Time in Therapeutic Range and Disease Outcomes in Elderly Japanese Patients With Nonvalvular Atrial Fibrillation.

BACKGROUND: The relationship between warfarin treatment quality and prognosis for Japanese patients with nonvalvular atrial fibrillation (NVAF) has not been studied thoroughly. Methods and Results: Data from the J-RHYTHM Registry were used to determine the time in therapeutic range (TTR) of the international normalized ratio (INR) of prothrombin time in elderly patients (≥70 years). Target INR was 1.6-2.6. Of 7,406 patients with NVAF in the database, 3,832 elderly patients (mean [±SD] age 77.0±5.0 years) constituted the study group. Of these patients, 459 did not receive warfarin and 3,373 received warfarin. Patients on warfarin were subdivided into 4 TTR groups: <40%, 40-59.9%, 60-79.9%, and ≥80%. During the 2-year follow-up, the incidence of thromboembolism and all-cause death was lower in patients with higher TTR (Ptrend<0.001); however, the incidence of major hemorrhage was higher in patients with TTR <40%. In multivariate analysis, compared with the no-warfarin group, TTR 60-79.9% and ≥80% were associated with lower thromboembolic risk, with hazard ratios (HR) of 0.34 (95% confidence interval [CI] 0.17-0.67; P=0.002) and 0.35 (95% CI 0.18-0.68; P=0.002), respectively, and lower all-cause death (HR 0.37 [95% CI 0.22-0.65; P<0.001] and 0.43 [95% CI 0.26-0.71; P=0.001], respectively). TTR <40% was associated with major hemorrhage (HR 5.57; 95% CI 2.04-15.25; P=0.001). CONCLUSIONS: In elderly Japanese patients with NVAF, TTR should be maintained ≥60% to prevent thromboembolism and all-cause death. TTR <40% should be avoided to prevent major hemorrhage.

Differences in amiodarone efficacy in relation to ejection fraction and basal rhythm in patients with implantable cardioverter defibrillators.

BACKGROUND: Atrial fibrillation (AF) and ventricular arrhythmias (VAs) are associated with increased morbidity and mortality. However, data are lacking concerning the association of AF and VAs. This study aimed to clarify the association between AF and VAs and to investigate the effect of amiodarone on the incidence of VAs in patients with implantable cardioverter defibrillators (ICDs). METHODS AND RESULTS: We enrolled 612 patients who had ICDs or who underwent cardiac resynchronization therapy with a defibrillator (CRT-D) and classified them into two groups (sinus rhythm [SR] group, n = 427; AF group, n = 185) according to their basal rhythm at enrollment. Patients with paroxysmal AF were grouped into the AF group. The incidence of VAs, i.e., ventricular tachycardia (VT) and ventricular fibrillation (VF), was significantly lower in the AF group than in the SR group (0.54 vs 0.95 episodes/person/year, P = 0.032). Furthermore, amiodarone use was significantly higher in the AF group than in the SR group (P = 0.003). Non-use of amiodarone was associated with a significant increase in the occurrence of VT/VF in the two groups. This beneficial suppressive effect of amiodarone on the incidence of VT/VF was present in the AF group regardless of left ventricular ejection fraction (LVEF). However, this effect of amiodarone was present only in patients with LVEF ≥ 40% in the SR group. CONCLUSIONS: Amiodarone was negatively associated with VT/VF occurrence and was frequently used in ICD/CRT-D patients with AF. VT/VF was controlled by amiodarone in all cases in the AF group but only in patients with an LVEF ≥ 40% in the SR group.

Significant correlation between renal 123I-metaiodobenzylguanidine scintigraphy and muscle sympathetic nerve activity in patients with primary hypertension.

