Although the global prevalence of both the overweight and obese is on the rise, there are variations among regions or countries, and sexes. Approximately half or more than half of the population are overweight/obese defined as body mass index ≥25 kg/m²in the Americas (61.1%), Europe (54.8%), and Eastern Mediterranean (46.0%) according to the World Health Organization, while a much lower prevalence is observed in Africa (26.9%), South-East Asia (13.7%), and the Western Pacific (25.4%). Females are more likely to be overweight/obese in the Eastern Mediterranean, Africa, South-East Asia and the majority of countries in the Americas and Western Pacific but not in the most of the countries in Europe. These region-sex-ethnicity differences in prevalence may be a clue to the causes of the obesity epidemic. Epidemiological studies done in the USA, Europe, and Asia found that higher BMI was significantly associated with increased incidence of coronary artery disease (CAD) and ischemic stroke, but the association with hemorrhagic stroke incidence was not always consistent. The association of BMI with CAD and ischemic stroke was generally independent of known mediators, which would indicate the importance of controlling or preventing overweight/obesity for the prevention of cardiovascular disease. (Circ J 2014; 78: 2807–2818)

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Buerger’s disease (thromboangiitis obliterans) is considered to be a nonatherosclerotic, inflammatory, and vaso-occlusive disease, although the details of the mechanisms of pathogenesis remain unknown. The occurrence of the disease is strongly related to tobacco abuse and its progression is closely linked to continued smoking. The purpose of this review article is to demonstrate the pathological characteristics of arteries affected with Buerger’s disease from a possible immunoreactive point of view. In addition, we present the mechanisms for preserving the architecture of the arterial wall in affected vasculatures. Thereafter, we discuss the possibility that the pathogenesis of Buerger’s disease is a type of endarteritis obliterans, deeply connected to the Notch pathway, distinct from arteriosclerosis obliterans and other vasculitides. (Circ J 2014; 78: 2819–2826)

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Congenital long QT syndrome (LQTS) is an inherited arrhythmia syndrome characterized by a prolonged QT interval on the 12-lead ECG, torsades de pointes and a higher chance of sudden cardiac death. LQTS segregates in a Mendelian fashion, which includes Romano-Ward syndrome with an autosomal dominant pattern as well as a rare autosomal recessive pattern (Jervell and Lange-Nielsen syndrome). Since 1957 when Jervell and Lange-Nielsen reported the first familial LQTS with congenital deafness, progress in understanding the genetic and electrophysiological mechanisms of LQTS has tremendously improved diagnostic methods and treatments. In the meantime, it has become evident that LQTS may not always be explained by a single gene mutation, but seems to follow a more complex genetic model intertwined with genetic common polymorphisms that have a mild to moderate effect on disease expression. In this review, we summarize the characteristics of LQTS (mainly LQT1–3) and briefly describe the most recent advances in LQTS clinical diagnostics as well as genetics. (Circ J 2014; 78: 2827–2833)

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Background:The clinical role of atrial fibrillation/atrial flutter (AF-AFl) and variables predicting these arrhythmias are not well defined in patients with arrhythmogenic right ventricular dysplasia (ARVD). We hypothesized that transthoracic echocardiography (TTE) and 12-lead electrocardiography (ECG) would be helpful in predicting AF-AFl in these patients.Methods and Results:ECGs and TTEs of 90 patients diagnosed with definite or borderline ARVD (2010 Task Force Criteria) were analyzed. Data were compared in (1) patients with AF-AFl and (2) all other patients. A total of 18 (20%) patients experienced AF-AFl during a median follow-up of 5.8 years (interquartile range 2.0–10.4). Kaplan-Meier analysis revealed reduced times to AF-AFl among patients with echocardiographic RV fractional area change <27% (P<0.001), left atrial diameter ≥24.4 mm/m²(parasternal long-axis, P=0.001), and right atrial short-axis diameter ≥22.1 mm/m²(apical 4-chamber view, P=0.05). From all ECG variables, P mitrale conferred the highest hazard ratio (3.37, 95% confidence interval 0.92–12.36, P=0.067). Five patients with AF-AFl experienced inappropriate implantable cardioverter-defibrillator (ICD) shocks compared with 4 without AF-AFl (36% vs. 9%, P=0.03). AF-AFl was more prevalent in heart-transplant patients and those who died of cardiac causes (56% vs. 16%, P=0.014).Conclusions:AF-AFl is associated with inappropriate ICD shocks, heart transplantation, and cardiac death in patients with ARVD. Evidence of reduced RV function and atrial dilation helps to identify the ARVD patients at increased risk for AF-AFl. (Circ J 2014; 78: 2854–2861)

