Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a rare, inherited cardiomyopathy characterized by ventricular arrhythmias, sudden cardiac death, and right ventricular dysfunction. Since the first major description of this disease, much has been learned about ARVD/C. One of the main breakthroughs was the discovery that mutations in desmosomal proteins are the most frequent genetic basis of ARVD/C. Today, genetic testing plays an important role in both the diagnosis of ARVD/C and cascade family screening. Much has also been learned concerning the optimal approaches to diagnosis. The 2010 Task Force Diagnostic criteria for ARVD/C represent the standard for diagnosis today. We have also learned much about the importance of proband status and the 24-h PVC count to assess sudden death risk, and the importance of exercise both in the development of ARVD/C in susceptible individuals and in defining the course of the disease. From a treatment perspective, placement of ICDs in specific subsets of patients with ARVD/C who are at increased risk of sudden death is important. The techniques of VT ablation have also evolved over time and are valuable components of our management strategies for the ARVD/C patient today. This review will provide an update on ARVD/C, with specific attention to some of the contributions to this field reported by the Johns Hopkins ARVD/C Program. (Circ J 2015; 79: 901–913)

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Atrial fibrillation (AF) is the most commonly observed rhythm disorder in clinical practice. It is associated with a high risk of thromboembolic stroke and increased cardiovascular mortality. Vitamin K antagonists (VKAs), the only oral anticoagulants used for thromboembolic prophylaxis in AF patients over the past 60 years, have been effective in reducing thromboembolic stroke, compared with placebo and aspirin, in this group of patients. However, VKAs have a very narrow therapeutic window, so regular monitoring of the therapeutic effect is obligatory for their use. The need for regular assessment of blood anticoagulation often causes dissatisfaction and reduces patients’ quality of life. Non-VKA oral anticoagulants (NOACs), such as dabigatran, a direct thrombin inhibitor, and 3 factor Xa inhibitors, namely rivaroxaban, apixaban, and edoxaban, have been developed in recent years and have increased the armamentarium available to the physician for thromboprophylaxis in non-valvular AF (NVAF) patients. This review describes the characteristics of NOACs, analyzing aspects related to their use in the thromboprophylaxis of NVAF patients. It also discusses how to optimize NOAC therapy in specific clinical conditions, such as renal or liver impairment, and concomitant assumption of drugs potentially interfering with NOACs action. Finally, it focuses on NOAC-related bleeding management in the setting of non-cardiac surgery or radiofrequency catheter ablation of NVAF. (Circ J 2015; 79: 914–923)

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Atherosclerosis is a chronic inflammatory disease of the arterial wall that is influenced by several risk factors, including hyperlipidemia and hypertension. Autoimmune diseases substantially increase the risk for cardiovascular disease (CVD). Although atherosclerotic CVD, such as myocardial and stroke, is much more prevalent than classical autoimmune conditions such as rheumatoid arthritis, psoriasis, and systemic lupus erythematosus, these types of pathology have many similarities, raising the possibility that therapies against autoimmune disease can have beneficial effects on CVD. Substantial clinical and experimental data support the potential for immunomodulatory approaches to combating both autoimmune and cardiovascular diseases, including classical immunosuppressants, anticytokine therapy, the targeting of T and B cells and their responses, and vaccination. In this review, we discuss experimental and clinical studies that have used immunomodulatory approaches to mitigate autoimmune reactions and examine their potential to prevent and treat atherosclerotic CVD. (Circ J 2015; 79: 924–933)

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In healthy individuals, the endothelium plays a fundamental role in normal health in the maintenance of vascular homeostasis. Endothelial cell (EC) dysfunction results in the development of several pathologies. In diabetes, in particular, sustained hyperglycemia, a characteristic of diabetes, contributes to EC dysfunction and consequently mediates the pathogenesis of diabetes-associated micro- and macrovasculopathies. Hyperglycemia-induced EC dysfunction is triggered by elevated levels of oxidative stress derived from several mechanisms, with the mitochondria as a key source, and is exacerbated by a subsequent hyperglycemia-induced self-perpetuating cycle of oxidative stress and aberrant metabolic memory. Recent reports have highlighted the importance of metabolic pathways in EC and suggested the therapeutic potential of targeting EC metabolism. This review focuses on the current knowledge regarding differences in the metabolism of healthy ECs vs. diabetes-associated dysfunctional ECs, and outlines how EC metabolism may be targeted for therapeutic benefit. (Circ J 2015; 79: 934–941)