BACKGROUND: Iodine-123 metaiodobenzylguanidine (123I-MIBG) scintigraphy is used as a noninvasive imaging method for assessing cardiac sympathetic nerve activity. We tested the hypothesis that renal 123I-MIBG imaging is correlated with muscle sympathetic nerve activity (MSNA) in patients with primary hypertension. METHODS: Thirty-one consecutive patients with primary hypertension were included. Multiunit MSNA was recorded from the peroneal nerve to evaluate direct efferent sympathetic nerve activity. Planar renal and cardiac 123I-MIBG images were acquired. Early and delayed kidney-to-mediastinum ratio (K/M), early and delayed heart-to-mediastinum ratio (H/M), and washout rates (WR) were calculated. RESULTS: In 27 of 31 patients, blood pressure was controlled on antihypertensive medication. Mean systolic and diastolic blood pressures were 118 ± 18 and 67 ± 15 mmHg, respectively. Although early and late K/M and H/M were not significantly correlated with MSNA, both cardiac and average renal WR were significantly correlated with MSNA (r = 0.45, P = .0035 and r = 0.68, P < .001, respectively). Right and left renal WR were similarly correlated with MSNA. Renal WR was significantly higher than cardiac WR (43.2% vs 25.8%, P < .001) in these patients with hypertension. CONCLUSIONS: Renal 123I-MIBG WR was significantly associated with multiunit MSNA. Renal 123I-MIBG imaging offers a noninvasive clinical methodology for assessing renal sympathetic nerve function.

Eplerenone might affect atrial fibrosis in patients with hypertension.

BACKGROUND: Eplerenone is reported to reduce the development of atrial fibrillation (AF). The aim of this study was to clarify the mechanism of eplerenone for AF prevention from the viewpoint of P wave morphology, which is reported to correlate with atrial fibrosis. METHODS: Thirty-five patients with hypertension, who were randomized to receive eplerenone (n = 16) or amlodipine (n = 19) for 1 year, were evaluated. P wave signal-averaged electrocardiography was recorded at baseline and 1 year after entry, and P wave duration (Ad) and P wave dispersion (P-disp) were obtained. Serum levels of intact procollagen type I N-terminal propeptide (PINP) and N-terminal procollagen-III peptide (PIIIP) were also measured. RESULTS: There were no significant differences in baseline clinical characteristics including Ad, P-disp, and the decrease in blood pressure at 1-year follow-up between the two groups. Ad and P-disp (mean ± standard deviation) significantly increased in patients on amlodipine after 1 year (140 ± 21 ms to 139 ± 19 ms vs 132 ± 10 ms to 136 ± 12 ms, P < 0.01 and 14 ± 7 ms to 9 ± 4 ms vs 12 ± 5 to 16 ± 8, P < 0.01, respectively). PINP was significantly more decreased in patients with eplerenone than amlodipine (56.6 ± 30.4 µg/mL to 46.6 ± 19.4 µg/mL vs 41.5 ± 16.2 µg/L to 48.7 ± 21.3 µg/L, P < 0.01). Percent changes of Ad, P-disp, PINP, and PIIIP were significantly smaller in patients with eplerenone than amlodipine (0.0 ± 4.7% vs 3.2 ± 4.4%, P < 0.05, - 28.6 ± 31.0% vs 46.3 ± 73.0%, P < 0.01, - 5.6 ± 38.1% vs 22.7 ± 42.7%, P < 0.05, and - 9.2 ± 25.1% vs 7.4 ± 19.0%, P < 0.05, respectively). CONCLUSIONS: Eplerenone reduced the increase of Ad and P-disp with a decrease of PINP and PIIIP, which might translate into reduction of atrial fibrosis. This study showed that eplerenone may be useful as upstream therapy for AF in patients with hypertension.

Clinical Impact of Ventricular Tachycardia and/or Fibrillation During the Acute Phase of Acute Myocardial Infarction on In-Hospital and 5-Year Mortality Rates in the Percutaneous Coronary Intervention Era.

