Efficacy and safety of apixaban in the patients undergoing the ablation of atrial fibrillation.

INTRODUCTION: Apixaban, a factor Xa (FXa) inhibitor, is a new oral anticoagulant for stroke prevention in atrial fibrillation (AF). However, little is known about its efficacy and safety as a periprocedural anticoagulant therapy for patients who had undergone catheter ablation (CA) for AF. METHODS AND RESULTS: We evaluated 342 consecutive patients who underwent CA for AF between April 2013 and March 2014 and received apixaban (n = 105) and warfarin (n = 237) for uninterrupted periprocedural anticoagulation. We retrospectively investigated the occurrence of bleeding and thromboembolic complications during the procedural period and compared them between the apixaban group (AG) and warfarin group (WG). Thromboembolic complications occurred in one (0.4%) patient in the WG. Major and minor bleeding complications occurred in one (1%) and four (4%) patients in the AG, and three (1%) and 12 (5%) patients in the WG. No significant difference in complications was observed between the AG and WG. Of importance, adverse event rates did not differ between the two groups after adjusting by a propensity score analysis. In preoperative tests of blood coagulation, there were significant differences in the prothrombin time, activated partial thromboplastin time, FXa activity, and prothrombin fragment 1 + 2 (F1+2) levels between the AG and WG. CONCLUSION: The use of apixaban during the periprocedural period of AF ablation seemed as efficacious and safe as warfarin.

Clinical outcome of implantable cardioverter defibrillators with recalled and non-recalled leads in Japanese patients. Increased failure rate of the Sprint Fidelis lead.

BACKGROUND: In recent years, there has been a series of recalls of popular implantable cardioverter defibrillators leads, and several reports have demonstrated an increasing rate of failure of such leads over time in Caucasian patients. However, little is known about the performance of these leads in Asian patients. The aim of this study was to investigate the rate of failure of the recalled leads and the characteristics as compared with non-recalled leads in Japanese patients. METHODS AND RESULTS: A retrospective chart review was conducted in 214 patients (75 Sprint Fidelis, 8 Riata, and 131 Sprint Quattro leads) who underwent implantation and follow-up at Nagoya University Hospital. During the follow-up period, 14 Sprint Fidelis leads (19%) and 1 Riata lead (13%) failed, but no abnormality was found in the Sprint Quattro, non-recalled leads. Five patients (4 Sprint Fidelis and 1 Riata, 33% of lead failure patients) received inappropriate shocks. The 3-, 4-, and 5-year lead survival rates in Sprint Fidelis leads were 95.1% (95% confidence interval [CI]: 89.6%-100%), 89.8% (95% CI: 82.1%-97.6%), and 88.0% (95% CI: 79.6%-96.4%), respectively. A previous device implantation before Sprint Fidelis lead was the only significant predictor for lead fracture (hazard ratio, 5.33; 95% CI: 1.55-18.4; P=0.008). CONCLUSIONS: The rate of Sprint Fidelis lead failure continues to increase over time in Japanese patients.

Clinical characteristics and predictors of super-response to cardiac resynchronization therapy: a combination of predictive factors.

BACKGROUND: Patients with greater improvement of cardiac function after cardiac resynchronization therapy (CRT) implantation are identified as "super-responders." However, it remains unclear which kind of preimplant assessments could accurately predict outcomes after CRT. Thus, we aimed to examine the essential predicting factors for super-response to CRT, and to construct an accurate predictable model. METHODS: We retrospectively analyzed the CRT patients who underwent implantation at Nagoya University Hospital. Super-responders are defined as those who show a relative reduction in left ventricular end-systolic volume ≥30% after 6 months of CRT. RESULTS: Eighty patients (mean age, 67.8 ± 10.2 years) were included. Twenty-two patients received upgrading procedure to CRT implantation. Six months after the implantation, 29 patients (36%) were super-responders. Multiple logistic regression analysis shows that consistent right ventricular pacing with a previous device (odds ratio [OR] 7.28, 95% confidence interval [CI] 1.52-34.9; P = 0.013), lack of prior history of ventricular arrhythmia (OR 5.32, 95% CI 1.52-18.6; P = 0.009), and smaller left atrial diameter (LAD) (OR 0.92, 95% CI 0.86-0.98; P = 0.014) are independent predictors for CRT super-responders. The use of a combination of these predictive factors could increase the certainty with which a greater response to CRT is predicted and the presence of such a combination could improve prognosis. CONCLUSION: Greater response to biventricular pacing occurs more frequently in patients with consistent right ventricular pacing, lack of prior history of ventricular arrhythmia, and smaller LAD. An association between patient background characteristics and a super-response to CRT was also identified.