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Background:Active fixation pacing leads with silicon cylinder tips have been used for their safety and flexibility. Measurement of baseline sensing/pacing characteristics before fixation of helix helps to identify the optimal pacing site, but we encountered difficulties in making these measurements despite multiple attempts with the model LPA 1200M lead. To identify the cause and overcome this complication, we compared 4 different retractable active fixation lead models, which enabled baseline sensing/pacing measurements before extension of helix.Methods and Results:We immersed 4 different lead tips and rings in a 0.18% saline solution, and measured the lead impedance before and after flushing of air bubble visible inside the lead tip. Before evacuation of the air bubble, the impedance of the model LPA 1200M lead was >4,000 Ω in 8 out of 10 measurements, although that of the other leads was within the measurable range. After evacuation of the air bubble, the lead impedance returned to within the measurable range. There was no prominent change in the impedance of the metal cylinder tip lead.Conclusions:Air bubbles may interfere with the measurement of baseline sensing/pacing characteristics before active fixation of pacing leads with cylindrical silicon tips. In the case of high impedance beyond the measurable range before extension of helix, the measurement should be repeated after fixation into the myocardium before suspecting lead dysfunction. (Circ J 2014; 78: 2862–2866)

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Background:Extracorporeal membrane oxygenation (ECMO) provides a rescue for children with severe cardiac failure. It has previously been shown that triiodothyronine (T3) improves cardiac function by modulating pyruvate oxidation during weaning. This study focused on fatty acid (FA) metabolism modulated by T3 for weaning from ECMO after cardiac injury.Methods and Results:Nineteen immature piglets (9.1–15.3 kg) were separated into 3 groups with ECMO (6.5 h) and wean: normal circulation (Group-C); transient coronary occlusion (10 min) for ischemia-reperfusion (IR) followed by ECMO (Group-IR); and IR with T3 supplementation (Group-IR-T3). 13-Carbon (¹³C)-labeled lactate, medium-chain and long-chain FAs, was infused as oxidative substrates. Substrate fractional contribution (FC) to the citric acid cycle was analyzed by¹³C-nuclear magnetic resonance. ECMO depressed circulating T3 levels to 40% of the baseline at 4 h and were restored in Group-IR-T3. Group-IR decreased cardiac power, which was not fully restorable and 2 pigs were lost because of weaning failure. Group-IR also depressed FC-lactate, while the excellent contractile function and energy efficiency in Group-IR-T3 occurred along with a marked FC-lactate increase and [adenosine triphosphate]/[adenosine diphosphate] without either decreasing FC-FAs or elevating myocardial oxygen consumption over Group-C or -IR.Conclusions:T3 releases inhibition of lactate oxidation following IR injury without impairing FA oxidation. These findings indicate that T3 depression during ECMO is maladaptive, and that restoring levels improves metabolic flux and enhances contractile function during weaning. (Circ J 2014; 78: 2867–2875)

