The mortality and morbidity of patients with stable angina pectoris (SAP) after percutaneous coronary intervention (PCI) in Japan differ from those in Western countries, although Japanese data are limited. We selected from the Shinken Database a single-hospital-based cohort of Japanese patients (n = 15,227) who visited The Cardiovascular Institute between 2004 and 2010 to undergo PCI. We followed-up the patients after PCI. A major adverse cardiac event (MACE) was defined as composite endpoints including all-cause death, acute myocardial infarction (AMI), and target-lesion revascularization (TLR). This study included 747 SAP patients (median follow-up period, 1,000 ± 703 days). The allcause mortality rate in SAP was 1.3% at 1 year, 2.7% at 3 years, and 6.1% at 5 years. The AMI rate was 0.5% at 1 year, 1.1% at 3 years, and 3.0% at 5 years, and the MACE rate was 14.0% at 1 year, 17.6% at 3 years, and 25.6% at 5 years. Moreover, new lesion PCI and heart failure admission continued to occur beyond 1 year after PCI without attenuation of their annual incidences up to 5 years. Multivariate analysis showed that poor left ventricular ejection fraction, chronic kidney disease (CKD), and absence of statin treatment were independent predictors of all-cause death of SAP patients after PCI. The results of the present study revealed the characteristics and long-term outcomes of Japanese SAP patients after PCI. The results of the present study suggest cardiorenal interaction and statin treatment play important roles in the long-term outcomes of Japanese CAD patients treated by PCI.

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The timing and incidence of neointimal calcification after stenting (NIC) is largely unknown. The purpose of our study was to elucidate the characteristics of NIC. The presence of NIC in patients who underwent intravascular ultrasound between June 30, 2009 and June 30, 2012 was analyzed. The patients were divided into two groups based on the follow-up period: < 365 days or ≥ 365 days. A total of 181 images were analyzed. Those with NIC had a lower estimated glomerular filtration rate [51 (6-60) versus 61 (52-72) mL/minute/1.73 m²; P < 0.01] and longer time after stenting [3198 (1710-3684) versus 211 (180-516) days; P < 0.01] compared to those without NIC. NIC during short-term follow-up was observed only in patients who were on hemodialysis. On the other hand, NIC in the long-term follow-up was observed only in patients with bare metal stents. The development of NIC was related to renal function and time after stenting. NIC in the short-term and the long-term follow-up was observed only in patients who were on hemodialysis and who were implanted with a bare metal stent, respectively.

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High-density lipoprotein (HDL) plays a key role in reverse cholesterol transport, and halts the progression of atherosclerosis. However, its localization in human vascular wall is not well understood. We discovered that by exciting at 470-nm and emitting at 515-nm light wavelengths, Fast green dye (FG) elicits brown fluorescence characteristic of HDL only. Therefore, the localization of native HDL in normal segments and plaques in excised human coronary artery was investigated by scanning their transected surface with color fluorescent microscopy (CFM) using FG as a biomarker, and the relationships between the localization of HDL and morphology of plaques and normal segments classifi ed by conventional angioscopy and histology were examined. The % incidence of HDL in 13 normal segments (NS) with thin (≦ 200 µm) intima, 28 NS with thick (200 µm <) intima, 41 white plaques (early stage of plaque growth), 15 yellow plaques (Y) without necrotic core (NC), and 20 Y with NC (advanced stage of plaque growth), was 30, 71 (P < 0.05 versus NS with thin intima and Y with NC), 83 (P < 0.05 versus NS with thin intima and Y with NC), 60, and 35, respectively. HDL begins to deposit in human coronary arterial wall in the early stage of atherosclerosis and deposits increase with plaque growth, but HDL decreases in plaques at an advanced stage of growth.

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The aim of this study was to investigate the association between the aortic valve calcium score (AVCS) and the coronary plaque burden using 64-slice multi-detector computed tomography (MDCT). Calcification of the aortic valve without significant aortic stenosis itself has been suggested to be a marker of atherosclerosis. In this study, we attempted to identify a quantitative correlation between AVCS and the coronary plaque burden assumed by the Gensini score. We retrospectively evaluated 200 patients (aged 40 - 88 years) who underwent MDCT and coronary angiography for chest pain. After exclusion of an aortic stenosis (peak velocity ≥ 2.0 m/s), the plaque burden of the coronary artery was determined by the Gensini score based on the plaque composition (calcified, mixed, or noncalcified plaque) of the CT angiogram. The calcific aortic valve group (AVCS > 0) showed no significant difference in the total plaque burden compared to the noncalcific aortic valve group (AVC = 0) (Gensini score 23.6 ± 15.1 versus 21.2 ± 17.5, P = 0.31). However, the calcified plaque burden was higher in the calcific aortic valve group (Gensini score by calcified plaque 9.1 ± 10.4 versus 5.5 ± 8.6, P = 0.008). In the subgroup of patients who had an AVCS of more than 90.0 (upper 75th percentile, n = 20), the AVCS showed a more significant correlation with the Gensini score by calcified plaque (r = 0.618, P < 0.01). Our results suggest that a high level of AVCS is associated with the calcified plaque burden of the coronary artery rather than the total plaque burden.