Compositional changes of human hair melanin resulting from bleach treatment investigated by nanoscale secondary ion mass spectrometry.

BACKGROUND/PURPOSE: It is important to understand the influence of bleach treatment on human hair because it is one of the most important chemical treatments in hair cosmetic processes. A comparison of the elemental composition of melanin between virgin hair and bleached hair would provide important information about the structural changes of melanin. To investigate the elemental composition of melanin granules in virgin black hair and bleached hair, these hair cross-sections are analyzed by using a nanoscale secondary ion mass spectrometry (NanoSIMS). METHODS: The virgin black hair and bleached hair samples were embedded in resin and smooth hair cross-sections were obtained using an ultramicrotome. NanoSIMS measurements were performed using a Cs(+) primary ion beam to detect negative secondary ions. RESULTS: More intensive (16) O(-) ions were detected from the melanin granules of bleached hair than from those of virgin black hair in NanoSIMS (16) O(-) ion image. In addition, it was indicated that (16) O(-) ion intensity and (16) O(-) /(12) C(14) N(-) ion intensity ratio of melanin granules in bleached hair were higher than those in virgin black hair. CONCLUSION: Nanoscale secondary ion mass spectrometry analysis of the cross-sections of virgin black hair and bleached hair indicated that the oxygen content in melanin granules was increased by bleach treatment.

Cystatin C as a predictor of mortality and cardiovascular morbidity after cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) has been reported to improve symptoms and cardiac performance in patients with severe heart failure (HF), but CRT recipients with advanced HF do not always experience improved mortality rates. Cystatin C has recently been involved in HF, but the association of serum cystatin C level with adverse events and long-term prognosis after CRT is unknown. This study investigated whether cystatin C level can predict mortality and cardiovascular events after CRT. METHODS AND RESULTS: A total of 117 consecutive patients receiving a CRT device for the treatment of advanced HF were assessed according to cystatin C level and long-term outcome after implantation of the device. Over a median follow-up of 3.2 years, 34 patients (29.1%) died and 59 patients (50.4%) developed cardiovascular events. Kaplan-Meier survival analysis indicated that elevated cystatin C level was significantly associated with higher all-cause mortality and prevalence of cardiovascular events, including hospitalization for progressive HF. After multivariate Cox regression analysis, serum cystatin C level and QRS duration, but not conventional echocardiographic parameters, were found to independently predict all-cause death or cardiovascular events. Of importance, only cystatin C level was an independent predictor of all-cause mortality after CRT. CONCLUSIONS: Cystatin C level independently predicts cardiac mortality or morbidity in patients receiving CRT. The assessment of cystatin C level could provide valuable information about long-term prognosis after CRT.

Alkaline peroxide treatment induces acquired unruly hair by apparently affecting distinct macrofibrils.

Individual hairs can be inherently curly; however, bleach treatment can cause damaged hairs to acquire a curl, a phenomenon we term acquired unintentional unruly hair. Because there have been no reports concerning acquired unintentional unruly hair, the influence of bleach treatment with alkaline peroxide that produce this phenomenon was investigated. First, it was validated that the radius of curvature in many curly hairs is reduced upon bleach treatment. Next, the influence of bleach treatment on the mechanical properties of inner components was studied by the force curve method using atomic force microscopy. This measurement revealed four types of macrofibrils-on the orthocortex- or the paracortex-like structure, and on the concave or the convex side-have different mechanical properties. Macrofibrils on the orthocortex-like structure on the convex side were especially influenced by alkaline peroxide treatment, and may be particularly important to acquired unintentional unruly hair.

＜Editors' Choice＞ Very long-term clinical outcomes after percutaneous coronary intervention for complex vs non-complex lesions: 10-year outcomes following sirolimus-eluting stent implantation.

Few studies have reported the long-term outcomes (>10 years) following first-generation drug-eluting stent implantation. In this single-center retrospective study, we investigated the very long-term clinical outcomes after first-generation sirolimus-eluting stent (SES) implantation in patients with complex lesions. The study included 383 consecutive patients who underwent initial SES implantation between July 2004 and January 2006; 84 and 299 of these patients reported a history of percutaneous coronary intervention (PCI) for complex and noncomplex lesions, respectively. Complex PCI was defined as having at least one of the following features: left main trunk PCI, implantation of ≥3 stents, bifurcation lesions with implantation of 2 stents, total stent length >60 mm, or chronic total occlusion. The target lesion revascularization (TLR) rate was significantly higher in the complex PCI than in the noncomplex PCI group (29.4% vs 13.0%, P=0.001), and we observed a significant intergroup difference in the late TLR (>1 year) rates (21.6% vs 9.5%, P=0.008). Late TLR continued over 10 years at a rate of 2.4%/year in the complex PCI and 1.1%/year in the noncomplex PCI group. Cox regression analysis revealed that complex PCI was related to TLR both over 10 years (hazard ratio 2.29, P=0.003) and beyond 1 year (hazard ratio 2.32, P=0.01). Cardiac death was more common in the complex PCI than in the noncomplex PCI group, particularly 4 years after PCI (15.8% vs 7.5%, P=0.031). Sudden death was the major cause of cardiac death beyond 4 years in the complex PCI group. These data indicate that long-term careful follow-up is essential for patients implanted with SES, especially those treated for complex lesions.