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Background:Right mini-thoracotomy and partial sternotomy are widely recognized as effective approaches in minimally invasive aortic valve replacement (AVR). The aim of this study was to evaluate the objective benefits of the respective approaches compared to the conventional approach.Methods and Results:A retrospective analysis was performed in 282 consecutive patients who underwent isolated and initial AVR at a single cardiovascular institute between May 2007 and December 2012. Mini-thoracotomy and partial sternotomy were performed in 62 (22%) and in 26 patients (9%), respectively. Propensity score matching produced 36 (mini-thoracotomy vs. full sternotomy) and 24 (partial sternotomy vs. full sternotomy) well-matched pairs. Compared to the conventional approach, mini-thoracotomy was associated with significantly shorter operative time (235±35 min vs. 272±73 min; P=0.009), lower prevalence of blood transfusion (42%, 15/36 vs. 67%, 24/36; P=0.025), and significantly shorter intensive care unit and postoperative hospital stay (1.4±0.8 days vs. 2.2±1.1 days, P=0.001; and 13.3±6.5 days vs. 21.5±10.3 days, P=0.001; respectively). There were no significant differences in operative and postoperative data between the partial sternotomy and full sternotomy groups.Conclusions:The objective benefits of right mini-thoracotomy included early rehabilitation and lower prevalence of blood transfusion. Significant advantages of partial sternotomy were not found. (Circ J 2014; 78: 2876–2881)

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Background:The timing of ventricular assist device (VAD) implantation is always a matter of debate, especially when a patient is referred from a non-VAD institute. We focused on objective noninvasive parameters at the time of admission to a VAD implant center and analyzed the factors predicting the necessity of early VAD.Methods and Results:We retrospectively analyzed advanced heart failure (HF) patients referred since January 2011, including patients less than 65 years old. They all had a history of hospitalization for HF management in non-VAD institutes within 1 month before referral. We excluded patients transferred with mechanical circulatory support. We enrolled 46 patients (40 males, 39.8±13.4 years old). Among them, 26 patients had a VAD implanted or died within 120 days. By multivariable logistic analysis using admission parameters, systolic blood pressure (BP) <93 mmHg [odds ratio (OR) 13.335], hemoglobin <12.7 g/dl (OR 12.175) and serum total cholesterol <144 mg/dl (OR 8.096) were significant predictors of early VAD requirement. We constructed a scoring system according to the ORs, and the area under the receiver-operating characteristic curve was 0.913.Conclusions:Low BP, low serum cholesterol and anemia on admission predict early VAD in advanced HF patients who have been treated in non-VAD institutes. Such patients should be promptly referred to a VAD implant center. (Circ J 2014; 78: 2882–2889)

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Background:Microalbuminuria, traditionally defined as urinary albumin/creatinine ratio (UACR) ≥30 mg/g, is a risk factor for mortality even in patients with preserved glomerular filtration rate (GFR). The prognostic impact of subclinical microalbuminuria, however, remains unknown in patients with chronic heart failure (CHF).Methods and Results:In the Chronic Heart Failure Analysis and Registry in the Tohoku District 2 Study, we enrolled 2,039 consecutive symptomatic CHF patients (median age, 67.4 years; 68.9% male) after excluding those on hemodialysis. On classification and regression tree analysis, UACR=10.2 mg/g and 27.4 mg/g were identified as the first and second discriminating points to stratify the risk for composite of death, acute myocardial infarction, HF admission and stroke, therefore subclinical microalbuminuria was defined as UACR ≥10.2 and <27.4 mg/g. There were 506 composite endpoints (24.8%) during the median follow-up of 2.69 years. On Kaplan-Meier analysis and multivariate Cox modeling, subclinical microalbuminuria was significantly associated with increased composite endpoints with hazard ratios of 1.90 (P<0.001) and 2.29 (P<0.001) in patients with preserved (>60 ml·min^–1·1.73 m^–2, n=1,129) or mildly reduced eGFR (30–59.9 ml·min^–1·1.73 m^–2, n=789), respectively. In patients with severely reduced GFR (eGFR <30 ml·min^–1·1.73 m^–2, n=121), >80% had microalbuminuria or macroalbuminuria, and only 9.1% were free from any composite endpoints.Conclusions:Subclinical microalbuminuria was associated with increased risk of cardiovascular events in CHF patients with mildly reduced or preserved renal function. (Circ J 2014; 78: 2890–2898)

