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Abstract Background Anti‐tachycardia pacing (ATP) delivered from an implantable device is a useful tool to terminate ventricular tachycardia (VT). But its real‐world efficacy for those patients having multiple VTs with varying VT rates has not been fully studied. Methods Using the Nippon‐storm study database, efficacy of patient‐by‐patient basis ATP programing for Japanese patients having both non‐fast (120‐187 bpm) and fast VT (≥188 bpm) was assessed. According to the useful criteria of ≥50% success termination by ATP, patients were divided into three subgroups; success ≥50% for both non‐fast and fast VT (both useful), ≥50% only for non‐fast VT (non‐fast VT useful), or ≥50% for neither non‐fast nor fast VT (neither useful). Results During a median follow‐up of 28 months, ATP terminated 184 of the 203 non‐fast VT episodes (91%) and 86 of the 113 fast VT episodes (76%) in all 41 patients. In the patient‐by‐patient analysis, efficacy of ATP was not different between non‐fast and fast VT in most of the patients (36/41 = 88%); 32 patients were in the both useful and four other patients in the neither useful. Neither ischemic nor non‐ischemic structural heart disease was associated with the ATP efficacy, whereas LVEF more than 37.0% and non‐prescribed amiodarone were characteristics of the patients classified into the both useful. Conclusions ATP well terminated both non‐fast and fast VT occurring in individual Japanese patients with various structural heart diseases in the real‐world device treatment and this finding further supports ATP programing for all device tachycardia detection zones in most patients with multiple VTs.

Background: The Nippon Storm Study was a prospective observational study designed to gather clinical data on implantable cardioverter-defibrillator (ICD) therapy in Japanese patients. Objective: The purpose of this subanalysis was to compare the incidence of ICD therapy in patients with left ventricular dysfunction owing to coronary artery disease (CAD) for primary and secondary prophylaxis of sudden cardiac death. Methods: We analyzed data of 493 patients with CAD and ICDs (men, 87%; age, 68 ± 10 years; left ventricular ejection fraction, 36% ± 13%; primary prophylaxis, 36%). All patients were followed up for at least 2 years. Propensity score matching was used to select patient subgroups for comparison: 133 patients with ICD for primary prophylaxis and 133 with ICD for secondary indications. Results: There were no significant differences between primary and secondary prophylaxis groups with respect to the incidence of appropriate ICD therapy within 2 years (0.153 vs 0.239; hazard ratio, 1.565 [95% confidence interval (CI), 0.898–2.727]; P = .114). Two-year electrical storm risks were 3.3% and 9.6% with HR = 3.236 (95% CI, 1.058–9.896; P = .039) in patients with primary and secondary prophylaxis, respectively. Conclusion: The incidence of ICD therapy received by patients with CAD for primary and secondary prophylaxis was not significantly different based on our propensity score–matched analysis. However, secondary-prophylaxis ICD therapy seems to be associated with a significantly higher risk for electrical storm than primary-prophylaxis ICD therapy.

Introduction: Various risk factors for the first inappropriate implantable cardioverter-defibrillator (ICD) therapy event have been reported, including a history of atrial fibrillation/atrial flutter (AF/AFL), younger age, and multiple zones. Nonetheless, which factors are concordant with real-world data has not been clarified, and risk factors for the second inappropriate ICD therapy event have not been well examined. This study aimed to clarify the risk factors for the first and second inappropriate ICD therapy events. Methods: We conducted a post-hoc secondary analysis of data from a multicenter, prospective observational study (the Nippon Storm Study) designed to clarify the risk factors for electrical storm. Results: The analysis included data from 1549 patients who received ICD or cardiac resynchronization therapy with defibrillator (CRT-D). Over a median follow-up of 28 months, 293 inappropriate ICD therapy events occurred in 153 (10.0%) patients. On multivariate Cox regression analysis, the risk factors for the first inappropriate ICD therapy event were younger age (hazard ratio [HR], 0.986; p = 0.028), AF/AFL (HR, 2.324; p = 0.002), ICD without CRT implantation (HR, 2.377; p = 0.004), and multiple zones (HR, 1.852; p = 0.010). “No-intervention” after the first inappropriate ICD therapy event was the sole risk factor for the second inappropriate ICD therapy event. Conclusions: Risk factors for the first inappropriate ICD therapy event were similar to those previously reported. Immediate intervention after the first inappropriate ICD therapy event could reduce the risk of the second inappropriate event.

Background: Patients with implantable cardioverter defibrillator (ICD) use for primary prevention (primary prevention patients) of sudden cardiac death have lower incidence of appropriate ICD therapy (app-Tx) compared with those with ICD use for secondary prevention (secondary prevention patients). However, detail analysis of a second app-Tx after a first app-Tx is still lacking. Objective: This study aimed to compare the incidence of a second app-Tx in primary vs secondary prevention patients. Methods: We conducted sub-analysis of the Nippon Storm Study, which was a prospective, observational study involving 985 patients with structural heart disease (left ventricular ejection fraction ≤ 50%). Of these, we selected 251 patients (62 ± 14 years old, 82% men) who experienced at least one appropriate ICD therapy, and compared occurrence of a second app-Tx between primary (n = 116) and secondary (n = 135) prevention patients. Results: There was no significant difference in the incidence of a second app-Tx between primary and secondary prevention patients (the cumulative incidence for a second app-Tx was 59% at 1 year and 79% at 3 years in primary prevention patients vs the cumulative incidence for the second app-Tx was 59% at 1 year and 75% at 3 years in secondary prevention patients).Additionally, we evaluated the incidence of a second app-Tx according to basal structural disease (ischemic and non-ischemic cardiomyopathy) and found no significant difference between primary and secondary prevention patients. Conclusion: Once app-Tx occurs, primary prevention patients acquire the high risk of subsequent ventricular arrhythmias because there is a comparable incidence of a second app-Tx in secondary prevention patients.

