3±5.0 mmHg 5.5 years after surgery. Four reoperations were done for infective endocarditis. The other 412 patients had less than mild regurgitation. No thrombo-embolic events were recorded. The mean follow-up period was 25.2±17.5 months. Freedom from reoperation was 96.7% with 73-month follow-up.Conclusions:Medium-term results were excellent. Original AVRec was feasible for the patients with AS. Long-term data will be presented in the future. (Circ J 2015; 79: 1504–1510)
Heart Failure
  • Fernanda Macedo de Oliveira Neves, Gdayllon Cavalcante Meneses, Nazare ...
    Type: ORIGINAL ARTICLE
    2015 Volume 79 Issue 7 Pages 1511-1519
    Published: June 25, 2015
    Released: June 25, 2015
    [Advance publication] Released: April 17, 2015
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    Background:Heart failure (HF) is a leading cause of hospitalization throughout the world, and the mortality rate remains elevated. HF is frequently complicated by acute kidney injury (AKI), worsening the patient’s prognosis. There have been no studies evaluating the role that endothelial glycocalyx damage plays in HF patients and its association with AKI and mortality.Methods and Results:We measured several endothelial biomarkers in 201 consecutive patients with acute decompensated HF (ADHF) during emergency department (ED) admission. In-hospital mortality, AKI development and 6-month mortality rates were assessed. ADHF patients with worsening renal function had higher levels of syndecan-1 but not those patients with stable chronic kidney disease. Syndecan-1 levels during ED admission were predictive for AKI during the hospital stay (AUC 0.741, P<0.001) and had an even better discriminatory capacity in more severe AKI (AUC 0.812, P<0.001). Additionally, after adjusting for several confounding factors, including biomarkers of endothelial function and endothelial cell activation, syndecan-1 remained associated with in-hospital mortality rates. On a Cox multivariate analysis regression, syndecan-1 was associated with 6-month mortality rates.Conclusions:The concentration of syndecan-1, a marker of glycocalyx damage measured during ED admission, is valuable in assessing the risk of developing AKI and in-hospital mortality. Its association with mortality is strong after 6-month follow-up. (Circ J 2015; 79: 1511–1519)
  • Yoichi Takaya, Fumiki Yoshihara, Hiroyuki Yokoyama, Hideaki Kanzaki, M ...
    Type: ORIGINAL ARTICLE
    Subject area: Heart Failure
    2015 Volume 79 Issue 7 Pages 1520-1525
    Published: June 25, 2015
    Released: June 25, 2015
    [Advance publication] Released: April 08, 2015
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    Background:Risk stratification of acute kidney injury (AKI) is important for acute decompensated heart failure (ADHF). The aim of this study was to determine whether clinical markers, such as the blood urea nitrogen/creatinine ratio (BUN/Cr) or BUN or creatinine values alone, stratify the risk of AKI for mortality.Methods and Results:In all, 371 consecutive ADHF patients were enrolled in the study. AKI was defined as serum creatinine ≥0.3 mg/dl or a 1.5-fold increase in serum creatinine levels within 48 h. During ADHF therapy, AKI occurred in 99 patients; 55 patients died during the 12-month follow-up period. Grouping patients according to AKI and a median BUN/Cr at admission of 22.1 (non-AKI+low BUN/Cr, non-AKI+high BUN/Cr, AKI+low BUN/Cr, and AKI+high BUN/Cr groups) revealed higher mortality in the AKI+high BUN/Cr group (log-rank test, P<0.001). Cox’s proportional hazard analysis revealed an association between AKI+high BUN/Cr and mortality, whereas the association with AKI+low BUN/Cr did not reach statistical significance. When patients were grouped according to AKI and median BUN or creatinine values at admission, AKI was associated with mortality, regardless of BUN or creatinine.Conclusions:The combination of AKI and elevated BUN/Cr, but not BUN or creatinine individually, is linked with an increased risk of mortality in ADHF patients, suggesting that the BUN/Cr is useful for risk stratification of AKI. (Circ J 2015; 79: 1520–1525)
  • Enrique Santas, Francisco Javier Chorro, Gema Miñana, José Méndez, Jai ...
