A novel catheter ablation strategy for non-paroxysmal atrial fibrillation combining cryoballoon, radiofrequency, and Marshall-vein ethanol ablations.

BACKGROUNDS: Catheter ablation for non-paroxysmal atrial fibrillation (non-PAF) remains challenging and more effective strategy has been required to reduce postoperative arrhythmia recurrences. This study aims to investigate the efficacy and safety of a novel extensive ablation strategy for non-PAF, that is based on a combination of cryoballoon (CBA), radiofrequency (RFA), and Marshall-vein ethanol ablations (EA-VOM). METHODS: The study was a single-center, retrospective observational study. We enrolled 171 consecutive patients who underwent de-novo catheter ablation for non-PAF under conscious sedation with a novel extensive ablation strategy that included CBA for pulmonary vein isolation (PVI) and left atrial roof ablation (LARA), RFA for mitral isthmus (MI) ablation, superior vena cava isolation, and other linear ablations and EA-VOM. Recurrence of atrial arrhythmias over 1 year, procedure outcomes, and procedure-related complications were investigated. RESULTS: A total of 139 (81.3%) patients remained in sinus rhythm during 1-year follow-up. Of the 139 patients, 51 patients (29.8%) received antiarrhythmic drugs. The mean procedure time was 204 ± 45 min. PVI and LARA ablation by CBA and MI block by RFA and EA-VOM were completed in 171 (100%) and 166 (97.1%) patients, respectively. No serious procedure-related complications were observed except for one case of delayed pericardial effusion. CONCLUSION: Approximately 80% of the study patients were AF-free during 1-year follow-up period after a single procedure based on the novel extensive ablation strategy combining CBA, RFA, and EA-VOM. This strategy for non-PAF may be preferred in terms of maintenance of sinus rhythm, safety even in high-risk patients, and relatively short procedure time.

Influence of acute beetroot juice supplementation on cold-induced vasodilation and fingertip rewarming.

PURPOSE: Vasoactive ingredients in beetroot (BR) such as nitrate are known to induce vasodilation in temperate conditions. This study investigated the effect of BR ingestion on cold induced vasodilation (CIVD) and rewarming of finger skin temperature (Tfing) during and after hand immersion in cold water. METHODS: Twenty healthy males (mean ± SD; age 22.2 ± 0.7 years, height 172.6 ± 6.0 cm, body mass 61.3 ± 11.7 kg) repeated a hand cold water immersion test twice with prior BR or water beverage ingestion (randomised order). They rested for 2 h in thermoneutral conditions (27 °C, 40% relative humidity) after consuming the beverage, then immersed their non-dominant hand in 8 °C water for 30 min. They then rewarmed their hand in the ambient air for 20 min. Skin temperature at seven body sites, Tfing, finger skin blood flow (SkBFfing), and blood pressure were measured. RESULTS: During hand immersion parameters of CIVD (Tfing and SkBFfing) were not different between BR and water conditions although skin temperature gradient from proximal to distal body sites was significantly smaller with BR (P < 0.05). During rewarming, SkBFfing and cutaneous vascular conductance were significantly higher with BR than with water (P < 0.05). The rewarming speed in Tfing and SkBFfing was significantly faster with BR at 15- (BR 1.24 ± 0.22 vs water 1.11 ± 0.26 °C/min) and 20-min rewarming (P < 0.05). Additionally, individuals with slower rewarming speed with water demonstrated accelerated rewarming with BR supplementation. CONCLUSION: BR accelerated rewarming in Tfing and SkBFfing after local cold stimulus, whereas, CIVD response during hand cold immersion was not affected by BR ingestion.

Hemopexin as a Potential Binding Partner of Arginine-Rich Cell-Penetrating Peptides in Serum.