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Heart failure (HF) is a highly prevalent disorder worldwide and, consequently, a burden on the healthcare systems of many nations. Although the effects of HF are systemic, many therapeutic targets are focused on cardiac dysfunction. The brain is closely related to the heart, but there are few reports on the relationship between these organs. We describe the effects of the brain on HF progression. Specific brain regions control sympathetic drive and neurohumoral factors, which play an important role in disease exacerbation. In addition, we review some of our previous studies on deranged cerebral metabolism and reduced cerebral blood flow during HF. Although the reasons underlying these effects during HF remain uncertain, we propose plausible mechanisms for these phenomena. In addition, the clinical implications of such conditions in terms of predicting prognosis are discussed. Finally, we investigate cognitive impairment in patients with HF. Cognitive impairment through cerebral infarction or hypoperfusion is associated with adverse outcomes, including death. This brief review of brain function during the development of HF should assist with future strategies to better manage patients with this condition. (Circ J 2015; 79: 942–947)

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The management of chronic heart failure (HF) with low ejection fraction (EF) has changed considerably over the past 30 years: the introduction of angiotensin-converting enzyme inhibitors (ACEIs), β-blockers, angiotensin-receptor blockers, mineralocorticoid-receptor antagonists and recently, the I_fblocker, ivabradine, has led to a significant reduction in overall mortality and HF mortality. Recently, a trial testing a dual inhibitor blocking the angiotensin-II receptor and neprylisin, the enzyme responsible for B-type natriuretic peptide degradation, showed that this complex molecule improved clinical outcomes compared with the ACEI enalapril. However, challenges remain in the management of HF, with suboptimal implementation of guideline-recommended therapies, a changing profile of patients who are older and have multiple comorbidities and a high rate of early rehospitalization for HF. Use of devices such as implantable cardiac defibrillators and cardiac resynchronization therapy are also associated with an improvement in outcomes in this condition. HF with preserved EF (HFpEF), a growing fraction of the HF population, remains a clinical dilemma: no pharmacological intervention has so far demonstrated any convincing benefit on outcome. Heterogeneity of the populations tested, role of comorbidities, difficulties in identifying patients with HFpEF, as well as a mismatch between the clinical phenotypes and the treatments tested, can explain the failure to find beneficial interventions. Overall, the management of HF after discharge remains fragmented and concerted action by all professionals concerned is needed. (Circ J 2015; 79: 948–953)

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It has been well described that many patients with heart failure (HF) have a normal left ventricular ejection fraction. This entity has been termed “heart failure with preserved ejection fraction (HFPEF)”. Significant advances have been made in understanding the clinical characteristics of HFPEF over the past 2 decades on the basis of large HF registries and randomized clinical trials. However, most multicenter clinical trials that investigated medical therapies in HFPEF have yielded disappointing results. HFPEF being a clinical syndrome involving multiple organ systems may be a potential explanation for treatment failure. In this review we discuss the prevalence of noncardiac comorbidities in HFPEF patients as well as their effect on the prognosis of HFPEF. (Circ J 2015; 79: 954–959)

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Background:Adaptive servo-ventilation (ASV) therapy is expected to be novel nonpharmacotherapy with hemodynamic effects on patients with chronic heart failure (CHF), but sufficient evidence has not been obtained.Methods and Results:A 24-week, open-label, randomized, controlled study was performed to confirm the cardiac function-improving effect of ASV therapy on CHF patients. At 39 institutions, 213 outpatients with CHF, whose left ventricular ejection fraction (LVEF) was <40% and who had mild to severe symptoms [New York Heart Association (NYHA) class: ≥II], were enrolled. After excluding 8 patients, 102 and 103 underwent ASV plus guideline-directed medical therapy (GDMT) [ASV group] and GDMT only [control group], respectively. The primary endpoint was LVEF, and the secondary endpoints were HF deterioration, B-type natriuretic peptide (BNP), and clinical composite response (CCR: NYHA class+HF deterioration). LVEF and BNP improved significantly at completion against the baseline values in the 2 groups. However, no significant difference was found between these groups. HF deterioration tended to be suppressed. The ASV group showed a significant improvement in CCR corroborated by significant improvements in NYHA class and ADL against the control group.Conclusions:Under the present study’s conditions, ASV therapy was not superior to GDMT in the cardiac function-improving effect but showed a clinical status-improving effect, thus indicating a given level of clinical benefit. (Circ J 2015; 79: 981–990)