Remote Management of Pacemaker Patients With Biennial In-Clinic Evaluation: Continuous Home Monitoring in the Japanese At-Home Study: A Randomized Clinical Trial.

BACKGROUND: Current expert consensus recommends remote monitoring for cardiac implantable electronic devices, with at least annual in-office follow-up. We studied safety and resource consumption of exclusive remote follow-up (RFU) in pacemaker patients for 2 years. METHODS: In Japan, consecutive pacemaker patients committed to remote monitoring were randomized to either RFU or conventional in-office follow-up (conventional follow-up) at twice yearly intervals. RFU patients were only seen if indicated by remote monitoring. All returned to hospital after 2 years. The primary end point was a composite of death, stroke, or cardiovascular events requiring surgery, and the primary hypothesis was noninferiority with 5% margin. RESULTS: Of 1274 randomized patients (50.4% female, age 77±10 years), 558 (RFU) and 550 (Conventional follow-up) patients reached either the primary end point or 24 months follow-up. The primary end point occurred in 10.9% and 11.8%, respectively (P=0.0012 for noninferiority). The median (interquartile range) number of in-office follow-ups was 0.50 (0.50-0.63) in RFU and 2.01 (1.93-2.05) in conventional follow-up per patient-year (P<0.001). Insurance claims for follow-ups and directly related diagnostic procedures were 18 800 Yen (16 500-20 700 Yen) in RFU and 21 400 Yen (16 700-25 900 Yen) in conventional follow-up (P<0.001). Only 1.4% of remote follow-ups triggered an unscheduled in-office follow-up, and only 1.5% of scheduled in-office follow-ups were considered actionable. CONCLUSIONS: Replacing periodic in-office follow-ups with remote follow-ups for 2 years in pacemaker patients committed to remote monitoring does not increase the occurrence of major cardiovascular events and reduces resource consumption. Registration: URL: https://clinicaltrials.gov; Unique identifier: NCT01523704.

Refractory ventricular fibrillation caused by caffeine intoxication.

A 30-year-old female with no history of cardiac or systemic disease presented with incessant ventricular fibrillation (VF) after an intake of 12 g of over-the-counter caffeine tablets for a suicidal purpose. Her VF was refractory, and repeated defibrillations were needed to attain a recovery of sinus rhythms. We then performed percutaneous cardiopulmonary support and therapeutic hypothermia to stabilize her circulation and prevent anoxic brain damage, respectively. A blood examination revealed an extremely high concentration of caffeine (172 mg/L). She fully recovered 16 days after her admission. Our findings reveal the potentially lethal arrhythmogenic nature of caffeine. .

Alogliptin, a dipeptidyl peptidase-4 inhibitor, regulates the atrial arrhythmogenic substrate in rabbits.

BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors were recently reported to have cardioprotective effects via amelioration of ventricular function. However, the role of DPP-4 inhibition in atrial remodeling, especially of the arrhythmogenic substrate, remains unclear. OBJECTIVE: We investigated the effects of a DPP-4 inhibitor, alogliptin, on atrial fibrillation (AF) in a rabbit model of heart failure caused by ventricular tachypacing (VTP). METHODS: Rabbits subjected to VTP at 380 bpm for 1 or 3 weeks, with or without alogliptin treatment, were assessed using echocardiography, electrophysiology, histology, and immunoblotting and compared with nonpaced animals. RESULTS: VTP rabbits exhibited increased duration of atrial burst pacing-induced AF, whereas administration of alogliptin shortened this duration by 73%. The extent of atrial fibrosis after VTP was reduced by 39% in the alogliptin-treated group. VTP rabbits treated with alogliptin displayed a 1.6-fold increase in left atrial myocardial capillary density compared with nontreated rabbits. A 2-fold increase in endothelial nitric oxide synthase (eNOS) phosphorylation was observed in the left atrium of alogliptin-treated rabbits compared with nontreated rabbits. Moreover, a nitric oxide synthase inhibitor (N(ω)-nitro-l-arginine methyl ester) blocked the beneficial effects of alogliptin on AF duration, fibrosis, and capillary density. CONCLUSION: Alogliptin shortened the duration of AF caused by VTP-induced fibrotic atrial tissue by augmenting atrial angiogenesis and activating eNOS. Our findings suggest that DPP-4 inhibitors may be useful in the prevention of heart failure-induced AF.