Background. The saline-induced distal coronary pressure/aortic pressure ratio predicted fractional flow reserve (FFR). The resting full-cycle ratio (RFR) represents the maximal relative pressure difference in a cardiac cycle. Therefore, the present study aimed to compare the results of saline-induced RFR (sRFR) with FFR. Methods. Seventy consecutive lesions with only moderate stenosis were included. The FFR, RFR, and sRFR values were compared. The sRFR was assessed using an intracoronary bolus infusion of saline (2 mL/s) for five heartbeats. The FFR was obtained after an intravenous injection of papaverine. Results. Overall, the FFR, sRFR, and RFR values were 0.78 ± 0.12, 0.79 ± 0.13, and 0.83 ± 0.14, respectively. With regard to anatomical morphology were 40, 18, and 12 cases of focal, diffuse, and tandem lesion. There was a significant correlation between the sRFR and FFR (R = 0.96, p

Background: Third-generation stents with abluminal biodegradable polymer (BP) might facilitate early healing. Therefore, we compared early healing between second-generation and third-generation stents using coronary angioscopy (CAS) and optical frequency domain imaging [OFDI]. Methods: We prospectively enrolled 30 consecutive patients with stent implantation for acute coronary syndrome (cobalt‑chromium [CoCr] everolimus-eluting stent [EES] [n = 10], BP-EES [n = 10], and BP-sirolimus eluting stent [SES] [n = 10]). All patients underwent CAS and OFDI 1 month after initial percutaneous coronary intervention. On OFDI, the stent coverage (SC), thrombus, and peri-strut low intensity area (PLIA) were assessed. CAS findings were recorded for the grade of SC, grade of yellow color (YC), and grade of the thrombus (TG). Results: On OFDI, the incidences of any thrombus at the 1-month follow-up were 70%, 80%, and 80% in the CoCr-EES, BP-EES, and BP-SES groups, respectively. The percentage of coverage was comparable among the groups (CoCr-EES 79.8 vs. BP-EES 79.9 vs. BP-SES 80.1%, P = 0.96). However, the number of struts with PLIA was numerically higher in the BP-SES group than in the CoCr-EES and BP-EES groups (46.4 ± 25.1 vs. 21.6 ± 13.2 vs. 22.0 ± 7.2%, P = 0.08). In the CoCr-EES, BP-EES, and BP-SES groups, mean grades of SC were 1.25 ± 0.5, 1.25 ± 0.5, and 0.85 ± 0.70 (P = 0.60); mean grades of YC were 0.75 ± 0.5, 0.80 ± 0.45, and 0.88 ± 0.37 (P = 0.65), and mean grades of TG were 1.00 ± 1.00, 1.20 ± 0.83, and 0.88 ± 0.64 (P = 0.75), respectively. Conclusion: Third-generation stents are not inferior to second-generation stents regarding stent coverage. However, PLIA on OFDI was often observed with BP-SESs, indicating involvement of the fibrin component. Keywords: Early healing, Coronary angioscopy, Optical frequency domain imaging

Abstract Background Glycosuria produced by sodium–glucose co-transporter-2 (SGLT-2) inhibitors is associated with weight loss. SGLT-2 inhibitors reportedly might reduce the occurrence of cardiovascular events. Epicardial adipose tissue (EAT) is a pathogenic fat depot that may be associated with coronary atherosclerosis. The present study evaluated the relationship between an SGLT-2 inhibitor (dapagliflozin) and EAT volume. Methods In 40 diabetes mellitus patients with coronary artery disease (10 women and 30 men; mean age of all 40 patients was 67.2 ± 5.4 years), EAT volume was compared prospectively between the dapagliflozin treatment group (DG; n = 20) and conventional treatment group (CTG; n = 20) during a 6-month period. EAT was defined as any pixel that had computed tomography attenuation of − 150 to − 30 Hounsfield units within the pericardial sac. Metabolic parameters, including HbA1c, tumor necrotic factor-α (TNF-α), and plasminogen activator inhibitor-1 (PAI-1) levels, were measured at both baseline and 6-months thereafter. Results There were no significant differences at baseline of EAT volume and HbA1c, PAI-1, and TNF-α levels between the two treatment groups. After a 6-month follow-up, the change in HbA1c levels in the DG decreased significantly from 7.2 to 6.8%, while body weight decreased significantly in the DG compared with the CTG (− 2.9 ± 3.4 vs. 0.2 ± 2.4 kg, p = 0.01). At the 6-month follow-up, serum PAI-1 levels tended to decline in the DG. In addition, the change in the TNF-α level in the DG was significantly greater than that in the CTG (− 0.5 ± 0.7 vs. 0.03 ± 0.3 pg/ml, p = 0.03). Furthermore, EAT volume significantly decreased in the DG at the 6-month follow-up compared with the CTG (− 16.4 ± 8.3 vs. 4.7 ± 8.8 cm3, p = 0.01). Not only the changes in the EAT volume and body weight, but also those in the EAT volume and TNF-α level, showed significantly positive correlation. Conclusion Treatment with dapagliflozin might improve systemic metabolic parameters and decrease the EAT volume in diabetes mellitus patients, possibly contributing to risk reduction in cardiovascular events.

Background The natural history and long‐term outcome in pediatric patients with idiopathic ventricular fibrillation (IVF) are poorly characterized. We sought to define the clinical characteristics and long‐term outcomes of a pediatric cohort with an initial diagnosis of IVF. Methods and Results Patients were included from an International Registry of IVF (consisting of 496 patients). Inclusion criteria were: (1) VF with no identifiable cause following comprehensive analysis for ischemic, electrical or structural heart disease and (2) age ≤16 years. These included 54 pediatric IVF cases (age 12.7±3.7 years, 59% male) among whom 28 (52%) had a previous history of syncope (median 2 syncopal episodes [interquartile range 1]). Thirty‐six (67%) had VF in situations associated with high adrenergic tone. During a median 109±12 months of follow‐up, 31 patients (57%) had recurrence of ventricular arrhythmias, mainly VF. Two patients developed phenotypic expression of an inherited arrhythmia syndrome during follow‐up (hypertrophic cardiomyopathy and long QT syndrome, respectively). A total of 15 patients had positive genetic testing for inherited arrhythmia syndromes. Ten patients (18%) experienced device‐related complications. Three patients (6%) died, 2 due to VF storm. Conclusions In pediatric patients with IVF, a minority develop a definite clinical phenotype during long‐term follow‐up. Recurrent VF is common in this patient group.