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Background:Poor survival outcomes for patients with severe heart failure (HF) and the donor shortage for heart transplantation warrant the development of myocardial regenerative therapy. We performed a multicenter, phase II study to evaluate the safety and efficacy of autologous skeletal myoblast sheets (TCD-51073).Methods and Results:In 3 study sites, we enrolled 7 patients with severe chronic HF due to ischemic heart disease despite maximal therapy, all of whom underwent transplantation of TCD-51073. No serious arrhythmia was reported, and no changes were noted in the frequency of ventricular extrasystole frequency. The primary efficacy endpoint of the change in left ventricular ejection fraction (LVEF) on gated blood-pool scintigraphy at 26 weeks after transplantation showed that 5 subjects were responders (classified as “improved” or “unchanged”). In addition, LVEF on echocardiography improved over time, with a change in LVEF of 7.1±2.8% at 26 weeks posttransplantation. Among the 7 subjects, 6 showed improvement in New York Heart Association functional class by at least 1 class. The 6-min walk distance was 410.1±136.1 m before transplantation and 455.4±103.7 m at 26 weeks after transplantation.Conclusions:This study demonstrated the feasibility and safety of the transplantation of TCD-51073 in the patients with severe chronic HF due to ischemic heart disease, suggesting that TCD-51073 might maintain or improve cardiac function, symptoms, and physical function. (Circ J 2015; 79: 991–999)

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Background:Large earthquakes have been associated with cardiovascular disease (CVD) mortality. In Japan, the 1995 Great Hanshin-Awaji (H-A) Earthquake was an urban-underground-type earthquake, whereas the 2011 Great East Japan (GEJ) Earthquake was an ocean-trench type. In the present study, we examined how these different earthquake types affected CVD mortality.Methods and Results:We examined death certificate data from 2008 to 2012 for 131 municipalities in Iwate, Miyagi, and Fukushima prefectures (n=320,348) and from 1992 to 1996 for 220 municipalities in Hyogo, Osaka, and Kyoto prefectures (n=592,670). A Poisson regression model showed significant increases in the monthly numbers of acute myocardial infarction (AMI)-related deaths (incident rate ratio [IRR] GEJ=1.34, P=0.001; IRR of H-A=1.57, P<0.001) and stroke-related deaths (IRR of GEJ=1.42, P<0.001; IRR of H-A=1.33, P<0.001) after the earthquakes. Two months after the earthquakes, AMI deaths remained significant only for H-A (IRR=1.13, P=0.029). When analyzing the standardized mortality ratio (SMR) after the earthquakes using the Cochran-Armitage trend test, seismic intensity was significantly associated with AMI mortality for 2 weeks after both the GEJ (P for trend=0.089) and H-A earthquakes (P for trend=0.005).Conclusions:Following the GEJ and H-A earthquakes, there was a sharp increase in CVD mortality. The effect of the disaster was sustained for months after the H-A earthquake, but was diminished after the GEJ Earthquake. (Circ J 2015; 79: 1000–1008)

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Background:Japanese patients with atrial fibrillation (AF) are generally small and lean, but knowledge of the clinical characteristics of those with low body weight (LBW: ≤50 kg) is limited.Methods and Results:The Fushimi AF Registry is a community-based prospective survey of AF patients who visited the participating medical institutions in Fushmi-ku, Japan. The BW and follow-up data were available for 2,945 patients. We compared the background and the incidence of clinical events during a median follow-up of 746 days between a LBW and non-LBW group. Patients in the LBW group accounted for 26.8% (788 patients) of the total. The LBW group was more often female, older, and had higher CHADS₂score. The incidence of stroke/systemic embolism (SE) during follow-up was higher in the LBW group (hazard ratio (HR): 2.19, 95% confidence interval (CI): 1.57–3.04; P<0.01), whereas that of major bleeding was comparable (HR: 1.05, 95% CI: 0.64–1.68; P=0.84). This trend was consistently observed in the subgroups stratified by age, sex, and oral anticoagulant prescription at baseline. Multivariate analysis as well as propensity-score matching analysis further supported the significance of LBW as a risk of stroke/SE.Conclusions:Patients in the LBW group had high risk profiles and showed a higher incidence of stroke/SE, but the incidence of major bleeding was not particularly high. (Circ J 2015; 79: 1009–1017)