Serum proteins affect the in vivo fate and cellular uptake of arginine-rich cell-penetrating peptides (CPPs) and drugs delivered by CPPs. Although the binding of CPPs to serum proteins may possibly reduce their cellular uptake to some extent, it may also prolong their circulation half-life in vivo. We aimed to identify novel binding proteins of arginine-rich CPPs in serum to better understand their in vivo fate and develop more sophisticated drug delivery systems using CPPs. Isothermal titration calorimetry analysis suggests that albumin, the most abundant protein in serum, binds to d-forms of oligoarginine; however, the dissociation constants are several tens of a micromolar. Candidate proteins with the potential of binding to arginine-rich CPPs in serum were then explored using nondenaturing polyacrylamide gel electrophoresis followed by mass spectrometry analysis. Studies using fluorescence correlation spectroscopy determined hemopexin as a potential binding partner of d-forms of arginine-rich CPPs, including d-octaarginine (r 8) and the d-form of the peptide, corresponding to HIV-1 Rev (34-50), with dissociation constants of submicromolar to micromolar range. Using flow cytometry and a split-luciferase-based system, the promotion effect of hemopexin on the total cellular uptake and cytosolic localization of cargos conjugated with these CPPs was confirmed. Therefore, this study elucidated hemopexin as a potential binding partner of d-arginine-rich CPPs that may affect their in vivo fate and cellular uptake.

Usefulness of the over-the-wire microelectrodes catheter in treatment of ventricular arrhythmia arising from the left ventricular summit.

BACKGROUND: This study was aimed to investigate the efficacy of the over-the-wire (OTW) microelectrodes catheter in coronary venous system (CVS) mapping and treatment of outflow tract ventricular arrhythmia (OTVA) arising from the vicinity of the left ventricular summit (LVS). METHODS: Consecutive 62 patients with idiopathic OTVA in whom the OTW microelectrodes catheter was routinely used for CVS mapping were analyzed. CVS mapping was performed for both main trunk (from great cardiac vein to anterior interventricular vein) and branches including the annular branch or septal branch. RESULTS: The earliest activation site (EAS) was within the CVS in 21 patients. Among them, the EAS was within the main trunk of the CVS in seven (33%) and within the branch of the CVS in 14 (67%) patients. Radiofrequency catheter ablation was started at an anatomically adjacent site to the EAS, which eliminated OTVA in 16 (76%) patients　(the endocardial LVOT in 10 and the aortic sinus of Valsalva in six patients). For the remaining five patients with unsuccessful catheter ablation at an anatomically adjacent site, targeted OTVA was eliminated by catheter ablation at the EAS within the CVS in two patients and by chemical ablation with ethanol injection in one patient, resulting in the overall success rate of 90% (19/21). CONCLUSION: The OTW microelectrodes-guided ablation of OTVA from the vicinity of the LVS was effective. In maximizing the efficacy of ablation, CVS branch mapping is important since the earliest activation was commonly recorded not in the main trunk but within the branch of the CVS.

Left ventricular lead placement using inner guiding catheter alone in cardiac resynchronization therapy device implantation.

BACKGROUND: Subselection inner catheters (Inner-Cath) are used adjunctively with outer guiding catheters (Outer-Cath) during cardiac resynchronization therapy (CRT) device implantation. This study aims to investigate the feasibility and efficacy of left ventricular lead placement (LV-LP) guided by Inner-Cath alone. METHODS: A total of 74 patients undergoing de novo CRT implantation were investigated. LV-LP was initially guided by Inner-Cath in 42 patients (Inner-Cath group) and Outer-Cath in 32 patients (Outer-Cath group). In the Inner-Cath group, a 7Fr Inner-Cath was advanced to the coronary sinus through a 7 Fr sheath inserted in a subclavian vein. In the Outer-Cath group, 9Fr or 10Fr Outer-Caths were used. Success rate of LV-LP, additional use of inner or outer catheters and procedure-related complications were compared between groups. RESULTS: LV-LP was successful in all patients in the Inner-Cath group, while LV-LP had to be abandoned in two patients (6.3%) of the Outer-Cath group due to CS perforation caused by Outer-Cath manipulation. Procedure time was significantly shorter in the Inner-Cath group (148 vs. 168 min; p = .024). Deployment of both an inner and outer cath became necessary less frequently for the Inner-Cath group (4.8% vs. 56.3%; p < .001). Mechanical CS injuries due to guiding catheter manipulation were only observed in the Outer-Cath group (0% vs. 15.6%, p = .013). CONCLUSION: LV-LP guided by Inner-Cath alone was feasible in over 95% of the patients without severe complications. This methodology for LV-LP may be preferable in CRT candidates with severe LV dysfunction in terms of shorter procedure time, smaller guiding sheath, and less procedure-related complications.