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Background:The effect of adiposity on response to cardiac resynchronization therapy (CRT) and long-term outcome in patients undergoing CRT has not been previously reported. This study assessed the impact of baseline body mass index (BMI) on cardiac reverse remodeling and prognosis following CRT.Methods and Results:A total of 247 CRT patients were included and divided into 4 groups according to baseline BMI. During 6-month follow-up, overweight and obese patients (BMI, 24–28 kg/m², ≥28 kg/m², respectively) were inclined to have better clinical and echocardiographic improvements (P<0.05) as well as higher response rate (P<0.001) than underweight and normal weight patients (BMI, <18.5 kg/m², 18.5–24 kg/m², respectively). During long-term follow-up, overweight and obese patients had lower all-cause mortality (P=0.015) and combined endpoint of death or HF hospitalizations (P=0.001) than underweight and normal weight patients. Compared with normal weight patients, underweight patients had a 2.29-fold increase in risk of combined endpoint events whereas overweight and obese patients had a reduction in the risk of death (66% and 58%, respectively) and combined endpoint events (52% and 38%, respectively).Conclusions:Patients with obesity and overweight derived more benefit from CRT. Higher BMI was independently associated with better clinical outcome in CRT patients. (Circ J 2014; 78: 2899–2907)

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Background:Melatonin decreases night-time blood pressure (BP) by increasing nitric oxide (NO) in endothelial cells. Whether serum asymmetric dimethylarginine (ADMA), a major endogenous competitive inhibitor of endothelial NO synthase, attenuates the association of melatonin with night-time BP and dipping in humans is unclear.Methods and Results:In this cross-sectional study of 852 community-based elderly individuals, serum ADMA, overnight urinary 6-sulfatoxymelatonin excretion (UME), and ambulatory BP were measured. Mean ADMA was 0.46±0.06 μmol/L. In the low-ADMA group (n=451), crude OR for nocturnal hypertension (NH) and non-dipper significantly decreased with a quartile increase in UME (P=0.023 and 0.001, respectively), but these associations were not observed in the high-ADMA group (n=401). Higher UME was significantly and inversely associated with adjusted OR for NH and non-dipper in the low-ADMA group (Q1, 1.00 and 1.00; Q2, 0.92 and 0.74; Q3, 0.57 and 0.51; Q4, 0.48 and 0.40; P=0.004 and 0.002, respectively) but not in the high-ADMA group (P=0.75 and 0.12, respectively). These association trends were also observed on continuous variable analysis (low ADMA, P=0.031 and 0.003; high ADMA, P=0.52 and 0.13; respectively).Conclusions:ADMA attenuates the association of endogenous melatonin with night-time BP and dipping in the general elderly population. (Circ J 2014; 78: 2908–2914)

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Background:It has been previously demonstrated that extracorporeal low-energy shock-wave (SW) therapy ameliorates left ventricular (LV) remodeling through enhanced angiogenesis after acute myocardial infarction (AMI) in pigs in vivo. However, it remains to be examined whether SW therapy also exerts anti-inflammatory effects on AMI.Methods and Results:AMI was created by ligating the proximal left anterior descending coronary artery in rats. They were randomly assigned to 2 groups: with (SW group) or without (control group) SW therapy (0.1 mJ/mm², 200 shots, 1 Hz to the whole heart at 1, 3 and 5 days after AMI). Four weeks after AMI, SW therapy significantly ameliorated LV remodeling and fibrosis. Histological examinations showed that SW therapy significantly suppressed the infiltration of neutrophils and macrophages at days 3 and 6, in addition to enhanced capillary density in the border area. Molecular examinations demonstrated that SW therapy enhanced the expression of endothelial nitric oxide synthase and suppressed the infiltration of transforming growth factor-β1-positive cells early after AMI. SW therapy also upregulated anti-inflammatory cytokines and downregulated pro-inflammatory cytokines in general.Conclusions:These results suggest that low-energy SW therapy suppressed post-MI LV remodeling in rats in vivo, which was associated with anti-inflammatory effects in addition to its angiogenic effects, and demonstrated a novel aspect of the therapy for AMI. (Circ J 2014; 78: 2915–2925)

