Despite many advances in percutaneous and surgical interventions in the treatment of coronary artery disease (CAD), up to one-third of patients are still either not candidates or receive suboptimal revascularization. Calpains are a class of calcium-activated non-lysosomal cysteine proteases that serve as a proteolytic unit for cellular homeostasis. Uncontrolled activation of calpain has been found to be involved in the pathogenesis of myocardial reperfusion injury, cardiac hypertrophy, myocardial stunning and cardiac ischemia. Inhibition of calpains has been shown to significantly attenuate myocardial stunning and reduced infarct size after ischemia-reperfusion. Calpain inhibition therefore serves as a potential medical therapy for patients suffering from a number of diseases, including CAD. (Circ J 2016; 80: 4–10)

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Myocardial infarction with non-obstructive coronary arteries (MINOCA) is an intriguing clinical entity that is being increasingly recognized with the more common use of coronary angiography during acute myocardial infarction. This review systematically addresses the contemporary understanding of MINOCA, including, (1) what are the diagnostic criteria, (2) when the diagnosis should be considered, (3) who is at risk, (4) why this new syndrome should be diagnosed, (5) how these patients should be managed, and (6) where to next? (Circ J 2016; 80: 11–16)

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Heart failure continues to be a leading cause of hospitalization worldwide, and acute heart failure (AHF) carries significant risk for short-term morbidity and mortality. Despite many trials of potential new therapies for AHF, there have been very few advances over the recent decades. In this review, we will examine mortality during and after AHF hospitalization, with an emphasis on available data on mode of death (MOD). We will also review data on the timing of different MOD after AHF and the effect of specific therapies, as well as what is known about the contribution of specific pathophysiological mechanisms. Finally, we discuss the potential utility of further study of MOD data for AHF and its application to drug development, risk stratification, and therapeutic tailoring to improve short- and long-term outcomes in AHF. (Circ J 2016; 80: 17–23)

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An understanding of the complexity of cardiac anatomy is required by all who seek, in the setting of cardiac disease, to interpret the images confronting them. Although the mysteries of cardiac structure have been extensively addressed, significant gaps continue to exist between the descriptions provided by morphologists and by those working in the clinical setting. In part, this reflects the limitations in providing 3D visualization of such a complicated organ. Current 3D imaging technology now permits visualization of the cardiac components using datasets obtained in the living individual. These advances, furthermore, demonstrate the anatomy in the setting of the heart as imaged within the thorax. It has been failure to describe the heart as it lies within the thorax that remains a major deficiency of many morphologists relying on the dissecting room to provide the gold standard. Describing the heart in attitudinally appropriate fashion, a basic rule of clinical anatomy, creates the necessary bridges between anatomists and clinicians. The rapid progression of cardiac interventional techniques, furthermore, emphasizes the need to revisit cardiac anatomy using a multidisciplinary approach. In this review, therefore, we illustrate the advantages of an attitudinally correct approach to cardiac anatomy. We then focus on the morphology of the arterial roots, revealing the accuracy that can now be achieved by clinicians using datasets obtained during life. (Circ J 2016; 80: 24–33)

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Primary and primordial prevention of cardiovascular disease (CVD) requires not only identification of risk factors, but also appropriate and timely therapy. In order to prevent the expected increase in prevalence of CVD, it is essential that clinicians are aware of behavioral cardiovascular risk factors. A basic review is critical to clarify the difference between physical activity and fitness, as well as to discuss the role each plays in cardiovascular outcomes. We discuss observational epidemiological studies and randomized control trials that have examined the effect of physical activity and cardiorespiratory fitness on CVD. (Circ J 2016; 80: 34–43)

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The American Heart Association Scientific Sessions were held in Orlando on November 7–15, 2015. The meeting attracted more than 18,000 participants, including physicians, research scientists, students, and paramedical personnel, from more than 100 countries. Sessions over the 5 days included a comprehensive and unparalleled education delivered via more than 5,000 presentations, with 1,000 invited faculty members and 4,000 abstract presentations from the world leaders in cardiovascular disease. It also displayed the newest cardiovascular technology and resources by more than 200 exhibitors. There were 19 trials scheduled in 6 late-breaking clinical trial sessions. The Systolic Blood Pressure Intervention Trial (SPRINT) aimed to determine the most appropriate targets for the systolic blood pressure among persons without diabetes. A total of 9,361 persons with systolic blood pressure of ≥130 mmHg and an increased cardiovascular risk, but without diabetes, were randomly assigned to a target systolic blood pressure of <120 mmHg (intensive treatment) or a target of <140 mmHg (standard treatment). A significantly lower rate of the primary composite outcome and all-cause mortality in the intensive-treatment group than in the standard-treatment group was observed. Summaries and overviews of the late-breaking trials, clinical science special report sessions, and sessions to which members of the Japanese Circulation Society contributed are presented. (Circ J 2016; 80: 51–57)