Successful off-pump reimplantation of the anomalous right coronary artery from the pulmonary artery: A case report.

Anomalous origin of the right coronary artery from the pulmonary artery (ARCAPA) is a rare occurrence that requires surgical repair, typically via cardiopulmonary bypass (CPB). In this study, we present the case of a patient with ARCAPA with a high risk of cerebral infarction and left main trunk stenosis. However, because of the high risk of cerebral infarction, CPB was no longer an option during surgical intervention. Instead, we performed off-pump reimplantation of the ARCAPA to the ascending aorta and coronary artery bypass grafting of the left coronary artery. The patient had an uneventful postoperative course. Based on the successful outcomes of this case, we suggest off-pump reimplantation of the ARCAPA to the ascending aorta as a useful alternative for patients who are not eligible to undergo CPB during surgical repair. .

Effect of food intake on respiratory chemosensitivity to CO2 in young adults.

BACKGROUND: Food intake augments CO2 production; however, minute ventilation is not augmented during exercise after food intake. Respiratory chemoreceptors respond to CO2 and influence respiration. We examined the effect of food intake on respiratory chemosensitivity to CO2 in young adults. METHODS: The hypercapnic ventilatory response was measured in eleven healthy individuals before and after food intake. To evaluate the respiratory chemoreflex response to CO2, minute ventilation was plotted against end-tidal PCO2 using data obtained with the rebreathing method. RESULTS: Sublingual temperature, CO2 output, minute ventilation, and end-tidal PCO2 were all significantly higher at baseline in the session after food intake than in the session before food intake. On the other hand, there was no significant difference in chemosensitivity to CO2 between the sessions before and after food intake (1.60 ± 0.62 vs. 1.53 ± 0.62 l min-1 mmHg-1). CONCLUSIONS: Food intake does not influence respiratory chemosensitivity to CO2 in young adults, which is different from infants. This suggests that control of respiration differs between young adults and infants and that the elevated minute ventilation after food intake in young adults is not caused by a change in respiratory chemosensitivity.

Clinical experience of idarucizumab use in cases of cardiac tamponade under uninterrupted anticoagulation of dabigatran during catheter ablation of atrial fibrillation.

Anticoagulants are prescribed for prevention of thromboembolic events (TE) of atrial fibrillation (AF), however, their effects have a negative impact on disastrous bleeding outcomes. Idarucizumab was developed to reverse the anticoagulation effects of dabigatran. This study aimed to retrospectively investigate the clinical efficacy and safety of idarucizumab in the setting of progressive emergent bleeding events associated with catheter ablation (CA). Dabigatran is given uninterruptedly as an anticoagulant in patients undergoing CA of AF. The capacity of idarucizumab to reverse the anticoagulant effects of dabigatran in patients with cardiac tamponade associated with CA was examined by measuring the activated partial thromboplastin time (aPTT), active clotting time (ACT), and prothrombin international normalizing ratio (PT-INR). The primary endpoint was effective hemostasis. This analysis included 21 patients receiving idarucizumab, given for restoration of hemostasis. In all 21 patients, hemostasis was restored at a median of 205.6 ± 14.8 min. Normal intraoperative cessation of bleeding was reported in 16 patients, and completion of hemostasis was also ascertained in the remaining four within 5 h. No TEs occurred within 72 h after the idarucizumab administration. Despite a significant reduction in the aPTT and ACT, no significant change was observed in PT-INR after administering idarucizumab. In emergency situations, idarucizumab was able to reverse dabigatran within a relatively short period without any serious adverse events.