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Background:Prasugrel is being developed in Japan as an antiplatelet therapy for use during percutaneous coronary intervention (PCI). Up to 70% of Japanese patients with coronary artery disease undergo elective PCI. The PRASugrel For Japanese PatIenTs with Coronary Artery Diseases Undergoing Elective PCI (PRASFIT-Elective) study investigated the efficacy and safety of different prasugrel dosing regimens in Japanese patients undergoing elective PCI.Methods and Results:A total of 742 patients scheduled for elective coronary artery stenting were enrolled. Patients were randomized to receive either prasugrel (20/3.75 mg, loading/maintenance dose) or clopidogrel (300/75 mg) in a double-blind manner. Endpoints, including cardiovascular events and bleeding, were assessed at weeks 24–48. The incidence rate of major cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal ischemic stroke) up to week 24 was 4.1% (15/370) and 6.7% (25/372) in the prasugrel and clopidogrel groups, respectively. Other incidence rates were: non-coronary artery bypass graft-related major bleeding, 0% and 2.2%; major/minor bleeding, 1.6% and 3.0%; and all bleeding events, 38.1% and 34.4% in the prasugrel and clopidogrel groups, respectively. The incidence rate of bleeding-related adverse events was similar in both groups, being 40.8% and 35.8% in the prasugrel and clopidogrel groups, respectively.Conclusions:These results support the risk-benefit profile of an adjusted dosing regimen of prasugrel in Japanese patients undergoing PCI. Larger studies are required to confirm these findings. (Circ J 2014; 78: 2926–2934)

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Background:The protective function of regulatory T cells (T_reg) has been identified in experimental atherosclerosis, but the contribution of T_regto the pathogenesis of human coronary artery disease (CAD) remains poorly understood. We investigated T_regand regulatory T-cell/effector T-cell (T_reg/T_eff) ratio in peripheral blood samples from CAD patients using a new strategy for precise identification of T_reg.Methods and Results:Peripheral blood samples were collected from 73 stable CAD patients (55 middle-aged CAD patients and 18 old CAD patients) and 64 controls (47 middle-aged controls and 17 young controls). CD3⁺CD4⁺FoxP3⁺T cells were divided into 3 fractions: CD45RA⁺FoxP3^lowresting T_reg(Fr1), CD45RA^–FoxP3^highactivated T_reg(Fr2), and CD45RA^–FoxP3^lownon-T_reg(Fr3). CAD patients had lower percentages of Fr1 and Fr2 and higher percentages of Fr3 and CD45RA^–Foxp3^–T_eff(Fr4+5) within the CD3⁺CD4⁺T-cell population compared to age-matched controls. T_reg/T_effratio (Fr1+2/Fr3+4+5) in CAD patients was also markedly lower than in controls (middle-aged control, 0.17±0.09 vs. middle-aged CAD, 0.10±0.05; P<0.001). The percentage of CD4⁺CD28^nullT cells within the CD4⁺T-cell population was negatively correlated with T_reg/T_effratio, excluding CD4⁺CD28^nullT cells <0.3% (r=–0.27, P<0.05). High-sensitivity C-reactive protein was also negatively correlated with T_reg/T_effratio (r=–0.22, P<0.05).Conclusions:CAD patients had reduced T_regand T_reg/T_effratio compared to healthy controls. The present findings may be helpful when developing immunotherapy for the prevention of CAD. (Circ J 2014; 78: 2935–2941)

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Background:QT hysteresis phenomenon exists in healthy subjects, and is more exaggerated in patients with coronary artery disease (CAD) and long QT syndrome. The purpose of this study was to establish an appropriate method to evaluate the magnitude of QT hysteresis, and assess the value of QT hysteresis index in the treadmill exercise test (TET) in predicting CAD.Methods and Results:A total of 138 subjects with suspected CAD and referred for TET and selective coronary angiography (SCA) were divided into positive (n=77) and negative (n=61) SCA groups. Dynamic ECG were recorded during TET. QT/RR curves were constructed and QTp (Q-T_peak) and QTe (Q-T_end) hysteresis indices were calculated for each subject. SYNTAX score in the positive SCA group was determined. The QTp and QTe hysteresis indices in the positive SCA group were significantly higher than in the negative SCA group. The combination of QTe hysteresis index and conventional TET criteria had the highest sensitivity and negative predictive value according to receiver operating characteristic curve, and was an independent predictor on multivariate logistic regression. QT hysteresis indices significantly correlated with SYNTAX score in the positive SCA group.Conclusions:QTe hysteresis index enhances the specificity of predicting CAD in TET. It improves the diagnostic value of TET for CAD significantly when combined with conventional criteria and is associated with the severity of CAD. (Circ J 2014; 78: 2942–2949)