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Background:We conducted a multicenter retrospective cohort study to elucidate the characteristics of intracranial hemorrhage (ICH) in patients with atrial fibrillation treated with non-vitamin K antagonist oral anticoagulants (NOACs).Methods and Results:We sent a questionnaire to the directors of 241 stroke centers in Japan to establish the clinical characteristics of NOAC-associated cerebral hemorrhage (CH), including hematoma size, hematoma enlargement (HE) and in-hospital mortality of patients treated in their institutions. We undertook a literature review to establish the clinical characteristics of warfarin-associated CH and compared these with our data. We received 174 responses (72.2%), of which 67 (38.5%) gave anonymous details of 130 eligible patients (male, 67.7%; mean age, 77.3±8.3 years, in-hospital mortality rate, 11.5%). We judged that 87 of the 130 patients had presented with CH: one-fifth had taken antiplatelet drugs. We found that the incidences of HE and mortality in the 87 patients presenting with NOAC-associated CH were lower than would have been expected in those with warfarin-associated CH (17% vs. 26%, and 16% vs. 35%, respectively).Conclusions:More than half the stroke center directors who responded to our questionnaire had not experienced cases of NOAC-associated ICH. Compared with warfarin, NOACs appear to present a lower risk of HE and death in patients with atrial fibrillation who develop CH. (Circ J 2015; 79: 1018–1023)

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Background:In hypertrophic cardiomyopathy (HCM) patients complicated with atrial fibrillation (AF), catheter ablation has been recommended as a treatment option. Meanwhile, prolongation of QTc interval has been linked to an increased AF incidence in the general population and to poor outcomes in HCM patients. However, whether QTc prolongation predicts arrhythmia recurrence after AF ablation in the HCM population remains unknown.Methods and Results:Thirty-nine HCM patients undergoing primary AF ablation were enrolled. The ablation strategy included bilateral pulmonary vein isolation (PVI) for paroxysmal AF (n=27) and PVI plus left atrial roof, mitral isthmus and tricuspid isthmus linear ablations for persistent AF (n=12). Pre-procedural QTc was corrected by using the Bazett’s formula. At a 14.8-month follow up, 23 patients experienced atrial tachyarrhythmia recurrence. Recurrent patients had longer QTc than non-recurrent patients (461.0±28.8 ms vs. 434.3±18.2 ms, P=0.002). QTc and left atrial diameter (LAD) were independent predictors of recurrence. The cut-off value of QTc 448 ms predicted arrhythmia recurrence with a sensitivity of 73.9% and a specificity of 81.2%. A combination of LAD and QTc (global chi-squared=13.209) was better than LAD alone (global chi-squared=6.888) or QTc alone (global chi-squared=8.977) in predicting arrhythmia recurrence after AF ablation in HCM patients.Conclusions:QTc prolongation is an independent predictor of arrhythmia recurrence in HCM patients undergoing AF ablation, and might be useful for identifying those patients likely to have a better outcome following the procedure. (Circ J 2015; 79: 1024–1030)

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Background:The aim of this study was to retrospectively evaluate the clinical and electrophysiological characteristics of elderly patients with typical atrioventricular nodal reentrant tachycardia (AVNRT), and to assess the acute safety and efficacy of slow-pathway radiofrequency (RF) ablation in this specific group of patients.Methods and Results:The present study retrospectively included a total of 1,290 patients receiving successful slow-pathway RF ablation for typical slow-fast AVNRT. Patients were divided into 2 groups: group I included 1,148 patients aged <65 years and group II included 142 patients aged >65 years. The required total procedure duration and total fluoroscopy exposure time were significantly higher in group II vs. group I (P=0.005 and P=0.0001, respectively). The number of RF pulses needed for a successful procedural end-point was significantly higher in group II than in group I (4.4 vs. 7.2, P=0.005). While the ratio of the anterior location near to the His-bundle region was significantly higher in group II, the ratio of posterior and midseptal locations were significantly higher in group I (P=0.0001). The overall procedure success rates were similar. There was no significant difference between the 2 groups in respect of the complications rates.Conclusions:This experience demonstrates that RF catheter ablation, targeting the slow pathway, could be considered as first-line therapy for typical AVNRT patients older than 65 years as well as younger patients, as it is very safe and effective in the acute period of treatment. (Circ J 2015; 79: 1031–1036)