In patients with Brugada syndrome (BS), VF occurred predominantly during the nocturnal period. Some patients also developed ESs. In addition to the circadian rhythm, patients showed weekly and seasonal patterns. The patients with ESs had peak episodes of VF on Saturday and in the winter and spring, while episodes of VF in patients with single VF events occurred most often on Monday with smaller seasonal variation. Except for age, there was no difference in the clinical or ECG characteristics between the patients with ESs and those with single VF episodes.

Brugada syndrome (BS) is characterized by ST-segment elevation in the right precordial leads and is associated with sudden cardiac death secondary to polymorphic ventricular tachycardia (PVT)/ventricular fibrillation (VF) in the absence of structural heart disease. Vasospastic angina (VSA) and neurally mediated syncope (NMS) are observed occasionally in BS patients, although their associations with BS remain controversial. The incidence of concomitant VSA and BS is 11–13%, and there might be an increased risk of VF when BS and VSA coexist, as reported in several previous studies. Whether the manifestation or augmentation of a coved-type electrocardiography (ECG) pattern is associated with coronary artery vasospasm is unclear. The significance of increased coved-type ST-segment elevation and its relation to arrhythmogenesis in BS is an important issue that needs to be resolved in future studies of concomitant BS and VSA. The coexistence of BS and VSA should always be taken into account in the management of both conditions, particularly when calcium antagonists are used. Previous reports suggest a high incidence of NMS in BS patients, and it is often difficult to differentiate between NMS and high-risk syncopal episodes due to ventricular tachyarrhythmias. Therefore, the identification of a therapeutic strategy to treat syncope in BS patients is often problematic. The autonomic nervous system is involved in arrhythmogenesis and may precipitate cardiac events in BS patients. To investigate BS, it may be useful to consider VSA and NMS as concomitant abnormalities. Future studies are needed to understand the relationship between BS and the autonomic nervous system.

Purpose: The aim of this study was to describe the recent conditions associated with implantable defibrillation therapy for individual underlying heart diseases. Methods: Ten thousand six hundred and five patients with implantable cardioverter-defibrillators (ICDs) or cardiac resynchronization therapy defibrillators (CRT-Ds) that were implanted from 2006 to 2010 were selected from the Japan Cardiac Device Therapy Registry database. They were divided into 12 disease categories and further divided into either primary or secondary prevention of sudden cardiac death. Results: The major underlying diseases of the patients in this cohort were ischemic heart disease (IHD, 35%), dilated cardiomyopathy (DCM, 25%), hypertrophic cardiomyopathy (HCM, 8%), and Brugada syndrome (Brugada, 8%). There were no structural heart diseases in this cohort; the incidence of IHD was relatively lower than that of western countries, while the incidence of cardiomyopathy was higher. The percentage of primary prevention (% primary) among the individual diseases varied. IHD was the most prevalent underlying condition in the patient cohort; however, the % primary was 33%, which was relatively lower than that of the other structural heart diseases. The % primary was relatively higher in patients with DCM (57%) and Brugada (47%). Over 5 years, the % primary gradually increased in patients with DCM, IHD, and HCM, with a particularly dramatic increase in those with DCM. A decrease in the % primary among patients with Brugada began in 2008. Conclusions: In patients that underwent implantable defibrillation therapy, there was a relatively lower % primary in the IHD group, and a substantial increase in the % primary in patients with DCM.

Background: Significance of an ST-T abnormality in subjects with no apparent heart diseases is to be determined. Subjects and methods: The study involved 44,990 adults (16,368 males and 28,622 females) aged 40-85 years who under went an annual health examination. Cardiovascular risks (CVRs) were considered positive if 1) body mass index was ≥ 25Kg/m2, 2) systolic blood pressure (BP) ≥ 130 mmHg and/or diastolic BP ≥ 85mmHg, 3) triglyceride ≥ 150 mg/ dl, 4) HDL-C level ≤ 40mg/dl for men and ≤ 50mg/dl for women, or 5) fasting blood glucose ≤ 110 mg/dl. The relation between CVRs and ST-T abnormalities were evaluated. Results: ST-T abnormalities were found in 6.49% in males, and more frequently in females: 8.45%. Each CVR and the number of combined CVRs were risk factors for ST-T abnormalities on ECG (P < 0.0001 for a trend). On the other hand, ECG-based LVH was found in 5.7% but showed no relation with CVRs or their com binations. ST-T abnormalities may represent preclinical cardiac involvement of CVRs more sensitively than LVH on ECG and ECG findings may be used in mass examinations. Conclusions: ST-T abnormalities without apparent heart diseas may be considered to be nonspecific but this cross-sectional study showed that they are related to CVRs and may be used as an early marker of preclinical cardiac damage by CVRs.

Diabetic cardiomyopathy and nephropathy induce endoplasmic reticulum stress (ERS) and ERS-initiated apoptosis. The primary function of 14-3-3 protein is to inhibit apoptosis, but the roles of this protein in protecting against cardiac ERS and apoptosis in the diabetic heart are largely unknown. In this study, we investigated the in vivo role of 14-3-3 protein in diabetic ERS and apoptosis using streptozotocin (STZ)-induced transgenic mice that showed cardiac-specific expression of a dominant negative (DN) 14-3-3η protein mutant. The expression levels of cardiac glucose-regulated protein (GRP) 78, inositol-requiring enzyme (Ire) 1α, and tumor necrosis factor receptor (TNFR)-associated factor (TRAF) 2 protein were significantly increased in the diabetic DN 14-3-3η mice compared with the diabetic wild-type. Moreover, cardiac apoptosis and the expression of CCAAT / enhancer binding protein homology protein (CHOP), caspase-12, and cleaved caspase-12 protein were significantly increased in the diabetic DN 14-3-3η mice. In conclusion, partial depletion of 14-3-3 protein in the diabetic heart exacerbates cardiac ERS and activates ERS-induced apoptosis pathways, at least in part, through the regulation of CHOP and caspase-12 via the Ire1α/TRAF2 pathway. The enhancement of 14-3-3 protein expression can be used as a novel protective therapy against ERS and ERS-initiated apoptosis in the diabetic heart. Keywords:: 14-3-3 protein, diabetes mellitus, endoplasmic reticulum stress, apoptosis, glucose-regulated protein (GRP) 78