Electrophysiological Assessment of Murine Atria with High-Resolution Optical Mapping.

Recent genome-wide association studies targeting atrial fibrillation (AF) have indicated a strong association between the genotype and electrophysiological phenotype in the atria. That encourages us to utilize a genetically-engineered mouse model to elucidate the mechanism of AF. However, it is difficult to evaluate the electrophysiological properties in murine atria due to their small size. This protocol describes the electrophysiological evaluation of atria using an optical mapping system with a high temporal and spatial resolution in Langendorff perfused murine hearts. The optical mapping system is assembled with dual high-speed complementary metal oxide semiconductor cameras and high magnification objective lenses, to detect the fluorescence of a voltage-sensitive dye and Ca2+ indicator. To focus on the assessment of murine atria, optical mapping is performed with an area of 2 mm × 2 mm or 10 mm x 10 mm, with a 100 × 100 resolution (20 µm/pixel or 100 µm/pixel) and sampling rate of up to 10 kHz (0.1 ms) at maximum. A 1-French size quadripolar electrode pacing catheter is placed into the right atrium through the superior vena cava avoiding any mechanical damage to the atrium, and pacing stimulation is delivered through the catheter. An electrophysiological study is performed with programmed stimulation including constant pacing, burst pacing, and up to triple extrastimuli pacing. Under a spontaneous or pacing rhythm, the optical mapping recorded the action potential duration, activation map, conduction velocity, and Ca2+ transient individually in the right and left atria. In addition, the programmed stimulation also determines the inducibility of atrial tachyarrhythmias. Precise activation mapping is performed to identify the propagation of the excitation in the atrium during an induced atrial tachyarrhythmia. Optical mapping with a specialized setting enables a thorough electrophysiological evaluation of the atrium in murine pathological models.

Lipase-catalyzed asymmetric synthesis of naphtho[2,3-c]furan-1(3H)-one derivatives by a one-pot dynamic kinetic resolution/intramolecular Diels-Alder reaction: Total synthesis of (-)-himbacine.

One-pot sequential reactions using the acyl moieties installed by enzymatic dynamic kinetic resolution of alcohols have been little investigated. In this work, the acryloyl moiety installed via the lipase/oxovanadium combo-catalyzed dynamic kinetic resolution of a racemic dienol [4-(cyclohex-1-en-1-yl)but-3-en-2-ol or 1-(cyclohex-1-en-1-yl)but-2-en-1-ol] with a (Z)-3-(phenylsulfonyl)acrylate underwent an intramolecular Diels-Alder reaction in a one-pot procedure to produce an optically active naphtho[2,3-c]furan-1(3H)-one derivative (98% ee). This method was successfully applied to the asymmetric total synthesis of (-)-himbacine.

Development of a new knock-in mouse model and evaluation of pharmacological activities of lusutrombopag, a novel, nonpeptidyl small-molecule agonist of the human thrombopoietin receptor c-Mpl.

Lusutrombopag (S-888711), an oral small-molecule thrombopoietin receptor (TPOR) agonist, has gained first approval as a drug to treat thrombocytopenia of chronic liver disease in patients undergoing elective invasive procedures in Japan. Preclinical studies were performed to evaluate its efficacy against megakaryopoiesis and thrombopoiesis. To investigate the proliferative activity and efficacy of megakaryocytic colony formation via human TPOR, lusutrombopag was applied to cultured human c-Mpl-expressing Ba/F3 (Ba/F3-hMpl) cells and human bone marrow-derived CD34-positive cells, respectively. Lusutrombopag caused a robust increase in Ba/F3-hMpl cells by activating pathways in a manner similar to that of thrombopoietin and induced colony-forming units-megakaryocyte and polyploid megakaryocytes in human CD34-positive cells. Because lusutrombopag has high species specificity for human TPOR, there was no suitable experimental animal model for drug evaluation, except for immunodeficient mouse-based xenograft models. Therefore, a novel genetically modified knock-in mouse, TPOR-Ki/Shi, was developed by replacing mouse Mpl with human-mouse chimera Mpl. In TPOR-Ki/Shi mice, lusutrombopag significantly increased circulating platelets in a dose-dependent manner during 21-day repeated oral administration. Histopathological study of the TPOR-Ki/Shi mice on day 22 also revealed a significant increase in megakaryocytes in the bone marrow. These results indicate that lusutrombopag acts on human TPOR to upregulate differentiation and proliferation of megakaryocytic cells, leading to platelet production.

