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Background Trends of oral anticoagulant (OAC) prescription and incidence of thromboembolism (TE) and/or major bleeding (MB) in patients with non-valvular atrial fibrillation (NVAF) in Japan are still unclear. Methods and results We used data from Shinken Database 2004-2012, which included all new patients attending the Cardiovascular Institute between June 2004 and March 2013. Of them, 2,434 patients were diagnosed with NVAF. Patients were divided into 3 time periods according to the year of initial visit: 2004-2006 (n=681), 2007-2009 (n=833), and 2010-2012 (n=920). OAC prescription rate steadily increased from 2004-2006 to 2010-2012. Between 2004-2006 and 2007-2009, irrespective of increased warfarin usage, MB tended to decrease, presumably due to low-intensity therapy and avoidance of concomitant use of dual antiplatelets, but TE did not improve. In 2010-2012, direct OACs (DOAC), preferred in low-risk patients, may have contributed to not only decrease TE, but also increase MB, especially extracranial bleeds. In high-risk patients in that time period, mostly treated with warfarin, incidence of TE and MB did not improve. Conclusions The 9-year trend of stroke prevention indicated a steady increase of OAC prescription and a partial improvement of TE and MB. Even in the era of DOAC, TE prevention was insufficient in high-risk patients, and DOAC were associated with increased extracranial bleeding. (Circ J 2016; 80: 639-649).

Background The association between ABO blood type and the activated partial thromboplastin time (aPTT) under dabigatran therapy in nonvalvular atrial fibrillation (NVAF) patients is unclear. Methods and results Between 2011 March and 2015 May, data on ABO blood type and aPTT under dabigatran were obtained for 396 NVAF patients (baseline aPTT, 166). The prevalence of blood type O tended to increase or significantly increase according to baseline aPTT, aPTT under dabigatran, and their difference (∆aPTT) (P=0.054, 0.001, and 0.012, respectively). Conclusions In these NVAF patients, a high aPTT value under dabigatran therapy was associated with blood type O.

Background: Prothrombin time (PT) distribution in Japanese nonvalvular atrial fibrillation (NVAF) patients under rivaroxaban therapy remains to be clarified. Methods and Results: Between May 2012 and July 2013, 115 NVAF patients received rivaroxaban (PT was measured in 94; reagent: recombiplastin). In these patients, (1) PT values were distributed widely from patient to patient and from peak to trough, (2) the time-dependence was obscure with sampling at any time in the outpatient clinic, and (3) the incidence of adverse events was too low for analyzing the relation with PT. Conclusions: We report the distribution of PT for Japanese NVAF patients under rivaroxaban therapy in real-world clinical practice. (Circ J 2014; 78: 763–766)

BACKGROUND Tobacco smoking is a well-known risk factor for cardiovascular disease, but controversial results have been reported regarding its relationship with atrial fibrillation (AF). Moreover, no study on the relationship between smoking and AF has yet been undertaken in a Japanese context. METHODS AND RESULTS We used data from the Shinken Database 2004-2011 (men/women, n=10,714/6,803, respectively), which included all new patients attending the Cardiovascular Institute between June 2004 and March 2012. AF was diagnosed in 1,698 and 598 men and women, respectively. In men, smokers were more prevalent in the AF than in the non-AF group (54.5% vs. 44.7%), whereas in women the prevalence of smokers was similar between AF and non-AF groups (14.4% vs. 15.4%). This discrepancy between the sexes seems to derive from a characteristic distribution pattern of smoking habit in women. After adjustment for various cofactors, smoking was independently associated with AF (odds ratio 1.54; 95% confidence interval 1.35-1.75; P

Background: Isolated non-compaction of ventricular myocardium (INVM) is characterized by persistent embryonic myocardial morphology without other cardiac anomalies. Congestive heart failure, critical arrhythmias, and systemic thromboemboli are known as major manifestations during childhood. Recently it was reported that there are some patients who seem apparently healthy in adult INVM. Clinical characteristics including that for electrocardiograms (ECG) of adult INVM, however, are unknown for Japanese subjects. Methods and Results: From 24,082 patients who underwent echocardiography between June 2000 and June 2007, 187 patients (0.78%, 41.3±16.8 years, 122 male) were identified as having INVM according to the criteria proposed by Oechslin et al. Although fatal ventricular arrythmias and thromboembolic events occurred in 2 patients and in 1 patient, respectively, the rest had no severe cardiac complications. Normal ECG findings were found only in 24.6% of the patients. Most of the ECG abnormalities, however, were non-specific: ST-T changes in 35.2% and bundle branch block in 14.9%. Notably, Brugada-like ECG was frequently seen in the present Japanese INVM patients (3.2%). The incidence of these ECG findings was not dependent upon the extent of non-compaction. Conclusions: The prevalence and ECG findings of adult Japanese INVM patients in a hospital-based clinical practice have been identified. (Circ J 2010; 74: 1431 - 1435)

Background: Inflammatory processes in the atria during systemic inflammation remain unclear, so this study tested the hypothesis that macrophages infiltrate the atrial myocardium mainly through the atrial endocardium with the contribution of fractalkine. Methods and Results: Sprague-Dawley rats were injected with lipopolysaccharide (LPS) to simulate inflammation in the atria. Inflammation was immunohistologically assessed by the presence of macrophages. Macrophage infiltration was diffuse throughout the atrial myocardium after LPS injection. At an earlier phase after LPS injection, the number of macrophages dramatically increased, mainly in the atrial endocardium, and the expression of fractalkine protein was markedly increased by treatment with LPS in the atrial endocardium. The LPS-induced increase in atrial macrophage infiltration was significantly suppressed by neutralizing the fractalkine protein (P