BACKGROUND: The aim of this study was to investigate the prognostic impact of acute-phase ventricular tachycardia and fibrillation (VT/VF) on ST-segment elevation myocardial infarction (STEMI) patients in the percutaneous coronary intervention (PCI) era. METHODS AND RESULTS: Using the database of the Osaka Acute Coronary Insufficiency Study (OACIS), we studied 4,283 consecutive patients with STEMI who were hospitalized within 12 h of STEMI onset and underwent emergency PCI. Acute-phase VT/VF, defined as ≥3 consecutive ventricular premature complexes and/or VF within the 1st week of hospitalization, occurred in 997 (23.3%) patients. In-hospital mortality risk was significantly higher in patients with acute-phase VT/VF than inthose without (14.6% vs. 4.3%, adjusted hazard ratio (HR) 1.83, P=0.0013). Among patients discharged alive, 5-year mortality rates were comparable between patients with and without acute-phase VT/VF. Subgroup analysis showed that acute-phase VT/VF was associated with increased 5-year mortality after discharge in high-risk patients (GRACE Risk Score ≥115; adjusted HR 1.60, P=0.043), but not in intermediate- or low-risk patients. CONCLUSIONS: Even in the PCI era, acute-phase VT/VF was associated with higher in-hospital deaths of STEMI patients. However, the 5-year prognostic impact of acute-phase VT/VF was limited to high-risk patients. (Circ J 2016; 80: 1539-1547).

Regional Differences in Frequency of Warfarin Therapy and Thromboembolism in Japanese Patients With Non-Valvular Atrial Fibrillation　- Analysis of the J-RHYTHM Registry.

BACKGROUND: The proportion of patients with atrial fibrillation (AF) treated with anticoagulation varies from country to country. In Japan, little is known about regional differences in frequency of warfarin use or prognosis among patients with non-valvular AF (NVAF). METHODS AND RESULTS: In J-RHYTHM Registry, the number of patients recruited from each of 10 geographic regions of Japan was based on region population density. A total of 7,406 NVAF patients were followed up prospectively for 2 years. At baseline, significant differences in various clinical characteristics including age, sex, type of AF, comorbidity, and CHADS2score, were detected among the regions. The highest mean CHADS2score was recorded in Shikoku. Frequency of warfarin use differed between the regions (P<0.001), with lower frequencies observed in Hokkaido and Shikoku. Baseline prothrombin time international normalized ratio differed slightly but significantly between the regions (P<0.05). On univariate analysis, frequency of thromboembolic events differed among the regions (P<0.001), with the highest rate seen in Shikoku. An inverse correlation was detected between frequency of thromboembolic and of major hemorrhagic events (P=0.062). On multivariate analysis, region emerged as an independent risk for thromboembolism. CONCLUSIONS: Thromboembolic risk, frequency of warfarin use, and intensity and quality of warfarin treatment differed significantly between geographic regions of Japan. Region was found to be an independent predictor of thromboembolic events. (Circ J 2016; 80: 1548-1555).

Risk Stratification for Ventricular Tachyarrhythmias by Ambulatory Electrocardiogram-Based Frequency Domain T-Wave Alternans.

BACKGROUND: Ambulatory electrocardiogram (ECG)-based T-wave alternans (TWA) quantified by the modified moving average method (MMA) can be used to identify patients at risk for sudden cardiac death. However, there is no information available on ambulatory ECG-based TWA as quantified by the frequency domain (FD) method to identify patients with an implantable cardioverter defibrillator (ICD) who are at high risk for ventricular tachyarrhythmias. Further, there are few data regarding the comparison of clinical utility of FD-TWA with MMA-TWA, heart rate variability (HRV), and heart rate turbulence (HRT). METHODS AND RESULTS: In 41 patients with ICD, of whom 14 patients had a past history of at least one appropriate ICD discharge, FD-TWA, MMA-TWA, HRV, and HRT were analyzed from 24-hour Holter ECG monitoring recordings. Only positive results of FD-TWA and abnormal HRV (standard deviation of all normal-to-normal intervals ≤111 ms) were significantly more frequently observed in patients with than without appropriate ICD discharge. Patients with FD-TWA positive had a significantly higher risk of appropriate ICD discharge than those with FD-TWA negative (50% vs 16%; odds ratio, 5.3 [95% confidence interval, 1.2-23.7], P = 0.02). When FD-TWA and HRV were combined, the specificity (93% vs 59%, P = 0.003) and predictive accuracy (83% vs 66%, P = 0.07) for the identification of patients with appropriate ICD discharge were greater than those for FD-TWA only. CONCLUSION: The ambulatory ECG-based FD-TWA might be useful to detect patients with ICD who are at high risk for ventricular tachyarrhythmias, and the combination of FD-TWA and HRV might improve the ability to detect such high-risk patients.