Slurs or notches at the terminal portion of the QRS complexes are called J waves, which may be associated with myocardial ischemia. We describe our experience with a case of a patient with acute inferior myocardial infarction in whom J waves were observed in the inferior leads with ST-segment elevation. The coronary artery was completely occluded, and during percutaneous intervention, ST-segment elevation was normalized first, followed by the disappearance of the J waves after full revascularization. On follow-up coronary angiography (CAG), the J waves in the inferior leads reappeared during the right CAG. The J waves were associated with an alteration of the electrical axis. J waves developing in association with myocardial ischemia seemed to be more sensitive to ischemia and might represent a depolarization abnormality.

An understanding of the clinical aspects of electrical storm (E-storms) in patients with implantable cardiac shock devices (ICSDs: ICDs or cardiac resynchronization therapy with defibrillator [CRT-D]) may provide important information for clinical management of patients with ICSDs. The Nippon Storm Study was organized by the Japanese Heart Rhythm Society (JHRS) and Japanese Society of Electrocardiology and was designed to prospectively collect a variety of data from patients with ICSDs, with a focus on the incidence of E-storms and clinical conditions for the occurrence of an E-storm. Forty main ICSD centers in Japan are participating in the present study. From 2002, the JHRS began to collect ICSD patient data using website registration (termed Japanese cardiac defibrillator therapy registration, or JCDTR). This investigation aims to collect data on and investigate the general parameters of patients with ICSDs, such as clinical backgrounds of the patients, purposes of implantation, complications during the implantation procedure, and incidence of appropriate and inappropriate therapies from the ICSD. The Nippon Storm Study was planned as a sub-study of the JCDTR with focus on E-storms. We aim to achieve registration of more than 1000 ICSD patients and complete follow-up data collection, with the assumption of a 5–10% incidence of E-storms during the 2-year follow-up.

ABSTRACT: We examined the effects of chlorpromazine on NO3- transport between erythrocytes (RBCs) and extracellular fluid. Chlorpromazine (10 μg/ml) did not influence NO3- movement in both whole blood and RBC suspension. Though an anion exchanger (AE1) inhibitor DIDS (4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid, 100 μM) did not alter NO3- movement in whole blood, it inhibited the movement in a concentration-dependent manner in the RBC suspension. The inhibition was abrogated by plasma and albumin concentration-dependently. Our results indicated that chlorpromazine had no effect on NO3- transport through AE1 and that the inertness of DIDS on AE1 in whole blood is due to interference by albumin in plasma.

We described a case of an 82-year-old male who presented with a granuloma entrapping the polyurethane-coated pacing lead at the site of contact on the atrium. He had been paced for 8 years without symptoms or signs suggestive of an allergic reaction to the pacemaker system and died from thrombosis of the superior mesenteric artery and heart failure. A histological examination of the nodule showed an incidental granuloma with multinucleated giant cells. No granuloma was found in the heart or the lung.

BACKGROUND: Many diseases associated with bone marrow transplantation (BMT) are caused by transplanted hematopoietic cells, and the onset of these diseases occurs after homing of donor cells in the initial phase after BMT. Noninvasive observation of donor cell homing shortly after transplantation is potentially valuable for improving therapeutic outcomes of BMT by diagnosing the early stages of these diseases. METHODOLOGY/PRINCIPAL FINDINGS: Freshly harvested near-infrared fluorescence-labeled cells were noninvasively observed for 24 h after BMT using a photon counting device to track their homing process. In a congenic BMT model, the homing of Alexa Fluor 750-labeled donor cells in the tibia was detected less than 1 h after BMT. In addition, subsequent cell distribution in an intraBM BMT model was successfully monitored for the first time using this method. In the allogeneic BMT model, T-cell depletion decreased the near-infrared fluorescence (NIRF) signals of the reticuloendothelial system. CONCLUSIONS/SIGNIFICANCE: This approach in several murine BMT models revealed that the transplanted cells homed within 24 h after transplantation. NIRF labeling is useful for tracking transplanted cells in the initial phase after BMT, and this approach can contribute to in vivo studies aimed at improving the therapeutic outcomes of BMT.

The reversal rate from clustering of cardiovascular disease (CVD) risk factors—components of the metabolic syndrome (MetS) is not known. Methods and Results. Among 35,534 subjects who received the annual health examinations at the NiigataHealth Foundation (Niigata, Japan), 4,911 subjects had clustering of 3 or more of the following CVD risk factors: (1) body mass index (BMI) ≥25 Kg/m2, (2) blood pressure ≥130 mm Hg in systolic and/or ≥85 mm Hg in diastolic, (3) triglycerides ≥150 mg/dL, (4) high-density lipoprotein cholesterol ≤40 mg/dL in men, ≤50 mg/dL in women, and (5) fasting blood glucose ≥100 mg/dL. After 5 years 1,929 subjects had a reversal of clustering (39.4%). A reversal occurred more often in males. The subjects with a reversal of clustering had milder level of each risk factor and a smaller number of risk factors, while BMI was associated with the least chance of a reversal. Conclusion. We concluded that a reversal of clustering CVD risk factors is possible in 4/10 subjects over a 5-year period by habitual or medical interventions. Gender and each CVD risk factor affected the reversal rate adversely, and BMI was associated with the least chance of a reversal.