    Type: ORIGINAL ARTICLE
    Subject area: Heart Failure
    2015 Volume 79 Issue 7 Pages 1526-1533
    Published: June 25, 2015
    Released: June 25, 2015
    [Advance publication] Released: April 09, 2015
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    Background:Tricuspid regurgitation (TR) is a common echocardiographic finding that has been related to adverse outcome under various clinical scenarios. Nevertheless, evidence supporting its prognostic value in heart failure (HF) is scarce, and, in most cases, contradictory. We evaluated the association of TR grade with 1-year all-cause mortality in acute HF (AHF).Methods and Results:We included 1,842 consecutive patients admitted for AHF. Mean age was 72.8±11.3 years, 51% were female and 45.5% had LVEF <50%. The severity of TR was graded in non-TR, mild (1), moderate (2), moderate-severe (3) and severe (4). At 1-year follow-up, 370 patients (20.1%) had died. In patients with LVEF ≥50%, a significant and positive association between TR severity and mortality was noted. Indeed, the HR for mortality for TR 3 and 4 vs. no TR/TR 1 were as follows: hazard ratios (HR), 1.68; 95% confidence intervals (95% CI): 1.08–2.60, P=0.02; and HR, 2.87; 95% CI: 1.61–5.09, P<0.001, respectively. In contrast, no association between TR grade and mortality (P=0.650) was observed in patients with LVEF <50% (P-value for interaction=0.033).Conclusions:A differential prognostic effect of TR severity on 1-year mortality was observed for LVEF HF status. The association was significant only in patients with LVEF ≥50%, with increasing mortality risk as TR became more severe. (Circ J 2015; 79: 1526–1533)
Imaging
  • Masaharu Kobayashi, Katsuyuki Hoshina, Sota Yamamoto, Youkou Nemoto, T ...
    Type: ORIGINAL ARTICLE
    Subject area: Imaging
    2015 Volume 79 Issue 7 Pages 1534-1541
    Published: June 25, 2015
    Released: June 25, 2015
    [Advance publication] Released: March 25, 2015
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    Background:Quantification of geometric changes of the stent graft (SG) in abdominal aortic aneurysm has been required for follow up of endovascular aneurysm repair (EVAR). The aim was to develop an image-based modeling system (V-Modeler) to investigate these changes over time.Methods and Results:V-Modeler was applied to investigate the migration of the SG. Three sets of computed tomography images were taken at 3 different times: (1) 5 days after the implantation; (2) 7 months later when the unilateral leg migrated upward; and (3) 10 months later when the limb had migrated into the common iliac aneurysm resulting in a type 1b endoleak. A spline function was used to represent the center lines of the SG to track its evolutional geometric changes in a three-dimensional manner. The characteristics of vascular geometry, as well as the SG geometry using geometric parameters such as length, curvature, torsion, angle of tangent vector (ATV), and migrated length, was evaluated. It was observed that the strong peak of the curvature in the distal area appeared, and a conversion of the torsion disappeared chronologically.Conclusions:The V-Modeler was developed, which not only can extract vascular geometry but also can identify geometric parameter, such as curvature, torsion, and ATV, to predict adverse events following EVAR. (Circ J 2015; 79: 1534–1541)
  • Takuma Tsuda, Hideki Ishii, Satoshi Ichimiya, Masaaki Kanashiro, Jyunj ...
    Type: ORIGINAL ARTICLE
    Subject area: Imaging
    2015 Volume 79 Issue 7 Pages 1542-1548
    Published: June 25, 2015
    Released: June 25, 2015
    [Advance publication] Released: March 27, 2015
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    Background:Until now, there have been few reports on the accuracy of in-stent restenosis (ISR) detection using high-definition computed tomography (HDCT). The purpose of this study was to assess ISR using HDCT with a new gemstone detector and to examine the diagnostic accuracy compared with invasive coronary angiography.Methods and Results:We evaluated 162 consecutive patients with 316 stents and the image quality (IQ) scores used to assess ISR, and analyzed whether stent strut thickness and diameter affected IQ score and assessability. In the 316 stents, 278 were diagnosed as assessable with HDCT (88.0%). IQ score for stent diameter ≥3 mm was significantly higher than that for stent diameter <3 mm, for stents with both thick struts ≥140 μm in thickness (mean IQ: 2.04±0.97 vs. 2.83±1.06, P<0.001) and thin struts <140 μm (mean IQ: 1.92±0.87 vs. 2.64±0.96, P=0.01). Assessability for stent diameter ≥3 mm was significantly higher than that for stent diameter <3 mm only for stents with thick struts (92.8% vs. 76.1%, P<0.001). Stent strut thickness, however, was not statistically significantly associated with either IQ score or assessability.Conclusions:In-stent lumens have high HDCT assessability, and HDCT is useful to evaluate thick-strut stents with diameter <3 mm. (Circ J 2015; 79: 1542–1548)
  • Kenichi Nakajima, Shinro Matsuo, Hiroshi Wakabayashi, Kunihiko Yokoyam ...