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Background:Feasibility and early results of transfemoral aortic valve implantation using the ACURATE neo/TF^TMself-expanding stent are reported.Methods and Results:The study group of 15 patients (mean age 83.3±6.0) was enrolled with a mean EuroSCORE and STS score of 21.9±11.6% and 7.5±3.1%, respectively. Clinical and echocardiographic evaluations were performed at baseline, discharge, 30 days and 6 months. The primary endpoint was all-cause mortality at 30 days. Transcatheter aortic valve implantation (TAVI) using the ACURATE neo/TF device was successful in 14 patients; 1 patient underwent valve-in-valve implantation because the prosthetic valve embolized during withdrawal of the delivery system. Conversion to surgery, coronary obstruction, peri-operative stroke, and pacemaker implantation did not occur at 30 days. Mean transvalvular gradients at discharge significantly decreased from 44.2±10.5 mmHg (preprocedural) to 7.7±3.1 mmHg (P<0.0001) and effective orifice area significantly increased from 0.77±0.12 to 1.69±0.25 cm²(P<0.0001). None or trace paravalvular leak was revealed in 50.0%, and no patient exhibited moderate or higher paravalvular leak. The overall mortality at 30 days and 6 months was 0% and 6.7%, respectively.Conclusions:A new self-expanding TF TAVI device, ACURATE neo/TF, is safe and effective in the treatment of severe aortic stenosis in elderly patients at high risk for surgery. (Circ J 2015; 79: 1037–1043)

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Background:This study evaluated the mid to long-term durability and hemodynamics of the small-size Mosaic bioprosthesis, a third-generation stented porcine bioprosthesis, for aortic valve replacement (AVR).Methods and Results:From 2000 to 2012, 207 patients (117 women; age, 74±8 years; body surface area, 1.48±0.25 m²) underwent AVR with a Mosaic bioprosthesis. The mean follow-up period was 3.5±2.7 years (maximum, 12.4 years) and the follow-up rate was 93.7%. A 19-, 21-, 23-, 25-, and 27-mm prosthesis was used in 103, 53, 35, 13, and 3 patients, respectively. The measured effective orifice area was 1.17±0.25, 1.29±0.19, 1.39±0.24, and 1.69 cm²for the 19–25 mm prostheses, and the mean transvalvular pressure gradient was 19.4±6.0, 18.5±5.8, 16.5±7.3, and 13.2±2.9 mmHg, respectively. The left ventricular mass regression was significant (P<0.05) with rates of 74.6±18.8%, 75.5±30.2%, 68.1±30.5%, 55.9±12.9%, and 49.2%, respectively. The 30-day mortality rate was 1.9% and the 5- and 10-year actuarial survival rates were 86.0% and 73.7%, respectively. Valve-related comorbidities occurred in 3 patients (structural valve deterioration [SVD] in 1 after 7.2 years, and prosthetic valve endocarditis in 2). Freedom from SVD at 10-year was 96.7%.Conclusions:The mid to long-term performance of the small Mosaic bioprosthesis was satisfactory, with excellent hemodynamics and few valve-related adverse events. (Circ J 2015; 79: 1044–1051)

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Background:This simulation trial aimed to compare the quality of cardiopulmonary resuscitation (CPR) with and without the newly-developed CPR support application on smartphones.Methods and Results:In this trial, participants were randomly assigned to either the CPR support application group or the control group, stratified by sex and previous CPR training. Participants’ CPR skills were evaluated by a 2-min case-based scenario test using the Leardal Resusci Anne PC Skillreporting Manikin System^®. The outcome measures were the proportion of chest compressions performed in each group and the number of total chest compressions and appropriate chest compressions performed during the 2-min test period. A total of 84 participants were enrolled and completed the protocol. All participants in the CPR support application group performed chest compressions, compared with only 31 (75.6%) in the control group (P<0.001). Among participants who performed chest compressions during the 2-min test period, the number of total chest compressions was significantly higher in the CPR support application group than in the control group (211.6±29.5 vs. 77.0±43.3, P<0.001). The number of appropriate chest compressions tended to be greater in the CPR support application group than in the control group, although it was statistically insignificant (30.3±57.3 vs. 17.2±28.7, P=0.246).Conclusions:In this cohort of laypersons, the newly-developed CPR support application for smartphones contributed to increasing the implementation rate and the number of total chest compressions performed and may assist in improving the survival rate for out-of-hospital cardiac arrests (UMIN000004740). (Circ J 2015; 79: 1052–1057)