Background: This study aimed to evaluate the characteristics and clinical outcomes (major bleeding [MB] and thromboembolic events [TEEs]) of atrial fibrillation (AF) patients with chronic kidney disease (CKD)who received direct oral anticoagulant (DOAC) therapy. Methods: Data prospectively collected from a single-center registry containing 2,272 patients with DOAC prescription for AF (apixaban [n=1,014], edoxaban [n=267], rivaroxaban [n=498], and dabigatran[n=493]) were retrospectively analyzed. Patients were monitored for two years and classified into the CKD (n=1460) and non-CKD groups(n=812). MB and TEEs were evaluated. Results: The mean age was 72±10 years, with the CHADS2,CHA2DS2-VASc, and HAS-BLED scores being 1.95±1.32, 3.21±1.67, and 1.89±0.96,respectively.Incidence rates of MB and TEEs were 2.3%/year and 2.1%/year, respectively. The CKD group was older and had lower body weight and higher CHADS2,CHA2DS2-VASc, and HAS-BLED scores than the non-CKD group. Kaplan–Meier curve analysis revealed that the incidence of MB and TEEs was higher in the CKD group. Multiple logistic regression analysis in the CKD group revealed that age and stroke history were independent determinants of TEEs, and low body weight tended to be a determinant of MB. The inappropriate low dose use was higher for apixaban than other DOACs in the CKD group. Consequently, for apixaban, the incidence of stroke was significantly higher in the CKD group than in the non-CKD group. Conclusion: Patients with CKD were characterized by factors that predisposed them to MB and TEEs, such as older age and low body weight. In a single-center registry, only treatment with apixaban in the CKD group led to a higher incidence of TEEs. [ABSTRACT FROM AUTHOR]

Aims To confirm the presence of tachycardia-induced slur or notch in the terminal portion of the QRS complexes in a general patient population. Methods and results A tachycardia-induced J wave was defined as a slur or notch in the terminal portion of the QRS complexes newly induced at short RR intervals during atrial premature contractions (APCs) or atrial electrical stimulation in the electrophysiological study (EPS). Twenty-three out of 2000 patients with general diseases were involved. All patients with aborted sudden cardiac death, ventricular fibrillation or a family history of sudden cardiac death were excluded. The mean age was 72 ± 9 years, and 11 patients were male (47.8%). When the RR interval was shortened from 821 ± 142 ms to 464 ± 52 ms in the conducted APCs (P  < 0.0001), J waves became diagnostic (0.02 ± 0.03 mV to 0.20 ± 0.07 mV, P  < 0.0001). J waves were confined to the inferior leads in 22 (95.7%) patients and were notched in 11 (47.8%) and slurred in 12 (52.2%) patients. The induction of J waves was accompanied by visible changes of the QRS morphology. When the post-APC RR interval was prolonged to 992 ± 305 ms (P  = 0.0154 vs. baseline), the J waves were similar to baseline levels. During the EPS, J wave induction was confirmed during atrial stimulation. There were no characteristic clinical or ECG features in the patients with tachycardia-induced J waves. Conclusions J waves can be newly induced by short RR intervals in a general patient population, and a conduction delay is the likely mechanism causing such J waves. [ABSTRACT FROM AUTHOR]

Electrocardiograms (ECGs) have been employed to medically evaluate participants in population-based studies, and ECG-derived predictors have been reported for incident atrial fibrillation (AF). Here, we reviewed the status of ECG in predicting new-onset AF. We surveyed population-based studies and revealed ECG variables to be risk factors for incident AF. When available, the predictive values of each ECG risk marker were calculated. Both the atrium-related and ventricle-related ECG variables were risk factors for incident AF, with significant hazard risks (HRs) even after multivariate adjustments. The risk factors included P-wave indices (maximum P-wave duration, its dispersion or variation and P-wave morphology) and premature atrial contractions (PACs) or runs. In addition, left ventricular hypertrophy (LVH), ST-T abnormalities, intraventricular conduction delay, QTc interval and premature ventricular contractions (PVCs) or runs were a risk of incident AF. An HR of greater than 2.0 was observed in the upper 5th percentile of the P-wave durations, P-wave durations greater than 130 ms, P-wave morpholyg, PACs (PVCs) or runs, LVH, QTc and left anterior fascicular blocks. The sensitivity , specificity and the positive and negative predictive values were 3.6-53.8%, 61.7-97.9%, 2.9-61.7% and 77.4-97.7%, respectively. ECG variables are risk factors for incident AF. The correlation between the ECG-derived AF predictors, especially P-wave indices, and underlying diseases and the effects of the reversal of the ECG-derived predictors on incident AF by treatment of comorbidities require further study. [ABSTRACT FROM AUTHOR]

Background: To know the underlying mechanisms of J waves, the response to atrial pacing was studied in patients with idiopathic ventricular fibrillation (IVF) and patients with non-IVF.Methods and Results: In 8 patients with IVF, the J-wave amplitude was measured before, during, and after atrial pacing. All patients had episodes of ventricular fibrillation without structural heart disease. The responses of J waves were compared with those of the 17 non-IVF control subjects who revealed J waves but no history of cardiac arrest and underwent electrophysiological study. The IVF patients were younger than the non-IVF patients (28±10 versus 52±14 years, respectively; P=0.002) and had larger J waves with more extensive distribution. J waves decreased from 0.35±0.26 to 0.22±0.23 mV (P=0.025) when the RR intervals were shortened from 782±88 to 573±162 ms (P=0.001). A decrease (≥0.05 mV) in the J-wave amplitude was observed in 6 of the 8 patients. In addition, 1 patient showed a distinct reduction of J waves in the unipolar epicardial leads. In contrast, J waves were augmented in the 17 non-IVF subjects from 0.27±0.09 to 0.38±0.10 mV (P<0.001): augmented in 9 and unchanged in the 8 subjects. The different response patterns of J waves to rapid pacing suggest different mechanisms: early repolarization in IVF patients and conduction delay in non-IVF patients.Conclusions: The response to atrial pacing was different between the IVF and non-IVF patients, which suggests the presence of different mechanisms for the genesis of J waves. [ABSTRACT FROM AUTHOR]