Oxidative Stress Induced Ventricular Arrhythmia and Impairment of Cardiac Function in Nos1ap Deleted Mice.

Genome-wide association study has identified that the genetic variations at NOS1AP (neuronal nitric oxide synthase-1 adaptor protein) were associated with QT interval and sudden cardiac death (SCD). However, the mechanism linking a genetic variant of NOS1AP and SCD is poorly understood. We used Nos1ap knockout mice (Nos1ap(-/-)) to determine the involvement of Nos1ap in SCD, paying special attention to oxidative stress.At baseline, a surface electrocardiogram (ECG) and ultrasound echocardiography (UCG) showed no difference between Nos1ap(-/-) and wild-type (WT) mice. Oxidative stress was induced by a single injection of doxorubicin (Dox, 25 mg/kg). After Dox injection, Nos1ap(-/-) showed significantly higher mortality than WT (93.3 versus 16.0% at day 14, P < 0.01). ECG showed significantly longer QTc in Nos1ap(-/-) than WT, and UCG revealed significant reduction of fractional shortening (%FS) only in Nos1ap(-/-) after Dox injection. Spontaneous ventricular tachyarrhythmias were documented by telemetry recording after Dox injection only in Nos1ap(-/-). Ex vivo optical mapping revealed that the action potential duration (APD)90 was prolonged at baseline in Nos1ap(-/-), and administration of Dox lengthened APD90 more in Nos1ap(-/-) than in WT. The expression of Bnp and the H2O2 level were higher in Nos1ap(-/-) after Dox injection. Nos1ap(-/-) showed a reduced amplitude of calcium transient in isolated cardiomyocytes after Dox injection. Administration of the antioxidant N-acetyl-L-cysteine significantly reduced mortality of Nos1ap(-/-) by Dox injection, accompanied by prevention of QT prolongation and a reduction in %FS.Although Nos1ap(-/-) mice have apparently normal hearts, oxidative stress evokes ventricular tachyarrhythmia and heart failure, which may cause sudden cardiac death.

Intravital imaging of Ca(2+) signals in lymphocytes of Ca(2+) biosensor transgenic mice: indication of autoimmune diseases before the pathological onset.

Calcium ion (Ca(2+)) signaling is a typical phenomenon mediated through immune receptors, such as the B-cell antigen receptor (BCR), and it is important for their biological activities. To analyze the signaling of immune receptors together with their in vivo dynamics, we generated stable transgenic mice with the Föster/fluorescence resonance energy transfer (FRET)-based Ca(2+) indicator yellow cameleon 3.60 (YC3.60), based on the Cre/loxP system (YC3.60(flox)). We successfully obtained mice with specific YC3.60 expression in immune or nerve cells as well as mice with ubiquitous expression of this indicator. We established five-dimensional (5D) (x, y, z, time, and Ca(2+)) intravital imaging of lymphoid tissues, including the bone marrow. Furthermore, in autoimmune-prone models, the CD22(-/-) and C57BL/6- lymphoproliferation (lpr)/lpr mouse, Ca(2+) fluxes were augmented, although they did not induce autoimmune disease. Intravital imaging of Ca(2+) signals in lymphocytes may improve assessment of the risk of autoimmune diseases in model animals.

High-fat diet increases vulnerability to atrial arrhythmia by conduction disturbance via miR-27b.