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Background:The purpose of the present study was to confirm the diagnostic accuracy of Global Registry of Acute Coronary Events (GRACE) risk score 1.0 (GRACE 1.0) and updated GRACE 1.0 (GRACE 2.0) for in-hospital and 360-day mortality in ST-elevation myocardial infarction (STEMI) in Japanese patients. GRACE 1.0 and GRACE 2.0 are the established predictive models in acute coronary syndrome, but their application to Japanese patients has not been fully verified.Methods and Results:The present study retrospectively analyzed 412 consecutive STEMI patients who had undergone primary percutaneous coronary intervention from January 2006 to September 2011. All causes of death during hospitalization were examined to confirm the diagnostic accuracy of GRACE 1.0 on receiver operating characteristic (ROC) analysis. Similarly, all causes of death during the 360 days after hospitalization were analyzed to confirm the diagnostic accuracy of GRACE 2.0. The average GRACE 1.0 score was 175.8±50.9. In-hospital and 360-day mortality were 13.1% and 15.5%, respectively. Area under the ROC curve, which describes the diagnostic accuracy of the GRACE 1.0 predicted in-hospital mortality and the GRACE 2.0 predicted 360-day mortality, was as high as 0.95 and 0.92, respectively.Conclusions:Both GRACE 1.0 and GRACE 2.0 had a high diagnostic accuracy for prediction of in-hospital and 360-day mortality in Japanese STEMI patients. (Circ J 2014; 78: 2950–2954)

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Background:Smoking cessation reduces the risk of cardiovascular disease (CVD) and improves clinical outcomes in public health. We studied the effect of smoking cessation on high-density lipoprotein (HDL) functionality.Methods and Results:We randomly treated 32 smokers with varenicline or a transdermal nicotine patch as part of a 12-week smoking cessation program (The VN-SEESAW Study). The plasma lipid profiles, plasma and HDL malondialdehyde (MDA) levels, HDL subfractions as analyzed by capillary isotachophoresis, cholesterol efflux capacity, and antiinflammatory activity of HDL were measured before and after the anti-smoking intervention. After smoking cessation, HDL-C, apoA-I levels and HDL subfractions were not significantly different from the respective baseline values. However, cholesterol efflux capacity and the HDL inflammatory index (HII) were significantly improved after smoking cessation. The changes in both parameters (%∆ cholesterol efflux capacity and ∆HII) were also significantly improved in the successful smoking cessation group compared with the unsuccessful group. The changes in cholesterol efflux capacity and HII also correlated with those in end-expiratory CO concentration and MDA in HDL, respectively.Conclusions:Our findings indicate that smoking cessation leads to improved HDL functionality, increased cholesterol efflux capacity and decreased HII, without changing HDL-C or apoA-I levels or HDL subfractions. This may be one of the mechanisms by which smoking cessation improves the risk of CVD. (Circ J 2014; 78: 2955–2962)

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Background:Mutations in at least 30 genes have been linked to hypertrophic cardiomyopathy (HCM). Due to the large size of the main HCM genes, Sanger sequencing is labor intensive and expensive. The purpose was to develop a next-generation sequencing (NGS) procedure for the main HCM genes.Methods and Results:Multiplex amplification of the coding exons ofMYH7,MYBPC3,TNNT2,TNNI3,ACTC1,TNNC1,MYL2,MYL3, andTPM1was designated, followed by NGS with the Ion Torrent PGM (Life Technologies). A total of 8 pools containing DNA from HCM patients were sequenced in a 2-step approach. First, a total of 60 patients (validation cohort) underwent both PGM and Sanger sequencing for the 9 genes. No false-negative variants were found on NGS (100% sensitivity), and a specificity of 97% and 80% was achieved for single-nucleotide and insertion/deletion variants, respectively. Second, the PGM was used to search for mutations in a total of 76 cases not previously studied (discovery cohort). A total of 19 putative mutations were identified in the discovery pools, which were confirmed and assigned to specific patients on Sanger sequencing.Conclusions:An NGS procedure has been developed for the main sarcomeric genes that would facilitate the screening of large cohorts of patients. In addition, this procedure would facilitate the uncovering of rare gene variants on a population scale. (Circ J 2014; 78: 2963–2971)