Differences in activated clotting time among uninterrupted anticoagulants during the periprocedural period of atrial fibrillation ablation.

BACKGROUND: Close monitoring of intraoperative activated clotting time (ACT) is crucial to prevent complications during the periprocedural period of atrial fibrillation (AF) ablation. However, little is known about the ACT in patients receiving new oral anticoagulant agents (NOACs). OBJECTIVE: The purpose of this study was to evaluate change in the ACT among anticoagulant agents used during the periprocedural period of AF ablation. METHODS: We examined 869 consecutive patients who underwent AF ablation between April 2012 and August 2014 and received NOACs (n = 499), including dabigatran, rivaroxaban, and apixaban, or warfarin (n = 370) for uninterrupted periprocedural anticoagulation. Changes in intraprocedural ACT were investigated among the anticoagulant agents. Furthermore, the incidence of periprocedural events was estimated. RESULTS: The average time in minutes required for achieving a target ACT >300 seconds was significantly longer in the dabigatran group (DG) and apixaban group (AG) than in the warfarin group (WG) and rivaroxaban group (RG) (60 and 70 minutes vs 8 and 9 minutes, respectively; P < .001). In addition, the proportion of patients who achieved the target ACT after initial heparin bolus was significantly lower in the DG and AG than in the WG and RG (36% and 26% vs 84% and 78%, respectively; P < .001). Furthermore, the incidence of periprocedural complications was equivalent among the groups. CONCLUSION: The average time required to reach the target ACT was longer in the DG and AG than in the WG and RG.

Feasibility and safety of uninterrupted dabigatran therapy in patients undergoing ablation for atrial fibrillation.

OBJECTIVE: Uninterrupted oral warfarin strategy has become the standard protocol to prevent complications during catheter ablation (CA) for the treatment of atrial fibrillation (AF). However, little is known about the safety and efficacy of uninterrupted dabigatran therapy in patients undergoing CA for AF. Therefore, this study investigated the safety and efficacy of uninterrupted dabigatran therapy and compared the findings with those for uninterrupted warfarin therapy. METHODS: Bleeding and thromboembolic events during the periprocedural period were evaluated in 363 consecutive patients who underwent CA for AF at Nagoya University Hospital, and received uninterrupted dabigatran (n=173) or uninterrupted warfarin (n=190) for periprocedural anticoagulation. RESULTS: A total of 27 (7%) patients experienced either bleeding or thromboembolic complications. Major bleeding complications occurred in 2 (1%) patients in the dabigatran group (DG) and 2 (1%) patients in the warfarin group (WG). Eight (5%) patients in the DG and 9 (5%) patients in the WG experienced groin hematoma, a type of minor bleeding complication. Meanwhile, no patient in the DG and 1 (1%) in the WG developed cerebral ischemic stroke. Overall, there was no significant difference between the groups for any category. The activated partial thromboplastin time (APTT) independently predicted periprocedural complications in the DG. CONCLUSION: Uninterrupted dabigatran therapy in CA for AF thus may be a safe and effective anticoagulant therapy, and appears to be closely similar to continuous warfarin; however, it is essential to pay close attention to the APTT values when using dabigatran during CA.

Impact of cardiac resynchronization therapy-defibrillator implantation on the association between body mass index and prognosis in patients with heart failure.

PURPOSE: This study aimed to examine the association between body mass index (BMI) and prognosis in heart failure patients after cardiac resynchronization therapy-defibrillator (CRT-D) implantation. METHODS: We retrospectively investigated 125 patients (33 overweight [BMI ≥25 kg/m(2)], 75 normal weight [BMI 18.5-24.9 kg/m(2)], and 17 underweight patients [BMI <18.5 kg/m(2)]) who underwent CRT-D implantation. The clinical outcome endpoints were all-cause death and appropriate shock therapy. RESULTS: During the follow-up period (mean 3.1 ± 1.8 years), 23 patients died (1 [3.0 %] overweight, 17 [22.7 %] normal weight, and 5 [29.4 %] underweight patients), and appropriate shock events were observed in 14 patients (2 [6.1 %] overweight, 10 [13.3 %] normal weight, and 2 [11.8 %] underweight patients). All patients survived shock therapy. After adjusting for confounding factors, overweight patients had significantly fewer outcomes relating to all-cause death and appropriate shock events (hazard ratio 0.27, 95 % confidence interval 0.08-0.91, p = 0.034) than normal weight patients. However, the prognostic difference between overweight and normal weight patients could be diminished as a result of the successful shock therapies (p = 0.067). Additionally, prognosis did not differ between overweight and normal weight patients among the responders, but did differ among the non-responders. The underweight patients had a poorer prognosis after CRT-D implantation compared with the other groups. CONCLUSIONS: Although high BMI was associated with better outcomes among heart failure patients with CRT-D implantations, the difference in the prognosis between overweight and normal weight patients was reduced because of defibrillator therapy and the improvement in cardiac function provided by CRT-D implantation.