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Background:Connexin43 (Cx43) is a major connexin that forms gap junction (GJ) channels in the heart and is also present in the cell membrane as unopposed/non-junctional hemichannels and in the inner mitochondrial membrane. By using carbenoxolone (CBX), a blocker of Cx43, the effect of the blockade of Cx43 on Ca²⁺waves and triggered arrhythmias in the myocardium with non-uniform contraction was examined.Methods and Results:Trabeculae were obtained from rat hearts. Force, [Ca²⁺]_i, and the diffusion coefficient were measured. Non-uniform contraction was produced with a 2,3-butanedione monoxime jet. Ca²⁺waves were induced by electrical stimulation. Inducibility of arrhythmias was estimated based on the minimal [Ca²⁺]_oat which arrhythmias were induced. The Ca²⁺spark rate was measured in isolated single rat ventricular myocytes. CBX reduced the GJ permeability, whereas it did not change force and [Ca²⁺]_itransients. CBX increased the Ca²⁺leak from the sarcoplasmic reticulum in trabeculae and increased the Ca²⁺spark rate in isolated single myocytes. CBX increased the velocity of Ca²⁺waves and further increased the inducibility of arrhythmias. Modulation of mitochondrial K_ATPchannels by diazoxide, cromakalim and 5-hydroxydecanoic acid affected the inducibility of arrhythmias increased by CBX.Conclusions:These results suggest that in diseased hearts, Cx43 plays an important role in the occurrence of triggered arrhythmias, probably under the modulation of mitochondrial K_ATPchannels. (Circ J 2016; 80: 76–84)

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Background:Subcutaneous implantable cardiac defibrillator (S-ICD) systems have a lower invasiveness than traditional ICD systems, and expand the indications of ICD implantations. The S-ICD standard defibrillation shock output energy, however, is approximately 4 times that of the traditional ICD system. This raises concern about the efficacy of the defibrillation and myocardial injury. In this study, we investigated the defibrillation efficacy and myocardial injury with S-ICD systems based on computer simulations.Methods and Results:First, computer simulations were performed based on the S-ICD system configurations proposed in a previous study. Furthermore, simulations were performed by placing the lead at the left or right parasternal margin and the pulse generator in the superior and inferior positions (0–10 cm) of the recommended site. The simulated defibrillation threshold (DFT) for the 4 S-ICD system configurations were 30.1, 41.6, 40.6, and 32.8 J, which were generally similar to the corresponding clinical results of 33.5, 40.4, 40.1, and 34.3 J.Conclusions:The simulated DFT were generally similar to their clinical counterparts. In the simulation, the S-ICD system had a higher DFT but relatively less severe myocardial injury compared with the traditional ICD system. Further, the lead at the right parasternal margin may correspond to a lower DFT and cause less myocardial injury. (Circ J 2016; 80: 85–92)

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Background:Since the introduction of PCI in 1977, it has evolved along with advances in the technology, improvement in operator technique and establishment of medical therapy. However, little is known of the improvement in clinical outcome following PCI.Methods and Results:Data from the Juntendo PCI Registry during 1984–2010 were analyzed. The patients were divided into 3 groups according to date of index PCI: POBA era, January 1984–December 1997; BMS era, January 1998–July 2004; and DES era, August 2004–February 2010. The primary endpoint was a composite of MACE including all-cause mortality, non-fatal MI, non-fatal stroke and revascularization. A total of 3,831 patients were examined (POBA era, n=1,147; BMS era, n=1,180; DES era, n=1,504). Mean age was highest in the DES era. The prevalence of diabetes and hypertension was higher in the DES and BMS eras than in the POBA era. Unadjusted cumulative event-free survival rate for 2-year MACE was significantly different across the 3 eras. Adjusted relative risk reduction for 2-year MACE was 56% in the DES era and 34% in the BMS era, both compared with the POBA era. Age, ACS, and LVEF were associated with the incidence of MACE.Conclusions:Clinical outcome of PCI improved across the 26-year study period, despite the higher patient risk profile in the recent era. (Circ J 2016; 80: 93–100)