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Background:The importance of ventricular pacing site in pediatric pacemaker therapy has gradually become recognized. We reviewed our experience with a left ventricular (LV)-prioritized pacing strategy.Methods and Results:Between 2000 and 2012, 60 patients underwent 76 permanent pacemaker implantations. Eight of the 29 reoperations involved ventricular lead repositioning for pacing-induced ventricular dysfunction. Freedom from ventricular lead failure was 96.3%, 86.8%, and 81.0% at 1, 3, and 5 years, respectively. The independent predictors of ventricular lead failure were age (P=0.026) and peak minimal energy threshold within 6 months (P=0.035). At the measured points, redo bipolar, steroid-eluting leads had significantly better pacing properties than did redo non-steroid-eluting, screw-in leads (P=0.0009–0.03). Ventricular lead repositioning was effective in the 5 patients with systemic LV pacing, whereas its efficacy was inconsistent in patients with single-ventricle or systemic right ventricular (RV) pacing. At a median follow-up of 59 months, the 28 patients with LV pacing had preserved ventricular function (LV fraction shortening, 0.34±0.09).Conclusions:The outcome of this LV-prioritized pacing strategy in pediatric patients was excellent, demonstrating preserved ventricular function. Bipolar, steroid-eluting, epicardial pacing leads achieved good pacing properties, even in reoperation patients. In children with systemic LV and RV pacing-induced ventricular dysfunction, a conversion to LV apex pacing was an attractive alternative to cardiac resynchronization therapy. (Circ J 2014; 78: 2972–2978)

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Background:Impairment of coronary flow reserve (CFR) has been generally demonstrated in diabetic patients and animals with microvascular complications but without obvious obstructive coronary atherosclerosis. There have been few studies investigating CFR in cases of relatively well-controlled therapy. The purpose of this study is to evaluate the effect of treatment with a Sphingosine-1-phosphate (S1P) receptor potent agonist, FTY720, on early diabetic rats in terms of CFR.Methods and Results:Male Sprague-Dawley (SD) rats were divided into 3 groups: (1) streptozotocin-uninjected rats (control rats); (2) streptozotocin-injected hyperglycemic rats (diabetic group); and (3) FTY720-fed and streptozotocin-injected hyperglycemic rats. FTY720 (1.25 mg/kg per day orally) was administrated for 9 weeks in SD rats (from 6 weeks old to 15 weeks old). CFR was evaluated by ¹³NH₃-positron emission tomography. No obvious pathological changes of macrovascular atherosclerosis were observed in each group. Diabetic rats had impaired CFR compared with the control group (1.39±0.26 vs. 1.94±0.24, P<0.05). Treatment with FTY720 for 9 weeks attenuated the heart histological changes and improved CFR in 32% of diabetic rats (1.84±0.36 vs. 1.39±0.26, P<0.05).Conclusions:In summary, long-term therapy with the Sphingosine-1-phosphate receptor agonist, FTY720, improved CFR by attenuating the heart histological changes, and it might have a beneficial effect on coronary microvascular function in diabetic rats. (Circ J 2014; 78: 2979–2986)

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Background:Wearable cardioverter-defibrillators (WCD) have been available in Japan since April 2014, but their application is still limited.Methods and Results:We report 9 patients with a WCD applied between April and September 2014. All patients were at high risk of life-threatening ventricular arrhythmias. During WCD use, 1 patient had sustained ventricular tachycardia and successful shock delivery; 6 (67%) subsequently underwent implantable cardioverter-defibrillator (ICD) therapy, while 2 had no requirement because of reduced risk, and 1 died of heart failure during WCD use.Conclusions:WCD is useful during acute-phase care of high-risk patients, and may help to avoid unnecessary ICD implantation. (Circ J 2014; 78: 2987–2989)

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