    Type: ORIGINAL ARTICLE
    Subject area: Imaging
    2015 Volume 79 Issue 7 Pages 1549-1556
    Published: June 25, 2015
    Released: June 25, 2015
    [Advance publication] Released: April 03, 2015
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    Background:The purpose of this study was to apply an artificial neural network (ANN) in patients with coronary artery disease (CAD) and to characterize its diagnostic ability compared with conventional visual and quantitative methods in myocardial perfusion imaging (MPI).Methods and Results:A total of 106 patients with CAD were studied with MPI, including multiple vessel disease (49%), history of myocardial infarction (27%) and coronary intervention (30%). The ANN detected abnormal areas with a probability of stress defect and ischemia. The consensus diagnosis based on expert interpretation and coronary stenosis was used as the gold standard. The left ventricular ANN value was higher in the stress-defect group than in the no-defect group (0.92±0.11 vs. 0.25±0.32, P<0.0001) and higher in the ischemia group than in the no-ischemia group (0.70±0.40 vs. 0.004±0.032, P<0.0001). Receiver-operating characteristics curve analysis showed comparable diagnostic accuracy between ANN and the scoring methods (0.971 vs. 0.980 for stress defect, and 0.882 vs. 0.937 for ischemia, both P=NS). The relationship between the ANN and defect scores was non-linear, with the ANN rapidly increased in ranges of summed stress score of 2–7 and summed defect score of 2–4.Conclusions:Although the diagnostic ability of ANN was similar to that of conventional scoring methods, the ANN could provide a different viewpoint for judging abnormality, and thus is a promising method for evaluating abnormality in MPI. (Circ J 2015; 79: 1549–1556)
Ischemic Heart Disease
  • Toyoharu Oba, Hideo Yasukawa, Takanobu Nagata, Sachiko Kyogoku, Tomoko ...
    Type: ORIGINAL ARTICLE
    Subject area: Ischemic Heart Disease
    2015 Volume 79 Issue 7 Pages 1557-1567
    Published: June 25, 2015
    Released: June 25, 2015
    [Advance publication] Released: March 31, 2015
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    Background:Remote ischemic preconditioning (RIPC) induced by transient limb ischemia is a powerful innate mechanism of cardioprotection against ischemia. Several described mechanisms explain how RIPC may act through neural pathways or humoral factors; however, the mechanistic pathway linking the remote organ to the heart has not yet been fully elucidated. This study aimed to investigate the mechanisms underlying the RIPC-induced production of Janus kinase (JAK)-signal transducer and activator of the transcription (STAT)-activating cytokines and cardioprotection by using mouse and human models of RIPC.Methods and Results:Screened circulating cardioprotective JAK-STAT-activating cytokines in mice unexpectedly revealed increased serum erythropoietin (EPO) levels after RIP induced by transient ischemia. In mice, RIPC rapidly upregulated EPO mRNA and its main transcriptional factor, hypoxia-inducible factor-1α (HIF1α), in the kidney. Laser Doppler blood flowmetry revealed a prompt reduction of renal blood flow (RBF) after RIPC. RIPC activated cardioprotective signaling pathways and the anti-apoptotic Bcl-xL pathway in the heart, and reduced infarct size. In mice, these effects were abolished by administration of an EPO-neutralizing antibody. Renal nerve denervation also abolished RIPC-induced RBF reduction, EPO production, and cardioprotection. In humans, transient limb ischemia of the upper arm reduced RBF and increased serum EPO levels.Conclusions:Based on the present data, we propose a novel RIPC mechanism in which inhibition of infarct size by RIPC is produced through the renal nerve-mediated reduction of RBF associated with activation of the HIF1α-EPO pathway. (Circ J 2015; 79: 1557–1567)
  • Francesco De Felice, Francesco Tomassini, Rosario Fiorilli, Andrea Gag ...