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Background:Postoperative atrial fibrillation (POAF) is a common complication of cardiac surgery and may result in stroke, heart failure and poor prognosis. This study evaluated a novel index of total atrial conduction time derived from the P-wave onset (lead II) to the peak A’ wave on tissue Doppler imaging (PA-TDI duration) in patients undergoing mitral valve surgery (MVS) for mitral valve regurgitation.Methods and Results:Seventy-three patients undergoing MVS had transthoracic echocardiography with tissue Doppler imaging preoperatively and were monitored postoperatively with continuous electrocardiographic telemetry for 14 days. Preoperative characteristics, echocardiographic data, operative data and postoperative findings were compared between patients with (n=44) and without (n=29) POAF. Postoperative cardiac events were higher in patients with than without POAF (12/44, 27% vs. 3/29, 10%; P=0.0798) and cerebral events occurred in only 2 POAF patients. On multivariate analysis the independent predictors of POAF were degenerative disease etiology (OR, 4.61; 95% CI: 1.41–15.0; P=0.0112) and PA-TDI duration (OR, 1.04; 95% CI: 1.01–1.07; P=0.0048). On ROC curve analysis a PA-TDI cut-off of 159.4 ms was optimal for predicting POAF.Conclusions:PA-TDI duration was an independent predictor of POAF after MVS. Patients with PA-TDI duration >159.4 ms should be considered high risk and treated appropriately to improve outcome. (Circ J 2016; 80: 101–109)

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Background:The aim of this study was to compare the short- and long-term outcomes of CABG in diabetes mellitus (DM) patients according to eGFR.Methods and Results:A total of 573 DM patients receiving CABG between 1997 and 2012 were stratified according to preoperative eGFR: normal or mild chronic kidney disease (CKD), eGFR ≥60 ml/min/1.73 m²; moderate CKD, eGFR 30–60 ml/min/1.73 m²; severe CKD, eGFR <30 ml/min/1.73 m²; and severe CKD requiring hemodialysis (HD). Off-pump and bilateral internal thoracic artery (BITA) grafting rates were 83.4 and 62.3%, respectively. Mediastinitis and in-hospital mortality rates were both 1.4%. On logistic regression analysis, preoperative congestive heart failure and CKD severity were independent predictors of postoperative renal failure and major complications. The mean follow-up period was 5.7 years (range, 0–15.5 years). Estimated 5-year survival (92.9±1.6%, 82.8±3.3%, and 47.3±7.0%, respectively, P<0.001) significantly decreased with declining kidney function. On Cox hazard modeling, CKD severity was an independent predictor of major cerebrocardiovascular events (normal/mild: hazard ratio [HR], 1; moderate: HR, 1.35; severe: HR, 1.83; HD: HR, 2.0, P=0.016) and of overall survival (normal/mild: HR, 1; moderate: HR, 1.65; severe: HR, 5.96; HD: HR, 10.93, P<0.001). BITA grafting was a strong protective factor for overall survival (HR, 0.63; P=0.022).Conclusions:In DM patients, early- and long-term outcomes after CABG are strongly influenced by CKD progression. (Circ J 2016; 80: 110–117)

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Background:Clinically distinct differences exist between East Asian and Caucasian subjects, but data for type 2 endoleak (T2EL) are limited in the East Asian population. The aim of this study was to analyze the characteristics of East Asian T2EL using a Japanese multicenter database.Methods and Results:Retrospective analysis of 832 endovascular aneurysm repairs performed from 2008 to 2014 were conducted. T2EL was observed in 234 cases (28.1%), and in 32 cases (3.8%) it led to sac expansion >5 mm caused by isolated T2EL (median follow-up, 35.6 months). On univariate and multivariate analysis, non-smoker status (odds ratio [OR], 2.216; P<0.001), Excluder stent graft (OR, 2.027; P<0.001), and T2EL at final angiogram (OR, 2.080; P<0.001) were risk factors for T2EL. On multivariate analysis for isolated T2EL with sac expansion, only non-smoker status remained (OR, 2.671; P<0.001). Other than T1EL, isolated T2EL was the most significant risk factor for sac expansion (OR, 18.486; P<0.001). Furthermore, out of 11 transarterial embolization procedures initiated, 4 led to rupture during follow-up.Conclusions:East Asian T2EL had a strong relationship with non-smoker status. Also, T2EL was a significant risk factor for sac expansion, which sometimes led to rupture even after intervention. Along with the high prevalence of T2EL observed, East Asian T2EL may not always be benign. (Circ J 2016; 80: 118–123)