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Sudden cardiac death is a serious problem in public health but the overall survival rate of out-of-hospital cardiac arrests (OHCAs) remains low. In this study, we identified clinical parameters to predict the prognosis of OHCA patients and proposed a simple prognostication score for prediction of their prognoses. The study population consisted of 750 consecutive patients with OHCAs of internal cause who were transported to our institute from July 2008 to June 2010. They were divided into survivors and nonsurvivors, and clinical parameters were compared between them to detect significant parameters for prediction of their prognoses. The population of those who survived at 1 month numbered 34. Multivariate analysis exhibited 10 independent predictive factors of survival, which included witnessed cardiac arrest and bystander-initiated CPR. When the prognostication score was calculated from these independent predictive factors, a score of ≥ 6 points indicated survival with a sensitivity of 88.6% and a specifi city of 97.6%. When the patients were divided into younger and older populations with a threshold of 70 years, these values were 94.1% and 96.1% in younger but 70.0% and 98.4% in older patients, respectively. In retrospective observation, a simple prognostication score was useful to predict patient prognoses in OHCAs, but its usefulness was limited in an older population.

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Patients with recently diagnosed atrial fi brillation (AF) tend to exhibit a longer fi brillation cycle length (FCL) than those having a longer clinical history. However, the electrophysiological properties of new-onset AF may vary because of the clinical background of patients. In this study, we evaluated clinical factors to identify the determinants of FCL in new-onset AF. Electrocardiograms (ECGs) recorded from 2008 through 2011 were analyzed using our digital ECG-profi ling system. In the 1,578 AF episodes recorded, 466 new-onset AF episodes were identifi ed using clinical referral history and previous ECGs. After evaluating FCL in these new-onset AF episodes, using a customized fibrillation wave analyzer with fast Fourier transform analysis, we divided the patients into a longer-FCL group and a shorter-FCL group using the median FCL (158 ms). Propensity score matching yielded 135 matched pairs of patients with comparable mean ages between the two groups. Four factors (brain natriuretic peptide levels, and use of angiotensin receptor blockers, calcium channel blockers or statins) exhibited a significant difference between the two groups. Multivariate analysis revealed that statin use was the only significant independent predictor of longer FCL (Odds ratio, 3.86; 95% CI, 1.659.63; P = 0.003). Among various clinical parameters, statin use was related to longer FCL at the time of new-onset AF in patients with AF.

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We previously defined “responders” as patients with increases in urine volume (UV) on day 1 after the administration of tolvaptan (TLV), and demonstrated that responders to TLV could be predicted with considerable accuracy by urine osmolality (U-OSM) levels. Responders and non-responders to TLV should be associated with different clinical courses after a certain time following TLV administration. Therefore, the aim of the present study was to validate our definition of responders by clinical parameters 1 week after administration of TLV. Data (n = 85) were obtained from inhospital patients with decompensated heart failure (HF) who had received TLV at 3.75-15 mg daily, and clinical data at 1 week after the administration of TLV were compared with those of baseline. Sixty patients (70.6%) were “responders”, in whom UV on day 1 increased after the administration of TLV compared with day 0. “Non-responders” were older, and had higher serum creatinine concentration and lower baseline U-OSM than “responders”. Serum creatinine concentration increased significantly in “non-responders”, but was unchanged in “responders”. Body weight, plasma B-type natriuretic peptide concentration, and HF symptom score decreased significantly in “responders”, but remained unchanged in “non-responders”. Increases in UV after the first administration of TLV were closely correlated with improvement of congestive HF after 1 week of TLV treatment, which verifi ed our defi nition of “responders” to TLV.