[Device treatment approaches targeting the sympathetic nervous system in patients with resistant hypertension].

A large percentage of patients with hypertension do not meet guideline blood pressure goal, which increases cardiovascular morbidity and mortality. Involvement of sympathetic nervous system has been recognized but our intervention for the system was limited to pharmacological therapy. The new interventions, such as intra-renal artery ablation and baroreflex activation therapies, directed toward the sympathetic nervous system, were intensely examined in various areas of cardiovascular disease. These interventions are promising with some conflicting results.

Proton trapping in yttrium-doped barium zirconate.

The environmental benefits of fuel cells have been increasingly appreciated in recent years. Among candidate electrolytes for solid-oxide fuel cells, yttrium-doped barium zirconate has garnered attention because of its high proton conductivity, particularly in the intermediate-temperature region targeted for cost-effective solid-oxide fuel cell operation, and its excellent chemical stability. However, fundamental questions surrounding the defect chemistry and macroscopic proton transport mechanism of this material remain, especially in regard to the possible role of proton trapping. Here we show, through a combined thermogravimetric and a.c. impedance study, that macroscopic proton transport in yttrium-doped barium zirconate is limited by proton-dopant association (proton trapping). Protons must overcome the association energy, 29 kJ mol(-1), as well as the general activation energy, 16 kJ mol(-1), to achieve long-range transport. Proton nuclear magnetic resonance studies show the presence of two types of proton environment above room temperature, reflecting differences in proton-dopant configurations. This insight motivates efforts to identify suitable alternative dopants with reduced association energies as a route to higher conductivities.

Efficacy of anti-tachycardia pacing for terminating fast ventricular tachycardia in Japanese implantable cardioverter defibrillator patients. Primary results of the SATISFACTION study.

BACKGROUND: Anti-tachycardia pacing (ATP) delivered by implantable cardioverter defibrillators (ICD) safely avoids painful shocks with minimum risk of tachycardia acceleration. The etiology of ventricular tachycardia (VT) in those studies, however, was predominantly coronary artery disease (CAD). Patient etiology differs by geography and could affect ATP efficacy rate. The primary objective of this study was to examine how often the first ATP therapy terminates fast VT (FVT) in Japanese ICD patients with regional etiologies. METHODS AND RESULTS: Seven hundred and fifteen patients received ICD or cardiac resynchronization therapy defibrillator with the function of ATP during capacitor charging. The primary endpoint was the first ATP success rate for terminating FVT with cycle length 240-320 ms. During a mean follow-up of 11.3 months, 888 spontaneous VT episodes were detected, including 276 FVT (31.1%) in 42 patients. The first-ATP success rate for FVT in the overall group (41% CAD, 59% non-CAD including 23% idiopathic VT) was 62.1% (61.7% adjusted). Success rate was not different between non-CAD and CAD patients (61.4% adjusted and 57.5% adjusted, respectively, P=0.75). Eight FVT episodes (2.9%) accelerated after the first ATP attempt, all of which were terminated by subsequent device therapy (additional ATP or shock). CONCLUSIONS: ATP efficacy for FVT was similar between ICD patients with and without CAD etiology.

Introduction of point-of-care testing in Japanese outpatient clinics is associated with improvement in time in therapeutic range in anticoagulant-treated patients.

BACKGROUND: Warfarin reduces the risk of stroke in patients with atrial fibrillation, but requires a moderate-to-high time in therapeutic range (TTR). We hypothesized that point-of-care (POC) testing for prothrombin time-internationalized normalized ratio (PT-INR) could improve the TTR in patients receiving warfarin. METHODS AND RESULTS: Eight outpatient clinics that introduced POC testing for PT-INR participated in this study. We identified 148 consecutive patients who received warfarin for at least 12 months before and after the introduction of POC testing. We compared the TTR before and after the introduction of POC testing for each patient. TTR after the introduction of POC testing was significantly higher than that beforehand (51.9%±33.0% vs. 69.3%±26.3%; P<0.0001). The improvement in TTR was statistically significant in patients who had low TTR (<70%) before the introduction of POC testing. After the introduction of POC, the time spent above the target INR showed no significant change (3.7%±10.6% vs. 3.3%±6.3%, P=0.7322), while that spent below the target INR improved significantly (44.4%±34.4% vs. 27.4%±27.6%, P<0.0001). CONCLUSIONS: The introduction of POC testing was associated with an improvement in TTR, mainly through a reduction in the time spent below the target INR.