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Background:Intricate repairs performed for adult mitral valve disease may not be feasible in young children because of their small annulus, future growth and also fragile tissue.Methods and Results:Mitral valve repair was performed in 51 patients (1980–2011) aged younger than 5 years. The median follow-up was 3.0 (maximum, 24.2) years. Commissural annuloplasty technique was performed solely in 19 of 37 patients with coexisting cardiac disease. In 2 patients, Alfieri’s edge-to-edge technique was used. Repairs for the remaining 30 patients used one of the following procedures: commissural closure (8), closure of the accessory cleft or hole (7), sliding leaflet technique (6), artificial chordal placement (6) and chordal shortening technique (3). There were 3 deaths. The postoperative degree of mitral regurgitation was mild or less in 41 patients (80.4%); 9 patients required reoperation for mitral regurgitation or stenosis. Freedom from reoperation for patients with isolated mitral regurgitation and those with other congenital heart disease at 10 years was 91.7±68.0% and 68.4±9.4%, respectively. Actuarial survival was 97.0±3.0% and 85.1±9.7%, respectively.Conclusions:Excellent survival rates were achieved after mitral valve repair in patients younger than 5 years. The incidence of both reoperation and significant regurgitation was acceptable. (Circ J 2016; 80: 124–129)

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Background:Sleep-disordered breathing (SDB) has been reported to influence mortality and occurrence of ventricular tachyarrhythmia in patients with chronic heart failure (CHF). It remains to be elucidated, however, whether respiratory therapy (RT) can affect the occurrence of fatal ventricular tachyarrhythmia in CHF patients with SDB.Methods and Results:We prospectively examined whether the severity of SDB was associated with fatal cardiac events in CHF patients and, if so, whether RT for SDB improved prognosis. We enrolled 95 patients with stable CHF, in whom SDB was examined on overnight polygraphy. The severity of SDB was quantified using the apnea-hypopnea index (AHI). All patients with AHI ≥10 (n=42) at initial evaluation were recommended to have RT, such as home oxygen therapy and continuous positive airway pressure, and 24 agreed to this. During the follow-up period of 29±17 months, 8 ventricular tachyarrhythmias occurred and 14 of the 95 patients died. On multivariate proportional hazard analysis AHI ≥5 was a risk factor for fatal arrhythmic events (P=0.026). Although RT significantly reduced AHI, it did not significantly reduce the event rates, but 4 patients with AHI <5 on RT had no fatal arrhythmic events or death.Conclusions:SDB is an independent prognostic factor and thus an important therapeutic target in CHF patients. (Circ J 2016; 80: 130–138)

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Background:Functional mitral regurgitation (FMR) is a common complication of heart failure (HF) and worsens in acute decompensation. It is unclear whether FMR on admission or discharge determines the outcome. This study aimed to elucidate the prognostic significance of FMR on admission or discharge in patients admitted with acute decompensated HF.Methods and Results:From 2006 to 2009, 349 patients admitted with acute decompensated HF were enrolled. They were followed with the composite endpoint of all-cause death and hospitalization for HF; 74 (21%) died and 113 (32%) developed the composite endpoint during 2.1±1.3 years. Moderate/severe FMR at discharge was associated with the composite endpoint (P=0.001), whereas that on admission was not. Multivariate Cox proportional hazard analysis showed that moderate/severe FMR (hazard ratio [95% confidence interval] =1.70 [1.03–2.73] P=0.04), logBNP, and NYHA class III/IV at discharge were independent determinants of the outcome. Moderate/severe FMR at discharge with BNP ≥200 pg/ml was prognostic, but BNP <200 pg/ml was no longer prognostic.Conclusions:Residual moderate/severe FMR after medical therapy for acute decompensated HF was associated with poor outcome, suggesting a potential target for further treatment of HF. (Circ J 2016; 80: 139–147)

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Background:The myocardial performance index (MPI) has emerged as a Doppler-derived index for global ventricular function capable of estimating combined systolic and diastolic performance. While several studies have reported its load-dependency, responses of the MPI to various hemodynamic changes have not been fully characterized.Methods and Results:The response characteristics of the MPI were examined and compared with ejection fractions (EF) by changing hemodynamic parameters within the physiological range in a lumped parameter model of the cardiovascular system. At baseline, the MPI was 0.42 and the EF was 0.68. Heart rate increase resulted in a decrease in EF and an increase in the MPI. Reduction in end-systolic elastance decreased EF and increased the MPI. Volume overload and ventricular stiffening did not affect EF but paradoxically reduced the MPI. Increased afterload due to higher systemic resistance resulted in a decrease in EF and increase in the MPI, but afterload increase caused by reduced arterial compliance led to a decrease in both EF and MPI. These MPI characteristics caused paradoxical improvement of the MPI during disease progression of chronic heart failure in a simulation of mitral regurgitation.Conclusions:The MPI is affected by a wider variety of hemodynamic parameters than EF. In addition, it is predicted to decrease paradoxically with volume overload, reduction in arterial compliance, or ventricular diastolic stiffening. These MPI characteristics should be considered when assessing cardiovascular dynamics using this index. (Circ J 2016; 80: 148–156)