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Self-care is a cornerstone for the successful management of heart failure (HF). The purpose of this study was to examine the impacts of HF self-care on prognosis in Japanese patients with HF. A total of 283 HF outpatients (age 64 ± 14, 70% male, 52% HFrEF) were enrolled. We asked patients to answer about their adhevence to 5 self-care behaviors (medication, eating a low-sodium diet, regular exercise, daily weight check, and treatment seeking behavior). On the basis of the results, we classified patients into a good self-care group and a poor self-care group. The primary outcome was HF hospitalization and/or cardiac death. In total, 65% of patients were classifi ed into the poor self-care group. During a median follow-up of 2 years, cardiac events occurred more frequently in the poor self-care group (22% versus 9.6%, P = 0.013). Poor self-care was an independent risk factor for cardiac events in Cox regression analysis adjusted for clinical parameters (hazard ratio = 2.86, P = 0.005). Poor self-care was also associated with an increased number of HF hospitalizations as well as an extended length of hospital stay for HF. Poor knowledge about HF was an independent determinant for poor self-care in multivariate logistic regression analysis (odds ratio = 0.92, P = 0.019). Insufficient self-care is an independent risk factor for cardiac events in Japanese patients with HF.

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The use of diuretics and ultrafiltration in acute heart failure syndrome (AHFS) has been investigated in a number of randomized controlled trials (RCTs). However, the benefits have been variable. We therefore performed a meta-analysis to examine the overall effect of all-cause mortality, rehospitalization, renal function, dyspnea relief, and adverse events in patients with AHFS. We identified RCTs by a systematic search of MEDLINE, EMBASE, and the Cochrane Controlled Clinical Trials Register Database. Eligible RCTs were those that enrolled patients with AHFS and involved comparison of diuretic versus ultrafiltration therapy. Five RCTs with a total of nearly 500 patients were included. Overall, ultrafi ltration therapy was not associated with significantly decreased risk of all-cause mortality (relative risk [RR], 0.977; 95% confidence interval [CI], 0.602 to 1.587; P = 0.925; I² = 0.0%), rehospitalization (RR, 0.903; 95% CI, 0.696 to 1.170; P = 0.440; I² = 77.4%), dyspnea score (weighted mean difference [WMD], 0.168; 95% CI, -0.318 to 0.653; P = 0.498; I² = 11.4%) and creatinine (WMD, 0.055 mg/mL; 95% CI, -0.101 to 0.210; P = 0.491; I² = 48.4%). However, there was significantly more weight loss (WMD, 1.333 kg; 95% CI, 0.186 to 2.479; P = 0.023; I² = 57.7%) and net fluid removal (WMD, 1459.432 mL; 95% CI, 275.911 to 2642.953; P = 0.016; I² = 25.2%) in the ultrafi ltration-therapy group. There was no significant difference in the risk of adverse events between the two groups. Compared with diuretic therapy, ultrafiltration produces greater weight loss and net fluid removal in a safe and effective manner.

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Cardiac output (CO) is often desirable for assessing the hemodynamic condition of a patient, especially in critically ill cardiac patients. Various noninvasive methods are available for this purpose. Inert gas rebreathing (IGR) and 2D-Doppler echocardiography methods have been validated. Based on the relationship between pulse wave transit time and stroke volume, the VISMO^® provides an estimated continuous cardiac output (esCCO) measurement using only an electrocardiogram, pulse oximeter wave, and cuff arterial blood pressure. Doppler echocardiography is being currently used in every day practice in this setting and IGR is a validated method, thus we wanted to assess the agreement between these 3 methods for noninvasive CO calculation and reproducibility of esCCO. Patients followed in our cardiology department received on the same day a CO analysis by esCCO, Doppler echocardiography and IGR. Thirty-four patients were included (16 women, mean age 65 ± 15 years). Bland and Altman plots showed a good agreement between IGR and 2D-Doppler echocardiography (bias = 0.31 L/minute). Though there was also an agreement between esCCO and the other 2, the bias was rather large: 1.18 L/minute with IGR and 1.51 L/min with 2D-Doppler echo. The intraclass correlation coefficient was poor whatever the methods. However, esCCO had a satisfactory reproducibility and accuracy compared rather well with the other 2. This method could be suitable for patient screening and monitoring.

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The aim of this study was to evaluate the short-term operative results of patients with Marfan syndrome who underwent thoracic or abdominal aortic surgery in a 4-year period in Japan. Data were collected from the Japan Cardiovascular Surgery Database (JCVSD). We retrospectively analyzed the data of 845 patients with Marfan syndrome who underwent cardiovascular surgery between January 2008 and January 2011. Logistic regression was used to generate risk models. The early mortality rate was 4.4% (37/845). Odds ratios (OR), 95% confi dence intervals (CI), and P values for structures and processes in the mortality prediction model were as follows: renal insufficiency (OR, 11.37; CI, 3.7234.66; P < 0.001); respiratory disorder (OR, 11.12; CI, 3.20-38.67; P < 0.001); aortic dissection (OR, 13.02; CI, 2.8060.60; P = 0.001); pseudoaneurysm (OR, 11.23; CI, 1.38-91.66; P = 0.024); thoracoabdominal aneurysm (OR, 2.67; CI, 1.22-5.84; P = 0.014); and aortic rupure (OR, 4.23; CI, 1.26-14.23; P = 0.002). The mortality prediction model had a Cindex of 0.82 and a Hosmer–Lemeshow P value of 0.56. In conclusion, this study demonstrated that renal insuffi ciency and respiratory disorder had great impact on the operative mortality of Marfan patients undergoing cardiovascular surgery. Because patients with aortic dissection or aortic rupture showed high operative mortality, close follow-up to avoid emergency operation is mandatory to improve the operative results. Achieving good results from surgery of the thoracoabdominal aorta was quite challenging, also in Marfan patients.