Polymethoxyflavones as agents that prevent formation of cataract: nobiletin congeners show potent growth inhibitory effects in human lens epithelial cells.

Posterior capsular opacification (PCO) is the most frequent complication and the primary reason for visual decrease after extracapsular cataract surgery. The proliferation and migration of leftover lens epithelial cells (LECs) after surgery may contribute to the development of PCO. To prevent PCO, a rational approach would be to inhibit both the proliferation and the migration of LECs using nontoxic xenobiotics. Nobiletin, one of the most abundant polymethoxyflavones (PMFs) in citrus peel, and its synthetic congeners displayed a potent inhibition of LEC proliferation. Structural features which enhance anti-proliferative activity have also been discussed.

Target international normalized ratio values for preventing thromboembolic and hemorrhagic events in Japanese patients with non-valvular atrial fibrillation: results of the J-RHYTHM Registry.

BACKGROUND: Target anticoagulation levels for warfarin in Japanese patients with non-valvular atrial fibrillation (NVAF) are unclear. METHODS AND RESULTS: Of 7,527 patients with NVAF, 1,002 did not receive warfarin (non-warfarin group), and the remaining patients receiving warfarin were divided into 5 groups based on their baseline international normalized ratio (INR) of prothrombin time (≤1.59, 1.6-1.99, 2.0-2.59, 2.6-2.99, and ≥3.0). Patients were followed-up prospectively for 2 years. Primary endpoints were thromboembolic events (cerebral infarction, transient ischemic attack, and systemic embolism), and major hemorrhage requiring hospital admission. During the follow-up period, thromboembolic events occurred in 3.0% of non-warfarin group, but at lower frequencies in the warfarin groups (2.0, 1.3, 1.5, 0.6, and 1.8%/2 years for INR values of ≤1.59, 1.6-1.99, 2.0-2.59, 2.6-2.99, and ≥3.0, respectively; P=0.0059). Major hemorrhage occurred more frequently in warfarin groups (1.5, 1.8, 2.4, 3.3, and 4.1% for INR values ≤1.59, 1.6-1.99, 2.0-2.59, 2.6-2.99, and ≥3.0, respectively; P=0.0041) than in non-warfarin group (0.8%/2 years). These trends were maintained when the analyses were confined to patients aged ≥70 years. CONCLUSIONS: An INR of 1.6-2.6 is safe and effective at preventing thromboembolic events in patients with NVAF, particularly patients aged ≥70 years. An INR of 2.6-2.99 is also effective, but associated with a slightly increased risk in major hemorrhage. (UMIN Clinical Trials Registry UMIN000001569)

Inducible atrial tachycardias with multiple circuits in a stepwise approach are associated with increased episodes of atrial tachycardias after catheter ablation.

BACKGROUND: Atrial tachycardia (AT) is commonly observed during catheter ablation (CA) in patients with atrial fibrillation (AF) undergoing a stepwise extensive CA. In this study, we examined the hypothesis that the presence of multiple inducible ATs (multiple-ATs), which allow for latent multiple reentrant circuits, might increase the potential for following AT episodes after CA. METHODS AND RESULTS: The study population consisted of 347 consecutive AF patients undergoing CA with a stepwise approach. A total of 366 ATs (tricuspid isthmus dependent, 101; mitral annulus, 62; septal, 26; roof dependent, 22; left atrial anterior wall, 13; upper loop, 8; surrounding the left pulmonary veins, 6; surrounding the right pulmonary veins, 6; left atrial appendage, 4; and Cs ostium, 3) occurring during the CA were found in 216 (62.2%) of 347 patients. Multiple-ATs (≥2) during the CA were observed in 93 (26.8%) of 347 patients. The incidence of AT episodes significantly increased as the number of inducible ATs increased (no AT, 7.8%; single AT, 13.7%; and multiple-ATs, 24.2%; P < .001), and multiple-ATs were an independent risk factor for AT episodes (3.07 [1.39-6.78]; P = .005). The impact of the multiple-ATs on the AT episodes was pronounced especially in the patients with coinducible residual AF (with coresidual AF vs without coresidual AF, 8.1% vs 47.7%; P < .001). CONCLUSIONS: The presence of an atrial substrate allowing for multiple-ATs was associated with increased AT episodes during follow-up.