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Background:The prognostic impact of new-onset atrial fibrillation (AF) is not fully elucidated.Methods and Results:We examined 4,818 consecutive stage C/D chronic heart failure (CHF) patients in the Chronic Heart Failure Analysis and Registry in the Tohoku District-2 (CHART-2) Study (n=10,219). At enrollment, 1,859 (38.6%) of them had AF. Compared with the 2,953 patients without AF, AF patients were characterized by higher age (71 vs. 68 years), lower estimated glomerular filtration rate (58.9 vs. 61.9 ml/min/1.73 m²), higher brain natriuretic peptide (152 vs. 74.5 pg/ml), similar left ventricular ejection fraction (56.8 vs. 56.5%), and a similar prescription rate of β-blockers (48.1 vs. 50.6%) and renin-angiotensin system (RAS) inhibitors (72.9 vs. 71.6%). Among the patients without AF at enrollment, 106 (3.6%) developed new AF during the median 3.2-year follow-up, which was associated with increased mortality (adjusted hazard ratio, 1.72; P=0.013). In contrast, neither paroxysmal nor chronic AF at enrollment was associated with increased mortality. The mortality rate was significantly high in the first year after the onset of new AF. On inverse probability of treatment weighting analysis using propensity score, RAS inhibitors and statins were associated with reduced incidence of new AF, and diuretics were associated with increase of new AF.Conclusions:Onset of new AF, but not a history of AF, is associated with increased mortality in CHF patients, especially in the first year. (Circ J 2016; 80: 157–167)

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Background:We assessed whether measuring pulmonary annular motion velocity could serve as a novel method of evaluating right ventricular outflow tract (RVOT) performance in pediatric patients with heart disease.Methods and Results:Tissue Doppler-derived pulmonary annular motion velocity was determined from the parasternal long-axis view of the RVOT. Pulmonary annular velocity was measured in children (age, 5–10 years) with an atrial septal defect (ASD), pulmonary arterial hypertension (PAH), surgically repaired tetralogy of Fallot (TOF) and healthy children (control). Pulmonary annular velocity waveforms comprised systolic bimodal (s1’ and s2’) and diastolic e’ and a’ waves in all groups. The peak velocity of s1’ and s2’ was significantly higher in the ASD group than in the controls (15.0±2.4 vs. 11.2±2.1 and 6.0±0.9 vs. 4.4±1.2 cm/s; P<0.01 and P<0.001, respectively). The s1’ and s2’ peak velocities were significantly lower in the PAH group (8.5±1.2 and 3.2±0.4 cm/s; P<0.05 for both), and in the group with TOF (5.3±2.2 and 3.4±1.4 cm/s; P<0.001 and P<0.05, respectively). The peak velocity of e’ was significantly decreased in the PAH and TOF, compared with the control group (6.8±1.6 and 8.2±2.9 vs. 11.9±1.9 cm/s; P<0.001 for both).Conclusions:Pulmonary annular motion velocity determined using tissue Doppler imaging is a promising method of assessing RVOT function. (Circ J 2016; 80: 168–176)

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Background:Left ventricular (LV) ejection fraction (EF) and QRS duration enable prediction of outcome in patients with systolic heart failure (SHF). We assessed the predictive value of global longitudinal strain (GLS) and mechanical dyssynchrony for prognosis in SHF patients.Methods and Results:Two-hundred and forty SHF patients with LVEF ≤40% were studied. Global LV function and intraventricular mechanical dyssynchrony were calculated as GLS and SD of the time to peak longitudinal strain (SDε) over 18 LV segments. The added value of GLS and SDε for outcome prediction was assessed using nested Cox models. Sixty-six patients (28%) reached the study endpoint of all-cause mortality/heart transplantation over a median follow-up period of 45 months. Baseline variables associated with adverse outcome were age, glomerular filtration rate, pulmonary artery systolic pressure, diabetes and LV end-systolic volume (model χ²=69.8). The predictive power of the clinical variables was greater with addition of GLS (χ²=81.1) or SDε (χ²=102.3) than with LVEF (χ²=73.9) or QRS duration (χ²=75.5; both P<0.005). GLS (HR, 1.88; P=0.03) and SDε (HR, 1.48; P=0.04) were independent predictors after adjustment for the baseline variables. Patients with impaired GLS (≥–7.8%) and mechanical dyssynchrony (SDε ≥72 ms) had poor outcome.Conclusions:Combined assessment of global LV function and mechanical dyssynchrony using speckle-tracking strain enabled the prediction of long-term outcome in SHF patients. (Circ J 2016; 80: 177–185)