    Type: ORIGINAL ARTICLE
    Subject area: Ischemic Heart Disease
    2015 Volume 79 Issue 7 Pages 1568-1574
    Published: June 25, 2015
    Released: June 25, 2015
    [Advance publication] Released: April 24, 2015
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    Background:The effect of abciximab on survival in patients with ST-elevation myocardial infarction (STEMI) complicated by cardiogenic shock (CS) undergoing primary percutaneous coronary intervention (PCI) is not clear.Methods and Results:We evaluated outcome in 410 consecutive patients with STEMI and CS who underwent PCI treated without (n=123) or with (n=287) abciximab. The endpoint was survival at 1-year follow-up. The predictors of death at 1 year were also investigated. The groups with and without abciximab had similar survival at 1-year follow-up. Propensity score-adjusted Cox proportional hazards model identified age (adjusted hazard ratio [HR], 1.02; 95% confidence interval [95% CI]: 1.01–1.03, P=0.001), oro-tracheal intubation (HR, 1.49; 95% CI: 1.12–1.96, P=0.05), post-PCI TIMI flow grade 0–1 (HR, 2.08; 95% CI: 1.52–2.83, P=0.0001) but not abciximab use (HR, 1.08; 95% CI: 0.70–1.60, P=0.60) as independent predictors of death at 1-year follow-up. Cox adjusted 1-year survival rates were 42.8% and 51.6%, (P=0.56) in patients treated without vs. with abciximab, respectively.Conclusions:Patients with STEMI complicated by CS undergoing PCI treated with or without abciximab have similar 1-year survival rates; age, final TIMI 0–1 and oro-tracheal intubation are predictors of death. (Circ J 2015; 79: 1568–1574)
Myocardial Disease
  • Ga Yeon Lee, Hyung-Kwan Kim, Jin-Oh Choi, Sung-A. Chang, Jae K. Oh, Eu ...
    Type: ORIGINAL ARTICLE
    Subject area: Myocardial Disease
    2015 Volume 79 Issue 7 Pages 1575-1584
    Published: June 25, 2015
    Released: June 25, 2015
    [Advance publication] Released: April 07, 2015
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    Background:Relative apical sparing pattern of longitudinal strain (RapSP-LS) was suggested in advanced cardiac amyloidosis (CA). It is unclear whether it is present in less advanced CA.Methods and Results:Patients with presumptive diagnosis of CA and mean left ventricular wall thickness (LVWT) ≤14 mm were recruited. Apart from RapSP-LS visually identified, relative apical longitudinal strain index (RapLSI) was defined as [average apical LS/(average basal LS+average mid-ventricle LS)]. Among 119 patients included, 47 were finally diagnosed with CA. RapLSI was higher in the CA group compared to other causes of increased mean LVWT (P<0.001), but with a significant range of overlap noted. In contrast, RapSP-LS visually assessed was noted in most CA patients (31/47, 66.0%) except in those with preserved LV ejection fraction, normal LVWT, and mildly decreased global LS, suggesting least advanced CA. On multivariate analysis of the added diagnostic role of RapSP-LS or RapLSI on top of clinical, electrocardiographic, and conventional echocardiographic parameters, addition of RapLSI produced only borderline increase in area under the curve of the multivariate model (P=0.05), whereas addition of RapSP-LS significantly increased it (P<0.001).Conclusions:Visual identification of RapSP-LS is useful in terms of added diagnostic value compared with quantitative calculation of RapLSI. Its clinical application, however, should be used with caution in patients with less advanced CA. (Circ J 2015; 79: 1575–1584)
  • Makoto Orii, Toshio Imanishi, Ikuko Teraguchi, Tsuyoshi Nishiguchi, Ya ...