Background Recent investigations have demonstrated that cerebral oxyhemoglobin (O2Hb) decreases during exercise in patients with left ventricular dysfunction, reflecting a cerebral hypoxia. We sought to establish a prognostic value of decreased cerebral O2Hb during exercise in cardiac patients, and to compare it with those of indexes obtained from cardiopulmonary exercise testing (CPX). Methods and Results A total of 344 consecutive patients with coronary artery disease were enrolled in the study. All the patients performed CPX, during which cerebral O2Hb was continuously monitored using near-infrared spectroscopy. There were 13 cardiac deaths and 78 cardiovascular events during the prospective follow-up period of 1,231±538 days. The change of O2Hb measured at the forehead from rest to peak exercise (ΔO2Hb) was significantly lower in non-survivors than in survivors (-1.5±3.3 vs 1.7±3.2 μmol/L, p=0.0004). By multivariate Cox proportional hazards analysis, ΔO2Hb and left ventricular ejection fraction (LVEF) were found to be independent prognostic markers for cardiac deaths. The ΔO2Hb, LVEF and peak oxygen uptake were found to be significant prognostic markers for cardiovascular events, mainly for heart failure worsening and sudden cardiac death. Conclusion The present findings suggest that a decrease in cerebral O2Hb during exercise predicts future cardiovascular events in patients with coronary artery disease. (Circ J 2008; 72: 1852 - 1858)

Background It has been recently reported that cerebral oxyhemoglobin (O2Hb) decreases during exercise in nearly 50% of patients with dilated cardiomyopathy. The present study evaluated whether the inhalation of supplemental O2 diminishes the decrease in cerebral O2Hb during exercise. Methods and Results Ten patients with a left ventricular ejection fraction

Background It is well-known that both B-type natriuretic peptide (BNP) and peak oxygen uptake (VO2) are independent predictors of mortality in patients with heart failure. This study investigates the predictive power of BNP and peak VO2 for survival in cardiac patients. Methods and Results A total of 609 patients with cardiac disease participated in the study. They underwent cardiopulmonary exercise testing to determine peak VO2, with BNP being measured before exercise testing During 502.5 median follow-up days, 29 patients died of cardiovascular disease. In the univariate Cox proportional hazards analysis, peak VO2 and BNP were both found to be significant prognostic indices for survival. The time-dependent ROC curve analysis (Heagerty 2006) was applied to 3 predictors: peak VO2, BNP, and then both, with gender and age as adjusted variables. The area under the curve (AUC) compared with the follow-up period curves of peak VO2 and the 2 combined variables (ie, BNP and peak VO2) were consistently over that of BNP. The integrated AUC indices were 0.80 (peak VO2), 0.81 (peak VO2 and BNP) and 0.70 (BNP), respectively. Conclusions These results indicate that peak VO2 is more potent than BNP for predicting the mortality in patients with mixed cardiac disease. (Circ J 2008; 72: 575 - 581)

Background Many pathological conditions induce electrical remodeling, possibly through intracellular Ca2+ overload, but the currently available L-type Ca2+ channel blockers may be detrimental because of their global negative inotropic effects. Methods and results To determine whether the L-type Ca2+ channel is identical throughout the heart, the distribution of the mRNAs and proteins comprising the L-type Ca2+ channel and its electrophysiological properties were analyzed in rat atria and ventricles. The mRNA of alpha2delta-2 (Cacna2d2) was more abundantly expressed in the atrium (approximately 5-fold) than in the ventricle. In contrast, alpha1C (Cacna1c) (Cav1.2) mRNA was significantly less abundant in the atrium. The level of the alpha1C (Cacna1c) (Cav1.2) protein was decreased (approximately 0.5-fold) and that of alpha2 delta-1 (Cacna2d1) was increased (approximately 2-fold) in the atrium compared with the ventricle. Although the peak ICa,L density showed no significant differences, voltage dependence of inactivation and activation of the current showed a more depolarized shift in the atrium than in the ventricle. Conclusion These results indicate that in the rat heart the L-type Ca2+ channel differs between the atrium and ventricle with regard to gene expression and electrophysiological properties.

Background End-tidal CO2 partial pressure (PETCO2) has been suggested as a noninvasive index reflecting cardiac output under constant ventilation. The aim of this study was to examine whether PETCO2 does reflect cardiac output, even during exercise, in patients with acute myocardial infarction (AMI) undergoing exercise training early after onset. Method and Results Patients aged 47-73 years were randomly assigned to either a training group (n=18) or a control group (n=18) 1 week after the onset of AMI. Those in the training group performed exercise training under supervision at the anaerobic threshold level for 2 weeks, while patients in the control group followed a conventional walking regimen. In the training group, but not in the control group, PETCO2 at the respiratory compensation point increased significantly from 39.1±3.5 to 41.1±3.7 mmHg (p

A 65-year-old man with Brugada-type electrocardiogram (ECG) was admitted to our hospital for chest pain, palpitation and faintness. In the cardiac electrophysiological study, no ventricular tachyarrthymia was induced either at baseline or after pilsicainide (50 mg) infusion. Intravenous administration of pilsicainide exaggerated ST-segment elevation in V(1-4) and converted it to the coved type in V(1), accompanied by severe chest pain. Coronary angiography revealed the vasospasm of the right coronary artery was induced by pilsicainide, not by ergonovine. This is the first case report of coronary vasospasm induced by a pure sodium channel blocker in a patient with Brugada-type ECG.