BACKGROUND: Lifestyle-related diseases, such as obesity and dyslipidemia are important risk factors for atrial fibrillation (AF). However, the underlying mechanism linking these diseases and AF has not been fully investigated. METHODS: Adult male mice were fed a high-fat diet (HFD) or vehicle (NC) for 2 months. Electrocardiography and in vivo electrophysiological study were performed. Mice were then sacrificed for quantification of mRNA, microRNA, and protein in atria, in addition to histological analysis. Conduction velocity (CV) in right atrium was measured by optical mapping in Langendorff perfused hearts. Cultured atrial cardiomyocytes were treated with palmitate with or without a specific microRNA inhibitor. Twelve hours after stimulation, cells were lysed, and subjected to analysis with qPCR and Western blotting. RESULTS: HFD mice showed prolonged P wave duration, increased inducibility of sustained atrial tachycardia, and reduced atrial CV than NC mice. HFD mice also showed increased expression in inflammatory cytokines, whereas fibrotic area and signals relating fibrosis were not changed. HFD mice demonstrated reduced expression of Cx40 in mRNA and protein levels, and its lateralized expression in atria. MicroRNA array analysis revealed that miR-27b expression was up-regulated in HFD mice, and luciferase assay confirmed the direct interaction between miR-27b and Cx40 3'UTR. In palmitate-stimulated atrial cardiomyocytes, miR-27b up-regulation and Cx40 down-regulation were observed, while expression of inflammatory cytokines was not altered. Inhibition of miR-27b with antisense oligonucleotides reversed the alteration caused by palmitate stimulation. CONCLUSION: HFD may increase the vulnerability to atrial arrhythmia by down-regulation of Cx40 via miR-27b, rather than fibrosis, which is independent of inflammation.

Relationship between perceived exertion and blood lactate concentrations during incremental running test in young females.

BACKGROUND: To investigate more practical handling of Borg's ratings of perceived exertion (RPE) and category-ratio scale of RPE (CR-10), we evaluated interrelationships between RPE, CR-10, and blood lactate concentrations (bLa) during incremental treadmill running tests for young females with different aerobic fitness levels. METHODS: Oxygen consumption, heart rate, bLa, RPE, and CR-10 were measured from distance runners (DR; n = 15), race walkers (RW; n = 6), and untrained females (UT; n = 11). These variables corresponding to the lactate threshold (LT) and onset of blood lactate accumulation (OBLA) were compared among these groups. RESULTS: The UT had significantly lower RPE at LT than DR and RW, although the CR-10 at LT was not significantly different among these groups. The CR-10 at OBLA was significantly lower for the UT than DR. The relationship between bLa and CR-10 was approximated well by two linear regression lines in all groups. The bLa at the intersection only for the RW was significantly lower than that at LT, however, such intersections were observed at CR-10 = 3.1 to 3.2 without significant group differences. The CR-10 scores at LT and intersections were not significantly different in each group. CONCLUSION: These results suggested that an intersection between CR-10 and bLa was observed at the CR-10 score around three points of first half regardless of the aerobic fitness levels in young females, and such CR-10 scores would be associated with LT.

Use of fructosyl peptide oxidase for HbA1c assay.

ARKRAY, Inc developed the world's first automatic glycohemoglobin analyzer based on HPLC (1981). After that, ARKRAY developed enzymatic HbA1c assay "CinQ HbA1c" with the spread and diversification of HbA1c measurement (2007). CinQ HbA1c is the kit of Clinical Chemistry Analyzer, which uses fructosyl peptide oxidase (FPOX) for a measurement reaction. This report mainly indicates the developmental background, measurement principle, and future of the enzymatic method HbA1c reagent.

Amiodarone-induced thyrotoxicosis late after amiodarone withdrawal.