The Brugada syndrome (BrS) is an arrhythmogenic disease associated with an increased risk of ventricular fibrillation and sudden cardiac death. The risk stratification and management of BrS patients, particularly of asymptomatic ones, still remains challenging. A previous history of aborted sudden cardiac death or arrhythmic syncope in the presence of spontaneous type 1 ECG pattern of BrS phenotype appear to be the most reliable predictors of future arrhythmic events. Several other ECG parameters have been proposed for risk stratification. Among these ECG markers, QRS-fragmentation appears very promising. Although the value of electrophysiological study still remains controversial, it appears to add important information on risk stratification, particularly when incorporated in multiparametric scores in combination with other known risk factors. The present review article provides an update on the pathophysiology, risk stratification and management of patients with BrS. [ABSTRACT FROM AUTHOR]

The patient was a 33-year-old male. Twenty years ago, he underwent radiofrequency catheter ablation for idiopathic sustained monomorphic ventricular tachycardia (VT) with an RBBB and superior axis pattern. The VT was inducible by programmed stimulation and entrained by rapid pacing. At this presentation, he developed palpitation and VT with the same morphology at the peak exercise on a treadmill with appearance of typical ECG pattern for Brugada syndrome (BrS). Pilsicainide induced the typical ECG pattern and premature ventricular beats (PVBs) of the same morphology as VT. The relationship between BrS and VT of left ventricular origin was discussed. [ABSTRACT FROM AUTHOR]

Background: Anticoagulation therapy is essential in atrial fibrillation (AF), and in Japan, less intense control is popular. Purpose: To assess the efficacy and safety with a special reference to low intensity warfarin therapy. Subjects and methods: In 488 out of 508 patients with non-valvular AF, prothrombin time-international normalized ratio (PT-INR) was kept at 1.6-2.59, and they were followed for 49.5 months: 2098 personyears. The mean age was 73.7 ± 9.9 years and 62% were male. The patients were divided by age: ≥70 years and <70 years, and by the intensity of warfarin therapy: PT-INR at 1.6-1.99 and at 2.0-2.59, respectively. The clinical data and event rates, ischemic stroke and major bleeding, were compared among the subgroups. Results: Heart failure, previous stroke, and higher CHADS2 score were more often reported in patients ≥ 70 years while males were involved more often as younger patients. A total of 166 of 339 patients ≥ 70 years and 69 of 149 patients <70 years belonged to the low intensity group. Ischemic stroke and major bleeding occurred in 1.47%/year and 1.27%/year, respectively but there was no difference between the two age groups and between the two intensities of warfarin therapy. Time in therapeutic range was a predictor for ischemic stroke. A fall of PT-INR to <1.6 was found in 41.9% with ischemic stroke and a rise >2.61 in 40.0% with major bleeding at the time of the events. Blunt trauma and concomitant use of antiplatelets were risks for intracranial hemorrhage in the patients ≥ 70 years. Conclusions: The event rates were similar between the low- (1.6-1.99) and high- (2.0-2.59) intensity warfarin therapy groups in aged patients: <70 years and ≥ 70 years. Time in therapeutic range and a transient fall or rise in PT-INR were risks for clinical events. Blunt head trauma and concomitant use of antiplatelets were risks for intracranial hemorrhage. [ABSTRACT FROM AUTHOR]

Abstract  In order to establish an efficient γδ T cell-mediated immunotherapy for hematological malignancies, we attempted to evaluate cytotoxicity against tumor cells by γδ T cells, which were generated from blood cells of patients with myeloma and lymphoma by culturing with zoledronate and a low dose of IL-2. Although γδ T cells were expanded in patients with myeloma and lymphoma as well as normal persons, the amplification rates of γδ T cells before and after culturing varied from patient to patient in myeloma and lymphoma. γδ T cells generated in patients with myeloma and lymphoma showed a potent cytotoxic ability against myeloma/lymphoma cell lines as shown in γδ T cells generated in normal subjects. In addition, γδ T cells generated in a patient with myeloma showed a cytotoxic ability against self myeloma cells freshly prepared from bone marrow. However, the same γδ T cells were demonstrated to be non-cytotoxic to normal cells of the patient. These data demonstrated that γδ T cells, which could be expanded in vitro from blood cells of patients with myeloma and lymphoma by culturing with zoledronate and IL-2, possess a sufficient cytotoxic ability against tumor cells. These findings suggested that in vitro generated patients’ γδ T cells could be applied to γδ T cell-mediated immunotherapy for hematological malignancies. [ABSTRACT FROM AUTHOR]

Abstract We examined effects of an angiotensin-II receptor blockers, candesartan cilexetil, in rats with dilated cardiomyopathy after autoimmune myocarditis. Candesartan cilexetil showed angiotensin-II blocking action in a dose-dependent manner in rats with dilated cardiomyopathy. Twenty-eight days after immunization, surviving Lewis rats were divided into four groups and given candesartan cilexetil at 0.05 mg/kg, 0.5 mg/kg or 5 mg/kg per day (Group-C0.05, n = 15, Group-C0.5, n = 15 and Group-C5, n = 15, respectively) or vehicle alone (Group-V, n = 15). After oral administration for 1 month, the left ventricular end-diastolic pressure and heart weight/body weight ratio were lower in Group-C0.05 (13.3± 1.1 mmHg and 3.7± 0.2 g/kg, respectively), in Group-C0.5 (8.0± 0.9 mmHg and 3.3± 0.1 g/kg, respectively) and in Group-C5 (5.5± 1 mmHg and 3.1± 0.1 g/kg, respectively) than in Group-V (13.5± 1.0 mmHg and 3.8± 0.2 g/kg, respectively). The area of myocardial fibrosis was also lower in Group-C0.05 (25± 3%), in Group-C0.5 (20± 3%), and in Group-C5 (12± 1%) than in Group-V (32± 4%). Furthermore, expressions of transforming growth factor-ß1 and collagen-III mRNA were suppressed in Group-C0.05 (349± 23% and 395± 22%, respectively), Group-C0.5 (292± 81% and 364± 42%, respectively) and in Group-C5 (204± 63% and 259± 33%, respectively) compared with those in Group-V (367± 26% and 437± 18%, respectively). These results suggest that candesartan cilexetil can improve the function of inefficient heart. (Mol Cell Biochem 269 : 137–142, 2005) [ABSTRACT FROM AUTHOR]