    Type: ORIGINAL ARTICLE
    Subject area: Myocardial Disease
    2015 Volume 79 Issue 7 Pages 1585-1592
    Published: June 25, 2015
    Released: June 25, 2015
    [Advance publication] Released: March 31, 2015
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    Background:We aimed to evaluate whether specific monocyte subsets could serve as surrogate markers of disease activity in cardiac sarcoidosis (CS) evaluated by 18F-fluoro-2-deoxyglucose positron emission tomography (18F-FDG PET).Methods and Results:We studied 28 patients with CS (8 men; mean age: 61±9 years) diagnosed according to consensus criteria. We divided the patients into 2 groups: known CS receiving corticosteroid therapy (Rx(+); n=13) and new-onset CS (Rx(−); n=15), and analyzed 3 distinct monocyte subsets (CD14+CD16, CD14++CD16+, and CD14+−CD16+). Monocyte subsets were also analyzed in 10 Rx(−) patients before and 12 weeks after starting corticosteroid therapy. Inflammatory activity was quantified by 18F-FDG PET using the coefficient of variation (COV) of the standardized uptake value (SUV). The proportion of CD14++CD16+monocytes in Rx(+) patients (10.8 [0.2–23.5] %) was significantly lower than in Rx(−) patients (23.0 [11.5–38.4] %, P=0.001). After corticosteroid therapy, the COV of the SUV was significantly improved from 0.32 [0.14–0.62] to 0.17 [0.04–0.43] (P=0.017). The proportion of CD14++16+monocytes showed a significant decrease from 22.2 [8.8–38.4] % to 8.4 [1.8–16.8] % (P=0.001). The decrease in the proportion of CD14++16+monocytes significantly correlated with the decrease in the COV of the SUV (r=0.495, P=0.027).Conclusions:CD14++16+monocytes are a possible surrogate marker of the therapeutic effect of corticosteroid therapy in CS. (Circ J 2015; 79: 1585–1592)
  • Toshiyuki Nagai, Nobutaka Nagano, Yasuo Sugano, Yasuhide Asaumi, Takes ...
    Type: ORIGINAL ARTICLE
    Subject area: Myocardial Disease
    2015 Volume 79 Issue 7 Pages 1593-1600
    Published: June 25, 2015
    Released: June 25, 2015
    [Advance publication] Released: April 16, 2015
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    Background:Cardiac involvement is the worst prognostic determinant in patients with sarcoidosis, but the long-term prognostic significance of corticosteroid therapy for cardiac sarcoidosis (CS) remains unclear.Methods and Results:We examined 83 consecutive patients diagnosed with CS. Patients were divided into 2 groups based on the presence or absence of corticosteroid therapy at diagnosis. Patients with corticosteroid therapy had lower age and higher rate of positive findings in the myocardium on gallium scintigraphy (Ga) at diagnosis than those without. LVEF, biomarkers, and use of cardiovascular medication were similar between the 2 groups. During the follow-up (7.6±4.4 years), corticosteroid therapy was associated with fewer long-term adverse events (overall, P=0.005; cardiac death, P=0.92; symptomatic arrhythmias, P=0.89; heart failure admission, P<0.0001) and a greater % increase in LVEF than those without (7.9±36.3% vs. –16.7±34.8%, P=0.03). On Cox proportional hazards modeling, corticosteroid therapy (HR, 0.41; 95% CI: 0.20–0.89) was an independent determinant of long-term adverse event-free survival, but age, sex, LVEF, and Ga findings were not.Conclusions:Corticosteroid therapy might have a beneficial effect on long-term clinical outcome in CS patients, particularly by reduction of heart failure admission and retarding the progression of LV systolic dysfunction. (Circ J 2015; 79: 1593–1600)
  • Nobutaka Nagano, Toshiyuki Nagai, Yasuo Sugano, Yoshiaki Morita, Yasuh ...