Dyeing regions of oxidative hair dyes in human hair investigated by nanoscale secondary ion mass spectrometry.

To develop more effective oxidative hair coloring products, it is important to understand the localization of colored chromophores, which are formed from oxidative dyes, in the fine structure of hair. However, the dyeing regions of oxidative hair dyes in the fine structure of hair have not been extensively examined. In this study, we investigated the distribution and localization of colored chromophores formed by an oxidative hair coloring product in the fine structure of human hair by using a stable isotope-labeled oxidative dye with nanoscale secondary ion mass spectrometry (NanoSIMS). First, formation of the colored chromophore from a deuterium-labeled oxidative dye was examined by visible spectra similarly to a study of its formation using nonlabeled oxidative dye. Furthermore, the formation of binuclear indo dye containing deuterium in its chemical structure was confirmed using time-of-flight secondary ion mass spectrometry (TOF-SIMS) analysis. As a result of the NanoSIMS image on a cross-sectional dyed hair, although deuterium ions were detected in whole hair cross-section, quite a few of them were detected at particulate regions. These particulate regions of the dyed black hair in which deuterium ions were intensely detected were identified as melanin granules, by comparing the dyeing behaviors of black and white hair. NanoSIMS analysis revealed that melanin granules of black human hair are important dyeing regions in oxidative hair coloring.

Mechanisms with clinical implications for atrial fibrillation-associated remodeling: cathepsin K expression, regulation, and therapeutic target and biomarker.

BACKGROUND: The cysteine protease cathepsin K (CatK) has been implicated in the pathogenesis of cardiovascular disease. We sought to determine the link between atrial fibrillation (AF) and plasma CatK levels and to investigate the expression of and therapeutic target for CatK in vivo and in vitro. METHODS AND RESULTS: Plasma CatK and extracellular matrix protein peptides (intact procollagen type I of N-terminal propeptide; carboxyl-terminal telopeptide of type I collagen [ICTP]) were measured in 209 consecutive patients with AF (paroxysmal AF, 146; persistent AF, 63) and 112 control subjects. In addition, the regulation of CatK expression was investigated in vivo and vitro. Patients with AF had higher plasma CatK and ICTP levels than did control subjects. Patients with persistent AF had higher levels of plasma CatK and ICTP than did patients with paroxysmal AF. CatK was correlated with ICTP concentration and left atrial diameter in all subjects. In rabbits, superoxide production, CatK activity, fibrosis, and the levels of atrial tissue angiotensin II, angiotensin type 1 receptor, gp91phox, phospho-p38 mitogen-activated protein kinase, and CatK were greater in those with tachypacing-induced AF than in controls, and these changes were reversed with angiotensin type 1 receptor antagonist. Olmesartan and mitogen-activated protein kinase inhibitor decreased the CatK expression induced by angiotensin II in rat neonatal myocytes. CONCLUSIONS: These data indicated that increased plasma CatK levels are linked with the presence of AF. Angiotensin type 1 receptor antagonist appears to be effective in alleviating atrial fibrosis in a rabbit AF model, partly reducing angiotensin type 1 receptor-p38mitogen-activated protein kinase-dependent and -independent CatK activation, thus preventing AF.

A case of fulminant myocarditis associated with novel N1H1 influenza successfully treated by percutaneous cardiopulmonary support system.

We report a case of fulminant myocarditis associated with N1H1 influenza virus infection. N1H1 was confirmed by a polymerase chain reaction assay and she was treated with oseltamivir phosphate. She was admitted to the hospital because of respiratory distress, however, echocardiography revealed severely depressed wall motion followed by refractory ventricular fibrillation. Extracorporeal circulation by emergent percutaneous cardiopulmonary support system was required to maintain hemodynamic stability. Cardiac function was spontaneously and gradually restored within a week. Findings from biopsy samples taken on day 1 and day 23 were consistent with acute myocarditis.