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Treatment of refractory Takayasu arteritis (TA) remains an unresolved clinical issue. Patients usually respond to glucocorticoid (GC) therapy, but often relapse on tapering of the GC dose. The aim of the present study was to assess the safety and efficacy of the interleukin-6 (IL-6) receptor antibody tocilizumab (TCZ) in patients with TA refractory to conventional therapies including GC. Four patients with TA who had shown GC resistance received TCZ infusions (8 mg/kg) every 4 weeks a total of at least 24 times (range, 24 to 51). Clinical symptoms, the serum levels of acute phase proteins and IL-6, GC dosage necessary to maintain remission, and cross-sectional imaging by enhanced CT and MRI were assessed. All patients achieved good clinical response and rapid normalization of the acute phase proteins such as C-reactive protein and serum amyloid A during the therapy with TCZ. The mean dosage of prednisolone could be reduced from 21.3 mg/day to 1.5 mg/day. Although the serum IL-6 level was transiently elevated in all patients after several TCZ infusions, it gradually recovered to the initial level. Along with the decrease of serum IL-6, two patients exhibited signifi cant reduction in thickened arterial lesions. No drug-related adverse effects were noted. In this small group of patients with refractory TA, TCZ therapy was effective and well-tolerated. Further larger studies should be conducted to confirm this finding.

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Recent reports assert that dental health is linked to an increased risk of cardiovascular disease. It is well known that Aggregatibacter actinomycetemcomitans (A.a.) is highly associated with heart disease. Indeed, we previously reported that A.a. affects the development of heart disease in a mouse model. However, no reports have clarified the relationship between A.a. and experimental autoimmune myocarditis (EAM). The aim of this study was to investigate the effects of A.a. on EAM in mice. EAM was induced via the injection of cardiac myosin into the mice. A.a. or PBS was then injected into the mice using a chamber implanted into the back of each mouse. The weight of the organs and echocardiograms were obtained and a pathological analysis and quantitative RT-PCR were performed. Echocardiography showed that no statistical difference was observed between the two groups. A histopathological analysis demonstrated that the number of areas affected by myocarditis in the A.a.-injected EAM group was significantly increased compared to that observed in the PBS-injected EAM group (P < 0.05). The hearts of the mice in the A.a.-injected EAM group exhibited signifi cantly increased expressions of MMP-9 mRNA compared to the hearts of the mice in the PBS-injected EAM group (P < 0.05). These results show that A.a. aggravated EAM via an enhanced MMP expression.

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Chemotherapy for malignant tumors has diversified, and recognizing its side effects has become more important than ever. Both cardiotoxicity and neurotoxicity are rare, but they are among the most serious side effects caused by 5-fluorouracil (5-FU). Capecitabine is an orally administered prodrug that converts preferentially to 5-FU within tumors, resulting in enhanced concentrations of 5-FU in tumor tissue. Given that it targets tumor tissue, capecitabine was expected to reduce the risk of side effects associated with fluoropyrimidine. Here, we present the case of a 62-year-old man with colorectal adenocarcinoma who simultaneously experienced cardiomyopathy with cardiogenic shock and cerebral leukoencephalopathy during treatment with capecitabine. During emergency coronary angiography, ST-segment elevation and severely reduced left ventricular wall motion were observed; however, no severe coronary stenosis or spasm was revealed. Furthermore, we present a review of the literature on capecitabine-induced cardiotoxicity. As of April 2013, 39 case reports on capecitabine-induced cardiotoxicity have been published; however, cardiomyopathy was very rare, with only 3 cases reported. It is important for physicians to be aware of the various rare, but potentially serious, adverse effects associated with capecitabine chemotherapy and to inform patients about the possibility of these side effects, including cardiotoxicity and neurotoxicity.

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Akihiro Shirakabe, MD has been named winner of the 2013 UEDA Heart Award. He received a diploma and ¥500,000 in award money.

The title of his article is as follows :

Long-Term Prognostic Impact After Acute Kidney Injury in Patients With Acute Heart Failure : Evaluation of the RIFLE Criteria.

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