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Background:The influence of glucose fluctuations (GF) on cardiovascular complications of diabetes mellitus (DM) has been attracting much attention. In the present study, whether GF increase susceptibility to ischemia/reperfusion in the heart was investigated.Methods and Results:Male rats were randomly assigned to either a control, DM, and DM with GF group. DM was induced by an injection of streptozotocin, and glucose fluctuation was induced by starvation and insulin injection. One sequential program comprised 2 hypoglycemic episodes during 4 days. The isolated hearts were subjected to 20-min ischemia/30-min reperfusion. The infarct size was larger in hearts with GF than those with sustained hyperglycemia. Activities of catalase and superoxide dismutase were decreased, and expressions of NADPH oxidase and thioredoxin-interacting protein were upregulated by GF accompanied by an increase of reactive oxygen species (ROS). Swollen mitochondria with destroyed cristae were observed in diabetic hearts; they were further devastated by GF. Microarray analysis revealed that the expressions of microRNA (miRNA)-200c and miRNA-141 were abundant in those hearts with GF. Overexpression of miRNA-200c and miRNA-141 decreased mitochondrial superoxide dismutase and catalase activities, and increased ROS levels. Meanwhile, knockdown of miRNA-200c and miRNA-141 significantly decreased ROS levels in cardiomyocytes exposed to GF.Conclusions:GF increased ROS generation and enhanced ischemia/reperfusion injury in the diabetic heart. Upregulated miRNA-200c and miRNA-141 may account for the increased ROS. (Circ J 2016; 80: 186–195)

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Background:Chronic kidney disease (CKD) is strongly associated with coronary artery disease (CAD), although the underlying pathophysiological mechanism remains unclear. Epicardial adipose tissue (EAT) has recently been recognized as an important source of various pro-inflammatory cytokines causing coronary atherosclerosis. This study investigated the relationship between CKD and EAT volume in association with high-risk plaque.Methods and Results:The study included 275 patients with an estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73 m²who underwent multidetector computed tomography (MDCT) for the evaluation of CAD. Patients were classified, according to eGFR, into a CKD group (30≤eGFR<60 ml/min/1.73 m²) or a non-CKD group (eGFR ≥60 ml/min/1.73 m²). MDCT was used to assess coronary plaque morphology and EAT volume. One hundred and ten patients with CKD were more likely to be older, have higher prevalence of hypertension, lower serum HDL-C, higher serum CRP, and larger EAT volume, than those without CKD (all P<0.01). On multivariate analysis age, hypertension, and EAT volume were significantly associated with eGFR (all P<0.01). EAT volume was associated with the presence of high-risk plaque, independent of traditional CAD risk factors (P=0.003).Conclusions:Patients with CKD had significantly increased EAT volume, which could be associated with the presence of high-risk plaque. (Circ J 2016; 80: 196–201)

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Background:Glycemic variability (GV) is associated with coronary plaque rupture at the culprit lesion in acute myocardial infarction (AMI). The present study determined the relationship between GV and coronary plaque vulnerability in the non-culprit vessel.Methods and Results:The present prospective study involved 46 patients with first-episode acute coronary syndrome (ACS) who underwent optical coherence tomography in the non-culprit vessel. The relationship between GV, assessed with continuous glucose monitoring system, and the presence of thin-cap fibroatheroma (TCFA) at the non-culprit plaque with mild-to-moderate stenosis in the non-culprit vessel, was assessed. GV was quantified using mean amplitude of glycemic excursion (MAGE). Patients were divided into tertiles according to MAGE. TCFA was observed in 13 (28%) of the 46 patients. Fibrous cap thickness was thinner (MAGE tertiles: high, 80±40 µm; intermediate, 152±122 µm; low, 155±102 µm; P=0.01), and TCFA was more common (MAGE tertiles: high, 50%; intermediate, 27%; low, 7%; P=0.03) in patients with high MAGE. On multivariate logistic analysis high MAGE was the only significant determinant of TCFA, independent of coronary risk factors (OR, 5.000; P=0.021), homeostasis model assessment of insulin resistance, and hemoglobin A_1c(OR, 5.674; P=0.018).Conclusions:High MAGE measured early after the onset of first-episode ACS correlated with thinner fibrous cap thickness and higher prevalence of TCFA at the non-culprit plaque in the non-culprit vessel. (Circ J 2016; 80: 202–210)