    Type: ORIGINAL ARTICLE
    Subject area: Myocardial Disease
    2015 Volume 79 Issue 7 Pages 1601-1608
    Published: June 25, 2015
    Released: June 25, 2015
    [Advance publication] Released: May 01, 2015
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    Background:Basal thinning of the interventricular septum (IVS) is an important diagnostic feature of cardiac sarcoidosis (CS), but its long-term prognostic significance remains unclear.Methods and Results:We examined 74 consecutive patients who were diagnosed with CS. Basal IVS thickness at a point located 10 mm from the aortic annulus was measured. IVS thickness at the left ventricular minor axis level (IVS) was also measured according to the recommended procedure of the American Society of Echocardiography. Patients were divided into 2 groups based on the presence or absence of basal IVS thinning, which was defined as basal IVS ≤4 mm and/or basal IVS/IVS ratio ≤0.6. Basal IVS thinning was observed in 21 patients and was associated with greater long-term adverse events during follow-up (5.1±2.5 years), although the baseline characteristics were comparable between groups (overall, P<0.01; all-cause death, P=0.53; symptomatic arrhythmias, P<0.01; heart failure admission, P=0.027). Multivariate analysis showed basal IVS thinning was an independent determinant of long-term adverse events (hazard ratio 2.86, 95% confidence interval 1.31–6.14) even after adjustment for existing prognostic variables.Conclusions:The presence of basal IVS thinning at the time of CS diagnosis was associated with poor long-term clinical outcomes, suggesting its prognostic significance in patients with CS. (Circ J 2015; 79: 1601–1608)
Pediatric Cardiology and Adult Congenital Heart Disease
  • Chun-Wei Lu, Jin-Chung Shih, Ssu-Yuan Chen, Hsin-Hui Chiu, Jou-Kou Wan ...
    Type: ORIGINAL ARTICLE
    Subject area: Pediatric Cardiology and Adult Congenital Heart Disease
    2015 Volume 79 Issue 7 Pages 1609-1617
    Published: June 25, 2015
    Released: June 25, 2015
    [Advance publication] Released: May 09, 2015
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    Background:Three risk estimation methods for predicting the cardiac outcomes of pregnancy in women with heart disease have been proposed. This study was designed to compare their prediction performance in an Asian cohort with congenital heart disease (CHD).Methods and Results:This study enrolled pregnant women with CHD who delivered their babies after the 20th gestational week between 1985 and 2011. Of 268 pregnancies in 190 women with CHD, 18 (6.7%) had cardiac complications. The incidence of maternal cardiac events among women with a CARPREG index of 0, 1 or 2 was 3.4%, 27.3% and 100%. The incidence was 2.7%, 8.6%, 11.1%, 40% and 17.6% for those with a ZAHARA score 0–0.5, 0.51–1.5, 1.51–2.5, 2.51–3.5 and >3.5. Among patients with a modified World Health Organization (WHO) classification I, II, III and IV, the incidence of maternal cardiac events was 0%, 4.0%, 12.2% and 25.7%. The c-statistic was 0.732 (95% confidence interval (CI): 0.589, 0.876; P<0.001) for the CARPREG score, 0.737 (95% CI: 0.611, 0.864; P=0.001) for the ZAHARA score and 0.827 (95% CI: 0.745, 0.909; P<0.001) for the WHO classification.Conclusions:All 3 risk estimation methods had good performance in predicting maternal cardiac outcomes; however, the modified WHO classification demonstrated superior discrimination and calibration. (Circ J 2015; 79: 1609–1617)
Peripheral Vascular Disease
  • Takuro Shirasu, Katsuyuki Hoshina, Satoshi Yamamoto, Kunihiro Shigemat ...
    Type: ORIGINAL ARTICLE
    Subject area: Peripheral Vascular Disease
    2015 Volume 79 Issue 7 Pages 1618-1623
    Published: June 25, 2015
    Released: June 25, 2015
    [Advance publication] Released: April 28, 2015
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    Background:Some patients with critical limb ischemia (CLI) lack symptoms of intermittent claudication (IC) before the onset of CLI. We studied the outcome of such patients, because this is currently unknown.Methods and Results:For retrospective exploratory analysis, we divided 225 patients (265 limbs) with CLI into 2 groups: 142 patients (172 limbs) without a history of IC (non-IC group) and 83 patients (93 limbs) with IC (IC group). We examined comorbid factors and found that a higher proportion of patients in the non-IC group failed to undergo arterial revascularization (49% vs. 20%, P<0.0001) due to progressed limb ischemia and infection. We then analyzed 140 patients (161 limbs) with revascularization. Patients in the non-IC group were more likely to have diabetes mellitus (P=0.03), hypoalbuminemia (P=0.02), advanced Rutherford’s classification (P=0.0007), worse ambulatory function (P=0.009), and longer postoperative stay (P=0.04). Amputation-free survival was lower in the non-IC group (P=0.005). On Cox regression anlaysis, hemodialysis (P=0.002), coronary artery disease (P=0.04), cerebrovascular disease (P=0.02), non-ambulatory status (P=0.02), and non-IC (P=0.01) were independent risk factors for lower amputation-free survival.Conclusions:Patients without IC before CLI onset have several unique features, and non-IC is an independent risk factor for poor outcome. (Circ J 2015; 79: 1618–1623)
Renal Disease
  • Yoshihiko Saito, Makoto Watanabe, Kazutaka Aonuma, Atsushi Hirayama, N ...