Thrombotic microangiopathy (TMA) is one of the lethal complications after hematopoietic stem cell transplantation (SCT). The levels of fragmented red cells (FRCs), thrombomodulin (TM), and factor VIII–related antigen in the blood are the most important markers for estimating TMA. However, the FRC level has been measured by using microscopy and the naked eye; therefore, an improvement in technology to objectively count FRC is necessary. We established a novel technique to sensitively measure FRC as glycophorin A dull–positive small particles using a flow cytometer and estimated its reliability in patients treated with SCT. The blood level of FRC was compared with other clinical data in 257 blood samples in 16 clinical courses after SCT of 15 patients. Sorted glycophorin A dull–positive small particles morphologically showed FRC. Measured FRC percentage had a weak correlation with serum levels of lactate dehydrogenase (LDH) and total bilirubin but not with TM level, whereas TM showed a weak correlation with the levels of aspartate aminotransferase and LDH. In a patient with fulminant TMA, decrement of the FRC level led to improvement in liver parameters after treatment, presumably due to the rapid clearance of FRC, and increased simultaneously with the levels of LDH and bilirubin by the TMA recurrence. Levels of FRC percentage and TM were independent parameters of TMA. This novel technique may be used as a standard methodology in diagnosing TMA. © 2003 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

We report a case of Graves? disease in a patient on regular hemodialysis. The patient also suffered from Wolff-Parkinson-White (WPW) syndrome and paroxysmal atrial fibrillation, which may both have been manifestations of the Graves? disease because of the increased oxygen demand. To our knowledge, this is the first case to illustrate the usefulness of the antithyroid agent propylthiouracil for Graves? disease complicated by endstage renal disease (ESRD) and WPW syndrome. [ABSTRACT FROM AUTHOR]

Coxsackievirus B is the most common cause of viral myocarditis and is particularly virulent in neonates and children. Adenovirus is also a leading cause of the disease. The determinant of tropism for both viruses is considered to be the expression of coxsackievirus and adenovirus receptor (CAR) in target organs. However, developmental change and physiological localization of CAR in the heart are unknown. We examined expression levels of CAR in rat hearts by quantitative real-time polymerase chain reaction and Western blot analysis and found that CAR decreased gradually during postnatal development, although CAR was detectable, even in adults. Immunohistochemistry revealed CAR on the whole surface of cardiomyocytes in immature rat hearts. In contrast, CAR was detected predominantly on intercalated disks in the adult heart and was accumulated especially at the contact point between the cultured cardiomyocytes, even though they were prepared from the neonatal rat heart. In conclusion, CAR was expressed abundantly on the whole surface of cardiomyocytes in immature rat hearts. Both the expression level and the localization of CAR are possible determinants of the susceptibility to viral myocarditis of neonates and children. [ABSTRACT FROM AUTHOR]

The present study was designed for identifying the protein synthesis in cytoplasm of dendritic cells transfected with in vitro transcribed mRNA and cellular total RNA extracted from tumor cells. Dendritic cells were generated from cord blood-CD34+ cells by culture with GM-CSF, SCF, and TNF-α, or from peripheral blood adherent cells or CD14+ cells by culture with GM-CSF and IL-4. Dendritic cells were transfected with in vitro transcribed EGFP mRNA or cellular total RNA, which was isolated from EGFP expressing K562, by electroporation using a square-wave pulse. Optimal in vitro transcribed EGFP mRNA transfection efficiency (>90%) was observed in a single electroporation of 1.75 kV/cm (electric field strength) with a pulse width of 250 μs. Although the intensity of EGFP expression in dendritic cells transfected with cellular total RNA was less compared with that in dendritic cells transfected with in vitro transcribed EGFP mRNA, a definite cytoplasmic synthesis of EGFP was demonstrated in dendritic cells transfected with cellular total RNA. The visual identi- fication of cytoplasmic expression of cellular total RNA in dendritic cells revealed that electroporation of tumor cell-derived RNA could be a useful tool to load dendritic cells with tumor antigens for establishing an efficient dendritic cell-based tumor immunotherapy. [ABSTRACT FROM AUTHOR]

Chronic myelogenous leukemia is caused by the acquisition of the reciprocal (9;22)(q34;q11) chromosomal translocation in hematopoietic stem cells. The fusion protein showed higher and aberrant tyrosine kinase activity. The inhibition of the tyrosine kinase activity of the protein represents a specific therapeutic strategy for bcr/abl-expressing leukemias. STI571 is a compound of the 2-phenylaminopyrimidine class that selectively inhibits the tyrosine kinase activity of the Abl protein tyrosine kinase. In this study, we evaluated the effects of STI571 on antigen presentation of dendritic cells generated from the patients with CML. The data showed that by the addition of STI571 the dendritic cells derived from CML clone showed an increased expression of CD1a, CD83, CD80 and CD86 by flow cytometry analysis and showed more intense abilities of allogeneic antigen presentation by mixed leukocyte culture, compared with the control cells without STI571. Our results suggested that STI571 not only has a direct cytotoxic effect on bcr-abl gene rearranged cells but also an indirect effect associated with increased anti-leukemic immunological function due to an intensified antigen presentation. Copyright © 2003 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Cites a study published in the 'British Journal of Haematology,' 1-deamino-8-d-arginine vasopressin (DDAVP) normalized the bleeding time in patients with platelet disorder characterized by defective calcium ionophore-induced platelet aggregation. Effectiveness of DDAVP in patients with various congenital platelet disorders; Mechanism by which DDAVP reduces bleeding time.