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Background:Limited data are available on the long-term clinical outcomes of coronary chronic total occlusion (CTO) patients who receive optimal medical therapy (OMT) compared with percutaneous coronary intervention (PCI).Methods and Results:Between March 2003 and February 2012, 2,024 patients with CTO were enrolled in a single-center registry. Among this patient group, we excluded CTO patients who underwent coronary artery bypass grafting and classified patients into the OMT group (n=664) or PCI group (n=883) according to initial treatment strategy. Propensity-score matching was also performed. The primary outcome was cardiac death. The median follow-up duration was 45.8 (interquartile range: 22.8–71.1) months. In the PCI group, 699 patients (79.2%) underwent successful revascularization. In the propensity-score matched population (533 pairs), there was no significant difference in the rate of cardiac death between the OMT and PCI groups (hazard ratio, 1.57; 95% confidence interval, 0.91–2.72, P=0.11). In the subgroup analysis, there were no significant interactions between the PCI strategy and cardiac death among several subgroups except that regarding collateral flow grades 0–2 vs. those with grade 3 (P=0.01).Conclusions:As an initial treatment strategy, PCI did not reduce cardiac death compared with OMT for the treatment of CTO in the drug-eluting stent era. (Circ J 2016; 80: 211–217)

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Background:To better understand the evolution of typical hypertrophic cardiomyopathy (HCM) to heart failure (HF), we investigated the relationship between serum biochemical abnormalities and changes in left ventricular (LV) remodeling.Methods and Results:Seventy-seven HCM patients were followed for 20 years. Creatine kinase (CK), CK-MB, lactate dehydrogenase (LDH), LDH-1, troponin T and myosin light chain-1 (MLC-1) were measured. Abnormal CK-MB elevation was observed in 64% of HCM patients. LDH-1 was not significantly different compared with the control subjects. Troponin T elevation was observed in 3 HCM patients and MLC-1 elevation was not observed. According to median CK-MB, HCM patients were divided into 2 groups: group H (CK-MB ≥2.5%, n=33) and group L (CK-MB <2.5%, n=44). During the follow-up period in group H, LV end-diastolic dimension increased (P<0.0001), fractional shortening decreased (P<0.0004), and left atrial dimension increased (P<0.0001). The markers reflecting LV hypertrophy were significantly decreased. In group L, LV end-diastolic dimension increased (P<0.02) and left atrial dimension increased (P<0.0001). HF was observed in 18 patients in group H and in 4 in group L. There were 14 HF deaths in group H and 2 in group L, and 3 sudden cardiac deaths in group H.Conclusions:Persistent elevation of cardiac enzymes in HCM patients indicates ongoing myocardial injury, ultimately resulting in death by HF. (Circ J 2016; 80: 218–226)

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Background:A therapeutic strategy in patients with atrial septal defect (ASD) and significant pulmonary arterial hypertension (PAH) remains controversial. This study aimed to assess the effect of PAH-specific medications and subsequent transcatheter shunt closure (ie, a treat and repair strategy) in these patients.Methods and Results:Among 646 patients with ASD, 22 patients (mean age of 56±20 years) who had PAH [mean pulmonary artery pressure ≥25 mmHg and pulmonary vascular resistance (PVR) ≥3 Wood units] underwent successful transcatheter ASD closure. Prior to the procedure, 8 patients received PAH-specific medications (PHM group) and 14 patients did not (non-PHM group). Initially, the PHM group had higher PVR compared with non-PHM group (9.6±3.8 vs. 4.2±1.0 Wood units, P<0.01). After treatment with PAH-specific medications, PVR in this group decreased to 4.0±0.8 Wood units (P<0.01). No adverse events were observed in either the PHM or non-PHM group during or after the transcatheter procedure. In the PHM group, during a treatment period of 52±48 months, the World Health Organization Functional Classification significantly improved (3.0±0.5 to 2.0±0.0, P<0.01), as well as in the non-PHM group (2.1±0.6 to 1.5±0.5, P<0.01).Conclusions:Treat and repair strategy provided substantial improvement and no worsening of the WHO-FC, even in patients with ASD and significant PAH. Long-term hemodynamic follow-up is mandatory to evaluate the ultimate efficacy and safety of this new strategy. (Circ J 2016; 80: 227–234)