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Background:The geographic distribution of cardiovascular (CV) health-care services has not been assessed systematically.Methods and Results:Data of the Japanese Circulation Society (JCS) annual survey were provided to the JCS working group with the permission of the JCS Scientific Committee. The status of CV practice in 2010 was then assessed in 47 prefectures retrospectively, along with national census and gross domestic product (GDP) data. The surveyed indices included resources (hospitals, beds and cardiologists), burden (number of inpatients), and outcome (CV mortality and autopsy) in each prefecture, which correlated well with respective populations or GDP. Inequality of geographic distribution was evident for pediatrics among the 47 prefectures, according to Lorenz curve, Gini coefficient or the maximum/minimum ratio for each index. According to the Gini coefficients, only the number of inpatients (medical or acute myocardial infarction) and beds for the total number of general hospitals or the hospitals surveyed in the present JCS study were lower than expected with regard to GDP.Conclusions:Geographic disparity of CV resources or burden was larger in pediatrics than in CV medicine or surgery. Improvement of equality in CV practice with regard to appropriateness and quality are the coming challenges for the JCS. (Circ J 2015; 79: 1058–1067)

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Background:Among variables obtained from cardiopulmonary exercise testing (CPXT), peak oxygen consumption (PV̇O₂) and the minute ventilation vs. carbon dioxide output (V̇E vs. V̇CO₂) slope were established as predictors of death of patients with heart failure (HF) at the cutoff points of 14 ml·min^–1·kg^–1and 34, respectively. However, a recent update of guideline-directed medical treatment (GDMT) might alter the implication of these variables.Methods and Results:We enrolled 77 HF patients receiving GDMT who had undergone symptom-limited CPXT between 2006 and 2014. Among them, 29 patients were re-hospitalized for HF and there were 13 cardiac deaths during the 4-year study period. Cox regression analyses demonstrated that the V̇E vs. V̇CO₂slope, peak heart rate, peak systolic blood pressure, and PV̇O₂were significant predictors of both re-admission and cardiac death at each cutoff point calculated by receiver-operating characteristic analyses. A new scoring system was constructed using the following criteria: 1 point was assigned to a variable meeting the cutoff point for re-admission; 2 points were assigned to that for cardiac death. The total scores calculated as the summation of each point (range, 0–8 points) had significantly highest area under the curves compared with each CPXT variable (P<0.05), and significantly stratified both event-free rate into 3 groups (P<0.05).Conclusions:A novel scoring system using 4 CPXT variables simultaneously predicted re-admission and cardiac death even in patients with HF receiving GDMT. (Circ J 2015; 79: 1068–1075)

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Background:The first few months after admission are the most vulnerable period in patients with acute decompensated heart failure (ADHF).Methods and Results:We assessed the association of the updated ADHF/N-terminal pro-B-type natriuretic peptide (NT-proBNP) risk score with 90-day and in-hospital mortality in 701 patients admitted with advanced ADHF, defined as severe symptoms of worsening HF, severely depressed left ventricular ejection fraction, and the need for i.v. diuretic and/or inotropic drugs. A total of 15.7% of the patients died within 90 days of admission and 5.2% underwent ventricular assist device (VAD) implantation or urgent heart transplantation (UHT). The C-statistic of the ADHF/NT-proBNP risk score for 90-day mortality was 0.810 (95% CI: 0.769–0.852). Predicted and observed mortality rates were in close agreement. When the composite outcome of death/VAD/UHT at 90 days was considered, the C-statistic decreased to 0.741. During hospitalization, 7.6% of the patients died. The C-statistic for in-hospital mortality was 0.815 (95% CI: 0.761–0.868) and Hosmer-Lemeshow χ²=3.71 (P=0.716). The updated ADHF/NT-proBNP risk score outperformed the Acute Decompensated Heart Failure National Registry, the Organized Program to Initiate Lifesaving Treatment in Patients Hospitalized for Heart Failure, and the American Heart Association Get with the Guidelines Program predictive models.Conclusions:Updated ADHF/NT-proBNP risk score is a valuable tool for predicting short-term mortality in severe ADHF, outperforming existing inpatient predictive models. (Circ J 2015; 79: 1076–1083)