Background and purpose Green tea consumption is inversely associated with death from stroke. The purpose of the present study was to assess whether it is inversely associated with subsequent stroke incidence and whether this association is preserved even with roasted tea leaves. Methods In 1998, 6358 Japanese adults (2087 men and 4271 women) aged 40–89 years without a history of stroke or heart disease completed a lifestyle questionnaire, including consumption of green tea or roasted tea. By the end of 2003, 110 stroke events (59 cerebral infarction events, 34 cerebral haemorrhage events, 15 subarachnoidal haemorrhage events and two stroke events of unspecified subtype) had been documented. Cox proportional hazards regression analysis was used to calculate the multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for total stroke events, cerebral infarction events and cerebral haemorrhage events according to consumption categories of green tea and roasted tea. Results A considerably lower risk was observed for total stroke incidence in both the middle (multivariable HR, 0.43; 95% CI, 0.25–0.74; P = 0.002) and the high (multivariable HR, 0.41; 95% CI, 0.24–0.70; P = 0.001) categories of green tea consumption. This inverse association was consistent even when cerebral infarction and cerebral haemorrhage were analysed separately. The consumption of roasted tea was not associated with stroke risk. Conclusions Green tea consumption is associated with a reduced risk of total stroke incidence, cerebral infarction and cerebral haemorrhage. [ABSTRACT FROM AUTHOR]

Although tyrosine kinase inhibitors is effective for dramatically reducing CML cells, it might be difficult to eradicate completely the CML stem cells. We aimed to clarify the safety and effects of WT1 peptide vaccination in combination with imatinib therapy for a CML patient. A 51 year-old male with CML in CP, who showed a resistance against imatinib therapy for 2.5 years, began to be treated with 9mer modified-type WT1 peptides in combination with standard dose of imatinib. Although every 2-week-administration of WT1 peptides for 22 weeks did not show definite effects on the quantification of bcr-abl transcripts, by changing the administration from every 2 weeks to 4 weeks bcr-abl transcripts decreased remarkably. After 11 months of every 4-week-administration of the peptides and 12 months post cessation of the peptides bcr-abl transcripts achieved to the level below detection by RQ/RT-PCR (complete molecular response). WT1/MHC tetramer+CD8+ CTLs, which appeared after the second administration of WT1 peptides and remained more than 15 in number among 106 CD8+ T cells throughout the administration of WT1 peptides, are still present in the blood on 14th month post cessation of the peptides. An in vitro study as to the cytotoxicity of lymphocytes induced by mixed lymphocyte peptide culture demonstrated that cultured lymphocytes possessed cytotoxicity against WT1 expressing leukemia cells and the cytotoxicity was WT1-specific and MHC class I restricted. The present study showed that WT1 peptide vaccination in combination with TKI is feasible and effective in the therapy for imatinib-resistant CML.

Background Cardiac involvement is a leading cause of death from sarcoidosis. Because the efficacy of corticosteroid treatment is limited in patients with cardiac manifestation, early diagnosis is important. However, cardiac involvement is difficult to identify at early stages and is often underdiagnosed. Therefore, this study aimed to identify electrocardiographic risk factors for cardiac events in patients with extracardiac sarcoidosis. Methods This prospective observational cohort study included 227 patients with extracardiac sarcoidosis who did not have any cardiac manifestation (age, 49 ± 17 years; women, 63%). We studied the association of electrocardiographic abnormalities with developing cardiac manifestations. Results During a follow-up of 6.3 ± 3.7 years, 11 patients developed cardiac events, including advanced atrioventricular block (4 patients), ventricular tachycardia (4 patients), and systolic dysfunction (3 patients). All patients had electrocardiographic abnormalities prior to the development of cardiac events. In multivariate analyses, the baseline heart rate and PR interval were associated with increased risk of developing cardiac events. The QRS duration and corrected QT interval were not associated with cardiac manifestations. The multivariate analyses also revealed that baseline conduction disorder, ST segment/T wave abnormalities, and fragmented QRS complexes were associated with cardiac events. Conclusions Electrocardiographic abnormalities occurred prior to cardiac events in extracardiac sarcoidosis. Patients with electrocardiographic abnormalities may require further evaluation for cardiac involvement and careful follow-up. [ABSTRACT FROM AUTHOR]

Treatment guidelines for atrial fibrillation (AF) used in Western countries describe female gender as a risk factor for thromboembolic events in patients with nonvalvular AF (NVAF). The present study aimed to determine the impact of gender on prognosis of Japanese patients with NVAF. A subanalysis of 7,406 patients with NVAF (mean age 70 years) who were followed- up prospectively for 2 years was performed using data from the J-RHYTHM registry. The primary end points were thromboembolic events, major hemorrhaging, total mortality, and cardiovascular mortality. Compared with male subjects (n[5,241), female subjects (n[ 2,165) were older and displayed greater prevalences of paroxysmal AF, heart failure, and hypertension but less prevalences of diabetes, previous cerebral infarction, and coronary artery disease. Male and female patients had mean CHADS2 (Congestive heart failure, Hypertension, Age of 75 years or more, Diabetes mellitus and prior Stroke or transient ischemic attack) scores of 1.6 and 1.8, respectively (p <0.001). Warfarin was given to 87% of male patients and 86% of female patients (p [ 0.760), and the 2 genders displayed similar mean international normalized ratio of prothrombin time values at baseline (1.91 vs 1.90, respectively, p[0.756). Multivariate logistic regression analysis indicated that male gender was an independent risk factor for major hemorrhaging (odds ratio 1.59, 95% confidence interval 1.05 to 2.40, p [ 0.027) and all-cause mortality (odds ratio 1.78, 95% confidence interval 1.25 to 2.55, p <0.002) but not for thromboembolic events (odds ratio 1.24, 95% confidence interval 0.83 to 1.86, p[0.297) or cardiovascular mortality (odds ratio 0.96, 95% confidence interval 0.56 to 1.66, p[0.893). In conclusion, female gender is not a risk factor for thromboembolic events among Japanese patients with NVAF who were treated mostly with warfarin. However, male gender is a risk factor for major hemorrhaging and all-cause mortality. [ABSTRACT FROM AUTHOR]