    Type: ORIGINAL ARTICLE
    Subject area: Renal Disease
    2015 Volume 79 Issue 7 Pages 1624-1630
    Published: June 25, 2015
    Released: June 25, 2015
    [Advance publication] Released: April 17, 2015
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    Background:The aim of this study was to investigate the incidence of contrast-induced nephropathy (CIN) according to renal function in patients with or without proteinuria after cardiac catheterization in Japan.Methods and Results:We conducted a multicenter prospective observational study involving 27 hospitals from all over Japan, which enrolled 906 patients with cardiac catheterization. CIN was defined as increase in serum creatinine ≥0.5 mg/dl or ≥25% from baseline between 48 and 72 h after exposure to contrast. The incidence of CIN in patients with estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m2was significantly higher than that in patients with eGFR ≥60 ml/min/1.73 m2. In patients without proteinuria, the incidence of CIN did not increase as eGFR decreased, but such a trend was observed in patients with proteinuria. Proteinuria was highly significantly associated with CIN in patients with eGFR 30–44 ml/min/1.73 m2(OR, 12.1; 95% CI: 2.81–82.8; P=0.0006) and eGFR <30 ml/min/1.73 m2(OR, 17.4; 95% CI: 3.32–321; P=0.0001). On multivariate logistic regression analysis, proteinuria (OR, 4.09; 95% CI: 1.66–10.0), eGFR (OR, 1.02; 95% CI: 1.00–1.04), contrast volume/eGFR (OR, 1.31; 95% CI: 1.04–1.65), and Ca antagonist use (OR, 3.79; 95% CI: 1.52–10.8) were significant predictors of CIN.Conclusions:Proteinuria and reduced eGFR are independent risk factors for CIN after cardiac catheterization. (Circ J 2015; 79: 1624–1630)
Valvular Heart Disease
  • Kenjiro Sato, Yasuhiko Sakata, Masanobu Miura, Soichiro Tadaki, Ryoich ...
    Type: ORIGINAL ARTICLE
    Subject area: Valvular Heart Disease
    2015 Volume 79 Issue 7 Pages 1631-1638
    Published: June 25, 2015
    Released: June 25, 2015
    [Advance publication] Released: May 01, 2015
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    Background:The risk of patients with aortic stenosis (AS) should be stratified not only by AS severity but also by comorbidities.Methods and Results:We aimed to develop a risk score for mortality in 412 patients with AS (pressure gradient ≥30 mmHg, mean age 74.9 years, male 52.4%) in the CHART-2 Study (n=10,219). During a 3-year follow-up, 73 (17.7%) patients died. Crude 3-year mortality of patients in New York Heart Association (NYHA) classes I, II, and III/IV was 9.5%, 16.5%, and 49.7%, respectively (P<0.001). Stepwise Cox regression analysis showed that the combination of 7 factors was the best model to predict the mortality of AS patients, who were scored according to their hazard ratios, including NYHA class III–IV (score 6), male sex (3), serum albumin level ≤4 g/dl (2), aortic peak flow ≥4.5 m/s (2), age ≥75 years (2), chronic kidney disease (2), and anemia (1). Receiver-operating characteristic analysis showed excellent association between the sum of the scores and 3-year mortality (area under the curve, 0.78). The multivariate Cox proportional hazard model demonstrated that the present risk score also well stratified the mortality risk.Conclusions:The present study demonstrates that, in addition to the classical prognostic factors related to symptoms and AS severity, various comorbidities are associated with mortality. Thus, the present comprehensive risk score may be useful for risk stratification of AS patients. (Circ J 2015; 79: 1631–1638)
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