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Background:We sought to examine whether epicardial and abdominal visceral adipose tissue distribution is associated with coronary atherosclerosis in patients with a coronary artery calcium (CAC) score of zero, assessed by coronary computed tomography angiography (CCTA).Methods and Results:We studied 352 patients with suspected coronary artery disease (mean age 61±11 years, 57% male) with a CAC score of zero who had undergone CCTA. Non-calcified coronary plaques (NCPs) were detected in 102 patients (29%); those causing ≥50% stenosis were found in 15 patients (4%). Patients were divided into 4 groups on the basis of CT-based epicardial adipose tissue (EAT) volume and abdominal visceral adipose tissue (VAT) area using the sex-specific median value. Multivariate analysis showed that the adjusted odds ratios for the presence of NCPs in the high VAT area/low EAT volume group, and the high VAT area/high EAT volume group were 2.80 (95% confidence interval [95% CI]: 1.25–6.35, P=0.01) and 2.68 (95% CI: 1.36–5.45, P=0.004), respectively. Interestingly, the low VAT area/high EAT volume group showed an equivalent adjusted odds ratio of 3.02 (95% CI: 1.33–6.90, P=0.008).Conclusions:EAT volume is eligible as a marker to be evaluated in addition to VAT area in patients with a CAC score of zero. (Circ J 2015; 79: 1084–1091)

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Background:Impaired glucose metabolism plays an important role in patients with acute myocardial infarction, but the clinical significance of glycemic variability (GV) early after the onset of ST-segment elevation myocardial infarction (STEMI) remains to be fully elucidated.Methods and Results:We prospectively investigated the clinical impact of GV, as determined by a continuous glucose monitoring system (CGMS), on left ventricular remodeling (LVR) assessed by cardiac magnetic resonance imaging (CMR) in 69 patients (63±13 years, 59 men) with a first reperfused STEMI within 12 h of onset. All patients were equipped with a CGMS when in a stable phase after admission and underwent repeat CMR at baseline and 7 months follow-up. Patients were divided into 2 groups according to the mean amplitude of glycemic excursions (MAGE). Patients in the upper tertile of MAGE were categorized as group High (H) and the other two-thirds as group Low (L). LVR was defined as an absolute increase in left ventricular end-diastolic volume index of ≥20%. LVR more frequently occurred in group H than in group L (56% vs. 11%, P<0.001). Multivariate analysis showed the higher MAGE group was an independent predictor of LVR in the chronic phase (odds ratio, 13.999; 95% confidence interval, 3.059 to 64.056; P=0.001).Conclusions:MAGE early after the onset of STEMI identified patients with LVR in the chronic phase. (Circ J 2015; 79: 1092–1099)

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Background:Red cell distribution width (RDW) is known to be associated with anemia and mortality in cardiovascular diseases, while anemia itself is related to increased mortality. RDW may also be related to cytokine activation. We investigated the potential of RDW to predict anemia-adjusted mortality in patients with adult congenital heart disease (ACHD) and we evaluated the relationships among RDW, anemia, and interleukin-6 (IL-6).Methods and Results:This was a single-center, retrospective cohort study. Blood RDW and IL-6 levels were measured in 144 patients with ACHD (median age [interquartile range (IQR)], 28 [22–36] years), 84% in New York Heart Association class I/II. During a mean 4.8-year follow-up, 21 (15%) patients died of cardiovascular causes. Elevated RDW (>15.0%) correlated significantly with mortality risk in a univariate analysis (RDW hazard ratio [HR]: 1.570; 95% confidence interval [CI]: 1.208–2.040 per 1 standard deviation increase; P=0.001). Elevated RDW levels correlated significantly with increased anemia-adjusted mortality (adjusted RDW HR: 1.912; 95% CI: 1.369–2.670; P<0.001). The high RDW group had significantly elevated serum IL-6 levels (RDW >15%, median [IQR], 3.7 [0.9–13.9] pg/ml vs. RDW ≤15%, 1.4 [0.8–2.5 pg/ml]; P=0.001), as did patients with anemia (anemia, 1.9 [0.9–5.2] pg/ml vs. no anemia, 1.4 [0.8–2.5 pg/ml]; P=0.021).Conclusions:Elevation of RDW may be related with increased IL-6 and anemia-adjusted cardiovascular mortality in patients with ACHD. (Circ J 2015; 79: 1100–1106)