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Background:The aim of this study was to evaluate the usefulness of paramalleolar arterial Bollinger score (PBS) for predicting postoperative outcome of infra-popliteal bypass surgery for critical limb ischemia (CLI).Methods and Results:A total of 104 consecutive patients (118 limbs) who underwent infra-popliteal (tibial or paramalleolar) arterial bypass surgery with an autologous vein conduit for the treatment of CLI (Rutherford 4–6) between January 2002 and December 2012 were classified according to PBS ≤45 or >45. Postoperative outcome was compared between these groups. Primary outcomes were major adverse limb events plus perioperative death, and amputation-free survival (AFS). The secondary outcomes were overall survival, limb salvage and secondary graft patency. More than 80% of patients had either diabetes mellitus (DM) or end-stage renal disease (ESRD) and 30 patients with 36 limbs had PBS >45. Compared with the PBS ≤45 group, the PBS >45 group had higher CVD and carotid stenosis rate, poor nutrition status and lower malignancy rate. On overall analysis, the PBS >45 group had worse outcome for AFS and survival but this was not statistically significant (P=0.12, NS). In DM or ESRD patients, the PBS >45 group had significantly worse outcome for both AFS (P=0.04, 0.02) and overall survival rate (P=0.04, 0.03).Conclusions:PBS successfully classified CLI patients with DM or ESRD who had worse outcome after infra-popliteal bypass surgery. (Circ J 2016; 80: 235–242)

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Background:The epidemiological data of pulmonary hypertension (PH) due to left heart disease (LHD) are limited. This study investigated hemodynamic and clinical factors associated with mortality in patients with PH due to LHD.Methods and Results:We conducted a retrospective review in 243 patients with PH due to LHD, defined as mean pulmonary arterial pressure ≥25 mmHg and pulmonary wedge pressure >15 mmHg at rest in right heart catheterization. Kaplan-Meier and Cox proportional hazard regression analyses were performed. Seventy-five patients died during an average follow-up of 52 months (range, 20–73 months). On multivariate analysis, only diastolic pulmonary vascular pressure gradient (DPG) ≥7 mmHg among hemodynamic measurements was a predictor of mortality. Elevated N-terminal pro-brain natriuretic peptide (NT-pro BNP), more severe New York Heart Association (NYHA) class, anemia, and renal dysfunction were more strongly associated with mortality. Mean right atrial pressure (RAP) and currently available markers of pulmonary vascular remodeling including transpulmonary pressure gradient (TPG) and pulmonary vascular resistance (PVR) had no effect on survival.Conclusions:DPG is weakly associated with mortality in PH due to LHD. Clinical factors such as NT-pro BNP, NYHA class, anemia and renal dysfunction are superior predictors. The prognostic ability of hemodynamic factors such as mean RAP, TPG, PVR and DPG is limited. (Circ J 2016; 80: 243–249)

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Background:The magnitude of the CHA₂DS₂-VASc score is associated with not only stroke incidence but also long-term outcomes. The association between sex and initial stroke severity in AF-related cardioembolic stroke patients has not been clarified. The present study aimed to elucidate the risk factors for initial stroke severity among patients with cardioembolic stroke enrolled in a multicenter registry.Methods and Results:We selected 12,701 patients (age, 77±10 years; 5,653 women) with AF-related cardioembolic stroke from the Japan Standard Stroke Registry Study between January 2000 and July 2013. Indicators of National Institutes of Health Stroke Scale (NIHSS) scores at admission were identified using a multiple linear regression. Increased NIHSS scores positively correlated with CHA₂DS₂-VASc score (ρ=0.197; P<0.001). The initial neurological deficits were more severe in women than in men (NIHSS scores, median [interquartile range] 14 [5–22] vs. 8 [3–18]; P<0.001). Multiple regression analysis revealed that higher age (standardized partial regression coefficient [β] 0.162; P<0.001), female sex (β 0.120; P<0.001), diabetes mellitus (β 0.020; P=0.019), dyslipidemia (β −0.076; P<0.001), congestive heart failure (β 0.039; P<0.001), vascular disease (β 0.030; P=0.001), prior stroke/TIA (β 0.085; P<0.001) and prior anticoagulant use (β −0.020; P=0.028) were associated with the NIHSS score at admission.Conclusions:Female sex was independently associated with the initial neurological severity among AF-related cardioembolic stroke patients. (Circ J 2016; 80: 250–255)

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