BACKGROUND: Amiodarone-induced thyrotoxicosis (AIT) may develop long after amiodarone withdrawal. This study sought to determine the incidence and clinical characteristics of AIT after amiodarone withdrawal. METHODS AND RESULTS: The incidence and clinical characteristics of AIT were examined retrospectively in 71 patients (51 males, mean age 65±13 years) whose amiodarone therapy had been discontinued after at least 1 month of administration. Five (7%) patients developed AIT late after amiodarone withdrawal (11±3 months): 2 patients exhibited exacerbation of heart failure by atrial fibrillation, 2 developed dyspnea on exertion, and 1 patient was asymptomatic. The patients who developed AIT had a high incidence of amiodarone-induced hypothyroidism during amiodarone therapy (100 vs. 24%, P=0.002), had received amiodarone therapy for longer (76±86 months vs. 16±22 months, P<0.001), with a larger cumulative dose (271.1±268.5 g vs. 63.4±86.5 g, P<0.001) compared with those who did not. In all 5 patients, AIT resolved spontaneously within 5 months without the use of steroids. CONCLUSIONS: Occurrence of amiodarone-induced hypothyroidism during amiodarone therapy and long duration of therapy may be cautionary markers of late AIT.

Discrete prepotential as an indicator of successful ablation in patients with coronary cusp ventricular arrhythmia.

BACKGROUND: Although coronary cusp (CC) ventricular arrhythmia (VA) can be treated by catheter ablation, reliable indicators of successful ablation sites have not been fully identified. METHODS AND RESULTS: This study comprised 392 patients undergoing radiofrequency catheter ablation for outflow tract-VA at 3 institutions from January 2007 to August 2012. The successful ablation site was on the left CC or right CC in 35 (8.9%) of the 392 patients. In 9 (26%) of these 35 patients, a discrete prepotential was recognized, 5 of whom had left CC-VAs and 4 of whom had right CC-VAs. Radiofrequency catheter ablation was successful at the site of the prepotential in all 9 of these patients. The duration of the isoelectric line between the end of the discrete prepotential and the onset of the ventricular electrogram was 27±13 ms. The time from onset of the discrete prepotential at the successful ablation site on the CC to the QRS onset (activation time) was 69±20 ms (range, 50-98 ms). Pace mapping was graded as excellent at the successful ablation site in only 1 patient. No discrete prepotential was recorded in any successful right outflow tract-VA ablation case in this study. CONCLUSIONS: A discrete prepotential was seen in 9 (26%) of 35 patients with CC-VA. In left and right CC-VA, the site of a discrete prepotential with ≥50 ms activation time may indicate a successful ablation site.

Bleeding events and activated partial thromboplastin time with dabigatran in clinical practice.

BACKGROUND: Dabigatran has demonstrated promising results for the prevention of strokes in patients with non-valvular atrial fibrillation (NVAF). However, there have been episodes of major bleeding, especially in elderly patients or those with renal dysfunction. The purpose of this study was to retrospectively examine the relationship between the bleeding events and activated partial thromboplastin time (APTT) values under dabigatran usage in the everyday clinical practice. Moreover, we investigated which factors would contribute to the APTT values. METHODS AND RESULTS: A total of 139 NVAF patients (112 men, 65 ± 11 years) were included. We evaluated the influence of the putative etiological variables and the bleeding score, HAS-BLED score, on APTT values: age greater than 70 years, renal function, gender, dose of dabigatran, and the concomitant prescription of a P-glycoprotein inhibitor. There were 50 patients with an age of ≥ 70 years (36.0%). A P-glycoprotein inhibitor was administered in 18 patients. During the observation period (median 120 days) there was 1 episode of asymptomatic cerebral infarction. There were no intrinsic major bleeding events, however, 11 patients had minor hemorrhagic events. The results of the APTT measurements exhibited a variety of values both among inter- and intra-individuals. On multivariable analysis, significant associations were found between the following risk factors and the APTT values: creatinine clearance, dose of dabigatran, and concomitant use of a P-glycoprotein inhibitor. The minor bleeding events did not correlate with the APTT values, nor HAS-BLED score. CONCLUSIONS: The APTT values became prolonged under dabigatran usage and exhibited a remarkable diversity. Although major bleeding did not occur unless APTT was prolonged excessively, minor bleeding arose irrespective of the APTT values even within the range of the APTT values not exceeding 80s.