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Background:The incidence of venous thromboembolism (VTE) in Asians is lower than in Caucasians, but the risk of VTE associated with hormone therapy (HT) in Taiwanese postmenopausal women has not been determined.Methods and Results:From Taiwan’s National Health Insurance Research Database, we established matched cohorts (HT users and nonusers) of postmenopausal women aged ≥50 years between 1 January 1998 and 31 December 2008. We calculated the 2-year incidence of VTE in HT users and nonusers. HT users and nonusers were matched 1:1 based on propensity-score matching. Cox regression hazard model was used to identify risk factors of VTE. We initially identified 499,594 HT users and 424,963 nonusers. There were higher percentages of cancer and cardiovascular events among the HT nonusers. After matching, the VTE incidence was 4.4 vs. 2.6 per 10,000 patient-years (adjusted hazard ratio 1.796, 95% confidence interval 1.272–2.537) in HT users and nonusers, respectively. The Cox regression hazard model showed that HT use, older age, malignancy, heart failure, and recent major surgery were independent risk factors for VTE.Conclusions:Although the incidence of VTE was very low among this cohort of Taiwanese postmenopausal women, oral HT was still associated with an increased risk of VTE. Therefore, physicians should be aware of other potential VTE risk factors when prescribing oral HT to postmenopausal women. (Circ J 2015; 79: 1107–1114)

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Background:The aim of this study was to examine the effects of different statins on the clinical outcomes of Japanese patients with coronary stent implants.Methods and Results:This study included 5,801 consecutive patients (males, 4,160; age, 69.7±11.1 years, mean±SD) who underwent stent implantation between April 2008 and March 2011. They were treated with a strong statin (n=3,042, 52%, atorvastatin, pitavastatin, or rosuvastatin), a regular statin (n=1,082, 19%, pravastatin, simvastatin, or fluvastatin) or no statin (n=1,677, 29%). The patients with chronic kidney disease (CKD) were divided into mild-to-moderate CKD (30≤eGFR<60, n=1,956) and severe CKD (eGFR <30, n=559). Primary endpoints included cardiovascular death and nonfatal myocardial infarction, including stent thrombosis and ischemic stroke. The clinical outcome for the primary endpoint in mild-to-moderate CKD patients treated with a strong statin (hazard ratio 0.50, 95% confidence interval 0.31–0.81; P=0.005) was significantly lower than in those on no statins, but that in the patients treated with a regular statin was not (P=0.160). The clinical outcome for the primary endpoint in severe CKD patients treated with a strong or regular statin was no different than not being on statin therapy (P=0.446, P=0.194, respectively).Conclusions:In patients with mild-to-moderate CKD, only strong statins were associated with lower risk compared with no statin, but regular statins were not. It is possible that taking a strong statin from the early stage of CKD is useful for suppression of cardiovascular events. (Circ J 2015; 79: 1115–1124)

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Background:Uric acid (UA) serves as an antioxidant in vascular endothelial cells. UA transporter 1 (URAT1) encoded by SLC22A12 is expressed in the kidney and vessels and its loss of function causes hypouricemia. The purpose of this study was to examine whether there is any endothelial dysfunction in patients with hypouricemia.Methods and Results:Twenty-six patients with hypouricemia (<2.5 mg/dl) and 13 healthy control subjects were enrolled. Endothelial function was evaluated using flow-mediated dilation (FMD). mRNA of UA transporters expressed in cultured human umbilical endothelial cells (HUVEC) was detected on RT-PCR. There was a positive correlation between FMD and serum UA in the hypouricemia group. URAT1 loss-of-function mutations were found in the genome of 21 of 26 patients with hypouricemia, and not in the other 5. In the hypouricemia groups, serum UA in homozygous and compound heterozygous patients was significantly lower than in other groups, suggesting that severity of URAT1 dysfunction may influence the severity of hypouricemia. Thirteen of 16 hypouricemia subjects with homozygous and compound heterozygote mutations had SUA <0.8 mg/dl and their FMD was lower than in other groups. HUVEC do not express mRNA of URAT1, suggesting the null role of URAT1 in endothelial function.Conclusions:Depletion of UA due to SLC22A12/URAT1 loss-of-function mutations causes endothelial dysfunction in hypouricemia patients. (Circ J 2015; 79: 1125–1132)

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