Nobiletin metabolites: synthesis and inhibitory activity against matrix metalloproteinase-9 production.

A divergent synthesis of nobiletin metabolites was developed through highly oxygenated acetophenone derivative. We used commercially available methyl 3,4,5-trimethoxybenzoate as a starting material for concise preparation of the key intermediate, 2'-hydroxy-3',4',5',6'-tetramethoxyacetophenone (I). These metabolites showed strong inhibitory activity against matrix metalloproteinase-9 production in human lens epithelial cells.

Time in the therapeutic range during warfarin therapy in Japanese patients with non-valvular atrial fibrillation. - A multicenter study of its status and infuential factors-.

BACKGROUND: Time in the therapeutic range (TTR) assesses the appropriateness of international normalized ratio of prothrombin time (PT-INR) control during warfarin therapy. We examined the status of and the factors influencing TTR in Japanese patients with non-valvular atrial fibrillation (AF). METHODS AND RESULTS: We enrolled 501 AF patients (mean age, 70 ± 10 years; males 66%; mean CHADS2 score 2.0 ± 1.2) taking warfarin for ≥ 2 years from 5 prefectures. The PT-INR therapeutic range was set up according to the 2008 Japanese Guideline. TTR was 64 ± 25% for all patients and varied from 56% to 74% with the institution. Time below and above TTR was 31 ± 26% and 5 ± 7%, respectively. TTR was not affected by gender or antiplatelet co-administration. TTR in patients < 70 and ≥ 70 years old was 46 ± 23% and 77 ± 17%, respectively (P < 0.0001). TTR in patients with CHADS2 score ≤ 1 and ≥ 2 was 59 ± 27% and 68 ± 23%, respectively (P < 0.0001). TTR in patients with warfarin doses < 2.0, 2.0-4.9, and ≥ 5.0 mg/day was 72 ± 22%, 63 ± 25% and 48 ± 24%, respectively (all P < 0.001). Multivariate analysis revealed age and warfarin dose as independent predictors of TTR. CONCLUSIONS: TTR is generally high in Japan, although it varies with institutions. Most of the time spent out of therapeutic range is below the range. TTR is influenced by age presumably because of the low range recommendation for elderly patients, and by warfarin dose presumably because of physicians' anxiety about the hemorrhage risk.

B-Ring-modified and/or 5-demethylated nobiletin congeners: inhibitory activity against pro-MMP-9 production.

Three metabolites and 12 analogues of nobiletin (1) were synthesized. Whereas nobiletin derivatives 2-4 inhibited pro-MMP-9 production similarly in both PMA- and TNF-α-stimulated human lens epithelial cells, the 2'-hydroxylated analogue 5a exerted marked inhibitory effects (IC(50): 0.4 µM) on PMA-treated cells, which were 170-fold more potent than those on TNF-α-treated cells. This activity may be closely related to PKC-mediated transcriptional regulation of pro-MMP-9.

Increased intraatrial conduction abnormality assessed by P-wave signal-averaged electrocardiogram in patients with Brugada syndrome.

BACKGROUND: Atrial fibrillation (AF) is observed in patients with Brugada syndrome (BS), especially those showing coved-type electrocardiogram (ECG) pattern. Using P-wave signal-averaged ECG (P-SAE), we investigated whether increased intraatrial conduction abnormality contributed to AF generation in BS patients. METHODS: Twenty BS patients and 20 age- and gender-matched healthy controls were enrolled. At the P-SAE recording, 12 of the 20 BS patients showed coved-type (C-BS) and eight showed saddleback-type (S-BS). The total duration (Ad) and root mean square voltage for the terminal 20 ms (LP(20) ) of the filtered P wave were measured. P-wave dispersion (P-disp) was defined as the difference between the maximum and minimum, measured from 16 precordial recording sites. RESULTS: BS patients had a significantly longer Ad (128.2 ± 7.6 vs 116.3 ± 8.2 ms, P < 0.0001), lower LP(20) (2.6 ± 0.9 vs 3.4 ± 0.8 µV, P < 0.01), and greater P-disp (15.5 ± 7.0 vs 7.4 ± 3.2 ms, P < 0.0001) than the controls. C-BS patients had significantly longer Ad (131.0 ± 7.2 vs 124.1 ± 6.8 ms, P < 0.05) and lower LP(20) (2.2 ± 0.6 vs 3.2 ± 1.0 µV, P < 0.05) than S-BS patients. All C-BS patients and only three S-BS patients had atrial late potential (100% vs 38%, P < 0.01). CONCLUSION: Intraatrial conduction delay and its heterogeneity may exist in BS patients, especially those showing coved-type ECG patterns. These atrial electrical abnormalities could be a substrate for atrial reentrant tachycardia such as AF.

Comparison of electrochemical impedance spectra for electrolyte-supported solid oxide fuel cells (SOFCs) and protonic ceramic fuel cells (PCFCs).

Protonic ceramic fuel cells (PCFCs) are expected to achieve high power generation efficiency at intermediate temperature around 400-600 °C. In the present work, the distribution of relaxation times (DRT) analysis was investigated in order to deconvolute the anode and cathode polarization resistances for PCFCs supported on yttria-doped barium cerate (BCY) electrolyte in comparison with solid oxide fuel cells (SOFCs) supported on scandia-stabilized zirconia (ScSZ) electrolyte. Four DRT peaks were detected from the impedance spectra measured at 700 °C excluding the gas diffusion process for ScSZ and BCY. The DRT peaks at 5 × 102-1 × 104 Hz and 1 × 100-2 × 102 Hz were related to the hydrogen oxidation reaction at the anode and the oxygen reduction reaction at the cathode, respectively, for both cells. The DRT peak at 2 × 101-1 × 103 Hz depended on the hydrogen concentration at the anode for ScSZ, while it was dependent on the oxygen concentration at the cathode for BCY. Compared to ScSZ, steam was produced at the opposite electrode in the case of BCY, which enhanced the cathode polarization resistance for PCFCs.

Comparison of Long-Term Outcomes Between Combination Antiplatelet and Anticoagulant Therapy and Anticoagulant Monotherapy in Patients With Atrial Fibrillation and Left Atrial Thrombi.

Background: Anticoagulation for patients with atrial fibrillation (AF) complicated by left atrial thrombi (LAT) is a frequent cause of bleeding complications, but risk factors remain unknown. Methods and Results: Of 3,139 AF patients who underwent transesophageal echocardiography, 82 with LAT under anticoagulation were included in this study. Patients treated with combination antiplatelet and anticoagulant therapy (n=31) were compared with those receiving anticoagulant monotherapy (n=51) to investigate the effects of antiplatelet agents during anticoagulation on bleeding complications. Over a mean (±SD) follow-up of 878±486 days, bleeding events occurred more frequently in the combination therapy than monotherapy group (58% vs. 20%; P<0.001), but there was no significant difference in embolic events (6.5% vs. 3.9%; P=0.606). Kaplan-Meier analysis also showed a significantly higher rate of bleeding events in the combination therapy group, but no significant difference in the rate of embolic events. Inverse probability of treatment weighting revealed that combination therapy was independently associated with an increased risk of bleeding (hazard ratio [HR] 2.98, 95% confidence interval [CI] 1.14-7.89, P=0.026), but not with the risk of embolic events (HR 0.30, 95% CI 0.04-2.59, P=0.275). Net clinical benefit analysis was almost negative for combination therapy vs. monotherapy. Conclusions: In patients with AF and LAT, combination therapy was significantly associated with an increased risk of bleeding events, but not with a reduced risk of embolic events.